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“AN INNOVATIVE MODEL TO QUANTIFY CORNEAL TRANSPARENCY IN DONOR CORNEAL BUTTONS� BACKGROUND: Assessment of corneal transparency in donor corneal buttons has only been performed qualitatively. The quantification of corneal transparency has implications with respect to clinical suitability of the donor cornea and research involving corneal transparency as an outcome measure. We present a simple, reproducible cost effective model of quantifying corneal transparency. METHOD: An Artificial anterior chamber was modified to create a central transparent passage. This was made possible by replacing the base of the chamber with Perspex and a water tight seal. An inlet and outlet tube was attached to the sides of the chamber. This was done to maintain a standardized pressure within the chamber when connected to an IV bottle. A corneal button rejected for corneal transplant was placed on the artificial anterior chamber and the chamber was filled with normal saline. A digital camera and a laser source were placed on either side of the chamber at predetermined intervals. Alignment was achieved so that the laser light passed through the center of the cornea. The image of the laser spot was acquired. To test this proof of concept, a human donor cornea rejected for human transplant was injected with intrastromal saline to create corneal haze. Pre and Post injection images were analyzed. The average pixel intensity was calculated. RESULTS: The mean pixel intensity of the cornea prior to injury was 111 and post-saline injury was 17.2. CONCLUSION: Laser scatter quantification can be an effective tool to measure corneal transparency in donor corneal buttons. The simple inexpensive set up and ease of analysis are advantages of this method of quantification. Pre and post injury measurements showed a marked difference in average pixel intensity. A102
Study of Pupil Dilatation Characteristics in patients from South India with topical Tropicamide -Phenylephrine
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Authors: Haseena1, Shreya Elsa1, Satheesh Solomon T Selvin2,Anupriya Arthur2, Thomas 1 Kuriakose2 Affiliations: Optometrist, CMC Vellore 2Consultant in Ophthalmology, CMC Vellore BACKGROUND: Pupil dilatation is essential in routine eye examination and is a prerequisite in many ocular surgeries/procedures. Various dilating agents have been tried and evaluated, but the combination of Tropicamide-Phenylephrine has proved to be most effective. The rapidity and estimated time, when known will help the clinical work flow.The racial properties determining the pigmentation of the iris also determines the rate and extent of pupil dilatation due to the property of the drug adhering to the melanin pigments. This study was undertaken to look at the above mentioned properties of the pupil in an Indian Population. AIMS AND OBJECTIVES: To study the time of onset and extent of dilatation, time taken for maximal dilatation and rate of dilatation in Indian eyes with instillation of a single drop of Tropicamide-Phenylephrine. MATERIALS AND METHODS: This was a cross sectional observational study conducted on 132 eyes (right) from 132 patients. Following baseline measurement, a single drop of Tropicamide (0.8%) with Phenylephrine (5%) was instilled and the pupil dilatation characteristics studied. Pupil diameter was measured by Optical Biometry for every 2 mins till 44 minutes or till the patient achieved full dilatation. RESULTS: The average onset of dilatation in our study population was at 9.0±5.2 min (2 to 24 min) from the time of instillation of drops. The mean time taken for full dilatation was 33.02±5.09 min (22 to 42 min) with mean amplitude of 2.39±0.68 mm (0.9 to 4.2 mm). The rate of dilatation of the pupil was 0.07±0.022 mm/sec (0.03 to 0.14 mm/min). CONCLUSION: 98.4% of patients dilated to their maximal dilatation within 44 min, average time of 33.03 min. An inverse association was seen between the time taken for dilatation and the baseline pupil diameter and a positive correlation to the time of onset of dilatation. A103
“AN INTELLIGENT SYSTEM FOR AUTOMATIC FOOTDROP CORRECTION IN STROKE PATIENTS USING FES. " Authors: Naveen G, Dr Sivakumar Balasubramanian, Mr Senthil Velkumar, Dr Judy John, Dr George Tharion, Dr Suresh Devasahayam. Departments and institution: Dept. of Bioengineering and Dept. of PMR, CMC Vellore.
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BACKGROUND: FES (Functional Electrical Stimulation) has emerged as one of the effective means of correcting footdrop, helping the stroke survivors to attain good foot clearance through active ankle dorsiflexion and achieve a natural gait. In spite of the advancements in post-stroke rehabilitation for automating footdrop correction, there have been inconsistency demonstrated positive effects due to the lack of evidence based practice guidelines and limited understanding of the mechanism of footdrop correction based on accurate gait phase detection. AIM: To assess the feasibility and effectiveness of a low cost, intelligent system incorporating manual mode and automatic mode of stimulation, using inertial motion sensors with FES device to correct foot-drop in stroke patients. PICO: 1. Patients: 2 Nos., (Age >18 years) with post-stroke foot-drop. 2. Intervention: Functional Electrical Stimulation. First, the calibrated system was tested on 6 normal volunteers, on 5 terrains: smooth floor, up a ramp, down a ramp, up the stairs and down the stairs. Next clinical trial was done in 2 stroke patients. The data collected was used to propose an intelligent algorithm for automatic footdrop correction. 3. Comparison: The ankle dorsiflexion, walking speed and asymmetry were compared with the baseline data without stimulation. Feedback was collected for evaluation of the patient satisfaction. 4. Outcome/Results & CONCLUSION: The algorithm validation proved the feasibility of having an automatic footdrop correction system. The baseline comparison showed improvement in ankle dorsiflexion, walking speed and symmetry with FES intervention. Feedback from patients showed a need to improve the instrumentation to make it more easy to use on daily basis. A104
Barriers to good Nutritional care in Type 1 Diabetes Mellitus patients Mini Joseph, Riddhi Das Gupta, AshaH Shyamasunder,Praveen VijayalakshmiAnand, NithyaDevanithi and Nihal Thomas
Gangadhara,
Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India
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BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the commonest metabolic disorders of childhood and occurs due to the autoimmune destruction of insulin producing islet beta cells predisposed by genetic and precipitated by environmental determinants. Appropriate nutrition therapy is essential to ensure sustained optimum growth and avoid hypoglycaemia. Preliminary study amongst these patients indicated a poor nutrient intake with a deficit in macronutrients and micronutrients. Hence the main objective of this study was to assess the major barriers to good nutrition in this group of patients. METHODOLOGY: This cross-sectional study was conducted amongst 50 young adults with Type 1 diabetes mellitus (18-45 years of age) visiting the Young Adults Type 1 Diabetes mellitus clinic (last 1 month) using a pre-tested questionnaire. The questionnaire consisted of 15 questions, each with five options that discussed the probable barriers faced by the patients in adhering to the nutrition advice given at the clinic. The patients were asked to choose the most suitable options. Percentage analysis was done to analyse the data. RESULTS: Snacks and food timings were irregular in 28% of the patients, the major reason being time constraints. However 72% followed the three meals and three snacks pattern. A small number of patients had irregular meal timings since they worked late shifts (11%) and 6% considered meal timings as irrelevant. Biscuits were preferred snacks for one-third of the patients due to easy availability and cost effectiveness (11%). Night snacks were skipped in 17% of them since they had a late dinner and hence not hungry. With regard to vegetable intake, the major barrier faced by 61% of the patients was lack of time to cook the vegetables. Although majority of the patients (61%) consumed rice only once a day, 28% ate rice more than twice due to ease in preparation and convenience. Work and responsibilities negatively impeded 39% of the patients from following the nutrition advice given at the clinic. Only 1/3rd of the patients diligently followed all the advice imparted in the clinic. The reasons for not following the diet were that they did not consider diet an important aspect of treatment (6%) and some of them felt low and depressed (11%).Recording the food intake accurately in the diary was cumbersome for 11% and 6% of them were illiterate; however 78% recorded the data accurately. Protein was not included in every meal because they did not buy it (6%) and 6% did not consider it important for them. It was reassuring to see that 78% of them adjusted the insulin according to their blood sugar levels and the others did not adjust the insulin because of lack of knowledge on insulin adjustments. CONCLUSION: The Type 1 Diabetes mellitus patients are a vulnerable group who require continuing intensive nutrition education to maintain acceptable glycaemic control. Every visit to the clinic is an opportunity to emphasize the principles of nutrition therapy and should be importunately enforced. Keywords: Type 1 Diabetes mellitus, barriers to glycaemic control, nutrition.
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Are the Type 1 Diabetes Mellitus patients more prone to developing Eating Disorders? Mini Joseph, AshaHesarghattaShyamasunder, Priya Mammen†and Nihal Thomas Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India;†Department of Child & Adolescent Psychiatry Unit, Mental Health Centre, Bagayam, Christian Medical College & Hospital, Vellore, Tamil Nadu, India BACKGROUND: The choice of type and quantity of food is vital to achieving glycemic control in Diabetes, more so in Type 1 Diabetes mellitus. The attention to detail could however reach a level of obsession of an eating disorder and thereby have a negative impact on glycemic control. We conducted a study to see if there was a risk of developing Eating Disorders amongst adolescent, young and middle aged adults with Type 1 Diabetes mellitus and whether it has an association with HbA1C levels. METHODS: A cross-sectional study was conducted on 113 Type 1 Diabetes mellitus patients and age-gender matched healthy controls. The two groups were screened using the Eating Attitude Test- 26 (EAT-26) questionnaire. RESULTS: EAT -26 identified Type 1 Diabetes as having a high risk for developing Eating Disorder when compared to those without diabetes (OR= 38.5 with 95% CI 8.7, 170.7; p<0.001). The risk of developing eating disorder increased with the duration of diabetes. There was no significant difference in the risk between males and females. The risk of developing eating disorder did not correlate with glycemic control. CONCLUSION: EAT -26 identified subjects with Type 1 Diabetes as high risk for developing eating disorder in comparison to those without diabetes. In our setting, this did not reflect on poor glycemic control. Keywords Eating Disorders; Type 1 Diabetes mellitus; EAT-26
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A106 Nutrient intake of patients with Morbid Obesity Mini Joseph1, Nitin Kapoor1, Shobana Ramasamy2, Stephen Amarjeet Jiwanmall3, Kattula Dheeraj3, Vijay Abraham4,Inian S.4, Thomas Paul1, Simon Rajaratnam1, Nihal Thomas1 1
Department of Endocrinology, Diabetes and Metabolism Christian Medical College & Hospital, Vellore, Tamil Nadu, India; 2Weill Cornell Medicine, New York, United States, 3Department of Psychiatry, Christian Medical College & Hospital, Vellore, Tamil Nadu, India;4Department of Upper GI Surgery, Christian Medical College & Hospital, Vellore, Tamil Nadu, India; INTRODUCTION: Morbid obesity is rapidly sweeping across the Indian continent. It is a serious health condition that negatively impacts the physical, mental and social well-being of an individual. The morbidly obese are at a higher risk for illnesses including diabetes, hypertension, Obstructive sleep apnoea, gastro-esophageal reflux disease, gallstones, depression, osteoarthritis, knee and back pain, heart disease and cancer. METHODOLOGY: The study was conducted on 101 morbidly obese individuals who attended the Bariatric clinic of Christian Medical College & Hospital, Vellore in Tamil Nadu over a period of 6 months from January to June 2016. Their anthropometric measurements including, height, weight, waist and hip circumference were measured using standard procedures. The dietary assessment was done using a 24 hour dietary recall along with a food frequency questionnaire. The study was approved by the Institutional review boardand informed consent was obtained from all the patients. RESULTS: Majority of patients followed the referral pattern of the hospital. More than 3/4th of the patients were females. Sixty per cent of them were educated till the school level. Nearly 63 per cent had Type 2 diabetes mellitus. The mean age of the male and female population was 41.3 + 15.5 years and 36.7 + 11.9 years respectively. Their mean BMI was 58.7 + 9.2 kg/m2 in the males and 47.8 + 12.4 kg/m2 in the females. Amongst the males, the mean waist circumference (126.93 + 20.71 cm) was greater than their hip measurements (121.0 + 34.92 cm). In contrast, the female population had a larger hip measurement (121.55 + 31.54 cm)than the waist circumference(116.5 + 31.76 cm). Dietary data indicated that majority were non-vegetarians. The mean daily intake of calories was 2254 kcal/day with a gross deficit in the intake of micro nutrients. The macronutrient distribution indicated a high fat diet (30% of total calories) and low proteins (13% of total calories) intake. Fried snacks, fast foods, sweets, carbonated drinks were frequently consumed by the patient population. The consumption of fruits and vegetables was below the daily recommended servings. The daily oil consumption in the Bengali patients was significantly higher indicating a high consumption of calorie dense foods.
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CONCLUSION: The obese patients require intense and frequent individualized counseling by a dedicated team of an endocrinologist, psychiatrist, dietician, bariatric surgeon and a social worker. This is required to make achievable changes in the quality of life of the morbidly obese patients. Keywords: Morbidly obese, nutrient intake, anthropometry A107
DEVELOPMENT AND VALIDATION OF THE VELLORE OCCUPATIONAL THERAPY EVALUATION SCALE (VOTES) TO ASSESS FUNCTIONING IN PEOPLE WITH MENTAL ILLNESS Reema Samuel, MOT, Lecturer in Occupational Therapy Paul SS Russell, MD, Professor of Psychiatry Tapan Kumar Paraseth, Occupational Therapy student Sharmila Ernest, BOT, Tutor in Occupational Therapy K.S.Jacob, Professor of Psychiatry Department of Psychiatry, Christian Medical College, Vellore. BACKGROUND: Available occupational therapy assessments focus on specific areas of functioning and are not standardised among the Indian mentally ill population. There is need for a scale to assess overall functioning specific to Indian population. AIM: To develop and validate an assessment scale to evaluate diverse aspects of functioning among people with mental illness in India. METHOD: Available instruments, which evaluate diverse aspects of functioning in people with mental illness, were retrieved and relevant items were selected by a committee of mental health experts and combined to form a comprehensive instrument. Face validity, content validity and feasibility were assessed and the new instrument was piloted among 60 patients with mental illness. The scale was found to have good internal consistency (Cronbach’s alpha =0.973), inter-rater reliability (ICC=0.99) and test re-test reliability (ICC =0.97). After review and modifications, the final version of the scale had 6 domains with 35 items: 5 components for ‘general behaviour’, interpersonal skills’, and “group skills’; 4 items for ‘intrapersonal skills’ and ‘activity configuration” and 12 for ‘task behaviour’. The scale was administered by two therapists on 151 consecutive clients between 18 to 60 years of age. They were also assessed using Global Assessment of Functioning (GAF) to assess criterion validity; Occupational Therapy Task Observation Scale (OTTOS), Social Functioning Questionnaire
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(SFQ) & Rosenberg Self Esteem Scale (RSES) to assess convergent validity and Pai & Kapur Family Burden Interview Schedule (FBIS) to assess divergent validity. The inter-rater and test retest reliability of the new instrument was also evaluated. RESULTS: The new scale had good internal consistency (Cronbach’s alpha 0.817), inter-rater reliability 0.928 (0.877-0.958)and test-retest reliability 0.928 (0.868-0.961).The correlation between the domains of general behaviour (PCC=-0.763,p=0.000), task behavior (PCC=-0.829,p=0.000), social skills (PCC=-0.351,p=0.000), intrapersonal skills (PCC=-0.208,p=0.010), instrumental ADL (PCC=-0.329,p=0.038) and leisure activities (PCC=-0.433,p=0.005) scores of VOTES with the corresponding domains in the other scales was statistically significant implying that the scale could adequately assess domain specific constructs. The correlation between the total score of VOTES and the total scores of OTTOS, SFQ and RSES together was also statistically significant suggesting convergent validity in overall assessment. The correlation between the total score of VOTES with that of FBI was not statistically significant, implying good divergent validity in that the VOTES did not assess different constructs. CONCLUSION: VOTES seems to be a promising tool to assess overall functioning of people with mental illness.
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SHORT DURATION PODCASTS AS ADJUNCT LEARNING TOOLS: PERCEPTIONS OF MEDICAL STUDENTS AND IMPACT ON ACADEMIC PERFORMANCE Author: Dr. Anand R Assistant Professor, Department of Biochemistry, Christian Medical College, Vellore, India Email: anandr@cmcvellore.ac.in; griffindoc@gmail.com BACKGROUND: Use of podcasts has several advantages in medical education. Short duration (1-5 minutes) podcasts are unique since, they can provide bursts of high-yield information before a student gets distracted. However, the information conveyed by them can be limited due to the time barrier and students may need prior knowledge on the topic to use them effectively. The perceptions and effectiveness short duration podcasts are not well understood and this study aimed at exploring the same. An exploratory analysis between students’ usage of 3MTLs and their academic performance was also undertaken. OBJECTIVE: To explore the effectiveness of short duration podcasts as adjunct learning tools in biochemistry and to assess its impact on academic performance of students.
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METHODS: First year medical students (N=94) were the participants in the study. Eight audio visual podcasts, each ≤ 3 minutes duration [referred to as 3-Minute Lessons (3MTLs)] were developed for two topics in biochemistry. The podcasts were provided as supplementary material to students along with didactic lectures on the topics. Following routine internal assessments, feedback was collected from students using a self-reported questionnaire. The academic performance of students was also compared based on their usage of 3MTLs. RESULTS: Feedback indicated that 3MTLs were well received by students as a useful and convenient revision tool. A significant proportion felt that 3 minutes were optimum while, an equal proportion suggested an increase in the duration to 5 minutes with more information. No difference was noted in assessment that followed 3MTL (Test3MTL) implementation between users and non-users. However, a pairwise comparison of Test3MTL with a test that preceded (TestP) and succeeded (TestS) showed significantly higher mean difference amongst students who used 3MTLs. In the comparison of Test3MTLvs TestP, the pairwise difference was 2.32 (99% CI: 0.32-4.3; P=0.009), while it was 4.2 (99% CI: 2.43-5.97; P<0.001) in the Test3MTLvs TestPcomparison. CONCLUSION: Overall, short duration podcasts were well received by students and show promise as useful adjunct tools in medical education.
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The diagnostic utility of the line probe assays for the detection of XDRTB Marilyn M Ninan, E Shalini, Joy S Michael INTRODUCTION: Tuberculosis (TB)remains a global crisis. Drug resistant TB in India is on the rise. Extensively drug resistant tuberculosis (XDRTB) is now being reported from several countries, including India. Conventional drug susceptibility testing (DST) methods are time consuming and there is a need for rapid molecular diagnosis. MTBDRsl (Hain LifeSciences), is a line probe assay(LPA) that detects resistance to fluoroquinolones and aminoglycosides, within 48 hours. Therefore we evaluated this assay on both smear positive sputum samples and culture isolates from patients with laboratory diagnosed MDR-TB METHODS: The assay was performed on 12 smear positive sputum samples (with at least 1+ AFB) and 61 Mycobacterium tuberculosis culture isolates obtained from patients diagnosed as multidrug resistant tuberculosis by Xpert MTB/Rif over the time period July 2015-July 2016. Of 73 samples processed by LPA, 46 had DST results by 1% proportion method. One sample was
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indeterminate, leaving 45 for analysis. Diagnostic accuracy indices were calculated against conventional DST methods. RESULTS: Sensitivity and specificity for detection of gyr A mutations were 92.95%(95% CI 76.5 -99.1%) and 72.2%(95%CI 46.5-90.3%). Sensitivity and specificity for detection of rrsmutations were 60%(95%CI 14.7-94.7%) and 100%(95%CI 91.2-100%). The prevalence of XDRTB was 6.7%(3/45) and preXDR(resistance to rifampicin, isoniazid and fluoroquinolones) was 57.8%(26/45). Of 29 isolates that had fluoroquinolone resistance, the most common mutation that coded for resistance was mut 3C with absence in WT3(12/29). Of 4 isolates that had aminoglycoside resistance, three had a mut1 with a corresponding absence in the WT1 band. CONCLUSION: This assay has good sensitivity for the detection of fluoroquinolone resistance, and moderate sensitivity for aminoglycoside resistance, though a larger study needs to be done to validate its clinical usefulness. A large proportion of preXDR patients with resistance to fluoroquinolones is present in South India, and treatment protocols for these patients may need tailoring accordingly. In addition the knowledge of mutation patterns may also help in tailoring drug regimens for this difficult to treat group of patients.
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Perception of medical students towards choice of specialty: validation of instrument and pilot study Prakash SS, Anand R Department of Biochemistry, Christian Medical College, Vellore. Email: sspcmc@cmcvellore.ac.in BACKGROUND: Most Indian medical students prefer to pursue a postgraduate degree of their choice. Several factors may influence their choice including background characteristics, personalities of students, specialty related characteristics and their preference to work in urban or rural areas. There is no validated instrument available to assess these parameters in our settings. AIM: To develop and validate an instrument to assess the perception of medical students while choosing a specialty for post graduation degree after MBBS MATERIALS AND METHODS: We have developed and validated a questionnaire to assess various aspects including the factors which influence career specialty choices among Indian medical students. The questionnaire was developed by the authors after literature survey. Content Validation by Experts (CVE; N=10) was carried out using a structured form. Response Process Validation (RPV) was undertaken among a subgroup of medical students (N=10). We developed a 12-item questionnaire after CVE and RPV. Finally, the questionnaire was pilot tested in another separate cohort of medical students (N=63). The study protocol was approved by the
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Institutional Review Board, CMC Vellore (IRB Min No. 9630 [OBSERVE] dated 23.09.2015). All statistical analyses were done in SPSS v. 16.0 RESULTS: The participants were enrolled in the study after obtaining written informed consent. Pilot study data showed that the questionnaire was able to test the awareness, certainty, most and least likely choices of specialty, factors affecting specialty choice, when medical students form specialty choice and their inclination towards serving in rural areas. A Cronbach’s alpha value > 0.7 was obtained when different factors were clustered and tested for inter-correlation between items. CONCLUSION: We have developed and validated an instrument which can reliably assess various aspects related to specialty choice among Indian medical students. We hope that this tool can be used to study the changing trends in the preferences of medical students and the factors that underlie their choice of specialty.
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Scrub typhus infection- role of WDF cell population data and scatterplots of Sysmex XN®9000 analyser in its identification and separation from other similar illnesses Ananthvikas Jayaram1, Sukesh Nair2, Joy Mammen2, Nitty Mathews2, Tulasi Geevar2, John Anthony Jude Prakash3, Valsan P Verghese4, Winsley Rose4, Alice Mathuram5, Karthik G5, Josephine2, Philip Jesuraj2 Departments of 1Pathology, 2Transfusion medicine and Immunohaematology, 3Microbiology, 4 Child Health Unit 3 and 5Medicine, Christian Medical College, Vellore INTRODUCTION: Scrub typhus is an under-recognized and emerging zoonosis, with infection causing changes in the WBCs that reflect on the cell counter WBC differential (WDF) scattergrams. Bacterial infections usually result in increased neutrophil side fluorescence (SFL) and decreased forward scatter (FSC) indicating left shift. Viral infections invariably cause variations in the High Fluorescent Lymphocyte Cell population (HFLC%). In cases of scrub typhus, both these phenomena were observed in our routine workflow. This study aimed to assess the utility of these parameters in combination to differentiate scrub typhus from the others. METHODS:EDTA blood samples from 99 cases and 83 age matched controls (141 and 93 blood samples respectively) were analysed in the CBC+Differential mode on a Sysmex XN®9000 platform with calibration, linearity and carry over tests verified and daily quality control checks performed. Clinical suspicion of scrub typhus and serologic positivity by IgM ELISA defined cases of scrub typhus. The routine and research parameters and WDF scattergram patterns from the cell counter were analysed. Samples from 449 healthy voluntary blood donors served to calculate the reference ranges. RESULTS: Scattergrams in scrub typhus revealed an increased height of the lymphocyte plot
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that tapered at the top, giving it a “rocket-trail” like appearance. This was accompanied by neutrophil changes of a mild left shift along the FSC and an increase in height along the SFL axis, resulting in a “golf club” like plot on the WDF scattergram (Figure 1). These correlated with the objective values of neutrophil cell population data and the HFLC%. These changes in the scattergrams and accompanying cell population data were quite sensitive and specific in identifying cases of scrub typhus. We also observed a higher neutrophil SFL and a lower neutrophil FSC on the day of presentation in patients who developed complications when compared to those who didn’t. On a subset of 18 patients who had follow up with response to therapy, the neutrophil SFL showed a tendency to return to normal in the first five days post initiation of therapy. CONCLUSIONS: Cell counter parameters early in the course of scrub typhus could help guide diagnosis leading to timely initiation of therapy, thereby improving patient outcome.
Figu re 1: Patterns seen in the SFL vs. SSC (rocket trail) and SFL vs. FSC (golf club) WDF plots in scrub typhus, and comparison with a normal WDF scatterplot.Legend- Pink- lymphocytes, Green- monocytes, Light blue- Neutrophils, Orange- Eosinophils A112
Atypical lymphocytes on peripheral smears along with scattergram morphology and objective cell population data are true to the changes in dengue infection, and reliably discriminate it from other febrile illnesses Ananthvikas Jayaram1, Sukesh Nair2, Joy Mammen2, Nitty Mathews2, Tulasi Geevar2, Asha Mary Abraham3, Valsan P Verghese4, Winsley Rose4, Alice Mathuram5, Karthik G5, Josephine2, Philip Jesuraj2
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Departments of 1Pathology, 2Transfusion medicine and Immunohaematology, 3Virology, 4Child Health Unit 3 and 5Medicine, Christian Medical College, Vellore INTRODUCTION: One of the biggest challenges associated with patient management in dengue is early and reliable diagnosis, which has traditionally relied on clinical findings with a high index of suspicion, laboratory parameters including leukopenia, thrombocytopenia, high hematocrit, elevated transaminases and a deranged coagulation test, followed by confirmatory serology for the NS1 antigen and/or IgM and IgG antibodies. However, in a resource limited setting, and in endemic areas where patients may not present with the classical clinical picture, diagnosis may prove challenging. Testing for all the differentials of an acute febrile illness could cause a stress on both the limited monetary and human resources. We observed characteristic atypical lymphocytes, or dengue ‘virocytes’, in peripheral smears of patients with dengue which were also represented on the cell counter as a High Fluorescent Lymphocyte Cell (HFLC%) population, and this study was conducted to validate these findings. METHODS: All patients with a clinical suspicion of dengue, i.e., fever of <10 days’ duration at the time when there was a dengue epidemic (September 2015 to December 2015), and had undergone serologic testing for dengue were included consecutively. Patients who tested positive for dengue NS1 antigen and/ or IgM antibody were considered as cases and those negative for these formed the control group. Those patients with positivity for dengue IgG alone were neither considered as cases nor as controls, and were analysed separately. Cell counter data was available from 168 cases (out of 445) and 184 controls (out of 568) and these patients formed the study group. Reference ranges for cell counter parameters were calculated from 449 healthy voluntary blood donors in the blood bank. RESULTS: Patients with dengue ranged from 4 months to 88 years in age, including 30% of patients who were less than 16 years of age. Most cases (~50%) presented between days 4 and 6 of fever. The High Fluorescent Lymphocyte Cell count (HFLC) was found to be consistently elevated in cases of dengue when compared with controls (87.3% of cases vs. 18.3% of controls). The reference range calculated for HFLC% was 0-0.96. ROC curve analysis of HFLC% in cases and controls showed an AUC of 0.9216, with 95% confidence intervals at 0.89 and 0.95, and an optimal sensitivity and specificity of 82.2% and 90.4% being obtained at a cut off value for HFLC% of 1.4%. The HFLC% value was found to increase gradually and reach a maximum value on day 5 of illness following which there was a decline, and this mirrored the variations observed in platelet counts which reached a nadir on day 5 of illness. The accompanying cell counter scattergrams showed a characteristic “tilted hour glass” or a “figure of 8” pattern in cases of dengue. Peripheral smears from cases almost always showed atypical lymphocytes with a peculiar morphology, i.e. large cells with intense deep blue staining of the cytoplasm, with a few cells showing cytoplasmic projections. CONCLUSION:
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We believe that better understanding of the HFLC% and its relationship to dengue, and its reliability in identifying cases of dengue, could aid in the early evaluation of cases of acute febrile illnesses, especially in resource limited settings, where the first sample sent for cell counts can also point toward a probable diagnosis, leading to prompt and timely initiation of supportive therapy and an overall improved outcome.
Figure 2: WDF scattergrams from 8 different cases of dengue with a ‘tilted hour glass’ or ‘figure of 8’ pattern of the pink lymphocyte plot. The first figure in the series shows a greyed out population as there was a poor separation. Legend- Pink- lymphocytes, Green- monocytes, Light blue- Neutrophils, Orange- Eosinophils A113
EPSTEIN BARR VIRUS RELATED DIFFUSE LARGE B CELL LYMPHOMA OF THE ELDERLY- ASSESSMENT OF FREQUENCY IN AN INDIAN TERTIARY CARE CENTRE AND COMPARISON OF THE MORPHOLOGICAL FEATURES OF THE EBER-ISH POSITIVE AND EBER-ISH NEGATIVE CASES Ananthvikas Jayaram1, Marie Therese Manipadam1, Auro Viswabandya2, Grace Rebekah3 Departments of 1Pathology, 2Clinical Hematology and 3Biostatistics OBJECTIVES: To identify cases of lymph nodal EBV Positive Diffuse Large B Cell Lymphoma (EBV+DLBCL) and assess the disease frequency in patients older than 45 years of age in a tertiary care centre in India, and to do a detailed histologic study of all cases to identify morphologic features that may help suspect EBV positivity.
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METHODS: We included cases of lymph nodal DLBCL occurring in patients older than 45 years of age, and excluded cases with a prior history of therapy for lymphoma, with a documented seropositive status, with features of a double hit or grey zone lymphoma on initial biopsy and cases with an initial presentation at an extranodal site with subsequent involvement of lymph nodes. Slides and blocks from 129 cases of lymph nodal DLBCL occurring in patients older than 45 years of age were retrieved from the department archives based on a keyword search. Clinical data including the age, gender, state of residence, clinical stage and international prognostication index score at presentation, presence/absence of B symptoms and details of marrow involvement at presentation were noted from the patient files. The histological parameters evaluated on the H&E stained slides were the pattern, morphologic subtype, reactive background, necrosis, multinucleate giant cells, tingible body macrophages, vascular proliferation, angioinvasion, intranodal fibrosis and perinodal extension. The available CD3, MIB-1 and EBV-LMP1 immunohistochemistry slides were assessed for percentage of positive cells. EBER-ISH stained slides were examined for proportion and pattern of staining, and a threshold of >10% positively staining cells was considered as a positive test. The statistical methods used included frequency table, Chi square test and Fisher’s exact test, with a p value of <0.05 considered as significant. RESULTS: EBER-ISH was not assessable in 5 of the 114 cases owing to an overwhelming background staining, and was positive in 7 of the remaining 109 cases with a calculated frequency of 6.42%. This frequency is lesser than that reported from Japan and Korea, and more than that reported from the USA and Europe. The mean age at presentation of patients with EBV+DLBCL in our study was 66 years, which is younger than the reported global average of 71-75 years. Among the histologic features, increased number of tingible body macrophages and prominent vascular proliferation were significantly different between the EBV positive and EBV negative groups of DLBCL (p value <0.05), while increased multinucleate giant cells showed a borderline significance (p value 0.06). There was a slight discordance between EBV-LMP1 and EBER-ISH, with 1 EBER-ISH positive case showing a negative staining for EBV-LMP1, which is known to occur. Edge artifacts and non-specific background staining for EBER-ISH were also seen more often in core biopsies, and could possibly have been related to formalin fixation.
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HUMAN IMMUNODEFICIENCY VIRUS-1 IGG ANTIBODY AVIDITY AMONG THE NEWLY DIAGNOSED, THOSE RESPOND TO ART AND AMONG INDIVIDUALS WITH VIROLOGICAL FAILURE Alex D1, Sachithanandham J2, Tennison IW3, Prasannakumar S2, Demosthenes JP2, Ramalingam VV2, Victor PJ4, Rupali P3, Fletcher GJ2, Kannangai R2 1Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu 2Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu 3Department of Infectious Disease,
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Christian Medical College, Vellore, Tamil Nadu 4Department of Medicine, Christian Medical College, Vellore, Tamil Nadu. INTRODUCTION: Recent (<6months) and long term HIV infection can be differentiated by antibody avidity testing. The viral kinetics can impact the humoral immune response and may modify the pathogenesis of the infection. OBJECTIVES: To determine the frequency of recent HIV-1 infections among the volunteers who attended ICTC at a tertiary care center using a commercial Limiting Antigen (LAg) avidity EIA, to compare the findings with an in-house avidity assay and to study the impact of ART on maturation of HIV-1 specific antibodies. METHODOLOGY: Samples from 117 treatment naïve HIV-1 infected individuals who attended ICTC and archived paired plasma of HIV-1 infected individuals prior to ART, 6-12 months following successful treatment and individuals who had virological failure were tested using a commercial LAgAvidity EIA. The normalized optical density (ODn) values obtained were compared with inhouse avidity assay values and band intensity in Western Blot. RESULTS: Of these, 117 HIV-1 infected individuals, 8 (6.83%) were found to be recently infected with HIV-1. The in-house avidity assay had a sensitivity of 100% (95% CI 63.09-100%) and specificity 99.08% (95% CI 94.99-99.98%) with good agreement (κ=0.94). The western blot analysis of samples from recently infected individuals showed weak or no band against pol proteins. The mean ODn values of samples from HIV-1 infected individuals (n=25) responding to treatment was significantly lower than the samples prior to treatment (ODn = 3.977±1.1 Vs ODn = 4.306± 0.97, p=0.0038) while there was an increase in the ODn values when individuals (n=7) had virological failure (p = 0.057). CONCLUSION: The frequency of recent HIV-1 infection is 6.83% in newly diagnosed HIV-1 cohort. Antiretroviral therapy had a significant effect on avidity of HIV-1 antibodies, possibly predicting virological failure. The modification of the indigenous assay allows the availability of testing for recent HIV-1 infection with low cost.
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A115
DETERMINATION OF DOSIMETRIC LEAF GAP USING DIFFERENT DETECTORS AND ITS IMPACT IN DOSE CALCULATION AND DELIVERY Author: Divya Lakshmi J; Co – Authors: Mr. Timothy Peace Balasingh, Mr. MohamathuRafic, Mr. Ebenezer Sumanbabu, Mr. Jose Solomon Raj, Mr. Amalan, Ms. Lijy joy, Department Of Radiotherapy, Christian Medical College (CMC), Vellore – 632 004. BACKGROUND: The radiation transmission through the rounded leaf end referred as dosimetric leaf gap (DLG) parameterhas to be incorporated into the TPS for accurate dose calculation. AIM: To determine the DLG value using different detectors namely ionization chamber, optically stimulated luminescence dosimeter (OSLD) and electronic portal imaging device (EPID) and also to develop a MATLAB software code to obtain a 2D DLG map in order to account for accurate DLG values of the entire field. METHODS AND MATERIALS: The Clinac 2100C/D linear accelerator was used to perform DLG measurements in which DLGionand DLGOSLD were measured for sweeping fields of different gap widths for central six MLC leaf pairs using 0.125 cc semiflex ionization chamber and nanodot OSL positioned perpendicular to the direction of the sweeping beam in three positions namely central axis, 1 cm inferior and superior from the central axis. An aS1000 EPID was used to determine DLGEPIDvalues. MATLAB software was used to obtain a 2D DLG map from which the DLG value at any point in the field can be determined. RESULTS AND CONCLUSION: The DLGion values measured in three detector positions were found to be 1mm, 1mm, and 1.25 mm. The DLGOSLDvalues were found to be 1.142 mm, 1.142 mm, 1.28 mm and the DLGEPID values were calculated as 0.875 mm, 1mm and 0.875 mm. Though ionization chamber is the standard dosimeter for DLG measurements, in order to eliminate the volume averaging effect, the highly sensitive OSL dosimeter which exhibits highly reproducible dose measurements even at low dose range can be used for DLG measurements. The determination of DLG values of individual MLC leaf of entire bank and modeling the TPS with the same can be achieved by using EPID which is a high resolution 2D detector.
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A116
HYPERGLUCAGONEMIA, RESTING ENERGY EXPENDITURE, INSULIN SENSITIVITY – A “PARADIGM SHIFT” IN THE PATHOGENESIS OF FIBROCALCIFIC PANCREATIC DIABETES (FCPD) IN ASIAN INDIANS? Authors: Roshna Ramachandran*, Shajith Anoop.S*, Padmanabhan V*, Praveen Gangadhara*, Riddhi Dasgupta*, Mercy Inbakumari*, Roshan Livingston¥, Akankasha Tiwari#, Anneka Wikramanayake #, Joe Fleming,§ Meredith Hawkins# , Nihal Thomas*, *Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India.§ Department of Biochemistry, Christian Medical College, Vellore, India¥ Department of Radiology, Christian Medical College, Vellore, India.# Einstein Diabetes Institute, Albert Einstein college of Medicine, New York, USA. Corresponding author: drroshna@gmail.com BACKGROUND: Studies in T2DM and T1DM have shown significant contribution of Resting Energy Expenditure (REE) to the metabolic milieu. Fibrocalcific pancreatic diabetes (FCPD), a unique form of secondary diabetes affecting lean Indians, has been traditionally associated with beta cell secretion defects. The contribution of energy expenditure and glucagon levels to overall metabolic dysregulation remains largely unexplained in this group of diabetes. OBJECTIVE: To evaluate alterations in resting energy expenditure (REE) in men with FCPD and analyze its association with insulin and glucagon dynamics in FCPD. METHODS: A cross sectional observational study was done from 2012 to 2015 in the department of Endocrinology. Age and BMI matched men with FCPD (n=20, mean age 30.9 ± 7.1yrs, BMI 19.79 ± 3kg/m2), Type I DM (n=15, mean age 28.6± 5.8yrs, BMI 19.7± 1.6kg/m2) and non diabetic controls (n=15, mean age 30 ± 8.1 yrs, BMI 19.1 ±2.28 kg/m2) were studied. REE was estimated using indirect calorimetry using Jaeger oxycon Pro and body composition was measured using Dual energy X-ray absoprtiometry (DEXA). Insulin secretion rates (ISR) were assessed using C-peptide deconvolution techniques and the glucagon secretion rate was calculated separately from the Area under the Curve (AUC) for glucagon secretion following an oral mixed meal challenge test over 180 minutes. Hepatic and peripheral insulin sensitivity (IS) was assessed using Euglycaemic Hyperinsulinemic pancreatic clamp procedure. RESULTS: Deconvolution analysis revealed significant reduction in Insulin secretion rates (ISR) in FCPD group (358.35 ± 244.95pmol/kg/min) compared to the non diabetic controls (984.28±245.01 pmol/kg/min)(p=0.000) though more than T1DM (34.27 ± 73.36 pmol/kg/min) (p=0.000). However the serial glucagon levels were significantly higher in FCPD group (26686.91 ±
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10302.25) in comparison to the control group (8222.2 ± 2037.5) and T1DM group (12516.2 ± 1074.46) (p=0.000). The hepatic and peripheral insulin sensitivity in the FCPD group was reduced in comparison to the non diabetic control group (p=0.01). REE in the FCPD group (1821 ± 431.08) had no significant difference from that in the T1DM (2280.19 ± 516.64) or non-diabetic control groups(1937.2 ± 556.24) after adjusting for BMI (p=0.98) and fat-free mass (p=0.69). In the FCPD group, while REE did not show any significant correlation with Insulin secretion rates (p=0.65), hepatic insulin sensitivity (EGP)(p=0.92) and peripheral insulin sensitivity (Rd)(p=0.86), increased glucagon secretion rates (r=0.556, p=0.01)was significantly correlated with REE. CONCLUSION: The finding of significantly increased glucagon levels despite extensive pancreatic destruction in FCPD is a novel finding that can have important pathogenic implications. Correlation of the glucagon levels with the REE points to a central role of increased glucagon in regulating metabolic pathways in FCPD, warranting further research into this unique concept. Key words: Resting energy expenditure, Fibro calcific pancreatic diabetes, Hyper glucagonemia
A117
Low expression of duodenal iron transporters may explain anaemia associated with chronic liver disease of alcoholic and viral etiology JithuV James¹, Joe Varghese1, Kavita Rasalkar1, Ramya Raghavan1, CE Eapen2and Molly Jacob1 Departments of Biochemistry1,Gastroenterology and Hepatology2 Christian Medical College, Vellore, India. BACKGROUND: Derangements in iron metabolism have been reported in patients with chronic liver disease (CLD). Body iron levels are mainly regulated by duodenal uptake of dietary iron. Very little is known about the effect of chronic liver disease on expression of proteins involved in duodenal iron absorption. AIM: To determine the expression of duodenal iron transporters in patients with CLD Method: Patients with CLD, of alcoholic (n=23) and viral (n=26) etiology, who were required to undergo a medically-indicated upper gastrointestinal endoscopy, were recruited into the study after obtaining informed consent. Patients who underwent an endoscopy for investigation of dyspepsia
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and who were found to have no endoscopic abnormalities served as control subjects (n=29). A sample of duodenal mucosal tissue was obtained from each patient and was used to determine gene expression (by quantitative PCR) and protein levels (by western blotting) of divalent metal transporter 1 (DMT1), ferroportin and duodenal cytochrome b (dcytb), all of which are involved in absorption of iron in the duodenum. Blood was obtained for estimation of haemoglobin and serum levels of ferritin, iron, hepcidin (the central regulator of iron homeostasis), C-reactive protein(CRP) and forliver function tests. RESULTS: Patients with CLD, irrespective of etiology, had significantly lower levels of hemoglobin when compared with control subjects.This was associated with lower levels of serum hepcidin in these patients. Serum iron levels tended to be lower in CLD patients while serum ferritinwas unaffected. Serum aspartate transaminase (AST) and CRP levels were significantly increased while that of albumin was decreased in CLD group. Gene expression levels of ferroportin and dcytb were decreased in patients with CLD, withexpression levels beinglower in those with viral CLD than in alcoholic CLD. At the protein level, DMT1 was significantly lower in patients with CLD of irrespective of etiology, while ferroportin was significantly decreased only in the group with viral CLD. CONCLUSIONS: The results of this study showed that patients with CLD had low expression of duodenal iron transporters, despite low serum hepcidin levels. The mechanisms underlying these discrepant findings are unclear. Whether the low haemoglobin in these patients is aninitiating event in or a consequence of the dysregulation of iron metabolism is also not known. Further work is warranted to elucidate the mechanisms involved. A118
DEVELOPMENT AND DOSIMETRIC VALIDATION OF SOFTWARE BASED A-SI EPID DOSIMETRY John Paul Puravath, Timothy Peace S,Amalan S, Jose Solomon Raj, Satish Kumar A, Department of Radiotherapy CMC Vellore BACKGROUND: In vivo dosimetry has become an inevitable part of external radiation therapy due to the complex advancements in radiation treatment. Conventional in vivo dosimeters have many disadvantages such as additional setup time, labour-intensive readout procedures, high cost and need for frequent calibration. The electronic portal imaging device which is an accessory of the modern linear accelerator has been calibrated for the in vivo exit dose measurement. AIM: The purpose of this work is to develop EPID-based in vivo dosimetry software for routine patient
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dosimetry and to perform phantom-based studies to validate the software by comparison with established in vivo dosimeters such as MOSFET and OSL dosimeters. METHODS AND MATERIALS: Electronic portal imaging device (aS1000) of Clinac 2100 C/D linear accelerator has been calibrated in our department for exit dose measurement, using ionisation chamber in direct calibration method. A software code was developed using MATLAB R2013a (8.1.0.604) to calculate the exit dose from the portal images based on the calibration performed. The developed software was used for the exit dose calculation of radiation beams irradiated on CIRS model 002LFC thorax phantom. The point dose verification of the EPID-based exit dose software was carried out using micro MOSFET, nano Dot OSLD dosimeters. RESULTS AND CONCLUSION: A software was developed for the exit dose measurement with graphical user interface based on the correlation functions obtained from the calibration data. From the obtained results of verification of EPID dosimetry using MOSFET,nano OSLD it is evident that the variation between the reference TPS value and the obtained EPID readings are in agreement with minimum observed deviation of 0.57 and maximum deviation was 2.82. It is hereby concluded that this software based a-Si EPID dosimetry can be a effective tool for the routine in vivo dosimetry.
Software User interface
A119
CLONAL IDENTIFICATION OF ACINETOBACTERBAUMANNIIIN ATERTIARY CARE CENTRE IN SOUTH INDIA Nithin Sam, ShaliniAnandan, SaranyaVijayakumar, RadhaGopi, BalajiVeeraraghavan INTRODUCTION:
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Acinetobacter baumannii is a major pathogen which causes severe nosocomial infection such as ventilator associated pneumonia and bacteraemia. A.baumanniireadily acquires resistance to a broad spectrum of antibiotics by acquiring resistant genes. It is associated with high mortality and morbidity rate, particularly in debilitated patients. In this study, A. baumannii strains isolated from patients requiring specialist care were assessed using molecular techniques for clonal similarity. MATERIALS AND METHODS: Through Antimicrobial susceptibility testing (AST) 17 random extensively drug resistant (XDR)invasive isolate of A. baumanniiwas selected from the month of June 2015 and November 2015.CarbAcineto NP was performed for the screening of carbapenemresistance, further the isolates were analysed for the presence of insertion sequence (IS),antimicrobial resistance genes (AMR), and virulence genes (Cpa1,Cpa2 and PKF)using polymerase chain reaction (PCR). The clonality of these isolates were identified by multilocus sequence typing (MLST) and using clonal typing PCR (M13, DAF4, ERIC 1 and 2)withbionumerics software. RESULTS: CarbAcineto NP for all isolate turned out to be positive. In AMR they have resistant genes like oxacillinases (OXA-51/23) and metallo β-lactamases (NDM, PER, TEM). The ISelement was found in the upstream region ofoxacillinase genes(IS F + OXA-51, IS F + OXA-23) which can induce high expression of those genes. Among the three virulent genes, PKF was predominantly found in all isolates. In MLST a total of 11 sequence type (ST) was identified in which 5 were new sequence type. The ST848 was found in 5 isolates, three from the month of June 2015 and two from the month of November 2015. Clonal typing PCR also gave similar patterns to that of MLST with minor variations. CONCLUSION: In this study, ST 848 was found to be a predominant circulating clone among the isolates obtained fromthe debilitated patients. Thus a high discriminative power in clonal identification can be obtained by clonal typing PCR and MLST, and can be used for outbreak surveillance.
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SERUM HEPCIDIN LEVELS IN DIABETES MELLITUS Padmanaban Venkatesan1, Joe Varghese1, Jasmine Prasad2, Molly Jacob1. Departments of Biochemistry1 and Community Medicine2, Christian Medical College, Vellore 632002, Tamil Nadu, India
INTRODUCTION:
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Diabetes mellitus is known to be associated with increased levels of body iron stores. The mechanisms that link these conditions are unclear. Hepcidin is known to play a key role in iron homeostasis. It is possible that changes in hepcidin may underlie the association between these two conditions. AIM: To estimate serum levels of hepcidin and iron-related parameters in adults diagnosed to have diabetes mellitus, and compare these with levels of these parameters in those without diabetes mellitus. METHODS: Informed consent was obtained to collect fasting blood samples from adult males who were diagnosed, for the first time, to have diabetes mellitus (DM). Age-matched males with fasting glucose values within the reference range served as control subjects. Each sample obtained was used to estimate haemoglobin, glucose, C-reactive protein (CRP), ferritin, total iron-binding capacity (TIBC), iron and hepcidin. Anthropometric measurements were also made on each subject. RESULTS: Twenty one subjects were studied in each group. Both groups were similar in age and anthropometric measurements. There were no differences in values of haemoglobin, TIBC, transferrin saturation and serum iron between controls and diabetics. Serum ferritin levels were significantly higher in those with DM when compared with controls. Serum hepcidin levels were similar in the 2 groups. Ratio of hepcidin to ferritin was significantly lower in those with DM when compared with control subjects. CONCLUSIONS: Serum ferritin, a marker of body iron stores, was significantly increased in subjects with diabetes mellitus, but hepcidin levels were not. However, these patients had lower hepcidin-ferritin ratio, showing that serum hepcidin levels were inappropriately low for the increased serum ferritin levels seen in these subjects. This suggests that the biological response of the body to increase hepcidin levels in response to increased body iron levels seems to be blunted in diabetic subjects.
A121
EFFECT OF CLEISTANTHIN C ON BLOOD PRESSURE OF RATS- HOW HELPFUL ARE ALPHA ADRENERGICS IN THE MANAGEMENT OF C.collinus POISONING? Sajal Clarence Singh, Sathya Subramani, Renu Raj R, Department of Physiology, Christian Medical College, Vellore
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BACKGROUND: Cause of death in Cleistanthus collinus poisoning is stated to be intractable hypotension not responding to vasoconstrictor drugs. In addition to adrenaline and nor adrenaline, Phenylephrine, a pure alpha agonist is also used in the treatment regimen of shock. In our lab, we have identified a new signaling pathway, where under a high NO environment, Phenylephrine causes vasodilatation (Plos One). Our lab has also identified that the major toxin in C.collinus boiled extract is Cleistanthin C. Therefore our research question was if the toxin induced hypotension was due the new pathway and if Phenylephrine would actually worsen the hypotension. AIM: To study the effects of alpha adrenergics on toxin induced hypotension in C.collinus poisoning. METHODS: Wistar rats were administered the lethal dose Cleistanthin C in 30% ethanol intravenously. Control group received 30% ethanol. Blood pressure was recorded through the carotid artery. Data was acquired through CMC DAQ. In case of fall in blood pressure, Phenylephrine was administered intravenously. Animals were observed for 8 hours or till death. RESULTS AND CONCLUSION: Control animals lived for 8 hours under anaesthesia and then were sacrificed. In test animals, IV Cleistanthin C led to significant decreased in diastolic BP only. Subsequent administration of IV Phenylephrine led to a precipitous drop in all components of blood pressure. It is therefore possible that administration of vasoconstrictors with alpha adrenergic agonism in C.collinus poisoning is what worsens hypotension. Counter intuitively, alpha blockers may be of help in treating vasoplegic shock. A122
PERFORMANCE OF THE ACHUTHA MENON CENTRE DIABETES RISK SCORE IN PREDICTING PREVALENT DIABETES IN TAMIL NADU, INDIA Authors: Anu Mary Oommen1, Vinod Joseph Abraham1, Thirunavukkarasu Sathish2,Kuryan George1Affiliations: 1 Christian Medical College, Vellore, Tamil Nadu, India2 Melbourne School of Population and Global Health, The University of Melbourne, VIC 3010, Australia OBJECTIVES: To examine the performance of the Achutha Menon Centre Diabetes Risk Score (AMCDRS)in predicting prevalent undiagnosed and totaldiabetes in Tamil Nadu, India and compare it with other Indian risk scores.
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METHODS: AMCDRS (includes age, family history of diabetes and waist circumference)was calculated for 4896 participants (30 to 64 years) of a cross-sectional survey (2010-12) in urban and rural Vellore, Tamil Nadu. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AROC) were calculated for the optimum cut-off point. RESULTS: Of 4896 participants, 274 (6.2%) had undiagnosed diabetes and 759 (15.5%) had total diabetes. AMCDRS score ≥ 4 identified 44.5% for further testing with sensitivity 75.1%, specificity 60.5%, PPV9.1%, NPV95.8% and an AROC of 0.639 (95% confidence interval [CI]: 0.6080.670) for undiagnosed diabetes. The corresponding figures for total diabetes were 75.1%, 60.5%, 25.9%, 93.0% and 0.731 (95% CI: 0.713-0.750), respectively. The prevalence of undiagnosed and total diabetes increased significantly with increasing risk scores. The AROC of AMCDRS was significantly lower than that of the Chaturvedi risk score for undiagnosed diabetes but was not significantly different from AROCs of other Indian risk scores for total diabetes. CONCLUSIONS: AMCDRS, a simple risk score, can be used to identify undiagnosed and total diabetes in India. AMCDRS performed similarly in predicting total diabetes compared to other Indian risk scores which in cluderelatively more difficult-to-measure variables (blood pressure, physical activity, body mass index). However, AMCDRS requires recalibration to improve its performance. A123
RISK FACTORS FOR STUNTING AMONG CHILDREN OF AGE GROUP 24 - 59 MONTHS – A COMMUNITY BASED CASE-CONTROL STUDY FROM VELLORE, SOUTH INDIA. Dr Sumanto Pal 1,Dr Venkata Raghava 2, Dr Gagandeep Kang 3, Dr. Jasmine Helan Kuryan George 2
4
and Dr
AIMS: To identify factors associated with stunting in children of age group 24 –59months in the Vellore Block Demographic Surveillance system with special emphasis on Environment and Sanitation.
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OBJECTIVE: To measure association between stunting and – 1. Environmental risk factors. 2. Socio-demographic risk factors. 3. Biological risk factors.
METHODS: Children in the age group 24 – 59 months residing in the Vellore Block DSS area and for whom anthropometry was done during Dec-2015 census were chosen as study population. 301 households were enrolled. Caregivers were administered semi-structured questionnaire, study child height and parent’s anthropometry was measured and environmental parameters were inspected. Drinking water samples were tested for a subset of 50 houses in each arm.
RESULTS: The significant risk factors are – 1. 2. 3. 4. 5.
Female [adjusted-OR 2.194 (95.% C.I 1.121 – 4.296)] Non-pucca house [adjusted-OR 2.534 (95.% C.I 1.206 – 5.324)] Spacing < 36-months [adjusted-OR 2.725 (95.% C.I 1.159 – 6.408)] Malnourished mother [adjusted-OR 13.504 (95.% C.I1.642– 111.090)] Poor water-handling score [adjusted-OR 2.156 (95.% C.I1.089– 4.268)]
CONCLUSION: Strategies for control of nutritional stunting should emphasise on environmental parameters such as water handling in addition to known biological risk factors.
A124
“PROGRESSION OF GESTATIONAL DIABETES TO TYPE 2 DIABETES MELLITUS: A NON-CONCURRENT COHORT STUDY IN SOUTHERN INDIA” Authors: 1. Dr. Kusum V Moray PG Registrar, Department of Community health, CMC Vellore 2. Dr. Jasmin Helan, Head of the Department, Department of Community health, CMC Vellore. 3. Dr. Kuryan George, Professor, Department Of Community Health, CMC Vellore
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4. Dr. Venkata Raghava M, Professor, Department of Community Health, CMC Vellore 5. Dr. Nihal Thomas, Professor in Endocrinology and Head, Department of Endocrinology, Diabetes and Metabolism& Vice Principal (Research), CMC Vellore 6. Dr. Antonisamy B., Professor and Head, Department of Biostatistics, CMC Vellore 7. Mrs. Janani Iswarya, Lecturer Grade II, Department of Clinical Biochemistry, CMC Vellore AIMS: To study cumulative risk of developing type2 diabetes mellitus in women who had gestational diabetes in Southern India OBJECTIVE: To estimate cumulative risk of developing type2 diabetes mellitus in women who had GDM as compared to women who did not have GDM in Vellore, Southern India. METHODS: The pregnant women who were screened for gestational diabetes at a secondary care hospital in Vellore from 1998 to 2011 were chosen as the study population; source of data wasthe laboratory registers of the hospital. Of the 2002 women, 1020 were excluded(addresses unavailable and > 50 Km from the hospital); there were 136 women with GDM and 846 women without GDM. Participants (51 GDM and 158 Non-GDM) were administered semi-structured questionnaire; 24hour food recall and International physical activity questionnaire. Patients were asked to come to the hospital for fasting, 2-hour post prandial blood glucose and HBA1c. RESULTS: The incidence of type 2 diabetes mellitus was 29 out of 51 in GDM group and 14 out of 140 cases in non-GDM group. Incidence rate ratio is 6.92 with 95% CI (3.68, 13.03). The cumulative risk of developing type 2 diabetes mellitus at 5, 10 and 15 years is 31.7%, 78.7%, 85.8% for GDM and 2.2%, 17.1%, 33.6% for Non-GDM groups respectively. CONCLUSION: Women with GDM have a high risk of progression to type 2 diabetes; they should be followed up after pregnancy periodically.
A125
GENERALIZED POISSON REGRESSION MODEL TO DETERMINE THE FACTORS FOR NUMBER OF UNDER-FIVE MALNOURISHED CHILDREN IN INDIA (BASED ON NFHS-III DATA) Devika Shanmugasundaram & Lakshmanan Jeyaseelan, Department of Biostatistics, Christian Medical College, Vellore, India
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BACKGROUND: In many epidemiological studies the presence of count type response variable is inevitable. Examples includes, number of episodes of diarrhoea, number of cigarettes consumed, number of days of abstinence to alcoholic drinks in a month, etc. Poisson regression (PR) models are generally used to analyze such kind of count data, which assumes to follow Poisson distribution. However, PR model is only appropriate if the mean and the variance of the response variable (count) is equidispersed. But in real time study, either the variance would be greater than the mean (over dispersed) or lesser than the mean (under dispersed). Applying standard PR model to these data leads to biased standard error which in turn leads to inefficient estimate of regression parameters resulted in misleading inferences. There are various other methods such as negative binomial and hurdle models are available to model over dispersed count data. In this study, we propose to use Generalized Poisson Regression (GPR) model as compared to PR model for an under dispersed count data and to find the predictors of the count outcome. OBJECTIVE: To study the characteristics (coverage probability) of GRP and PR models for an under dispersed count data using simulation study. To find the predictors of the count variable defined as number of under-five malnourished children in an Indian family using GPR model. MATERIALS & METHODS: The data for the study was obtained from NFHS-III conducted in 2005-06. The outcome of our present study is the number of under-five malnourished child in each household in India. A total of 25,466 under-five children aged 0 to 59 months is used for the analysis. Both PR and GPR models were used to study the factors for malnutrition (stunting). RESULTS & CONCLUSION: GPR model as compared to PR is found to be appropriate to study the differentials of number of under-five malnutrition because of it’s under dispersion property. Our study found that factors related with hygiene related and poverty related are significantly associated with malnutrition.
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DECREASED RATE OF INFECTION WITH H PYLORI IN PATIENTS WITH DYSPEPSIA MAY EXPLAIN THE DECLINING FREQUENCY OF PEPTIC ULCER DISEASE Amit Kumar Dutta, Viswanath Reddy D, Venkatkrishnan H, Ashok Chacko BACKGROUND AND AIM:
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Recent data from Asian countries including India has shown a significant decline in the frequency of peptic ulcer disease (PUD) in patients with dyspepsia compared to the past. H. pylori is considered the most important risk factor for PUD and we aimed to assess whether the frequency of H. pylori infection in dyspeptic patients has declined compared to the past to explain the decreasing frequency of PUD. METHODS: Patients >15 years of age with dyspeptic symptoms were prospectively recruited in this study from 2010 to 2013 after obtaining informed consent. Patients were divided into three age groups; 15-30 years, 31-50 years and >50 years and the minimum sample size required in the three groups with a power of 90% was 259, 256 and 188 respectively. All patients underwent upper gastrointestinal endoscopy and rapid urease test was done on gastric mucosal biopsy to detect H pylori. The clinical and demographic features and socioeconomic status were recorded. The study was approved by the institute review board. RESULTS: We included 1000 patients with dyspepsia during the study period. Their mean age was 40.0+13.3 years and 69.3% were males. Infection with H pylori was detected in 419 (41.9%) patients. Among men, H pylori was present in 45.7% while the frequency of infection in women was lower at 33.2% (p<0.001)). In the 15-30 years age group (n=303), the frequency of infection was 42.6% while it was 48.3% in the 31-50 years group(n=350) and 34.9% in the above 50 years group (n=347). Male sex was a significant risk factor for infection on multivariate analysis (p<0.001) CONCLUSION: The current prevalence of H pylori infection in dyspeptic patients is much lower than previous reports and may explain the declining frequency of PUD. A127
UTILITY OF TISSUE ELAFIN AS ANIMMUNOHISTOCHEMICAL MARKER FOR DIAGNOSIS OF ACUTE SKIN GVHD – A PILOT STUDY AUTHORS: Gauri Mahabal1, Leni George1, Dincy Peter1, Mandeep Bindra2, Meera Thomas2, Biju George3, Alok Srivastava3, Vikram Mathews3, Susanne Pulimood1. DEPARTMENTS: 1Department of Dermatology,2Department of Pathology,.3Department of Haematology, Christian Medical college, Vellore.
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BACKGROUND: Acute graft versus host disease(GVHD) is an important complication of allogeneic hematopoietic stem cell transplantation(aHSCT). Histopathology, though useful for ruling out clinical mimics ofskin GVHD, has limited sensitivity and specificity. Novel diagnostic modalities are needed for GVHD.Hence we evaluatedelafinexpression byimmunohistochemistryfor diagnosis of acute skin GVHD. AIM: To evaluate elafin immunohistochemistry for acute skin GVHD. METHODOLOGY: After IRB approval, we recruited 20 consecutive patients who underwent aHSCT and developed rash within first 100 days. Clinical diagnosis of the etiology of rash was assigned by treating physicians. Skin biopsies were taken on day of rash. Immunohistochemistry for elafinwas interpreted by a pathologist blinded to histopathological diagnosis. Staining of 50% of epidermis was considered positive. RESULTS: Among the 20 patients(17 males; mean age 16.5 years) recruited, there were 24episodes of rash during which biopsies were performed. Median daypost-HSCTfor onset of skinrash was 21(range: 6-45). The median skin stage of GVHDwas II (range: I – III) and themedian histopathological grade was 1 (range: 0-3). Clinical diagnosis of GVHD was made in 17 (70.8%) episodes while other diagnoses were made in 7 (29.2%). During 17 episodes of clinically diagnosed acute cutaneous GVHD, histopathology was consistent with GVHD in only 14(82.3%) whileall the patients had positive elafinimmunohistochemistry. Among the 7 episodes of non-GVHDrash, 6(85.7%) were negativewhile 1 patient with an engraftment syndromeshowed positive staining for tissue elafin. Immunohistochemistry was able to detectGVHD in 3 patients of GVHD who did not show histopathological findings consistent with GVHD.The sensitivity and specificity of elafin immunohistochemistry for predicting clinical skin GVHD is 100% and 85% respectively. CONCLUSION: Tissue elafin is a highly sensitiveimmunohistochemicalmarkerfor acute skin GVHD.However, larger studiesshould be performed in order to validate these results.
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A128
SAFETY AND EFFICACY OF LEFT ATRIAL APPENDAGE CLOSURE WITH THE AMPLATZER CARDIAC PLUG IN VERY HIGH STROKE AND BLEEDING RISK PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION. Kebernik J1, Jose J1,2, Abdel-Wahab M1, Stöcker B1, Geist V1, Richardt G1. Segeberger Kliniken Germany, CMC Hospital Vellore, India. INTRODUCTION: Limited data exist on the outcomes after left atrial appendage closure (LAAC) with the Amplatzer™ Cardiac Plug (ACP; St. Jude Medical, Minneapolis, MN, USA) in patients with atrial fibrillation (AF) with very high stroke and bleeding risks, the subset expected to benefit most from this procedure. The objective of this study was to report clinical outcomes after LAAC with the ACP device in a very high stroke and bleeding risk cohort of patients with nonvalvular AF and contraindications to oral anticoagulation (OAC). METHODS: LAAC using the ACP device was performed in 96 patients with AF who had median CHA2DS2VASc and HAS-BLED scores of 5 and 3, respectively. Post-procedure, patients received dual antiplatelet therapy for 6 months. A transesophageal echocardiography (TEE) was scheduled at 6 months. RESULTS: Procedural success was 100%. Procedural-related complications occurred in 7.3% (pericardial effusion, 4.2%; thromboembolic events, 2.1%; device embolization, 1.0%). Additional thromboembolic events occurred in three patients during follow-up (92.7% follow-up). After 93.4 patient-years of follow-up, the annual rates of thromboembolic and major bleeding events were 3.2% and 1.1%, respectively. In those with TEE follow-up (70%), complete LAAC with no leaks was observed. Thrombus formation on the device was noted on TEE in two patients. CONCLUSION: LAAC using the ACP device was associated with an acceptable low rate of embolic and bleeding events after a median follow-up of 9 months in a cohort of patients with AF who were amongst the highest stroke and bleeding risks reported so far in LAAC trials. KEYWORDS: Amplatzer™ Cardiac Plug; Atrial fibrillation; Left atrial appendage closure; Oral anticoagulation; Stroke; Thromboembolism
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A129
ASSOCIATION BETWEEN THE DEGREE OF DEVICE OVERSIZING AND CLINICAL OUTCOMES IN THE RANDOMIZED CHOICE TRIAL COMPARING COREVALVE AND SAPIEN XT TRANSCATHETER AORTIC VALVE IMPLANTATIONS John Jose1,2, M. Abdel-Wahab1 1. Vellore
Segeberger Kliniken Germany, 2.
CMC
Hospital
BACKGROUND: A certain degree of transcatheter heart valve (THV) oversizing is considered to be important for current devices to prevent significant paravalvular leakage, which is associated with worsened survival after transcatheter aortic valve implantation (TAVI). Data on degree of device oversizing and its impact on clinical outcomes are limited.We aimed to study the effect of degree of oversizing on clinical outcomes in the CHOICE randomized trial comparing balloon expandable and self expandable valves. METHODS: The multicenter CHOICE trial randomized 241 high surgical risk aortic stenosis patients (undergoing transfemoral TAVI) in a 1:1 fashion to receive either SapienXT (balloonexpandable) or CoreValve (self-expandable valve). Primary endpoint of this trial was the VARC defined rate of device success. 178 patients,who had a 3-dimensional multidetector computed tomography (MDCT) data for degree of device oversizing were included in the present posthoc analysis. Oversizing was determined as perimeter oversizing (%)= (THV perimeter/annulus perimeter-1) x100 and area oversizing (%)= (THV area/annulus area-1) x100. Patients were divided into 2 groups for the analysis- moderate oversizing group (upto 20% area oversizing or upto 9.5% perimeter oversizing) and large oversizing group (more than 20% area oversizing or 9.5% perimeter oversizing). Comparison of periprocedural and 1-year clinical outcomes for Sapien XT and CoreValve were performed in the two oversizing groups.
RESULTS: There were 129 patients in the large oversizing group (SapienXT,n=51; CoreValve,n=78) and 49 in the moderate oversizing group (SapienXT,n=39; CoreValve,n=10). In the moderate oversizing group, device success occurred in 92.3% of the Sapien XT patients as compared to50% of the CoreValve group (p=0.005). In the large oversizing group, device success occurred in 98% of the Sapien XT patients as compared to 82.1% of the CoreValve group (p=0.005). More than mild aortic regurgitation (by angiographic core lab assessment) occurred more with CoreValve implantations in both the oversizing groups (30% versus 7.7%;p=0.09 for moderate oversizing and 2% vs 14%;p=0.03 for large oversizing).CoreValves in the large oversizing groupalso
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received significantly more no. of post dilatations (50% vs14%; p<0.001). Need for second valve was significantly higher for CoreValves in the moderate oversizing group (30% vs 0; p=0.007).There were no immediate mortality or annulus rupture in either groups. Need for pacemaker was higher for CoreValve patients in the moderate oversizing group (55.6% vs 17.6%; p=0.03), with no significant difference in the rates between moderate and large oversized CoreValves.At 1 year, no Sapien XT patient had more than mild aortic regurgitation (AR). AR occurred respectively in 50% and 12.7% of the moderate and large oversizing groups of CoreValve implantations at 1year. There were no significant difference between the deivces with regard to cumulative mortality, cumulative stroke rate and cumulative rates of hospitalisations at 1 year in the two groups. CONCLUSIONS: Balloon expandable TAVI group had less periprocedural and 1 year rates of AR as well as higher device success rate as compared to the self-expanding valve group, irrespective of the degree of oversizing. For self expanding valves, device success was higher in the large oversized group as compared to the moderate one. These findings underscore the importance of significant device oversizing with the self expanding valve.
A130
CLINICAL BIOPROSTHETIC HEART VALVE THROMBOSIS AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION: INCIDENCE, CHARACTERISTICS AND TREATMENT OUTCOMES John Jose1,2, Dmitriy S. Sulimov2, Mohamed El-Mawardy2, Takao Sato2, Abdelhakim Allali2, Erik W. Holy2, BjĂśrn Becker2, Martin Landt2, Julia Kebernik2, Bettina Schwarz2, Gert Richardt2, and Mohamed Abdel-Wahab.2 Christian Medical College Hospital Vellore, India 1. Heart Center, Segeberger Kliniken GmbH (Academic Teaching Hospital of the Universities of Kiel, LĂźbeck and Hamburg), Bad Segeberg, Germany
BACKGROUND: Limited data exists on clinical transcatheter heart valve (THV) thrombosis. The study aim was to determine the incidence, characteristics and treatment outcomes of patients diagnosed with clinical THV thrombosis. METHODS: Retrospective analysis of prospectively collected data from a single center registry that included642 consecutive patients who underwent transcatheter aortic valve implantation (TAVI) between 2007 and 2015 (649 implantations: self-expanding valves=309; balloon-
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expandable=284; mechanically-expanding=56). Postinterventional oral anticoagulation (OAC) was indicated in 267 patients, while 378 patients received dual antiplatelet therapy for at least 3 months post procedure. All patients underwent scheduled clinical and echocardiographic followup. RESULTS: Overall incidence of valve thrombosis was 2.8% (n=18). No patient on OAC developed thrombosis. Of the detected thrombosis cases, 13 had balloon-expandable, 3 had self-expanding and 2 had mechanically-expanding valves. Thrombosis occured significantly more often following valve-in-valve procedures as compared to native valve procedures (OR: 5.01,95%CI:1.71-14.68;p=0.01). Median time to diagnosis of valve thrombosis was 181 days. Median NT-proBNP level was 1318(IQR:606-1676)pg/ml. Mean transvalvular gradient and valve area were 34Âą14mmHg and 1.0Âą0.46cm2, respectively. Hypoattenuating areas with reduced leaflet motion were observed in nine out of ten patients who had CT. Initiation of OAC resulted in significant reduction of transvalvular gradient and clinical improvement. There were no deaths related to valve thrombosis. CONCLUSION: Clinical THV thrombosis is more common than previously considered, characterized by imaging abnormalities, increased gradients and NT-proBNP levels. Postinterventional anticoagulation appears to be effective in prevention and treatment of valve thrombosis. Randomized control trials are needed to define optimal antithrombotic therapy after TAVI.
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Figure
1.
Study
flow
chart
Figure 2 A & B. Incidence of valve thrombosis. Incidence of valve thrombosis based on postprocedural therapy, procedure type and device type.
Figure 3. Box plots showing changes in the mean transvalvular aortic gradient, aortic valve area and NT pro BNP levels. A repeated measure ANOVA with a ‘Greenhouse-Geisser’ correction showed statistically significant difference in the mean values of mean transvalvular aortic gradient (F [1.459, 24.801] =35.202,p<0.001) and aortic valve area (F [1.593, 25.484] =16.766, p<0.001), panel A and B. There was a statistically significant difference in the median NT proBNP levels (chi square= 7.8, p=0.02), panel C. Post hoc analysis with Wilcoxon signed-ranks test was conducted with a Bonferroni correction applied, resulting in a significance level set at p < 0.017.
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A131
A STUDY ON PLASMA ELAFIN –A BIOMARKER FOR SKIN GVHD Authors: L George 1, G Mahabal 1, D Peter 1, SA Pulimood 1, B Poonkuzhali 2, M Ezhilpavai2, ML Kavitha 2, Fouzia NA 2, B George 2, V Mathews 2 , A Srivastava2 Department of Dermatology1 Department of Haematology 2 BACKGROUND: Skin rashes are common following hematopoeitic stem cell transplantation (HSCT). Recently plasma elafin was identified as a biomarker for skin GVHD and may be useful in distinguishing skin GVHD from other rashes after HSCT. AIM: To evaluate elafin as biomarker for skin GVHD METHODOLOGY: All patients undergoing allogeneic HSCT between November 2013 and November 2015 were included. Heparinised blood samples were collected prior to HSCT and at onset of significant rash and plasma elafin levels measured. In patients without a rash, repeat sample was sent on day 28 (controls). Skin biopsy was performed in the presence of a rash. For analysis, patients were divided into 3 groups: patients with skin GVHD, patients with non GVHD skin rash and patients with no rash (controls). RESULTS: A total of 298 patients with a median age of 16 years (range: 1 - 61) and a male predominance (197: 96) underwent HSCT. A total of 168 plasma elafin samples were analysed which included GVHD rash in 89 (52.9 %), nonGVHD rash in 54 (32.14%) and controls in 25 (14.88%). The median elafin value at baseline for the entire cohort was 16784 pg /ml (range 1205 -158586). The median value at onset of skin rash was 35588 (range: 2899 - 371582) in the GVHD group compared to 30068(range: 3396 - 406017) in those with a nonGVHD rash and 24704(range: 4824-109276) among controls [p = 0.114). The median rise in elafin (ratio of elafin value at rash compared to baseline value) was 2.27 in the GVHD group compared to 1.76 for non GVHD rash and 1.13 in the control group (p=0.000). However the difference between GVHD and nonGVHD rash was not statistically different (p = 0.095) CONCLUSION: Rise in plasma elafin levels may be useful in distinguishing between skin GVHD and other rashes following HSCT.
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A132
EFFICACY AND SAFETY OF PALONOSETRON VERSUS ONDANSETRON IN PREVENTION OF CHEMOTHERAPY INDUCED NAUSEA AND VOMITING (CINV) IN CHILDREN Narendra Chaudhary, Deepthi Boddu, Rikki R John, Maha Sampath Gowri*, W. Nalini Nesadeepam, Leni G Mathew Pediatric Hematology Oncology Unit, Department of Child Health, *Department of biostatistics, Christian Medical College, Vellore-632004, Tamilnadu, India. BACKGROUND: Palonosetron, being a long acting antiemetic, is potentially more effective, cheaper and convenient antiemetic for prevention of CINV. We compared efficacy and safety of PG(palonosetron+dexamethasone) with OG(ondansetron+dexamethasone) in prevention of CINV in children receiving moderately(MEC) and highly emetogenic chemotherapy(HEC). METHODS: A prospective single center non-blinded randomized controlled trial was done among children (3-17 years) with cancer receiving first cycle of chemotherapy. Sample size was calculated to give 20% superiority of palonosetron versus ondansetron based on published data on adult patients. Children with brain tumours and comorbidity causing vomiting were excluded. Dose of palonosetron was 5 mcg/kg single dose for 72 hours. Outcome variables (nausea, vomiting, adverse effects, and need of rescue antiemetics) were statistically tested with chi squire test. RESULTS: Two hundred children (mean age 8 years, male:female=1.8:1) were randomized to allocate study groups. Demographic data, diagnosis, chemotherapy schedules and drug cost of antiemetics were comparable among study groups. Zero emesis in acute(<24 hours), delayed(24-120 hours) and overall phase(0-120 hours) was observed in 88%, 88% and 81% of cases respectively for PG versus 84%, 79% and 72% respectively for OG(P=0.42, 0.09 and 0.21 respectively). Complete response rate (no nausea and no vomiting) in acute, delayed and overall phase was 87%, 86% and 79% respectively for PG versus 81%, 72% and 65% respectively for OG(P=0.25, 0.015 and 0.03 respectively). Rescue antiemetics (metoclopramide and/or lorazepam) were used in 5 children in PG versus 4 children in OG(P=0.73). The efficacy of the 2 drugs was same when analyzed separately for MEC or HEC. Side effects were mild (constipation, abdominal pain and headache) and comparable among both the groups. CONCLUSION: Efficacy, safety and drug cost of palonosetron(5 mcg/kg) was comparable with ondansetron but due to less frequent dosing, palonosetron was more suitable for busy health care facilities. Prevention of nausea in delayed phase was better with palonosetron.
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A133
HEALTH RELATED QUALITY OF LIFE IN MORBIDLY OBESE SOUTH INDIAN WOMEN Nitin Kapoor1, Shobana Ramasamy1, Mini Joseph2, Stephen Amarjeet Jiwanmall3, Dheeraj Kattula3, Vijay Abraham4, Inian S. 4, Thomas Paul1, Simon Rajaratnam1, Nihal Thomas1 1
Department of Endocrinology, Diabetes and Metabolism Christian Medical College & Hospital, Vellore, Tamil Nadu, India; 1Weill Cornell Medicine, New York, United States, 3Department of Psychiatry, Christian Medical College & Hospital, Vellore, Tamil Nadu, India; 4Department of Upper GI Surgery, Christian Medical College & Hospital, Vellore, Tamil Nadu, India; PURPOSE: This study analyzed the HRQOL in morbidly obese women (Body Mass Index ≥35 Kg/m 2) attending a bariatric clinic in South India and aimed to ascertain the best anthropometric measure of obesity that correlated with HRQOL in these women. BACKGROUND: The prevalence of obesity is increasing worldwide, reaching epidemic proportions even in many developing countries, attributable to shifts in diet and lifestyle. Obesity is correlated with increased health risks including cardiovascular disease, hypertension, and diabetes mellitus. South Asians have higher body fat percentage at lower BMI’s compared to their caucasian counterparts, and thus, have the same health risks at lower stages of obesity. The increased medical and psychiatric conditions and mobility restrictions associated with obesity has a direct impact on the HRQOL of these individuals. Being a chronic disorder which is often difficult to treat, it is imperative to assess and improve the HRQOL of these individuals, in addition to managing comorbidities and multi-disciplinary attempts to reduce weight. METHODS: This study was conducted in a multispecialty bariatric clinic. Data from patients attending this clinic was obtained for a duration of 6 months. We collected demographic details, their anthropometry (i.e. Weight (in Kg’s), Body Mass Index (Kg/m2), waist circumference (in cm’s), and waist height ratio) and HRQOL from all morbidly obese women who attended clinic and consented to be a part of the study. HRQOL was assessed by using a previously validated obesity related quality of life questionnaire comprised of assessment of obesity’s impact on physical distress, self-esteem, sexual and work life. Statistical analysis was done using the SPSSv.16.0 software (IBM Corp., USA).
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RESULTS: This study analyzed data pertaining to the 108 consecutive morbidly obese female patients who attended a bariatric clinic over a period of 6 months. The study divided the female patient population into two groups by the overall mean QOL total score (<=50% as the Poor QOL group and > 50% as the good QOL group). Morbidly obese females with QOL scores lower than 50 percent had statistically significantly fewer children (1.41±1.150, p=.016), higher BMI’s (42.10±6.27 kg/m2, p=.001), higher hip circumference values (124.71 ± 11.91 cm, p=.001), and lower waist to hip ratios (.92±.08, p=.032) compared to their counterparts with QOL scores higher than 50%. A strong, statistically significant positive correlation between number of children and QOL was found (r=.339, n=55, p<.05). Strong statistically significant negative correlations were also determined between QOL and BMI (r=-.404, n=67, p<.01) and QOL and Hip Circumference (r=-.378, n=64, p<.01). Regression best fit lines further demonstrated the strongest correlation between BMI and QOL with an R2 value of .163, with hip circumference arising as the next strongest correlated variable (R2 value of .143). CONCLUSION: In a cohort of morbidly obese south Asian females, higher BMI is most significantly correlated with lower health related quality of life, both overall and in specific physical and psycho-social scores, when compared to other anthropometric measures (including waist circumference and waist-hip ratios). A134
NAIL FOLD DERMOSCOPY IN PATIENT WITH SCLERODERMA IN A TERTIARY CENTRE INTRODUCTION: Nail fold dermoscopy is a noninvasive technique which aids in the diagnosis of scleroderma and also helps in predicting the stage and extent of microvascular damage. OBJECTIVE: To study the nail fold dermoscopy in patients with scleroderma and its correlation with systemic manifestations. METHODOLOGY: A prospective study was conducted in the department of Dermatology between February 2014 to September 2015. Thirty five patients were recruited during the study period. Dermoscopy of the nail fold capillaries was performed using a Heine delta 20 dermoscope. The various patterns looked for included normal, scleroderma and non specific pattern. The scleroderma pattern was further classified as early, active and late pattern. The prevalence was expressed in term of percentage along with 95% confidence interval. The association of dermoscopic capillary pattern with various clinical manifestations was evaluated using χ² tests.
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RESULTS: The male:female ratio was 1:6. Diffuse type of disease was seen in 91% of the patients and only 9% had limited disease. The commonest dermoscopy pattern was dilated capillaries (91.4%) followed by dropouts (62.9%). All patients had abnormal dermoscopic pattern, of which scleroderma pattern was present in 77.1%(n=27) and non specific pattern was present in 22.9%(n=8). Among the patients with scleroderma pattern, 5(14.3%) had early pattern, 15(42.9%) had active pattern and 7(20%) had late pattern. The mean duration of illness was less in patients with early scleroderma pattern as compared to active and late pattern. In patients with interstitial lung disease and oesophageal reflux, the commonest dermoscopy feature was active pattern. In patients with cardiac involvement active and late pattern were the commonest patterns seen. No association was found between the dermoscopy pattern and Rodnan skin scores, Raynaud’s phenomenon or systemic manifestations. CONCLUSION: The commonest dermoscopic pattern seen was scleroderma active pattern. Dermoscopic patterns didnot correlate with systemic manifestations and Rodnan skin score. A135
Elucidation of the role of Insulin secretion, Insulin sensitivity and Adiposity in the pathogenesis of Diabetes in Asian Indians with ‘lean’ Body Mass Index ( < 18.5 kg/m2)utilizing “Euglycemic-Hyperinsulinemic Pancreatic Clamp” techniques. Authors: Riddhi Dasgupta, Praveen G*, Chaithanya Murthy*, Padmanabhan V*, Shajith Anoop.S*, Roshna Ramachandran*, Mercy Inbakumari*, Roshan Livingstone¥, Joe Fleming,§ Akankasha Tiwari, Anneka Wikramanayake, Meredith Hawkins# , Nihal Thomas*, *Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India. ¥ Department of Radiology Christian Medical College, Vellore, India. § Department of Biochemistry, Christian Medical College, Vellore, India # Einstein Diabetes Institute, Albert Einstein college of Medicine, New York, USA. BACKGROUND AND HYPOTHESIS: Dysregulation of glucose and lipid metabolism in ”Lean diabetes” in India remains sparsely researched. This study was performed to decipher the role of insulin secretion and sensitivity defects and altered fat distribution in the pathogenesis of this unique form of diabetes. METHODOLOGY: In this prospective study over a period of 3 years(2012-2015), a total of 50 age matched males including 10 lean diabetes(BMI18.3 ± 0.1 kg/m2) ,10 T2DM(BMI:25.8±1.1kg/m2), 15 T1DM subjects (BMI:20.5±1.6 kg/m2)and 15 non-diabetics(BMI 19.5 ± 2.3 kg/m2)& were included. ‘Lean-Diabetes’ (defined as diabetes in those with BMI<18.5kg/m2)subjects were negative for auto-antibodies, pancreatic calculi, pancreatic exocrine insufficiency & MODY genetic
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mutations. Insulin secretion was assessed by C-peptide deconvolution techniques after a mixed meal challenge test. Peripheral and hepatic insulin sensitivity was analyzed through hyperinsulinemic-euglycaemic pancreatic clamp procedures.1H-Nuclear-magnetic-resonancespectroscopy was performed to assess hepatic, intra & extra myocellular lipid distribution RESULTS: Insulin secretion rate was lowest for lean diabetes(15± 3.0 pmol/ kg/ min) as compared to nondiabetics (794 ±321.3 pmol/kg/min),T2DM (231.0 ±166 pmol/kg/min) & T1DM (27.5 ± 61 pmol/kg/min) groups(p< 0.001). In the lean DM group, hepatic insulin resistance was significantly higher(p < 0.001) than non-diabetics and T1DM groups while peripheral insulin sensitivity showed no significant difference(p=0.1). Hepatic and myocellular lipid content in lean DM was significantly less than the T2DM (p=0.001) group but was similar to the T1DM & nondiabetic groups (p=0.15) CONCLUSION: These findings show that ‘lean’ Diabetes in Asian Indian males is an unique disorder characterized by reduced insulin secretion, increased hepatic insulin resistance and reduced hepatic and myocellular lipid distribution. These findings can have significant implications for devising therapeutic interventions for this intriguing form of diabetes KEY WORDS: Asian Indians, BMI, Lean Diabetes , Hyperinsulinemic - Euglycaemic clamp, Mixed meal challenge test, MRS. A136
EVALUATION OF PYROSEQUENCING ASSAY FOR THE RAPID DETECTION OF RESISTANCE TO RIFAMPICIN AND SECOND-LINE DRUGS IN MYCOBACTERIUM TUBERCULOSIS CLINICAL ISOLATES. Author: Aishwarya G, Dhananjayan S, Rekha Pai, Joy S Michael. Institute: Department of Clinical Microbiology, Department of General Pathology, Christian Medical College, Vellore.
INTRODUCTION: Drug resistant tuberculosis is a major global public health problem. Early diagnosis of drugresistant tuberculosis (TB) is essential for minimizing the risk of Mycobacterium tuberculosis (MTB) transmission. The conventional culture based drug susceptibility testing (DST) methods for detection of drug-resistant M. tuberculosis are laborious and time consuming. Pyrosequencing (PSQ) assay has the ability to rapidly detect multiple mutations conferring resistance to many of the anti-tuberculosis drugs.
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OBJECTIVES: To evaluate PSQ assay for the rapid detection of resistance to Rifampicin (RIF) Fluoroquinolones (FQ) and Aminoglycosides in MTB clinical isolates MATERIALS AND METHODS: This is a prospective study for a period 1.5 years in which 64 MTB clinical isolates were evaluated for the detection of mutations in rpoB gene (Rifampicin), gyrA gene (Fluoroquinolones), and rrs gene (Aminoglycosides) by PSQ assay. DNA extraction from MTB clinical isolates was performed using Tris-HCl buffer and chloroform. The amplification of respective target genes was done followed by sequencing using the PyroMark Q24 ID system. The PSQ results were compared with the conventional drug susceptibility testing done in the laboratory. RESULTS AND DISCUSSION: By PSQ the most predominant mutation observed in rpoB gene, gyrA gene and rrs gene was TCG531TTG (82%), GAC94GGC (55%). A1401G (72%) respectively. The sensitivity of PSQ assay for the detection of resistance to RIF, FQ, CAP and KAN was 100%, 100%, 40% and 50% respectively. The specificity of the PSQ assay was 100%. CONCLUSION : The PSQ assay is a rapid and effective method for detecting and characterising drug resistance mutations from MTB clinical A137
PERFORMANCE OF RISK ASSESSMENT TOOLS FOR OSTEOPOROSIS IN SOUTH INDIAN RURAL ELDERLY MEN
PREDICTING
Anil Satyaraddi, Sahana Shetty, Nitin Kapoor, Dukhabandhu Naik, Nihal Thomas, Thomas V Paul. Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore. BACKGROUND: Osteoporosis in elderly men is an under recognised problem. This study attempts to look at the performance of osteoporosis self-assessment tool for Asians (OSTA) and male osteoporosis risk estimation score (MORES) for predicting osteoporosis in south Indian rural men
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METHODS: Five hundred and twelve men above 65 years of age from a south Indian rural community were recruited by cluster random sampling. All subjects underwent detailed clinical, anthropometric and bone mineral density measurement at lumbar spine and femoral neck using dual-energy Xray absorptiometry scan. A T score ≤ -2.5 was diagnostic of osteoporosis. Scores for OSTA and MORES were calculated at various cut offs and their sensitivities and specificities for predicting osteoporosis were derived. RESULTS: The prevalence of osteoporosis was found to be 16% at femoral neck and 23% at spine. OSTA with a cut-off value of ≤ 2 predicted osteoporosis with a sensitivity and specificity at lumbar spine of 94% and 17% and at femoral neck of 99% and 18% . MORES with a cut-off value of ≥ 6 predicted osteoporosis at spine with a sensitivity of 98% and specificity of 15% and at femoral neck , they were 98% and 13% respectively. CONCLUSION: OSTA and MORES were found to be useful screening tools for predicting osteoporosis in Indian elderly men. These tools are simple, easy to perform and cost effective in the context of rural Indian setting. KEYWORDS: Osteoporosis in men; OSTA; MORES; Screening tool. A138
INFLUENCE OF DURATION OF ABSTINENCE BEFORE TRANS VAGINAL OOCYTE RETRIEVAL (TVOR) ON THE ASSISTED REPRODUCTIVE TECHNOLOGY (ART) TREATMENT OUTCOME Study question: Whether longer or shorter period of abstinence affect the outcome of ART cycles? BACKGROUND: The abstinence period advised by WHO is mainly advocated prior to diagnostic semen analysis. However, these guidelines have been extrapolated to therapeutic treatments like Intra uterine insemination (IUI) and ART. There is paucity of studies regarding optimum abstinence period prior to ART.
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METHODS: Retrospective study analysing the duration of abstinence before TVOR in couples who underwent assisted reproduction methods ie.,IVF/ICSI in Reproductive Medicine Unit from Jan 2011 to Dec 2015. We included 1039 couples who underwent fresh ART cycle during study period. RESULTS: We divided the included couples into three groups: Group I- with abstinence <2 days had 4 patients(0.38%) while Group II- with abstinence 2-7 days constitutes 872 patients(83.93%) and Group III- with abstinence >7 days had 163 patients(15.69%). Outcome measures analysed are : Fertilization rate following IVF, Fertilization rate following ICSI, Cleavage stage grade I embryo rate, Implantation rate, Clinical pregnancy rate and Miscarriage rate. Results are awaited.
A139
SAFETY PROFILE OF PIRFENIDONE IN IDIOPATHIC PULMONARY FIBROSIS INTRODUCTION: Idiopathic Pulmonary Fibrosis (2) is a type of Idiopathic Interstitial Pneumonia which had recent shift in understanding of pathogenesis from inflammatory to aberrant wound healing and fibrosis. This led to a change in treatment from steroids and immunosuppressant previously used to newer antifibrotic agents like. Pirfenidone (1). This drug at maximal doses it is found to reduce the rate of decline of lung function and increase progression free survival, but it has been seen that maximal doses are not tolerated due to side effects and the tolerance of Indian patients may be different compared to their Western counterparts. There is a paucity of such studies in the Indian population. OBJECTIVES: 1. To evaluate safety profile of Pirfenidone in patients with IPF – incidence and severity of side effects 2. To evaluate disease progression – rate of decline of FVC and 6 minute walk distance. METHOD: This is an observational study on cases diagnosed to have Idiopathic Pulmonary Fibrosis, based on clinic radiological criteria; who are initiated on Pirfenidone therapy as per FDA guidelines; starting at 200mg thrice daily and incrementing weekly till maximal dose is reached at 40mg/kg bodyweight). The side effects occurring were noted and severity graded on CTCAE criteria and managed. Dose adjustments were made as required. At baseline, 3 months and 6 months symptoms, radiographs, FVC and 6 minute walk distance were carried out to assess disease progression.
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RESULTS: In all 30 cases were recruited in a 1.5 year period. 63% were males and 37% females and the mean age was 62 years. The mean baseline FVC was ( 47.6% of predicted) and 6 min walking distance was 356.5 metres. A total of 72% had been treated with Prednisolone only and 4% with Immunosuppressants in addition and 22% received NAC . One patient had just commenced Pirfenidone recently. Three month follow-up was completed in all 30 subjects, 6 months in 9. Two subjects were lost to follow-up and 1 patient expired due to acute exacerbation. It was found that side effects were encountered in 75% of the subjects within a mean duration of treatment of ---%. The major one being gastrointestinal (83%) and dermatological (16%).None of the patients had serious adverse event requiring cessation of therapy. Since only few patients could perform spirometry serially – initially or on follow-up – decline of FVC or 6 minute walk was not assessed. CONCLUSION: Pirfenidone is an antifibrotic agent with predominantly GI side effects, which requires proper patient education and early detection to prevent loss of compliance to the medication. The GI side effects seem more frequent and the dermatological side effects less frequent in the Indian population, when compared to studies of other populations. KEYWORDS: Pirfenidone, Idiopathic Pulmonary Fibrosis, antifibrotic, gastrointestinal, skin, side effects. A140
DOES INSULIN RESISTANCE PRECEDE THE ONSET OF DIABETES IN EUGLYCEMIC SUBJECTS WITH TROPICAL CALCIFIC PANCREATITIS? A “PANCREATIC-CLAMP” STUDY FROM INDIA Authors: Praveen Gangadhara*, Shajith Anoop.S*, Roshna Ramachandran*, Riddhi Dasgupta*, Anneka Wikramanayake# , Eric Frenzy# , Roshan Livingstone¥, Joe Fleming,§ Meredith Hawkins# Nihal Thomas* *Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India. ¥ Department of Radiology Christian Medical College, Vellore, India. § Department of Biochemistry, Christian Medical College, Vellore, India # Einstein Diabetes Institute, Albert Einstein college of Medicine, New York, USA.
BACKGROUND AND HYPOTHESIS: Tropical chronic pancreatitis (TCP) is a juvenile form of chronic calcific non-alcoholic pancreatitis, seen almost exclusively in the developing countries of the tropical world. Though insulin secretion defects are well-known in Fibro calculous pancreatic diabetes (FCPD) - a late stage of TCP, the metabolic milieu of TCP remains unexplored. Our study aimed to detect any changes in insulin sensitivity , insulin secretion and body fat composition that presage the onset of diabetes in TCP .
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METHODOLOGY: In this cross-sectional study over a period of 2 years(2014-2016),, a total of 40 age matched males including 10 TCP subjects (Mean age: 33.5±6.43years), Mean BMI: 20.5± 2.63kg/m 2),10 non-diabetics (Mean age:29.±7.6years,BMI:19.5±2.3kg/m2) and 20 FCPD subjects (Mean age:30.9 ± 7.12years,Mean BMI;19.7± 3.0kg/m2) were included. Insulin secretion was assessed by C-peptide deconvolution techniques after a mixed meal challenge test. Peripheral and hepatic insulin sensitivity was analyzed through “Euglycemic-Hyperinsulinemic pancreatic clamp” procedures. Body composition analyses were measured using DEXA. Resting energy expenditure was measured using Indirect Calorimetry. 1H-Nuclear-magnetic-resonancespectroscopy was performed to assess hepatic, intra-and extra- myocellular lipid distribution. RESULTS: The insulin secretion rate was highest for TCP group(1223±497pmol/kg)as compared to nondiabetic (984±245pmol/kg) and FCPD (358±245pmol/kg).In the TCP group hepatic insulin resistance was significantly higher (p < 0.001)than non-diabetics but no significant difference was observed with the FCPD group(p=0.08) while peripheral insulin sensitivity showed no significant difference between the groups(p=0.1).Resting Energy expenditure was significantly higher(p=0.02) in TCP subjects as compared to FCPD. Significantly increased total and truncal Fat percentage (p<0.0001) were also seen in the TCP group. However, no significant differences were observed for Hepatic, intra myocellular and extra myocellular lipid content when compared between TCP, FCPD and non- diabetic subjects. CONCLUSION: Our study, using the first of its’ kind “pancreatic clamp techniques” in the world, suggests that increased hepatic insulin resistance, increased adiposity and altered energy expenditure precedes the onset of diabetes mellitus in TCP. Given the subsequent complexities in managing pancreatic diabetes, our findings can have significant therapeutic implications. KEY WORDS: Asian Indians, Diabetes, BMI, Hyperinsulinemic -Euglycaemic clamp, DEXA, MRI. Resting Energy expenditure, Normal Glucose Tolerance, Impaired Glucose Tolerance. A141
DOES INITIATION OF METFORMIN IN FIRST TRIMESTER OF PREGNANCY AFFECT MATERNAL AND FETAL OUTCOMES IN ASIAN INDIAN WOMEN WITH GESTATIONAL DIABETES MELLITUS(GDM)? Authors: Vanlalhruaii, Riddhi Das Gupta, JijI E. Mathews*, Annie Regi*, Vishalakshi**, HS Asha, Thomas V Paul, Nihal Thomas *Department of Obstetrics and Gynecology, Christian Medical College, Vellore, Tamil Nadu, India **Department of Biostatistics and Clinical Epidemiology, Christian Medical College, Vellore, Tamil Nadu, India Department of
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Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India Corresponding author: riddhi_dg@rediffmail.com BACKGROUND AND HYPOTHESIS: Metformin has emerged as an oral anti-diabetic agent which is as effective and as safe as insulin in the treatment of Gestational Diabetes Mellitus (GDM).However, it is not yet recommended for use in the first trimester in Gestational Diabetes Mellitus(GDM). AIM OF THE STUDY: To evaluate the maternal and fetal outcomes in women with GDM initiated on metformin within the first trimester. MATERIALS: In this retrospective study, 540 women with GDM were included of which 186 had been initiated on metformin alone in first trimester(Group A), 203 had been initiated on metformin alone after the first trimester(Group B) and 151 had been initiated on insulin alone during any trimester of their pregnancy(Group C). Women with pre-gestational diabetes and hypertension were excluded. The incidence of primary (composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma,5-minute APGAR score less than 7 and prematurity)and secondary(composite of neonatal anthropometric measurements ,maternal glycemic control, maternal hypertensive complications, postpartum-glucose tolerance and acceptability of treatment)outcomes were compared between the groups. RESULTS: A total of 184(47.30 %) subjects taking metformin required supplemental insulin of which 99(53.22 %)were in Group A and 85(41.87 %)in Group B. Although not statistically significant, a higher fasting plasma glucose level at the time of diagnosis was seen in Group A(120.67Âą 29.56 mg %)compared to Group B(116.10Âą 44.49 mg %).Among primary outcome variables, premature birth was numerically higher (9.9%) in Group A compared to Group B (6.9%) patients(p=0.54) and Group C (9.3%)patients(p= 0.537).No other individual primary or secondary outcome variables showed statistically significant difference. The composite of primary and secondary outcomes in group A showed no significant difference from Group B (p=0.33)or Group C(p=0.56). CONCLUSION: Metformin when initiated in the first trimester in women with GDM has no significant adverse fetal or maternal outcomes when compared to those initiated on metformin after first trimester or those on insulin during pregnancy.
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A142
PRE-STORAGE LEUKOREDUCTION OF RED CELLS AT COLD AND ROOM TEMPERATURE: COMPARISON OF EFFICACY AND CLINICAL IMPACT FOLLOWING TRANSFUSION 1
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Authors: Siddharth Mittal , Mary P Chacko , Dolly Daniel , Joy Mammen , Amal Raj , 2
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Chengalath Manoras Mathew , Santosh Varughese
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Department of Transfusion medicine & Immunohaematology , Department of Cardiothoracic 2
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surgery , Department of Nephrology CMC hospital, Vellore BACKGROUND: Donor leukocytes present in blood components have been implicated in transfusion related complications including FNHTR (febrile non haemolytic transfusion reaction). Some studies have shown that leukocyte removal by filtration is more effective when conducted at cold temperature as opposed to standard room temperature. AIM: To achieve significant decrease in residual WBC count and incidence of acute transfusion reaction among patients transfused with leukoreduced bags processed at cold temperature (2-6 degrees Celsius) in comparison to bags processed at room temperature (20-24 degrees Celsius). MATERIAL AND METHODS: In first part of the study, blood bags collected from first 4 donors daily were processed for leukoreduction at room and cold temperature respectively (2 bags at each temperature). Residual WBC counts in bags processed at two temperatures were assessed using Nageotte haemocytometry and flow cytometry. In second part of the study (non-randomized clinical trial) leukoreduced bags were processed at either room or cold temperature for 6 months each and issued to patients. Post-transfusion monitoring was done for any episode of acute transfusion reaction especially FNHTR. RESULTS AND CONCLUSION: The median WBC count among leukoreduced units filtered at room and cold temperature was 0.1 x 106 and 0.02 x 106 WBCs/unit respectively and difference is statistically significant. Leukoreduction at cold temperature is significantly superior to room temperature and there is no difference in RBC recovery at either temperature. The rate of FNHTR among transfused patients is less with leukoreduced bags filtered at cold temperature in comparison to room temperature. However further sampling will be needed to confirm this finding.
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A143
AMBULATION AUGMENTATION IN LOW LEVEL PARAPLEGICS RESISTANCE BANDS- A PILOT RANDOMIZED CONTROL TRIAL
USING
BACKGROUND: Walking in low paraplegics usually with Knee Ankle Foot Orthoses and crutches is 5 times slower and >9 times energy consuming as able bodied walkers causing low compliance, wastage of resources and leaves them immobile and dependent. We need to address this inefficiency but in India, alternative augmentative devices are impractical. OBJECTIVE: Develop a simple, affordable, readily available, light, aesthetic, fail safe, and customizable augmentative device, not requiring added expertise, training or resources to put to use, to improve walking efficiency thus improve compliance, productivity and independence. I am trying to use Resistance-Bands to achieve this, look at safety and feasibility and compare effect on gait and energy parameters via RCT. DESIGN: Prospective Pilot RCT, followed by Partial cross over and Pre vs Post design. PARTICIPANTS: Motor complete T10-L1 (lack lower limb power) Paraplegics trained to walk using KAFOs and Crutches. INTERVENTION: Novel use of Resistance-Bands as add-on to KAFOs. MAIN OUTCOMES: Speed (10meter walk test), Endurance (6 minute walk test), Energy expenditure (Physiological Cost Index-PCI), Step Length, Cadence and Acceptability questionnaire (OPUS). RESULTS: Part 1: (RCT)=intervention caused statistically significant increase in Step length and reduction in energy expenditure. Device was overall well accepted. Part 2: (Partial cross over)=also statistical significance increase in step length and decreased PCI in Control group. Part 3: (Pre-Post intervention)=statistically significant increase in step length, speed and endurance with a statistically significant decreased PCI.
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CONCLUSION: Addition of resistance-bands to already existing KAFO-crutch combination augments efficiency of gait-speed, step length, endurance, while decreasing energy consumption. This has the potential to increase walking compliance and limit waste of limited resources. The device is acceptable, safe and feasible.
A144
EVALUATION OF DIFFERENT SCREENING TOOLS FOR PREDICTING OSTEOPOROSIS IN RURAL SOUTH INDIAN POSTMENOPAUSAL WOMEN Kripa Elizabeth Cherian, Nitin Kapoor, Sahana Shetty, DukhabandhuNaik, Nihal Thomas, Thomas Vizhalil Paul Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India. BACKGROUND: Postmenopausal osteoporosis is an important public health problem which is under recognized in an India context. Identifying and treating them is vital to prevent fragility fractures and their associated morbidity and mortality. Measurement of Bone Mineral Density (BMD) by Dual Energy X-ray Absorptiometry (DXA) scans is the “gold standard” for the diagnosis of osteoporosis. However, limited availability and high cost associated with performing these scans warrant alternative methods to screen for osteoporosis risk and refer the high risk subjects for the DXA scanning. OBJECTIVES: To assess the diagnostic performance of 4 internationally validated tools [Simple Calculated Osteoporosis Risk Estimation(SCORE), Age Bulk One or Never Estrogen (ABONE), Osteoporosis Risk Assessment Instrument (ORAI) and Osteoporosis Self-Assessment Tool for Asians(OSTA)] for the diagnosis of osteoporosis in rural south Indian postmenopausal women. To assess the utility of FRAX® (Fracture Risk Assessment Tool) and calcaneal QUS (Quantitative Ultrasound) in predicting risk of osteoporosis. MATERIALS AND METHODS: It was a cross-sectional study conducted over 18 month period involving 2108 ambulatory postmenopausal women from a rural community in Vellore district of southern India. All of them were assessed with SCORE, FRAX®, ABONE, ORAI and OSTA tools. BMD was estimated by DXA scan (Hologic Discovery QDR 4500-W) at femoral neck and lumbar spine. QUS was performed in 850 subjects. Sensitivity and specificity were calculated for the risk assessment tools and QUS for predicting the osteoporosis at femoral neck (T-score ≤-2.5). Receiver Operating Characteristic (ROC) curve was constructed for each tool and for QUS and the area under the curve (AUC) was calculated.
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RESULTS: The percentage of women with femoral neck osteoporosis was 27%.The sensitivities of SCORE, FRAXÂŽ,ABONE,ORAI and OSTA were 97,34,91,85.7,87.9% and specificities were 20.6, 94.7, 33.5, 40.6 and 43.6% respectively for the diagnosis of femoral neck osteoporosis. When ROCs were constructed, the area under curve(AUC) was good only for SCORE(0.806) and the performance of rest were under fair category(0.714-0.766). CONCLUSION: In our large cohort of rural postmenopausal women, SCORE screening tool was found to be useful with good sensitivity and good AUC for femoral neck osteoporosis. There was a significant trade off seen between sensitivity and specificity for most of the screening tools( a high sensitivity and a low specificity) while FRAXÂŽ assessment at hip had higher specificity and suboptimal sensitivity. A145
EVALUATION OF HUMORAL IMMUNITY IN BILATERAL BRONCHIECTASIS WITH NO APPARENT AETIOLOGY Dr Rohit K O, Dr Balamugesh T, MD Tuberculosis and Respiratory Medicine INTRODUCTION: Infectious causes continue to be the leading aetiology in developing countries like India. Among non - infectious bronchiectasis cases, majority may not have a definite aetiology even after extensive evaluation. Immunodeficiency along with Immunoglobulin G subtype deficiency is found in a significant number of patients. In India immunological causes of bronchiectasis is not well studied. OBJECTIVES: To evaluate of humoral immunity in patients with bilateral bronchiectasis by quantitative assessment of Immunoglobulin (Ig) G subtypes, IgG, IgM, IgE & IgA levels. To evaluate Allergic Broncho pulmonary Aspergillosis by Aspergillus specific IgE assay in bronchiectasis. METHOD: This is an observational study done in diagnosed cases of non-tuberculous bilateral bronchiectasis. Humoral immunity was assessed through quantitative analysis of Immunoglobulins (IgG, IgM, IgE, IgA) and IgG subtypes. Clinical and radiological evaluation for other common causes and routine bronchiectasis work also was done.
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RESULTS: Among the 158 cases evaluated majority were young and middle aged males. Immunoglobulin deficiency was found in 16.4% cases with selective IgM deficiency was the most common. IgG subtype deficiency was found in 5% of patients. 3% cases were diagnosed to have ABPA. ANA and Rheumatoid factor was positive in 8.8% and 5.7% of patients respectively. Other causes were Kartagener syndrome (5), Cystic fibrosis (3) and Young syndrome (2). In 52% of patients no specific aetiology could be identified. CONCLUSION: Bronchiectasis needs proper evaluation and clinical assessment to diagnose the specific aetiology. Immunoglobulin deficiency including IgG subtype deficiency needs to be evaluated if there is no direct evidence for any definite aetiology. Keywords: IgG subtypes, Immunodeficiency, bronchiectasis, ABPA, immunoglobulin, Kartagener syndrome A146
THE ROLE OF ULTRASONOGRAPHY IN THE NON-INVASIVE ASSESSMENT OF UPPER AIRWAY FOR DECANNULATING TRACHEOSTOMY IN PATIENTS WITH ACQUIRED BRAIN INJURY – A PILOT STUDY Samuel Barnabas Sikha, Physical Medicine and Rehabilitation Dr Judy Ann John BACKGROUND: In patients with acquired brain injury who are on prolonged tracheostomy tube for airway management, decannulation is one of the steps in rehabilitation. Endoscopy is used to assess vocal cord mobility and airway prior to decannulation. Ultrasonography is a non-invasive test used widely for varied applications. The present study evaluated role of ultrasonography in the assessment of airway prior to decannulation. METHODS: Patients with acquired brain injury were screened. Inclusion criteria: Age 18 to 70 years, capping of tracheostomy for ≥ 24 hour with SpO2 ≥ 90%. Exclusion criteria: Pregnant women, patients on mechanical ventilation, active chest infection, non co-operative patients. Participants, who fulfilled the criteria and gave a valid consent, airway was assessed by ultrasonography. Within 72 hours post-ultrasonography, airway was assessed by radiography of the neck and later by endoscopy.
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STATISTICS: It was a pilot study. Sample size was 24. For categorical data, the frequency and percentage was presented. Further the Chi-square and Fisher exact tests were done to evaluate association. All statistical analysis was performed using SPSS software version 16.0 RESULTS: Out of 30 patients screened 24 were included. Vocal cord assessment by ultrasonography revealed a sensitivity of 81.25% and specificity of 87.5%. A statistically significant association between vocal cord mobility as assessed by ultrasonography and decannulation was observed (p value 0.002). A statistically significant association was observed between vocal cord mobility on ultrasonography and aspiration on endoscopy (p value 0.01). CONCLUSION: The observations noted suggest ultrasonography alone may be used to assess vocal cord mobility and airway in centers with either lack of infrastructure to perform an endoscopy. A trial with a larger sample size is required prior to application of these results to a larger population.
A147
COMPARISON OF STANDARD OUTPATIENT SCREENING TOOLS AND NERVE CONDUCTION STUDIES FOR THE DIAGNOSIS OF DIABETIC PERIPHERAL Dr. Saraswathi Ramanathan, Dr. Raji Thomas, Professor and Head, Department of PMR. For MD Medical specialty, PG, for Oral Presentation INTRODUCTION: Diabetic peripheral neuropathy(DPN) is a common complication of diabetes mellitus, leading to foot ulcers, gangrene and amputation. Reported prevalence of DPN ranges from 10-90%, due to differences in screening tools and gold standard used. This study aims to compare various outpatient screening tools and nerve conduction studies(NCS) to diagnose DPN. OBJECTIVES: 1. To study occurrence of DPN based on standard outpatient clinical tools and NCS. 2. To compare results of biothesiometry, Semmes Weinstein monofilament(SWMF) testing, NCS and MNSI (Michigan Neuropathy Screening Instrument). 3. To study sensitivities and specificities of the above screening tools, sural radial amplitude ratio (SRAR) and minimal F wave latency, using NCS as gold standard.
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METHODS: In a cross sectional observational study, on 48 patients with type 2 diabetes, excluding patients with ulcers, amputations and other causes of neuropathy. MNSI, biothesiometry, SWMF and NCS including F waves and SRAR calculation were done and occurrence of DPN calculated. Results of the above were compared using Chi square test and diagnostic accuracies were calculated taking NCS as gold standard. RESULTS AND CONCLUSIONS: Occurrence of DPN was 29.1%, 56.25%, 41.66% and 8.3% based on NCS, biothesiometry, MNSI and SWMF respectively. Clinical neuropathy according to MNSI was significantly related to NCS (p=0.041), SWMF (p=0.013) and biothesiometry (p=0.001). MNSI, biothesiometry, SWMF, SRAR and minimal F wave latency had a sensitivity of 64.3%, 78.6%, 14.3%, 100% and 78.6% and specificity of 67.6%, 52.9%, 95.1%, 20% and 67.6% respectively, with reference to NCS. NCS, though considered the gold standard for DPN diagnosis, is cumbersome, time consuming, painful and needs expertise. Biothesiometry, SRAR and F wave together had a sensitivity and specificity of 71.4% and 91.2% respectively. Hence, combination of these three evaluations, can help to limit the need for conventional NCS to selected cases. KEY WORDS: DPN, biothesiometry, NCS, SRAR, F wave
A148
YTTRIUM - 90 RADIOSYNOVIORTHESIS IN HAEMOPHILIC ARTHROPATHY Authors: Dr Saumya Sara Sunny, Dr Julie Hephzibah, Dr David Mathew, Dr Nylla Shanthly, Dr Regi Oommen Department: Nuclear Medicine, Christian Medical College, Vellore BACKGROUND: Radiosynoviorthesis utilises beta-emitting radionuclides injections into the joint space. It is minimally invasive and has no major side-effects. The beta emissions cause fibrosis of the chronic hypertrophic synovium in hemarthrosis thereby decreasing recurrent bleeding episodes. It also decreases the bone and cartilage damage, preventing arthropathy and related morbidity. In our institution, Yttrium – 90 (Y 90) radionuclide injections has been widely used since 2001. METHODS: Retrospective analysis of patients who have undergone the Y 90 synovectomy from January 2001 to January 2016 was done. Among them, all patients with a minimum follow up of 6 months were selected. The response in terms of decrease in the number of bleeding episodes, symptomatic improvement and the requirement of factor supplementation were evaluated.
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RESULTS: A total of 167 patients (243 joints) with haemophilia had undergone radiation synovectomy over the last 15 years. The age of patients ranged from 5 years to 43 years and included 113 male and 2 female patients. Total of 115 patients (155 joints) had a minimum follow up of 6 months after the first injection. Fifteen joints received a second injection. The treatment response was analysed based on the number of bleeding episodes and symptomatic improvement for the follow up period of minimum 6 months. The response was categorised as complete (nil bleeding episodes), partial (decrease in the number of the bleeding episodes) and no response. In 155 joints, 61 (39.3%) had complete response, 87 (56.5%) partial response and 7 (5%) no response. Fifteen joints received a second injection. Further follow up data was available at the end of two years for 89 joints. In 80 joints which had a single injection, 29 (36.25%) had complete response, 46 (57.5%) partial response and 5 (6.25%) no response. Of the 9 joints which received second injection, 4 had complete response and 5 had partial response. Factor supplementation was required in 33/155 joints (21.2%) during the entire period of follow up. Overall, following Yttrium synovectomy, benefit (complete or partial response) was seen in 148/155 joints (95.5%) upto 6 months which lasted in 84/89 joints (94.4%) upto 2 years. CONCLUSION: Radiosynoviorthesis is a simple, non-invasive and effective modality which considerably decreases the bleeding episodes in the haemophiliac joints. A significant number of patients were benefitted with a single injection. This treatment procedure also improves the quality of life remarkably. A149
IS CSF LACTATE USEFUL IN DIFFERENTIATING SCRUB TYPHUS MENINGITIS FROM ASEPTIC, BACTERIAL AND TUBERCULOUS MENINGITIS? Shalabh Arora, KPP Abhilash BACKGROUND: Scrub typhus, caused by Orientia tsutsugamushi, is increasingly being recognized as a cause of meningoencephalitis in endemic areas such as the Indian subcontinent. Prompt differentiation of scrub typhus meningitis from other forms of meningitides (bacterial, tuberculous and viral) may be challenging as most clinical and laboratory features are often overlapping.
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AIM: To evaluate the diagnostic performance of cerebrospinal fluid (CSF) lactate as a potential biomarker for differentiation of scrub typhus from other causes of acute meningitis. MATERIALS AND METHODS: In this prospective observational study, we recruited 113 consecutive patients admitted with acute meningitis at a university teaching hospital in India between August, 2014 and August, 2016. Patients were divided into four etiological groups – scrub typhus, bacterial tuberculous (TB) and viral. We analyzed and compared the CSF lactate in addition to clinical, laboratory and CSF parameters between these groups. The diagnostic accuracy of CSF lactate was assessed using receiver operating characteristic (ROC) curve. RESULTS: 33 cases of scrub typhus, 26 cases of bacterial meningitis, 26 cases of TB meningitis and 28 cases of viral meningitis were included in the analysis. CSF lactate levels were significantly different in scrub (3.52 ± 1.87 mmol/l) vs. bacterial (7.98 ± 6.04 mmol/l), tuberculous (5.75 ± 2.67 mmol/l) and aseptic (2.63 ± 0.93 mmol/l) meningitis (p<0.001). ROC curve analysis showed that a CSF lactate cut-off point of 2.9 mmol/l had a sensitivity of 52% (95% CI 34-69%), specificity of 68% (95% CI 48-84%), positive predictive value of 65% (95% CI 44-83%) and negative predictive value of 54% (95% CI 37-71%) for differentiation of scrub typhus from viral meningitis. Other CSF parameters (CSF white cell counts, protein and glucose) were also significantly different between the groups (p<0.05 for all comparisons). CONCLUSION: Our findings suggest that CSF lactate is a rapid, reliable and cost-effective test for the differential diagnosis of various CNS infections; and should be used in combination with conventional CSF parameters in the initial diagnostic work-up of acute meningitis. KEYWORDS: Scrub typhus, Meningitis, Meningoencephalitis, Lactic acid, CSF Lactate
A150 LONG TERM EFFECTS OF HIGH BIRTH WEIGHT ON CHILDHOOD HEALTH STATUS IN SOUTH INDIA Ahikam Devadason J1, Annarani Jose1, Anu Anna Binny1, Arjun Ambat1, Deepa Susan Thomas1, Divya Bennet1, Julie Jacob1, Namrata Mathew1, Rahul Jaic Sam1, Rebecca Mridula Singh1,
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Thomas Cherian1, Uplabdhi Dan1, Karun Saathveeg Sam1, Pottipad Rejoice1, Dr Martina Shalini2, Dr Kanagalakshmi3, Dr. Biswajit Paul4, Dr Jasmin Prasad5. Departments and Institution: 1MBBS Students 2PG Registrar, 3Assistant professor, 4Assosciate professor, 5Professor, Community Medicine, CMC Vellore. BACKGROUND: Childhood overweight is an emerging issue in India. A recent study in Chennai among the school going children and adolescents showed 15.45% prevalence of obesity.But there are no studies in India to prove the association between high birth weight and childhood overweight. So this study was carried out to bridge this knowledge gap. AIM: To determine the association between high birth weight and childhood overweight, developmental delay and chronic morbidity and proportion of these variants in high birth weight babies compared to normal weight babies of 6-10 years in Kaniyambadi block . METHODS: This non-concurrent cohort study was carried out among the households with children of 6- 10 years in Kaniyambadi block. Details regarding attainment of developmental milestones, mental development and anthropometry were collected after obtaining informed consent. Data collected was entered in Epidata and analyzed with SPSS. RESULTS AND CONCLUSION: Out of the 144 children assessed, 75% (N=9) among the overweight children and 33.3% (N=44) among the non-overweight children had high birth weight with relative ratio of 5.15. [p value: .009 and CI : 1.46-18.20]. 83.3% (n=10) of the overweight children but only 41.7% (n=53) of the non-overweight children used bus and other motorized vehicle to travel to school. High birth weight did not have any bearing on the intellectual development of the child. Thus, high birth weight is a definite risk factor in becoming overweight in childhood. A151
VITAMIN B12 DEFICIENCY: DO ACID SUPPRESSING MEDICATIONS HAVE A ROLE TO PLAY? A CROSS SECTIONAL STUDY IN A TERTIARY CARE SETTING IN SOUTH INDIA Arunava Saha1, Ramya I2 1Medical student (MBBS), Christian Medical College, Vellore, 2 Department of Medicine, Christian Medical College, Vellore BACKGROUND: Vitamin B12 deficiency is a relatively common but understudied problem worldwide. The only source being animal protein, and dependent on the stomach acids for absorption, people are
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prone to develop deficiency, particularly those taking acid suppressing medications. Over the counter use of acid suppressing medications such as PPIs and H2 blockers is rampant in India, but no proper studies have been conducted to determine the prevalence and risk factors of Vitamin B12 deficiency amongst the population of South India. OBJECTIVES:   
To determine the prevalence of Vitamin B12 deficiency in the community. To determine the prevalence of use of acid suppressing medications, and its correlation, if any, to development of B12 deficiency. To determine the other factors implicated in developing Vitamin B12 deficiency such as vegetarian diet, use of other concomitant medications, over dosage of acid suppressing medications.
MATERIALS AND METHODS: It was a prospective study conducted by the aid of an interviewer administered structured questionnaire amongst patients presenting to Medicine OPD for whom serum Vitamin B12 levels were ordered. The test results were obtained from Clinical Biochemistry and the Electronic Health Records. RESULTS: A total of 250 patients were included in the study, out of which 118 had a positive history of use of acid suppressing medications (53 males and 65 females) and 132 (65 males and 67 females) did not have any history of consumption of such medications. A total of 38 patients had diagnosed serum Vitamin B12 deficiency (15.2%). Presence of Vitamin B12 deficiency had statistically significant associations with use of acid suppressing medications (OR=2.46), the weekly intake of the number of such drugs and overdosing of such drugs (OR=8.97). However, vegetarianism and use of concomitant medications did not have any statistically significant association. CONCLUSIONS: Use of acid suppressing medications is associated with development of Vitamin B12 deficiency. Over the counter usage of such drugs and overuse further worsen the problem. Awareness about the potential side effects and the need to avoid overusage of such drugs must be emphasized amongst the common masses, and adequate supplementation is warranted to avoid long term complications.
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A152
BABINSKI SIGN VERSUS FINGER AND FOOT TAPPING TESTS IN CLINICAL DETECTION OF CORTICOSPINAL TRACT LESIONS Authors: Dan Anna Teddy¹, Vedavati Bandyopadhyay ¹, AT Prabhakar², Visalakshi Jeyaseelan³, Vivek Mathew² 1-MBBS student, 2-Department of Neurological sciences, 3-Department of Statistics BACKGROUND: The Babinski sign is a well-known sign of corticospinal tract CST dysfunction and has been given lot of clinical significance in complete neurological examination. However its validity and reliability is variable and depends on clinical expertise¹,²,3. Slowness of finger and foot tapping are less well known signs of corticospinal tract lesions and there is limited literature on its reliability and validity in clinical detection of CST lesions4,5. In this study, we studied the utility of finger and foot tapping as opposed to Babinski’s sign in detecting CST (corticospinal tract) lesions. METHOD: In this cross sectional study, 3 groups of 125 members each with CST lesions, non-CST neurological illness and normal subjects respectively were examined by two medical students and a neurologist for Babinski sign and finger and foot tapping. Following this a complete neurological examination was done. The examiners were blinded to the allotment of groups. Neuroimaging and relevant clinical examination was considered to be the Gold standard for diagnosis of CST lesions. Finger tapping- subject asked to tap on a flat surface using index and middle finger alternately. Foot tapping- subject asked to tap on the floor using the forefoot while the heel remains in contact with the floor. The outcome measures were reliability and accuracy. Inter-observer reliability was measured using kappa statistic and accuracy was be measured by sensitivity and specificity. RESULTS: Of one hundred and twenty five patients with corticospinal tract lesions, 40 % had strokes, 22.4% mass lesions, 16 % cervical myelopathy, 19.2% non-structural lesions and 2.4% had thoracic myelopathy. The sensitivity for Babinski sign was 49.6% and specificity was 85.5%. The sensitivity for finger and foot tapping was 79.4% and specificity was 88.4%. The interobserver agreement between the medical students and the neurologist was greater for finger and foot tapping (Kappa = 0.83) when compared to Babinski sign (Kappa = 0.45). CONCLUSIONS:
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Finger and foot tapping is a valid and reliable test in the clinical diagnosis of corticospinal tract lesions. The reliability and validity of Babinski sign is variable and is dependent on clinical experience and hence its clinical value must not be over emphasized. A153
PLASMA DNA LEVELS AS DIAGNOSTIC BIOMARKER IN DEEP VEIN THROMBOSIS (DVT) MANARA SHRESTHA, DEPARTMENT OF VASCULAR SURGERY AND HEMATOLOGY AT THE CHRISTIAN MEDICAL COLLEGE, VELLORE INTRODUCTION: Despite a range of tests like d-dimer, venography and ultrasonography to diagnose deep vein thrombosis each has significant potential limitations. Clot formation involves fibrin, red cells, neutrophils and platelets in clot formation. These undergo nuclear membrane dissolution, chromatin de-condensation and cytolysis to release DNA into plasma. A simple blood test (plasma DNA) has tremendous potential applicability as adjunct for diagnosing deep vein thrombosis. MATERIALS AND METHODS: We assessed if plasma DNA levels were elevated in patients with deep vein thrombosis as compared to normal controls using a prospective case-control design. This was done in the Department of Vascular Surgery, CMC Vellore from September 2014 to September 2016. All patients with acute DVT diagnosed by Duplex ultrasound were included in the study (n=100) which was compared with normal controls (n=100). Patients were excluded if the age was less than 18 years, unwilling to consent or pregnant at the time of study. Blood collected from the cases and controls was processed and stored in Haematology Lab. The serum samples were centrifuged at 3000g for 15 min, treated with 10mmol/L-EDTA (pH 8) immediately after centrifugation. Plasma was diluted (1:10; v: v) in phosphate-buffered saline. Diluted plasma was then mixed with 50 mL of PBS containing Sytox Green (final concentration 2 mM) to label DNA. Fluorescence was recorded using fluorometer with a 485 excitation and 538 emission filter set. Autofluorescence was considered as background and determined in samples mixed with PBS without Sytox Green. The amount of captured plasma DNA was proportional to the resulting color development and enabled quantification of levels by use of a calibration curve constructed with known amounts of DNA. Sample size had been calculated with a reported sensitivity and specificity of 81%. Statistical analysis was done to compare mean ,median and SD among two groups. RESULTS: The mean plasma DNA was 2019.00in patients with DVT as compared to732.00 in controls. The median and IQR (25th and 75th percentile) were used as the summary statistics, since the
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standard deviation was high in the test group. Mann Whitney U test / Rank sum test was used for comparison which revealed that the difference in the two groups was statistically significant (P <0.001). CONCLUSION: Plasma DNA is elevated in patients with DVT. It may have a role as an adjunct diagnostic test with utility in patients for whom a duplex scan cannot be performed. The presence of plasma DNA in patients with DVT also points to a possible role of neutrophils in the etiopathogenesis of DVT. A154
EFFICACY OF PROGRESSIVE MUSCLE RELAXATION ON ANXIETY, FATIGUE AND QUALITY OF SLEEP AMONG CANCER PATIENTS UNDERGOING RADIATION THERAPY Anitha L, Shirley David, Ilavarasi Jesudoss, Selvamani B, Bijesh Yadev Community Health Nursing, College of Nursing, Christian Medical College, Vellore BACKGROUND: Anxiety, fatigue and Sleep problems are highly prevalent in cancer patients undergoing radiation therapy. Progressive muscle relaxation is a promising approach in reducing the anxiety, fatigue and increasing the sleep quality associated with cancer and its treatment. AIM: The aim of this study is to investigate the efficacy of progressive muscle relaxation on anxiety, fatigue and quality of sleep among cancer patients undergoing radiation therapy. METHODS: A quasi experimental design was adopted to assess the level of anxiety, fatigue and quality of sleep before and after progressive muscle relaxation between the experimental and control group. The study was conducted in the radiation therapy, outpatient department at the Christian Medical College, Vellore. A total of 75 subjects (35 in each group) were recruited by simple random technique who fulfilled the inclusion criteria. The instruments used for data collection included Zung Self-rating Anxiety Scale (SAS), Functional Assessment of Chronic Illness TherapyFatigue Scale (FACIT-FS), Pittsburgh Insomnia Rating Scale (PIRS). Progressive muscle relaxation was given to the experimental group, but not to the control group. The efficacy of progressive muscle relaxation was measured after 7 days of the treatment. RESULTS:
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The progressive muscle relaxation significantly reduced anxiety, fatigue and improved quality of sleep in the experimental group than in the control group (p<.001 respectively). The study revealed that there is a weak positive correlation between anxiety and fatigue, anxiety and quality of sleep, fatigue and quality of sleep (r=0.413, p<.001; r=0.483, p<.001; r= 0.412, p<.001 respectively). There is no significant association of anxiety, fatigue and quality of sleep with socio demographic and clinical variables. CONCLUSION: The findings indicated that progressive muscle relaxation would reduce anxiety, fatigue and improve quality of sleep among cancer patients undergoing radiation therapy. Keywords: Anxiety, fatigue, quality of sleep, progressive muscle relaxation, A155
EFFECTIVENESS OF BLUNT PRESSURE TECHNIQUE IN PAIN RESPONSE AND SATISFACTION AMONG PATIENTS RECEIVING INTRAMUSCULAR INJECTION Authors: Dinesh Kumar. S, Junior Lecturer, College of Nursing, CMC, Vellore. The Co-authors are - Mrs. Jasmin Anand, Professor, Mrs. Amala Rajan, Professor, College of Nursing, CMC, Vellore, Dr. Georgene Singh, Professor, Dept of Anesthesia, CMC, Vellore - Mr. Bijesh YAdav, Sr.Demonstrator, Dept of Biostatistics, CMC, Vellore BACKGROUND: Pain is an ageless universal phenomenon. It is considered to be the’ fifth vital sign’. There are about 16 million injections given per year worldwide. Pain originating from IM injection should not be underestimated, because a painful injection might incite severe fear of injection, which may lead a patient to delay seeking medical help. OBJECTIVE: The study was intended to determine the effectiveness of blunt pressure technique in pain response and satisfaction among patients receiving intramuscular injection. The association of pain and satisfaction with selected demographic and clinical variable and also the relationship between pain and satisfaction were explored. METHODOLOGY: Using a Quantitative approach, an experimental study with post test only design was undertaken for 6 weeks. Patients receiving intramuscular injection in the 24 hour injection room of emergency department were selected using consecutive sampling technique. The subjects were randomly allocated to control and experimental groups. Patients with infectious skin diseases, bleeding disorder, trauma and injury, cognitive impairment were excluded from the study. Control group received injection using traditional technique and experimental group received
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injection using blunt pressure technique where the intramuscular injection was given with the application of plastic oval disc over the skin with multiple blunt pins. Numeral Rating Scale and satisfaction questionnaire were used to collect the data.
RESULTS: The mean pain response in the standard technique was 3.15±1.44 and in the blunt pressure technique was 1.01±0.98. The difference in pain response was found to be statistically significant (p<0.000). It also identified that 58% subjects were highly satisfied with the intramuscular injection procedure and a weak negative correlation was seen between pain response and the satisfaction of the patients receiving intramuscular injection (ρ= -0.015). Pain was significantly associated with occupation of the subjects. CONCLUSION: Blunt pressure technique was found to be effective in reducing the pain response. Key words: Bluntpressure, Pain, Intramuscular injection A156
NURSES’ PERCEPTION TOWARDS CARE OF PATIENTS WITH COMFORT CARE ORDER CONTEXT: A patient with Comfort Care (Do-Not-Resuscitate) order receives all other care except cardiopulmonary resuscitation during a cardiac or respiratory arrest, yet there are studies indicating that care of patients is affected by the placement of this order. Nurses being the frontline caregivers have also shown to have different perception towards the order. OBJECTIVES: The study was aimed to assess the nurses’ perception towards Comfort Care order and to identify the relationship between nurses’ perception towards Comfort Care order with their demographic characteristics. METHODOLOGY: A descriptive approach was undertaken to assess the nurses’ perception towards Comfort Care order. A total of 271 nurses were selected using proportionate, random sampling method (lots method). The Perception Scale on Comfort Care order, a self administered questionnaire designed by the investigator was used to assess the nurses’ perception towards the order. RESULTS:
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The findings suggest that nurses have moderately favourable (50.6%) and favourable (49.4%) attitude towards care of patients with Comfort Care order. Nurses had differing views regarding minimization of mechanical ventilator, withdrawal of the order with improvement in condition and necessity of dialysis therapy. Majority of the nurses disagreed on high cost medical treatment (60.2%) and the use of aseptic technique (67.9%) for these patients. There was no significant association between nurses’ perception towards the order with their demographic characteristics. CONCLUSION: Nurses have moderately favourable attitude towards the order but they did differ in certain aspects of patient care. Further research has to be done to determine the barriers and rectify the discrepancies that follow with the order. KEYWORDS: Nurses, Perception, Comfort Care order A157 PREVALENCE OF ORAL PROBLEMS AMONG CLIENTS WITH TYPE II DIABETES MELLITUS (TYPE II DM) AND EFFECTIVENESS OF VIDEO ASSISTED TEACHING (VAT) ON KNOWLEDGE, ATTITUDE AND PRACTICE(KAP) ON ORAL CARE AMONG THE TYPE II DM Irene Dorathy, Rajeswari Siva, Suseela John, Rabin Chacko, Tunny Sebastian Community Health Nursing, College of Nursing, Christian Medical College, Vellore BACKGROUND: Oral problem is the sixth complication of Diabetes Mellitus as it is more prevalent in them. But the awareness about oral health is very poor when compared to the knowledge about other complications of Diabetes mellitus. OBJECTIVE: The main objective of this study was to assess the prevalence of oral problems and to assess the effectiveness of a Video Assisted Teaching on the Knowledge, Attitude and Practice on oral care among the Type II DM. METHODS: A pre experimental study was conducted among 150 clients with type II diabetes mellitus in the selected urban area of Vellore district. Oral examination was done for 150 samples to assess the prevalence of oral problems and VAT on oral care was administered to 50 samples among them and the sample were selected using simple random technique(computer generated number). Questionnaire prepared by the investigator was used to assess the KAP on oral care before and after the VAT. Chi square analysis was used to find out the association between the selected demographic variables, clinical variables and oral problems, Knowledge attitude and practice. Wilcoxon signed rank test was used to see the difference in KAP before and after VAT. Spearman’s correlation coefficient was used to find relationship between knowledge, attitude and practice.
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RESULTS: The prevalence of periodontitis was high (64.7%) among the Type II Diabetes Mellitus and there was less awareness about oral care. Only 28% of them had known about the oral problems in diabetes mellitus. There was also significant difference in the knowledge, attitude and practice (p<0.001) on oral care after the Video assisted teaching which signifies the effectiveness of Video assisted teaching.
CONCLUSION: Health education can improve the oral health of the clients with Diabetes Mellitus which in turn will help them keep their blood sugars under control. Key Words: Oral problems, Periodontitis, Knowledge, attitude and Practice regarding oral care of Type II DM, Video Assisted Teaching. A158
RISK FACTORS FOR TESTICULAR CANCER, KNOWLEDGE, ATTITUDE AND PRACTICE REGARDING TESTICULAR SELF-EXAMINATION BACKGROUND: Testicular cancer is the most commonly occurring cancer among young adult males of 15 to 35 years and India has one of the lowest prevalence rates. TC is often diagnosed late. The aim of the study is to assess the risk factors for TC and the knowledge, attitude and practice of men regarding TSE METHODOLOGY: Using a Quantitative approach, a descriptive study was undertaken to perform the study for 6 weeks period. Self-administered questionnaires and systematic random technique was used to collect data from 230 men in selected areas of CMC, Vellore. RESULTS: The participants were mostly in the 26-35 years of age range (51.7%) and majority of them were married (60.6%) and Hindus (56.5%). Among the subjects 68.2% had one or more risk factors for TC. Most of the participants had inadequate knowledge (60.4%), favorable attitude (60.9%) and inadequate practice (96.1%) of TSE. There was statistically significant association between knowledge, attitude and practice of TSE with selected demographic variables (p<0.05). There was positive correlation between knowledge and attitude (r = 0.680), knowledge and practice (r = 0.402) and attitude and practice (r =0.409) of TSE (p < 0.01). CONCLUSION:
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Men have inadequate knowledge regarding TC and TSE. Findings show that having good knowledge and attitude about TSE was associated with performing TSE. Implications for practice are that health care providers should scale-up health education about TSE to empower young adult males with knowledge and skills required for early cancer detective practices. Key words: Testicular Cancer, Testicular self-examination (TSE)
A159
SLEEP QUALITY, PHYSICAL, AND PSYCHOLOGICAL OUTCOMES IN NURSES WITH LOW BACK PAIN FROM A TERTIARY HOSPITAL, SOUTH INDIA Emmanuel, N. M.1, Ezhilarasu, P. 2 1,2Department of Continuing Nursing Education & Research, College of Nursing, Christian Medical College, Vellore, India INTRODUCTION: Low back pain (LBP) affects 80% of the population globally. In India, the prevalence of LBP among nurses is reported to be 66%1. Evidence suggests that chronic LBP is associated with functional disability, anxiety, and depression. Poor sleep quality also significantly contributes to functional disability, anxiety, and depression. PURPOSE/AIM: The purpose of the study was to assess the sleep quality of nurses with low back pain in a tertiary care setting, South India and to determine the relationship of sleep quality with the physical and psychological parameters such as pain intensity, functional disability, anxiety, and depression. MATERIALS AND METHODS: A descriptive cross-sectional study design was adopted. All the nurses working in main hospital, willing to participate in the study, and available during the data collection period were screened for LBP. Among the nurses with LBP, 193 subjects were selected using systematic random sampling technique. Study was approved by the Institutional Review Board, permissions were obtained from the Nursing Superintendent of the hospital, and informed written consent was obtained from the subjects. Subjects were asked to complete the following questionnaires: Pittsburgh Sleep Quality Index (PSQI), Short-form McGill Pain Questionnaire (SFMP), Oswestry Low Back Pain Disability Questionnaire (ODI), Zung Self-rating Anxiety (ZSA) and Depression (ZSD) scales. Descriptive and inferential statistics such as frequency, mean, standard deviation, and Pearson’s correlation were used for data analysis. RESULTS: Among 1284 nurses screened, 686 (53.4%) had LBP. Of the 193 nurses included in the study 68.4% of the nurses had good quality of sleep. Majority of the subjects had minimal disability
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(68.4%), moderate pain (81.3%), and normal anxiety (56.3%) and depression (91.7%) levels. The average scores of the outcomes were as follows: PSOI: 4.32+2.8; SFMP: 1.6+1.2; ODI: 8.0+7.0; ZSA: 34.7+7.7; ZSD: 36.5+9.6. There was a significant positive correlation between sleep quality and pain intensity (r=.355, p<.01), disability (r=.376, p<.01), anxiety (r=.297, p<.01), and depression (r=.233, p<.001) indicating that poor sleep quality will increase the pain perception, level of disability, anxiety, and depression. Improving sleep quality will decrease the physical and psychological manifestations of patients with low back pain and hence improve the quality of life of nurses with LBP.
CONCLUSION(S): Further research is required to study the effectiveness of good sleep quality on the physical and psychological outcomes. Sleep quality should be considered as one of the outcome measures while treating patients with LBP. KEYWORDS: Low back pain, nurses, sleep quality, pain, disability, anxiety, depression. A160 PARENTING STRESS AND PREVALENCE OF COMMON MENTAL DISORDERS AMONG PARENTS OF CHILDREN AND ADOLESCENTS WITH PSYCHIATRIC DISORDERS *Ms. Mythily Vandana S. Charles, M.Sc. (N) **Mrs. Helen Sujatha Charles, M.Sc. (N), M. Phil ***Dr. Priya Mary Mammen, D.N.B (Psychiatry) BACKGROUND: Parents of children with psychiatric disorders are at risk for experiencing high levels of parenting stress which can be detrimental to their psychological wellbeing. Little research has focused on assessing the prevalence of Common Mental Disorders among parents of children with psychiatric disorders in India. OBJECTIVE: To assess the prevalence of Common Mental Disorders and the levels of parenting stress among parents of children with psychiatric disorders, and the association between parenting stress, Common Mental Disorders and socio-demographic and clinical variables. METHODOLOGY: Ninety subjects attending the outpatient department of Child and Adolescent Psychiatry unit at the Department of Psychiatry, CMC, Vellore, were selected using consecutive sampling technique. The subjects were administered the Parental Stress Scale (PSS) to assess levels of
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parenting stress and the Revised Clinical Interview Schedule (CIS-R) to assess the presence of a Common Mental disorder. RESULTS: 51.1% of the parents had low levels of parenting stress. Prevalence of Common Mental Disorders among the parents was 13.3%. Mixed Anxiety Depressive disorder was the most common presentation in 7.8% of the parents. There was a significant association between levels of parenting stress and Common Mental Disorders (p=0.002). There was a significant association between levels of parenting stress, level of education of the parents (p<0.001), duration of patient’s psychiatric illness (p=0.019), duration of the patient’s treatment (p=0.010) and the type of psychiatric disorder (p=0.008). There was a significant association between Common Mental Disorders, occupation of the parent (p=0.039), socio-economic status (p=0.023), age of onset of illness in the patient (p=0.047) and number of hospitalizations of the patient (p=0.049). CONCLUSION: Though levels of parenting stress and prevalence of Common Mental Disorders have been identified to be lower in this study population, the findings of the study can assist nurses in understanding parenting stress and in promoting the mental health of the parents. Key words: Parents, Parenting stress, Common mental disorders A161
EFFECTIVENESS OF SIMULATION BASED TEACHING PROGRAM ON KNOWLEDGE AND SKILL OF NURSING PERSONNEL ON NEONATAL RESUSCITATION Authors: Pamila S. Selvi, MSc (N), Dorathy D, MSc (N), Anil Kuruvilla, MD Obstetrics & Gynecology Department, Christian Medical College, Vellore, Tamilnadu, India BACKGROUND: Neonatal Resuscitation is an important aspect while caring for new born babies. Nurses who care for new born babies must possess knowledge and skill regarding neonatal resuscitation so as to initiate resuscitation at the bedside to save the life of the baby and prevent complications.Neonatal Resuscitation program is a widely adopted training program in the world and is required for nurses who attend deliveries, working in maternity department and places where new born babies are being handled. Neonatal Resuscitation requires coordination and cooperation among all providers; however, a lack of leadership and teamwork during resuscitation often associated with a lack of confidence. Current resuscitation guidelines recommend the use of simulation-based education as an instructional methodology to improve patient safety and health. Every delivery warrants for at least one person to be present who is skilled in neonatal resuscitation and has responsibility for only the new born baby (AHA, 2010). Approximately 60 seconds (“The Golden Minute”) are allotted in Neonatal Resuscitation for
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completing the initial steps, re-evaluating and beginning ventilation if required. Using traditional static classroom learning methods to teach neonatal resuscitation is no longer adequate. Learners are not prepared to work in dynamic complex environments without additional training. Although high-tech simulators are exciting, to date most advances in simulation have been made through low-fidelity, low-cost approaches. This is important because simulation has tremendous potential to be used globally, removing the patient from the healthcare practitioner's learning curve and improving patient safety.
AIM: This study was designed to assess the effectiveness of simulation based teaching program on knowledge and skill of nursing personnel on neonatal resuscitation using a low fidelity simulator METHODS: A pre experimental (one group pre-test post-test) design was employed to test the research hypothesis using a sample of 52 nursing personnel. Knowledge and skill was assessed using a self-administered questionnaire and observation checklist respectively. Comparisons were analyzed with chisquare RESULTS: The study reveals that there is a significant increase in knowledge (p<0.001) and skill (p<0.001) of nursing personnel in the post-test. Their mean scores (out of 52) regarding knowledge were 12.00 (SD 3.68) (pre-test), 18.4(SD 3.41) (post-test), regarding skill their mean scores were 5.40 (SD 3.16) (pre-test), 14.96 (SD 2.82) (post-test). There is a strong positive correlation between the knowledge and skill of the nursing personnel during pre-test and post-test (r=0.599, p<0.001 and r=0.448, p=0.001 respectively). Data revealed that there is no significant relationship between knowledge and demographic variables whereas there is a significant association of skill and demographic variables (current area of work (p<0.011) and place of education (p<0.034). CONCLUSION: This study recommends that teaching should be supplemented with additional, ongoing practice and educators must provide creative strategies that assist acquisition of knowledge and skill. Overall, participants expressed that simulation based teaching benefited them. A162
AWARENESS AND PRACTICES OF FOOT CARE AND FOOTWEAR AMONG DIABETIC PATIENTS WITH HIGH RISK FOOT BACKGROUND:
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In India, Diabetic foot complications are responsible for high morbidity and mortality. An estimated 50% of non-traumatic amputations are performed in Diabetics. Inappropriate footwear and improper foot care are thought to be the major contributors for high risk foot. Nurses play a vital role in educating these patients. OBJECTIVES: To assess the awareness and practices of foot care and footwear among Diabetic patients with high risk foot, also its association with demographic and clinical variables. METHODOLOGY: A quantitative descriptive design was used. The study was conducted at CMCH, Vellore. Simple random sampling was used to screen the diabetic patients with high risk foot using SIGN risk stratification. Consecutive sampling was used to assess the awareness and practices of foot care and footwear. Data was collected using an interviewer guided questionnaire. Data analysis was done using SPSS. Descriptive and inferential statistics was used to interpret the data. RESULTS: 47.9% of the subjects had inadequate foot care awareness, 60% had inadequate footwear awareness, 71.4% had inadequate foot care practices and 70.5% had inadequate footwear practices. There was a positive relationship between foot care awareness and foot care practices (r =0.480 at p < 0.01). Increase in footwear awareness correlated with corresponding increase in adequacy of practices (r =0.621 at p < 0.01). There was a strong association of foot care awareness (p=0.049) and foot care practices (0.046) with the educational status of the subjects. CONCLUSION: Majority of the subjects had inadequate awareness and practices of foot care and footwear. Nurses need to educate these patients and identify those with high risk foot status and systematically guide them. Key words: Foot care and footwear awareness, foot care and footwear practices, high risk foot
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NOVEL STRETCH SENSOR TO MEASURE CALF VENOUS HEMODYNAMICS AUTHORS – Albert A Kota 1, Syrpailyne Wankar 2, Dheepak Selvaraj1 1Department of Vascular Surgery 2Department of Bioengineering Christian medical college and hospital, Vellore OBJECTIVE: To describe a novel stretch sensor used as a strain gauze plethysmograph to measure calf pump venous hemodynamics.
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METHODS: Three in-house semiconductor strain stretch sensors have been used to form a load cell with an elastic band to convert physiological movement to a proportional tension. Using CMC data acquisition software hemodynamics were recorded. RESULTS: Venous volume, venous filling index, ejection fraction and residual venous volume were calculated in 5 subjects.
CONCLUSIONS: A simple non-invasive stretch sensor has been developed as a strain gauze plethysmograph to provide quantitative information on the calf venous hemodynamics.
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HAM (HUMAN AMNIOTIC MEMBRANE) VERSUS COLLAGEN IN TREATMENT OF SUPERFICIAL SECOND DEGREE BURNS IN CHILDREN
THE
AUTHORS: Aureen Ruby D’Cunha, Susan Jehangir, Reju Joseph Thomas, Grace Rebekah DEPARTMENT & INSTITUTION: Department of Paediatric Surgery, Christian Medical College, Vellore
BACKGROUND: To date no single ideal wound cover has been described for burns wounds. HAM was the first biological dressing used owing to its versatility. Collagen sheets are the standard of care and are available sterile off the shelf. AIMS: A comparative study to assess the time to healing and scarring when using (i) HAM and (ii) Collagen sheet in the topical treatment of superficial second degree burns in children. METHODS: A prospective controlled clinical trial on 43 children with superficial second degree scald burns treated in Paediatric Surgery was performed. HAM and collagen were applied to different halves of each wound and they were followed up by serial photographs till complete wound healing and at 3 and 6 months. RESULTS:
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Mean age at presentation was 1.5years. The median time to presentation was 3 hours and time to dressing application was 3.5hours. Minor wound infections were encountered in 8 children of whom 3 children required removal of the dressing. There were no significant differences in the time taken to healing. HAM produced better scarring when compared with Collagen. CONCLUSIONS: HAM and Collagen provide a single application painless dressing for superficial second degree burns. HAM is cheaper and universally available. The rate of wound healing is comparable while HAM seems to produce a better scar.
A165 A PROSPECTIVE OBSERVATIONAL STUDY TO DETERMINE THE AETIOLOGY OF POSTMENOPAUSAL BLEEDING AND CORRELATION OF ENDOMETRIAL THICKNESS IN ENDOMETRIAL CARCINOMA IN OUR POPULATION Authors: Dr.Carolin Solomi.V., Dr.Jessie Lionel, Dr. Elsy Thomas, Anitha Dorairaj. Obstetrics and Gynaecology. Dr. Carolin Solomi.V. M.S Obstetrics and Gynaecology. Dr. Jessie Lionel. OBJECTIVE: 1. To determine the most common cause of postmenopausal bleeding (PMB) in our menopausal women. 2. To determine the correlation of endometrial thickness in endometrial carcinoma and to set a cut-off thickness. METHODS: This prospective observational study was conducted in Christian Medical College Hospital, Vellore between February 2016 to July 2016 in the department of Obstetrics and Gynaecology. We included all postmenopausal women who presented any time after one year of menopause with vaginal bleeding. Detailed history, clinical examination, per speculum and per vaginal examination was done systematically to evaluate the clinical diagnosis of postmenopausal bleeding. Details of the patient including her age, age of menarche, age of menopause, parity, body mass index, amount of bleeding, number of episodes of postmenopausal bleeding, associated co morbidities and any drug intake like hormone therapy, and anticoagulants are noted, following which, the diagnostic evaluation for postmenopausal bleeding is done by using transvaginal ultra sonogram and the endometrial thickness was determined. Endometrial biopsy is done after ultrasound and the histopathological report was correlated. RESULTS:
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Total 144 patients were included in our study. Mean age of PMB was 56.6 years. Mean age of developing malignancy was 58.8 years when compared to 55.71 years in benign conditions which is statistically significant. Risk factors for endometrial malignancy like nulliparity, increasing BMI, medical co-morbidities like diabetes and hypertension had statistically significant correlation in our study. Other risk factors like, early menarche, late menopause, drug intake, family h/o malignancies did not show any association in our study. Based on the histopathological findings, atrophic endometrium constituted for 19.4%, endometrial polyps 16.66%, endometrial cancer 15.27%, cancer cervix 14.48%, endometrial hyperplasia 9.72%, ovarian cancers 4.16%, proliferative endometrium 2.08%, secretory endometrium 2.77% and others with no specific histopathological diagnosis 15.27%. Of the total pipelle sampling done, 7.3% had tissue inadequate for evaluation. In our study, 43.75% of women with postmenopausal bleeding had malignancies and 56.25% had benign conditions. The prevalence of endometrial cancer in our study population was 14.6% with 95% CI (9.3%-21.5%). By transvaginal ultrasound, endometrial thickness of 4mm was set as a cut-off thickness to discriminate women who are at risk for endometrial malignancies with a sensitivity of 96.97%, specificity of 15.5% and a negative predictive value of 92.3%.We also found that, the risk of developing endometrial cancer is increased five times when the endometrial thickness is >=4mm (Odds ratio 5.91). CONCLUSION: All women with postmenopausal bleeding should be evaluated even if it is the first episode. Transvaginal ultrasound and pipelle sampling still holds good for evaluation of PMB. In developing countries like India, cervical cancer evaluation should also be a part in evaluating PMB. Endometrial thickness of >=4mm correlates well with malignancy in Indian women too. Hence, women with endometrial thickness of <4mm need not have any other with invasive tests like endometrial biopsy, unless there is recurrent bleeding or ultrasound features suggestive of any abnormalities like adnexal mass.
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PEDICLED LATTISMUS DORSI FLAP IN HEAD AND NECK RECONSTRUCTION- A CASE SERIES Authors: Dr Abhijit Gundale ,Dr A J Tirkey,Dr Rajinikanth J. Departments and institution: Surgery Unit 1,CMC Vellore. BACKGROUND: Lattisimus Dorsi flap (LD flap), the first myocutaneous flap reported in the literature has been infrequently used in head and neck reconstructions. Easy to harvest, this flap can be raised simultaneously as a two-team approach with minimal added morbidity. Our case series report the technique, functional outcomes and post operative complications with utilizing LD flap in head and neck reconstruction.
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RESULT: Over a period of 12 months, LD flap was done for 12 patients. Tissue coverage was provided for eleven oral cavity cancer resections and one parotid skin defect. Out of those eleven cases one case was recurrent SCC of the buccal mucosa wherein option for standard regional flap was exhausted. Complete flap necrosis was seen in three cases while partial flap necrosis was seen in 2 cases. There were donor site morbidity issues in five patients. There was no delay in initiating adjuvant RT in any of these patients. CONCLUSION: Lattisimus dorsi myocutaneous flap is a viable alternative as a pedicled flap for head and neck reconstruction, especially as bipaddled flap in through and through buccal defects, where patients are unfit for long hours of surgery or those who can’t afford a free flap. Careful planning of the incision and taking precautions while tunneling the flap sub-pectorally can minimize the morbidity. A167
TO STUDY THE ROLE OF TRANSCUTANEOUS PARTIAL PRESSURE OF OXYGEN MEASUREMENT IN PATIENTS WITH CHRONIC VENOUS DISEASE Dr. Ludia John, General Surgery, MS General Surgery, Dr. Pranay Gaikwad and Dr. Sunil Agarwal OBJECTIVES: Primary Objective In patients with chronic venous disease C 4-6, – To measure transcutaneous partial pressure of oxygen in the involved limb. Secondary Objectives •
– To correlate clinical staging of chronic venous disease and TcpO2 levels. – To compare the TcpO2 levels in the involved limb and the normal limb. METHODS: a. Setting: Patients with the complaints of chronic venous disease presenting to vascular surgery were selected. Following informed consent and assent they were worked up for confirmation of diagnosis and ruling out other diagnosis. b. Participants: They were selected after assessment on the basis of the inclusion and exclusion criteria. •
Inclusion criteria – ~ Patients presenting with unilateral chronic venous disease (Clinical Stage 4-6).
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Exclusion criteria – ~ Presence of arterial disease ~ Auto immune condition like vasculitis ~ Presence of active infection ~ Pedal edema due to other causes (lymphedema, renal failure, hepatic The above mentioned factors were excluded because they affect the TcpO2 levels and give incorrect values. The healthy leg of the same patient was used as the control. c. Data Sources/measurement: • TcpO2 level in the diseased leg and normal leg was measured with the TcpO2 monitor TINA (Radiometer, Denmark) in vascular lab. • The values obtained in the diseased leg and the normal leg were be compared. •
RESULTS: The transcutaneous oxygen content is supposed to be a reflection of the microcirculatory state of the underlying tissue, both in health and disease. Its content or partial pressure should decrease with severe diseased state in CVD, with values being lowest in Stage C6 i.e. active venous ulcer. A higher TcPO2 would mean a better state of health of the tissue. The null hypothesis stated that TcPO2 does not reflect the microcirculation in CVD. Given below are the results of this study. Prevalence of chronic venous insufficiency is higher among females as seen in many population studies.(7,22) In this study of the total 96 patients included in the study, 85 were males (88.5 %) & 11 were females (11.5 %). Hence the prevalence of CVI in this study population was lesser in females and was higher in males. This study was conducted among patients presenting themselves to the clinic for treatment and is not representative of the Indian population. There were no Indian studies available for comparison. Prevalence of CVI was found to increase with age.(23) In our study 59.4% of patients were above the age of 40. The TcPO2 had a fair accuracy in detecting diseased state i.e. advanced stages of CVD (C4 to C6), when compared to the normal limb. The values were significantly lower in C5 and C6 disease, both in supine and dependent position. In the study conducted by Franzeck et al, TcPO2 was measured and correlated with videomicoscopy to look at the microvasculature. The mean of controls was 56.8 and the mean of the affected TcPO2 was 47.7. The difference was not significant and the p value was > 0.05. In our study TcPO2 was measured at the site of maximal change which would reflect the poor microcirculation internally. TcPO2 in controls was 32.05 and in the cases was 23.28. The difference was found to be statistically significant with a p value of .000. There was no co-relation with video microscopy. In a study conducted by Barnikol et al, where mean of 4 TcPO2 measurements was taken for each patient with C6 disease. The mean of the controls was 63.0 and mean of patients with C6 disease was 17.9. In our study the mean TcPO2 in C6 was 24.22 and in controls was 32.05. The difference was statistically significant in our study and the above mentioned study. The greater difference in the means in the study conducted by Barnikol et al, would be probably since there were 4 measurements taken around the ulcer and is more accurate that a single measurement. But
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even a single measurement at the site of greatest skin change was statistically significant as shown by our study. Two studies had recommended a cut-off value of 40 mm Hg to predict diseased state. In supine position, this value had a sensitivity of 95 percent, but a very low specificity of 20 percent. In dependent position this value had a sensitivity of approximately 50 percent with a specificity of 80 percent. A particular “cut-off” value could not be recommended as the increase in sensitivity came at the expense of specificity and a high false positive rate. The study also found that the TcPO2 were significantly lower in the supine position compared to dependent position, thus demonstrating the effect of limb position on TcPO2 values.
A168
A STUDY ON PREVALENCE OF VOIDING AND DEFECATORY DYSFUNCTION IN POSTMENOPAUSAL WOMEN WITH PELVIC ORGAN PROLAPSE Dr. Nanthini Saravanan1*, Dr. Lilly Varghese1, Dr. Vaibhav Londhe1, Dr. Nitin Kekre2, Dr. Aruna Kekre1* Dept. of Obstetrics and Gynaecology- Unit-II, Christian Medical College and Hospital, Vellore 632 004. Dept. of Urology- Unit-II, Christian Medical College and Hospital, Vellore -632 004. OBJECTIVE: The purpose of this study was to evaluate the prevalence of voiding and defecatory dysfunction in postmenopausal women with pelvic organ prolapse. STUDY DESIGN: This is a cross sectional study of Sixty post-menopausal women with pelvic organ prolapse of stage II or greater patients , admitted for surgery in Gynaecology department at CMC, Vellore between October 2015 to August 2016 were recruited ,Examined with POP-Q system to stages the prolapse and interviewed with validated questionnaire to evaluate LUTS and QOL and Defecatory symptoms. Pre- and post-operative uroflow and PVR were measured. In this study, voiding dysfunction was defined as Qmax <15ml/sec or PVR ≥100ml. Defecatory dysfunction was defined using CRADI-8 score (PFDI-20). The statistical analysis was done by using SPSS version 21 and P value < 0.05 was considered as statistically significant. RESULTS: The overall prevalence of voiding dysfunction in this study was 68% and the defecatory dysfunction was 60%.The higher stage of prolapse and anterior compartment had significant correlation with voiding dysfunction. Women with posterior compartment defect had more
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defecatory dysfunction with the odds ratio of 2.49 (95% CI=0.773-7.993). Stages of POP did not correlate with severity of LUTS and QOL. Pre-operative voiding dysfunction resolved post operatively in 93%, the P value <0.000 which was highly significant. The POP-Q points Ap and Bp were significantly higher in women with defecatory dysfunction (P = 0.02 and P = 0.04) . CONCLUSION: The prevalence of voiding and defecatory dysfunction in postmenopausal women with POP was 68% and 60% respectively. Points Ap and Bp of POP-Q stage had positive correlation with defecatory dysfunction. Pre-operative voiding dysfunction significantly resolved after vaginal hysterectomy and pelvic floor repair (P ≤ 0.000). Keywords: pelvic organ prolapse, voiding dysfunction, defecatory dysfunction, POP-Q stage. A169
PERINATAL OUTCOMES FOLLOWING ASSISTED TECHNOLOGY TREATMENT IN A TERTIARY CARE RETROSPECTIVE STUDY
REPRODUCTIVE HOSPITAL : A
AIM: To assess the perinatal outcomes following Assisted Reproductive Technology (ART) treatment performed in a tertiary care hospital in South India over a sixteen year period. BACKGROUND: Advances in Assisted Reproductive Technology, has led to the increase in complications like multiple pregnancies,increased operative interferences during delivery and adverse perinatal outcomes like increased perinatal mortality. Lack of ART birth registry in India and paucity of information pertaining to perinatal outcomes and congenital anomalies following ART pregnancies is a serious limitation. Therefore we conducted this study to assess the perinatal outcomes in ART pregnancies . MATERIAL AND METHODS: It was a retrospective study with the study period of 18 years from year 1996 to 2014. Total 1307 patients conceived following assisted reproductive technology . Data collected by chart reviews, e- mail and phone contacts was analysed using Windows SPSS software 15. MAIN OUTCOME MEASURES: 1. 2. 3. 4. 5. 6.
Total Pregnancies ( Pre- clinical and clinical pregnancies) Preterm and term deliveries Mode of delivery Multiple pregnancy rate Live births , still births, early neonatal deaths Birth- weight
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7. Congenital anomalies RESULTS: Out of total 1307 pregnancies 1157 were analyzed, rest were lost to follow up. 74.8% resulted in delivery; 10.1% in biochemical pregnancy, 12.1% in abortions and 2.5% in ectopic pregnancies. Out of total deliveries 57.9% resulted in singleton births, 27.9% in twins & 7.6% in triplet deliveries. Out of total 803 births 4 were stillborn and 26 had early neonatal deaths reaching perinatal mortality rate of 36.25%. Pre term delivery rate was 34.%. 17.8% had vaginal delivery, 3 % had operative vaginal delivery and 79.2 % had caesarean delivery. The rate of congenital malformation was 2.2%.
CONCLUSION: Assisted Reproductive Technology is an effective treatment but higher multiple pregnancy rates and increased Caesarean section rates is a concern. A170
STUDY OF THE PREOPERATIVE MARKERS IN PREDICTING LEAK IN BOWEL ANASTOMOSIS DR. SAMEER M D, GENERAL SURGERY, MS GENERAL SURGERY. SUKRIA NAYAK OBJECTIVES: The purpose of this study will be to identify patient, clinical and biochemical factors that may be associated with intestinal anastomotic leak following small and large bowel anastomosis. METHODS: This is a prospective observational, quality improvement study in a cohort of 100 patients undergoing small and large bowel resection in the Division of Surgery at Christian Medical College, Vellore. The outcome was to look for correlation of preoperative markers with anastomotic leak within 30 days of postoperative period. Some of the predictor variables were Age, ASA score, Hemoglobin, Albumin, Pre albumin, Preoperative diagnosis using Short Form General Health Survey. Univariate analysis was done to show the significant variables associated with anastomotic leak. Significant variables were analyzed using logistic regression model. The prognostic role of pre albumin for the anastomotic leak was assessed using ROC curve analysis. RESULTS:
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In our study, Leak rate was 21% (21/100). In univariate analysis, 6 factors were associated with anastomotic leak – Age >45 years, ASA score of II, Hemoglobin ≤ 9.0 gm/dl, Serum Albumin ≤ 3.0 gm/dl, Serum Pre-Albumin ≤ 20 mg/dl, Preoperative diagnosis of Malignancy. Of these variables, 4 were found to be independent predictors of anastomotic leak using logistic regression model. Age > 45 years (OR-23.2, 95% CI 2.3-237.6), ASA score of II (OR-6.6, 95% CI 1.3-32.4), Serum Pre-Albumin ≤ 20 mg/dl (OR-8.1, 95% CI 1.6-41.3), Malignancy (OR-6.6, 95% CI 1.0-42.1) KEY WORDS: Anastomotic leak, small and large bowel, preoperative factors, pre-albumin.
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A171
DO RADIAL SHOCKWAVES SAFELY MODULATE GROWTH AT THE PHYSIS? PRELIMINARY SHORT TERM OUTCOMES IN ORGAN CULTURE AND IMMATURE RABBITS Ramesh Sa,b, Zaman Fb, Sävendahl Lb, Madhuri Va a Paediatric Orthopaedics unit, Christian Medical College, Vellore, India b Department of Women's and Children's Health, Paediatric Endocrinology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden BACKGROUND: Shockwaves (SW) are being used in the treatment of musculoskeletal conditions. We explored the effect of radial SW on growth plate cartilage in a rat metatarsal and rabbit model. A positive or negative effect on growth could be harnessed for therapeutic growth modulation while no change establishes safety. MATERIAL AND METHOD: Organ culture: The middle three metatarsal bones were micro dissected from the hind paws of rat foetuses at 20 days of gestation. Following day, bones (n=15/group) received 500 impulses of SW: Group 1: 5Hz, 90mJ, Group 2: 5Hz, 120mJ, Group 3: 10Hz, 180mJ. The control group bones were untreated. Bone length was measured on day 0, 4, 7 and 14. Histology was performed at day 14. In vivo study: New Zealand white rabbits (n=3 each) received low dose of 1500 impulse, 5Hz, 90mJ, 4 times/month and high dose of 3000 impulse, 5Hz, 180mJ, thrice/month on the right distal femur, left being control. After one month, GPs were assessed by histomorphometry, immunostaining for PCNA (cell proliferation), COL-X (hypertrophy) and TUNEL (apoptosis). RESULTS: Metatarsal bone growth: A significant (P<0.05) increase in bone length was observed in high dose group (112 µm) when compared to control (94 µm). Histology revealed cell necrosis in high energy group. A significant increase in hypertrophic cell size was observed in group 2 (19.9 µm) and group 3 (17.22 µm) as compared to control (13.02 µm).
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RABBIT BONE GROWTH: Growth plate height increased in low (13.7%) and high dose (15.2%) group. Normalized to control, only high dose group had significant (P<0.05) increase in cell proliferation (69%). COLX secretion increased in low (25%) and high energy (36%) groups. Apoptosis was insignificant in articular cartilage (AC) and GP. Final bone length remained unchanged. CONCLUSION: Histological changes indicate that SW may potentially cause bone lengthening and confirms safety for articular surfaces. Further studies would confirm the effect on bone length at maturity. A172
FOCUSED PARATHYROIDECTOMY UNDER LOCAL ANAESTHESIA AND MILD SEDATION ADMINISTERED AND MONITORED BY SURGEON – A PROSPECTIVE EVALUATION OF SAFETY, SATISFACTION AND OUTCOMES AUTHOR’S NAME AND AFFILIATION: SEN S*, CHERIAN AJ*, RAMAKANT P*$, REKA K#, PAUL MJ*, ABRAHAM DT* *DEPARTMENT OF ENDOCRINE SURGERY, CMC VELLORE- 632004 # DEPARTMENT OF BIOSTATISTICS, CMC VELLORE-632004 $ NOW WORKING AT: KING GEORGE’S MEDICAL COLLEGE (KGMC), LUCKNOW INTRODUCTION: Focused parathyroidectomy is treatment of choice in PHPT due to single gland adenoma in patients with concordant imaging on parathyroid scintigraphy and ultrasound. To avoid delays due to lack of anaesthesia time, this can be performed under local anaesthesia (LA) in a select group of patients. MATERIALS AND METHODS: All consecutive patients with PHPT from Oct 2015 to July 2016, planned for focused parathyroidectomy, were evaluated for suitability to perform this procedure under LA after institutional ethics approval. If feasible, they were consented and outcomes were noted. OBSERVATION AND RESULTS: 24/46 underwent the procedure under LA with mild sedation. All patients had a biochemical cure in the immediate post operative period. 1/ 24 was converted to General Anaesthesia (GA) due to bleeding. 1/ 24 patient had voice change post operatively, 14 /24 had hypocalcaemia postoperatively requiring oral or intravenous calcium. The mean length of scar was 4.38 + 0.17 cm. The mean gland weight and maximum dimension were 2502.08 + 466 mg and 2.383+ 0.20 cm respectively. On Visual Analog Score (VAS), the mean score was 2.67+ 0.339and 1.83+ 0.197 in 1st and 2nd post operative day respectively.
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The mean ‘procedure’ and ‘operating’ times were 75.08 + 5.055 and 53.33+ 3.453 minutes respectively. The mean satisfaction score (1-5) with LA and surgery were 4.71+ 0.112 and 4.88 +0.069 respectively. CONCLUSIONS: Focused parathyroidectomy under LA could be monitored and performed safely by a surgeon ensuring both biochemical cure and adequate patient satisfaction for a select group of patients. KEYWORDS: PHPT- Primary Hyperparathyroidism, Focused parathyroidectomy, LA-Local Anaesthesia A173 CYTOGENETIC ANALYSIS OF PATIENTS WITH RECURRENT PREGNANCY LOSS: A RETROSPECTIVE STUDY OF 2000 CASES FROM A TERTIARY CARE HOSPITAL Singhal P1 ,Yuvrani S1, Kamath MS2, Aleyamma TK2, Mathews J3, Regi A3, Lionel J3, Danda S4, Srivastava VM1 1
Cytogenetics Unit, 2Reproductive Medicine Unit, 3Departments of Obstetrics and Gynaecology, 4 Department of Clinical Genetics, Christian Medical College, Vellore INTRODUCTION: Sporadic chromosomal anomalies are an important and untreatable cause of recurrent pregnancy losses (RPL) predominantly in the first trimester of gestation. Numerical or structural chromosomal rearrangements in gametes may be de novo or inherited and may lead to major genetic imbalance and fetal loss. OBJECTIVE: The objective of this study was to determine the spectrum and frequency of chromosomal abnormalities (CA) in individuals with a history of recurrent pregnancy loss (RPL). METHODS: This retrospective study evaluated the cytogenetic data of all the individuals with two or more consecutive pregnancy losses from 2001 to 2015, which included the karyotyping of the couples and molecular method like (FISH) Fluorescence In situ hybridisation wherever required. RESULTS: The study group consisted of 2014 patients (1055 males and 959 females).Males ranged in age from 25 to 57 years (median 29.8) and females from 19 to 45 years (median 25.7). CA were found in 93/2014 (4.6%) of total patients evaluated. Structural abnormalities (SA) were seen in 67 patients (72.1%) and numerical abnormalities (NA) in 26 patients (27.9%). The major groups of SA were balanced (50.5%) and Robertsonian translocations (~13%). Less common SA were inversions and marker chromosomes. The NA were mainly due to mosaicism for sex
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chromosome aneuploidies (26.9%). Heteromorphism including inversions of chromosome 9 which are considered to be normal variants were also seen in 0.9 % of patients. CONCLUSION: The frequency (4.6%) of CA among our patients with RPL is similar what has been reported in the literature. CA may cause RPL, infertility or birth of children with abnormal phenotypes. Therefore, it is important to perform cytogenetic analysis because it not only helps to predict the pregnancy outcome but also determine whether an abnormality is de novo or familial by screening siblings and other extended members of family, especially those who wish to conceive. This will enable physicians and families to make appropriate decisions for management of this very distressing condition. KEY WORDS: RPL, chromosomal abnormalities, translocations, aneuploidy. A174
THE INVERSION 16 IN ACUTE MYELOID LEUKEMIA. INTRODUCTION: Rearrangements of the core binding factor beta (CBFß) gene on chromosome 16, band q22 are associated with a good prognosis in acute myeloid leukemia (AML) . The inversion (16)(p13.1q22) is the typical abnormality in this group and results in the formation of a CBFß/MYH11 fusion gene .It accounts for ~ 4% of the AML-associated abnormalities and is usually associated with AML M4 with eosinophilia or M2 . Trisomy 22 is the most common secondary change . MATERIALS AND METHODS: G banded karyotypes of all patients with the inversion 16 seen in the Department of Haematology between January 2003 and December 2015 were correlated with blood and bone marrow findings. RESULTS: The inversion 16 accounted for 33/2487 (1.3 %) patients with AML. There were 27 adults and six children ranging from 1-58 years of age (median age 33); eighteen were females (55%). The median haemoglobin was 8.9g/dl (1.6-14.4 g/dl), the median WBC count, 51.9 × 109/L (range 1294.9 × 109/L) and the median platelet count, 27×109/L (range 6 -192 × 109/L). The FAB subtypes were AML M4 (twenty one), M2 (six), AML not otherwise characterized (three), JMML (one) and M1 (two). The bone marrow blast percentage ranged from 5-91%. Abnormal eosinophils were seen in ten patients with AML M4 and two with AML M2. The inversion 16 was solitary in 18 (55%), associated with a single additional abnormality in four (12%) and with two or more additional abnormalities in eleven (33%).The common additional abnormalities were trisomy 8 (nine patients), trisomy 22 (eight) and trisomy 9 (two).
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CONCLUSION: Our data is similar to the literature except for trisomy 8 being the most common secondary change. The inversion 16 can be overlooked unless the morphology of the metaphases is good. FISH analysis or molecular testing is helpful for confirmation of this abnormality, especially if the bone marrow shows myelomonocytic leukemia or abnormal eosinophils or if a solitary trisomy 22 is present. A175
DOES DAILY USE OF RESISTANT STARCH IN DIET REDUCE THE INCIDENCE AND SEVERITY OF ACUTE BOWEL SYMPTOMS IN PELVIC RADIOTHERAPY? A RANDOMIZED CONTROL TRIAL Balukrishna Sasidharan, Viswanathan P.N, Prasanna Samuel, Ramadass Balamurugan, Pugazhendhi Srinivasan, B.S. Ramakrishna, Christian Medical College, Vellore PURPOSE: The purpose of the study is to look at the benefit of administration of an oral prebiotic starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix. MATERIAL/METHODS: The study was conducted between 2011 and 2014 in 104 patients receiving radical chemoradiotherapy for carcinoma cervix. Patients were randomized to two arms receiving 30 gm of resistant starch or digestible starch on a daily basis through out the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. All of them underwent LDR brachytherapy of 30 Gy at completion of external beam radiotherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two randomized groups and analysed. Stool short chain fatty acid concentrations were measured at baseline at 2 nd and 4th week and after 6 weeks of completion of radiotherapy in both study arm and placebo arm and reported. 2 patients progressed during therapy and were not included in analyses and two patients discontinued the intervention. A per protocol analyses was done. RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the amylase resistant starch group. This difference was seen at 4th week and continued in the subsequent weeks till the end of radiation. Both groups had
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similar reported toxicity at 6 weeks post intervention. Both groups were also found to have similar incidence of grade 2 and above diarrhea. The non-digestible starch group was found to have 8% incidence as compared to 2% in the other group at the 5th and 6th week. The short chain fatty acid concentrations were found to be not significantly different in the groups at any point. CONCLUSION: The study failed to demonstrate a benefit in administration of resistant starch in excess of normal diet to patients receiving pelvic radiotherapy. This may be postulated to be due to concurrent use of chemotherapy and decrease in intestinal probiotics. A176
COMPARISON OF LDL-C (LOW-DENSITY LIPOPROTEIN CHOLESTEROL) VALUES OBTAINED BY DIRECT ESTIMATION AND BY CALCULATIONS Jagadish R1, Joe Varghese1, Victoria Job2 and Molly Jacob1,Department of Biochemistry1 and Clinical Biochemistry2,Christian Medical College, Vellore BACKGROUND: A recent report suggests that LDL-C values calculated using a new formula proposed by Martin et al (2013) showed good concordance with values obtained by the gold standard method. The new formula has been suggested to be superior to the Friedewald’s formula, which has been used for the same purpose. AIM: The aim of the present study was to test the hypothesis that use of the new formula,as described by Martin et al (2013), would yield LDL-C values with better concordance with values obtained by direct enzymatic estimation, than theFriedewald’s formula. MATERIALS AND METHODS: De-identified fasting lipid profile data of 49,268 patients, analyzed in the Department of Clinical Biochemistry, Christian Medical College, Vellore, (August to October 2014), were obtained. LDL-C was also calculated using both the Friedewald’s formula and the new formula published by Martin et al (2013). Intraclass correlation coefficient (ICC) was used as a measure of the degree of agreement between the methods. All statistical analyses were performed using R V.3.2.2 with ‘ICC’ package. RESULTS: Values of LDL-C calculated, by both the formulae, showed near-perfect to fair agreement with LDL-C values measured by a direct enzymatic method (ICC=0.40- 0.93), when non-HDL-C (high density cholesterol) exceeded 130 mg/dL and when triglyceride (TG) levels were greater than 400mg/dL. However, the degree of agreement of calculated values (by both formulae) was poor (ICC=0.2) when TG levels exceeded 400 mg/dL and non-HDL-C levels were < 130 mg/dL.
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CONCLUSIONS : In our setting the new formula suggested by Martin et al (2013) was found to give values of LDL-C with better concordance with values obtained by the direct enzymatic method for estimation of LDL-C. It also provided better NCEP (National Cholesterol Education Program)based guideline risk classification than the Friedewald’s formula. A177
INSULIN RESISTANCE IS ASSOCIATED WITH DYSREGULATION OF IRON HOMEOSTASIS IN A MOUSE MODEL OF TYPE 2 DIABETES MELLITUS Joe Varghese, Jithu V James and Molly Jacob Departments of Biochemistry, Christian Medical College, Vellore, India BACKGROUND: It has been reported that increased body iron stores is associated with increased incidence of type 2 diabetes mellitus (T2DM). However, the mechanisms that link insulin resistance (IR), the hallmark of T2DM, and regulation of iron homeostasis are not clearly understood. It is not known whether increased body iron is a cause or consequence of IR. There is very little information on the effect of IR on hepcidin, the chief iron regulatory hormone. In addition, there is no information on the effect of IR on body iron distribution. In view of this, a systematic timecourse study was carried out to determine the interplay between IR and iron homeostasis in a mouse model of diet-induced obesity, which served as a model of type 2 diabetes mellitus. METHODS: Male C57Bl/6 mice were fed a high-fat diet (HFD) or control diet for various time periods (up to 24 weeks). Development of glucose intolerance and insulin resistance was monitored by performing glucose tolerance tests (GTT) and insulin tolerance tests (ITT). Subsets of mice were euthanized after 4, 8, 12, 16, 20 and 24 weeks of feeding with the HFD or control diet. Quantitative real-time PCR and western blot analyses was used to estimate the expression of various parameters of interest in the liver. Iron content was measured in the liver, spleen, gonadal white adipose tissue (gWAT) and skeletal muscle by a spectrophotometric assay. RESULTS: High-fat feeding induced obesity, hepato-steatosis, and insulin resistance in mice; these changes were seen after 8 weeks of HFD feeding and were maximal after 20 and 24 weeks. HFD significantly dampened the activation of the Akt pathway of insulin signalling in the liver. Consistent with decreased insulin signalling, expression of lipogenic and gluconeogenic genes were not altered in response to hyperinsulinemia induced by HFD. In the liver, there was a significant decrease in iron levels after 12 weeks of HFD feeding. Decreased iron stores was also indicated by increased hepatic expression of TfR1 (involved in iron import) and decreased expression of ferritin (involved in iron storage) and ferroportin (involved in export of iron).
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Serum hepcidin was significantly lower after 20 and 24 weeks of HFD feeding. No significant differences were seen in iron contest of adipose tissue, skeletal muscle and spleen at any of the time points studied. CONCLUSIONS: High-fat feeding induced IR and dysregulation of iron homeostasis in the mouse model of T2DM. Onset of IR (at 8 weeks) appeared to precede the onset of iron dysregulation (at 12 weeks). High-fat feeding resulted in significant decreases in hepatic iron and serum hepcidin levels. However, there was no evidence of increased iron levels in adipose tissue and skeletal muscle to suggest re-distribution of iron to these sites.
A178
SYMPATHETIC VASODILATION – SHOULD WE USE ALPHA BLOCKERS TO TREAT SEPTIC SHOCK? Renu Raj R1, Bhavithra Megan1, Sathya Subramani11 Christian Medical College, Vellore, Tamil nadu. Alpha adrenergic activation is known to cause vasoconstriction through Inositol triphosphate mediated calcium release from sarcoplasmic reticulum. We found that alpha adrenergic activation causes vasodilatation (from basal state) under conditions of high nitric oxide availability. The results will be discussed. AIM: To demonstrate the conditions under which Phenylephrine, an alpha adrenergic agonist, induces vasodilation. METHOD: Spiral strip of a small artery isolated from goat leg (obtained from a slaughter house) was suspended in an organ bath (25 ml), filled with physiological salt solution at 37◌C, and aerated with carbogen (95% O2 & 5% CO2). One end of the strip was attached to a force transducer connected to a data acquisition system (Power lab). Drugs were added to the organ bath; changes in tension were recorded and analyzed. RESULTS: Under control conditions, PE caused vasoconstriction. But when NO levels are higher, (for eg, when an excess of the substrate L-Arginine is provided), PE decreased vessel tension. Alpha adrenoreceptor blockers and endothelial nitric oxide synthase blocker but not beta blocker prevented vasodilation by L-Arginine/PE. Adrenaline and noradrenaline (and not isoproterenol) also reduced vessel tension in the presence of L-Arginine. Relieving NO from having to stimulate the enzyme sGC (either by sGC blockers or by enhancing cGMP levels which by negative feedback probably inhibits sGC) led to PE-induced vasodilatation. PMA (Phorbol
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myristate acetate), an agonist which stimulates Protein Kinase C was able to prevent the ability of PE to reduce vascular tension in a high NO environment. CONCLUSION: Reduction of vessel tone by PE through alpha adrenoceptors is dependent on NO, but is independent of cGMP. The findings have implications in treatment of conditions with high NO levels, for eg, septic shock. A179 FALLOPIAN TUBAL CHANGES IN SEROUS OVARIAN TUMORS, USING P53 AS AN IMMUNOHISTOCHEMICAL MARKER Kiran Maruti Gore, Ramani Manoj Kumar Department of General Pathology, CMC Vellore BACKGROUND: Ovarian tumors are the seventh most common cause of death by cancer among women. Serous carcinomas arise either de novo or from a fallopian tube which shows specific pathological changes much prior to the development of the ovarian carcinoma. It may be beneficial to detect these initial changes to make an early diagnosis of these cancers in high- risk individuals. AIM: To assess the utility of STIC (Serous Tubal Intraepithelial Carcinoma) and p53 staining patterns as precursor lesions for serous ovarian tumors diagnosed in one year. METHODS: We examined the immunohistomorphological changes in fallopian tubes of 85 serous tumors and 10 controls reported during the year 2015. RESULTS AND CONCLUSIONS: The fallopian tubes from 85 serous ovarian tumor sepcimens reported in 2015 were examined for the presence of serous tubal intra-epithelial carcinoma (STIC) and for p53 expression by IHC. STIC was present in 30/85 (41%) of all serous tumors, 23/42 (55%) of high grade serous carcinomas (p= <0.01), and 7/43 (8%) of other serous tumors and none of the controls. This suggests that STIC has role in the pathogenesis of these tumors. Abnormal p53 expression was exclusively seen in high grade serous carcinomas: (20/42, 48%), (p<0.05). Prominent atypical histological features seen in fallopian tubal epithelium with abnormal p53 expression were increased N/C ratio, epithelial stratification, loss of cellular polarity and irregular nuclear chromatin.
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These findings suggest that STIC and abnormal p53 expressions in fallopian tubes might be the precursors of high grade serous carcinomas. p53 signature is considered as a precursor lesion, was seen only in 4/95 cases, which included 3 high grade serous carcinoma cases and 1 control case. None of the benign or borderline cases showed p53 signatures. This finding also suggests that prediction of development of high grade serous carcinomas can be suggested with these changes.
A180
THE HISTOLOGICAL DIFFERENTIATION OF TUBERCULOSIS FROM CROHN’S DISEASE IN MUCOSAL BIOPSIES WITH GRANULOMATOUS INFLAMMATION FROM THE UPPER GASTROINTESTINAL TRACT. Dr.Sangeetha Ramakrishna Pillai, Department of General Pathology. BACKGROUND: Tuberculosis and Crohn’s disease are both granulomatous diseases of the gastrointestinal tract with numerous overlapping features. Several studies have documented the differentiating clinical and histological features in the lower gastrointestinal tract. However, no studies have attempted to distinguish upper gastrointestinal Tuberculosis from Crohn’s disease. AIM: To identify the histopathological features useful in distinguishing Tuberculosis from Crohn’s disease in mucosal biopsies with granulomatous inflammation from the upper gastrointestinal tract. METHODS: A total of 40 cases (20 cases each of Tuberculosis and Crohn’s disease) with a minimum of one year clinical follow up was selected from a total of 98 cases, over a ten year period (January 2005-December 2014). The clinical, endoscopic and histopathological features were examined and entered into a database created in the Epidata software. The statistical methods used included frequency table, Chi square test, Mannwhitney’s U test and a p value of <0.05 was considered significant. RESULTS AND CONCLUSIONS: Granulomatous inflammation of the upper gastrointestinal tract is more likely to be Crohn’s disease if the duration of the illness is longer, endoscopy is normal and intensity of granulomatous inflammation and other inflammatory changes is mild. Tuberculosis is more likely to be associated with shorter duration of symptoms, dyspepsia, endoscopic changes, significant lymph node involvement on CT, more severe granulomatous inflammation and other inflammatory changes. Involvement of the esophagus and duodenum by granulomatous inflammation is also more common in Tuberculosis.
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A181
SHAPE, HEIGHT AND POSITION OF THE LINGULA AS A SURGICAL LANDMARK FOR BILATERAL SAGITTAL SPLIT OSTEOTOMY OF MANDIBULAR RAMUS IN INDIANS Dr Vandana Nathan, Dr Ivan James Prithishkumar, Dr Rabin Chacko, Dr. Prasanna Samuel , Department of Anatomy, Christian Medical College, Vellore BACKGROUND: The most commonly used landmark to ascertain position of mandibular foramen intraoperatively in bilateral sagittal split ramus osteotomy (BSSO) and inferior alveolar nerve block is tip of lingula. AIMS: This study aims to investigate the shape, height, and position of the lingula in relation to surrounding structures for BSSO and inferior alveolar nerve block. METHODS: 80 dried adult Indian mandibles were studied. The shape, position and height of lingula was measured relative to other oro-surgical landmarks such as internal oblique ridge, external oblique ridge, mandibular notch, posterior border of ramus of mandible, occlusal plane, etc. RESULTS: The shape of the lingula was classified into triangular (R=7.5 %; L=13.75%), truncated(R=37.5%; L=28.75%), nodular(R=47.5%; L=38.75%) or assimilated types(R=7.5%; L=18.75%). The mean height of lingula is 8.8mm. The mean position of lingula from its tip to internal oblique ridge(Mean 10.2mm; R=10.6mm; L=9.85mm; p value <0.001); to external oblique ridge (16.95mm); to posterior border of ramus (14.97mm); to mandibular notch (13.19mm); above occlusal plane (Mean= 3.5mm± 2.67); below occlusal plane (Mean 8.21mm ± 0.64); occlusal plane to lingula in mandibular sides without teeth (10.05mm ± 2.61). CONCLUSION: The results of the study would provide important and easily feasible landmarks to the maxillofacial surgeons in planning their surgical interventions.
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A182
A MORPHOLOGICAL STUDY OF ACUTE MYELOID LEUKEMIA (AML) AND CORRELATION WITH CLINICAL PARAMETERS AND RESULTS OF CYTOGENETIC ANALYSIS AND MUTATION SCREENING. Amey Baitule, Arpana Palle, Vivi M Srivastava BACKGROUND: Acute myeloid leukemia is an aggressive neoplasm characterized by uncontrolled proliferation of blasts in the bone marrow and/or peripheral blood. It is a biologically diverse disease characterized by a wide spectrum of morphologic presentations, cytogenetic abnormalities and gene mutations. Morphological examination, cytogenetic analysis and mutation screening facilitate the systematic and accurate categorization of this heterogeneous neoplasm into distinct clinico-pathological subtypes, which in turn can predict the prognostic outcome and therapeutic response of the patient. In spite of the recent technological advances in diagnostic modalities of AML, conventional morphology still remains the most basic, cost-effective and most commonly employed first-line modality for the initial diagnosis of AML world over, and especially so in resource poor nations. So we describe these diverse presentations of AML with an emphasis on the morphological aspects of the disease and their correlation with cytogenetic analysis, mutation screening and other clinical parameters. AIMS:
To describe the morphology of bone marrow aspirate smears in AML. To correlate the morphology with results of cytogenetic analysis and mutation screening. To categorize AML using both the French-American-British(FAB) and the World Health Organization(WHO) classification systems.
MATERIALS AND METHODS: We included 156 newly diagnosed AML presenting to this institution over a period of one year from January 2015 to December 2015 in this study.
Bone marrow aspirate smears and peripheral blood smears were examined, a differential count was performed and parameters such as blast lineage and presence of dysplasia were assessed. Cytogenetic analysis using karyotyping was carried out in 142 of the 156 patients. Mutation screening for NPM1, FLT3-ITD and FLT3-TKD genes was carried out for 47 patients. A review of the bone marrow aspirates of patients with recurrent cytogenetic abnormalities was done and distinctive morphologic and cytochemical findings were noted for correlation.
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RESULTS AND CONCLUSIONS:
The median age of the patients was 32 years (range: 7 months to 76 years). Using the FAB classification, the most common subtype was AML-M2(37%). Cytogenetic analysis – Abnormal karyotypes were seen 62% of our patients. Recurrent genetic abnormalities o (15;17)(q22;q12) – 15% (most common) o t(8;21)(q22;q22.1) - 8% o Other abnormalities ~1-2% of patients. Other common cytogenetic abnormalities observed were o Trisomy 8 – 9% o Monosomy 7 – 8% o Complex karyotypes (3 or more abnormalities) – 13% o Monosomal karyotypes – 9%. Mutation screening – The proportion of patients with the NPM1 and FLT3 gene mutations was as follows: NPM1 -47% (22/47) Patients with normal karyotype & NPM1 mutation - 74% (20/27). FLT3-ITD -19% (9/47). FLT3-TKD -17% (8/47). Concomitant NPM1 and FLT3 mutations -28%(13/47). Using the 2016 revision to the WHO classification of AML, the proportion of patients belonging to the various subtypes are as follows– AML with recurrent genetic abnormalities (AML-RGA) -42% AML, not otherwise specified (AML, NOS) -37%. AML with myelodysplasia-related changes(AML-MRC) -21%
We conclude that morphology plays an indispensable role in the diagnosis of AML, and that the awareness of the morphologist/pathologist regarding the subtle morphological features which may prompt further referral for molecular and cytogenetic investigations, plays a significant role in guiding the patient’s management in AML, especially in centers where facilities for cytogenetic and/or mutation screening are not readily available.
A183
PREVALENCE AND TRENDS OF STATIN USE AMONG HIGH RISK GROUPS (DIABETES, CORONARY HEART DISEASE) IN TAMIL NADU, SOUTH INDIA Authors: Anu Mary Oommen, Khushboo Nand, Vinod Joseph Abraham, Kuryan George Affiliation: Department of Community Health, Christian Medical College, Vellore, Tamil Nadu, India
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ABSTRACT Background: Population based prevalence of statin use indicates accessibility to health care for cardiovascular diseases. This study assessed current statin use among those with diabetes and/or coronary heart disease in Tamil Nadu, India and trends in use among rural diabetics four years later. Methods: A community based WHO STEPS cross sectional survey was conducted in rural and urban Vellore, Tamil Nadu among 6196 adults aged 30 to 64 years, in 2010-12. Diabetics were identified as those on diabetic medication (known diabetics) or with fasting blood sugar ≥ 126 mg/dl. A randomly selected sample of 245 diabetics from the rural cohort of diabetics identified earlier (on diabetic medication or newly detected with fasting sugar ≥ 126 mg/dl in 2010-12) was resurveyed in 2016 and their medication history updated. RESULTS In 2010-12, 61 with diagnosed coronary heart disease and 510 with known diabetes (on diabetic medication) were identified. Among those with coronary heart disease, 40% of urban and 33% of rural subjects were on statins. Statin use among known diabetics aged ≥ 40 years with LDL ≥ 70 mg% was 13.4% and 7.6% among urban and rural diabetics respectively. Adjusting for age and sex, urban residence and education (≥ 8th grade) were significantly associated with use of statins. The proportion of rural diabetics aged ≥ 40 years on statins increased from 7.7% in 2010-12 to 16.9% in 2016 as seen in the follow up study. CONCLUSIONS Statin use for coronary heart disease was below 50%, but higher than the use for primary prevention among diabetics, which however, is rising slowly. Reasons for low statin use need to be explored to improve access to preventive measures, especially in rural areas, to decrease cardiovascular mortality.
A184
NUTRITIONAL STATUS AND INTELLECTUAL DEVELOPMENT IN CHILDREN: A COMMUNITY-BASED STUDY FROM RURAL SOUTHERN INDIA. Jacob A, Thomas L, Stephen K, Marconi S, Noel J, Jacob KS, Prasad J BACKGROUND: There is a dearth of recent data on the relationship between nutritional status and intellectual development among children in India. To determine whether such a relationship exists, we studied children in a rural area of Tamil Nadu.
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METHODS: We stratified villages in Kaniyambadi block, Tamil Nadu, and recruited consecutive children who satisfied the study criteria. We assessed nutritional status by measuring height and weight and recording chronological age, and calculated indices weight-for-age, height-for-age, weightforheight and their Z scores. We assessed intellectual development using the Indian adaptation of the Vineland Social Maturity Scale. We used a case-control framework to determine the relationship and logistic regression to adjust for common confounders. RESULTS: We recruited 114 children between the ages of 12 and 72 months. Z score means (weight-for-age -1.36; height-for-age -1.42; weight-for-height -0.78) were much less than 0 and indicate undernutrition. Z score standard deviations (weight-for-age 1.04; height-for-age 1.18; weightforheight 1.06) were within the WHO recommended range for good quality of nutrition data suggesting reduced measurement errors and incorrect reporting of age. The frequency distributions of population Z scores suggest high undernutrition, wasting and medium stunting. A tenth of the population (9.6%) had values to suggest borderline/below average intelligence (social quotient <89). Lower height-forage, height-for-age Z score and weight-for-height Z score were significantly associated with a lower social quotient. These relationships remained statistically significant after adjusting for sex and socioeconomic status using logistic regression. CONCLUSION: Chronic undernutrition, wasting and stunting and their association with lower intellectual development demand an urgent re-assessment of national food policies and programmes.
A185 BURDEN OF NON COMMUNICABLE DISEASES IN TRIBAL SOUTHERN INDIA-A COMMUNITY BASED CROSS SECTIONAL STUDY Charles Ruban1, Manjunath K1, Jasmine Prasad1, , Thomas N2, Mini Joseph2, John J1 1Department of community health, 2Department of Endocrinology, Diabetes & metabolism, Christian medical college, Vellore BACKGROUND: This cross-sectional study was conducted among the residents of Jawadhu hills which is situated in Vellore and Tiruvannamalai districts of Tamil Nadu. The main objective of this study was to estimate the prevalence of diabetes mellitus, hypertension, dyslipidaemia and metabolic syndrome and their risk factors among the residents of Jawadhuhills aged between 30-60 years. METHODS: This study was conducted in 14 villages of Jawadhu hills in Tiruvannamalai district. Two stage cluster sampling method was used. Villages were selected by probability proportionate to size sampling. Consecutive Households were selected from village starting point in clockwise
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direction as per the algorithm until the required sample size was obtained. Totally 480 people (males-225 & females-255) were surveyed from February 2016 to July 2016 using modified WHO-STEPS questionnaire. Socio demographic factors, behavioural and metabolic risk factors and anthrometric measures were collected. Fasting and post prandial (2 hour) blood glucose were collected for 480 people by using glucometer. Among the subset of 138 people (one participant from alternate household) fasting lipid samples were collected. Results: Of thesubjects (480) studied, 3.3%had diabetes mellitus,7.6% had prediabetes, 17.7% had hypertension. Among the sub group of 138 people, 51.5% had abnormalities in any one of the lipid parameters. 16.7% of the study population had hypercholestremia, 24.6% had hyper triglyceridemia,26.8% had low HDL,18.1% had high LDL,10.8% had high total cholesterol/HDL ratio(>4.5) and 12.3% had metabolic syndrome. Out of 480 people,11.7% had low physical activity(less than the WHO recommended). Using Asian cutoff, prevalence of obesity, overweight and central obesity were 20% , 4.8% were obese, and 9.8% respectively. Most participants were from low socio economic status. Alcohol use and smoking is common among men (72.9%and 64% respectively). In the multivariate analysis, overweight was significantly associated with hypertension and dyslipidaemia. Low levels of physical activity and obesity were associated with and metabolic syndrome. Conclusion: Prevalence of diabetes in this tribal population is low (3.3%). However, 51.5% had dyslipidaemia and 17.7% had hypertension. High prevalence of behavioural and metabolic risk factors calls for urgent intervention. A186 NUTRIENT INTAKE OF THE TRIBAL POPULATION OF JAWADHU HILLS Charles Ruban1, Mini Joseph2, Manjunath K1, Thomas N2 John J1 , Jasmine Prasad1, 1Department of community health, 2Department of Endocrinology, Diabetes & metabolism, Christian medical college, Vellore BACKGROUND: A cross-sectional study was conducted among 138 residents (male (66) & female (72)) of Jawadhu hills. This remote area is an extension of the Eastern Ghats and spreads across parts of Vellore and Tiruvannamalai districts in the northern part of the state of Tamil Nadu. The main objective of this study was to assess the adequacy of the food and nutrient intake of the residents living in the Jawadhu hills. METHODS: Fourteen villages were surveyed and the dietary data was obtained by 24 hour recall method and food frequency method (past one month) using standardised vessels. RESULTS: The mean age of the residents was 43.5 + 9.3 years. Majority of them hailed from the poorer strata of the society according to modified Kuppasamy scale and this is reflected in their food intake.The nutritional data indicates that this population consumed three major meals per day.
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The mean energy intake was 1684.6 + 180.8 and 1467.4 + 152.1 calories/day in the male and female population respectively. Polished rice was the staple food and constituted the major calories in their diet. The intake of proteins was below the recommended allowances for Indians (males: 40.6 + 4.5gm/day; females: 36.3 + 4.4 gm/day). Cereals were the major source of proteins in their diet. Horse gram was the popular pulse which was cooked into a thin gruel and consumed on a daily basis in 95% of the population. The more expensive proteins sources like poultry, flesh foods, fish, milk and milk products were consumed less frequently. More than three-fourth of the population consumed milk, beef, eggs and fish occasionally (less than twice a month) and chicken was consumed fortnightly.There was a gross deficit in the intake of minerals like Calcium and Iron in both the male and female population. Vitamins like thiamine, riboflavin, niacin, folic acid, carotene and Vitamin C did not meet the daily requirements in this population. This is because of inadequacy in the intake of fruits and vegetables which were consumed on a weekly basis, since it was not locally grown. The poor purchasing power of the families were the major impediment in including these micronutrients foods to the diet. CONCLUSION: Encouraging kitchen gardens with cultivation of geographically appropriate vegetables will ensure adequate supply of micronutrients in the family meal. Subsidised supply of nutri-grains like millets, pulses and vegetables through the Public Distribution system will ensure accessibility to this vulnerable hill population and improve the quality of their diet. A187 IMPACT OF HAZARDOUS DRINKING ON FAMILY FUNCTIONING IN RURAL SOUTH INDIA- A CROSS SECTIONAL STUDY. Dr Martina Shalini 1, Dr Shantidani Minz 2, Dr Anuradha Rose3 , Dr. Jasmine Helan 4 BACKGROUND: Alcohol use disorder is currently linked to over 200 diseases and injuries. In addition, it also affects the family through marital discord, financial problems. Understanding the effect of alcohol on the family as a whole will be useful in addressing family issues in programmes aimed at helping hazardous drinkers. AIM: To assess the impact of hazardous drinking on family functioning. The objectives of the study were to estimate the prevalence of hazardous drinking among married men in the 25-60 age group and to study the effect of hazardous alcohol consumption on family dysfunction. METHODS: A community based cross sectional study was conducted in rural southern India. The AUDIT (Alcohol Use Disorders Identification Test) questionnaire was administered to 750 married men in the 25-60 age group. In the second phase 150 wives selected by simple random sampling were interviewed to assess family functioning. We used perception of family functioning by wives,
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quality of life, presence of domestic violence and presence of any common mental health disorders to assess the effect of drinking pattern on the family. RESULTS: The prevalence of hazardous alcohol consumption among married men in the 25- 60 years’ age group was 31.5%. Women whose husbands were hazardous alcohol consumers were at 4.33 times higher risk of experiencing domestic violence. While a higher proportion of women with hazardous drinkers as husband’s (49%) vs 34% in the non-hazardous /abstainers group perceived their family as dysfunctional, the difference was not statistically significant. The risk of low perception of family functioning was 3.7 times higher in women experiencing domestic violence compared to women who did not experience domestic violence. CONCLUSIONS: Prevalence of domestic violence was significantly higher in families of hazardous drinkers. While other measures of family functioning like perception of family dysfunction and quality of life was associated with domestic violence, there was no direct association to pattern of drinking. 1. 3rd Year PG Registrar, MD Community Medicine, Department of Community Health, CMC, Vellore 2. Professor, Department of Community Health, CMC Vellore 3. Associate Professor, Department of Community Health, CMC Vellore. 4. Head of the Department, Department of Community Health, CMC Vellore A188
ASSESSMENT OF THE HEALTH RELATED QUALITY OF LIFE AMONG ADULTS WITH EPILEPSY LIVING IN KANIYAMBADI BLOCK OF VELLORE DISTRICT AND FACTORS ASSOCIATED WITH POOR QUALITY OF LIFE AMONG THEM AIM: To assess the Health Related Quality Of Life (HRQOL) of persons living with epilepsy in Kaniyambadi block of Vellore district OBJECTIVE: To assess the Health Related Quality Of Life (HRQOL) of persons aged 18 years and above living with epilepsy residing in Kaniyambadi block, Vellore. and to identify the risk factors associated with poor HRQOL
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METHODOLOGY: This was a community based cross sectional study conducted in Kaniyanbadi block of Vellore district. The Individuals aged 18 years and above, identified as having seizure disorder or epilepsy from records maintained by Community Medicine department and living in Kaniyambadi Block for at least 6 months were included in the study and interviewed using QOLIE-31 questionnaire. The domains included seizure worry, emotional, cognitive, medication and social effects. RESULTS: In the study the overall mean score for quality of life was 65.2 out of 100 (standard deviation16.37). the respondents scored lowest on social participation with a mean score of 54.22, and, highest with absence of medication effects with a mean score of 91.96. The factors associated with low scores were anxiety (OR 3.83, P value 0.036).,depression (OR 3.8, P value 0.036).and unemployed status(OR 6.9, P value 0.009). CONCLUSIONS: Individuals with epilepsy should be routinely screened for depression and anxiety and offered treatment for the same. Social participation by people with epilepsy should be encouraged. A189 A CROSS SECTIONAL AUDIT OF THE FREQUENCY OF ERROR PRONE ABBREVIATIONS IN INPATIENT PRESCRIPTIONS IN A TERTIARY CARE CENTRE Jacob J1, Rabindranath 2, Mathew BS1 1
- Department of Pharmacology1, Christian Medical College Hospital, Vellore, T.Nadu 2 - Quality Management Cell, Christian Medical College Hospital, Vellore, T Nadu BACKGROUND The use of medical abbreviations is a common practice in many hospitals. They are believed to save time, space and are thought to be easily understood but on the contrary, the use of abbreviations, symbols and dose designations are frequently misinterpreted. In addition, clarity is compromised because of illegible handwriting and the words/numbers being in close proximity to each other. In an effort to promote safe practices, the Institute for safe medication practices (ISMP) and the U.S. Food and Drug Administration (FDA) recommend that ISMP’S list of error prone abbreviations, symbols, and dose designations be considered when writing a prescription.
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Aim To determine the frequency and the type of error prone abbreviations in inpatient prescriptions in the wards in the Christian Medical College Hospital, Vellore. METHODOLOGY All wards in CMC Hospital, were surveyed from 11.05.2015 to 16.05.2015, in which up to five patients were selected from each ward. This was based on the decision to include one tenth of the total number of patients admitted in the ward on that particular day. A cross sectional audit was done on every fourth/fifth patient starting from bed no. 1. The prescription written in the inpatient chart for that particular day was audited based on the ISMP’s list of error prone abbreviations and symbols. RESULTS The error prone abbreviations were classified into Type A, B and C. Type A errors: Drug name abbreviations Type B errors: Dose designations and other information and Symbols like μ, ×, @ etc. Type C errors: Other general Abbreviations used in prescribing like improperly placed commas or doses and units written together. Medication charts of 225 inpatients were audited in 73 wards of CMCH, Vellore. In total of 225 patient prescriptions, it was observed that 1456 drugs were prescribed, which showed a total of 1294 errors. From the total of 225 prescriptions, 56, 71 and 98 patient prescriptions were surveyed from the Medical, Surgical and Higher Speciality Departments respectively. And there were 413, 397 and 646 drugs prescribed in total in the Medical, Surgical and Higher Speciality Departments respectively. Of the 225 patient prescriptions, three prescriptions showed all the three errors Type A, B and C. Amongst all the errors, type B error was noted to be the maximum, 703 out of 1294(54.3%) errors followed by Type C error which was 45.3% of total errors. The major type B errors included 542 OD for once daily, 50 U for units, 35 errors with use of SLASH as a symbol ;42 errors with “@” instead of “at” and 22 “μ” for “microgram” errors. Type A was noted in only four patient prescriptions. Amongst type C error, 154 patient prescriptions had the dose and unit written together, 9 prescriptions had large doses without properly placed commas and one prescription had a naked decimal point. Of the total errors in the respective speciality, the percentage of type B errors was 60.8%, 46.7% and 54.7% in Medical, Surgical and Higher Speciality respectively. CONCLUSION We observed a total of 1294 error-prone abbreviations (from 1456 drugs prescribed in 225 patient prescriptions) in our inpatient hospital setting when a cross sectional audit was performed in every ward in the hospital. This could lead to serious errors in management in a clinical setting. This highlights the need to create awareness amongst clinicians in avoiding the use of such abbreviations whilst writing prescriptions.
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A190 TRISOMY 8 IN ACUTE MYELOID LEUKEMIA
Yuvarani S 1, Palle A 3 Abraham A2, Fouzia N.A2, Anup J Devasia2, Nisham P.N 2, Anu Korula 2, George B2, Mathews V2, Srivastava A2, Srivastava VM1. 1
Cytogenetics Unit, 2Dept of Haematology, 3Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore. INTRODUCTION & BACKGROUND: Trisomy 8 is the most frequent cytogenetic aberration in acute myeloid leukemia (AML), occurring in 10% to 15% of all AML. When trisomy 8 occurs as the sole abnormality it is associated with an intermediate to poor prognosis. Trisomy 8 may also be associated with additional abnormalities. In the recurrent genetic abnormalities (RGA) associated with AML, trisomy 8 is a frequent secondary change. PATIENT/ MATERIAL AND METHODS: All patients with AML and trisomy 8 seen in the Department of Haematology, Christian Medical College, Vellore from January 2003 to December 2015 were included in the study. G-banded karyotypes were reported according to the International System for Human Cytogenetics Nomenclature (ISCN). Cytogenetic, blood and bone marrow findings were correlated. RESULTS: Trisomy 8 was seen in 235/2487 AML (9.4%). The majority (61%, 144/235) were males. There were 206 adults (88%) and 29 children (median age 39, range 1-76 years).The median haemoglobin was 8.1g/dl (range 2.3-15.1g/dl), median WBC 4 ×109/L (range 0.3-537 ×109/L), and median platelet count, 33×109/L (range 2-400 ×109/L). The morphological subtypes of AML with trisomy 8 were: AML M1-21; AML M2-41; AML M3-39; AML M4-13 ; AML M4E0-2; AML M5-15; AML M6-12; AML M7-3; MDS-AML-4; AML with myelodysplasia-related changes -22; AML not further classified-62. The trisomy 8 was solitary in 29% of patients (68/235). Trisomy 8 was seen in association with the RGA t(15;17), t(8;21) and inversion 16 in 39 (23%), 7(4%), and 9(5%) of patients respectively. The other RGA seen were the inversion 3, t(9;11) and t(6;11) in 0.6% - 3% of patients. Other commonly seen abnormalities were trisomies 21 (23%), 4, 19, and 22 (11-12%) and monosomies 5, 7 and 17 and the deletion 5q (5 -10%). Complex karyotypes with three or more abnormalities were seen in 31% of patients, most of whom had AML not further classified (42%), AML-M2 (16%) and AML with myelodysplasia-related changes (15%). CONCLUSIONS: The frequency (9.4%) of trisomy 8 in AML is similar to the literature. In the majority (71%) of our patients, trisomy 8 was seen in association with other abnormalities, notably the t(15;17) and
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trisomy 21(23% each). The median age of our patients is lower than what has been reported (39 vs. 47-64 years) reflecting the overall lower median age of AML in our country. REFERENCE 1. Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia: a Southwest Oncology Group study . Sandra R. Wolman, Holly Gundacker, Frederick R. Appelbaum, and Marilyn L. Slovak, © 2002 by The American Society of Hematology 2. Patients with Isolated Trisomy 8 in Acute Myeloid Leukemia Are Not Cured with Cytarabinebased Chemotherapy: Results from Cancer and Leukemia Group B 84611 John C. Byrd,2 David Lawrence,Diane C. Arthur, Mark J. Pettenati,Ramana Tantravahi, Mazin Qumsiyeh,Judith Stamberg, Frederick R. Davey, Charles A. Schiffer, and Clara D. Bloomfield ,vol 4, 1235-1241, May 1998. 3. Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup Markus Schaich, Richard F. Schlenk, Haifa K. Al-Ali, Hartmut Döhner, Arnold Ganser,Gerhard Heil, Thomas Illmer, Rainer Krahl, Jürgen Krauter, Cristina Sauerland, Thomas Büchner,Gerhard Ehninger, Haematologica 2007; 92:763-770 ©2007 Ferrata Storti Foundation 4. The significance of trisomy 8 in de novo acute myeloid leukemia: the accompanying chromosome aberrations determine the prognosis. Claudia Schoch, Detlef Haase, Christa Fonatsch, Torsten Haferlach, Helmut Lofler, Brigitte Schlegelberger, Dieter-Kurt Hossfeld, Reinhard Becher, Maria Cristina Sauerland, Achim Heinecke, Bernhard Wormann, Thomas Buchner and Wolfgang Hiddemann. British Journal of Haematology 1997,99,605-11.
A191 DOES DAILY USE OF RESISTANT STARCH IN DIET REDUCE THE INCIDENCE AND SEVERITY OF ACUTE BOWEL SYMPTOMS IN PELVIC RADIOTHERAPY? A RANDOMIZED CONTROL TRIAL Balukrishna Sasidharan, Viswanathan P.N, Prasanna Samuel, Ramadass Balamurugan, Pugazhendhi Srinivasan, B.S. Ramakrishna Christian Medical College, Vellore
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PURPOSE: The purpose of the study is to look at the benefit of administration of an oral prebiotic starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix. MATERIAL/METHODS The study was conducted between 2011 and 2014 in 104 patients receiving radical chemoradiotherapy for carcinoma cervix. Patients were randomized to two arms receiving 30 gm of resistant starch or digestible starch on a daily basis through out the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. All of them underwent LDR brachytherapy of 30 Gy at completion of external beam radiotherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two randomized groups and analysed. Stool short chain fatty acid concentrations were measured at baseline at 2nd and 4th week and after 6 weeks of completion of radiotherapy in both study arm and placebo arm and reported. 2 patients progressed during therapy and were not included in analyses and two patients discontinued the intervention. A per protocol analyses was done. RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the amylase resistant starch group. This difference was seen at 4th week and continued in the subsequent weeks till the end of radiation. Both groups had similar reported toxicity at 6 weeks post intervention. Both groups were also found to have similar incidence of grade 2 and above diarrhea. The non-digestible starch group was found to have 8% incidence as compared to 2% in the other group at the 5th and 6th week. The short chain fatty acid concentrations were found to be not significantly different in the groups at any point. CONCLUSION: The study failed to demonstrate a benefit in administration of resistant starch in excess of normal diet to patients receiving pelvic radiotherapy. This may be postulated to be due to concurrent use of chemotherapy and decrease in intestinal probiotics.
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A192 COMPARISON OF RESPONSE TO NEOADJUVANT THERAPY USING MRI TUMOR REGRESSION GRADING IN PATIENTS WITH LOCALLY ADVANCED RECTAL CANCER BELOW 25 YEARS OF AGE AND ABOVE 25 YEARS OF AGE DEPARTMENT: Department of Radiodiagnosis, Christian Medical College, Vellore AUTHORS: Dr. Shibi Paul, Dr. Anu Eapen DESIGNATION: Assistant professor Grade II (first year) AIMS AND OBJECTIVES: The aim of this study was to compare the MRI findings, and response to neoadjuvant therapy using MRI tumor regression grading in patients with rectal cancer below the age of 25 years with patients more than 25 years of age. MATERIALS AND METHODS: Partly retrospective and partly prospective study approved by the institutional review board. 27 patients below 25 years of age and 115 older patients above 25 years of age with locally advanced rectal cancer were included in the study. Both the subsets of patients had MRI for initial staging and for restaging following neoadjuvant therapy. The various MRI features of the tumor, TNM staging, MRI tumor regression grade and histological features of the tumor were assessed. RESULTS: On bivariate analysis, the incidence of tumors with MRI T2 high signal intensity in patients ≤ 25 years of age was higher, 48.1 % compared to 19.3% in patients >25 years of age. The incidence of poor response to neoadjuvant therapy (by MRI tumor regression grade) was significantly more common in younger patients (66.7%) compared to older patients (40.9%). Factors like age less than 25 years, T2 high signal intensity, presence of EMVI, mucinous tumors and poorly differentiated tumors were significantly associated with poor response to neoadjuvant therapy. T2 high signal in MRI and presence of EMVI were found to be two independent predictors for poor response.
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A193 LONGITUDINAL ASSESSMENT OF NUTRITIONAL STATUS OF CHILDREN DURING TREATMENT OF ACUTE LYMPHOBLASTIC LEUKAEMIA Magdalenal R1, Rikki R John1, Narendra K Chaudhary1,Deepti Boddu1, Sarah
Authors: Mathai2,
L. Jeyaseelan3, Leni G Mathew1 Departments: Pediatric Hematology/Oncology1, Pediatric Endocrinology2, Biostatistics3 Christian Medical College, Vellore
BACKGROUND AND AIM It is essential to know the nutritional status (NS) of children undergoing treatment of acute lymphoblastic leukemia (ALL) to implement appropriate intervention which in turn will influence the outcome. In this study, we assessed the NS of a group of children from diagnosis to completion of ALL treatment. METHODS NS of 191 children(129 boys, 62 girls) aged 2-15 years diagnosed to have ALL between 20042012 , were assessed using data from their medical records at diagnosis, twice during treatment at the beginning of delayed intensification(DI) and maintenance phase(M) and at end of treatment(EoT). Using CDC BMI centile charts, theirNS was classified as:BMI <5th centileundernourished(UN), 5-85th centile - well-nourished(WN), >85th centile- overweight (OW) and≼ 95th centile –obese (O). Chi-square test and logistic regression analyses were done. RESULTS At diagnosis 42% were UN, 50% WN and 8% OW/O.Of the 81 UN, 53% continued to be UN at DI, 28% at M and 25% remained UN at EoT. However, 60% in this group moved from UN toWN and 15% to OW/O by the end of treatment. The transition in NS of those who were WN at diagnosis showed that 13% became UN at DI and 3% remainedUN at EoT. However, the incidence of obesity increased from 10% at DI to 35% by EoT in this group. Those who were OW/O to startwith, largely remained in the same NS throughout treatment. There was no difference in the NS at diagnosis based on gender, age, type of leukemia and risk stratification for treatment. Girls were 1.5 times significantly more likely to remain undernourished during treatment as compared to boys (p=0.06) CONCLUSIONS While the prevalence of UN reduced during the course of treatment from 42% at diagnosis to 12% at end of treatment, that of OW/O increased from 8% to 30%. The NS of children on
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treatment of ALL changes during treatment and therefore a close vigilance is required to implement appropriate intervention. A194 WHY IS IGA NEPHROPATHY AGGRESSIVE IN INDIANS? THE GRACE IGANI STUDY: EPIDEMIOLOGY AND LONGITUDINAL FOLLOW UP Suceena Alexander1, Rajan Babu1, Anila Korula1, Smitha M Mathai1, Visalakshi Jeyaseelan1, Vijayakumar Theophilus1, Gagandeep Kang1, Vinoi George David1, Anjali Mohapatra1, Anna T Valson1, Shibu Jacob1, Shailesh T Kakde1, Babu Ponnusamy2, Charles Pusey3, Terence Cook3, Mohamed R Daha4, Marc Seelen4, Jonathan Barratt5, John Feehally5, Santosh Varughese1, George T John6 Affiliations: 1. Christian Medical College, Vellore, India; 2. C-CAMP, Bangalore, India; 3. Imperial College London, UK; 4. University Medical Center Groningen, The Netherlands; 5. University of Leicester, UK; 6. Royal Women’s Hospital, Brisbane, Australia Background: In India about 30-40% of IgA Nephropathy (IgAN) patients (pts) have nephrotic syndrome and renal dysfunction at presentation1. Objectives: To study the epidemiology and disease characteristics of IgA nephropathy in South Asia. To study the baseline and follow-up associations among low and high risk groups scored by ARR criteria2. Results: This is a single center prospective longitudinal cohort study in South India started from March 2015. 111 out of 154 adult (≥18 yrs) pts diagnosed to have IgAN among 1400 native kidney biopsies till March 2016, were included in the study. Out of the 43 excluded pts, 14 did not consent, 6 had eGFR<10ml/min/1.73m2, 10 were on HD, 5 had diabetes, 8 had prior immunosuppression and one had chronic pulmonary infection. 60 (54.1%) &51 (45.9%) were in the low risk (ARR score <22) high risk groups (ARR score ≥22) respectively. Table 1 shows the characteristics of the two groups at baseline and at follow-up. 40 (66.7%) of low risk and 37 (72.5%) of high risk pts have at least one follow up visit and the median (IQR) duration of follow-up was 5.5mo (3 to 7) and 3mo (3 to 6) respectively. Table 1 Characteristics
Low Risk (n=60) Baseline
Low Risk p (n=40)
High Risk High Risk P (n=51) (n=37)
Follow-up
Baseline
Age yrs; mean±SD
35.8±10.3
36.7±9.4
Gender (M:F)
43:17
34:17
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Follow-up
BMI kg/m2; mean±SD
24.9±4.8
24.6±3.6
HTN n(%)
41(68.3)
49 (96.1)
Urine protein >3g/day, 7 (11.7) n(%)
34/50 (68)
Low serum 13/45 complement C3 n(%) (28.9)
11/39 (28.2)
S. Albumin mean±SD
3.7±0.44
g/dl; 4.2±0.42
24 hour urine protein 1808.5±1 g/day; mean±SD 311.8*
824.7±101 <0.001 4319.4±21 3.8* 61.8**
2388.1±158 0.8**
0.016
S. Creatinine (S.Cr) 1.5±0.68# mg/dl; mean±SD
1.4±0.69
<0.001 3.1±0.98##
4.0±3.43
0.002
S. Cystatin C (S.CysC) 1.6±0.7$ (normal range: 0.53 0.95mg/dl); mean±SD
1.7±1$
<0.001 2.6±0.81$$
3.2±1.3$$
0.005
MDRD eGFR 62.4±34# ml/min/1.73m2; mean±SD
67.4±32.8
<0.001 26.1±15##
24.8±14.6
<0.001
CKD EPI creatinine 61.6±33.3 73.9±34 eGFR ml/min/1.73m2; # mean±SD
<0.001 26.2±16.5## 27±16.7
<0.001
CKD EPI cystatin C 59.3±30.3 62±34$ eGFR ml/min/1.73m2;
<0.001 27.5±12.1$$ 22.6±11.1$$
0.009
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$
mean±SD
CKD EPI creatinine- 62.4±32.2 67.4±35.2 $ cystatin C eGFR $ ml/min/1.73m2; mean±SD
S. hsCRP mean±SD
mg/dl; 17±23.8
<0.001 27.1±15.4$$ 23.1±12.5$$
8.2±12.8
MEST M1; n(%)
5/54 (9.3)
6/48 (12.5)
MEST E1; n(%)
18/53 (34)
27/47 (57.4)
MEST S1; n(%)
36/54 (66.7)
48/48 (100)
MEST T1 & T2; n(%)
42/54 (77.8)
49/49 (100)
ACEI/ARB use; n(%)
52 (86.7)
18 (35.3)
Oral prednisolone use; 42 (70) n(%)
42 (82.4)
Mycophenolic acid 10 (16.7) (MPA) use; n(%)
14 (27.5)
Fish Oil use; n(%)
20 (39.2)
2 (3.3)
Rapid progressors (CKD EPI Cr GFR ≥5ml/min/1.73m2/yr or
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9(22.5)
12 (32.4)
0.001
≥0.42ml/min/1.73m2/m o); n(%)
0@
7 (13.7) @@
0@
4 (7.8) @@
0@
3 (5.9) @@
CKD EPI Cr GFR ≤10 ml/min/1.73m2 on follow-up; n(%)
RRT n(%)
at
follow-up;
Death; n(%)
*
N=39 # N=22 $ N=40 @N=60 **N=32 ##N=37 $$N=17 @@N=51
Immunosuppression was given in pts with ≥1g/day of proteinuria and/or renal dysfunction. Non adherence to steroids and MPA was present in 3 pts each. There were 15 infective episodes mostly of skin and GI system with one death probably attributed to CNS infection. Steroid toxicity was present in 12 pts and 3 pts had intolerance to MPA. Conclusions: There was significant decrease in proteinuria and improvement in eGFR with treatment in low risk group but though proteinuria improved among high risk group, there was significant worsening of eGFR. Among those with follow up, 54.9% were rapid progressors, in spite of aggressive treatment. RRT was started in 7.8% and 3 died on follow up. References: 1. Chacko et al. Nephrology (Carlton) 10, 496–503 (2005). 2. Tanaka et al. Clin J Am Soc Nephrol 8, 2082-90 (2013). Sponsor: Early Career Fellowship, Wellcome UK Trust/ DBT India Alliance
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A195 RADIOMIC SIGNATURES IN CARCINOMA CERVIX – NON INVASIVE IMAGING BIOMARKER TO PREDICT OUTCOME OF TREATMENT Jeba Karunya R1 Saikat Das1 Santanu Samanta1, Paul Gopu1,Devakumar D2, Subhashini John1 Department of Radiotherapy unit 21, Department of Nuclear Medicine2 INTRODUCTION: “Radiomics”(1) refers to the extraction and analysis of large amounts of advanced quantitative imaging features with high throughput analysis of medical images like computed tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI). The process involves converting ultra-structural imaging features into minable data by image processing (2). Clinicopathological correlation of radiomic features is still translational. Association of tumour tissue parameters like stage, hypoxia, metabolism, angiogenesis and survival with radiomic parameters have been reported in lung and head and neck cancer(3). Several studies have uncovered the underlying correlation between gene expression profiles and radiographic imaging phenotype showing potential of such tools as imaging biomarker. Ganeshan et al showed that tumour heterogeneity in lung cancers on CT correlated with survival(4) and texture parameters correlated with histopathology(5). Coroller et al suggested that CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma. This present study was aimed to relate radiomic features derived from image processing of CT scan with treatment related volume change of the tumor and outcome in carcinoma cervix. METHODS AND MATERIALS: CT abdomen and pelvis and MRI pelvis images of 24 patients who had carcinoma cervix were retrieved. All these patients completed low dose RT with chemotherapy followed by EBRT with concurrent cisplatin and brachytherapy. Tumour volume was manually delineated on these pre and post treatment images. Forty two 3D-radiomic features, quantifying phenotypic differences based texture, were extracted from the computed tomography images of these patients using a 3D slicer software. Statistical analysis was done by SPSS software (version 15). RESULTS: The change of 42 machine derived radiomic image parameters after treatment were analysed by t- test and 8 parameters (Global Text GLV, Global Text Variance, GLRM Text RLV, Global Text RLN, NGTDM Text Busyness, NGTDM Text Coarseness, NGTDM Text Strength and GLSZM Text GLN) were selected based on significant change. On Multivariate anaylsis, taking change of volume as dependent variable and these 8 radiomic parameters as independent variable, the change in Global Text RLN, GLSZM Text GLN and NGTDM Text Busyness were found to be statistically significant predictors (P=0.009,P=0.058 and P=0.030 respectively) of volume change pre and post treatment. The volume change was correlated with Global Text RLN,GLSZM Text GLN and NGTDM Text busyness (R = 0.75,0.53 and 0.47). The functional MRI derived Apparent Diffusion Coefficient(ADC) was correlated with NGTDM Text Coarseness,(R = 0.62).
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CONCLUSION: CT based Radiomic signatures has the potential to predict treatment outcomes as indicated by the tumour volume shrinkage due to treatment in cervical cancer. Further investigations to use this translational tool as a non invasive imaging biomarker is needed. Abbreviations: GLSZM: Gray –Level Size Zone Matrix, NGTDM: Neighbourhood Gray – Tone Difference matrix GLV: Gray – Level Variance GLN: Gray – Level uniformity RLN: Run Length Non uniformity RLV: Run Length Variance BIBLIOGRAPHY: Kumar V, Gu Y, Basu S, Berglund A, Eschrich SA, Schabath MB, et al. Radiomics: the 1. process and the challenges. Magn Reson Imaging. 2012 Nov;30(9):1234–48. 2. Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RGPM, Granton P, et al. Radiomics: Extracting more information from medical images using advanced feature analysis. Eur J Cancer. 2012 Mar;48(4):441–6. 3. Parmar C, Leijenaar RTH, Grossmann P, Rios Velazquez E, Bussink J, Rietveld D, et al. Radiomic feature clusters and prognostic signatures specific for Lung and Head & Neck cancer. Sci Rep. 2015;5:11044. 4. Ganeshan B, Panayiotou E, Burnand K, Dizdarevic S, Miles K. Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival. Eur Radiol. 2012 Apr;22(4):796–802. Ganeshan B, Goh V, Mandeville HC, Ng QS, Hoskin PJ, Miles KA. Non-small cell lung 5. cancer: histopathologic correlates for texture parameters at CT. Radiology. 2013 Jan;266(1):326– 36. A196 THE INSULIN SENSTIVITY PATTERN IN MATURITY ONSET DIABETES OF YOUNG (MODY) PATIENTS K.Felix Jebasingh1, Aaron Chapla1, Padmanaban V2, Thomas V Paul1, Geethanjali Arulappan2, Jeyaseelan L3, Mercy, Nihal Thomas1 1
Department of Endocrinology, Diabetes & Metabolism, 2Biochemistry, 3Biostatistics, Christian Medical College, Tamil Nadu, Vellore.
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AIMS AND OBJECTIVES: To study the first and the second phases of insulin secretion and sensitivity patterns in patients with MODY compared with controls. MATERIALS AND METHODS: The study comprised of 14 patients with MODY and 7 Non diabetic controls (N=7).All patients with MODY and controls underwent a 180 minute Frequent Sampling Intravenous Glucose Tolerance Test (FSIVGTT). Indices of β-cell functions were estimated from plasma glucose and C-peptide concentrations using the minimal model technique. The First phase (Phi1), second phase (Phi-2) of insulin secretion was calculated from de-convolution of serum C-peptide concentrations, Insulin sensitivity(SI) and Glucose effectiveness(SG) were derived utilizing SAAM-II(Simulation, Analysis, and Modelling) software. Student’s T test was used for comparison between two groups, and ANOVA for multiple groups. Statistical significance was taken at P<0.01. RESULTS: The mean age of patients with MODY and controls were 36.00±9.51 and 39.00±4.24 years respectively. In comparison with controls, patients with MODY had a reduced first (Phi1- 42.61± 65.74 Vs 175.61±04.91, P= 0.01) as well as reduced second phase of insulin secretion(Phi212.48 ±9.53 Vs 24.26±5.72, P=0.01). Insulin sensitivity (SI- 0.01±0.008 Vs 0.015±0.004) and Glucose effectiveness (0.001 ± 0.001 Vs 0.0008 ± 0.001) were similar compared to controls. CONCLUSION: So, secretory beta cell dysfunction is the primary defect in patients with MODY predisposing them to developing diabetes and occurs without insulin resistance.
A197 BONE HEALTH AND IMPACT OF TENOFOVIR TREATMENT IN MEN WITH HEPATITIS B RELATED CHRONIC LIVER DISEASE Kattiparambil Gangadharan Sajith1, Nitin Kapoor2,Sahana Shetty2, Ashish Goel1, Uday Zachariah1, Chundamannil Eapen Eapen1, Thomas Vizhalil Paul2 1
Department of Hepatology, 2Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Objective: To study the impact of HBV related Chronic liver disease (CLD) and its treatment with Tenofovir on bone health in Indian subjects.
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Material and Methods: This cross sectional study included men between 18 and 60 years and comprised of three groups: Group 1 was treatment naĂŻve HBV related chronic liver disease (n=79), Group 2 -those with HBV related chronic liver disease on Tenofovir for at least 1 year duration(n=136), Group 3- normal age, sex and body mass index (BMI)matched healthy controls (n=58). Bone biochemistry and bone mineral density were studied. Results: More subjects with hepatitis B related CLD (Group 1 and Group 2) were found to have vitamin-D deficiency and a higher serum C-Terminal telopeptide when compared to age, sex and BMI matched controls (Group 3). A lower mean BMD and a higher prevalence of low bone mass at the spine and forearm was found in treatment naĂŻve patients with hepatitis B related CLD(Group 1) whereas the femoral neck was most affected in Tenofovir treated patients(Group 2) (P <0.05). Age, BMI and a high viral load (>10,000) emerged as significant risk factors for low bone mass at femoral neck. Conclusion: The impact of hepatitis B related CLD and its treatment on bone health is significant. Bone health need to be periodically evaluated in these subjects especially in older men who are lean and have a higher viral load. However, long term follow-up studies are needed to look at the impact of treatment for adverse bone health in these subjects. A198 IMPACT OF PRIMARY HYPERPARATHYROIDISM AND ITS TREATMENT ON BONE MINERAL DENSITY, BONE MINERAL PARAMETERS, INSULIN RESISTANCE, BODY COMPOSITION AND QUALITY OF LIFE- A PROSPECTIVE STUDY FROM INDIA. Shrinath Shetty1, Sahana Shetty1, Nitin Kapoor1, M.J Paul2, Deepak Abraham2, Julie Hephzibah3, Nihal Thomas1, Thomas Paul1 1
Departments of Endocrinology, Diabetes & Metabolism, 2Endocrine Surgery, 3Nuclear Medicine, Christian Medical College, Vellore. AIMS: To study changes in bone mineral density, bone mineral parameters, metabolic profile, body composition and quality of life at base line and 6 months following parathyroidectomy in subjects with primary hyperparathyroidism (PHPT). MATERIAL AND METHODS: This prospective study was conducted over 18 months with first 12 months of recruitment and next 6 months for follow up. Sixty eight patients with PHPT who underwent surgery were compared with 117 age, BMI and sex matched controls. Bone mineral density(BMD), total fat mass(FM) and visceral adipose tissue(VAT) by DXA scan , bone mineral parameters and bone turnover markers(BTMs) were assessed at baseline and after 6 months.Thirty patients completed 6 months follow up. RESULTS: Among the 68 patients (48 males,20 females) with PHPT,the most common presentation was renal calculi(61.7%) followed by bony involvement(29.4%).There was a
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significant improvement in QoL and BMD on follow up(at all sites) along with normalization of bone biochemistry and a decrease in BTMs(P<0.05).There was a significant increase in BMI, FM and VAT(P<0.05).There was a non-significant increase in HOMA–IR. CONCLUSION There was a significant improvement in bone health and QoL following curative parathyroidectomy.A significant increase noted in BMI and VAT mass on follow up needs to be further studied with regards to definite clinical outcomes like diabetes mellitus. A199 DIAGNOSTIC ACCURACY OF NON-CONTRAST MAGNETIC RESONANCE ANGIOGRAPHY IN PERIPHERAL ARTERIAL DISEASE AS COMPARED TO CONTRAST ENHANCED MAGNETIC RESONANCE ANGIOGRAPHY AND COMPUTED TOMOGRAPHY ANGIOGRAPHY: ABSTRACT: Presenter: Dr. Soumya Susan Regi Designation: Assistant Professor- Grade II, Radiodiagnosis, CMC Vellore A) AIM: The aim of this study was to assess the diagnostic performance of ECG-gated non-contrastenhanced b-SSSP (balanced steady state free precision) Magnetic Resonance Angiography at a magnetic field strength of 1.5 Tesla in patients with peripheral arterial occlusive disease. B) OBJECTIVES: 1) To compare the diagnostic efficacy of non-contrast MR Angiography with contrast MR Angiography and Computed Tomography (CT) Angiography in patients with PAOD, in terms of the quantitative assessment of the degree of stenosis and the quality of the images obtained. 2) To assess the inter-observer variability in the evaluation of the degree of stenosis and the quality of the images obtained. 3) To compare with other non-invasive imaging modalities in cases of discrepancies. C) CONCLUSIONS: In this prospective study, non-contrast MR angiography was compared with contrast MR/ CT Angiography, in 170 arterial segments. i) Overall the estimation of the degree of stenosis of the arteries in the non-contrast MRA was found to be similar to the gold standard (CE-MRA / CT angiography). The noncontrast MR Angiography was however found to overestimate the length of the stenosis, especially when the length of the stenosis was relatively shorter. ii) Overall quality of non-contrast MRA images was found to be nearly as good as the gold standard (CE-MRA / CT angiography). The quality was excellent for aorto-iliac segments, good for femoro-popliteal segments and poor in the infra-popliteal segments. In a few of the cases, the quality of the non-contrast MRA images was found to be better than the CE-MRA.
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iii) In the aorto-iliac region, the sensitivity of the non-contrast MRA for detecting a significant stenosis was found to be 75 % and the specificity 92.9%, with a positive predictive value of 66.7 % and a negative predictive value of 95.1%. Weighted Kappa was found to be 0.646, suggestive of good correlation. iv) In the femoro-popliteal region, the sensitivity of the non-contrast MRA was found to be 93.3 % and the specificity 97.8%, with a positive predictive value of 93.3 % and a negative predictive value of 97.8 %. Weighted Kappa was found to be 0.911, suggestive of excellent correlation. v) In the legs, the sensitivity of the non-contrast MRA was found to be 58.3 % and the specificity 47.2%, with a positive predictive value of 42.4 % and a negative predictive value of 63 %. Weighted Kappa was found to be 0.052, suggestive of poor correlation(63). In summary, non-contrast MR angiography was found to be comparable to the contrast MR / CT angiography in the evaluation of the arteries of the lower limbs, in peripheral arterial disease. Non-contrast MR angiography can hence be used as an alternative and safe imaging modality in the evaluation of PAOD, thus avoiding the risks associated with contrast MR/ CT angiography. In few instances, it proved to be even better than the contrast MRA. Non-contrast MRA is especially helpful in assessing the aorto-iliac vessels and femoro-popliteal vessels with slightly suboptimal imaging of infra-popliteal arterial segments. Further studies and more robust noncontrast MRA techniques need to be developed for better evaluation of the infrapopliteal arteries. A200 TO STUDY THE ROLE OF ABORTION, INDUCED OR SPONTANEOUS, IN DEVELOPING SYSTEMIC SCLEROSIS IN LATER LIFE. Authors Akhila Sosa Jones1, Shreya Susan Koshy1, , Grace Rebekah2 , John Mathew3 Department and Institution 1 – 3rd year MBBS students, Christian Medical College Vellore, Tamil Nadu, India – 632004 2 – Department of Biostatistics, Christian Medical College Vellore, Tamil Nadu, India – 632004 3 – Department of Clinical Immunology and Rheumatology, Christian Medical College Vellore, Tamil Nadu, India – 632004 *Corresponding author: Dr. John Mathew, Physician , Dept. Rheumatology, Christian Medical College, Vellore (TN) -632004. Address for communication:
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Clinical Immunology and
Phone – 0416 2282529 Email – johnmathew@cmcvellore.ac.in
BACKGROUND Systemic sclerosis is an autoimmune disease for which there are multiple aetiologies which have not been proven conclusively. In a study conducted on fetomaternal microchimerism in women who had undergone termination of pregnancy, it was found that there was a significant fetal-maternal transfusion of cells, even after a first-trimester termination of pregnancy. Like many other autoimmune diseases, women are more affected by systemic sclerosis than men. From the history of women diagnosed with systemic sclerosis, it was observed that a large number of them had undergone abortion before they developed the disease. Abortions result in greater fetal cell traffic into maternal body. The presence of foreign cells in the body can induce an autoimmune reaction similar to graft versus host reaction, which might lead to the development of systemic sclerosis. Aim To study the incidence of abortions, induced or spontaneous, in developing systemic sclerosis in later life. Methods This was a case control study that was conducted in the Department of Clinical Immunology and Rheumatology between January 2015 to September 2016 after a written informed consent from each individual. This study was approved by the IRB prior to initiation. Study was conducted among women of age group 18-70, who were diagnosed with Systemic Sclerosis and fulfilled the classification criteria for Systemic Sclerosis by American College of Rheumatology (ACR). Among them the history of abortion was asked. The obtained data was then compared with a control group patients. Patients with fibromyalgia attending the Rheumatology department were taken as controls. The comparison was to find whether there were increased abortions in women with systemic sclerosis. This could give information whether there could be a possible role for abortion in the aetiology of systemic sclerosis. A sample size of 45 case and 45 control was calculated using nMaster. Statistical analysis was performed using SPSS v16.0. Results A total of 93 patients were studied of which 48 were cases and 45 controls. 25 (52.08%) among the cases and 27 (60%) among the controls had abortions. Among the 25 cases with abortion, 20 had induced abortion and 5 had spontaneous abortion. Among the 27 controls, 20 had induced abortion whereas 7 had spontaneous abortion. The Odds Ratio was 0.7246 which meant there was no significant association Discussion
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The possibilities for inability to show an association could be that fibromyalgia itself has an association with abortions which has not been described before. It could be that there is no association between abortions and developmental of systemic sclerosis in later life Conclusion In our study we did not find any significant association between abortion and development of systemic sclerosis in later life, compared to patients with fibromyalgia Key words Systemic sclerosis, fetomaternal microchimerism, spontaneous abortion, induced abortion, fibromyalgia Word count: 555 References 1.
Diana W. Bianchi, Antonio Farina, William Weber, Laurent C. Delli-Bovi, Matthew DeRiso, John M. Williams, Katherine W. Klinger. Significant fetal-maternal haemorrhage after termination of pregnancy: Implications for development of fetal cell microchimerism, American Journal of Obstetrics and Gynecology, Volume 184/, March 2001, Pages 703-706 2. Johnson, K. L., Nelson, J. L., Furst, D. E., McSweeney, P. A., Roberts, D. J., Zhen, D.-K. and Bianchi, D. W. (2001), Fetal cell microchimerism in tissue from multiple sites in women with systemic sclerosis. Arthritis & Rheumatism, 44: 1848–1854, Annals of the Rheumatic Diseases, 1988; 47, 441-444 3. Silman A L, Black Carol Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: a controlled study, Annals of the Rheumatic Diseases, 1988; 47, 441-444 A201 Prevalence of Hepatotoxicity in patients on treatment with Anti-Tuberculosis Therapy in a Tertiary Care Center: A Retrospective Survey Arunava Saha1, Blessed Winston A2, Saibal Das2, Aniket Kumar2, Joy S Michael3, Balamugesh T4, Margaret Shanthi FX2 1
Medical student (MBBS), Christian Medical College, Vellore, Departments of 2Pharmacology, 3 Microbiology, 4Pulmonary Medicine, Christian Medical College, Vellore BACKGROUND: Tuberculosis is a major health burden worldwide, and India being the leading nation in tuberculosis harbours 2-2.5 million cases presently. Anti-tuberculosis drug induced liver injury is a serious adverse effect, which causes substantial morbidity and mortality, complicating the TB treatment. Patients taking anti-TB drugs may develop severe hepatotoxicity that may progress to liver failure and death if the offending drug is not stopped promptly.
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AIM: This study was conducted to evaluate the prevalence and risk factors associated with antiTB drug induced hepatotoxicity in a tertiary care hospital in India over a period of 5 years. METHODS: This retrospective study was done with the patients presenting to the Departments of Pulmonary Medicine and General Medicine with a diagnosis of sputum positive pulmonary tuberculosis from 1st January 2008 to 31st December 2012 (5 years). The liver function test results and other relevant clinical data were obtained from the in/out-patient charts and ‘CHIPS’ database. RESULTS: 787 patients were identified, out of which only 253 came for follow-up, and had at least one LFT result done after initiation of therapy. Out of the 253 patients, 24 patients (9.48%) of the studied population developed drug induced hepatotoxicity. On further analysis, alcohol consumption (OR= 2.6065), concomitant infections like Hepatitis B (OR= 9.9130) and HIV (OR= 1.6200) had statistically significant association with anti-TB drug induced hepatotoxicity. CONCLUSION: A finding of 9.48% prevalence of hepatotoxicity is considerably high. Hence a baseline LFT before initiating anti-TB treatment and close monitoring of liver toxicity during the therapy should be adopted on a routine basis to attenuate the burden of anti-TB drug induced hepatotoxicity. A202 Inter-rater reliability of Full Outline of Unresponsiveness (FOUR) Score and Glasgow Coma Scale (GCS), among intubated patients in the intensive care unit of a tertiary care hospital in South India Alka Sara Saju¹, Ranjitha Chacko¹, Vishalakshi Jayaseelan2, Ilavarasi Jesudoss¹, Departments of Medical Nursing1 and Biostatistics2, Christian Medical College, Vellore, India Background The Glasgow coma scale (GCS) is widely used for assessing the sensorium of patients. However, verbal response, which is a part of the GCS scale, cannot be assessed in intubated and mechanically ventilated patients. Full Outline of Unresponsiveness (FOUR) is an alternative scoring system to GCS which does not include verbal response. The aim of this study was to compare the inter-rater reliability of the FOUR score compared to GCS score among intubated patients admitted in intensive care unit (ICU). Method In this prospective observational study, scoring of FOUR and GCS scores were performed by two health care professionals (Nurse- Nurse/ Physician-Physician/ Physician-Nurse) who are randomly selected by lot method. Each individual in the selected pair, independently assessed both FOUR and GCS Scores for same patient within a time interval of 30 minutes. Scoring was done only once for
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each patient. Receiver operating characteristic (ROC) analysis was done to assess the predictive value of the scores for in-hospital mortality. Results The required sample size to show an inter-rater agreement of about 0.7 was calculated as 240 ratings, with 80% power and 5% level of significance. But within the study period only 142 pairwise scores were obtained. In the present study intra-class correlation for FOUR score was 0.926 with 95% confidence interval (CI) of 0.898-0.946 and for GCS it was 0.877 with 95%CI of 0.8330.910. The Cronbach’s α showed a high degree of internal consistency for both FOUR score (α = 0.961) and for GCS (α = 0.935). Both FOUR and GCS were good predictors for in-hospital mortality and no significant differences were observed in area under the ROC curve. Conclusion Although the FOUR score appeared to have better intra-class correlation when compared with GCS, there was no statistically significant difference between the two. It is possible that a larger sample size is required to detect statistically significant difference between the scores. On current evidence, the small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in the ICU. A203 ROLE OF NOTCH1 IN THE DERIVATION OF NEURAL STEM CELLS FROM HUMAN MESENCHYMAL STEM CELLS: EXPLORING THE UNDERLYING MECHANISM. Authors: Katari Venkatesh, L. Vinod Kumar Reddy, Dwaipayan Sen* Departments and institution: Cellular and Molecular Therapeutics Laboratory, Centre for Biomaterials, Cellular and Molecular Theranostics, VIT University, Vellore-632014 *Corresponding Author Background: Neural stem cell (NSC) transplantation is a promising strategy for restoring neuronal functional network in various neurodegenerative diseases and spinal cord injuries. However, the availability of NSCs for clinical use is limited because of serious ethical concerns. Therefore it is imperative to develop novel methods to get unlimited population of NSCs to clinical application. Aim: To derive human NSCs from MSCs and exploring the role of notch signaling pathway in the process. Methods: The neurospheres were generated using human Wharton’s jelly MSCs (HWJ-MSCs) by inducing with epidermal growth factor (EGF) and fibroblast growth factor (FGF) and enzymatically dissociated using accutase into single-celled neural stem cells (NSCs). The clonal anlaysis of NSCs was examined through the soft-agar colony assay. The time-dependent expression of neural stem cell markers (Nestin, Sox2, Pax6) were analyzed through semi-
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quantitative polymerase chain reaction (RT-PCR). The expression of nestin in NSCs was immunophenotypically characterized using immunofluorescence. Role of the Notch signaling pathway was analyzed using a Îł-secretase inhibitor-DAPT. The functionality of MSC-derived NSCs was analyzed through its tri-potential differentiation ability into astrocytes (GFAP, GLUL), oligodendrocytes (Olig2, MBP) and neurons (MAP2, NEFH). The markers for the respective cell types were determined through RT-PCR and immune-fluorescence. Results: The characterized HWJ-MSCs were successfully derived into neurospheres and dissociated into NSCs. The expression of NSC marker (Nestin) in the culture further confirms the in vitro generation of NSCs (Figure 1). Notch inhibition by DAPT treatment downregulated the expression of the NSC marker Nestin, indicating that the process is dependent on Notch signaling (Figure 1) which was further verified by reduction in the numbers of neurosphere formation in presence of the Notch inhibitor. The expression of tri-lineage markers in the NSC differentiated culture clearly explains the tri-potential characteristic feature of NSCs. In addition, upon tri-potential differentiation of NSCs in the presence of Notch inhibitor, the neuronal (MAP2, NEFH) and glial markers (GFAP, GLUL and MBP) were significantly down-regulated indicating the role of Notch in efficient tri-potential differentiation of NSCs as well. Conclusion: These results suggest that the efficient derivation of NSCs (and their subsequent lineage commitment) from human MSCs requires Notch signaling pathway. Thus, large quantity of NSCs obtained through the use of human MSCs may have potential therapeutic interventions to treat various neurodegenerative diseases.
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Figure 1: Generation of neurospheres from human mesenchymal stem cells. a. Flow cytometric analysis of MSCs using positive and negative markers. b. Neurospheres c. Scanning electron micrograph of neurospheres at 10K magnification. d. Nestin positive neurospheres. e. Semi quantitative PCR to detect Nestin expression with our without Notch inhibition.
A204 Vitexin- A promising antidiabetic molecule from Acanthus ilicifolius G. A. Gayathri1 and Mahalingam Gayathri1 1 School of Biosciences & Technology, Department Biotechnology, VIT University, Vellore 632014, Tamil Nadu, India. Background Type 2 diabetes is a multifactorial disorder that accounts for about 85-90% of diabetes. Currently available drugs are focused for single target and fail to alleviate secondary complications and side effects. Medicinal plants and their chemical entities are recognized as complimentary medicine which exerts multiple targets. Recently, we reported on antidiabetic effect of methanolic leaf extract Acanthus ilicifolius in diabetic rats. Aim The main objective was to evaluate the in vitro antidiabetic activity and in silico validation of vitexin isolated from methanolic leaf extract of Acanthus ilicifolius. Methods Inhibitory effects of vitexin on α amylase, α glucosidase and glucose diffusion were performed (2011, Sudha et al). Cytotoxicity by MTT assay and glucose uptake assay of vitexin were performed on L6 cell line from rodent skeletal muscle cells. The binding of vitexin with the targets GLUT-4 and PPAR-γ is also evaluated using in silico molecular docking approach. Results Vitexin showed significant (p≤0.005) inhibition on α amylase, α glucosidase and glucose diffusion and also increases peripheral uptake of glucose in L6 skeletal muscle cell lines which does not produce any significant cytotoxicity. The binding energy pattern of vitexin with the targets GLUT4 and PPAR- γ crucial residues validates its functionality. Conclusion In vitro and in silico studies demonstrate that the vitexin exhibits excellent antidiabetic activity. In vivo experimental validation of the vitexin is in progress to develop as a new therapeutic agent. Key words: Type 2 diabetes, Acanthus ilicifolius, in vitro and in silico.
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A205 ANTIMUTAGENIC PROPERTIES OF NARINGENIN AGAINST MITOXANTRONEAN IN VITRO AND IN VIVO STUDY K.Chandan1, K.Premkumar2 1
VIT University, School of Bio-Science & Technology, Vellore, TamilNadu, India
2
Bharathidasan University, Assistant professor, Cancer genetics & Nano-medicine laboratory, Department of Biomedical science, Bharathidasan University, Trichy, TamilNadu, India.
BACKGROUND Mitoxantrone, is an anti-cancer chemotherapy drug and topoisomerase inhibitor. It distrupts DNA synthesis in both healthy and cancer cells by intercalation between the DNA bases. Miroxantrone lacks the ability of selectively targeting the cancer cell. The normal cells most commonly affected by chemotherapy are the blood cells. Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables and it possess antimutagenic activity AIM To investigates the effect of naringenin against the genotoxic doses of mitoxantrone by assessing chromosomal aberrations (CA), mitotic index (MI) in cultured human lymphocytes and bone marrow micronucleus test in mice. METHODS MTT assay, Chromosomal aberration analysis, Mitotic index analysis, Bone marrow micro nucleus test RESULTS For selecting the concentration of naringenin and mitoxantrone its cytotoxic effect on hepG2 cell line was carried out. 1µM, 2µM of mitoxantrone and 20µM of naringenin were used for further treatment in lymphocyte culture and bone marrow micro nuclei test. Mitotic index result shown 20µM of naringenin has its effect in increasing the mitotic index as single compound or in combination with 1µM mitoxantrone. Similarly, chromosomal aberration was reduced when 20µM naringenin. Bone marrow micro nuclei test result shows that the effect mitoxantrone on formation of MnPCE was increased in dose dependent manner. CONCLUSION 1µM, 2µM of naringenin has the potential to reduce the genotoxicity induced by 1µM, 2µM of mitoxantrone, thereby reducing the chances of developing secondary tumours during the therapy.
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A206 CYTOTOXICITY STUDIES OF ANTIDIABETIC POTENTIAL STRAIN ALTERNARIA LONGIPES VITN14G ISOLATED FROM MANGROVE PLANT AVICENNIA OFFICINALIS IN HEP 2 CELL LINES R.Nathiya1, Gayathri Mahalingam1* Department of Biotechnology, School of Biosciences & Technology, VIT University, Vellore 632014, Tamil Nadu, India Email: gayathrigopinath@vit.ac.in
Background: A total of 19 different endophytic fungi were isolated from the mangrove plant Avicennia officinalis. The respective crude extract of isolated endophytic fungi was evaluated for its in vitro anti diabetic activity. The effective crude extract was further explored for its cytotoxic activity using Hep 2 cell lines. Methods: Ethyl acetate (EtOAc) crude extract of Alternaria longipes VITN14G were isolated using standard protocols. The Hep 2 cell lines were grown in flask containing 10% minimum essential medium (MEM). Different concentration from 100 µg to 6.25 µg of crude extract was tested on Hep 2 cell lines using 96 wells micro titre plate. The plate was then incubated at 37®Cfor 12 hours under 5% CO2 atmosphere. The cytotoxic concentration 50 (CC50) of crude extract was observed by the changes present in the morphology of the cells for every 24 hrs. The results were recorded for 3 days. Results: The ethyl acetate crude extract of Alternaria longipes VITN14G showed non-toxic with the concentration of 100 µg / ml on Hep 2 cell lines. The in vitro cytotoxic effect on Hep 2 cell lines was studies and there was no detectable changes in the morphology were observed like cell death, cell shrinkage etc. Conclusion: EtOAc extract of endophytic fungi Alternaria longipes VITN14G exhibited satisfactory anti-diabetic activity against type 2 diabetes and showed non toxic against Hep 2 cell lines. Thus the ethyl acetate crude extract can be further subjected to compound isolation for the development of drug in the management of type 2 diabetes. Keywords: Alternaria longipes VITN14G, Avicennia officinalis, cytotoxicity, diabetes.
A207 STRUCTURAL STABILITY AMONG HYBRID ANTIMICROBIAL PEPTIDE CECROPIN A (1-8) - MAGAININ 2 (1-12) AND ITS ANALOGUES – A COMPUTATIONAL APPROACH B. Senthilkumar and R. Rajasekaran*
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Department of Biotechnology, School of Bio Science and Technology, VIT University, Vellore 632014, Tamil Nadu, India Background: Cecropin A-Magainin 2 (CA-MA) hybrid antimicrobial peptide (AMP), a combination of two naturally occurring AMPs, cecropin A and magainin 2 is preferred widely in pharmaceutical applications as an antibacterial drug of choice. A stable CA-MA can exhibit a strong antibacterial activity with a reduced cytotoxicity in mammalian cells. Aim: In this study, three AMP structures native CA-MA hybrid and its tryptophan substitutes CA-MA L2 and CA-MA A2 was computationally studied to analyze their structural stability and functionality. Methods: Three dimensional structural constraints of native CA-MA hybrid and its mutants were retrieved from Protein Data Bank. The energy minimized structures were subjected to conformational sampling using tCONCOORD program. The obtained trajectories were dynamically analyzed for determining its structural and functional territory and select the stable CA-MA as template for drug scaffold. Results: Computational analysis like, intra-molecular interactions (25), relative stability (3.22) and instability index (-14.28) performed on static CA-MA structures, showed an increase in structural stability of native CA-MA hybrid. Additionally, static and dynamic analysis of the generated peptide ensembles also supports CA-MA with a RMSD (3.98Å), RMSF (0.202Å), Rg (11.98Å), ovality (3.33), hydrogen bond occupancy and hydrophobicity (69.7%) along with hydrogen bond composition, strength (-4.212 kcal/mol) and distribution comparatively. Hydrogen bond plays a vital role in secondary structure determination, the distribution of secondary structure throughout the generated ensemble of native CA-MA hybrid showed a concrete conservation of stable helical content with a high helical stability (52.25%) and computed free energy (-1.74 kcal/mol) in membrane mimicking environment than other mutants proving its functional activity comparatively. Conclusion: This study illustrates the parameters responsible for the stability of native CA-MA hybrid, which could be used for designing stable AMP biodrugs with low cytotoxicity in future. The result can be potentially extended to other AMPs to assist in their exploitation as peptide drugs.
A208 SCREENING OF OXALATE DEGRADING BACTERIA FROM THE GUT OF EXPERIMENTAL RATS FED WITH OXALATE RICH DIET Yogita Mehraa, Pragasam Viswanathana* a Renal Research Lab, SBST, CBMR,VIT University, Vellore, TN, India
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Background Calcium oxalate stone formation is a multifactorial etiology with high morbidity and economic burden due to greater recurrence rate. Studies indicated that stone formers found to lack intestinal oxalate degrading bacteria’s in their gut, which eventually leads to hyperoxaluria. Aim Screening of oxalate degrading bacteria from the gut of experimental rats fed with oxalate rich diet Methods Albino male Wistar rats (n=36) were divided into 3 groups with 6 animals each. Group 1: control (normal diet), Group2: 2% sodium oxalate supplemented with normal diet, Group 3: 4.5% sodium oxalate supplemented with normal diet. Urinary oxalate, calcium, magnesium and creatinine were estimated at the end of every week for a period of 2months. At every tenth day animals were sacrificed from each group for the isolation of oxalate degrading bacteria and the kidneys were excised and stored in 10% formalin for histopathology studies. Results The levels of urinary oxalate and calcium were markedly elevated in rats fed with oxalate supplemented diet. However the increase in urinary oxalate and calcium (p<0.001) excretions over the course of the study were significant only in the 4.5% oxalate diet fed rats. In case of magnesium, the increase in urinary excretion was not marked. Von Kosa staining indicated the calcium oxalate crystal deposition in the renal tissues of the rats fed with 4.5% oxalate diet. In contrast, no deposition was observed in the tissues of 2% oxalate diet fed rats. A significantly more numbers of colonies were obtained in oxalate medium D from the gut of 4.5% oxalate diet fed rats compared to other groups. Conclusion Significant increases in the oxalate degrading bacteria were obtained from the gut of rats supplemented with higher concentration of oxalate. Further studies are underway to identify the bacteria and to prepare consortia for excess oxalate degradation in stone formers in the form of probiotic health drink. A209 GARLIC OIL NANOEMULSION MITIGATES PODOCYTE INJURY IN HIGH FAT FED PREDIABETIC WISTAR RATS Yuvashree Muralidarana, Gokulakannan Ragavana, Ganesh Nachiappa Rajeshb, Pragasam Viswanathana* a Renal Research Lab, CBMR, SBST, VIT University, Vellore, TN, India
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b
Department of Pathology, JIPMER, Dhanvantrinagar, Puducherry, India
Background: Free fatty acids in obese increase NF-κβ expression by downregulating PPAR-γ activity, which eventually leads to prediabetes mediated podocyte injury. Garlic oil with proven PPAR-γ agonist activity could ameliorate podocyte injury. The bioavailability of garlic oil is improved by nanoemulsification. Aim: To investigate the effect of GARLIC OIL NANOEMULSION (GNE) on podocyte injury in high fat fed prediabetic rats ascertained with microalbuminuria (MA).
Methods: Male Wistar rats (n=60) were segregated into control group (Con), high fat diet (HFD) fed Prediabetic group (PDia), Telmisartan (10mg/Kg) treated prediabetic group (PDia + Tel), Garlic oil nanoemulsion (50mg/kg) treated prediabetic group (PDia + GNE), Garlic oil (50mg/kg) treated prediabetic group (PDia + GO). Before and after treatment, oral glucose tolerance test (OGTT), urinary albumin/creatinine ratio (UACR), protein/creatinine ratio (UPCR), lipid, serum albumin, protein and lipid profile were estimated in all groups. Haematoxylin & Eosin (H & E) staining, Periodic acid schiffs base (PAS) staining and Oil Red O staining were carried out. Relative mRNA expression of podocin and NF-κB in renal tissues was detected by RT-PCR. Results: GNE and GO administration showed a similar effect on lipid profile, ectopic fat deposition and OGTT. However, UACR (p<0.01) and UPCR (p<0.001) attenuated significantly on GNE treatment, which showed a marked amelioration in mesangial cellularity, mesangial expansion, tubular and glomerular basement membrane thickening. In addition, GNE significantly suppressed NF-κB expression (p<0.01) and promoted podocin gene expression (p<0.0001) in renal tissues. Conclusion: GNE is an effective therapeutic formulation to increase the bioavailability of GO that governs protection against glomerular dysfunctioning by inhibiting NF-κB expression within 4 weeks.
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POSTERS
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P101
IDENTIFICATION OF ABNORMAL HAEMOGLOBIN VARIANTS DURING HBA1C MEASUREMENT IN ROUTINE DIABETIC FOLLOW UP Janani Iswarya.S1, Victoria job1,Department of Clinical Biochemistry1, Eunice S Edison2, Department of Hematology2,Christian Medical College, Vellore BACKGROUND: Glycated Hemoglobin(HbA1C) is a biochemical marker widely used to monitor the long term glycemic control and it is formed as the result of irreversible non enzymatic glycation at one or both N-terminal valines of the beta Hb chain. Depending on the determination method used, the concentration of HbA1c is approximately 4–6% in healthy patients without diabetes. Methods include to measure HbA1c are cation exchange HPLC, boronate affinity, electrophoresis, and immunoassays. Despite of the advancements in the method used to evaluate HbA1c, increasing number of variants have been reported to cause false HbA1c results. HPLC methods usually indicate the presence of an hemoglobin variant, but they lack the resolution necessary to differentiate between them. They may demonstrate additional peaks in the chromatograms and these may be combined with clinically low or high results. AIM: To identify the Hb variants from the randomly selected patient samples during the measurement of HbA1C in routine diabetic follow up. METHOD: HbA1c values were measured by Ion Exchange High Pressure Liquid chromatography (VARIANT II TURBO HbA1C kit). Hemoglobin variants were analyzed by VARIANT II HPLC System (Bio-Rad, Hercules, CA). DNA was extracted, and the molecular analysis was performed by direct DNA sequencing of β globin and α globin genes. RESULTS: The findings are tabulated below. NO Hb (g/Dl) MCV (fi) 1
14.5
*
4.2
Hb (%) 2.8
2
11.8
85.2
0.9
1.9
21.6%
3
12
*
0.9
2.0
34.2%
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HbF (%)
A2 Unkown Variant (%) 32.8
Genetic variant identified HBB:c.352C>T HbTsukumi HBA1:c272A>C Hb J-Rajappen HBA2.c.63 C>G Hb Le-Lamentin
4
10.9
79.6
0.7
2.8
9.7%
HBB:c.4G>A Hb South Florida
*Not Available CONCLUSION: Presence of Hb variants during HbA1c measurement poses a great challenge to the clinicians in the management of diabetes though they are benign variants. Efforts should be taken to identify and record these unusual variants in our diabetic population. P102
DIETARY MODIFICATIONS BY NEWLY DIAGNOSED CHRONIC KIDNEY DISEASE PATIENTS BEFORE VISITING DIETITIAN Jayalakshmi K*, Mahendri.N.V., Department of Dietetics, Christian Medical College, Vellore632 004 BACKGROUND : Diet therapy is the corner stone of management of chronic kidney disease (CKD) unless instituted at the earliest on diagnosis. In India the availability of dietitiansare limited.Hence newly diagnosed CKD patients modify their diet based on doctors’ general diet advice which may be incomplete and might compromise nutrition status. As initial diet modifications studies on newly diagnosed CKD patients are scanty the current study was undertaken. AIM: To assess dietary modifications adopted by newly diagnosed CKD patients. METHOD: A cross sectional study, using purposive sampling, was conducted on newly diagnosed 40 CKD patients of age between 25 to 75 years who were referred to the diet clinic, tertiary care centreIndia.After obtaining oral consent, data was collected regarding demographic data and food intake by interview using pre tested questionnaire. RESULTS: Out of 40 subjects 32(80%) were men and 8 (20%) were women. The period of diagnosis ranges from 15 days to 6 months. 98% of the subjects were nonvegetarian. The foods avoidedwere nonvegetarian40%,fruits 38%, milk and milk product 38%, pulses30%, green leafy vegetables 15%and salt5%. The intake of salt 90%, fruits 45%, nonvegetarian 40%, pulses30%, milk & milk products32%, green leafy vegetables25% were reduced.Source of information about diet modifications were clinicians 87% and others 13%.
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CONCLUSION: The current study reveals that diet advice by the clinicians is inadequate; hence CKD patients should be referred to a dietitian for individualized diet counseling.
P103
DISTINCT UPPER AND LOWER BODY FAT DEPOTS DEMONSTRATE OPPOSING ASSOCIATIONS WITH CARDIOMETABOLIC RISK IN ASIAN INDIANS Authors: Mahasampath Gowri1, Belavendra Antonisamy1, Finney S Geethanjali2, Fredrik Karpe3, Caroline HD Fall4, Nihal Thomas5, Thomas V Paul5, Senthil K Vasan3 1
Departments of Biostatistics, Christian Medical College, Vellore, India 2Department of Clinical Biochemistry, Christian Medical College, Vellore, India 3Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, United Kingdom 4MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, United Kingdom 5Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India BACKGROUND & AIM: The paradoxical association between android and gynoid fat depots in relation to type 2 diabetes and cardiovascular disease is well documented in several populations. There is no evidence of similar relationships among Asian Indians. The current study evaluated the associations between total fat, regional fat and lean mass with cardiometabolic traits in a cohort of 1,080 individuals (male: 581 and female: 499) aged 41 years. METHOD& RESULTS: Regional body fat depots (android, gynoid, visceral), total fat and lean mass were measured using Hologic DXA. Our results show that android, visceral and total fat mass are associated with increased risk for type 2 diabetes, impaired fasting glucose, insulin resistance, hypertension and dyslipidema and these associations are attenuated, yet remain significant when adjusted for age and total fat mass. Android fat was associated with greater risk compared to visceral fat and total fat for all endpoints. Contrastingly, gynoid fat mass and leg display protective associations with cardio metabolic traits, with stronger effects observed with gynoid fat in women for all traits, particularly for insulin resistance (OR 0.52; 95%CI 0.32,0.84). We provide the first evidence of dichotomy of upper and lower adiposity depots in relation to cardiometabolic risk in Asian Indians. Keywords: Android, gynoid, visceral fat, insulin resistance, Asian Indians
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P104
NUTRITIONAL DATA OF DIABETES MELLITUS PATIENTS WITH LOW BMI Mini Joseph, Riddhi Das Gupta, Praveen Gangadhara, Roshna, Shajith, Nithya, Ruth Volenaand Nihal Thomas Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India BACKGROUND : Fibro calculus pancreatic diabetes (FCPD) is an uncommon form of diabetes secondary to chronic pancreatic calculi and is not associated with alcohol abuse. The pre-diabetes condition is called Tropical Chronic Pancreatitis (TCP). Type1Diabetes Mellitus (T1DM) occurs due to the autoimmune destruction of insulin producing islet beta cells predisposed by genetic and precipitated by environmental determinants. Patients with the above forms of Diabetes have a low Body Mass Index (BMI). OBJECTIVE: The main objective was to determine if there were significant differences in the nutrient intake between these groups of DM patients. METHODOLOGY: All FCPD, TCP and T1DM patients visiting the Endocrine Department in the last 3 months were included in this study. The study sample included 50 subjects, age-gender matched, (FCPD n=15; TCP n=11; T1DM n=24) and informed consent was obtained from all of them. The 24 hour recall method along with a food frequency questionnaire was used to get information on their nutrient intake. The nutrient intake was calculated using the Nutritive value of commonly used Indian Foods by ICMR 2010. RESULTS: The mean age (33.44 + 7.6 years), mean BMI (20.1 + 3.13kg/m2) and mean glycosylated haemoglobin (8.03 + 2.41%) of the patients were comparable between the groups. The T1DM patients had the longest duration of DM ranging between 2-20 years and highest HbA1C of 9.1 + 2.6%. The mean HbA1C of TCP patients was 5.7 + 0.5%. Dietary data indicated that the percentage of calories from fats and proteins were significantly below the RDA, along with a deficit in the intake of micronutrients in all the three groups. One way Anova indicated that there was a significant difference in the intake of proteins (p=0.015), carbohydrates (p<0.001), fats (p<0.001) and energy (p=0.002) between the groups. The fibre intake was comparable between the groups. DISCUSSION: The dietary data revealed a deficit in intake of energy, macronutrients and micronutrients amongst these Low BMI Diabetes mellitus patients. There is an urgent need to educate our patients on nutrition therapy to ensure appropriate balanced nutrition so that it has a significant impact on their long term glycaemic control.
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Keywords: Fibro calculus pancreatic diabetes, Tropical Chronic Pancreatitis, Type 1 diabetes mellitus, low BMI, nutrition. P105
A MONO DYNAMIC FINF PLANNING TECHNIQUE FOR PMRT WITH NODAL REGION AND DOSE DYNAMIC FLUENCE VERIFICATION Mohamathu Rafic K1, Timothy Peace Balasingh1, Ebenezer Suman Babu1, Rabi Raja Singh1 1 Department of Radiotherapy, Christian Medical College, Vellore 632004, India OBJECTIVE: This study focuses on incorporation of a mono-dynamic Field-in-Field (MD-FinF) technique and dose dynamic fluence verification using electronic portal imaging device (EPID) with an intention to overcome the limitations imposed by conventional techniques. MATERIALS AND METHOD: The MD-FinF tangential beams with direct anterior field for nodal region in single isocenter treatment plans were generated in Eclipse planning system and delivered using Clinac 2100C/D dual energy linear accelerator integrated with an aS1000 EPID. FinFs fields with optimum beam weight were added primarily from the medial tangent, fitted to beam’s eye view of entire target volume. All the static FinFs created from the medial tangent portal were converted into a dose dynamic portal. Gamma () evaluation for the dose dynamic portals were performed with 3%/ 3 mm dose difference and distance to agreement (DD and DTA) criteria using portal dosimetry software. RESULTSS AND DISCUSSION: MD-FinF plans showed excellent dose coverage (V95%; >95%), higher degree of conformity (TDCI ≤1.25) and homogeneity (TDHI ≤0.12) for entire target volume without compromising the OAR sparing for PMCW with nodal region. Incorporation of MD-FinFs considerably reduced the lower and higher isodose spread to the ipsilateral lung, heart and healthy tissue without affecting dose homogeneity. Further, evaluation showed more than 96% pixel pass rate in the dose matrices confirming the efficacy of the MD-FinFs. Moreover, the MD-FinF plan offers less probability for geometrical miss in highly irregular PMCW with nodal radiotherapy. CONCLUSION: We conclude that the novel mono-dynamic FinF technique using conformal static field arrangements would facilitate easier plan execution and faster dose delivery and promises to be a suitable treatment option for the complex PMCW with regional nodes.
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P106
PULSED SHORTWAVE DIATHERMY FOR MANAGEMENT OF ILIOPSOAS HEMATOMA IN PERSONS WITH HEMOPHILIA – RESULTSS FROM A SINGLE CENTRE Merlyn Tilak1, ArunPaul1, Divya Singh1, Judy Ann David1, Abraham S. Singh 2, Fouzia.N.A2 , Anu Korula2 , Aby Abraham2 , Alok Srivastava2 , 1 2
Department of Physical, Medicine and Rehabilitation, Christian Medical College, Vellore. Department of Haematology, Christian Medical College, Vellore.
INTRODUCTION AND OBJECTIVES: Iliopsoas hematoma is reported as the most severe type of muscle hematomas, with significant morbidity. Pulsed shortwave diathermy (PSWD) is used as an adjunct to physical therapy for the enhanced resolution of hematoma and prevention of rebleed and pseudotumour. Despite its use in the management of Iliopsoas hematoma, to date there are no reports on outcomes following PSWD in management of Iliopsoas hematoma. The aim of this study was therefore to review the data of patients treated for Iliopsoas hematoma from Christian Medical College, Vellore, retrospectively and to report the clinical presentation, the physical therapy protocol including PSWD and the outcome. PATIENTS AND METHOD: A total of 37 subjects received PSWD and physical therapy following haemostatic therapy. All subjects were on episodic therapy, presenting with varying degrees of pain in hip, groin, thigh, low back, lower abdomen and gluteal region, tenderness and hardness in the lower abdomen, hip in partial flexed position, sensory and motor loss in the distribution of femoral nerve. RESULTS: The mean time period before starting physical therapy was 7.19 ± 2.11 days and the mean duration of physical therapy was 4.08 ± 0.72 weeks. The results show a significant reduction in pain score and hip flexor tightness and significant improvement in the sensory and motor scores following PSWD and the physical therapy protocol (p value = 0.000). The follow up ultrasound was done for a relatively low proportion of subjects (20%). The subjects who underwent PSWD (18.9%) showed complete resolution of hematoma. Subjects (25%) who did not receive PSWD and physical therapy reported repeat bleeds. CONCLUSION: We conclude that following haemostatic therapy, PSWD may be required as an adjunct to physical therapy protocol for the complete resolution of Iliopsoas hematoma and prevention of
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rebleed. However, heterogeneity in the baseline characteristics and the therapy given to the study subjects warrants caution while interpreting the results. Conflicts of Interest: The authors declared no conflicts of interest.
P107
MANAGEMENT OF FLEXION DEFORMITY OF THE KNEE JOINT IN PERSONS WITH HAEMOPHILIA- AN ALGORITHMIC APPROACH Merlyn Tilak1, Arun Paul1, Anumeha Srivastava1, Divya Singh1, Judy Ann David1, Abraham S. Singh2, Fouzia.N.A2, Anu Korula2, Aby Abraham2, Alok Srivastava2 1 Department of Physical Medicine and Rehabilitation, Christian Medical College Vellore. 2 Department of Haematology, Christian Medical College Vellore. INTRODUCTION AND OBJECTIVES: Flexion deformity (FD) of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) impacting independent mobility. There is limited literature on the physical management of this condition. We have extensively managed FD by various nonsurgical techniques. This report describes our algorithmic approach and outcome of therapy in PWH treated by these methods. PATIENTS AND METHOD: A total of 28 subjects, mean age of 16±7 years, were treated for FD of the knee. The average duration of FD was 12 months (range: 0.5 to 78). The protocol included progressive graded physical therapy (PT) followed by serial casting (SC) with plaster of Paris (POP). Under prophylactic factor cover, manipulation under anaesthesia (MUA) with POP casting was done in carefully selected cases. Functional correction (FC) was defined as extension loss of 10 to ≤ 20 degrees and complete correction (CC) as extension loss ≤10 degrees. Surgery was done when adequate correction could not be achieved conservatively. RESULTS: The mean duration of graded PT was 3.18±1.96 weeks. FC was obtained by 8 subjects (28%) with reduction in extension loss from 38.75±19.41 to 17±3.66 degrees, with no associated joint bleeds in >95% of treatment days. SC was done for 13 subjects and FC was achieved for 4 subjects (30%), with a reduction in extension loss from 32.5±2.89 to 17.5±2.89 degrees. Out of the 9 subjects who underwent MUA with POP casting, FC was obtained for 6 subjects (67%), with reduction in extension loss from 36.67±4.08 to 19±2.45 degrees. The mobility status was assessed using Functional Mobility Scale, which improved from 1.64±0.95 to 3.29±0.71. Surgery was done for only 4 subjects (14%) who achieved CC from an extension loss of
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65±26.14 to 6.25±4.79 degrees. The average duration for correction using this protocol was 7.8 weeks (range: 3.5 to 52). CONCLUSION: This study shows that functional correction of FD of the knee can be achieved using conservative methods in >80% of PWH with significant improvement in their mobility (p value= 0.000). Conflicts of Interest: The authors declared no conflicts of interest. P108
ASSESSING THE ADJUSTED NECK CIRCUMFERENCE AND THE STOP BANG SCORE IN PATIENTS UNDERGOING POLYSOMNOGRAPHY FOR SUSPECTED SLEEP APNEA PURPOSE: To evaluate the correlation of the adjusted neck circumference score (ANCS) and the STOPBANG score with severity of obstructive sleep apnea (OSA). METHOD: All patients referred to our sleep center were screened using the ANCS and STOPBANG. ANCS consists of the sum of four measures including neck circumference (cm=#points), history of hypertension (4 points), history of snoring (3 points) and history of night-time choking or gasping (3 points). STOP BANG score is a sum of 8 components (Snoring, Tiredness, Observed apneas, Blood Pressure, BMI>35Kg/m2, Age >50, NC>40cm & Gender male.) present or not. These sum are compared to the sleep study results. Patients with OSA (Apnea Hypopnea Index (AHI)>5) were included. RESULTS: 188 patients,128 male (68.1%) 60 females(31.9%)were screened. 162 patients had OSA (AHI>5/hr) and 26 did not. 48 patients (29.6%) had mild OSA (AHI 5 to 15, Average 10) with an average age of 51 years, average body mass index (BMI) of 29.5 Kg/sq meter, ANCS of 45.2 and average STOPBANG score of 4. 42 patients (25.9%) had moderate OSA (AHI 16 to 30,Average 21/hr) with an average age of 52.8, average BMI 31.7, ANCS of 48.3 and STOPBANG of 5. 72patients (43.83%) had severe OSA (AHI>30,Average 56) with an average age of 53, BMI 31, ANCS of 50 and STOPBANG of 5.3. CONCLUSIONS: The ANCS can be used to distinguish mild from moderate to severe OSA. However, the score does not show a significant correlation with AHI. CLINICAL IMPLICATIONS:
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While the ANCS provides a general assessment of the severity of OSA, it does not discriminate the precise severity. A better clinical screening tool is needed to prioritize patients for polysomnogram P109
METABOLIC IMAGING OF THE SKELETAL MUSCLE: ANDMULTIVOXEL SPECTROSCOPY USING A 3T MR SCANNER
SINGLE
Roshan S Livingstone1, Abel J Thomas1, Padmanabhan V2, Riddhi Das Gupta2, Nihal Thomas2 and Meredith Hawkins3 1Departments of Radiology, CMC Vellore 2Department of Endocrinology, CMC Vellore3Diabetes research and training center, Albert Einstein College of Medicine Corresponding author: roshanlivingstone@gmail.com BACKGROUND : An association between insulin sensitivity and accumulation of lipids in the skeletal muscle has been reported in literature. The non-invasive method of quantifying lipid content using Magnetic resonance spectroscopy (MRS) has a few limitations due to muscle fibre orientation and bulk magnetic susceptibility effects. AIMS AND OBJECTIVES: To evaluate lipid content in the soleus and tibialis anterior (TA) muscle and validate the single voxel (SV) and MR spectroscopic imaging (MRSI) technique in the evaluation of lipid content in the soleus muscle. METHODS AND MATERIALS: Fifty five subjects who underwent SV and MRSI techniques of the soleus and TA muscle using a Philips 3T Interaachieva MR scanner were included in the study.This study was approved by the Institutional Research Board and Ethicscommittee (institutional review board no. 7722/2012). Water suppressed and non-water suppressed spectral data was acquired using point-resolved spectroscopy sequence (PRESS) withrepetition time (TR)/echo time (TE) of 4000/36ms, with 32 averages for a voxel size of 15x15x15 mm3.The spectroscopic data was analysed using Javabased magnetic resonance user interface software. RESULTS AND CONCLUSION: The mean intramyocellular lipid (IMCL) and mean extramyocellular lipid (EMCL) content expressed in percentage of water resonance frequency in soleus was 1.75 and 1.8; for TA muscle, it was 2.9 and 3.3 respectively. The IMCL from soleus muscle using both SV and MRSI methods show correlation with BMI, with SV showing a stronger correlation (r = 0.57, p = 0.00) compared to MRSI(r=0.35, p=0.02). The SV method for soleus shows significant correlation
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with total body fat (r=0.431, p=0.00) and leptin (r=0.34 and p=0.04) while no correlation was found with MRSI method. The IMCL in soleus muscle was not affected by the placement of voxel, magic angle or the bulk susceptibility effects. Hence, for soleus muscle, MRSI method can be considered if the splitting of peaks are not visualised in SV method. P109
COMPARISON OF SERUM HUMAN EPIDIDYMIS PROTEIN4 Vs CA125 IN WOMEN WITH ADNEXAL MASSES *S. Vanitha,**Dr. Akalya,** Dr. Abraham Peedicayil, *Dr. Victoria job biochemistry ** Obstetrics &Gynaecology
*Clinical
BACKGROUND : Ovarian cancer is the seventh most common cancer with a high mortality ratio. At least 70% of ovarian cancers are identified in advanced stages. Adnexal masses can either arise from the uterus, fallopian tubes, broad ligament or ovaries. It is necessary to differentiate the adnexal masses and make a correct diagnosis because the management is different for each type of mass. However, it is difficult to differentiate the origin of Adnexalmasses only by clinical examination. A correct diagnosis allows forplanning the extentof the surgery. The proportions of malignant masses in premenopausal and postmenopausal women are 10% and 40% respectively. Hence it is important to assess the risk in women with pelvic masses in order to decide the type of surgery. The non-invasive tools available to differentiate benign and malignant massesare CA125, RMI and ROMA. Though CA125 is elevated in 85% ofadvanced stages, it is only elevated in 50% of early stage cancers. Hence, there is a need for an accurate and reliable test. Serum HE4 is the new tumor marker which is found to be more sensitive and specific than CA125. Evaluation of HE4 has not been reported in India so far. AIM: To compare diagnostic test characteristics of serum HE4 and CA125 in diagnosing ovarian cancer in women with adnexal masses.
MATERIALS AND METHODS: Total of 90 women of age 16-80yrs with adnexal mass, planned for surgery were included in this study. There were 32 patients with ovarian malignancy and 58 patients with benign ovarian masses. Of the 90 women, 27 were postmenopausal and 53 were premenopausal women. HE4 was measured usingCobas E170 by Electrochemiluminescenceimmunoassay and CA125using IMMULITE 2000by chemiluminescentimmunometric assay. RESULTS: Sensitivity
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CA 125 (%)
HE4 (%)
C
o Specificity c l us
premenopausal
57.1
92.9
postmenopausal
61.1
83.3
premenopausal
97.8
65.3
postmenopausal
66.7
100
CONCLUSION: Though HE4 is more sensitive and specific, the combination of these markers help in differentiation of Adnexal masses. HE4may help in early diagnosis of cancer. But it requires further detailed study with a large sample size. P110
ROTAVIRUS GASTROENTERITIS IN CHILDREN <5 YEARS HOSPITALIZED AT A TERTIARY TEACHING HOSPITAL IN SOUTH INDIA Authors: Sasirekha,KarthickNandhan, ArchanaSriraman, SidharthaGiri, Sudhir Babji, Gagandeep Kang. Department& Institution: Wellcome Trust Research Laboratory, Christian Medical College, Vellore INTRODUCTION: In India, an estimated 100,000 children die each year because of rotavirus gastroenteritis. Rotavirus is a wheel shaped (rota) virus belonging to the family Reoviridae. About 20–70% of hospitalizations due to acute gastroenteritis (AGE) are attributable to rotavirus. OBJECTIVE: To estimate the burden of AGE due to rotavirus in children <5 years of age hospitalized at a tertiary care teaching hospital in south India over a period of 2 years.
METHOD: Stool samples collected from children <5 years of age hospitalized with AGE at Christian Medical College (CMC), Vellore, during a 2 year period (July, 2014- June, 2016) were included in the study.The samples were collected after obtaining informed consent from parents/guardian. The stool samples were stored at -700C prior to testing. All stool samples were initially screened for group A rotavirus by ELISA (Rotaclone). The ELISA positive samples were then genotyped (VP7/G and VP4/P typing) using reverse transcription PCR (RT-PCR).
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RESULTS AND DISCUSSION: A total of 813 children <5 years hospitalized with AGE at CMC, Vellore were enrolled during the 2 year period (June, 2014- July, 2016), of which stool samples were collected from 733 children. 203 (27.7%) samples were positive for group A rotavirus by ELISA (Rotaclone). Of the 203 ELISA positive samples, genotyping for group A rotavirus strains using RT-PCR showed the following results: completely typed (169 samples, 83.25%). The common rotavirus genotypes were G1P[8] (n=112, 55.2%), andG9P[4] (n=29, 14.3%), followed by G2P[4] (n=8, 3.9%) andG10P[11] (n=7, 3.4%)and G3P[8] (n=4, 2%) and G12P[6] (n=3, 1.5%) CONCLUSION: Rotavirus was associated with 27.7% of children <5 years hospitalized with AGE. G1P [8] , G9 P[4]were the common genotypes associated with the cases of AGE.
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CONTRAST SENSITIVITY AND GLARE VISUAL ACUITY IN DIFFERENT MORPHOLOGICAL TYPES OF CATARACT IN AN INDIAN POPULATION Ms Abhriya Dey, Ms Chris Jacob, Dr Satheesh ST Selvin, Dr Thomas Kuriakose, Department of Ophthalmology, Christian Medical College, Vellore BACKGROUND : Cataract increases the intraocular light scatter which affects the retinal image contrast and the sensitivity. Many patients complain of glare or visual quality drop at different levels/morphological types of cataract, which affect the visual ability in daily routine. Traditionally, visual acuity is the only standard measure to look for the extent of vision drop as a pre requisite to cataract surgery. PURPOSE: To quantify the change in contrast sensitivity and glare induced visual acuity in various morphological types of cataract in Indian population, which when known can be used to develop a protocol to advice the timing of surgery. MATERIALS AND METHODS: This study was a cross sectional observational study and was done at the department of Ophthalmology, Christian Medical College, Vellore. All patients admitted for cataract surgery between February and April 2016, with best corrected visual acuity (BCVA) of Snellen equivalent of 6/60 or better above 40years of age were enrolled after an informed consent. LogMAR vision, Contrast sensitivity using a Pelli- Robson chart was measured with and without induced glare by using Brightness Acuity Tester were measured pre and post operatively. Paired t test with
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Bonferroni’s correction and Chi square analysis were used for statistical analysis apart for mean & SD for categorical variables. RESULTS: 78 patients participated in the study and were categorised according to their morphological types. When induced with high glare group 1 (Nuclear Sclerosis) had a drop in the LogMAR VA (Mean Difference 0.159, 7 letters) and the contrast sensitivity (Mean 0.502, 3 step drop), group 2 (Posterior subcapsular cataract) had a drop in the LogMAR VA (Mean 0.143, 7 letters and the contrast sensitivity (Mean 0.622, 3.5 step drop) and the group 3 (combined) had a drop in the Log MAR VA (Mean 0.199, 7 letters) and the contrast sensitivity (Mean 0.536, 4.5 step drop). There was no significant drop on induction with low glare. CONCLUSIONs: All the three morphological types of cataract showed a significant drop in LogMAR visual acuity and contrast sensitivity. Low glare did not have any significant effect whereas high glare is had a significant effect in Log MAR vision and the contrast sensitivity. Contrast sensitivity testing maybe more sensitive and serve as an adjunct tool to traditional visual acuity testing in quantifying the level of visual dysfunction in cataract patients. Key Words: Contrast Sensitivity, Brightness Acuity tester, Cataract, LogMAR, Glare P112
EVALUATING THE FEASIBILITY OF VESTIBULAR REHABILITATION USING GOOGLE CARDBOARD BASED VIRTUAL ENVIRONMENTS Authors: Aravind Nehrujee1, Lenny Vasanthan2, Anjali Lepcha3, Sivakumar Balasubramanian4 Departments and institution: Department of Bioengineering, CMC, Vellore PMR, CMC Vellore ENT, CMC, Vellore BACKGROUND : Vestibular rehabilitation therapy (VRT) is proven effective for vestibular dysfunctions. Classical peripheral vestibular rehabilitation is a lengthy and costly process. Virtual reality based therapy is an emerging technology that can be used in vestibular rehabilitation to provide visual habituation exercises for individuals with vestibular disorders. Most of the virtual reality systems vestibular rehabilitation systems though found effective had limitations of expensive, bulky and complicated for use. AIM: The aim of the study was to explore the use of a low-cost and highly portable virtual reality based games in the treatment of individuals with vestibular disorders and to examine the feasibility of using such a system.
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METHOD: The system was developed with an objective to provide individualized training and assessment with a fairly simple user interface and setup. With the advent of low-cost VR in mobile phones, gamification of exercises to challenge the vestibular system could lead to a recovery in a nonclinical environment. Since none of the mobile virtual reality headsets were tested for feasibility, the initial objective was to do an evaluation of the system developed. Games mimicking conventional exercises were developed and the subjects (healthy and patients) were asked to use the system. The evaluation was done through the System Usability Questionnaire (SUS) and the simulator sickness questionnaire (SSQ). RESULTS AND CONCLUSION: Patients reported simulator sickness symptoms after using the system while healthy subjects did not report any, which is encouraging. The simulator sickness reported in patients suggest that the game was able to cause retinal slip, and thus an error in the head movement. The results are motivating as the games could help in VOR modification and thus rehabilitation. The system is found to be highly usable (SUS score of 90%), and it provides a low-cost immersive way to provide rehabilitation, making the recovery process interesting and more engaging. P113
BANKED BLOOD CAN BE ATTARCTIVE, BUT HARMFUL AS WELL Dharini.s , vinayak shukla , aplha mathew , sankar.m , karthi.m dept of ctvs , cmch , vellore -04 INTRODUCTION: Paediatric patients , require banked blood to prime the extracorporeal circuit in cpb during cardiac surgery They require blood owing to their small circulating volume and the intolerance to severe hemodilution & stress placed by bypass. PURPOSE: We regularly use banked blood in the circuit to maintain a desired hematocrit of 24 – 30 % on bypass We add blood based on a calculation : Bv+pv+13(cplegia volume)25 – bv* preop hct divided by 50 The initiative for such a study is that in one patient , after priming with blood was complete and bypass initiated patient fibrillated and arrested which had never happened before. We found out that the potassium content n banked blood was around 12meq PRE BYPASS ULTRA FILTRATION Since that incident , we reguarly prefer pre bypass ultrafiltration , where the banked blood is made to pass through a separate hemofilter additional dilutional volume is added and potassium levels are normalized
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PRE BYPASS ULTRA FILTRATION Since that incident, we reguarly prefer pre bypass ultrafiltration , where the banked blood is made to pass through a separate hemofilter additional dilutional volume is added and potassium levels are normalized CIRCUIT
QUANTIFICATION OF CORNEAL TRANSPARENCY USING ANTERIORSEGMENT OPTICAL COHERENCE TOMOGRAPHY AND ITSVARIATION WITH CLINICAL GRADES PURPOSE: To quantify normal corneal transparency by Anterior Segment Optical coherence tomography (AS-OCT) by measuring the average pixel intensity. To analyze the variation in the average pixel intensity in Nebula and Macula corneal opacities. Method: This is an observational cross-sectional study of 38 eyes from 19 patients with Nebula or Macula corneal opacities greater than 3 mm and a normal contralateral cornea. Anterior segment OCT was performed centered on the opacity with a 3mm cruciate protocol. A similar image is taken of the contralateral clear cornea in the same quadrant. The average pixel intensity was calculated in a standardized manner using MATLAB software. Result: The average pixel intensity of the normal cornea was 99.58 Âą 21.8 (2 SD). The average pixel intensity of the nebular and macular corneal opacities were 115.5 and 141.1 respectively. The differences were statistically significant. Conclusion: Anterior segment OCT images can be used to quantify corneal transparency. Average pixel intensity is a measure that varies significantly with varying corneal opacification
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P114
WEIGHT CHANGES IN AMBULATORY POST OPERATIVE CABG PATIENTS DURING HOSPITALIZATION K. Kavitha* Mahendri. N.V., 632 004
Department of Dietetics, Christian Medical College, Vellore-
BACKGROUND: Post discharge weight changes in the coronary artery bypass graft (CABG) surgery have been studied extensively. However, studies on post-operative weight changes in the first week of surgery in non-complicated cases during hospitalization is limited, hence this study was undertaken. AIM: To study the weight change on the first week of surgery (5th day) in post op ambulatory CABG patient shifted from Intensive care unit (ICU) to ward. METHOD: 50 patients of age 35-75 years of both genders who got admitted in a tertiary care center to undergo CABG surgery between July 2015 and August 2015 were selected randomly for the study. Patient’s weight was measured in hospital dress before surgery and on 5th day post-surgery using electronic scale and height was measured using wall fixed height scale. Oral consent was obtained before anthropometric measurement. RESULTS: Of the 50 Patients,40 (80%) were men and 10(20%) were women. The mean weight was 65kg (range 45-86) and BMI 25kg /m2 (range 19-35). Weight status of subjects was normal (18.5 -22.9 kg /m2)-30, over weight (23-24.9 kg /m2) -13 and obese (>25 kg /m2)7. Post-operative weight loss was observed among men1-2 kg in 22 (55%), 2-3kg in 7 (17.5%), 7kg in 1 (2.5%). Weight gain was observed in 5 (1-3 kg) and no weight change in remaining 5. Among women 1-2kg weight loss was noticed in 6, 4kg in one, while 3 gained 1-3kg. CONCLUSION: Except 5 all the study subjects studied experienced weight changes. 74% of the subjects had weight loss on the 5thpost-operative day. This warrants further study on the role of nutritional factors in the post op weight loss in the first week among CABG patients. P114
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THE EFFECT OF AN ACTIVITY BASED OCCUPATION GROUP ON ANXIETY IN MOTHERS OF BABIES ADMITTED IN THE NEONATAL INTENSIVE CARE UNIT Rima Mary Philip, Hima J B*, Tunny Sebastian**, Dr. Santhanam Sridhar*, Sanjeev M Padankatti, Departments of Occupational Therapy, Neonatology* and Biostatistics**, Christian Medical College, Vellore, Tamilnadu, India BACKGROUND : Hospitalization of newborns always is a frightening and stressful experience for mothers; more than 25% of mothers of babies admitted in the neonatal intensive care unit (NICU) have moderate to severe anxiety(1). Thismay later lead to depression, altered parenting behavior and perception of parental competence and affect the parent- infant interaction. These in turn affect the child’s health, cognitive and emotional development (2). Activities have traditionally been used as a therapeutic modality in Occupational therapy. Involvement in an activity-based group through a purposeful activity, was thought to provide parent-parent interactions which may reduce their sense of isolation, distract them from negative thoughts, create an outlet for expression of feelings and promote coping(3). This study was done to assess the feasibility of applying the principles of activity-based group therapy to mothers whose infants are admitted in the NICU andto assess the effect of their participation on their anxiety levels. METHODOLOGY: Mothers of babies admitted in the NICU who consented to participate, had a working knowledge of Tamil or English and whose infants were likely to stay for 4 weeks for the treatment were contacted. They were invited to take part in an activity-based group of 1 hour duration once a week for 4 weeks. The study was a case control study conducted in two phases. Mothers satisfying the inclusion criteria were recruited over 4 weeks and their anxiety levels assessed but no intervention was done. They served as the control group. In the intervention phase, mothers participated in 4 activity group sessions, conducted once a week. They had a pre- test and posttest before and after every session using the state-trait anxiety inventory [STAI-S], to assess the anxiety levels. RESULTS: Nine teen mothers were included in the study with 8 in the experimental group and 11 in the control group. The baseline demographic characteristics and anxiety levels in both the groups were comparable, with 73% of the mothers having a moderate to very high level of anxiety. There was a significant reduction in the anxiety levels in the intervention group when compared to the control group at the post test (p= 0.005). In the experimental group, there was a significant reduction in the mean anxiety scores at the posttest of the first (p=0.019), second (p=0.026), and the fourth session (p=0.011) when compared with the pre test scores. CONCLUSION:
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From this study, we found that activity based group therapy was practically feasible and culturally appropriate and could be used as an effective intervention in reducing anxiety in mothers in the NICU. This is a cost effective intervention which does not depend on literacy, and can therefore be universally implemented. P115
NOVEL FLEX-ANKLE PROSTHETIC FOOT FOR CHILDREN WITH TRANSTIBIAL AMPUTATION- A PILOT CASE- SERIES Sathiya Moorthy C*, Kavin A**, Vinoth Jacob B*** * Bachelor in Prosthetics & Orthotics, Final Year Student, CMC ** Engineer, Rehab-P&O Services, CMC *** Prosthetist & Orthotist, R&O Services, CMC AIM: 1) To check the feasibility of fabricating and using a new type of flex-ankle prosthetic foot for children with transtibial (TT) amputation 2) To assess the ankle kinematics and energy efficiency of the new prosthesis by observational and instrumented gait analysis. BACKGROUND : Lower limb amputations in children are commonly due to congenital deformities and trauma such as road accidents, electrocution and fire cracker injuries. Birth prevalence of congenital deformities could range between 0.3 to 2.1 per 1000 live births [1]. The prosthetic options for children aged 4 to 7 years have limitations such as rigid foot pieces. Jaipur foot was specifically designed for Indian population it has been designed to offer plantar flexion and dorsiflexion [2]. The commonly available foot piece for child prosthesis is of Solid Ankle Cushion Heel (SACH) type, which has a rigid ankle joint, and does not support ankle movement for active children. This inspired us to fabricate a novel foot piece for children that would address these limitations. METHOD: Three children with unilateral trans-tibial amputation aged 4 to 7 years with a healthy residual limb were recruited. They were provided with customized TT prosthesis with newly designed flex-ankle prosthetic foot, which incorporates Micro-Cellular Rubber (MCR) in the metatarsal, ankle and heel regions. A minimum of three days gait training was provided.. Follow-up assessment was done after a subsequent continuous usage of prosthesis at home environment for three weeks with video gait and instrumented gait analysis. RESULTS: The observational video gait analysis suggested that all children were able to walk with a normal gait pattern. The mean Physiological Cost Index (PCI) was 0.679 Âą 0.12 SD, which is within the range for normal walking, implying that the new prosthesis is energy efficient. The mean
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walking speed was 46±7 m/min. The ankle angles obtained from kinematic data showed a mean plantar flexion of 2 degrees and dorsiflexion of 10 degrees. All three children reported the use of the new prosthesis to be very satisfactory. None of them reported any adverse events. CONCLUSION: It is feasible to fabricate, fit and satisfactorily use the new design prosthesis with the indigenous flex-ankle foot piece for children with transtibial amputation. Gait analysis confirmed that ankle flexion is possible with this design, and that walking with the new prosthesis is energy efficient. P116
STUDY OF PREVALENCE AND DIVERSITY OF NON-POLIOVIRUS ENTEROVIRUS SEROTYPES AMONG ASYMPTOMATIC INFANTS IN SOUTH INDIA USING MOLECULAR METHODS Sophia Silas, Ira Praharaj, Mohammad Azharuddin KO, David James Allen, Nicholas Grassly, Gagandeep Kang INTRODUCTION: Human Enterovirusare positive sense RNA viruses that belong to the genus ENTEROVIRUS of the PICORNAVIRIDAE family. With more than 100serotypes, some of these human enteroviruses can cause asymptomatic infections whereas others have been implicated in conditions such as meningitis, encephalitis, paralysis, myocarditis, HFMD etc. Human Enteroviruses are classified into four species, EV-A to EV-Dwith multiple serotypes within each genogroup. OBJECTIVE: To study the diversity of non-polio Enterovirus serotypes in guts of asymptomatic infants in Vellore district, South India METHOD: Stool samples from infants aged 6-11 monthsparticipating in a mOPV3 vaccine response study were tested for the presence of enteroviruses with a pan-Enterovirus qPCR. Samples that were positive for Pan-EV with Ct cut-off of 30 were chosen for performing semi-nested PCR assaystargeting VP1 region forEnterovirus A, B and C. Sanger sequencing was performed for the second round PCR amplicons. The “Enterovirus genotyping tool” from National Institute for Public Health and the Environment (RIVM, Netherlands) was then used for enterovirus species and genotype determination.
RESULTSs & Discussion: Of the 754 infants tested, n=265(35.1%) were positive for non-polio enteroviruses. Sequencing results were available for n=256 infantsof which one or more Enterovirusserotypes were identified in stool samples from n=244. The commonest genogroup of Enterovirus was
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Enterovirus B in n=176 (72.1% of all positives).Enterovirus A serotypes were found in n=85 (34.8%), while Enterovirus C serotypes were found in n=51(20.9%). Out of 11 different EnterovirusA serotypes identified, the most common wereCV A6 and CV A10 . Out of 39 different Enterovirus B serotypes,the common serotypes were- E-14, E-21, E-11 (Echoviruses) [E-14- 9.8%, E-21-6.4% and E-11-5.7% of all samples tested] andEnterovirus C had EV-C99 (10.2% of all samples tested) identified as its common serotype. CONCLUSIONs: 35.1% of asymptomatic infants tested were positive for Enterovirus infections and a wide diversity of Enterovirus serotypes was observed. CV-A6, which is associated with hand foot and mouth disease was among the most prevalent serotypes among asymptomatic infants. Other common serotypes identified were CV-A10, Echovirus-14 and EV-C99. OBJECTIVE OF STUDY: To determine the prevalence of Retinopathy of Prematurity in the premature and low birth weight babies presenting in the Department of Ophthalmology, Christian Medical College, Vellore. MATERIALS AND METHOD: This was Retrospective chart analysis of all infants, who were referred from the neonatology department to the Eye department. The study period was from January 2011 to December 2013. Charts were collected from our medical record department. Infants of age less than or equal to 32weeks of gestation with birth weight less than or equal to 1500gm were included in the study. The children were referred to the eye department four weeks after delivery. The data including hospital number, name, gender, gestational age, gestational age during examination, birth weight, stages of ROP at first visit were entered into an excel sheet and analyzed. Missing data when possible was got from the clinical work station using the neonatology records. RESULTS: A Total of 130 infants were identified . Off this 99 neonates fulfilled inclusion criteria. Out of 99 infants 85(85.9%) had no ROP and 14(14.1%) had ROP, four (28.57%) had stage I, 7(50%) had stage II, and 3(21.42%) had stage III . None of the studied neonates had ROP at stages 4 or 5. Worse eye was taken as ROP stage for the neonate for analysis. The reason for the low incidence in our study can be due to many reasons. One possible reason was the setting. Since our children came to the OPD after discharge it is possible that only the healthier children came to us. The other reason is that the ROP which is well known to regress by itself would have done so by the time the children came to us. Though unlikely, the other reason is that the care in our neonatology is so good that the incidence of ROP is low. There was a significant relationship between gestation age and prevalence of ROP in our study.
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CONCLUSION:Since this study has a major limitation in the type of patients studied it will not be wise to make any conclusions based on this study. Nursery based screening and outcomes are the best way to study this problem and compare with other data.
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EXPRESSION PATTERN OF CANDIDATE PROGNOSTIC MARKERS INCLUDING RAD51, IPMK, SIAH2, COPS6 AND SF3B1 AMONG PATIENTS WITH GLIOBLASTOMA MULTIFORME Authors: Bimal Patel*, Geeta Chacko, Rekha Pai, Ari G. Chacko, Asta Bjork Jonsdottir, Ashok Venkitaraman BACKGROUND : Glioblastoma multiforme (GBM) are the most common of the high-grade gliomas, accounting for approximately 12–15% of all intracranial neoplasms and 60-75% of astrocytic tumours. Due to their invasive nature, glioblastomas cannot be completely resected and despite progress in radio/chemotherapy, less than half of patients survive more than a year. The development of new molecular markers is expected to lead to improved diagnosis and prognosis and to aid in the clinical management of gliomas. Few markers including RAD51, IPMK, SIAH2, COPS6 and SF3B1 have been found to be promising among other gliomas but have never been investigated among GBMs. AIMS AND OBJECTIVES: To assess the pattern of expression of RAD51, IPMK, SIAH2, COPS6 and SF3B1 genes among patients with GBM diagnosed between the years January 2005 to December 2013 by relative quantification and correlate the data with clinical follow-up. MATERIAL AND METHOD: All cases diagnosed as glioblastoma multiforme irrespective of the age group which had fresh tissue stored in the tumour bank were included in this study. RNA extracted from the frozen tissue samples was converted to cDNA and the target genes (RAD51, IPMK, SF3B1, SIAH2 and COPS6) were amplified using Taqman master mix (Applied Biosystems, USA) on the 7500 realtime PCR system (Applied Biosystems, USA). The SDS software version 1.2 was used for analysis of Ct and ΔCt values. The RNA expression values were calculated in terms of the fold change using the 2-ΔΔCt. Log transformed values were used to determine the expression pattern. RESULTS: A total of 100 cases of GBMs were included in this study. Higher expression of RAD51 was seen in a significant number (p=0.032; 74.7 %) of GMBs tested while the expression pattern among all the remaining four genes ((p=0.892, p=0.121, p=0.765 and p=0.959 respectively) did
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not alter much from the baseline values. This data was correlated with the follow up information where the median duration of follow up was 35 months (n=79). GBMs with higher expression of RAD51 appeared to be associated with higher overall survival when compared to those with low expression. However this trend was not statistically significant. Other candidate genes did not show any correlation to the overall survival (OS). CONCLUSION: RAD51 expression is higher in GBMs while IPMK, SF3B1, SIAH2 and COPS6 do not show any significant change in expression than the normal. In addition, higher RAD51 expression correlated with better OS, though this needs to be validated on a larger data set.
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CLINICAL AND RADIOLOGICAL PROFILE OF COHORT OF CHILDREN WITH KRABBES DISEASE Mahalakshmi Chandran, SangeethaYoganathan, Suresh Babu, Maya Thomas, Karthik Muthusamy, Kushpu Sundarajan, Department of Neurological Sciences, Christian Medical College, Vellore BACKGROUND: Krabbes disease is an autosomal recessively inherited white matter degenerative disorder caused by the deficiency of galactocerebrosidase, a lysosomal enzyme. In this series, we describe the clinical and radiological profile of a cohort of children with proven Krabbes disease. MATERIALS AND METHODS Blood samples of thirty-four patients with clinical possibility of Krabbes disease during the period February 2015 to September 2016 were analysed for galactocerebrosidase enzyme. Diagnosis of Krabbes disease was confirmed in six patients. The clinical and radiological profile of these patients with Krabbes disease was extracted from the hospital database. Galactocerebrosidase was analysed in Neurochemistry Laboratory spectrophotometrically by adding cell lysates in glass stoppered tubes and subsequently adding TNPALGalactocerebroside, sodium taurocholoate, oleic acid, and citrate buffer with pH 4.5. The mixture was incubated at 370C for 18 hrs. The reaction was stopped by adding Dole’s mixture and Heptane. The upper heptane layer was read spectrophotometrically at 330nm. Galactocerebrosidase enzyme level more than 1.2 nmoles/hour/mg protein is considered normal. RESULTS: Among the 34 patients tested, 6 of them had significantly low level of Galactocerebrosidase proving the diagnosis of Krabbe’s disease. Of these six patients, four children had an infantile onset disease and two had onset of symptoms in juvenile period. Global developmental delay was observed in all four children with infantile onset disease. Regression of motor milestones
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and seizures were observed in all six patients. Family history was positive in two patients and consanguinity was documented in only one patient. Excessive irritability, recurrent pyrexia, sleep disturbances and exaggerated startle were found in children with early onset disease. Bipyramidal signs were documented in all children. Nerve conduction studies had revealed motor and sensory motor polyneuropathy in three patients. Computerized tomography data was available in three patients and hyperdensity of thalami and/or corticospinal tract was seen. Magnetic resonance imaging had shown T2W hyperintensities involving the deep and periventricular white matter, brainstem, posterior limb of internal capsule, along corticopsinal tract, cerebellar peduncles and dentate nuclei or thalamic hypointensity. Delayed myelination was seen in only one patient. Out of 6 patients 3 patients had no enzyme activity and 3 patients had partial enzyme activity. CONCLUSION: Krabbes disease is an inherited leukodystrophy often diagnosed based on the characteristic clinical phenotype, radiological findings and enzyme study. P119
VALIDATING ESTIMATION
ION
CHROMATOGRAPHY
(IC)
FOR
WATER
FLUORIDE
BONDU, Joseph Dian; R. Selvakumar; FLEMING, Jude Joseph. Department of Clinical Biochemistry Christian Medical College, Vellore, Tamil Nadu, India. BACKGROUND : A variety of methods, including the Ion Selective Electrode (ISE), have been used for estimation of fluoride levels in drinking water. But as these methods suffer many drawbacks, the newer method of IC has replaced many of these methods. AIM: The study aimed at (i) validating IC for estimation of fluoride levels in drinking water and (ii) to assess drinking water fluoride levels of villages in and around Vellore district using IC. Materials and METHODs: 49 paired drinking water samples were measured usingISEand IC method (Metrohm). Water samples from 165 randomly selected villages in and around Vellore district were collected for fluoride estimation over 1 year. RESULTS: Standardization of IC method showed good within run precision, linearity and coefficient of variance withcorrelation coefficient R2= 0.998. The Limit of Detection (LOD) was 0.027ppm and limit of quantification (LOQ) was 0.083 ppm. Among 165 villages, 46.06% of the villages recorded water fluoride levels >1.00ppm from which 19.39% had levels ranging from 1- 1.5ppm,
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10.91% had recorded levels 1.5-2 ppm and about 12.73% had levels of 2.0-3.0 ppm. Most (44.42%) of these villages belonged to Jolarpertalukwith moderate to high (0.86- 3.56ppm) water fluoride levels. CONCLUSION: Ion Chromatography method has been validated and is therefore a reliable method in assessment of fluoride levels in the drinking water.While the residents of Jolarpettaluk (Vellore distict) are found to beat a high risk of developing dental and skeletal fluorosis.
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DOES VITAMIN D DEFICIENCY AND RENAL DYSFUNCTION PLAY A ROLE IN THE PATHOGENESIS OF FLUOROTOXIC METABOLIC BONE DISEASE (FMBD) BONDU, Joseph Dian; R.Selvakumar; FLEMING, Jude Joseph.Department of Clinical Biochemistry Christian Medical College, Vellore, TamilNadu, India. AIM: The study aimed at studying the role of fluoride in renal tubular damage and the role of vitamin D deficiency in the pathogenesis of FMBD. MATERIALS AND METHOD: Thirty-six male Sprague-Dawley rats were divided into 6 groups (n=6); 3 groups received Vitamin D deficient diet whereas the other 3 groups were fed Vitamin D replete (control) diet. Serum levels of 25OHD, calcium, phosphorus, creatinine, ALP, albumin, PTH, Osteocalcin and CTX were measured after exposing rats to varied levels of fluoride in drinking water. Full body DEXA scans were used to examine changes in bone morphology pre and post exposure to fluoride. Renal function was assessed by measuring serum creatinine, urine fluoride and Cystatin C. Histopathological examination of sections of bone and kidney tissue was also performed. RESULTS: DEXA scans revealed a significant decrease in the BMD and BMC (p<0.05) but significant increase in fat mass (p<0.05) and fat percentage (p<0.01) in Vitamin D deficient rats preexposure to fluoride, with no significant change in biochemical parameters. The BMD of the control groups and the Vitamin D deficient groups increased (p<0.05) with the increasing levels of fluoride in drinking water. Serum ALP, bone fluoride content, Osteocalcin, CTX and urine fluoride increased with increasing levels of fluoride in drinking water. Serum creatinine and cystatin C levels showed a mild increase among rats treated with high levels of fluoride. Light microscopic examination revealed mild thickening and increased osteoid in most (80%) of the Vitamin D deficient rats exposed to high levels of fluoride. Renal tubular changes were found only in two rats (one from each group.)
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CONCLUSION: Fluoride affects osteoblastic activity and predisposes to deposition of fluoride in bone. These effects are accentuated in the presence of Vitamin D deficiency. But renal tubular may be present in selected cases.
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DISTINCTIVE BIOCHEMICAL PATTERN ALTERATION MULTIPLE ENDOCRINE NEOPLASIA TYPE1 (MEN1)
OBSERVED
IN
Yesudas Sudhakar, Victoria Job Department Of Clincial Biochemistry Christian Medical College Vellore Tamilnadu India 632004 BACK GROUND: Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease with an incidence of 0.1-15 cases per million individuals worldwide (1). Forty-two percent (range 20%– 61%) of the patients will develop a gastrin-secreting neuroendocrine . Gastrinoma mostly arises from pancreas or duodenum that induces excess secretion of gastrin . Zollinger-Ellison syndrome (ZES) is the most common reason for gastrinoma , non–beta islet cell (islet of Langerhans ) of the pancreas stimulates the acid-secreting cells of the stomach . Typical symptoms include abdominal pain, secretory diarrhea, esophagitis. Serum gastrin level is of great significance, while final diagnosis depends on pathological and immunohistochemical analysis. Surgical management remains the only curative treatment for gastrinoma (3). CASE: We report a 43 year old Women diagnosed with MEN type 1 syndrome and had surgery for primary hyperparathyroidism and developed severe hypothyroidism and hypocalcaemia after thyroidectomy and follow up done on the same patient and had developed chronic pancreatitis and type п Diabetes Mellitus and had renal stone and mild chronic renal failure and later reported with epigastric and left hypochondrial pain after food .So physical examination, gastroscopy and investigation for fasting gastrin levels were done and was reported to be 5820 pg/ml normal range,( 25-100 pg/ml). Gastroscopy revealed an ulcer and biopsy identified an NET and the patient had developed Zollinger-Ellison syndrome by pancreatic neuroendocrine tumor and was treated with H2 blockers. The patient underwent follow-up and no evidence of recurrence was observed during this period. CONCLUSION: Proton pump inhibitor medication is the therapy of choice to control acid secretion in virtually all patients .The most important predictor of poor survival is the presence of hepatic metastases. There are no controlled surgical trials for curative surgery in metastatic gastrinoma . It has been
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suggested that peptide-radio receptor therapy is especially effective in metastasized gastrinoma with partial remission in 47% of patients with gastrinomas. Data on biochemical pattern alterations in metastasized gastrinoma in MEN Type1 is limited. So further studies are required to get a better understanding of this disease. P122
STEM CELL EXPANSION AND DELIVERY USING HYDROGELS Authors:Deepti Rana1 and Murugan Ramalingam1,2 Departments and Institution: 1 Centre for Stem Cell Research, A Unit of Institute for Stem Cell Biology and Regenerative Medicine-Bengaluru, Christian Medical College Campus, Vellore 632002, India 2 WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan BACKGROUND: Biomaterials are an intriguing option for site-specific stem cell delivery, among which cell-laden hydrogels have been recently emerged as a promising strategy to fix and deliver the stem cells within the human body[1]. AIM: Development of cell-laden hydrogels suitable for stem cell expansion and delivery METHOD: In this study, we designed and investigated the impact of polyacrylamide/alginate (PAM/Algi) hydrogels for encapsulation and growth of human bone marrow-derived mesenchymal stem cells (hBMSCs) with five different ratios (1:1, 1:2, 1:3, 1:4 and 1:5). The gels were characterized for their swelling behaviour and other physicochemical properties. Based on the results, PAM/Algi hydrogel of 1:5 ratios has been selected for cell culture. For comparison, hBMSCs were cultured under a defined condition using three different culture systems, such as on the tissue culture plate (TcP 2D system), on the gel (OnG 3D system) and in the gel (InG 3D system), and studied for the viability (live/dead analysis), adhesion (DAPI/Alexa fluor 546 analysis) and proliferation (CCK-8 analysis) of the encapsulated stem cells. RESULTSS AND DISCUSSION: All the materials used in this study were supported the growth of hBMSCs. The results of TcP 2D and OnG 3D systems were found to be comparable in terms of cell attachment, viability and proliferation. In contrast, InG 3D system showed slightly less viability than the other systems but supported a significant proliferation in 7 days (see Figure 1). The cells cultured in InG 3D system showed morphology and cellular behaviour quite similar to native tissue-like growth.
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Figure 1. Live/Dead micrographs of hBMSCs monolayer culture in three different culture systems, stained with calcein AM and ethidium homodimer on day 1 and day 7, for viability analysis. Samples were analysed with fluorescent microscope. (A) live/dead image of hBMSCs cultured in 96-well plate i.e., 2D, (B) cultured on the gel system i.e., 3D OG, (C) cultured in the gel system i.e., 3D IG, on day 1 respectively. Figure (D), (E) and (F) shows cell cultured in 2D, 3D OG and 3D IG systems on day 7 respectively. Scale bar is 100 Âľm. CONCLUSION: The overall results suggest that cell-laden gels based on PAM/Algi biomaterial can be custom designed suitable for stem cell expansion and delivery.
P123 EVALUATION OF RAPID AND CAPTURE ELISA TEST IN DENGUE VIRUS DETECTION Anand K1, Asha MA1, David S1, Kannangai R1, 1Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu BACKGROUND: Dengue virus belongs to the genus Flaviviruswith 4 serotypes, each causing illness ranging from asymptomatic or mild febrile illness to severe haemorrhagic disease. Secondary dengue infection has been shown to be a significant risk factor for the development ofhaemorrhage or shock. In this study, we compared results obtained from immunochromatography rapid device cards (IC RD) with capture ELISAs to determine accuracy indices.
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AIM: We comparedrapid immuochromatography device with capture ELISAs to correlate with clinical conditions of suspecteddengue patients. METHOD: Samples from patients with suspected dengue were tested with IC RD test as well as capture ELISA. NS1, IgM and IgG markers were testedby rapid devices (PanBio and SD Bioline) and Capture ELISAs (PANBIO, SD Bioline and InBios).Any 2 ELISA positives results were taken as gold standard for comparing test results of rapid devices. RESULTS: 80 samples were tested for NS1 antigen; IgM antibody and34 samples were tested for IgG antibody by rapid and ELISA. The overall accuracy indices as follows Rapid Test
SD NS1
SD IgM
PANBIO IgM
SD IgG
PANBIO IgG
Sensitivity
94.59%
59.46%
60.53%
80.00%
80.00%
Specificity
97.67%
100.00%
72.09%
92.86%
78.57%
Positive Predictive Value
97.22%
100.00%
65.71%
94.12%
84.21%
Negative Value
95.45%
74.14%
67.39%
76.47%
73.33%
Predictive
CONCLUSION: Immuochromatographic rapid tests have poor sensitivity and specificity compared to ELISA.However, further evaluation needs to be done with larger sample size.
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ESTABLISHMENT OF EFFICIENT LENTIVIRAL SHRNA KNOCKDOWN TOOLS FOR HIGH THROUGHPUT RNAI SCREEN STUDIES IN HSCS Authors:Aneesha Nath1, Abhirup Bagchi1, Thiyagaraj Mayuranathan2, Krittika Nandy1, Shaji R Velayudhan1, 2. Departments:1 Centre for Stem Cell Research, 2Department of Haematology. BACKGROUND : The advent of RNA interference (RNAi) has revolutionised the field of science by making it possible to carry out large scale studies of gene function. ShRNAs and siRNAs are most commonly used to carry out knock down studies but several shortcomings of shRNAs such as off target effects and severe toxicities have limited their use. In order to address this problem the concept of shRNAmiR has evolved which offers several advantages over the conventional
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shRNAs being used. Since shRNAmiRs are expressed from Pol II promoters, they are less prone to cause toxicities and off target effects thus making it feasible to carry out tissue specific RNAi studies. Currently used miR 30 based backbones and the Sherwood algorithm used to design shRNAs has given promising results and has enabled the construction of shRNA libraries wherein multiple targets can be screened for monitoring a specific biological process. However the current libraries use 5-7 shRNAs against a particular target and moreover the knockdown efficiencies of the different shRNAs varies thus making it tedious to decipher the results in high throughput screens. Therefore, it is essential that the best backbone and algorithm is used to carry out high throughput RNAi screening studies. AIM OF THE STUDY: 1) Validation of the knockdown efficiencies of different shRNAs designed by Sherwood algorithm cloned into existing ultramiR backbones. 2) Identification of a new miRNA scaffold with increased biogenesis which can lead to improved knockdown. METHOD: 1) The shRNAs targeting different epigenetic factors were cloned into hCMV and hEF1αultramiR backbone using Gibson assembly. Viruses were made from the plasmids and were transduced into HeLa cells to assess the knockdown efficiencies. 2) To identify several novel miRNA scaffolds with increased biogenesis erythroid specific miRNAs with high reads such as miR486, miR92, miR191, miR181, miR10a, let7a-1 etc were selected from the RNA sequencing data. These miRNAs were cloned into a lentiviral backbone driven by the hCMV promoter and were checked for their expression levels by transducing them into HeLa cells. RESULTSS AND CONCLUSION: 1) shRNAs against SETD7, DNMT3A, BMI1 gave good knockdown efficiencies (>80%) in both hCMV and hEF1α backbone. On the contrary, some shRNAs such as KDM1A and SUV39H2 gave good knockdown in hCMV backbone as compared to hEF1α backbone thus confirming that hCMV is a stronger promoter as compared to hEF1α.Furthermore, our results also showed that hCMV promoter can be used to carry out efficient knockdown and overexpression studies and they can also be used to make efficient shRNA libraries for RNAi screen. 2 ) miR 486 and miR 181 showed the highest levels of expression (>80 fold) followed by miR10a and let 7a-1 (>30 fold).Thus these miRNAs can be used as efficient scaffolds for constructing shRNAmiRs which will further lead to better knockdown levels.
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P125
DIFFERENTIAL TOXICITY PROFILING OF BUSULFAN AND TREOSULFAN IN ENDOTHELIAL CELLS IN VITRORELEVANCE TO STEM CELL TRANSPLANTATION AUTHORS: Balaji Balakrishnan, Ezhilpavai Mohanan, Stallone Ilangeswaran, Poonkuzhali Balasubramanian DEPARTMENT & INSTITUTION: Department of Haematology, Christian Medical College, Vellore, TamilNadu, India BACKGROUND: Haematopoietic stem cell transplant (HSCT) is an established curative treatment option for a variety of haematological malignancies and non-malignant diseases. However, the success of this procedure is often limited by regimen related toxicity (RRT) resulting from endothelial damage caused by the drugs used in the conditioning regimen. Busulfan and treosulfan (a structural analog of busulfan) two widely used alkylating agents as HSCT conditioning regimens differ in their toxicity profile, but the reason for this difference in toxicity between these two drugs is not clear. We compared the effect of these two drugs on endothelial cells to identify the factors causing the differences in toxicity.
MATERIALS AND METHOD: HUVEC (Human Umbilical Vein Endothelial Cells) and HHSEC (Human Hepatic Sinusoidal cells) were treated with busulfan (200 μM, 300 μM and 500 μM) or treosulfan (3 μM, 10 μM and 30 μM) for 48 hours. The differential cytotoxicity of these drugs on the endothelial cells were assessed (Apoptosis by annexin V staining and autophagic acidic vesicular organelles (AVOs) by acridine orange (1 μg/ml) staining). Gene expression changes in the endothelial cells after treatment with busulfan or treosulfan were assessed using SA Biosciences Endothelial Cell Biology PCR Array. RESULTSS AND CONCLUSIONS: Busulfan treatment resulted in a dose dependent increase in apoptosis; however, treosulfan treatment even at the highest concentration (30 μM) resulted in a minimal apoptosis (22% in HHSEC and 46% in HUVEC). When examined for autophagy, HHSEC treated with treosulfan showed a significant increase in AVOs suggesting that the reduced toxicity to treosulfan is probably mediated by autophagy. Further, the gene expression profile in endothelial cells treated with or without the two drugs (Busulfan and Treosulfan) showed upregulated inflammatory (upto 9 fold) and apoptosis genes (upto 2.4 fold) with busulfan treatment whereas treosulfan treated cells did not show significant increase in inflammatory or apoptosis related gene expression thereby explaining the relatively less apoptosis observed with treosulfan. In addition, there was
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an increased expression cell adhesion related gene like SELL, SELPG and VEGFA in busulfan treated cells whereas treosulfan induced only SELL. However this effect could be cell-type specific and hence need further validation. Further, overexpression of angiogenesis related genes OCLN and KLK3 (which are generally expressed at very low levels in these cells), were also observed with both the drugs. This study suggests that the differences in toxicity profile between these 2 drugs are due to differential gene expression pattern in endothelial cells. Further studies are warranted to elucidate the exact mechanism involved in endothelial damage in order to reverse this damage.
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MODULATION OF TYROSINE KINASE INHIBITOR (TKI) RESISTANCE BY TARGETING NUCLEAR HORMONE RECEPTORS (NHRS) IN CHRONIC MYELOID LEUKEMIA (CML) Authors: Bharathi M Rajamani, Sreeja Karathedath, Shaji R. V., Vikram Mathews, Poonkuzhali Balasubramanian Department and Institution: Department of Haematology, Christian medical college, vellore. BACKGROUND : Despite the impressive success of molecular targeted therapy in CML with TKIs, a proportion of patients exhibit suboptimal response (SOR) to these drugs. There are limited options for those patients who develop intolerance or SOR to TKI. NHRs are attractive but less explored therapeutic targets in leukemia. AIM: Our aim is to identify the role of other NHRs in CML drug resistance has not been explored extensively. METHOD: Based on the in-vitro sensitivity data, CML cell lines KU812, EM2 were identified as sensitive and Lama-84, KCL22 were grouped as resistant to Imatinib (Table-1). To identify the NHRs and co-regulators that are differentially expressed between imatinib sensitive and resistant cell lines, we performed the NHR RT2 PCR profiler array (SA biosciences, Germany). Expression of each gene was normalized using five housekeeping genes (β-actin, GAPDH, β2 microglobulin, HGPRT & RPLP0) and the data was analyzed using SA biosciences web based analysis software. RESULTS & CONCLUSION: We observed that few NHRs were differentially expressed (by2 -5.6 fold) between resistant and sensitive cell lines. Among these, AHR, AR, ESR1, ESRRG, PPARG, RXRA, RXRB and THRA were found to be up-regulated in the sensitive cell lines compared to the resistant cell lines. To
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understand the effect of these NHRs in sensitizing resistant CML cells to Imatinib, we used ligands specific for these NHRs (Table-1). KCL22 cells were pretreated with NHR ligands (for 24hrs), followed by increasing concentrations of Imatinib (2.5uM-100μM). As expected, ligands of PPARγ, RXR, AR, and THRA (Fig-1) significantly improved imatinib sensitivity, while the ligands for AHR, ESR1 and ESRRG1 did not. To further explore the functional relevance of these NHRs in overcoming TKI resistance we compared the RNA expression of hOCT1 (IM (Fig-2), suggesting the possibility of overcoming TKI resistance in CML CD34+ cells using ligands of PPAR being evaluated in the lab. Our finding suggests that ligands to NHRs, especially RXR, AR and THRA in addition to PPARγ when used in combination with TKIs could overcome TKI resistance. Further studies are warranted to confirm the mechanistic effects of these ligands in modulating drug resistance in CML.
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P127
ALPHA RECEPTOR ACTIVATION PROFILE FOR SYMPATHETIC VASODILATION Bhavithrabharathi S, Renu Raj R, Sathya Subramani Christian Medical college, Vellore Phenylephrine is a known vasoconstrictor which acts through alpha adrenergic receptor. Contrary to what is known, a study published by our department shows that phenylephrine decreases vascular tension in goat artery strip under specific circumstances. Phenylephrine induced vasodilation occurs through alpha adrenergic receptor and is nitric oxide dependent. The aim of this study is to identify the subtype of alpha adrenergic receptor producing vasodilation in goat artery strip OBJECTIVE: To test if phenylephrine induced vasodilation is affected by subtype specific blockers of alpha receptors METHOD: Artery isolated from fresh goat leg was cut into spiral strip and suspended in an organ bath (25 ml), filled with physiological salt solution at 37ºC, aerated with carbogen. One end of the strip was connected to a force transducer and recorded using a data acquisition system (powerlab). Drugs were added to the organ bath and the change in tension was recorded & analyzed using Igor pro software. RESULTS: While 400μM L-Arginine (Nitric oxide donor) per se did not change tension, subsequent addition of phenylephrine (100μM) decreased tension (n=5,p=0.043 with Wilcoxon signed ranked test (WSR) L-Arginine/Phenylephrine induced vasodilation wasabolished byprazosin (non-specific α1 blocker) (n=6,p=0.006 with Mann-Whitney U test (MWU test)) L-Arginine/Phenylephrine induced vasodilationwas abolished by BMY-7378 (α1D blocker) (n=4,p=0.014 with MWU test) and not abolished by RS-17053 (α1Ablocker) (n=4,p=0.461 with MWU test) When α1Areceptor was blocked by RS-17053, subsequent addition of phenylephrine produced vasodilation even without excess nitric oxide (n=5,p=0.042 with WSR test) and that vasodilation was prevented by L-NNA (Nitric oxide synthase blocker) (n=1) CONCLUSION: Phenylephrine acts through alpha-1Dreceptor to produce vasodilation under high nitric oxide environment in goat artery strip. Co-activation of α1A& α1Dadrenergic receptor is essential for vasoconstriction. Unbalanced activation of just α1D receptor (while α1Ais blocked) results in vasodilation and such vasodilation is nitric oxide dependent.
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P127
ARRAYED REALTIME PCR ASSAY FORMAT (TAQMAN ARRAY CARDS) FOR STUDYING DIARRHEAL ETIOLOGY IN INFANTS AND CHILDREN FROM SOUTH INDIA Blossom Benny1, R.Revathy1, Mohammad Azharuddin KO1, Ira Praharaj1, Jie Liu2, Eric Houpt2, Gagandeep Kang1 1Christian Medical College, Vellore; 2University of Virginia INTRODUCTION: Acute diarrhea can be caused by several infectious agents, to detect which varied laboratory methods need to be employed. Molecular methods have enabled using a single platform to detect various agents of diarrhea. In developing country settings, recent studies have shown the presence of multiple enteropathogens both in diarrheal as well as surveillance samples collected from infants/children. OBJECTIVES: The objective of this study was to use enteropathogen TAC assays to detect multiple enteropathogen targets in diarrheal and surveillance stool samples from infants belonging to a birth cohort. We also aimed to predict the association of different pathogens at different quantities (estimated by molecular methods) with diarrhea. METHOD: 60 infants from a birth cohort study involving >200 infants were chosen. Diarrheal stool samples (N=277) and surveillance stool samples (N=485) collected over a 2 year period from these infants were used for extraction of total nucleic acid.TNA was used for performing Taqman array card assays targeting >30 enteropathogens (bacteria, viruses and parasites). For the association of different enteropathogens with diarrhea, the percentage of diarrheal samples and surveillance samples positive for a particular pathogen were calculated and odds ratio of the pathogen (at different molecular quantities) being present in diarrheal samples was estimated. RESULTS: Viral targets, Rotavirus(OR=2.5) and Astrovirus(OR=1.97) were strongly associated with diarrhea even at low molecular quantities (Ct cut-off 35 cycles). The association grew stronger when higher molecular quantities (lower Ct cut-off values) were used(rotavirus OR=8.75; astrovirus OR=2.56 at Ct cut-off 30). Association of bacteria like Shigella spp (OR=1.57) and ETEC (OR=2.49) with acute diarrhea was found to be higher than EAEC (OR=0.9).Giardia was found more in surveillance samples than diarrheal samples(OR=0.66). This indicates that Giardia is not associated with acute diarrhea in our settings, although it may be important in persistent diarrhea. CONCLUSION: Taqman array card assays for enteropathogens enabled us to test for >30 enteropathogens in a single assay. The possibility of detecting multiple targets and of quantifying them using this tool
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enables us to study the association of specific enteropathogens with diarrhea in Indian settings where children have been found to harbour multiple enteropathogens even while asymptomatic. P128
WHOLE GENOME ANALYSIS OF SEVEN SUSCEPTIBLE HYPERVIRULENT K.PNEUMONIAE ISOLATED FROM BACTERAEMIA Chaitra Shankar, Laura E.B. Nabarro,BalajiVeeraraghavan,DhiviyaPrabaa M.S., Naveen Kumar D.R. Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India INTRODUCTION: Hypervirulent K.pneumoniae(hvKp)strainsare being increasingly reported worldwide. They are susceptible to most antimicrobials and possess a number of virulence characters. rmpA and rmpA2 are molecular markers while phenotypically string test can be used for identification. They mostly belong to K1/K2 types and commonly associated with CC23. K.pneumoniae has four important virulence factors which consists of capsule, lipopolysaccharide, siderophores and fimbriae. The hypermucoviscous nature and other virulence factors contribute to the increased severity of infections caused by hvKp although the strain might be susceptible to first and second line antibiotics. OBJECTIVES: Literature available till date describe hvKp strains among the liver abscess cases.We aimed at molecular characterization of hypervirulent strains from bacteraemia by whole genome sequencing. The clinical outcome of the patients were correlated with molecular results. METHOD: Seven K.pneumoniae from bacteraemia isolated in 2015 that were string test positive and susceptible to all first and second line antimicrobials were included in the study. PCR was performed for the detection of rmpA, rmpA2, magA and k2A genes. Whole genome sequencing by Ion Torrent was performed for determination of other virulence genes. Assembly was done by SPAdes version 5 and genome annotated by RAST and Patric. RESULTS AND DISCUSSION: All the seven isolates carried rmpA and rmpA2 genes. Four isolates belonged to ST23 but only three among them were of K1 type possessing magA gene. One isolate belonged to ST420 and two isolates were of novel sequence types ST2319 and ST2320. Isolate belonging to ST2320 was of K1 type. Three non-K1 isolates did not belong to K2 type either.hvKp commonly are associated with ST23 and K1/K2 types. All isolates harboured mrkDgene coding for type3 fimbriae which aids biofilm formation. Genes coding for siderophores such as aerobactin, yersiniabactin, and enterobactin;allantoin metabolism and iron uptake were also present. Four cases were hospital acquired and survived. Three community acquired cases expired.
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CONCLUSION: HvKp is no longer restricted to liver abscess and cause severe invasive infections. Though susceptible to antimicrobials, presence of several virulence factors leads to high mortality. K1 serotype no longer is restricted to CC23 as we report novel ST2320 belonging to K1 type. P129
EVALUATION OF EFFECTS OF VARIOUS TEMPERATURES ON POTENCY OF PREMIXED ISOPHANE INSULIN IN EXPERIMENTAL ANIMAL MODEL DeepasreeSukumaran1, Aniket Kumar 1, A. Blessed Winston1, Kalpana Ernest 1, Kurien George 2,Margaret Shanthi1 1. Department of Pharmacology, Christian Medical College,Vellore, India 2. Department of Community Health and Development (CHAD), Christian Medical College, Vellore, India OBJECTIVE: To determine the effect of storage temperatures in the potency of premixed isophane insulin (Insulin mixtard) in animal model. METHODS: 18 male rats of 20weeks*age and weighing 300g** were equally divided into 3 groups.Human mixtard insulin vials along with saline vials were stored at 3 temperatures, 5°C, 25°C and 40°C. Each group of rats served as its own control and received normal saline at respective temperatures. Each rat was injected intraperitoneally with either insulin (0.25U/kg body weight) or an equivalent quantity of normal saline (control) stored at the same temperature. Blood sampling was done by rat tail cut method on following days: 1, 7, 21 and 35. After overnight fasting, blood glucose levels were measured using glucometer® at various time points: 0 hour (predose), 0.5 hour,1 hour,1.5hours and 4hours, 6hours and8hours after administration of insulin.The results were analyzed using R statistical programming, version 3.1.2. RESULTS: There was no significant reduction in the potency of insulin stored at a particular temperature over days from day 1 to day 35.A significant decrease in potency was observed for insulin kept at 40°C on day 1, 7 and 35.(P<0.05) CONCLUSION: There was a significant decrease in potency of insulin stored at 40°C whereas insulin stored at lower temperatures,5°C and 25°C didn’t lose their potency over a period of 35 days. The
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apparent insulin resistance seen in rural areas during summers could be attributed to the reduction in the potency of insulin at higher temperatures. KEY WORDS: Premixed isophane insulin, temperature, potency, glucose. *indicates mean age: 20+/-2 weeks **indicates mean weight: 250-300g
P130
MOLECULAR IDENTIFICATION OF SEROLOGICALLY INDISTINGUISHABLE STRAINS OF SHIGELLA USING NEXT GENERATION SEQUENCING Dhiviya Prabaa M.S, Shalini A, Naveen Kumar D.R, Revathi G, Francis Y, Balaji v Christian Medical College, Vellore BACKGROUND : Shigellosis is a bacterial infection of the colon that causes diarrhea and a common cause of morbidity in young and elderly, especially in low income countries. Although Shigellosis is a self limiting disease, it may be associated with the mild to life threatening complications. Further antimicrobial resistance has complicated the empirical therapy for treatment of shigellosis. Interestingly, non-agglutinating Shigella from various parts of India seems to be increasing which further worsen the situation as immunity to Shigella infection in humans are serotype specific. METHODOLOGY: Totally 27 non-agglutinable Shigella isolates were identified during the year 2011 - 2015. Of which, Eight isolates were randomly sequenced using Ion Torrent (PGM) sequencer with 400-bp read chemistry (Life Technologies) according to manufacturer’s instructions. The data was assembled de novo using AssemblerSPAdes v5.0.0.0 embedded in Torrent suite server version 5.0.3. The annotation was performed in PATRIC, the bacterial bioinformatics database and analysis resource and NCBI Prokaryotic Genomes Automatic Annotation Pipeline (PGAAP).Oantigen sequence of the whole genome were compared with those available in the NCBI database through PATRIC. RESULTS: The raw reads assembly of all the isolates showed greater than 50x coverage. Of the eight, Five isolates were identified to be S. boydii (n = 3), S. flexneri 6 and S. flexneri 2a (n = 1) each based on the similarity of O-antigen genes arrangement. Sequences of the remaining three isolates did not match with any Shigella sequences in the NCBI database. This whole genome sequences has been deposited at GenBank.
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CONCLUSION: In recent years, non-agglutinating Shigella seems to be steadily increasing. None of the molecular methods could reliably detect Shigella serotypes and has several limitations such as inability to discriminate between atypical E. coli and Shigella spp. Although only limited accessible genome data is available for comparative analysis of the whole genome sequences, this study highlights the need for availability of open access database for identification of nonagglutinable Shigella. P131
CLINICAL UTILITY OF ISTH BLEEDING ASSESSMENT TOOL AND THROMBOELASTOGRAPHY(TEG) IN ASSESSMENT OF PATIENTS REFERRED FOR EVALUATION OF BLEEDING DISORDERS Authors: Pragya Kafley, Ramya V and Sukesh C Nair, Departments and institution: Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore BACKGROUND: Evaluation of bleeding disorders is incomplete without a proper history,having said that history taking itself is a challenge in bleeding disorders as bleeding symptoms are experienced by the normal and diseased people alike. Having understood the importance of guided and standardized questions different Bleeding Assessment tools were devised. Apart from history , in the lab diagnosis of bleeding disorders there is no single test that evaluates the complete coagulation process. The advent of global tests of hemostasis like TEG aims to overcome that. AIM: To determine the clinical utility of ISTH BAT and TEG in evaluation of patient with increased bleeding tendency. METHOD: A total of 223 patients who were referred to our lab for investigation of hemostasis were enrolled into the study. The questionnaire was administered and the bleeding score was calculated, Per protocol the TEG was done for all patients and the TEG was analyzed. Sensitivity, Specificity, Negative and Positive predictive value(NPV,PPV) of Bleeding score, TEG and Bleeding Score and TEG taken together in identifying bleeding disorders were calculated. ¡
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RESULTS AND CONCLUSION: The Sensitivity, specificity, PPV and NPV for BAT were 92%, 63.3%,75.9% and 86.4% respectively . The Sensitivity, Specificity PPV and NPV of TEG were 86.0%, 85.7%, 89.7% and 80.9%. When both these modalities were taken together the sensitivity, specificity , PPV and NPV were 97.5%, 56.6%, 76.3% and 94.4 %. This study concludes that TEG and BAT can both be used as a good screening tool for patients with bleeding disorders either alone or in conjunction with each other. With a high NPV , if both these parameters are normal then bleeding disorders can be excluded. P132
CLINICO-PATHOLOGICAL FEATURES OF PRIMARY NON HODGKIN LYMPHOMAS OF THE FEMALE GENITAL TRACT – A 10-YEAR STUDY Amey M Baitule, Mayank Gupta, Department of General Pathology CMCH, Vellore BACKGROUND: Primary non Hodgkin lymphomas (NHL) involving the female genital tract(FGT) are exceedingly rare tumors with combined incidence in the entire FGT being <1%. In the order of frequency, Diffuse large B cell lymphoma (DLBCL), Burkitt lymphoma and follicular lymphoma are the common NHLs involving the FGT. A misdiagnosis/delayed diagnosis is often inevitable due to the non-specific clinical and radiological presentations. To gain further insights into these tumours, we present clinicopathological profiles of nine cases with primary NHL of the FGT diagnosed at our institute over a period of 10 years. RESULTS / CASE REPORTS: The age of the patients ranged between 3 years to 75 years. Most patients (6/9) presented with abdominal distension and mass in abdomen. Ovarian involvement was evident in seven patients; four with bilateral involvement, two of which also had tumour in the uterus, and remaining three with unilateral involvement). There were two patients with isolated uterine involvement and one patient with a vaginal vault growth. A diagnosis of DLBCL was made in eight patients based on the morphology and immune histochemical(IHC) profile (CD20+ and high Mib proliferation index). Two of these patients had features of double hit lymphoma. One patient was diagnosed with Burkitt lymphoma (Cd20+, CD10+, Bcl6+, Bcl2- and Mib-1-100%). None of the cases had a clinical or radiological suspicion of NHL. CONCLUSION: The pathologist’s cognizance about these tumours and proper evaluation of morphological and immune histochemical features is essential for accurate identification and subtyping of NHL, thereby facilitating further management.
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P133
CORRELATION BETWEEN SABIN 1 VIRUS SHEDDING AND SUBSEQUENT SEROCONVERSION IN INDIAN CHILDREN VACCINATED WITH BIVALENT ORAL POLIO VACCINE (BOPV) Authors: Pavithra D1, Anand K2, Jayalakshmi V1, Mohan Raj M1, Sidhartha Giri1, Asha Mary Abraham2, Gagandeep Kang1 Departments & Institution: Welcome Trust Research Laboratory1, Department of Clinical Virology2, Christian Medical College, Vellore BACKGROUND: Shedding of oral polio vaccine (OPV) after vaccination indicates effective replication of the vaccine virus in the gut. This results in mounting an optimal antibody response to the vaccine virus, as evidenced by few studies. AIM: To evaluate the effect of Sabin 1 shedding on day 7 after vaccination on subsequent sero conversion in Indian children aged 1 to 4 years. METHOD: A total of 218 children aged 1 to 4 years, who were vaccinated with last dose of OPV atleast six months previously, were recruited from Vellore district as part of a vaccine response study. Blood samples were collected before and 28 days after administration of a dose of bOPV from all the children. Stool samples were collected 7 days after administration of bOPV to determine OPV shedding. Neutralization test was performed on the serum samples according to WHO protocol to determine antibody response to Sabin 1. For the day 7 stool samples, singleplex realtime PCR was performed using serotype specific primers and probes targeting the VP1 region of the Sabin 1 poliovirus genome. RESULTS: Of the 218 children, 20.6 % (45) children seroconverted after 28 days of vaccination, while 79.4% (173) children did not seroconvert. Of the 45 children who seroconverted, 30 (66.7%) children shed the vaccine virus on day 7, whereas, 15 (33.3%) children did not shed. Of the 173 children who did not seroconvert, 12 (7%) children shed the vaccine virus, and 161 (93%) did not shed. The median Ct value for children who were shedding the vaccine virus and subsequently seroconverted was 27.76, while for those who did not seroconvert but were shedding the virus was 35.54. CONCLUSION: There was a strong correlation between Sabin 1 shedding on day 7 and subsequent sero conversion (after 28 days of vaccination) in Indian children.
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P134
EXPANDED DIAGNOSTIC APPROACH TO HEPATITIS E VIRUS DETECTION IN PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE - A PILOT STUDY. Authors: Runal J Steve¹, John G Fletcher², Raghavendran A², Visalakshi³, Uday G Zachariah4, Ashish Goel4, C E Eapen4, Priya Abraham² Institute: ¹Departments of Clinical Microbiology, ²Clinical Virology, ³Biostatistics, 4Hepatology, Christian Medical College, Vellore. INTRODUCTION: Acute decompensation of pre-existing chronic liver disease (CLD), known as acute on chronic liver failure (ACLF) is associated with high mortality. Hepatitis E virus (HEV) as a potential cause was studied. OBJECTIVES: To evaluate the role of HEV in ACLF patients using a quantitative HEV PCR, HEV antigen ELISA and IgM anti-HEV antibody detection ELISAs. MATERIALS AND METHODS: In this prospective cross-sectional study, blood samples were collected from 50 ACLF (cases) as defined by standard guidelines and 50 patients with stable CLD (controls) from January 2015 to August 2016, after obtaining consent. A real time polymerase chain reaction (PCR) for quantification of HEV RNA in plasma was employed. Additionally, WANTAI HEV antigen ELISA and two IgM detection ELISAs (MP Diagnostics HEV IgM ELISA and WANTAI HEV IgM ELISA) were compared using plasma from cases and controls. RESULTS AND DISCUSSION: 35 Ethanol alone was attributed as a cause of underlying CLD in 60% of cases and 24% of the controls. Ethanol was the leading cause of acute insult in ACLF (54%) cases. HEV infection accounted for 20% of cases. Other causes were hepatitis A and hepatitis B infection, drugs and autoimmune hepatitis. Coinfection with HEV in HBV and HCV patients were seen in this study. Ten ACLF patients (20%) had 1-3 markers of HEV versus two (4%) among controls (p = 0.0138). Among ACLF cases, one had HEV viremia (403 IU/ml) and detectable HEV antigen. MP Diagnostics HEV IgM ELISA was more sensitive while the WANTAI HEV IgM ELISA (IgM capture assay) was more specific. Agreement between both these assays was 0.638 (kappa value).
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CONCLUSION: This study shows that alcohol is a major contributing factor for both underlying CLD and ACLF. HEV also have a significant role in causing ACLF, suggesting a need for a vaccination in such patients. P135
CLEAR CELL SARCOMA LIKE TUMOUR OF GASTROINTESTINAL TRACT PRESENTING AS RECTOSIGMOID POLYP: A CASE STUDY AUTHORS: Rushni S, Dipti Masih , INSTITUTION: Department of General Pathology, Christian Medical College & Hospital, Vellore. INTRODUCTION: Clear cell sarcoma-like tumours of the gastrointestinal tract (CCSLTGT) is a rare malignant neoplasm that usually occurs in the small bowel, stomach, or large bowel, with a predilection for young adults. The alternate designation “malignant gastrointestinal neuroectodermal tumour” (GNET) has recently been proposed. We describe a case of CCSLTGT involving the rectosigmoid junction in a 50 year old female, who presented with bleeding per rectum. The search for CCSLTGT involving the rectosigmoid junction from the literature was unsuccessful; we believe that this is the first reported CCSLTGT in this location. CASE REPORT: A 50 yr old female presented with complaints of bleeding per rectum since one year. Digital rectal examination, CT abdomen and rigid sigmoidoscopy showed a polypoidal ulceroproliferative growth ~5x5cm, 10 cm from the anal verge. The tumour was excised by open Hartmann’s procedure which revealed a polypoidal mass measuring 6x5x3cm. Microscopically the tumour was composed of nests, sheets of elongated to epithelioid spindled cells. On immunohistochemistry tumour cells showed strong cytoplasmic and nuclear positivity for S100 and cytoplasmic positivity for Synaptophysin. The cells were negative for CD117, DOG1, HMB45, SMA, Desmin, H caldesmon, Myogenin and CD34. Correlating with histomorphology and immunohistochemistry the case was diagnosed as CCSLTGT. CONCLUSION: CCSLTGT is a tumour arising in the wall of the gastrointestinal tract displaying an epithelioid or spindle cell morphology, negative for GIST markers, positive for S-100, lacking any specific markers of melanocytic differentiation and with presence of EWSR1 rearrangements. KEY WORDS: Clear cell sarcoma-like tumours of the gastrointestinal tract, CCSLTGT, rectosigmoid polyp, GNET. .
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IMMUNOPHENOTYPE CHARACTERIZATION OF PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: A SINGE CENTRE EXPERIENCE Faranaz Khamruddin, Ansu Abu Alex, Kotteeswari Kathirvel, Hari Krishnan Babu, Aby Abraham, Alok Srivastava, Biju George, Poonkuzhali Balasubramanian, Vikram Mathews. Department of Haematology, Christian Medical College, Vellore, India. BACKGROUND : Acute promyelocytic leukemia (APL) is a sub type of acute myeloid leukemia (AML) characterized by a reciprocal translocation between chromosome 15 and 17 [t(15;17)]. AIM: We undertook a retrospective study to immunophenotypically (IPT) characterize and correlate clinical outcomes of patients with APL diagnosed in our center. METHOD: Clinical data from 122 APL patients (diagnosed between 2011 and 2016) was analyzed. For IPT CD13, CD33, CD34, HLA-DR, CD117, CD56, CD64, CD19, CD11b antibodies were used and was done according to standard protocols. The data was acquired using FACS Calibur (BD, Mansfield, MA, USA) and analyzed by CELLQuest Pro software (BD). RT-PCR was performed according to standard protocol as a part of diagnosis. RESULTS: The median age was 31 years (2-60 years) of which 86 (70.5%) were females and 36 (29.5%) were males. All the patients were positive for RT-PCR (PML-RARA) of which 68 (55.7%) patients were bcr1, 5 (4.1%) were bcr2 and 49 (40.2%) were bcr3 isoforms respectively. The median total WBC count was 7.3 x 109/L (4.0 -180.7). The median blast percentage by IPT was 86% (17-97). The median expression of CD13 was 68.4%(9.2-99.3),CD33 was 92.2 % (1.299.8), CD34 was 0.9% (0.04-97.7) and HLA-DR was 3.2% [(0.1-65). Five (4%) cases had coexpression of CD34 and HLA-DR (>20%)] at diagnosis. The median CD56 was 0.8% [0.02-72; only 10 patients had aberrant expression of CD56 (>20%)]. The median CD117 was 30% (0.0885.2%), CD64 was 24% (0.2-93.9%), CD11b was 1.5% (0.1-80.7%) and CD19 was 0.3 [0.03 – 33.6%; only one case each had aberrant expression of CD19 and CD11b (>20%)] respectively. Early deaths accounted for 15 patients (12.3%) and 19 patients (15.6%) relapsed during the study. The overall survival (OS) was 87.7% and the event free survival (EFS) was 72.1%. CONCLUSION: This study demonstrates that there is a significant heterogeneity in the IPT of APL patients at diagnosis. However, this did not correlate with clinical outcomes or PML-RARA isoforms.
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BONE MARROW MICRO-ENVIRONMENT MEDIATED DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA INTRODUCTION & BACKGROUND : Accumulating evidence suggests that bone marrow stromal environment act as an asylum for leukemic cells and allows them to survive chemotherapy, eventually leading to disease recurrence. Our aim is to delineate the mechanism underlying stromal environment mediated drug resistance (EMDR) in AML cells, which could potentially lead to new targeted therapies for AML. PATIENT/ MATERIAL AND METHOD: In order to mimic the bone marrow micro-environment, we have developed an in-vitro stromal cell co-culture system, where the myeloid leukemic cell lines (HL-60, U937 & K562) and primary AML cells was co-cultured with stromal cell line (HS-5) and exposed to different concentration of daunorubicin (DNR) &Cytarabine (Ara-C). After 48 hours, the percentage of viability was calculated by Annexin V- 7AAD staining using flow cytometry. Gene expression profiling was done using Agilent Human Whole Genome 8x60K Gene Expression Array (Genotypic technologies, Bengaluru). RESULTS: Co-culture experiments demonstrates that there is a significant stroma mediated protective effect on myeloid leukemic cell lines to DNR (p < 0.001) and Ara-C (p < 0.01), the same phenomenon was observed in primary AML cells [DNR p < 0.001, Ara-C p < 0.01 (n=26)]. In order to decipher the molecular mediators of this resistance we did a microarray analysis of U937 cells co-cultured with HS-5 comparing control. We found that 1067 genes were differentially regulated (>2 fold), out of which 699 genes were up regulated and 368 genes were down regulated. The functions significantly enriched for differentially regulated genes are cell proliferation, apoptosis, immune response, cell adhesion, cytokines and signalling pathways like PI3-Akt, JAK STAT, WNT signalling. CONCLUSION: Our preliminary results suggest there is a significant EMDR in AML. However the mechanisms underlying this effect should be explored further in greater detail. Elucidating the molecular mechanisms involved is likely to result in promising combination therapies to reduce chemotherapy resistance and relapse, and thereby improve survival in AML.
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VACCINE VIRUS SHEDDING AND ITS EFFECT ON SEROCONVERSION IN INDIAN CHILDREN VACCINATED WITH BIVALENT ORAL POLIO VACCINE (BOPV) Authors: Hanusha J1, Anand K2, Jayalakshmi V1, Mohan Raj M1, Sidhartha Giri1, Asha Mary Abraham2, Gagandeep Kang1 Departments & Institution: Wellcome Trust Research Laboratory1, Department of Clinical Virology2, Christian Medical College, Vellore BACKGROUND : OPV shedding after vaccination indicates vaccine virus replication in the gut which results in an optimal immune response to OPV, as evidenced by few studies. AIM: To evaluate the effect of Sabin 3 shedding on day 7 after vaccination on subsequent seroconversion in Indian children aged 1 to 4 years. METHOD: A total of 218 children aged 1 to 4 years, who were vaccinated with last dose of OPV atleast six months previously, were recruited from Vellore district as part of a vaccine response study. Blood samples were collected from all the children and they were administered a dose of bOPV. Blood samples were collected after 28 days of vaccination to evaluate antibody response. Stool samples were collected on day 7 (post-vaccination) to determine OPV shedding. Neutralization test was performed on the serum samples according to WHO protocol to determine antibody titre against Sabin 3 poliovirus. For the day 7 stool samples, singleplex real-time PCR was performed using serotype specific primers and probes targeting the VP1 region of the Sabin 3 poliovirus genome. RESULTS: 68 (31.2%) children who were seroconverted after 28 days of vaccination, while 150 (68.80%) children were not seroconvert. Of the 68 children who seroconverted, 47 (69.1%) children shed the vaccine virus on day 7, whereas, 21 (30.9%) children did not shed. Of the 150 children who did not seroconvert, 9 (6%) children shed the vaccine virus, and 141 (94%) did not shed. The median Ct value for children who were shedding and seroconverted was 27.81, while for those who did not seroconvert but shedding the virus was 36.28. The post-vaccination geometric mean titre (GMT) for Sabin 3 for children who seroconverted and were shedding the virus on day 7 was 459.82. For those who seroconverted but did not shed the vaccine virus, the postvaccination GMT was 275.46. The pre-vaccination GMT for the 218 children was 32. CONCLUSION: There was a strong correlation between Sabin 3 shedding on day 7 and subsequent seroconversion (after 28 days of vaccination) in Indian children.
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DURATION OF HUMORAL IMMUNITY FOLLOWING ADMINISTRATION OF A SUPPLEMENTAL DOSE OF INACTIVATED POLIO VACCINE (IPV) IN INDIAN CHILDREN AGED 1-4 YEARS Authors: Jayalakshmi V1, Pavithra D1, Hanusha J1, Sidhartha Giri1, Jacob John2, Asha Mary Abraham3, Gagandeep Kang1 Author affiliations: Wellcome Trust Research Laboratory1, Department of Community Medicine2, Department of Clinical Virology3, Christian Medical College, Vellore INTRODUCTION: As per “The Polio Eradication and Endgame Strategic Plan 2013-2018�, IPV has been introduced in all OPV using countries since the last quarter of 2015. Few studies have demonstrated boosting of short term humoral immunity after IPV administration in children already primed with OPV, but no study has evaluated the duration of humoral immunity after IPV administration. AIM: The aim of the study was to evaluate the duration of humoral immunity to poliovirus, in OPV immunized children, 6 months and 12 months after a single supplemental dose of IPV to children who did not receive a supplementary IPV dose. METHOD: It was a single centre, open-label randomized controlled trial (CTRI/2014/09/004979) conducted in Vellore, India, with 3 groups enrolling a total of 900 children aged 12-59 months (300 each in control, IPV-6 month, and IPV-12 month arms). Blood samples were collected at recruitment from the control group and 28 days after IPV administration in the IPV-6 and IPV-12 month groups, to evaluate anti-poliovirus neutralizing antibodies against all three poliovirus serotypes (PV1, PV2, PV3). Repeat blood samples were collected after 5 months of IPV administration (IPV-6 month arm) and after 11 months in the IPV-12 and control arm. RESULTS: The pre-vaccination geometric mean titres (GMT) of neutralizing antibodies against PV1, PV2, and PV3 respectively were: control arm (103.14, 186.64, 53.01), IPV-6 arm (737.34, 847.68, 839.55), IPV-12 arm (833.08, 910.61, 851.06). After 5 months (IPV-6 month) and 11 months (IPV-12 month, control), the GMT were: control arm (67.59, 121.82, 34.47), IPV-6 arm (162.60, 265.61, 242.44), IPV-12 arm (142.33, 242.52, 180.10). CONCLUSION: Although the antibody titres in the IPV-6 month and IPV-12 month arms waned with time, nonetheless, the antibody titres remained significantly higher in both these arms compared to the control arm.
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P140
ESTIMATION OF THE TARGET ATTAINMENT OF SERUM CONCENTRATION OF 5 FLUOROURACIL (5-FU) WITH DOSES 1 AND 3 IN PATIENTS WITH COLORECTAL MALIGNANCY- FOLFOX 6 REGIMEN Jacob J1, Mathew BS1, , Chacko RT2, Singh A2, Bharathbhai PS2, Mathew SK1, Prabha R1, Fleming DH1 Department of Pharmacology and Clinical Pharmacology1,Department of Medical Oncology2, Christian Medical College Hospital, Vellore, Tamil Nadu BACKGROUND : 5 Fluorouracil(5-FU) continues to serve as the backbone of systemic combination chemotherapy for treatment of colorectal malignancy in the adjuvant and metastatic disease setting. The standard of care in our hospital in relation to the dosing of 5-FU is based on body surface area.But literature suggests that body surface area based 5-FU dosing has several limitations, and that pharmacokinetic (PK) guided dosing of 5-FU improves clinical efficacy with reduced toxicity. The recommended therapeutic area under the concentration vs time curve (AUC) for 5FU is 20 to 25 mg.h/l. Ratio of AUC of 5-FU/DHFU >0.9 , in bolus regimens is suggestive of increased toxicity.1 AIM: To determine the concentrationof 5-FU and its metabolite, dihydrofluoro uracil (DHFU) at different time points, in the interdosing period, indose 1 and dose 3 in patients with colorectal malignancy receiving the FOLFOX 6 regimen- an interim analysis METHODS: This was an observational study,in patients diagnosed with colorectal malignancy and prescribed FOLFOX 6 regimen. This included administration of 400 mg/m2 of 5-FU as bolus which was followed by continuous infusion of2400 mg/m2(using Baxter infusion pump for 44 hours). Specimens were collected before the start of the bolus,then immediately after the end of bolus, thenat 5,15 and 30 min after the end of the bolus. Specimens were also collected at 2, 8, 18 and 43 hrs after the start of the continuous infusion (for both dose 1 and dose 3). All the specimens were extracted and 5-FU andDHFU concentration was measured by high performance liquid chromatography(HPLC). Pharmacokinetic analysis was performed and the AUCof 5-FU and DHFU was determined. RESULTS: To date, the concentrations of 5-FU was measured in 12 patients after the first dose, of which 6 patients had a repeat measurement with the third dose.The mean (SD) of Cmax (at the end of
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bolus) for 5-FU at dose 1 and dose 3 was17.72 (5.6)and 19.93(9.75)Âľg/ml respectively. The mean (SD) of 5-FU steady state concentration,after 18 hours of infusion with dose 1 and dose 3 was 0.43 (0.14) and 0.51 (0.2)Âľg/ml respectively. The mean(SD) of 5-FU AUC in dose 1 and dose 3 was 24.5 (9.37) mg.h/L and 26.84 (7.28)mg.h/L respectively.The mean(SD) of DHFU AUC in dose 1 and dose 3 was30.40(8.76)mg.h/L and 31.72 (13.11) mg.h/L respectively. Only twoout of 12 patients had achieved the target therapeutic range for 5-FU AUC with dose 1, with the remaining five patients having a higher AUC and five having a lower AUC.In dose 3, two out of six patients had achieved the recommended therapeutic range for 5-FU AUC with remaining three having a higher 5-FU AUC and one patient having a lower AUC. Of the four patients who had a ratio of 5-FU/DHFU AUC >0.9 with dose 1, two patients developed diarrhoea. However two patients with mucositis and fever, had a ratioof 5-FU/DHFU AUC <0.9. CONCLUSION: Our study showed that only 17% of patients achieved target AUC with dose 1, when dosing of 5FU was based on body surface area .This suggests that therapeutic drug monitoring may have a significant role in dose optimization of 5-FU, in colorectal malignancy. P141
EVALUATION OF SINGLEPLEX REAL-TIME RT-PCR ASSAYS FOR THE TECTION OF ASYMPTOMATIC NOROVIRUSGENOGROUPS I AND II INFECTION IN INDIAN CHILDREN Authors: Maheshwari K, Nirmal Kumar, Mohanraj M, SidharthaGiri, Gagandeep Kang Department& Institution: Wellcome Trust Research Laboratory, Christian Medical College, Vellore INTRODUCTION: Real-time PCR assays are being used since the last few years, mostly in developed countries, for the detection of norovirusgenogroups I and II (GI and GII) from stool.The Taqman array card (TAC) format is a real time PCR platform with a high sensitivity and specificity that can be used to detect multiple pathogens or pathogen targets in a single assay. Very few studies from developing countries have used these real-time PCR platforms for norovirus detection from stool samples. OBJECTIVES: To evaluatesingleplex real time reverse transcriptase PCR (RT-PCR) assays in the detection of norovirus genogroup I and II from stool compared to Taqman array card (TAC) assays. METHODs: A total of 120 stool samples collected from infants aged 6-11 months in Vellore district as a part of vaccine response study were selected. Of the 120 samples, 24 (20%)and 73 (60.8%) were positive for norovirus genogroup I and II by TAC assays. For the PCR assays, viral RNA
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extraction was performed for the 120 stool samples using QIAamp Viral RNA extraction protocol followed by real-time RT-PCR. RESULTS: Of 120 stool samples, 21 (17.5 %) and 67 (55.83%) samples were positive for GI and GII by the Singleplex real time reverse transcriptase PCR assays. Considering TAC assay as a gold standard for norovirus detection, the sensitivity and specificity of singleplex real time reverse transcriptase PCR assay for GI detection was 83.3% and 98.95% respectively. For GII detection, the sensitivity and specificity of singleplex real time RT-PCR was86.3%and 91.4%, compared to TAC assay. CONCLUSION: Single plex real time PCR assays are highly sensitive and specific in the detection of norovirus geno group I and II from stool samples. P142
POLYMERIC GRADIENT HYDROGEL FOR INTERFACIAL TISSUE ENGINEERING Authors: Keerthana Ramasamy1, Lakshmi priya Manickam*1, Deepti Rana1, Murugan Ramalingam1,2 Department and institution: 1 Centre for Stem Cell Research (CSCR), A Unit of the Institute for Stem Cell Biology and Regenerative Medicine-Bengaluru, Christian Medical College Campus, Vellore 632002, India 2 WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan *Presenting Author: Lakshmipriya Manickam. Email: lakshmipriya93m@gmail.com BACKGROUND : Interfacial tissue engineering and high throughput screening of cells often require scaffolds with gradient features to optimize cell-matrix interactions andstudy native cellular microenvironmental cues. Therefore, it is necessary to develop high-throughput screening platforms to screen cell-material interactions in 3D culture format that could be applied to screen hydrogels scaffolds. AIM: To develop a chemical as well as mechanical gradient hydrogel system using Poly (ethylene glycol) diacrylate (PEGDA) hydrogels. METHOD: Theexperimental conditions for gradient hydrogel formation were optimized using two different concentrations of PEGDA(5% and 40%) by photo-polymerization using a crosslinker. Gradient formation was confirmed by using Tryphan blue dye. Physiochemical characterizations of gradient hydrogel were done using FTIR to analyze chemical bonding that took place during polymerization; thermal stability was analyzed by using TGA and DSC. In vitro enzymatic
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biodegradation study was performed and further, mechanical testing was performed using InstronMicrotester 5848. RESULTS and CONCLUSION: Chemical bonding and thermal property analysis results validated gradient formation. Further, in vitro degradation result showed varying rate of degradation along the gradient. Outcome of mechanical testing confirmed change in mechanical strength of gradient from one end to the other: region with 40% PEGDA had high mechanical strength whereas region with 5% PEGDA had low mechanical strength. Thus, this study demonstrated preparation and characterization of PEGDA gradient hydrogels and this can be used for interfacial tissue engineering andhigh throughput screening. Keywords: Interfacial tissue engineering; High throughput screening; Cell-matrix interaction; Gradient hydrogels; Mechanical strength P143
CHARACTERISTICS OF HBV IN TREATMENT NAÏVE HIV CO INFECTED INDIVIDUAL Demosthenes JP 1, Sachithanandham J1, Pulimood SA2, Zachariah U3, Varghese GM 4, Jeyaseelan L5 , Daniel HD1, Fletcher GJ1, Abraham P1 , Kannangai R1 . 1
Department of Clinical Virology, 2Department of Dermatology, 3Department of Hepatology, 4 Department of Medicine, 5Department of Biostatistics Christian Medical College, Vellore, Tamil Nadu. BACKGROUND : HIV-HBV co-infection has become a major health problem across the world. There is an increase in the morbidity and mortality among this co- infected group. The increased life expectancy of HIV patients due to ART has also reported to accelerate the progression of liver disease in co-infected individuals. So understanding the disease progression in treatment naïve individuals is vital for a better management of this condition. AIM: This study is aimed to examine the virological markers involved in the disease progression of treatment naïve HIV-HBV co-infected individuals METHOD: A cross sectional study was carried out among treatment naïve HIV study subjects. Three groups were identified for the study, 65 HIV mono- infected, 73 HBV mono-infected and 34 HIV-HBV co-infected. Blood samples was collected and analyzed for Virological markers by ELISA and RT-PCR. RESULTS:
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Among 34 dual infected patients, there was a significant increase in the HBV DNA level and aspartate-amino-transferase (AST) when compared with HBV mono-infected. (p=0.0049), (p=0.0055). HIV- HBV co-infected persons had significantly lower CD4 counts (p= 0.0096). Also the HBeAg levels among co-infected group were significantly higher. (p=0.0187) .Though the decrease in CD4 count implies faster disease progression in HIV co- infected group, the viral load observed in HIV mono-infected did not correlate. Markers like HBsAg and alanine-aminotransferase (ALT) were not statistically different, but showed a median increase in the coinfected group. CONCLUSION: HIV co-infection has a significant impact on HBV markers which could have serious implication on outcome. P144
A 5’UTR POLYMORPHISM IN NT5E GENE INFLUENCES OUTCOME IN PATIENTS WITH ACUTE MYELOID LEUKEMIA UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH FLUDARABINE BASED CONDITIONING REGIMEN Ezhilpavai Mohanan1, John C. Panetta2, Kavitha M. Lakshmi1, Anup J Devasia1, Anu Korula1, Fouzia NA1, Nisham P.N1, Aby Abraham1, Biju George1, Alok Srivastava1, Vikram Mathews1 and Poonkuzhali Balasubramanian1 1
Department of Haematology, Christian Medical College- Vellore, 2Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN; BACKGROUND & AIM: Allogeneic hematopoietic stem cell transplantation (Allo-SCT) with fludarabine (Flu) based reduced intensity or toxicity reduced conditioning regimen withBusulfan or Melphalan (Flu/Bu; Flu/Mel) has improved HSCT outcome in patients with AML.Limited reports on the Pharmacokinetics (PK) of Flu in patients with malignant hematological diseases undergoing Allo-SCT suggest that Flu AUC is associated with transplant related mortality (TRM) (LongBoyle et al, 2011). We prospectively analyzed the PK and pharmacogenetics (PG) of Fluon AlloSCT outcome in patients with AML receiving Flu/Bu or Flu/Mel based regimen. METHOD: Flu PK was assessed in 48 adult AML patients receiving Flu/Bu(targeted)(N=27)or Flu/Mel (N=21) regimen prior to Allo-SCT using a validated LC-MS/MSmethod and the concentration was expressed as mol/ml. Genetic polymorphismsthat influence Flu PK (NT5E 5’-UTR variant rs2295890)was screened using pre- HSCT genomic DNA. The influence of Flu PK and PG on clinical outcome endpoints such as overall survival (OS) and event-free survival (EFS)was evaluated using cox regression analysis.
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RESULTS: Althougha significant inter-individual variation in the Flu clearance (1.2mL/h/m2(0.5-4.3); 8.6 fold) and AUC (46ď mol*h/ml (24-101); 4.2 fold)(Table)was observed, none of the PK parameters were associated with EFS/OS. Patients carrying NT5E 5’UTR variant showed significantly better OS (p=0.016) and EFS(p=0.007) (Figure) compared to those carrying wild type genotype. We have previously reported that this variant is associated with decreased Flu Clearance in patients with aplastic anemia and thalassemia receiving Flu based conditioning regimen (Mohanan et al, Blood. December 06, 2014; 124 (21): 3884; Mohanan et al, Blood. December 03, 2015; 126 (23): 3120). Although not significant, the Flu clearance was lower in the NT5E variants in this cohort as well. It can be extrapolated that patients carrying the variant genotype of the NT5E polymorphism, have decreased relapse incidence (Wild type-8; Variants1) and hence better EFS and OS post HSCT, due to decreased clearance and increased systemic exposure to Flu. This finding need to be validated in a larger number and in patients with other disease conditions undergoing HSCT with Flu based regimen, in order to achieve the goal of personalizing conditioning regimen.
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TAENIA SOLIUM LARVAL ANTIGENS INDUCE A CANCEROUS MILIEU IN CELLS OF THE BRAIN Mohammed Azharuddin KO1, Rajshekhar V1, Oommen A2, Prabhakaran V1. 1 Department of Neurological Sciences, Christian Medical College, Vellore, TamilNadu. 2 Gudalur Adivasi Hospital, Gudulur, The Nilgiris, TamilNadu.
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INTRODUCTION: Taenia solium larvae commonly infect the brain and parasite suppression of host immunity leads to long lasting infections. Chronic host immune suppression also underlies induction of cellular cancer milieus and several studies indicate association between T. solium larval infection of the brain {neurocysticercosis, (NCC)} and brain cancer although the mechanistic relationship is not known. OBJECTIVE: The aim of our study was to elucidate cancer mechanism(s) induced by T. solium larval antigens in cells of the central nervous system. METHODOLOGY: BV2 (mouse) and CHME5 (human) microglial cells were stimulated in culture with 0.5, 1.0, 2.5 and 5gm T. solium larval antigens for 2-72 hours to induce a chronic inflammatory milieu and to determine chromosomal instability. Nucleoplasmic bridges were evaluated at 72 hours by micronuclei assay. Total and phospho-p53, H2AX and N-myc proteins and mRNA were determined in the cells by western blots and qPCR respectively. Pro-inflammatory cytokine IL12 was determined in cell culture supernatants by ELISA. RESULTS: Nucleoplasmic bridges were significantly increased in T. solium larval antigen stimulated cells at 72 hours. Phosphorylated p53 tumor suppressor mRNA and protein were significantly decreased and phosphorylated H2AX, N-myc oncoprotein / mRNA and IL-12 significantly increased in cells stimulated with T. solium larval antigens for 16 to 24 hours. Discussion and CONCLUSION: Long exposure to T. solium larval antigens increased pro-inflammatory reactions, oncogene activity and chromosomal instability and lowered tumor suppression in mouse and human microglial cells. These cellular mechanisms suggest that chronic T. solium larval infections of the brain may have the potential to induct cancerous pathways in the brain.
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SHEDDING OF NOROVIRUS GI AND GII BEFORE AND AFTER A DIARRHEAL EPISODE IN INDIAN CHILDREN <3 YEARS OF AGE Authors: Mohanraj M, Maheshwari K, Nirmal Kumar, Sidhartha Giri, Gagandeep Kang Department and affiliations: Wellcome Trust Research laboratory, Christian Medical College, Vellore BACKGROUND : Norovirus has been found to be associated with about 18% of diarrheal disease worldwide in children <5 years of age. Norovirus can persist after a diarrheal illness for 3 weeks or longer for
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children in developing countries. Reverse transcription real-time PCR (RT-qPCR) is a sensitive method for detection of norovirus in stool samples. AIM: To evaluate shedding of norovirus before and after a diarrheal episode in Indian children <3 years of age using RT-qPCR. Materials and METHODs: 10 children positive for norovirus genogroup I (GI) diarrhea and 10 children positive for GII diarrhea were selected for the study. These children were part of a birth cohort study for rotavirus infection and disease, which was conducted in Vellore, India between 2002-2006. A total of 373 children were followed upto the age of 3 years. As part of this study, surveillance stool samples were collected every 2 weeks along with diarrheal samples from all children. All the diarrheal samples were tested for norovirus GI and GII. For each of the 20 children who had an episode of either norovirus GI or GII diarrhea, stool samples collected within +/- 6 weeks of a diarrheal episode were selected for testing by a multiplex RT-qPCR capable of detecting GI and GII. RESULTSs: Of the 10 children with norovirus GII diarrhea, 4 kids (40%) were shedding the virus for 3-7 weeks. 3 children excreted the virus for 6-7 weeks and 1 child for 3 weeks. The period of shedding norovirus in stool varied from 1-2 weeks before the diarrheal episode and upto 3-6 weeks after the diarrheal episode. No such pattern was found for the 10 children with GI diarrhea. Asymptomatic infections with GII in children with GI diarrhea and vice versa were also seen. CONCLUSION: Children from developing countries such as India shed norovirus for variable periods before and after a diarrheal episode. P147
EXTRAPOLATION OF TIME FOR PROBABLE RADIATION SKIN INJURIES FROM VARIOUS TUBE ANGULATIONS DURING PTCA PROCEDURES a
Anna Varghese, a Roshan S Livingstone, b Paul V George aDepartment of Radiology, Christian Medical College,Vellore b Department of Cardiology, Christian Medical College,Vellore AIM To measure radiation dose from various angiographic projections and extrapolate the time required to induce radiation related skin injuries from cardiac interventions performed in angiography suite.
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BACKGROUND: Radiation induced skin injuries are reported in literature in patients undergoing cardiac interventions involving prolongedfluoroscopic screening and when threshold dose exceeds 2Gy. METHODS AND MATERIALS: A prospective study on radiation dose, exposure parameters and time duration for each beam projection for 38 patients who underwent percutaneous coronary angioplasty (PTCA) usingPhilips Allura Clarity FD 10 angiography system were studied. A Dose area product (DAP) meter was used to measure radiation dose. Threshold dose of 2Gy was extrapolatedfrom exposure timefor each angiographic beam projection.Low and medium dose setting were adopted during fluoroscopic screening. RESULTS: Among the various projections, left anterior oblique, LAO45o– CAU35oreached 2Gy in 55mins using low dose and 21 mins using medium dose fluoroscopy settings. In contrast, use of cine acquisitions would reach dose of 2Gy in 3 mins forthis projection. Continuous exposure in this projectionmay affect the right scapula region on the patient. Increased time duration withoverlapping fields from multiple projections has an increased risk for developing skin effectswhen not collimatedappropriately. CONCLUSION: This study provides information on time required from angiographic projection to reach threshold dose during fluoroscopy and cine acquisitions.Avoiding overlapping projections on a specific area and adopting low dose fluoroscopy modes will enable safe practices from complex interventions. No ill effects of radiation was observed during this study.
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WHOLE GENOME SEQUENCING APPROACH FOR DETERMINING THE COLISTIN RESISTANCE MECHANISMS IN KLEBSIELLA PNEUMONIAE: FIRST REPORT FROM INDIA 1
Agila K Pragasam, 1Chaitra S, 1Francis Y, 1Radha G, 1Baby Abirami S, 2Biju George, 1 Santhosh Varghese, 3Indranil B, 1Balaji V. 1Department of Clinical Microbiology, Christian Medical College, Vellore, India, 2Department of Haematology, Christian Medical College, Vellore, India,3University of Kansas Medical Centre, US
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BACKGROUND : Antimicrobial resistance is on the rise globally. Colistin has long been a reserve drug used for the treatment of drug resistant pathogens. The usage of colistin has increased over the years leading to slow emergence of resistance. Colistin resistance is mainly mediated by the alteration in the LPS of bacterial outer membrane with the addition of L-Ara4-N and PEtN molecules. These alterations are mediated by mutations in the genes namely; mgrB, phoP, phoQ, pmrA, pmrB, pmrC and crrABC involved in lipd A modifications. Recently, plasmid mediated resistance due to mcr-1 gene has also been reported OBJECTIVE: The objective of this study is to use whole genome sequencing approach to determine the mechanisms of resistance to colistin in clinical isolates of K. pneumoniae isolated from a terriary care centre in India METHOD: Eight colistin resistant K.pneumoniae were isolated from blood culture at Christian Medical College, Vellore, India. Antimicrobial susceptibility testing was performed and minimum inhibitory concentration (MIC) was determined for colistin and polymyxin B by broth-micro dilution method. Whole genome sequencing was performed using Ion Torrent PGM platform using 200 bp read chemistry. Analysis was done to determine the presence of mutations in mgrB, phoP, phoQ, pmrA, pmrB, pmrC and crrABC genes and plasmid mediated of mcr-1and mcr-2 gene RESULTS & DISCUSSION: The eight isolates were resistant to all the antimicrobials expect tigecycline. MIC of colistin and polymyxin B were ranged from 4 to 1024 Âľg/ml and 0.5 to 2048 Âľg/ml respectively. Mutational analysis revealed that, multiple mutations were observed in the chromosomal genes involved in lipid A modifications. No mutations were in pmrA and pmrD genes and mcr-1 and mcr-2 gene was absent in all the isolates. The most significant were mutations in mgrB gene. Among the eight isolates, four, three and one were belonged to sequence types ST 231, ST14 and ST147 respectively. CONCLUSION: Overall, from this study, multiple numbers of alterations have been observed. This includes silent mutations, point mutations, insertions and/or deletions. Mutations in the chromosomal genes were responsible for resistance to colistin in this study. Inappropriate usage of colistin in the clinical setting should be avoided, as selection pressure may contribute for colistin resistance.
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P149
EVALUATION OF VP6 REAL-TIME PCR IN THE DETECTION OF ROTAVIRUS FROM STOOL SAMPLES OF CHILDREN <5 YEARS WITH ACUTE GASTROENTERITIS Authors: Karthick Nithyanandhan, PriyaHamavathy, SidharthaGiri, Gagandeep Kang Department and institution:Wellcome Trust Research Laboratory, Christian Medical College, Vellore. BACKGROUND : A variety of methods are used to detect rotavirus in stool samples. These include enzyme immunoassays, and reverse transcription PCR (RT-PCR). These routine methods, however, suffer from some limitations. In the last few years, real-time PCR assays targeting the VP6 gene have been used for rotavirus detection in stool. METHOD: A total of 50 stool samples collected from children <5 years hospitalized with acute gastroenteritis (AGE) were selected for the study. Of these, 40 samples were positive and 10 were negative for rotavirus by conventional VP6 PCR. For the study, 20% stool suspensions were used for RNA extraction. This was followed by complementary DNA (cDNA) generation and amplification of the VP6 gene by real-time PCR. RESULTS: Of the 50 stool samples, 40 (80%) were found to be rotavirus positive while 10 (20%) samples were negative for rotavirus by the VP6 real-time PCR assay. Considering conventional RT-PCR as the gold standard, the sensitivity and specificity of the real-time PCR assay was 100% and 100% respectively. There was complete concordance between the results of conventional VP6 PCR and real-time PCR assays. CONCLUSION: VP6 real-time PCR assay for rotavirus is highly sensitive and specific for rotavirus detection from stool samples.
P150
METABOLIC UNCOUPLERS SENSITIZE ACUTE MYELOID LEUKEMIC CELLS TO ARSENIC TRIOXIDE Nithya Balasundaram ,Saravanan Ganesan, Hamenth Kumar Palani, Ansu Abu Alex, Sachin David, Anu Korula, Biju George, Poonkuzhali Balasubramanian, Vikram Mathews.
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Department of Haematology, Christian Medical College, Vellore. BACKGROUND : Arsenic trioxide (ATO) is used as a single agent frontline therapy for the treatment of acute promyelocytic leukemia (APL) with a 5year survival rate of 80 %. Non- APL myeloid leukemic cells are generally resistant to ATO, extending the use of ATO in non-APL myeloid leukemia will be of greater importance due its minimal toxicity in comparison to the conventional chemotherapeutic agents used in the treatment of AML. AIM: The primary objective of the study is to evaluate the mechanisms of resistance to ATO in nonAPL myeloid leukemia. MATERIAL AND METHOD: AML cell lines U937 and THP1 are used to study the ATO resistance in vitro. Inhibitory concentration 50 of ATO (IC50) was assessed by a MTT assay. Cell lines were treated with ATO and oxidative phosphorylation (OXPHOS) uncoupler FCCP for 48hours and the percentage of viable cells are measured using Annexin V - 7AAD staining FACS. RESULTS: ATO has been reported to directly inhibit the glycolytic pathway; this effect is believed to contribute to its cytotoxic effect in APL. Hence, we studied the metabolic dependency of myeloid leukemic cells which promotes survival even in the presence of ATO. Towards that we assessed the sensitivity of the cell lines to OXPHOS uncoupler.FCCP treatment alone did not reduced the viability of these cells significantly in comparison to ATO alone, suggesting the ability of these cells to uncouple their metabolic pathway from OXPHOS to glycolysis when inhibited. However, when FCCP was combined with ATO it significantly restored the sensitivity of the cell lines to ATO. The data suggests that the non-APL myeloid leukemic cells could be sensitized to ATO by combining ATO with OXPHOS uncouplers. CONCLUSION: Uncoupling the metabolic dependency of the myeloid leukemic cell lines could be potentially exploited to sensitize them to ATO .It is also important to note that a number of molecules that are FDA approved and used in the clinic also have OXPHOS uncoupling activity and could potentially be evaluated for their synergistic activity with ATO in leukemia. P151
FREQUENCY OF CROSS-RESISTANCE TO RILPIVIRINE, ETRAVIRINE AND TENOFOVIR AMONG HIV-1 SUBTYPE C PATIENTS FAILING ART REGIMEN Veena V Ramalingam1, Demosthenes JP1, Rupali P 2, Varghese GM2 , Abraham O C2, Zachariah A2, Rajesh Kannangai1
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1
Department of Clinical Virology, 2Department of Medicine, Christian Medical College, Vellore, Tamil Nadu BACKROUND : Non-nucleoside reverse transcriptase inhibitors (NNRTIs), especially nevirapine and efavirenz, in addition to the nucleoside reverse transcriptase inhibitors (NRTIs) gained a definite place in the treatment of HIV-1 infection. Emergence of drug induced cross resistance following HIV therapy has a significant impact on the effectiveness of ART program. AIM: This study was aimed to determine the resistance profile and the rate of cross-resistance in HIV1 infected patients failing an efavirenz or nevirapine regimens and without tenofovir. METHOD: A total of 85 samples were collected from HIV-1 infected individuals failing ART regimen during 2012-2016. Out of 85, 38 (44.7%) patients received nevirapine based regimen and 47 (55.3%) received efavirenz based regimen. Among 85 individuals, 45 (52.9%) patients were not on tenofovir based regimen. None of the patients received either rilpivirine or etravirine regimen. Viral RNA was extracted from the stored plasma. The amplification and sequencing of pol gene was carried out and drug resistance mutations were analyzed using Stanford data base. In this study, mutations score of >30 was taken as resistance. RESULTS: Out of 85 samples included in the study, 48 (56.5 %) and 43 (50.6%) patients showed cross resistance to rilpivirin and etravirine respectively. Twenty four (53.3%) out of 45 showed cross resistance to tenofovir. The frequently detected NNRTI mutations were K103N (44.71%), Y181C (35.29%) and G190S (27.06%). K103N mutation was observed alone in 3.5% of patients or combination with one to three of other NNRTI mutation in 96.5% of cases and all patients were failing NVP and EFV regimen. M184V (91.76%) was the most predominant NRTI mutation and was observed alone in 9.4% participants, followed by T215Y (44.71%) and K70R (42.35%). K65R is the signature mutation of tenofovir and seen in 10 (22.2%) patients who were not on tenofovir regimen. CONCLUSION: Frequent cross resistance to tenofovir (53.3%), rilpivirin (56.5 %) and etravirine (50.6%) were observed among HIV-1 subtype C infected individuals experiencing failure to ART regimen. Though tenofovir, RPV and ETR were considered as drugs with high genetic barrier, this study showed more than 50% of individuals had high/intermediate resistance to these drugs without exposure. Hence, inclusion of these drugs in the second line regimen may not be effective in half of the patient population who are failing the fi
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P153
CANDIDATE GENE ANALYSIS FOR RISK OF ISCHEMIC STROKE IN INDIAN POPULATION Raja Solomon, B.S.B.Salomi,Christhunesa S. Christudass, Sanjith Aaron, Department of Neurological Sciences, Christian Medical College, Vellore – 632 004, Tamilnadu Stroke mostly occurs in patients with one or more risk factorssuch as age, hypertension, smoking, diabetes mellitus, hyperlipidemia or obesity.However, there are a significant proportion of them who suffer from ischemic stroke in the absence of these risk factors.Genetic predisposition resulting from mutations in the coagulation factor genes is linked to an increased risk of ischemic stroke. Factor V Leiden mutation, FII/ G20201A and MTHFR/C677T have been identified to have a significant association with the risk of ischemic stroke. However, these genetic variantsalone do not explain for the high incidence of stroke.Probably there are other polymorphisms in the genes involved in coagulation which might be playing a role. We attempted a case-control study involving160 ischemic stroke patients and 285 healthy controls, to study the role of some of the candidate gene polymorphisms, such as KNG1/T1742C, FXII/C46T, SERPINC1/G786A, Protein Z/G79A with the risk of ischemic stroke. Genomic DNA was isolated from the peripheral blood sample and the polymorphisms were studied using PCR-RFLP technique. Odds ratios were calculated and Chi-square analysis was carried out. Our results show a significant association between CC genotype of KNG1/T1742C, CT and TT genotypes of FXII/C46T with the risk of ischemic stroke. AA genotype of SERPINC1/G786A shows a trend of association with the risk of ischemic stroke. In our study Protein Z/G79A, does not show any association with the risk of ischemic stroke. Early studies have shown that C allele of KNG1/T1742C is associated with decreased aPTT levels,T allele of FXII/C46T with low plasma FXII activity and A allele of SERPINC1/G786A with lower anticoagulant activity. Thus our studies correlate with the functional consequences of the polymorphisms. However we need to extend the study with more samples to come to confirm our results. P154
MECHANISM OF HYPOTENSION IN CLEISTANTHUS COLLINUS POISONING Renu Raj R1, A Soosai Manickam1, Bhavitra S1, Sathya Subramani1 1 Christian Medical College, Vellore, Tamilnadu Cleistanthus collinus is a common plant poison used for suicides in Tamil Nadu. Cleistanthin C is the major toxin in the boiled aqueous extract of C.collinus. Refractory hypotension due to vasodilatation is the major cause of death in patients. While investigating vasodilatory mechanisms in a goat arterial strip, we identified a new signaling pathway in which, alpha adrenergic stimulation causes paradoxical vasodilatation in
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high NO environment. Here we report that Cleistanthin C acts through the new pathway, leading to vasodilatation, when there is simultaneous alpha adrenergic activation OBJECTIVE: To study the effects of Cleistanthin C on vascular tension in goat arterial strip. METHOD: Spiral strip of a section of small artery isolated from the goat leg was suspended in an organ bath (25 ml), filled with physiological salt solution at 37◦C, aerated with carbogen (95% O2 & 5% CO2). One end of the strip was attached to a force transducer connected to a data acquisition system (Power lab). Drugs were added to the organ bath; changes in tension were recorded and analyzed. RESULTS: Cleistanthin C (100µM) per se did not produce any change in the vascular tension. But subsequent addition of PE (100µM) resulted in vasodilatation (n=6, P=0.028 with Wilcoxon signed rank (WSR) test). Cleistanthin C/ PE induced vasodilatation was abolished in the presence of L- NNA (1mM) (n=4, P=0.011 with Mann- Whitney U test). Cleistanthin C/ PE combination did not produce vasodilatation in the presence of prazosin (10µM) (n=5, P=0.008 with Mann- Whitney U test) but produced vasodilatation in the presence of propranolol (10µM) (n=4, P=0.394 with Mann – Whitney U test) CONCLUSION: Cleistanthin C creates an environment in which alpha adrenergic stimulation results in vasodilatation, which is nitric oxide-dependent.
P155
FECALCALPROTECTIN AS A NON-INVASIVE BIOMARKER FOR INFLAMMATORY BOWEL DISORDER: DETERMINING A CUT-OFF FOR SOUTH INDIAN ADULTS Authors: Revathi R.1, Ira Praharaj1, A.J. Joseph2,Balasubramaniam KA2,SitaraSwarnaRao Ajjampur1, Gagandeep Kang1 Departments & Institution:Wellcome Trust Research Laboratory,Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Department of Gastroenterology, Christian Medical College
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BACKGROUND : Inflammatory bowel disease (IBD) and Irritable bowel syndrome (IBS) are common conditions that may present with a similar symptoms complex of abdominal pain and altered bowel habits. Endoscopy is commonly used but is invasive and expensive. Although, fecalcalprotectin has been shown to be a reliable marker for IBD in western countries(cut-off=50µg/g), the levels of this biomarker has been found to be generally higher in the Indian population. It is, therefore, important to determine a cut-off which can be applicable to adults in our settings. AIM: To compare the levels of fecalcalprotectinin patients with IBD to the healthy controls and the patients with IBS, and to determine a cut-off value for fecalcalprotectin for diagnosing IBD. METHOD: A total of 176adults (clinically confirmed IBD=66 patients, IBS =79, healthy community controls=31)wereincluded in this study. Stool samples were collected and estimation of fecalcalprotectin levels was done using a quantitative ELISA kit (Epitope Diagnostics IVD kit).Fecalcalprotectin levels were expressed in µg/g of stool. Sensitivity and specificity of the test using different cut-off values was calculated and ROC analysis was done. RESULTS and CONCLUSION: Of the 176 adults studied, median calprotectin levels were significantly higher in patients with confirmed IBD (median= 179ug/g, maximum= 2002 µg/g)compared to the healthy controls and IBS patients whose median concentrations were less than the limit of detection(<25µg/g). The area under the ROC curve (AUC) to analyse the cut-off was 0.84 (95% CI= 0.77 to 0.90). Using ROC statistics, a cut-off value of 92.6µg/g indicated the presence of IBD with a sensitivity of 71.21% and specificity of 96.26%. The positive likelihood ratio was also highest at this cut-off. Fecal calprotectin is a sensitive and specific marker in measuring the activity of IBD, and FC cut-off of more than 92.6µg/g can be used as a diagnostic biomarker of IBD for south Indian adults.
P156
GENOMIC ANALYSIS OF COLISTIN RESISTANT DETERMINANTS ACINETOBACTER BAUMANNII USING NEXT GENERATION SEQUENCING
IN
Saranya Vijayakumar, Balaji Veeraraghavan, Naveen Kumar D R, Dhiviya Prabaa M S, Yamuna Devi Baktavachalam, Baby Abirami,S, Radha Gopi BACKGROUND : Infections due to multi-drug resistant Acinetobacter baumanniihas emerged as a major clinical problem. Currently, colistin is considered to be the last-resort therapy against this pathogen. However, decreased susceptibility to colistin isincreasingly reported worldwide. Thepurpose of
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this study is to characterizeresistance mechanisms associated with colistin resistancein A. baumanniiusing next generation sequencing. MATERIALS AND METHOD: A total of 96A. baumanniiblood isolates (both colistin susceptible and resistant by disc diffusion)collected from January 2014 to July 2016were included in this study. Minimum inhibitory concentration (MIC) of colistin was determined by broth micro dilution (BMD).Threeclinical isolates with colistin MIC of 64 wereselected for whole genome sequencing to identify single nucleotide mutations that could be responsible for reduced colistin susceptibility.The presence of acquired mcr-1 / mcr-2 genes and the sequence type of the isolates were determined using Res Finder and MLST databases respectively. RESULTS AND DISCUSSION: Of the 96 tested, 10 isolates were colistin resistant with MIC ranged between 8 – 64 Οg/ml. Mutations within pmrB, lpxD and lpsB genes were identified. All the 3 colistin resistant isolates had a single conservative mutation (A444V)and two conservative mutations (K4Q and E117K)withinpmrB andlpxD gene respectively. Within lpsB gene, 6 novel mutationswere identified of which 3 were conservative (Q216K, L329V, H334N), 1 semi-conservative (S219E) and 2 non-conservative (H218G, I331T). No mutations were seen within pmrA, lpxA and lpxC genes. Plasmid mediated mcr-1 / mcr-2 genes were absent in all the 3 isolates. Of the 3 colistin resistant isolates, 2 belongs to ST-848 and one isolate belongs to ST-451. CONCLUSION: The present study identified that,colistin resistance among clinical isolates ofA. baumannii is associated with mutations in the two component regulatory system, pmrAB and loss of lipopolysaccharide by mutations in lipid A biosynthesis genes.Previous studies have shown that A444V and E117K mutations within pmrB and lpxD genes respectively were associated with colistin resistance. Novel mutations within lpsB gene was identified in all the 3 colistin resistant isolates. However, further studies are needed to prove the contribution of such novel mutations in the development of colistin resistance in A. baumannii.
P157
CROSS TALK BETWEEN LEUKEMIC AND STROMAL CELLS INDUCE OSTEOBLAST DIFFERENTIATION IN STROMAL CELLS : A POSSIBLE ROLE IN LEUKEMIC NICHE AND DRUG RESISTANCE Authors: Saravanan Ganesan1, Hamenth Kumar Palani1, Vairavan Lakshmanan2, Nithya Balasundaram1, Ansu Abu Alex1, Neha Vyas3, Dasarathi Palakodeti2, Vikram Mathews1.
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Departments and institution: 1- Department of Haematology, Christian Medical College, Vellore, India. 2- Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bengaluru, India. 3- Molecular Medicine Department, St. John's Research Institute, St. John's National Academy of Health Sciences, Bengaluru, India. BACKGROUND: Bone marrow microenvironment acts as a sanctuary for the leukemic cells to establish a niche and protect themselves from chemotherapeutic agents. There are numerous reports on bone marrow micro-environment mediated drug resistance (EMDR) in leukemia. There are very limited data available on the effect of leukemic cell interaction on the stromal cells. AIM: We undertook a study to evaluate the changes induced by leukemic cells (NB4) on the HS-5 stromal cell line. RESULTS AND CONCLUSION: After 2 days of co-culture with NB4 cells, the RNA from HS-5 stromal cells were subjected to gene expression profiling and small RNA sequencing. In a gene expression profiling, we observed an enrichment of Wnt signaling and BMP signaling pathway. When we subjected the array to functional analysis, a significant enrichment of osteoblast differentiation genes was observed in the stromal cells co-cultured with leukemic cells in comparison to HS-5 cells alone. A stringent miRNA analysis revealed 21 miRNA were differentially regulated in the HS-5 cells co-cultured with leukemic cells in comparison to HS-5 cells alone. In consistent with the gene expression profile, we observed that most of the miRNA differentially regulated were involved in the regulation of osteoblast differentiation (hsa-miR-33b-5p, hsa-miR-210-3p, hsa-miR-2225p, etc.). As previously published, we also observed upon co-culture with leukemic cells, there was a down-regulation of NF-kB pathway and increased Wnt signalling in HS-5 cells. This was demonstrated by documenting decreased translocation of p65 subunit and increased B-catenin in the nuclear compartment of HS-5 cells on day 2 and day 7 of co-culture. We observed that there is an increased expression of osteoblast differentiation transcription factor (RUNX2) in HS-5 cells upon co-culture on day 2 by real time PCR and western blot. We further validated this using functional assays such as alkaline phosphatase activity and alizarin red S staining. Similar differentiation effects were seen in HS-5 cells when it is co-cultured with other malignant cells (U937, U266 and Jurkat) . This study demonstrates a possible role of leukemic cells in establishing leukemic niche in the bone marrow by inducing osteoblast differentiation of stromal cells. The role of this leukemic cell induced osteoblast differentiation of stroma in drug resistance against various chemotherapeutic agents needs further evaluation.
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P157
FATE OF IKAROS IN MULTIPLE MYELOMA CELLS UPON TREATMENT WITH LENALIDOMIDE AND PROTEASOME INHIBITOR Authors: Saravanan Ganesan Nithya Balasundaram, Hamenth Kumar Palani, Ansu Abu Alex, Sachin David, Anup Joseph Devasia, Biju George, Poonkuzhali Balasubramanian, and Vikram Mathews Departments and institution: 1- Department of Haematology, Christian Medical College, Vellore, India. BACKGROUND: Recent evidences suggests that the efficacy of Lenalidomide (LEN) depends upon its ability to degrade IKZF1 and IKZF3 proteins via cereblon dependent ubiquitin proteasome pathway [Science. 2014 Jan 17; 343(6168): 301–305]. Based on this model it would theoretically be antagonistic to combine LEN with proteasome inhibitors (PI). However, it is well recognized that there is significant synergism when LEN is combined with PI and this combination is routinely and effectively used in the clinic. The mechanism of synergy and the fate of IKZF1 and IKZF3 when these two agents are combined is poorly understood. AIM: We undertook a series of experiments to study the fate of IKZF1 when this combination of drugs was used in multiple myeloma cells. RESULTS AND CONCLUSION: Combining LEN (1uM) along with bortezomib (BTZ; 1nM) a PI showed a significant kill on U266 cells (myeloma cell line) on day 5 post treatment (n=3; P=0.02) when compared to either of the agents alone. In an MTT assay, the synergism was well documented with a combination index of 0.5. Next we assessed the function of proteasome (chymotrypsin activity) when LEN was combined with PI. We observed that LEN alone does not interfere with proteasome activity. It was noted that BTZ alone at the concentration used (5 nM) was able to effectively inhibit the activity of proteasome. It was also observed that combining these two agents does not interfere with BTZ action in inhibiting proteasome complex. As a result of efficient proteasome inhibition, we observed an accumulation of ubiquitinated proteins in the BTZ and LEN + BTZ treated cells when compared to control and LEN alone treated cells. Next, we looked for the fate of IKZF1 in U266 cells treated with LEN, BTZ and in combination of both the drugs. As reported, we observed a degradation of IKZF1 in U266 cells upon treatment with LEN. While we did not see any degradation of IKZF1 in BTZ alone treated cells. It was noted that in combination treated cells (LEN+BTZ) there was a degradation of IKZF1. In spite of significant proteasome complex inhibition, degradation of IKZF1 was observed which suggested a proteasome independent mechanism. It is well known that proteasome inhibition results in upregulation of the autophagy pathway which in turn can degrade the accumulated ubiquitinated proteins. We noted that upon treatment with BTZ or LEN+BTZ an induction of autophagy was
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observed, as evidenced by an increase in generation of LC3II bands on an immunoblot. To support our hypothesis that IKZF1 is degraded by autophagy in the absence of proteasome complex, we pre-treated the U266 cells with an autophagy inhibitor (3-methyladenine) followed by treatment with LEN and BTZ and noted an accumulation of IKZF1 proteins. We also observed a downregulation of IKZF1 target genes IRF4 and c-MYC by 12 and 24 hours in the combination treated cells (data not shown). Taken together this data demonstrates that there is (i) significant in-vitro synergism between the two agents (ii) the combination additively induces autophagy pathway (iii) IKZF1 protein can be degraded via this autophagy pathway in the presence of effective proteasome inhibition. While additional mechanisms of synergy between these two agents cannot be excluded, further enhancing autophagy pathway in these cells by drugs like sirolimus (autophagy inducer in myeloma cells) could potentially improve the synergy between these two drugs.
P158
ROLE OF MIRNA IN MICRO-ENVIRONMENT MEDIATED DRUG RESISTANCE IN ACUTE PROMYELOCYTIC LEUKEMIA TO ARSENIC TRIOXIDE Authors: Saravanan Ganesan1, Vairavan Lakshmanan2 , Hamenth Kumar Palani1, Nithya Balasundaram1, Ansu Abu Alex1, Sachin David1, Anu Korula1, Biju George1, Poonkuzhali Balasubramanian1, Neha Vyas3, Dasarathi Palakodeti2, Vikram Mathews1. Departments and institution: 1- Department of Haematology, Christian Medical College, Vellore, India. 2- Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bengaluru, India. 3- Molecular Medicine Department, St. John's Research Institute, St. John's National Academy of Health Sciences, Bengaluru, India. BACKGROUND: Role of stromal microenvironment in drug resistance has been extensively reported for several cancers. We have demonstrated earlier that there is significant microenvironment mediated drug resistance (EMDR) to arsenic trioxide (ATO) in acute promyelocytic leukemia (APL) and that this was predominantly driven by upregulation of the NF-kB pathway in the malignant cell. In our current study we have probed the molecular mechanism of ATO resistance in further detail. The role of microRNA (miRNA) in mediating this cross talk, if any, has not been reported on. AIM: We undertook a study to evaluate the potential role played by miRNA in EMDR to ATO in APL. RESULTS AND CONCLUSION: Using NGS based small RNA sequencing we identified two miRNA’s that were differentially regulated in NB4 cells upon coculture with HS5 stromal cells (FDR corrected p values < 0.05).
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The two miRNAs were hsa-miR23a-5p (downregulated) and hsa-miR125a-3p (upregulated). These miRNAs have also been previously reported to be involved in NFkB regulation, specifically miR125a-3p has been reported to be involved in activation of the NFkB pathway and miR23a-5p can be repressed by the same pathway. These results were consistent with our earlier reported observations that NFkB pathway is dysregulated and enhances drug resistance to ATO. We also observed miR23a-5p mimics were able to restore the sensitivity of NB4 cells to ATO even in the presence of stromal cells. Consistent with the above small RNA sequencing and our previously reported microarray data, using quantitative proteomics approach we have identified that both NFkB signaling and metallothionein 2A (MT2A) levels are upregulated in leukemic cells upon stromal coculture. MT 2A is a known target for has-mir23a-5p. MT’s are known to sequester heavy metals such as arsenic and could potentially reduce their cytotoxic effect. The role of metallothionein in ATO resistance in APL and possibly other leukemia’s needs further evaluation. This data along with that reported earlier by us illustrates multiple levels of regulation of the NFkB pathway and resistance to ATO by stromal cell co-culture.
P159
NUDT15 C.415C>T VARIANT EXPLAINS 6-MP TOXICITY IN PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA AUTHORS: Stallon Ilangeswaran, Ezhilpavai Mohanan, Nisham P.N, Amirthavani G, Biju George, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian DEPARTMENT & INSTITUTION: Department of Haematology, Christian Medical College, Vellore, Tamil Nadu, India BACKGROUND: Incorporation of thiopurines in maintenance chemotherapy has improved treatment outcomes in ALL. Thiopurines have narrow therapeutic indices owing to severe toxicity, which is moderately explained by the presence of thiopurine methyl transferase (TPMT)genetic variants (TPMT *2 *3A *3B or *3C). However, rarity of TPMT polymorphisms in Indian population (Desire et al, 2009) fails to explain thiopurine-induced toxicity, suggesting that additional factors may contribute to the variability in thiopurine metabolism. Recent reports havesuggested a coding variant (c.415C>T (*3))in NUDT15 gene to be a determinant of thiopurine toxicity in the Asian population. NUDT15 dephosphorylates the thiopurine active metabolites therebyreducing cytotoxic effects of thiopurines and the NUDT15*3 variant shows reduced or loss of enzymeactivity. We screened for NUDT15 polymorphism in ALL patients on 6-MP maintenance therapy with myelosuppression, for whom TPMT polymorphism status was requested. MATERIALS AND METHODS: Twenty-eight ALL patients with the median age of 15yrs (2-57yrs) who underwent 6-MP maintenance therapy were included in this study. Genomic DNA isolated from peripheral blood was used for screening NUDT15 polymorphism by PCR followed by Sanger sequencing
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RESULTS AND CONCLUSIONS: NUDT15*3 variant was seen in 15 (10 heterozygous and 5 homozygous variant)of the 28 patients. One of these patients had TPMT *3C heterozygous genotype and was not positive for NUDT15 variant. Twenty two of these 28 patients had 6-MP dose reduction. TPMT polymorphisms in Asian population is rare and NUDT15*3 variant frequency alone explains 22% of variability in mercaptopurine intolerance in childhood ALL (Yanget al. J. Clin. Oncol, 2015).In addition to TPMT polymorphism, a screening panel including NUDT15 c.415C>T, as well as other polymorphisms in known genes involved in 6-MP metabolism would be necessary to understand the genetic basis of 6-MP intolerance in patients with ALL for personalizing 6-MP therapy.
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PREDICTIONOF THE STAGE SPECIFIC ROLE OF NOVEL FACTORS IN REPROGRAMMING BY COMBINING FACS ANALYSIS WITHRNAI BASEDCANDIDATE GENE KNOCKDOWN Sumitha Prameela Bharathan1,2, Aneesha Nath1, Abhirup Bagchi1 and Shaji Ramachandran Velayudhan1,2 Departments and institution 1
Centre for Stem Cell Research, 2Department of Haematology , CMC campus, Vellore, Tamil Nadu BACKGROUND: Induced pluripotent stem cells (iPSCs), with their property of self renewal and pluripotency, are promising alternative to embryonic stem cellsin basic science research and regenerative medicine. Pluripotency induction is a slow and inefficient multi-step process and involves retuning several molecular and cellular pathways of somatic cells to a state similar to that in ESCs. Since many of these pathways are linked with tumorigenesis in other cellular context, to ensure the safety in therapeutic use of human iPSCs (hiPSCs), it is critical to understand molecular mechanism of pluripotency induction. Gene regulation studies attempting to identify novel regulatory factors in reprogramming investigate the effect of candidate gene overexpression and knockdown on overall reprogramming outcome, and hence such studies have limited sensitivity in identifying the stage specific role of factors. AIM: This study aimedat assessing the potential of FACS based analysis of reprogramming cells subjected to candidate gene knockdown for predicting the stage specific role of selected factors. METHODS: Briefly, candidate genes were knockdown in fibroblasts and then subjected to OSKM mediated reprogramming using polycistronic hSTEMCCA lentiviral vector. The reprogramming cells were
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analysed for coexpression kinetics fibroblast marker, CD13 and pluripotency markers, SSEA-4 and TRA-1-60 to estimate the percentage of cells belonging to different stages of reprogramming designated by various combinations of these markers. The enrichment or depletion of cells in different reprogramming stages from fibroblasts subjected gene knockdown compared to control cells and reprogramming stage affected by gene knockdown were identified. RESULTS AND CONCLUSION Using this strategy, GRHL2, SETD7 and KDM2A were predicted to play a key role in downregulation of fibroblast specific gene expression, whereas PRDM14, PRDM12 and KDM2B seemed to act in the late stages inhibiting the induction of TRA-1-60. Thus, combining FACS based coexpression analysis of specific markerswith candidate gene regulation in reprogramming cells can help in rapid identification of stage specific role of candidate factors in reprogramming. P160
ARE RYANODINE RECEPTORS DEPOLARIZATION IN HEART?
IMPORTANT
FOR
DIASTOLIC
Teena Maria Jose, Jesi W, Sathya Subramani, Christian Medical College, Vellore INTRODUCTION: It is known that during systole there is release of Ca2+ from SR (sarcoplasmic reticulum) via RyR (Ryanodine receptor) which is important for excitation contraction coupling. There is release of SR Ca2+ during diastole also. This released calcium will get extruded via sodiumcalcium exchanger (NCX). Since the stoichiometry of NCX is 3Na+:1Ca2+, calcium extrusion will result in an inward current. This current called INCX is important for late diastolic depolarization of SA (sinoatrial) nodal cells of heart. Diastolic Ca2+ release from SR can occur through RyR (Ryanodine receptor) or IP 3R (Inositol 1, 4, 5 triphosphate receptor). This study will assess the role of RyRs in pacemaker function. OBJECTIVE: To study the changes in heart rate after perfusing isolated rat heart with normal ECF solution followed by addition of 100 Âľm Ryanodine. MATERIALS AND METHODS: Isolated hearts of male Wistar rats in Langendorff mode was used in this experiment (n=12). It was perfused with normal extracellular solution for first 15 minutes to record basal HR (heart rate). Then 0.25% DMSO (control) or 100ÂľM Ryanodine in 0.25% DMSO was added to the normal extracellular solution and HR was recorded for 15 minutes. This was followed by wash with normal extracellular solution.
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HR was calculated from surface ECG recorded with the help of surface electrodes using CMC daq (computerised data acquisition system). RESULTS: Control group (0.25% DMSO) shows that the heart rate does not change with time (p=0.075, with WSR (Wilcoxan signed rank test).With Ryanodine 100µM there is decrease in heart rate (p=0.028).Compared to control Ryanodine 100µM decreased the heart rate 55.56% (p=0.004, with MWU (Mann-Whitney U test). CONCLUSION: Both Ryanodine receptors and IP3 receptors are important for pacemaking. P161
TO STUDY THE ROLE OF ABORTION, INDUCED OR SPONTANEOUS, IN DEVELOPING SYSTEMIC SCLEROSIS IN LATER LIFE Authors: Akhila Sosa Jones1, Shreya Susan Koshy1, , Grace Rebekah2 , John Mathew3 Department and Institution 1 – 3rd year MBBS students, Christian Medical College Vellore, Tamil Nadu, India – 632004 2 – Department of Biostatistics, Christian Medical College Vellore, Tamil Nadu, India – 632004 3 – Department of Clinical Immunology and Rheumatology, Christian Medical College Vellore, Tamil Nadu, India – 632004 *Corresponding author: Dr. John Mathew, Physician , Dept. Clinical Immunology and Rheumatology, Christian Medical College, Vellore (TN) -632004. BACKGROUND: Systemic sclerosis is an autoimmune disease for which there are multiple aetiologies which have not been proven conclusively. In a study conducted on fetomaternal microchimerism in women who had undergone termination of pregnancy, it was found that there was a significant fetalmaternal transfusion of cells, even after a first-trimester termination of pregnancy. Like many other autoimmune diseases, women are more affected by systemic sclerosis than men. From the history of women diagnosed with systemic sclerosis, it was observed that a large number of them had undergone abortion before they developed the disease. Abortions result in greater fetal cell traffic into maternal body. The presence of foreign cells in the body can induce an autoimmune reaction similar to graft versus host reaction, which might lead to the development of systemic sclerosis. AIM: To study the incidence of abortions, induced or spontaneous, in developing systemic sclerosis in later life.
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METHODS: This was a case control study that was conducted in the Department of Clinical Immunology and Rheumatology between January 2015 to September 2016 after a written informed consent from each individual. This study was approved by the IRB prior to initiation. Study was conducted among women of age group 18-70, who were diagnosed with Systemic Sclerosis and fulfilled the classification criteria for Systemic Sclerosis by American College of Rheumatology (ACR). Among them the history of abortion was asked. The obtained data was then compared with a control group patients. Patients with fibromyalgia attending the Rheumatology department were taken as controls. The comparison was to find whether there were increased abortions in women with systemic sclerosis. This could give information whether there could be a possible role for abortion in the aetiology of systemic sclerosis. A sample size of 45 case and 45 control was calculated using nMaster.Statistical analysis was performed using SPSS v16.0. RESULTS: A total of 93 patients were studied of which 48 were cases and 45 controls. 25 (52.08%) among the cases and 27 (60%) among the controls had abortions. Among the 25 cases with abortion, 20 had induced abortion and 5 had spontaneous abortion. Among the 27 controls, 20 had induced abortion whereas 7 had spontaneous abortion. The Odds Ratio was 0.7246 which meant there was no significant association. DISCUSSION: The possibilities for inability to show an association could be that fibromyalgia itself has an association with abortions which has not been described before. It could be that there is no association between abortions and developmental of systemic sclerosis in later life. CONCLUSION: In our study we did not find any significant association between abortion and development of systemic sclerosis in later life, compared to patients with fibromyalgia. Key words: Systemic sclerosis, fetomaternal microchimerism, spontaneous abortion, induced abortion, fibromyalgia P162
PREVALENCE OF HEPATOTOXICITY IN PATIENTS ON TREATMENT WITH ANTI-TUBERCULOSIS THERAPY IN A TERTIARY CARE CENTER: A RETROSPECTIVE SURVEY
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Arunava Saha1, Blessed Winston A2, Saibal Das2, Aniket Kumar2, Joy S Michael3,Balamugesh T4,Margaret Shanthi FX2 1 Medical student (MBBS), Christian Medical College, Vellore, Departments of 2Pharmacology, 3 Microbiology, 4Pulmonary Medicine, Christian Medical College, Vellore BACKGROUND: Tuberculosisis a major health burden worldwide, and India being the leading nation in tuberculosis harbours 2-2.5 million cases presently. Anti-tuberculosis drug induced liver injury is a serious adverse effect, which causes substantial morbidity and mortality, complicating the TB treatment. Patients taking anti-TB drugs may develop severe hepatotoxicity that may progress to liver failure and death if the offending drug is not stopped promptly. AIM: This studywas conducted to evaluate the prevalence and risk factors associated with anti-TB drug induced hepatotoxicity in a tertiary care hospital in India over a period of 5 years. METHODS: This retrospective study was done with the patients presenting to the Departments of Pulmonary Medicine and General Medicine with a diagnosis of sputum positive pulmonary tuberculosis from 1st January 2008 to 31st December 2012 (5 years). The liver function test results and other relevant clinical data were obtained from the in/out-patient charts and ‘CHIPS’ database. RESULTS: 787 patients were identified, out of which only 253 came for follow-up, and had at least one LFT result done after initiation of therapy.Out of the 253 patients, 24 patients (9.48%) of the studied population developed drug induced hepatotoxicity. On further analysis, alcohol consumption (OR= 2.6065), concomitant infections like Hepatitis B (OR= 9.9130) and HIV (OR= 1.6200) had statistically significant association with anti-TB drug induced hepatotoxicity.
CONCLUSION: A finding of 9.48% prevalence of hepatotoxicity is considerably high. Hence a baseline LFTbefore initiating anti-TB treatment and close monitoring of liver toxicity during the therapy should be adopted on a routine basis to attenuate the burden of anti-TB drug induced hepatotoxicity.
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P163
INTER-RATER RELIABILITY OF FULL OUTLINE OF UNRESPONSIVENESS (FOUR) SCORE AND GLASGOW COMA SCALE (GCS), AMONG INTUBATED PATIENTS IN THE INTENSIVE CARE UNIT OF A TERTIARY CARE HOSPITAL IN SOUTH INDIA Alka Sara Saju¹, Ranjitha Chacko¹, Vishalakshi Jayaseelan2, Ilavarasi Jesudoss¹, Departments of Medical Nursing1 and Biostatistics2, Christian Medical College, Vellore, India BACKGROUND: The Glasgow coma scale (GCS) is widely used for assessing the sensorium of patients. However, verbal response, which is a part of the GCS scale, cannot be assessed in intubated and mechanically ventilated patients. Full Outline of Unresponsiveness (FOUR) is an alternative scoring system to GCS which does not include verbal response. The aim of this study was to compare the inter-rater reliability of the FOUR score compared to GCS score among intubated patients admitted in intensive care unit (ICU). METHOD: In this prospective observational study, scoring of FOUR and GCS scores were performed by two health care professionals (Nurse- Nurse/ Physician-Physician/ Physician-Nurse) who are randomly selected by lot method. Each individual in the selected pair, independently assessed both FOUR and GCS Scores for same patient within a time interval of 30 minutes. Scoring was done only once for each patient. Receiver operating characteristic (ROC) analysis was done to assess the predictive value of the scores for in-hospital mortality. RESULTS: The required sample size to show an inter-rater agreement of about 0.7 was calculated as 240 ratings, with 80% power and 5% level of significance. But within the study period only 142 pairwise scores were obtained. In the present study intra-class correlation for FOUR score was 0.926 with 95% confidence interval (CI) of 0.898-0.946 and for GCS it was 0.877 with 95%CI of 0.8330.910. The Cronbach’s α showed a high degree of internal consistency for both FOUR score (α = 0.961) and for GCS (α = 0.935). Both FOUR and GCS were good predictors for in-hospital mortality and no significant differences were observed in area under the ROC curve. CONCLUSION: Although the FOUR score appeared to have better intra-class correlation when compared with GCS, there was no statistically significant difference between the two. It is possible that a larger sample size is required to detect statistically significant difference between the scores. On current evidence, the small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in the ICU.
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P164
ADULT DIAPHRAGMATIC DISEASES: OUR EXPERIENCE Beulah Roopavathana. S, Abinaya R N, Tripti Jacob, Suchita Chase, SukriyaNayak AIM: To analyze our spectrum of cases with review of embryological basis and clinic anatomical insight into diaphragmatic pathology in adults. METHODOLOGY: Prospectively stored electronic database of patients with diaphragmatic pathology was collected from September 2011 to August 2016 RESULTS: 13 patients with diaphragmatic pathology, namely Traumatic rupture in 5, eventration in 4, Bochdalek hernia in 2 and Morgagni hernia in 2. There was definite male preponderance, with predominant left sided pathology and traumatic etiology being commoner. Laparoscopic access was used thrice, with 1 conversion. Prosthetic repair used in 6, which includes polypropylene mesh used in sandwich fashion in 3, dual mesh in 3. There was no recurrence in our series with follow-up details available in 11 patients. CONCLUSIONS: High index of suspicion is needed to diagnose delayed diaphragmatic injuries following trauma.Sandwich technique is a novel cost effective way of managing diaphragmatic eventration. Laparoscopic repair is a safe and feasible option in both elective and emergency setting.It pays a surgeon well to revisit phrenic nerve anatomy, to avoid its injury during diaphragmatic repair. P165
TO STUDY THE SAFETY AND EFFICACY OF MESENCHYMAL STROMAL CELLS (MSC) IN THE TREATMENT OF RECURRENT HIGH FISTULA-IN-ANO - A PILOT STUDY DEPARTMENT: Surgery unit IV OBJECTIVES: - To assess the feasibility and safety of Mesenchymal stromal cells (MSC) as a treatment option for recurrent high fistula-in-ano. - To study the efficacy of Mesenchymal Stromal Cells (MSC) in the treatment of recurrent high fistula-in-ano. -
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METHOD: Patients with recurrent high fistula-in-ano of crypto glandular origin (n = 7) underwent injection of heterologous Mesenchymal stromal cells (MSC), 40 million units into the fistula tract and were followed up for a total of 2 months. If healing was not detectedclinically at the end of 1 month, the patients underwent a repeat injection of Mesenchymal stromal cells (MSC) into the fistula tract. All patients were followed up at the end of 2 months clinically and MRI was done for patients who had clinical healing only. All patients were followed up for a duration of 4 months or till they were labeled as recurrence requiring another form of intervention. RESULTS: There were no adverse effects, reactions or worsening of primary disease in all 7 patients who underwent injections of Mesenchymal Stromal Cells (MSC) into the fistula tract. All patients were followed up for a period of 4 months and the procedure appeared to be safe, with no additional risk. At the end of 1 month fistula healing was observed in 4 out of 7 patients (57%) assessed clinically. Two patients had persistent fistula tracts and underwent a repeat sitting of MSC injection. At the end of 2 months 3 out of 7 (43%) patients had clinically healed fistula tracts and at the end of 4 months 1 out of 7 patients had clinically healed. Imaging done at 2 months following procedure revealed persistence of the fluid filled fistula tract in all the patients.
CONCLUSION: The injection of heterologous MesenchymalStromal Cells (MSC) in the treatment of chronic non-healing crypto glandular fistula-in-ano appeared to be safe. However it did not heal the fistula tracts in this pilot study. KEYWORD: Mesenchymal Stromal Cells (MSC), Recurrent high fistula-in-ano, Cryptoglandular. P166
APPLICATION OF SMARTPHONE PHOTOGRAPHY AND 3G WIRELESS INTERNET TECHNOLOGIES IN FREE FLAP MONITORING: A PROSPECTIVE STUDY Vasanth Mark Samuel, Pranay Gaikwad, ASridharamurthy, Rajinikanth J, A J Tirkey, C T Thomas , J C Muthusami BACKGROUND: Fate of the microvascular free flaps (MFF) is directly related to the surgeon’s skill and experience, diligent postoperative monitoring, and re-exploration at the earliest to salvage the
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failing flap. In keeping with the times, the smartphone photography and 3G wireless technologies may have a role to play alongside the other methods to monitor MFFs. MATERIALS AND METHODS: A prospective study was doneto assess the feasibility of utilizing the smartphone and 3G wireless internet technologies (S3GWIT) in the postoperative monitoring of MFFs (with a visible skin paddle) for the oral cancer post-extirpation defects.Photographs of each patient were sent postoperativelyto two surgeons using the S3GWITevery six hours for 120 hours. Clinical and photographic methods of monitoring were compared between the findings of three surgeons. The clinical monitoring findings were available to the operating surgeon (OPS) and the observing surgeon-2 (ObS-2) while the photographs were available to the OPS and the observing surgeon-1 (ObS-1).The indications to re-explore and salvage rates were calculated using standard statistical methods. RESULTS: Thirty free flaps were studied with 100% survival rate at 120 hours. Five patients were reexplored and salvaged completely. Re-exploration was indicated for the neck hematoma (4 patients) and post-anastomotic venous thrombosis (1 patient in whom the venous congestion was identified on a photograph). The accuracy rate with the use of photographs was 100%. CONCLUSION: The Smartphone photography with 3G internet technology has proven to be a useful adjunct in free flap monitoring with a success rate of 100% in identifying a venous thrombosis and salvage the flap. Incorporation this technique in the current protocols of free flap monitoring may help identify impending flap failures.
P167 EVALUATION OF EXTRACAPSULAR EXCISION IN THE MANAGEMENT OF BENIGN PAROTID TUMOURS ABSTRACT: Comparison Between Extracapsular Excision And Superficial Parotidectomy In The Management Of Benign Parotid Tumours INTRODUCTION: Benign parotid tumours require surgical management in the form of superficial parotidectomy which removed the entire superficial lobe of the parotid gland. We evaluated the feasibility of extracapsular excision to remove the tumour with a margin, to assess morbidity without compromising on oncosurgical principles.
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OBJECTIVES: The primary objective was to compare the incidence and severity of facial nerve palsy between the two groups of patients who underwent either extracapsular excision or superficial parotidectomy. The secondary objectives were to assess surgical margins and cosmesis following either operation. METHODS: This was a randomized control trial with 44 patients; 22 who underwent extracapsular excision and 22 who underwent superficial parotidectomy. Post operatively, the incidence of immediate facial nerve palsy in both the groups was documented on post operative days 2, 7 and 10. This was graded with the Modified House Brackmann Score. RESULTS : The incidence of facial nerve palsy was comparable between extracapsular excision and superficial parotidectomy. There was no statistically significant difference in the margin status of excised specimens between both the groups. Extracapsular excision provided superior cosmesis compared to extracapsular excision. CONCLUSION: Extracapsular excision is an acceptable alternative to superficial parotidectomy in the treatment of benign parotid tumours. It is superior cosmetically while not compromising on surgical clearance. Long term studies are needed to compare recurrence rates between the two operations.
P168
INDICATIONS FORSPLENECTOMY – DIAGNOSIS VS THERAPEUTIC? Department and College: Surgery Unit 4, Christian Medical College &Hospital, Vellore. Authors: Abinaya R N, Suchita Chase, SukriaNayak BACKGROUND: Splenectomy is performed as a diagnostic and therapeutic procedure for a wide spectrum of indications.This study was peformed to look for evolving indications and its outcome.
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METHODS: Patient undergoing elective and emergency splenectomy in our surgical unit from September 2011 to July 2016 were included. The indications for operation, its diagnostic significance and the outcomes were analysed. RESULTS: From September 2011 to July 2016, totally 68 patients underwent splenectomy. Out of 68 patients, 13 patients had emergency splenectomy. There were 49 open operations, 4 laparoscopic converted to open operations and 15 had laparoscopic splenectomy. The splenectomy was performed as a therapeutic intervention in 46 patients(68%) and as a diagnostic modality in 22 patients(32%). The indications for therapeutic intervention were splenic abscess(2), splenic cyst(4), trauma(8), ITP(20) and anemia(12). The indications for diagnostic splenectomy were pyrexia of unknown origin in 7 patients and splenomegaly with anemia or pancytopenia in 15 patients. The objective of the operation was achieved in 43 patients(63%). The success rate for each indication: diagnosis(12 of 22 patients,55%), thrombocytopenia(12 of 20 patients,60%), anemia(5 of 12 patients,42%) and as a primary treatment(12 of 14 patients,86%). Postoperative morbidity within 30 days of surgery was seen in 9 patients(13%) and 2 patients(0.03%) died within 30 days of surgery.
CONCLUSION: Splenectomy is an effective procedure in the diagnosis of some diseases and as therapeutic means in selected patients as mainline treatment. However, splenectomy should be performed only after careful evaluation for the risks and the potential benefits to the patient. P169
UMBILICAL PILONIDAL SINUS – AN UNCOMMON SITE FOR A COMMON DIAGNOSIS Authors: Dr. Shona Rachel Mathuram, Dr. Abinaya Nadarajan, Dr. Sukria Nayak, Department : Surgery IV BACKGROUND: Pilonidal sinus is a common condition encountered but the occurrence at the umbilicus is rare. Due to the various causes for discharge from the umbilicus and its atypical presentation, umbilical pilonidal sinus is not well recognized. AIM: To study the clinical profile of patients with umbilical pilonidal sinus and to outline an approach based on the severity of the condition.
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METHODOLOGY: Retrospectively all umbilical pilonidal sinus operated from September 2011 to September 2016 in Surgery unit 4 were included. RESULTS: Totally 7 patients with a diagnosis of umbilical pilonidal sinus was recruited from the hospitals electronic database. All 7 patients were males between the age groups of 18yrs to 23yrs. The most common clinical presentation was discharge from the umbilicus which was noted in all 7 patients. Umbilicectomy was performed for 6 patients and one patient was managed with sinus exploration and hair extraction. The diagnosis was made based on the intraoperative findings of a tuft of hair in the sinus tract and the post operative biopsy showing a foreign body giant cell reaction with chronic inflammation. There was no recurrence noted. CONCLUSION: The clinical and demographic profile of our patients were similar to that found in literature. The recent management of umbilical pilonidal sinus is more conservative by preserving the umbilicus and performing hair extraction. This has shown less recurrence in literature. If there is a high clinical suspicion of umbilical pilonidal sinus a conservative approach can be adapted.. P170
10MG VERSUS 5MG INITIATION DOSE OF WARFARIN TO ACHIEVE ADEQUATE ANTICOAGULATION IN THE TREATMENT OF ACUTE DEEP VEIN THROMBOSIS - A RANDOMIZED CONTROL TRIAL Authors: Srujan Sharma1, Indrani Sen2, L. Jeyaseelan3, Sukria Nayak1 and Sunil Agarwal2. Departments: 1. General Surgery 2. Vascular Surgery 3. Biostatistics. Institution: Christian Medical College, Vellore BACKGROUND: Current practices in the treatment of acute deep vein thrombosis involve oral anticoagulation to maintain an INR between 2 and 3, most commonly with Warfarin. Researchers have tried to establish how best to achieve this target quickly, safely and effectively but with varying results. AIM: To determine if the 10mg initiation dose achieves anticoagulation faster than the 5mg dose, / while maintaining safety and efficacy. METHODS: A randomized control trial was performed on inpatients diagnosed to have acute deep vein thrombosis and being started on Warfarin. Sample size calculated for a superiority trial, with alpha value 5%, power 95%, with 10mg reaching primary end point by 4.2 days and 5mg
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reaching same by 5.6 days and a standard deviation of 1.4 days, and no predicted cross-over is 26 in each arm. A target sample size of 60 was decided to account for attrition. Consenting participants who met selection criteria were randomly allocated to either a 10mg or a 5mg initiation group and received therapy accordingly. The patients were monitored until they reached the primary end point of two consecutive INR values between 2 and 3, or a secondary end point such as death, bleeding complication or withdrawal from the study. RESULTS AND CONCLUSION: The 10mg arm of the trial reached therapeutic INR value faster than the 5mg arm with a p-value of 0.02. There was no statistically significant increased risk of bleeding. Further studies are required before these results can be translated to changes in clinical guidelines. P171
FOLLICULAR VARIANT OF PAPILLARY THYROID CANCER DEVELOPING IN DYSHORMONOGENETIC GOITRE - A CASE REPORT Raj kumar J, Apourva G, Cherian AJ, Paul MJ, Abraham DT. Department of Endocrine surgery. INTRODUCTION: Dyshormonogenetic goitre is an autosomal recessive disease resulting in congenital hypothyroidism due to defective hormone synthesis or secretion. While only a minority of them present with goitre at birth others are usually asymptomatic. It can be associated with congenital renal or urologic abnormalities. Rarely, it can develop well differentiated thyroid carcinoma in a long standing goitre. CASE REPORT: We report a series of three cases among siblings with dyshormonogenetic goitre. All three of them were diagnosed with congenital hypothyroidism in the early infancy period. One of them had goitre at birth. All of them developed a multinodular goitre in the childhood. One of them had associated sensory neural hearing loss suggestive of Pendred’s syndrome. Per chlorate test was positive on all patients. All of them underwent total thyroidectomy. Histopathology was suggestive of dyshormonogentic goitre in all patients with foci of follicular variant of papillary cancer in two of them. One of them required radioactive iodine ablation in view of residual thyroid disease. CONCLUSION: Although dyshormonogentic goitre is a benign disease, evidence of papillary cancer development in a long standing goitre suggests need for a high index of suspicion among clinicians.
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P172
CLINICAL PREDICTORS FOR EARLY POST OPERATIVE URINARY RETENTION: A PROSPECTIVE COHORT STUDY DEPARTMENT: OBSTETRICS AND GYNAECOLOGY, CHRISTIAN MECICAL COLLEGE, VELLORE NAME OF THE CANDIDATE: Dr. V.ANNIE PRASANTHI DEGREE AND SUBJECT: M.S IN OBSTETRICS AND GYNAECOLOGY NAME OF THE GUIDE: Dr. ARUNA KEKRE OBJECTIVES: The aim and objectives of this study was to 1. Determine the prevalence of post-operative urinary retention in patients who had pelvic reconstructive surgery. 2. Study the clinical predictors for early post-operative urinary retention. METHODS: This study was an observational cohort study. This study was approved by institutional review board. Study was done among the patients who underwent pelvic reconstructive surgery in Christian Medical College, Vellore between August 2014 and July2015. Informed written consent was taken from all the patients. The following clinical predictors were studied: Age, body mass index, menopausal status, size of genital hiatus, degree of prolapse, tone of levator ani muscle, pre-operative post void residue, type of anaesthesia, type and technique of surgery, operation time and intra-operative blood loss. INCLUSION CRITERIA: Patients who are planned for pelvic reconstructive surgery which include pelvic floor repair with or without vaginal hysterectomy and vault prolapse repair. EXCLUSION CRITERIA: Patients with pelvic organ prolapse who are planned for hysterectomy with concomitant mid urethral sling surgeries and those who require long term catheterization due to intra operative complications. SUMMARY OF THE METHODOLOGY
PELVIC RECONSTRUCTIVE SURGERY PRE OP WORK UP
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Stage Of POP,POP Q, LAM Tone, Uroflowmetry and PVR PELVIC RECONSTRUCTIVE SURGERY 7th Annual Research Day Type of surgery, TBL, Type of anaesthesia, Duration of surgery
Catheterization max 72 hours
Encourage to void 6-8 hours
Difficulty in voiding PVR >300 ML but asymptomatic
PVR >/< 300 ML but with signs of distension
Encourage to void
Recatheterize for 72 hours
Voiding freely
Unable to void Recatheterize for 7 days or CIC for 7 days
Voiding freely
Unable to void
Urodynamic evaluation
STATISTICAL ANALYSIS: Prevalence of POUR was given as a percentage and 95% confidence interval for the prevalence was estimated. Descriptive of continuous covariates and categorical risk factors are presented with mean (SD) and frequencies (%) respectively. Chi-square test or Fisher’s exact test is used to assess the association between the clinical predictors and early post-operative urinary retention in univariate analysis. Clinical predictors which are significant at less than 0.10 level of significance in univariate analysis are taken into multiple logistic regressions to assess its independent association with early post-operative urinary retention. p-value of less than 0.05 was considered to be statistically significant in multiple logistic regression to indicate the corresponding risk factor as an independent predictor.Association of risk factors with postoperative urinary retention in multiple logistic regression were presented with odds ratio and its 95% confidence interval.
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RESULT AND CONCLUSION: The prevalence of early post-operative urinary retention after pelvic reconstructive surgery was 12.85 %.Covert retention was seen in 55.55% (n =5) of the patients while 44.44% (n=4) had overt retention. Stage of the prolapse III was an independent predictor for early post operative urinary retention (P value was 0.042) Other variables : age, BMI, menopause, size of genital hiatus, tone of LAM, pre-operative PVR, anaesthesia, type of surgery, operation time, and intra-operative blood loss were statistically insignificant as predictors for early post operative urinary retention. Patients who are overweight (OR: 2.29) have higher risk for POUR than patients with normal BMI (OR: 1). This is however not statistically significant. KEYWORDS: Post operative urinary retention, post void residue, pelvic organ prolapse and body mass index. P173
SIMILAR REGENERATION OF CARTILAGE WITH ALLOGENEIC CHONDROCYTETRANSPLANTATION CARTILAGE DEFECTS IN RABBIT KNEES
AUTOLOGOUS AND IN ARTICULAR
Authors P.R.J.V.C. Boopalan1, 5,Solomon Sathishkumar2, Viju Daniel Varghese1, Sabareeswaran Arumugam3, Vijayaraghavan Amarnath4, Elizabeth Vinod2. Departments and institution: 1. Department of Orthopaedics, Christian Medical College, Vellore, India 2. Department of Physiology, Christian Medical College, Vellore 3. Histopathology laboratory, Biomedical Technology Wing, Shree Chitra Tirunal Institute for Medical Sciences and Technology 4. Bone and Joint Hospital, Tiruchirappalli. 5. Center for Stem Cell Research, Christian Medical College, Vellore BACKGROUND: Articular cartilage defects in the knee have a very poor capacity for repair due to avascularity of the hyaline cartilage. There are several treatment options available for articular cartilage injuries, but none has been satisfactory, leading to formation of fibrocartilage which cannot function like the normal hyaline cartilage. Treatment by autologous chondrocyte transplantation has shown promising results. Allogeneic chondrocyte transplantation has also shown reasonable success in animals.
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AIM: The aim of this study was to compare allogeneic chondrocyte transplantation withautologous chondrocyte transplantation in the treatment of experimentally created articular cartilage defects in rabbit knee joints.
METHODS: Twelve adult New Zealand rabbits were used for this study. Cartilage was harvested from the left knee joints of six rabbits [R1-R6] and subjected to enzymatic digestion to obtain chondrocytes.The harvested chondrocyteswere cultured to confluence and cell sheets obtained. In the second surgery, a 3.5 mm chondral defect was created in the right knee of 12 rabbits. The chondrocyte cell sheets obtained were transplanted as autologous in 6 rabbits (R1–R6) and as allogenic in 6 other rabbits (R7-R12).At the end of 12 weeks the rabbits were euthanized and right knee joints were evaluated. Histopathological evaluation included Hematoxylin and Eosin, Safranin-O staining for assessment of tissue morphology and proteoglycan matrix. Quality of the repair tissue was assessed by the modified Wakitani histological grading scale. Mann-Whitney test was used for statistical comparison between the autologous and allogenic groups. RESULTS AND CONCLUSION: Both autologous and allogenic chondrocyte transplantation resulted in the regeneration of hyaline /mixed hyaline cartilage. The total histological scores between the two groups showed no significant difference (P=0.429).Allogenic chondrocyte transplantationseems to be as effective as autologous chondrocyte transplantation in cartilage regeneration, with the added advantages of increased cell availability and reduced morbidity of a single surgery. P174
VALIDATION OF A MODIFIED QUESTIONNAIRE TO ASSESS DROOLING IN CHILDREN WITH CEREBRAL PALSY Authors- Anjana Job, Naina Picardo, Syed KA, Varghese AM Presentor-Naina Picardo Department-Department of ENT 2,CMC ,Vellore BACKGROUND: Drooling of saliva is a common problem in children with cerebral palsy. In addition to causing impairment in articulation, drooling also affects socialization, interpersonal relationships and integration into society for these children. There are various methods to assess drooling which measure directly the amount of saliva drooled. However the most convenient and popular method is the use of questionnaires which are mostly western based and need slight modification for the Indian scenario
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AIM: Validation of a modified questionnaire for the assessment of drooling in children with cerebral palsy. METHOD: The modified questionnaire was administered to parents of children with cerebral palsy willing to participate in the study.The drooling score was compared with objective tests, namely cotton pad test and drooling quotient. Internal consistency was assessed using the Cronbach’s alpha, test retest reliability by Intraclass Correlation and sensitivity analysis by the Receiver operating characteristic curve. RESULTS: The modified questionnaire was found to be easy to administer.The Cronbach’s alpha coefficient was between 0.867 and 0.879 which implies a high degree on internal consistency. The intraclass correlation and the test retest reliability was found to be statistically significant with a p value < 0.001 which show that the questionnaire was highly reliable for repeat administration as well as administration by different investigators. The ROC Area was found to be 0.94 with a standard error of 0.02 with a 95% confidence interval of 0.88 to 0.99, which suggests that the score has great specificity, closer agreement between specificity and sensitivity and excellent precision. CONCLUSION: Our modified questionnaire was easy to administer, highly reliable and valid with high internal consistency.A score of 24 on the questionnaire was found to be the most sensitive and specific point to discriminate between the mild and severe droolers in children with cerebral palsy P175
PRENATAL PROGNOSTIC MARKERS OF SURVIVAL IN FETUSES DIAGNOSED WITH CONGENTIAL OBJECTIVES: To assess the prognostic markers for neonatal survival in fetuses diagnosed with Congential diaphragmatic hemia (CDH) in a tertiary care hospital from March 2015-June.2016 MATERIAL AND METHODS: Data collected from medical records of women with fetuses diagnosed with CDH and those of neonatepost delivery.
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RESULTS: Prenatal diagnosis of CDH was made in 12 fetuses. Seven fetuses (58.33%) were diagnosed at less than and five (41.66%) were after 24 weeks. Out of twelve, 11 fetuses had left sided CDH. Liver was found to be up in 16.66% (two fetuses). The lung head ration (LHR) was>1 in 92% fetuses (range 0.9-3.4). The observed / expected LHR was greater than 35%. in all fetuses 25% hadpolyhdramnios and 16% had other associated anomalies. Karyotype was carried out in 50% fetuses and all were normal. Seven women (58.33%) delivered with us. The rest delivered elsewhere, out of which two pregnancies were terminated and one ended inearly neonatal death and details of other two unknown. Among inborn, four (57.14%) had surgery with a survival rate of 50% . Three (42.85%) were discharged in clinically unstable condition. Out of the six babies that died in neonatal period 8.33% were diagnosed <24 weeks gestation. Only one had diagnosis made after 24 weeks. Overall mortality rate was 75% (assuming 3 patients discharged in unstable condition succumbed). CONCLUSION: Gestational age at time of prenatal diagnosis is a reliable prognostic marker for neonatal survival. Both LHR and O/E LHR showed poor correlation with neonatal survival.
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TREATMENT OF COMMON EAR PROBLEM RESPONSIBLE FOR HEARING LOSS – ROLE OF PAEDIATRIC TYMPANOPLASTY IN NATIONAL PROGRAMME FOR PREVENTION AND CONTROL OF DEAFNESS Alok Rathi *, NainaPicardo, Mary John AIM: To study the clinical profile and treatment outcomes of tympanoplasty in paediatric population MATERIALS AND METHODS: Three and half year retrospective study of children who underwent tympanoplasty for chronic otitis media (mucosal type) in a tertiary hospital from January 2012 to Aug 2015 was conducted. Age, gender, size and site of perforation, status of operated and contralateral ear, surgical technique, concomitant other surgical procedures, pre-operative and post-operative hearing levels were noted.
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RESULTS: Total of 100 patients were studied of which 68 came for three to six months follow up. Age group ranging from 6-16 years were included in the study. Average duration of ear symptoms was 7-11 years. Hearing loss was directly proportional to duration of ear discharge with more than eight years constituting to air-bone gap of 24 dB. Our success rate in graft uptake was 92.1% with hearing restoration rate of 99%. CONCLUSION: Chronic otitis media is one of the important cause of repairable hearing loss in children accounting for severe loss of physical and economic productivity. The degree of hearing loss is directly proportional to duration of ear discharge. Rate of success of tympanoplasty in children increases to more than 90% after the age of seven years with restoration of hearing. P177
A RARE RETROPERITONEAL TUMOUR – IVC LEIOMYOSARCOMA Authors: Dr.Coelho Victor , Dr. Beulah Roopavathana, Dr.Sukriya Nayak. Departments and institution: Department of General Surgery Unit IV Christian Medical College and Hospital, Vellore. 1)Post-graduate Department of General Surgery Unit IV. 2) Associate Professor Department of General Surgery Unit IV. 3) Professor and Head of Department of General Surgery Unit IV. SUMMARY: A 54 year old lady presented with complaints of intermittent right lower abdominal pain and fullness for the last two months. Examination of the abdomen revealed a 12*10cm ill defined retroperitoneal mass occupying the right hypochondrium and the iliac region. Preoperative imaging revealed increased vascularity from the right renal artery, and angio-embolisation of the same was performed. Laprotomy and excision of the IVC tumour was performed. Postoperatively there was a transient increase in the serum creatinine levels which normalized wuth adequate hydration. INTRODUCTION : Leiomyosarcomas are rare tumours that may arise from any smooth muscle source. They are reported to represent 10%-37% of all soft tissue sarcomas arising in the retroperitoneum. Retroperitoneal leiomyosarcomas occur most commonly in the fifth to seventh decade (1). Primary tumours of the inferior vena cava (IVC) are rare , with leiomyosarcoma (LMS) representing the vast majority (95%). Greater than 50% of all vascular LMSs occur in the IVC. Prognosis is often poor due to advanced stage at diagnosis. Surgical excision of the tumour and affected IVC with negative margins is the only treatment shown to improve survival. (2,3,4).
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CONCLUSION: An enhanced retroperitoneal heterogenous mass along the IVC should be a warning and consideration of diagnosis of IVC LMS and an aggressive resection of the lesion should be carried out. This is the only treatment that has been proven to have survival benefits. P178
DIAGNOSTIC YIELD OF LYMPH NODE BIOPSY REVISITED INTRODUCTION: This study determined the diagnostic yield of lymph node biopsy. The following were analysed: (1) overall diagnostic yield of lymph node biopsies at Christian Medical College and Hospital, Vellore (hereafter, CMC); (2) disease specific yield of lymph node biopsies with a primary focus on tuberculosis; (3) site specific yield and (4) referral pattern specific yield . METHODS: Data were retrieved from a registry by a qualified medical personnel. A surgical audit was conducted on the records of all 547 patients who underwent lymph node biopsies at CMC over a 7-month period. (‌) RESULTS: Overall diagnostic yield was obtained in 324 samples (59.2%).Disease specific yield in reference to tuberculosis was 29.8%.Site specific yield was found to be statistically significant for the cervical group 52.8%. Supraclavicular lymph nodal biopsies were found to have superior diagnostic yield. Referral pattern specific yield was found to be significantly better for Haematology. CONCLUSIONS: Higher proportion of negative yield of lymph node biopsy, supports the introduction of coordinated problem based referral , with regular audits of practice. Histopathology is an important diagnostic tool in extrapulmonary tuberculosis. Supraclavicular lymph nodes when present should be preferentially subjected to biopsy. Keywords: lymph node biopsy, haematological malignancy, audit
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outpatients,
lymphadenopathy,
infectious
disease,
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DESCRIPTIVE ANALYSIS OF VENTRAL HERNIA SURGICAL SITE INFECTION OVER 3 YEARS – SINGLE CENTRE EXPERIENCE Dany sunny, Titus D.K. INTRODUCTION: Ventral hernia surgeries are considered clean surgeries(without enterotomies). However their infection rates are higher than normal clean surgeries. The reported incidence of wound infection following ventral hernia repair was 6-24 % while clean surgeries were 1-4%. In this study we have analysed our unit experience on ventral hernia repair wound infection. METHODOLOGY: In our unit over 3 years we had a total of 138 ventral hernia repair cases, out of which 15 cases had wound infection/ mesh infection( infection rate 11%). These 15 cases were analysed for predisposing factors for wound infection, co morbid conditions, operation technique, pre and post operative antibiotic protocol, post operative complications and hospital stay. RESULTS: Out of 15 cases of wound infection 2 had mesh infection and 13 had surgical site infections. Four patients were above 60 years of age(ave:49.5) and 6 people having BMI more than 30 (ave:28.4). five patients had diabetes mellitus. Among fifteen cases 2 had intra operative enterotomies , 3 had prior infected mesh , 3 had other surgeries combined with hernia repair and one had obstructed hernia. 5 out of 15 wound infections were diagnosed in the same admission. Five patients had on lay, 3 had sub lay, 2 had primary repair and 5 had intra peritoneal dual/ biological mesh repair. All 15 received pre operative antibiotics and 6 received post operative antibiotics. Among 15 patients 13 had pus culture sensitivity done. Commonest organisms were E.coli, pseudomonas, enterococcus and staph aureus. . Most of them are sensitive to either amikacin or oxacillin. Four of fifteen patients had readmissions and 4 had reoperations. Their hospital stay varied from 5 days to 45 days with an average of 11 days. CONCLUSION: Ventral hernia surgeries wound infection rates are higher than regular clean surgeries. The incidence of wound infection is higher with associated procedures like cholecystectomy and panniculectomy. Patients with previous history of infected mesh and recurrent incisional hernias have higher chance of developing wound infection.
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P179
ROLE OF CA 19-9 IN COMPLEX OVARIAN TUMORS Thomas DS1, Sebastian A1, Thomas V1, Thomas A1, Chandy R1, Job V2,Peedicayil A1 1 Department of Gynaecologic Oncology,2Department of Clinical Biochemistry, CMC Hospital, Vellore BACKGROUND: Cancer antigen 19-9 (CA 19-9) is a tumor-associated mucin glycoprotein antigen that may be elevated in healthy individuals as well as in patients with benign and malignant tumors.It is useful in the management of pancreatic and other gastrointestinal tumors. CA 19-9 is also found to be elevated in various benign and malignant ovarian tumors. AIM: To study the pattern of serum CA19-9 in complex ovarian tumors. METHODS: The study design was cross sectional and was based on data collected from medical records. Patients with a complex ovarian mass, who were investigated with CA 19-9 and had undergone surgery, were included in the study. The study duration was 2 years from January 2014 to December 2015. A total of 268 patients (116- benign and 152 malignant) with complex ovarian mass and elevated CA 19-9 underwent surgery during the study period. RESULTS: CA 19-9 was elevated in 68 patients (25.4%). The median CA 19-9 values were similar in the benign and malignant groups. CA 19-9 was elevated in 30(26%) of the benign tumors and in 38 (25%) of the malignant tumors. Among patients with benign tumors , elevation of CA 19-9 was seen in 48% of dermoids, 29.6% of benign mucinous tumors, 14.3% of serous cystadenoma and in 16.3% of other benign tumors(7/43). There was significant increase in CA 19-9 values associated with bilaterality of benign tumors(Mann Whitney U statistic =160;Z score=-2.575, p= 0.010). Among patients with borderline and malignant tumors, the CA 19-9 was elevated in 32.3%(11/34) of the mucinous neoplasms, 21.6%(21/97) of non mucinous epithelial tumors and in 22.2% (4/18)of the non epithelial tumors. The sensitivity of CA 19-9 is 25 %, specificity is 74%, positive predictive value is 55.9%, negative predictive value is 43 %. The positive LR is 0.96 and the negative LR is 1.01. CONCLUSION: CA 19-9 is elevated in several conditions but most likely to be raised in dermoid cysts and mucinous tumours. CA 19-9 is not useful to rule in or rule out malignant ovarian tumors. CA199 levels need to be interpreted along with clinical and radiological findings.
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P180
RADIATION INDUCED SARCOMA – A RARE ENTITY Authors: Dr Abhijit Gundale, Dr A J Tirkey, Dr Rajinikanth J Departments and institution: Surgery Unit 1 ,CMC, Vellore BACKGROUND: Radiation induced sarcomas are rare entities. Their incidence has been reported to be 0.16% .They arise from the previously irradiated tissues with prolonged latency period. METHODS: We report rare case of radiation induced sarcoma in 38 year old male involving the floor of mouth following the treatment of squamous cell carcinoma of right lateral border of tongue. He underwent neoadjuvant chemotherapy followed by wide local excision , neck dissection,strap muscle flap reconstruction and post operative radiation. Diagnosis of radiation induced sarcoma was done by history ,latency period and biopsy. He underwent surgical management for the same RESULTS AND CONCLUSION: This case will review the literature pertinent to Radiation Induced Sarcoma and its management. P181
NEED TO LOOK BEYOND WHAT WE SEE: RETROPHARYNGEAL NODAL METASTASES IN ORAL MINOR SALIVARY GLAND MALIGNANCY Paudel D, Tirkey A, Janakiram R INTRODUCTION: Nodal metastasis is sign of poor prognosis in oral cancer and metastasis to retropharyngeal node is even so as it may lead to secondary invasion of the carotid artery rendering the disease inoperable. 1 Evaluation of the retropharyngeal node are not performed routinely as a part of head and neck examination and routinely retropharyngeal lymph nodes are not included in standard neck dissection so the understanding of retropharygeal neck nodes are solely based on imaging till date.2 The incidence of retropharyngeal nodal metastasis from oral cancer is very rare , reported incidence is of only 0.6% in our study confirms and there are no data regarding metastasis from minor salivary gland tumors.3 Case A young lady presented with a lesion in the oral cavity of one month duration. Examination revealed an ulcerative lesion involving the retro-molar trigone. A single IB lymph node was palpable Imaging showed a lesion involving the retro-molar trigone infiltrating adjacent soft tissues including masticatory muscles. CT also showed a large retropharyngeal node.PET CT
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was done to rule out synchronous primary, which showed uptake in the retropharyngeal node. She underwent surgery followed by IMRT. PRESENTING FEATURES: A young lady presented with a lesion in the oral cavity of one month duration. Examination revealed an ulcerative lesion involving the retro-molar trigone. A single IB lymph node was palpable. Computer tomography revealed an enhancing soft tissue density in the left retro-molar trigone, with loss of fat planes with the tongue, anterior pillar and medial pterygoid; with no evidence of mandibular or pterygoid erosion. Sub-centimetric but necrotic node was noted in left level IB and an 18mm necrotic left retropharyngeal node was noted. The PET CT revealed uptake in the retro-molar trigone, retropharyngeal node and IB node. She underwent wide excision, marginal mandibulectomy, comprehensive neck dissection, transcervical excision of left retropharyngeal lymph node, radial artery forearm free flap reconstruction and hatchet flap closure of forearm donor site.Immuno-histochemical examination confirmed epithelial myoepithelial carcinoma with multiple lymph nodal metastasis with extra-capsular extension (pT1N2b). Post operatively she recovered well and received adjuvant IMRT. She completed her first follow up 2 months back and doing well clinical examination was unremarkable. DISCUSSION: Retropharyngeal nodal metastasis in oral cancer is rare event and diagnosis is based on radiological evaluation mainly computed tomography. Anatomically retropharyngeal group of nodes are divided in to lateral and medial group .Any nodes in medial group are considered positive but lateral retropharyngeal space usually contains some lymph node. Any node bigger than 10 mm on computed tomography with central necrosis with rim enhancement anteriorly toward the atlas between the internal carotid artery and prevertebral musculatures are considered to be significant.4 The diagnosis of retropharyngeal node in our case was based on this CT scan criteria and uptake on PET CT. There are two purposed pathways of spread of metastasis to retropharyngeal nodes one is retrograde of spread of disease from enlarged upper cervical nodes and other is direct lymhatic drainage from oral cavity in case of posteriorly extending lesions.3 In our case lesion was in retromolartrigone and with Level Ib node any of the above pathways of spread is possible. The treatment for LRPLN depends on the treatment of the primary tumor. When surgery plus neck dissection is performed for the primary tumor and imaging examinations show distinct enlargement of LRPLN, the most effectiveapproach is trans-cervical removal of retropharyngeal nodes.1 Retropharyngeal nodal metastasis is bad prognostic factor McLaughlin et al noted a statistically significant difference between patients who showed radiographic evidence of RPLN metastasis and those who did not with respect to neck recurrence, distant metastasis, and disease-free and overall survival.5Neil DG et al found no statisticallysignificant difference between patients with
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andwithout pathologically proven RPLN metastasis in terms of local recurrence, regional recurrence distant metastasis, disease-free survival, and overall survival.6 Conclusion: Management of LRPLN metastasis in oral cancer patients remains a difficult challenge for oral surgeons, but early detection by CT or MRI and surgery combined with postoperative radiation therapy is likely to yield the best local Control.
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COMPONENT SEPARATION- AN ADJUNCT IN DIFFICULT ABDOMINAL WALL RECONSTRUCTION Authors: Dr.Pradeep Zechariah, Dr. Beulah Roopavanthana. S, Dr. Suchita Chase, Dr. Sukriya Nayak Department : Surgery Unit IV BACKGROUND: Ventral hernias complicate 2-20% of all laprotomies. Primary repair without mesh has shown high rate of recurrence. Bridging large defects with prostheic has shown high post-operative morbidity and recurrences. In 1990, Ramirez described the Component separation technique which has proven to be and effective approach in restoring abdominal contour in a tension free fashion. Ramirez’s technique has been used widely to repair large defects and has undergone many modifications over the years. One such variation, which uses an endoscpoic approach described in 2003(Lowe et al), has shown lower complication rates with similar recurrence rates. AIM: To determine the ideal surgical technique to restore dynamic abdominal contour in large ventral hernias METHODOLOGY: A review of prospectively stored surgical database of patients in whom component separation technique was used in abdominal wall reconstruction. Results – In our instituition, 19 component separation surgeries were performed(2014-2015). Midline closure was acheived in all 19 cases with an overall complication rate of 42%., seroma, being the most frequent morbidity. CONCLUSION: Open component separation, though, an effective technique to restore abdominal contour has shown high incidence of post-operative morbidity. This opens out new avenue for use of technology in improvising surgical technique thereby reducing our morbidity as demonstrated in a few international studies
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P183
A PROSPECTIVE OBSERVATIONAL STUDY OF THE FOLLOW UP OF MEDICAL MANAGEMENT OF EARLY PREGNANCY FAILURE Dr. Pushplata Kumari, Department of Obstetrics and Gyneacology, M.S. Branch II (Obstetrics and Gynaecology), Dr. Jiji E. Mathews, Professor and HOU 5 Department of Obstetrics and Gynaecology Christian Medical College and Hospital, Vellore, 632004, India OBJECTIVES: To study the need for further treatment following discharge after medical management for early pregnancy loss and find out the clinical predictors that can help in predicting complete expulsion after medical method of termination. METHODS: In this prospective observational study women, who were admitted for termination by medical method after diagnosis of early pregnancy failure in first trimester, were enrolled after informed consent.We followed the detail about the treatment given, dose regimen used for termination and further modality of treatment that was used if incomplete expulsion was suspected.Symptoms, sonologic and clinical findings prior to and after termination werenoted. After discharge women were followed by telephonic call at 1week,4 weeks and 6 weeks and were inquired about following symptoms: fever, persistent spotting, foul smelling vaginal discharge or pelvic pain. Need for hospital readmission or consultation to doctor were also followed.Categorical variables were summarised using counts and percentages. Quantitative variables were summarised using mean and standard deviation or median and range.Two sample t tests were used to compare means between the two groups and Chi square test was used to compare the proportions between the two study groups. For non-normal variables, Mannwhitney’s U test was carried out. For all the analysis, 5% level of significance was considered to be significant. RESULTS: Fifty-nine percentages of women had complete expulsion after medical method used for treatment of early pregnancy failure.The outcomes were not affected by the age, gestation age, body mass index or symptom before termination, previous history of medical termination of pregnancy, pelvic infectious disease or dysfunctional uterine bleeding. The outcomeswere not related to the Misoprostol dosage regimen used or the number of dosage used.The women who were presumed to have complete expulsion after medical method had persistent symptom for variable duration till 6 weeks, but none of the symptom were severe enough requiring readmission or physician consultation and subside itself without any intervention over a period of 1-2 week. After treatment with misoprostol presence of spotting per vagina (17.9% vs 1.72 % p value= 0.05) with or without abdominal pain, and presence of the echogenicity in ultrasound examination (93.2% vs 66.7% p value = 0.02) were the predictor of persistent of symptoms.The cut off measurement of endometrial thickness for diagnosis of persistence of symptom was 1213mm (sensitivity 76.19% and specificity 83.64%). Keywords: early pregnancy failure, medical methods of termination, surgical methods of termination, clinical predicators of complete expulsion.
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P184
EMERGENCY MICROVASCULAR FREE FLAPS FOR RECONSTRUCTION IN LIMB TRAUMA Authors: Dr Rahul Gorka, Dr ElvinoBarreto, Dr GeleyEte, Dr Gaurav Chaturvedi. Departments and institution:Department of Burns, Plastic and Reconstructive Surgery, CMC Vellore. BACKGROUND: Severe degrees of salvageable acute limb trauma with tissue loss, present to us at odd hours of the day or night. Some of these are not amenable to conventional local flaps and present coverage dilemmas to the average reconstructive surgeon. These morphological and functional reconstruction issues are easily sorted out if we resort to the available modality of free tissue transfer on an emergency basis. Good Plastic Surgery centres do employ these more aggressive techniques and methods supporting the ‘‘as-early-as possible’’ path, which has become the rule in dealing with emergency reconstructive interventions. Earlier methods of conventional reconstruction, based on a delay, for various periods of time, with loss of man-hours and excessive hospital stay, also caused an additional loss of soft tissue and bone. Primary reconstruction with excellent functional and aesthetic results is now possible in those cases where previously the wounds had to be managed by dressings followed by complex reconstructive methods or where the severity of the trauma and sometimes, inertia to operate at odd times for long durations led to amputation of the extremity. AIM: We present our experience of emergency free flaps being done by Department of Plastic, Reconstructive and Microvascular Surgery Department, to treat traumatic limb injuries. METHODS: We performed a retrospective observational study of 14 patients who underwent lower-extremity reconstruction at our institution during last 10-months period. In these patients, we evaluated causes,size and sites of defects, types of flaps, operative time, Hospital stay, Flap Survival rate, and complications. RESULTS AND CONCLUSION: The advantages of free flap are: Single stage operation; reducing the number of surgical procedures, anaesthetic risk and duration of hospitalization; Greater patient comfort with simple positioning; early mobilisation of injured part; Introduction of vascularized tissue with permanent blood supply resulting in faster wound healing.The use of top-quality tissue in covering soft-tissue loss, and precocity in reconstructing injuries and restoring function, are major prerequisites for obtaining a good surgical result. The latest research, availability of a great
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number of both simple and complex free flaps coupled with a positiveintent to salvage the injured limb despite all oddshas spurred the development of the concept of the ‘‘emergency free flap.’’ We concluded that majority of the 14 patients who underwent emergency free flap cover for limb reconstruction had better and early wound healing, lesser Complications. shorter hospital stay leading to lesser cost of treatment. P185
RANDOMIZED CONTROLLED TRIAL OF USE OF DRAIN VS. NO DRAIN IN OPEN INCISIONAL HERNIA MESH REPAIR Name of the candidate: Dr. Rahul Lakshminarayanan, Department: General Surgery, Unit IV, CMC Vellore, Degree and Subject: M.S. General Surgery Name of the guide: Dr.Sukria Nayak AIMS: The aim of the study is to assess the outcome of drain placement Vs no drain use, in patients undergoing open mesh repair of incisional hernias in the Department of General Surgery, Unit 4. OBJECTIVES: To assess and compare the occurrence of seroma, hematoma and wound infection in the two groups. 2. To assess and compare the duration of hospital stay in both the groups. 1.
BACKGROUND: Evidence in literature comparing the outcome following incisional hernia repair with or without drains is scarce. A meta-analysis comparing the same was unable to find suitable randomized controlled trials carried out in this regard. To this effect a randomized controlled trial is proposed to compare the outcome following incisional hernia repair with versus without the use of drains. METHODS: From April 2014 to August 2015, 62 patients pre-operatively planned for sublay or onlay mesh repair were randomised to drain or no drain allocation following informed consent. Their outcomes, specifically seroma/ hematoma, wound infection and duration of hospital stay, were analysed till 30 days post-operatively. RESULTS: There were a total of 17 seromas and 5 infections among all the patients. The incidence of seromas, hematomas and surgical site infections was 24.1%, 3.2% and 8.1% respectively. There was no significant difference in the outcome with regard to drain placement. There was a significant reduction in the duration of hospital stay among the patients in whom no drain was placed (p value <0.05). There was no positive correlation of outcomes to co-morbid illnesses (diabetes mellitus, systemic hypertension, ischemic heart disease, chronic kidney disease, COPD
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or hypothyroidism). There was no correlation type of repair, BMI, duration of incisional hernia or size of the defect. CONCLUSIONS: There was no significant reduction in the outcome of seromas, hematomas or surgical site infections with regard to drain placement. There was a significant reduction of duration of hospital stay in patients for whom drain is not placed. Keywords: incisional hernia, mesh repair, drain, seroma, hematoma, infection, hospital stay.
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A CASE OF POLY AMENORRHOEA
CYSTIC
OVARIAN
SYNDROMEWITH
PRIMARY
Dr. Nanthini Saravanan, Dr. Lilly Varghese,Dr. VaibhavLondhe, Dr. ArunaNitinKekre Dept. of Obstetrics and Gynaecology- Unit-II, CMC & H, Vellore -632 004. BACKGROUND: Polycystic ovarian syndrome affects 5-7% of women of childbearing age.Predominantly in the age group of 15 to 30 years in Indian population.Finding of polycystic ovarian morphology on ultrasound is not unique to the clinical disorder of PCOS. Polycystic ovarian syndrome may present with plethora of symptoms.Although, secondary amenorrhea is more common with PCOS, presenting with primary amenorrhea is unusual. CASE: We report a rare case of primary amenorrhea due to polycystic ovarian syndrome in 19 yrs old girl. Clinical examination revealed normal height with well developed breast and pubic hair growth with features of hyperandrogenism. Hormonal assay, karyotyping and radiological imaging with histopathology examination revealed the cause of primaryamenorrhea as PCOS. CONCLUSION: PCOS, an ill-defined symptom complex needs its due attention. Adolescent girls with primaryamenorrhoea due to PCOS exhibit increased features of the hyperandrogenism, this may represent a more severe spectrum of a common condition.
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P187
CHITOSAN GELATIN SCAFFOLD WITH ALIGNED FIBERS FOR MUSCLE TISSUE REGENERATION- AN IN VITRO STUDY Authors: Banteilang Nonglang1, Karthikeyan Rajagopal2, Dhirendra Katti3, Vrisha Madhuri1,2. Presenting author: Karthikeyan Rajagopal, Departments and Institution: 1. Paediatric Orthopaedics Unit, 2.Center for Stem Cell Research (a unit of inStem, Bengaluru), Christian Medical College, Vellore. 3. Department of Biological Sciences & Bioengineering (BSBE), Indian Institute of Technology, Kanpur. BACKGROUND: Skeletal muscles have an intrinsic ability to repair its damaged tissue owing to the presence of satellite stem cells. However,muscle damage (>20%)fails to repairleading to loss offunctional activity. Current treatmentsresultin significant donor site morbidity and hence tissue engineering provides an alternative for repairing severe muscle defects.The volumetric muscle loss when treated with cells/cell-seeded hydrogel fails to regenerate the fibers with native orientation resulting in poor muscle conductivity.We hypothesize that scaffolds with aligned fibers will provide cues for cells to orientthemselves similar to native tissue architecture. AIM: To study and compare the suitability of human satellite cells seeded on a chitosan aligned fibers and fibrin glue. METHODS: After informed consent, satellite cells from muscle tissue (n=5) were isolated, expanded and characterized. At second passage, cells were seeded on a. Fibrin glue (FG), b. Chitosan gelatin(CG)scaffolds and cultured for two weeks. Cytotoxicity and DNA proliferation assay were done to test the biocompatibility of these scaffolds. Cell distribution was assessed using SEMand histology. Immunohistochemistry and gene expression were performed to assess the myogenic potential of the cell-seeded scaffolds. RESULTS: Cells cultured on FG and CG showednegligible (<10%) cell death and distribution was found to be uniform. DNA proliferation assay shown that the FG scaffolds support better cells proliferation than the CG. Gene expression analysis shown Desmin and Myogenin were highly expressed in CG than FG which implies CG scaffold was more myoconductive in nature. CONCLUSION: Invitro testingshowed that CG scaffold with aligned fibers supported the growth of satellite cells and promotedmyogenesis. Further tweaking in terms of cell attachment may lead to a better scaffold for muscle tissue regeneration.
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P188
A STUDY OF CLINICAL PREDICTORS OF PATHOLOGICAL COMPLETE RESPONSE AND ASSESSMENT OF TUMOUR REGRESSION PATTERNS FOLLOWING NEOADJUVANT CHEMORADIATION IN SQUAMOUS CELL CARCINOMA OF THE OESOPHAGUS INTRODUCTION: Multimodality therapy is the accepted standard of care in locally advanced oesophageal cancer. With the optimization of treatment strategies, pathological complete response (PCR) to neoadjuvant chemoradiation has been on the rising trend. In the light of this, various trials have questioned the role of surgery in patients with a PCR. Prior to following a watch and wait approach, we need to identify the patients who can develop a complete response. In this study we looked at the various patient factors and assessed their association with PCR. We also evaluated the tumour regression patterns in the oesophagectomy specimen to see if we could identify a uniform regression pattern in all these patients. METHODS: Patients who satisfied the inclusion criteria were assessed both retrospectively (since 2005) and prospectively (till July 2016). Various patient factors were assessed by a univariate analysis followed by a multivariate analysis. In second part of the study 19 patients both squamous cell carcinoma and adenocarcinoma ,were prospectively recruited and layer wise TRG reporting was performed in the pathology specimen. Results: Of the 86 patients, 37 had PCR. On univariate analysis; lymph node status, length and stage of the tumour have shown significant association. On multivariate analysis; lymph node status and post therapy clinical staging have shown significant association with development of PCR. In the second aspect of the study, we found that there is no specific pattern of regression. CONCLUSION: Lymph node status and post therapy clinical stage had significant association with PCR. Our observation of tumour regression patterns suggests that there is no single follow up strategy to effectively detect recurrences if we adopt a watch and wait approach.
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P189
AN EPIPHANY IN THE PANDORA’S BOX INTRODUCTION: This report presents a case of recurrent primary mullerian adenocarcinoma of the abdominal wall otherwise known as an Extragenital malignant mixed mullerian tumour. There is only one such prior localization in literature. By this, we intend to contribute to the understanding of etiopathogenesis of this rare, nevertheless interesting clinical condition and point out the difficulties in efficacious management. CASE OUTLINE: A 39 year old lady presented with a rapidly growing painful anterior abdominal wall mass. There was history of excision, elsewhere, of a similar swelling four months ago. The surgical histopathology there was suggestive of a metastatic adenocarcinoma possibly of an ovarian primary. The slide review here was not conclusive, so she underwent an imaging guided biopsy of the tumour. It was suggestive of a low grade adenocarcinoma of the anterior abdominal wall. Efforts to look for a primary were in vain. On request, further immunoprofiling was done which delivered the histological surprise of Mullerian origin adenocarcinoma. In keeping with the recommendations in literature, patient was offered chemotherapy with carboplatin and paclitaxel. Reassessment showed disease progression. So, she underwent wide local excision of the tumour followed by abdominal wall reconstruction. She received 22 fractions of adjuvant radiotherapy to the abdominal wall and kept on follow up . Unpromisingly, she developed a recurrence within two months of completion of treatment. An interdisciplinary discussion came to the consensus of offering her further chemotherapy with cyclophosphamide and tamoxifen . CONCLUSIONS: Extragenital mullerian tumours have diverse origins. Their treatment protocols should be individualized. Benefit of chemotherapy should be offered to the patient in view of embryological correlation. Prognosis had been uniformly poor in prior reports. KEY WORDS: Extragenital malignant mullerian tumours, Surgical management, Chemotherapy in mullerian origin tumours, Anterior abdominal wall primary mullerian adenocarcinoma. P190 OBJECTIVE: The aim of this randomised controlled trial is to compare the safety and efficacy of oral misoprostol with intravenous oxytocin for induction in prelabour rupture of membranes at term (PROM).
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BACKGROUND: Different methods exists for active managementof PROM.Traditional method of induction with oxytocin needs continuous intravenous access and titration of dose which restricts patient mobility even in early labour. More recently induction with oral misoprostol, followed by infusion with oxytocin if required has been used. METHODS: This prospective randomized study included 134 women admitted to the department of Obstetrics and Gynaecology department at Christian Medical College Hospital, vellore with PROM at term. Women are randomly assigned to one of the two groups (groups A or B):Group A received 50μg of oral misoprostol every 4 hours for a maximum of three doses in nulliparous and maximum of two doses in multiparous. Group B received intravenous oxytocin starting with a dose of 2 mU/min with incremental increase of 2-4mU/min till adequate contractions occur. Primary outcome was induction to delivery interval, vaginal delivery within 24hours and caesarean section rate. Secondary outcomes were measures of effectiveness, maternal and neonatal complications, measures of satisfaction. RESULTS: This study showed clinically lesser incidence in caesarean section rate in oral misoprostol group compared to oxytocin group (9(13.43%) and 17(25.37%) respectively; p<0.081) with no significant difference in induction to delivery time interval( GoupA12.77±7.14h and Group B 11.73±5.52h; p value0.6774) .There was no difference in maternal and neonatal morbidity in both the groups. CONCLUSION: Oral misoprostol for induction of labour with women with PROM results in a significant decrease in caesarean section rate without any difference in induction to delivery interval.It is the preferred method to traditional intravenous oxytocin for induction of labour as it does not need IV access which restricts ambulationin early labour . P191
ANAPLASTIC THYROID CARCINOMA- OUR EXPERIENCE OF 12 YEARS INTRODUCTION: Anaplastic thyroid carcinoma constitutes less than 2 % of all cases of thyroid carcinoma worldwide. Median survival of these patients is about 5 months and 1 year survival rate is 20%. We present our data on the incidence of anaplastic thyroid carcinoma with its clinicopathological profile and patient outcome from 2004 to 2016 in Christian Medical College, Vellore.
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METHODS: We conducted a retrospective study of biopsy proven cases of anaplastic thyroid carcinoma seen in our institution from 2004 to 2016. The cases were analysed with regards to age at presentation, presenting complains, local signs which may predict the advanced nature of the disease and the pathological features of the tumour seen. RESULTS: We had a total of 61 cases of biopsy proven Anaplastic thyroid carcinoma. Mean age at presentation was 59.4 years with a higher incidence in women. Most of the these patients presented with long standing goiters with history of recent rapid increase in size or local pressure symptoms. Vocal cord palsy was seen in 15 of the 61 patients. 25 patients had distant metastasis at time of presentation with lung being the most common site. The mean survival was 5 months. CONCLUSION: Patients who present with rapidly progressive neck mass with signs of local infiltration, anaplastic thyroid carcinoma should be considered as a differential diagnosis and measures taken to expedite the diagnosis and to stage the disease. Anaplastic thyroid carcinoma is a rapidly progressive disease with a high mortality rate and limited treatment options, hence these should be discussed with the patient and care givers. P192
NUTRIENT INTAKE OF THE TRIBAL POPULATION OF JAWADHU HILLS Charles Ruban1, Mini Joseph2, Manjunath K1, Thomas N2 John J1 , Jasmine Prasad1, 1 Department of community health, 2Department of Endocrinology, Diabetes & metabolism, Christian medical college, Vellore BACKGROUND: a cross-sectional study was conducted among 138 residents (male (66) & female (72)) of jawadhu hills. this remote area is an extension of the eastern ghats and spreads across parts of vellore and tiruvannamalai districts in the northern part of the state of tamil nadu. the main objective of this study was to assess the adequacy of the food and nutrient intake of the residents living in the jawadhu hills. METHODS: fourteen villages were surveyed and the dietary data was obtained by 24 hour recall method and food frequency method (past one month) using standardised vessels.
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results: the mean age of the residents was 43.5 + 9.3 years. majority of them hailed from the poorer strata of the society according to modified kuppasamy scale and this is reflected in their food intake.the nutritional data indicates that this population consumed three major meals per day. the mean energy intake was 1684.6 + 180.8 and 1467.4 + 152.1 calories/day in the male and female population respectively. polished rice was the staple food and constituted the major calories in their diet. the intake of proteins was below the recommended allowances for indians (males: 40.6 + 4.5gm/day; females: 36.3 + 4.4 gm/day). cereals were the major source of proteins in their diet. horse gram was the popular pulse which was cooked into a thin gruel and consumed on a daily basis in 95% of the population. the more expensive proteins sources like poultry, flesh foods, fish, milk and milk products were consumed less frequently. more than three-fourth of the population consumed milk, beef, eggs and fish occasionally (less than twice a month) and chicken was consumed fortnightly.there was a gross deficit in the intake of minerals like calcium and iron in both the male and female population. vitamins like thiamine, riboflavin, niacin, folic acid, carotene and vitamin c did not meet the daily requirements in this population. this is because of inadequacy in the intake of fruits and vegetables which were consumed on a weekly basis, since it was not locally grown. the poor purchasing power of the families were the major impediment in including these micronutrients foods to the diet. conclusion: encouraging kitchen gardens with cultivation of geographically appropriate vegetables will ensure adequate supply of micronutrients in the family meal. subsi dised supply of nutrigrains like millets, pulses and vegetables through the public distribution system will ensure accessibility to this vulnerable hill population and improve the quality of their diet. P193
burden of non communicable diseases in tribal southern india-a community based cross sectional study charles ruban1, manjunath k1, jasmine prasad1, , thomas n2, mini joseph2, john j1 1department of community health, 2department of endocrinology, diabetes & metabolism, christian medical college, vellore background: this cross-sectional study was conducted among the residents of jawadhu hills which is situated in vellore and tiruvannamalai districts of tamil nadu. the main objective of this study was to estimate the prevalence of diabetes mellitus, hypertension, dyslipidaemia and metabolic syndrome and their risk factors among the residents of jawadhuhills aged between 30-60 years.
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METHODS: This study was conducted in 14 villages of jawadhu hills in tiruvannamalai district. Two stage cluster sampling method was used. Villages were selected by probability proportionate to size sampling. Consecutive households were selected from village starting point in clockwise direction as per the algorithm until the required sample size was obtained. Totally 480 people (males-225 & females-255) were surveyed from february 2016 to july 2016 using modified who-steps questionnaire. Socio demographic factors, behavioural and metabolic risk factors and anthrometric measures were collected. Fasting and post prandial (2 hour) blood glucose were collected for 480 people by using glucometer. Among the subset of 138 people (one participant from alternate household) fasting lipid samples were collected. Results: Of thesubjects (480) studied, 3.3%had diabetes mellitus,7.6% had prediabetes, 17.7% had hypertension. Among the sub group of 138 people, 51.5% had abnormalities in any one of the lipid parameters. 16.7% of the study population had hypercholestremia, 24.6% had hyper triglyceridemia,26.8% had low hdl,18.1% had high ldl,10.8% had high total cholesterol/hdl ratio(>4.5) and 12.3% had metabolic syndrome. Out of 480 people,11.7% had low physical activity(less than the who recommended). Using asian cutoff, prevalence of obesity, overweight and central obesity were 20%, 4.8% were obese, and 9.8% respectively. Most participants were from low socio economic status. Alcohol use and smoking is common among men (72.9%and 64% respectively). In the multivariate analysis, overweight was significantly associated with hypertension and dyslipidaemia. Low levels of physical activity and obesity were associated with and metabolic syndrome.
CONCLUSION: Prevalence of diabetes in this tribal population is low (3.3%). However, 51.5% had dyslipidaemia and 17.7% had hypertension. High prevalence of behavioural and metabolic risk factors calls for urgent intervention. P194
NUTRITIONAL STATUS AND INTELLECTUAL DEVELOPMENT IN CHILDREN: A COMMUNITY-BASED STUDY FROM RURAL SOUTHERN INDIA Jacob A, Thomas L, Stephen K, Marconi S, Noel J, Jacob KS, Prasad J BACKGROUND:
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There is a dearth of recent data on the relationship between nutritional status and intellectual development among children in India. To determine whether such a relationship exists, we studied children in a rural area of Tamil Nadu. METHODS: We stratified villages in Kaniyambadi block, Tamil Nadu, and recruited consecutive children who satisfied the study criteria. We assessed nutritional status by measuring height and weight and recording chronological age, and calculated indices weight-for-age, height-for-age, weightforheight and their Z scores. We assessed intellectual development using the Indian adaptation of the Vineland Social Maturity Scale. We used a case-control framework to determine the relationship and logistic regression to adjust for common confounders. RESULTS: We recruited 114 children between the ages of 12 and 72 months. Z score means (weight-for-age -1.36; height-for-age -1.42; weight-for-height -0.78) were much less than 0 and indicate undernutrition. Z score standard deviations (weight-for-age 1.04; height-for-age 1.18; weightforheight 1.06) were within the WHO recommended range for good quality of nutrition data suggesting reduced measurement errors and incorrect reporting of age. The frequency distributions of population Z scores suggest high undernutrition, wasting and medium stunting. A tenth of the population (9.6%) had values to suggest borderline/below average intelligence (social quotient <89). Lower height-forage, height-for-age Z score and weight-for-height Z score were significantly associated with a lower social quotient. These relationships remained statistically significant after adjusting for sex and socioeconomic status using logistic regression. CONCLUSION: Chronic undernutrition, wasting and stunting and their association with lower intellectual development demand an urgent re-assessment of national food policies and programmes. P195
ASSESSMENT OF THE HEALTH RELATED QUALITY OF LIFE AMONG ADULTS WITH EPILEPSY LIVING IN KANIYAMBADI BLOCK OF VELLORE DISTRICT AND FACTORS ASSOCIATED WITH POOR QUALITY OF LIFE AMONG THEM AIM: To assess the Health Related Quality Of Life (HRQOL) of persons living with epilepsy in Kaniyambadi block of Vellore district OBJECTIVE: To assess the Health Related Quality Of Life (HRQOL) of persons aged 18 years and above living with epilepsy residing in Kaniyambadi block, Vellore. and to identify the risk factors associated with poor HRQOL
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METHODOLOGY: This was a community based cross sectional study conducted in Kaniyanbadi block of Vellore district. The Individuals aged 18 years and above, identified as having seizure disorder or epilepsy from records maintained by Community Medicine department and living in Kaniyambadi Block for at least 6 months were included in the study and interviewed using QOLIE-31 questionnaire. The domains included seizure worry, emotional, cognitive, medication and social effects. RESULTS: In the study the overall mean score for quality of life was 65.2 out of 100 (standard deviation16.37). the respondents scored lowest on social participation with a mean score of 54.22, and, highest with absence of medication effects with a mean score of 91.96. The factors associated with low scores were anxiety (OR 3.83, P value 0.036).,depression (OR 3.8, P value 0.036).and unemployed status(OR 6.9, P value 0.009). CONCLUSIONS: Individuals with epilepsy should be routinely screened for depression and anxiety and offered treatment for the same. Social participation by people with epilepsy should be encouraged. P196
IMPACT OF HAZARDOUS DRINKING ON FAMILY FUNCTIONING IN RURAL SOUTH INDIA- A CROSS SECTIONAL STUDY Dr Martina Shalini 1, Dr Shantidani Minz 2, Dr Anuradha Rose3 , Dr. Jasmine Helan 4 3rd Year PG Registrar, MD Community Medicine, Department of Community Health, Professor, Department, Department of Community Health, CMC Vellore BACKGROUND: Alcohol use disorder is currently linked to over 200 diseases and injuries. In addition, it also affects the family through marital discord, financial problems. Understanding the effect of alcohol on the family as a whole will be useful in addressing family issues in programmes aimed at helping hazardous drinkers. AIM: To assess the impact of hazardous drinking on family functioning. The objectives of the study were to estimate the prevalence of hazardous drinking among married men in the 25-60 age group and to study the effect of hazardous alcohol consumption on family dysfunction. METHODS: A community based cross sectional study was conducted in rural southern India. The AUDIT (Alcohol Use Disorders Identification Test) questionnaire was administered to 750 married men
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in the 25-60 age group. In the second phase 150 wives selected by simple random sampling were interviewed to assess family functioning. We used perception of family functioning by wives, quality of life, presence of domestic violence and presence of any common mental health disorders to assess the effect of drinking pattern on the family. RESULTS: The prevalence of hazardous alcohol consumption among married men in the 25- 60 years’ age group was 31.5%. Women whose husbands were hazardous alcohol consumers were at 4.33 times higher risk of experiencing domestic violence. While a higher proportion of women with hazardous drinkers as husband’s (49%) vs 34% in the non-hazardous /abstainers group perceived their family as dysfunctional, the difference was not statistically significant. The risk of low perception of family functioning was 3.7 times higher in women experiencing domestic violence compared to women who did not experience domestic violence. CONCLUSIONS: Prevalence of domestic violence was significantly higher in families of hazardous drinkers. While other measures of family functioning like perception of family dysfunction and quality of life was associated with domestic violence, there was no direct association to pattern of drinking. P197
A CROSS SECTIONAL AUDIT OF THE FREQUENCY OF ERROR PRONE ABBREVIATIONS IN INPATIENT PRESCRIPTIONS IN A TERTIARY CARE CENTRE Jacob J1, Rabindranath 2, Mathew BS1 1 - Department of Pharmacology1, Christian Medical College Hospital, Vellore, T.Nadu 2- Quality Management Cell, Christian Medical College Hospital, Vellore, T Nadu BACKGROUND: The use of medical abbreviations is a common practice in many hospitals. They are believed to save time, space and are thought to be easily understood but on the contrary, the use of abbreviations, symbols and dose designations are frequently misinterpreted. In addition, clarity is compromised because of illegible handwriting and the words/numbers being in close proximity to each other. In an effort to promote safe practices, the Institute for safe medication practices (ISMP) and the U.S. Food and Drug Administration (FDA) recommend that ISMP’S list of error prone abbreviations, symbols, and dose designations be considered when writing a prescription. AIM :
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To determine the frequency and the type of error prone abbreviations in inpatient prescriptions in the wards in the Christian Medical College Hospital, Vellore. METHODOLOGY: All wards in CMC Hospital, were surveyed from 11.05.2015 to 16.05.2015, in which up to five patients were selected from each ward. This was based on the decision to include one tenth of the total number of patients admitted in the ward on that particular day. A cross sectional audit was done on every fourth/fifth patient starting from bed no. 1. The prescription written in the inpatient chart for that particular day was audited based on the ISMP’s list of error prone abbreviations and symbols. RESULTS: The error prone abbreviations were classified into Type A, B and C. Type A errors: Drug name abbreviations Type B errors: Dose designations and other information and Symbols like μ, ×, @ etc. Type C errors: Other general Abbreviations used in prescribing like improperly placed commas or doses and units written together. Medication charts of 225 inpatients were audited in 73 wards of CMCH, Vellore. In total of 225 patient prescriptions, it was observed that 1456 drugs were prescribed, which showed a total of 1294 errors. From the total of 225 prescriptions, 56, 71 and 98 patient prescriptions were surveyed from the Medical, Surgical and Higher Speciality Departments respectively. And there were 413, 397 and 646 drugs prescribed in total in the Medical, Surgical and Higher Speciality Departments respectively. Of the 225 patient prescriptions, three prescriptions showed all the three errors Type A, B and C. Amongst all the errors, type B error was noted to be the maximum, 703 out of 1294(54.3%) errors followed by Type C error which was 45.3% of total errors. The major type B errors included 542 OD for once daily, 50 U for units, 35 errors with use of SLASH as a symbol ;42 errors with “@” instead of “at” and 22 “μ” for “microgram” errors. Type A was noted in only four patient prescriptions. Amongst type C error, 154 patient prescriptions had the dose and unit written together, 9 prescriptions had large doses without properly placed commas and one prescription had a naked decimal point. Of the total errors in the respective speciality, the percentage of type B errors was 60.8%, 46.7% and 54.7% in Medical, Surgical and Higher Speciality respectively. CONCLUSION: We observed a total of 1294 error-prone abbreviations (from 1456 drugs prescribed in 225 patient prescriptions) in our inpatient hospital setting when a cross sectional audit was performed in every ward in the hospital. This could lead to serious errors in management in a clinical setting. This highlights the need to create awareness amongst clinicians in avoiding the use of such abbreviations whilst writing prescriptions.
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P198
BONE HEALTH AND IMPACT OF TENOFOVIR TREATMENT IN MEN WITH HEPATITIS B RELATED CHRONIC LIVER DISEASE Kattiparambil Gangadharan Sajith1, Nitin Kapoor2,Sahana Shetty2, Ashish Goel1, Uday Zachariah1, Chundamannil Eapen Eapen1, Thomas Vizhalil Paul2 1 Department of Hepatology, 2Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India OBJECTIVE: To study the impact of HBV related Chronic liver disease (CLD) and its treatment with Tenofovir on bone health in Indian subjects. MATERIAL AND METHODS: This cross sectional study included men between 18 and 60 years and comprised of three groups: Group 1 was treatment naïve HBV related chronic liver disease (n=79), Group 2 -those with HBV related chronic liver disease on Tenofovir for at least 1 year duration(n=136), Group 3normal age, sex and body mass index (BMI)matched healthy controls (n=58). Bone biochemistry and bone mineral density were studied. RESULTS: More subjects with hepatitis B related CLD (Group 1 and Group 2) were found to have vitaminD deficiency and a higher serum C-Terminal telopeptide when compared to age, sex and BMI matched controls (Group 3). A lower mean BMD and a higher prevalence of low bone mass at the spine and forearm was found in treatment naïve patients with hepatitis B related CLD(Group 1) whereas the femoral neck was most affected in Tenofovir treated patients(Group 2) (P <0.05). Age, BMI and a high viral load (>10,000) emerged as significant risk factors for low bone mass at femoral neck. CONCLUSION: The impact of hepatitis B related CLD and its treatment on bone health is significant. Bone health need to be periodically evaluated in these subjects especially in older men who are lean and have a higher viral load. However, long term follow-up studies are needed to look at the impact of treatment for adverse bone health in these subjects.
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IMPACT OF PRIMARY HYPERPARATHYROIDISM AND ITS TREATMENT ON BONE MINERAL DENSITY, BONE MINERAL PARAMETERS, INSULIN RESISTANCE, BODY COMPOSITION AND QUALITY OF LIFE- A PROSPECTIVE STUDY FROM INDIA
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Shrinath Shetty1, Sahana Shetty1, Nitin Kapoor1, M.J Paul2, Deepak Abraham2, Julie Hephzibah3, Nihal Thomas1, Thomas Paul1B 1 Departments of Endocrinology, Diabetes & Metabolism, 2Endocrine Surgery, 3Nuclear Medicine, Christian Medical College, Vellore. AIMS: To study changes in bone mineral density, bone mineral parameters, metabolic profile, body composition and quality of life at base line and 6 months following parathyroidectomy in subjects with primary hyperparathyroidism (PHPT). MATERIAL AND METHODS: This prospective study was conducted over 18 months with first 12 months of recruitment and next 6 months for follow up. Sixty eight patients with PHPT who underwent surgery were compared with 117 age, BMI and sex matched controls. Bone mineral density(BMD), total fat mass(FM) and visceral adipose tissue(VAT) by DXA scan , bone mineral parameters and bone turnover markers(BTMs) were assessed at baseline and after 6 months.Thirty patients completed 6 months follow up. RESULTS: Among the 68 patients (48 males,20 females) with PHPT,the most common presentation was renal calculi(61.7%) followed by bony involvement(29.4%).There was a significant improvement in QoL and BMD on follow up(at all sites) along with normalization of bone biochemistry and a decrease in BTMs(P<0.05).There was a significant increase in BMI, FM and VAT(P<0.05).There was a non-significant increase in HOMA–IR. CONCLUSION: There was a significant improvement in bone health and QoL following curative parathyroidectomy.A significant increase noted in BMI and VAT mass on follow up needs to be further studied with regards to definite clinical outcomes like diabetes mellitus. P199
LONGITUDINAL ASSESSMENT OF NUTRITIONAL STATUS OF CHILDREN DURING TREATMENT OF ACUTE LYMPHOBLASTIC LEUKAEMIA Authors: Magdalenal R1, Rikki R John1, Narendra K Chaudhary1,Deepti Boddu1, Sarah Mathai2,L. Jeyaseelan3, Leni G Mathew1 Departments: Pediatric Hematology/Oncology1, Pediatric Endocrinology2, Biostatistics3 Christian Medical College, Vellore BACKGROUND AND AIM: It is essential to know the nutritional status (NS) of children undergoing treatment of acute lymphoblastic leukemia (ALL) to implement appropriate intervention which in turn will
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influence the outcome. In this study, we assessed the NS of a group of children from diagnosis to completion of ALL treatment. METHODS: NS of 191 children(129 boys, 62 girls) aged 2-15 years diagnosed to have ALL between 20042012 , were assessed using data from their medical records at diagnosis, twice during treatment at the beginning of delayed intensification(DI) and maintenance phase(M) and at end of treatment(EoT). Using CDC BMI centile charts, theirNS was classified as:BMI <5th centileundernourished(UN), 5-85th centile - well-nourished(WN), >85th centile- overweight (OW) and≼ 95th centile –obese (O). Chi-square test and logistic regression analyses were done. RESULTS: At diagnosis 42% were UN, 50% WN and 8% OW/O.Of the 81 UN, 53% continued to be UN at DI, 28% at M and 25% remained UN at EoT. However, 60% in this group moved from UN toWN and 15% to OW/O by the end of treatment. The transition in NS of those who were WN at diagnosis showed that 13% became UN at DI and 3% remainedUN at EoT. However, the incidence of obesity increased from 10% at DI to 35% by EoT in this group. Those who were OW/O to startwith, largely remained in the same NS throughout treatment. There was no difference in the NS at diagnosis based on gender, age, type of leukemia and risk stratification for treatment. Girls were 1.5 times significantly more likely to remain undernourished during treatment as compared to boys (p=0.06) CONCLUSIONS: While the prevalence of UN reduced during the course of treatment from 42% at diagnosis to 12% at end of treatment, that of OW/O increased from 8% to 30%. The NS of children on treatment of ALL changes during treatment and therefore a close vigilance is required to implement appropriate intervention. P200
COMPARISON OF RESPONSE TO NEOADJUVANT THERAPY USING MRI TUMOR REGRESSION GRADING IN PATIENTS WITH LOCALLY ADVANCED RECTAL CANCER BELOW 25 YEARS OF AGE AND ABOVE 25 YEARS OF AGE
Authors: Dr. Shibi Paul, Dr. Anu Eapen AIMS AND OBJECTIVES: The aim of this study was to compare the MRI findings, and response to neoadjuvant therapy using MRI tumor regression grading in patients with rectal cancer below the age of 25 years with patients more than 25 years of age.
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MATERIALS AND METHODS: Partly retrospective and partly prospective study approved by the institutional review board. 27 patients below 25 years of age and 115 older patients above 25 years of age with locally advanced rectal cancer were included in the study. Both the subsets of patients had MRI for initial staging and for restaging following neoadjuvant therapy. The various MRI features of the tumor, TNM staging, MRI tumor regression grade and histological features of the tumor were assessed. RESULTS: On bivariate analysis, the incidence of tumors with MRI T2 high signal intensity in patients ≤ 25 years of age was higher, 48.1 % compared to 19.3% in patients >25 years of age. The incidence of poor response to neoadjuvant therapy (by MRI tumor regression grade) was significantly more common in younger patients (66.7%) compared to older patients (40.9%). Factors like age less than 25 years, T2 high signal intensity, presence of EMVI, mucinous tumors and poorly differentiated tumors were significantly associated with poor response to neoadjuvant therapy. T2 high signal in MRI and presence of EMVI were found to be two independent predictors for poor response.
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DIAGNOSTIC ACCURACY OF NON-CONTRAST MAGNETIC RESONANCE ANGIOGRAPHY IN PERIPHERAL ARTERIAL DISEASE AS COMPARED TO CONTRAST ENHANCED MAGNETIC RESONANCE ANGIOGRAPHY AND COMPUTED TOMOGRAPHY ANGIOGRAPHY Dr. Soumya Susan Regi, Assistant Professor- Grade II, Radiodiagnosis, CMC Vellore AIM: The aim of this study was to assess the diagnostic performance of ECG-gated non-contrastenhanced b-SSSP (balanced steady state free precision) Magnetic Resonance Angiography at a magnetic field strength of 1.5 Tesla in patients with peripheral arterial occlusive disease. OBJECTIVES: 4) To compare the diagnostic efficacy of non-contrast MR Angiography with contrast MR Angiography and Computed Tomography (CT) Angiography in patients with PAOD, in terms of the quantitative assessment of the degree of stenosis and the quality of the images obtained. 5) To assess the inter-observer variability in the evaluation of the degree of stenosis and the quality of the images obtained. 6) To compare with other non-invasive imaging modalities in cases of discrepancies.
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CONCLUSIONS: In this prospective study, non-contrast MR angiography was compared with contrast MR/ CT Angiography, in 170 arterial segments. vi) Overall the estimation of the degree of stenosis of the arteries in the non-contrast MRA was found to be similar to the gold standard (CE-MRA / CT angiography). The noncontrast MR Angiography was however found to overestimate the length of the stenosis, especially when the length of the stenosis was relatively shorter. vii) Overall quality of non-contrast MRA images was found to be nearly as good as the gold standard (CE-MRA / CT angiography). The quality was excellent for aorto-iliac segments, good for femoro-popliteal segments and poor in the infra-popliteal segments. In a few of the cases, the quality of the non-contrast MRA images was found to be better than the CE-MRA. viii) In the aorto-iliac region, the sensitivity of the non-contrast MRA for detecting a significant stenosis was found to be 75 % and the specificity 92.9%, with a positive predictive value of 66.7 % and a negative predictive value of 95.1%. Weighted Kappa was found to be 0.646, suggestive of good correlation. ix) In the femoro-popliteal region, the sensitivity of the non-contrast MRA was found to be 93.3 % and the specificity 97.8%, with a positive predictive value of 93.3 % and a negative predictive value of 97.8 %. Weighted Kappa was found to be 0.911, suggestive of excellent correlation. x) In the legs, the sensitivity of the non-contrast MRA was found to be 58.3 % and the specificity 47.2%, with a positive predictive value of 42.4 % and a negative predictive value of 63 %. Weighted Kappa was found to be 0.052, suggestive of poor correlation(63). In summary, non-contrast MR angiography was found to be comparable to the contrast MR / CT angiography in the evaluation of the arteries of the lower limbs, in peripheral arterial disease. Non-contrast MR angiography can hence be used as an alternative and safe imaging modality in the evaluation of PAOD, thus avoiding the risks associated with contrast MR/ CT angiography. In few instances, it proved to be even better than the contrast MRA. Non-contrast MRA is especially helpful in assessing the aorto-iliac vessels and femoro-popliteal vessels with slightly suboptimal imaging of infra-popliteal arterial segments. Further studies and more robust noncontrast MRA techniques need to be developed for better evaluation of the infra-popliteal arteries. P202
RADIOMIC SIGNATURES IN CARCINOMA CERVIX – NON INVASIVE IMAGING BIOMARKER TO PREDICT OUTCOME OF TREATMENT Jeba Karunya R1 Saikat Das1 Santanu Samanta1, Paul Gopu1,Devakumar D2, Subhashini John1 Department of Radiotherapy unit 21, Department of Nuclear Medicine2
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INTRODUCTION: “Radiomics”(1) refers to the extraction and analysis of large amounts of advanced quantitative imaging features with high throughput analysis of medical images like computed tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI). The process involves converting ultra-structural imaging features into minable data by image processing (2). Clinicopathological correlation of radiomic features is still translational. Association of tumour tissue parameters like stage, hypoxia, metabolism, angiogenesis and survival with radiomic parameters have been reported in lung and head and neck cancer(3). Several studies have uncovered the underlying correlation between gene expression profiles and radiographic imaging phenotype showing potential of such tools as imaging biomarker. Ganeshan et al showed that tumour heterogeneity in lung cancers on CT correlated with survival(4) and texture parameters correlated with histopathology(5). Coroller et al suggested that CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma. This present study was aimed to relate radiomic features derived from image processing of CT scan with treatment related volume change of the tumor and outcome in carcinoma cervix. METHODS AND MATERIALS: CT abdomen and pelvis and MRI pelvis images of 24 patients who had carcinoma cervix were retrieved. All these patients completed low dose RT with chemotherapy followed by EBRT with concurrent cisplatin and brachytherapy. Tumour volume was manually delineated on these pre and post treatment images. Forty two 3D-radiomic features, quantifying phenotypic differences based texture, were extracted from the computed tomography images of these patients using a 3D slicer software. Statistical analysis was done by SPSS software (version 15). RESULTS: The change of 42 machine derived radiomic image parameters after treatment were analysed by t- test and 8 parameters (Global Text GLV, Global Text Variance, GLRM Text RLV, Global Text RLN, NGTDM Text Busyness, NGTDM Text Coarseness, NGTDM Text Strength and GLSZM Text GLN) were selected based on significant change. On Multivariate anaylsis, taking change of volume as dependent variable and these 8 radiomic parameters as independent variable, the change in Global Text RLN, GLSZM Text GLN and NGTDM Text Busyness were found to be statistically significant predictors (P=0.009,P=0.058 and P=0.030 respectively) of volume change pre and post treatment. The volume change was correlated with Global Text RLN,GLSZM Text GLN and NGTDM Text busyness (R = 0.75,0.53 and 0.47). The functional MRI derived Apparent Diffusion Coefficient(ADC) was correlated with NGTDM Text Coarseness,(R = 0.62). CONCLUSION: CT based Radiomic signatures has the potential to predict treatment outcomes as indicated by the tumour volume shrinkage due to treatment in cervical cancer. Further investigations to use this translational tool as a non invasive imaging biomarker is needed. Abbreviations: GLSZM: Gray –Level Size Zone Matrix, NGTDM: Neighbourhood Gray – Tone Difference matrix
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GLV: Gray – Level Variance GLN: Gray – Level uniformity RLN: Run Length Non uniformity RLV: Run Length Variance
P203 DOES DAILY USE OF RESISTANT STARCH IN DIET REDUCE THE INCIDENCE AND SEVERITY OF ACUTE BOWEL SYMPTOMS IN PELVIC RADIOTHERAPY? A RANDOMIZED CONTROL TRIAL Balukrishna Sasidharan, Viswanathan P.N, Prasanna Samuel, Ramadass Balamurugan, Pugazhendhi Srinivasan, B.S. Ramakrishna. Christian Medical College, Vellore PURPOSE: The purpose of the study is to look at the benefit of administration of an oral prebiotic starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix. MATERIAL/METHODS : The study was conducted between 2011 and 2014 in 104 patients receiving radical chemoradiotherapy for carcinoma cervix. Patients were randomized to two arms receiving 30 gm of resistant starch or digestible starch on a daily basis through out the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. All of them underwent LDR brachytherapy of 30 Gy at completion of external beam radiotherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two randomized groups and analysed. Stool short chain fatty acid concentrations were measured at baseline at 2 nd and 4th week and after 6 weeks of completion of radiotherapy in both study arm and placebo arm and reported. 2 patients progressed during therapy and were not included in analyses and two patients discontinued the intervention. A per protocol analyses was done. RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the amylase resistant starch group. This difference was seen at 4th week and continued in the subsequent weeks till the end of radiation. Both groups had
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similar reported toxicity at 6 weeks post intervention. Both groups were also found to have similar incidence of grade 2 and above diarrhea. The non-digestible starch group was found to have 8% incidence as compared to 2% in the other group at the 5th and 6th week. The short chain fatty acid concentrations were found to be not significantly different in the groups at any point. CONCLUSION: The study failed to demonstrate a benefit in administration of resistant starch in excess of normal diet to patients receiving pelvic radiotherapy. This may be postulated to be due to concurrent use of chemotherapy and decrease in intestinal probiotics.
P204
THE INSULIN SENSTIVITY PATTERN IN MATURITY ONSET DIABETES OF YOUNG (MODY) PATIENTS K.Felix Jebasingh1, Aaron Chapla1, Padmanaban V2, Thomas V Paul1, Geethanjali Arulappan2, Jeyaseelan L3, Mercy, Nihal Thomas1 1 Department of Endocrinology, Diabetes & Metabolism, 2Biochemistry, 3Biostatistics, Christian Medical College, Tamil Nadu, Vellore. AIMS AND OBJECTIVES: To study the first and the second phases of insulin secretion and sensitivity patterns in patients with MODY compared with controls. MATERIALS AND METHODS: The study comprised of 14 patients with MODY and 7 Non diabetic controls (N=7).All patients with MODY and controls underwent a 180 minute Frequent Sampling Intravenous Glucose Tolerance Test (FSIVGTT). Indices of β-cell functions were estimated from plasma glucose and C-peptide concentrations using the minimal model technique. The First phase (Phi1), second phase (Phi-2) of insulin secretion was calculated from de-convolution of serum C-peptide concentrations, Insulin sensitivity(SI) and Glucose effectiveness(SG) were derived utilizing SAAM-II(Simulation, Analysis, and Modelling) software. Student’s T test was used for comparison between two groups, and ANOVA for multiple groups. Statistical significance was taken at P<0.01. RESULTS: The mean age of patients with MODY and controls were 36.00±9.51 and 39.00±4.24 years respectively. In comparison with controls, patients with MODY had a reduced first (Phi1- 42.61± 65.74 Vs 175.61±04.91, P= 0.01) as well as reduced second phase of insulin secretion(Phi212.48 ±9.53 Vs 24.26±5.72, P=0.01). Insulin sensitivity (SI- 0.01±0.008 Vs 0.015±0.004) and Glucose effectiveness (0.001 ± 0.001 Vs 0.0008 ± 0.001) were similar compared to controls. CONCLUSION:
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So, secretory beta cell dysfunction is the primary defect in patients with MODY predisposing them to developing diabetes and occurs without insulin resistance. P205
WHY IS IGA NEPHROPATHY AGGRESSIVE IN INDIANS? THE GRACE IGANI STUDY: EPIDEMIOLOGY AND LONGITUDINAL FOLLOW UP Authors: Suceena Alexander1, Rajan Babu1, Anila Korula1, Smitha M Mathai1, Visalakshi Jeyaseelan1, Vijayakumar Theophilus1, Gagandeep Kang1, Vinoi George David1, Anjali Mohapatra1, Anna T Valson1, Shibu Jacob1, Shailesh T Kakde1, Babu Ponnusamy2, Charles Pusey3, Terence Cook3, Mohamed R Daha4, Marc Seelen4, Jonathan Barratt5, John Feehally5, Santosh Varughese1, George T John6 Affiliations: 1. Christian Medical College, Vellore, India; 2. C-CAMP, Bangalore, India; 3. Imperial College London, UK; 4. University Medical Center Groningen, The Netherlands; 5. University of Leicester, UK; 6. Royal Women’s Hospital, Brisbane, Australia BACKGROUND: In India about 30-40% of IgA Nephropathy (IgAN) patients (pts) have nephrotic syndrome and renal dysfunction at presentation1. OBJECTIVES: To study the epidemiology and disease characteristics of IgA nephropathy in South Asia. To study the baseline and follow-up associations among low and high risk groups scored by ARR criteria2.
RESULTS: This is a single center prospective longitudinal cohort study in South India started from March 2015. 111 out of 154 adult (≥18 yrs) pts diagnosed to have IgAN among 1400 native kidney biopsies till March 2016, were included in the study. Out of the 43 excluded pts, 14 did not consent, 6 had eGFR<10ml/min/1.73m2, 10 were on HD, 5 had diabetes, 8 had prior immunosuppression and one had chronic pulmonary infection. 60 (54.1%) &51 (45.9%) were in the low risk (ARR score <22) high risk groups (ARR score ≥22) respectively. Table 1 shows the characteristics of the two groups at baseline and at follow-up. 40 (66.7%) of low risk and 37 (72.5%) of high risk pts have at least one follow up visit and the median (IQR) duration of follow-up was 5.5mo (3 to 7) and 3mo (3 to 6) respectively. Table 1 Characteristics
243
Low Risk Low Risk p (n=60) (n=40)
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High Risk High Risk p (n=51) (n=37)
Baseline
Follow-up
Baseline
Age yrs; mean±SD
35.8±10.3
36.7±9.4
Gender (M:F)
43:17
34:17
BMI mean±SD
HTN n(%)
kg/m2; 24.9±4.8
24.6±3.6
41(68.3)
49 (96.1)
Urine protein 7 (11.7) >3g/day, n(%)
34/50 (68)
Low serum 13/45 complement C3 n(%) (28.9)
11/39 (28.2)
S. Albumin mean±SD
3.7±0.44
g/dl; 4.2±0.42
24 hour urine protein 1808.5±13 g/day; mean±SD 11.8*
824.7±101 <0.001 4319.4±21 3.8* 61.8**
S. Creatinine (S.Cr) 1.5±0.68# mg/dl; mean±SD
1.4±0.69
S. Cystatin C 1.6±0.7$ (S.CysC) (normal range: 0.53 0.95mg/dl); mean±SD
MDRD eGFR 62.4±34# ml/min/1.73m2;
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Follow-up
2388.1±158 0.8**
0.016
<0.001 3.1±0.98##
4.0±3.43
0.002
1.7±1$
<0.001 2.6±0.81$$
3.2±1.3$$
0.005
67.4±32.8
<0.001 26.1±15##
24.8±14.6
<0.001
mean±SD
CKD EPI creatinine 61.6±33.3# eGFR ml/min/1.73m2; mean±SD
73.9±34
<0.001 26.2±16.5## 27±16.7
<0.001
CKD EPI cystatin C 59.3±30.3$ eGFR ml/min/1.73m2; mean±SD
62±34$
<0.001 27.5±12.1$$ 22.6±11.1$$
0.009
CKD EPI creatinine- 62.4±32.2$ cystatin C eGFR ml/min/1.73m2; mean±SD
67.4±35.2
<0.001 27.1±15.4$$ 23.1±12.5$$
0.001
S. hsCRP mean±SD
mg/dl; 17±23.8
$
8.2±12.8
MEST M1; n(%)
5/54 (9.3)
6/48 (12.5)
MEST E1; n(%)
18/53 (34)
27/47 (57.4)
MEST S1; n(%)
36/54 (66.7)
48/48 (100)
MEST T1 & T2; 42/54 n(%) (77.8)
49/49 (100)
ACEI/ARB use; n(%)
18 (35.3)
Oral
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52 (86.7)
prednisolone 42 (70) 7th Annual Research Day
42 (82.4)
use; n(%)
Mycophenolic acid 10 (16.7) (MPA) use; n(%)
14 (27.5)
Fish Oil use; n(%)
20 (39.2)
2 (3.3)
Rapid progressors (CKD EPI Cr GFR ≥5ml/min/1.73m2/yr or ≥0.42ml/min/1.73m2/ mo); n(%)
9(22.5)
12 (32.4)
CKD EPI Cr GFR ≤10 ml/min/1.73m2 on follow-up; n(%)
0@
7 (13.7) @@
RRT at n(%)
0@
4 (7.8) @@
0@
3 (5.9) @@
follow-up;
Death; n(%)
*
N=39 # N=22 $ N=40 @N=60 **N=32 ##N=37 $$N=17 @@N=51
Immunosuppression was given in pts with ≥1g/day of proteinuria and/or renal dysfunction. Non adherence to steroids and MPA was present in 3 pts each. There were 15 infective episodes mostly of skin and GI system with one death probably attributed to CNS infection. Steroid toxicity was present in 12 pts and 3 pts had intolerance to MPA. CONCLUSIONS: There was significant decrease in proteinuria and improvement in eGFR with treatment in low risk group but though proteinuria improved among high risk group, there was significant worsening of eGFR. Among those with follow up, 54.9% were rapid progressors, in spite of aggressive treatment. RRT was started in 7.8% and 3 died on follow up.
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P206
TRISOMY 8 IN ACUTE MYELOID LEUKEMIA Yuvarani S 1, Palle A 3 Abraham A2, Fouzia N.A2, Anup J Devasia2, Nisham P.N 2, Anu Korula 2, George B2, Mathews V2, Srivastava A2, Srivastava VM1. 1Cytogenetics Unit, 2Dept of Haematology, 3Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore. INTRODUCTION & BACKGROUND: Trisomy 8 is the most frequent cytogenetic aberration in acute myeloid leukemia (AML), occurring in 10% to 15% of all AML. When trisomy 8 occurs as the sole abnormality it is associated with an intermediate to poor prognosis. Trisomy 8 may also be associated with additional abnormalities. In the recurrent genetic abnormalities (RGA) associated with AML, trisomy 8 is a frequent secondary change. PATIENT/ MATERIAL AND METHODS: All patients with AML and trisomy 8 seen in the Department of Haematology, Christian Medical College, Vellore from January 2003 to December 2015 were included in the study. G-banded karyotypes were reported according to the International System for Human Cytogenetics Nomenclature (ISCN). Cytogenetic, blood and bone marrow findings were correlated. RESULTS: Trisomy 8 was seen in 235/2487 AML (9.4%). The majority (61%, 144/235) were males. There were 206 adults (88%) and 29 children (median age 39, range 1-76 years).The median haemoglobin was 8.1g/dl (range 2.3-15.1g/dl), median WBC 4 ×109/L (range 0.3-537 ×109/L), and median platelet count, 33×109/L (range 2-400 ×109/L). The morphological subtypes of AML with trisomy 8 were: AML M1-21; AML M2-41; AML M3-39; AML M4-13 ; AML M4E0-2; AML M5-15; AML M6-12; AML M7-3; MDS-AML-4; AML with myelodysplasia-related changes -22; AML not further classified-62. The trisomy 8 was solitary in 29% of patients (68/235). Trisomy 8 was seen in association with the RGA t(15;17), t(8;21) and inversion 16 in 39 (23%), 7(4%), and 9(5%) of patients respectively. The other RGA seen were the inversion 3, t(9;11) and t(6;11) in 0.6% - 3% of patients. Other commonly seen abnormalities were trisomies 21 (23%), 4, 19, and 22 (11-12%) and monosomies 5, 7 and 17 and the deletion 5q (5 -10%). Complex karyotypes with three or more abnormalities were seen in 31% of patients, most of whom had AML not further classified (42%), AML-M2 (16%) and AML with myelodysplasia-related changes (15%). CONCLUSIONS: The frequency (9.4%) of trisomy 8 in AML is similar to the literature. In the majority (71%) of our patients, trisomy 8 was seen in association with other abnormalities, notably the t(15;17) and
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trisomy 21(23% each). The median age of our patients is lower than what has been reported (39 vs. 47-64 years) reflecting the overall lower median age of AML in our country. P207
GARLIC OIL NANOEMULSION MITIGATES PODOCYTE INJURY IN HIGH FAT FED PREDIABETIC WISTAR RATS Yuvashree Muralidarana, Gokulakannan Ragavana, Ganesh Nachiappa Rajeshb, Pragasam Viswanathana*aRenal Research Lab, CBMR, SBST, VIT University, Vellore, TN, India b Department of Pathology, JIPMER, Dhanvantrinagar, Puducherry, India BACKGROUND: Free fatty acids in obese increase NF-κβ expression by downregulating PPAR-γ activity, which eventually leads to prediabetes mediated podocyte injury. Garlic oil with proven PPAR-γ agonist activity could ameliorate podocyte injury. The bioavailability of garlic oil is improved by nanoemulsification. AIM:
To investigate the effect of garlic oil nanoemulsion (GNE) on podocyte injury in high fat fed prediabetic rats ascertained with microalbuminuria (MA). METHODS: Male Wistar rats (n=60) were segregated into control group (Con), high fat diet (HFD) fed Prediabetic group (PDia), Telmisartan (10mg/Kg) treated prediabetic group (PDia + Tel), Garlic oil nanoemulsion (50mg/kg) treated prediabetic group (PDia + GNE), Garlic oil (50mg/kg) treated prediabetic group (PDia + GO). Before and after treatment, oral glucose tolerance test (OGTT), urinary albumin/creatinine ratio (UACR), protein/creatinine ratio (UPCR), lipid, serum albumin, protein and lipid profile were estimated in all groups. Haematoxylin & Eosin (H & E) staining, Periodic acid schiffs base (PAS) staining and Oil Red O staining were carried out. Relative mRNA expression of podocin and NF-κB in renal tissues was detected by RT-PCR. RESULTS:
GNE and GO administration showed a similar effect on lipid profile, ectopic fat deposition and OGTT. However, UACR (p<0.01) and UPCR (p<0.001) attenuated significantly on GNE treatment, which showed a marked amelioration in mesangial cellularity, mesangial expansion, tubular and glomerular basement membrane thickening. In addition, GNE significantly suppressed NF-κB expression (p<0.01) and promoted podocin gene expression (p<0.0001) in renal tissues. CONCLUSION:
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GNE is an effective therapeutic formulation to increase the bioavailability of GO that governs protection against glomerular dysfunctioning by inhibiting NF-κB expression within 4 weeks. P208
VITEXIN- A ILICIFOLIUS
PROMISING
ANTIDIABETIC
MOLECULE
FROM
ACANTHUS
G. A. Gayathri1 and Mahalingam Gayathri 1School of Biosciences & Technology, Department Biotechnology,VIT University, Vellore 632014, Tamil Nadu, India.
BACKGROUND Type 2 diabetes is a multifactorial disorder that accounts for about 85-90% of diabetes. Currently available drugs are focused for single target and fail to alleviate secondary complications and side effects. Medicinal plants and their chemical entities are recognized as complimentary medicine which exerts multiple targets. Recently, we reported on antidiabetic effect of methanolic leaf extract Acanthus ilicifolius in diabetic rats. AIM The main objective was to evaluate the in vitro antidiabetic activity and in silico validation of vitexin isolated from methanolic leaf extract of Acanthus ilicifolius. METHODS Inhibitory effects of vitexin on α amylase, α glucosidase and glucose diffusion were performed (2011, Sudha et al). Cytotoxicity by MTT assay and glucose uptake assay of vitexin were performed on L6 cell line from rodent skeletal muscle cells. The binding of vitexin with the targets GLUT-4 and PPAR-γ is also evaluated using in silico molecular docking approach. RESULTS Vitexin showed significant (p≤0.005) inhibition on α amylase, α glucosidase and glucose diffusion and also increases peripheral uptake of glucose in L6 skeletal muscle cell lines which does not produce any significant cytotoxicity. The binding energy pattern of vitexin with the targets GLUT4 and PPAR- γ crucial residues validates its functionality. CONCLUSION In vitro and in silico studies demonstrate that the vitexin exhibits excellent antidiabetic activity. In vivo experimental validation of the vitexin is in progress to develop as a new therapeutic agent. Key words: Type 2 diabetes, Acanthus ilicifolius, in vitro and in silico.
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P209
SCREENING OF OXALATE DEGRADING BACTERIA FROM THE GUT OF EXPERIMENTAL RATS FED WITH OXALATE RICH DIET Yogita Mehraa, Pragasam Viswanathana*aRenal Research Lab, SBST, CBMR,VIT University, Vellore, TN, India BACKGROUND Calcium oxalate stone formation is a multifactorial etiology with high morbidity and economic burden due to greater recurrence rate. Studies indicated that stone formers found to lack intestinal oxalate degrading bacteria’s in their gut, which eventually leads to hyperoxaluria. AIM Screening of oxalate degrading bacteria from the gut of experimental rats fed with oxalate rich diet METHODS Albino male Wistar rats (n=36) were divided into 3 groups with 6 animals each. Group 1: control (normal diet), Group2: 2% sodium oxalate supplemented with normal diet, Group 3: 4.5% sodium oxalate supplemented with normal diet. Urinary oxalate, calcium, magnesium and creatinine were estimated at the end of every week for a period of 2months. At every tenth day animals were sacrificed from each group for the isolation of oxalate degrading bacteria and the kidneys were excised and stored in 10% formalin for histopathology studies. RESULTS The levels of urinary oxalate and calcium were markedly elevated in rats fed with oxalate supplemented diet. However the increase in urinary oxalate and calcium (p<0.001) excretions over the course of the study were significant only in the 4.5% oxalate diet fed rats. In case of magnesium, the increase in urinary excretion was not marked. Von Kosa staining indicated the calcium oxalate crystal deposition in the renal tissues of the rats fed with 4.5% oxalate diet. In contrast, no deposition was observed in the tissues of 2% oxalate diet fed rats. A significantly more numbers of colonies were obtained in oxalate medium D from the gut of 4.5% oxalate diet fed rats compared to other groups. CONCLUSION Significant increases in the oxalate degrading bacteria were obtained from the gut of rats supplemented with higher concentration of oxalate. Further studies are underway to identify the bacteria and to prepare consortia for excess oxalate degradation in stone formers in the form of probiotic health drink.
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P210
ROLE OF NOTCH1 IN THE DERIVATION OF NEURAL STEM CELLS FROM HUMAN MESENCHYMAL STEM CELLS: EXPLORING THE UNDERLYING MECHANISM Authors: Katari Venkatesh, L. Vinod Kumar Reddy, Dwaipayan Sen* Departments and institution: Cellular and Molecular Therapeutics Laboratory, Centre for Biomaterials, Cellular and Molecular Theranostics, VIT University, Vellore-632014 *Corresponding Author BACKGROUND: Neural stem cell (NSC) transplantation is a promising strategy for restoring neuronal functional network in various neurodegenerative diseases and spinal cord injuries. However, the availability of NSCs for clinical use is limited because of serious ethical concerns. Therefore it is imperative to develop novel methods to get unlimited population of NSCs to clinical application. Aim: To derive human NSCs from MSCs and exploring the role of notch signaling pathway in the process. METHODS: The neurospheres were generated using human Wharton’s jelly MSCs (HWJ-MSCs) by inducing with epidermal growth factor (EGF) and fibroblast growth factor (FGF) and enzymatically dissociated using accutase into single-celled neural stem cells (NSCs). The clonal anlaysis of NSCs was examined through the soft-agar colony assay. The time-dependent expression of neural stem cell markers (Nestin, Sox2, Pax6) were analyzed through semi-quantitative polymerase chain reaction (RT-PCR). The expression of nestin in NSCs was immunophenotypically characterized using immunofluorescence. Role of the Notch signaling pathway was analyzed using a γ-secretase inhibitor-DAPT. The functionality of MSC-derived NSCs was analyzed through its tri-potential differentiation ability into astrocytes (GFAP, GLUL), oligodendrocytes (Olig2, MBP) and neurons (MAP2, NEFH). The markers for the respective cell types were determined through RT-PCR and immune-fluorescence. RESULTS: The characterized HWJ-MSCs were successfully derived into neurospheres and dissociated into NSCs. The expression of NSC marker (Nestin) in the culture further confirms the in vitro generation of NSCs (Figure 1). Notch inhibition by DAPT treatment downregulated the expression of the NSC marker Nestin, indicating that the process is dependent on Notch signaling (Figure 1) which was further verified by reduction in the numbers of neurosphere formation in presence of the Notch inhibitor. The expression of tri-lineage markers in the NSC differentiated culture clearly explains the tri-potential characteristic feature of NSCs. In addition, upon tri-potential differentiation of NSCs in the presence of Notch inhibitor, the neuronal
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(MAP2, NEFH) and glial markers (GFAP, GLUL and MBP) were significantly down-regulated indicating the role of Notch in efficient tri-potential differentiation of NSCs as well. CONCLUSION: These results suggest that the efficient derivation of NSCs (and their subsequent lineage commitment) from human MSCs requires Notch signaling pathway. Thus, large quantity of NSCs obtained through the use of human MSCs may have potential therapeutic interventions to treat various neurodegenerative diseases
FIGURE 1: Generation of neurospheres from human mesenchymal stem cells. a. Flow cytometric analysis of MSCs using positive and negative markers. b. Neurospheres c. Scanning electron micrograph of neurospheres at 10K magnification. d. Nestin positive neurospheres. e. Semi quantitative PCR to detect Nestin expression with our without Notch inhibition.
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P211
CYTOTOXICITY STUDIES OF ANTIDIABETIC POTENTIAL STRAIN ALTERNARIA LONGIPES VITN14G ISOLATED FROM MANGROVE PLANT AVICENNIA OFFICINALIS IN HEP 2 CELL LINES R.Nathiya1, Gayathri Mahalingam1* Department of Biotechnology, School of Biosciences & Technology, VIT University, Vellore 632014, Tamil Nadu, India BACKGROUND: A total of 19 different endophytic fungi were isolated from the mangrove plant Avicennia officinalis. The respective crude extract of isolated endophytic fungi was evaluated for its in vitro anti diabetic activity. The effective crude extract was further explored for its cytotoxic activity using Hep 2 cell lines. METHODS: Ethyl acetate (EtOAc) crude extract of Alternaria longipes VITN14G were isolated using standard protocols. The Hep 2 cell lines were grown in flask containing 10% minimum essential medium (MEM). Different concentration from 100 µg to 6.25 µg of crude extract was tested on Hep 2 cell lines using 96 wells micro titre plate. The plate was then incubated at 37®Cfor 12 hours under 5% CO2 atmosphere. The cytotoxic concentration 50 (CC50) of crude extract was observed by the changes present in the morphology of the cells for every 24 hrs. The results were recorded for 3 days. RESULTS: The ethyl acetate crude extract of Alternaria longipes VITN14G showed non-toxic with the concentration of 100 µg / ml on Hep 2 cell lines. The in vitro cytotoxic effect on Hep 2 cell lines was studies and there was no detectable changes in the morphology were observed like cell death, cell shrinkage etc. CONCLUSION: EtOAc extract of endophytic fungi Alternaria longipes VITN14G exhibited satisfactory antidiabetic activity against type 2 diabetes and showed non toxic against Hep 2 cell lines. Thus the ethyl acetate crude extract can be further subjected to compound isolation for the development of drug in the management of type 2 diabetes. KEYWORDS: Alternaria longipes VITN14G, Avicennia officinalis, cytotoxicity, di
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P212
STRUCTURAL STABILITY AMONG HYBRID ANTIMICROBIAL PEPTIDE CECROPIN A (1-8) - MAGAININ 2 (1-12) AND ITS ANALOGUES – A COMPUTATIONAL APPROACH B. Senthilkumar and R. Rajasekaran* Department of Biotechnology, School of Bio Science and Technology, VIT University, Vellore 632014, Tamil Nadu, India BACKGROUND: Cecropin A-Magainin 2 (CA-MA) hybrid antimicrobial peptide (AMP), a combination of two naturally occurring AMPs, cecropin A and magainin 2 is preferred widely in pharmaceutical applications as an antibacterial drug of choice. A stable CA-MA can exhibit a strong antibacterial activity with a reduced cytotoxicity in mammalian cells. AIM: In this study, three AMP structures native CA-MA hybrid and its tryptophan substitutes CA-MA L2 and CA-MA A2 was computationally studied to analyze their structural stability and functionality. METHODS: Three dimensional structural constraints of native CA-MA hybrid and its mutants were retrieved from Protein Data Bank. The energy minimized structures were subjected to conformational sampling using tCONCOORD program. The obtained trajectories were dynamically analyzed for determining its structural and functional territory and select the stable CA-MA as template for drug scaffold. RESULTS: Computational analysis like, intra-molecular interactions (25), relative stability (3.22) and instability index (-14.28) performed on static CA-MA structures, showed an increase in structural stability of native CA-MA hybrid. Additionally, static and dynamic analysis of the generated peptide ensembles also supports CA-MA with a RMSD (3.98Å), RMSF (0.202Å), Rg (11.98Å), ovality (3.33), hydrogen bond occupancy and hydrophobicity (69.7%) along with hydrogen bond composition, strength (-4.212 kcal/mol) and distribution comparatively. Hydrogen bond plays a vital role in secondary structure determination, the distribution of secondary structure throughout the generated ensemble of native CA-MA hybrid showed a concrete conservation of stable helical content with a high helical stability (52.25%) and computed free energy (-1.74 kcal/mol) in membrane mimicking environment than other mutants proving its functional activity comparatively.
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CONCLUSION: This study illustrates the parameters responsible for the stability of native CA-MA hybrid, which could be used for designing stable AMP biodrugs with low cytotoxicity in future. The result can be potentially extended to other AMPs to assist in their exploitation as peptide drugs. P213
ANTIMUTAGENIC PROPERTIES OF NARINGENIN AGAINST MITOXANTRONEAN IN VITRO AND IN VIVO STUDY K.Chandan1, K.Premkumar2 1 VIT University, School of Bio-Science & Technology, Vellore, TamilNadu, India 2 Bharathidasan University, Assistant professor, Cancer genetics & Nano-medicine laboratory, Department of Biomedical science, Bharathidasan University, Trichy, TamilNadu, India. BACKGROUND: Mitoxantrone, is an anti-cancer chemotherapy drug and topoisomerase inhibitor. It distrupts DNA synthesis in both healthy and cancer cells by intercalation between the DNA bases. Miroxantrone lacks the ability of selectively targeting the cancer cell. The normal cells most commonly affected by chemotherapy are the blood cells. Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables and it possess antimutagenic activity AIM: To investigates the effect of naringenin against the genotoxic doses of mitoxantrone by assessing chromosomal aberrations (CA), mitotic index (MI) in cultured human lymphocytes and bone marrow micronucleus test in mice. METHODS: MTT assay, Chromosomal aberration analysis, Mitotic index analysis, Bone marrow micro nucleus test RESULTS: For selecting the concentration of naringenin and mitoxantrone its cytotoxic effect on hepG2 cell line was carried out. 1µM, 2µM of mitoxantrone and 20µM of naringenin were used for further treatment in lymphocyte culture and bone marrow micro nuclei test. Mitotic index result shown 20µM of naringenin has its effect in increasing the mitotic index as single compound or in combination with 1µM mitoxantrone. Similarly, chromosomal aberration was reduced when 20µM naringenin. Bone marrow micro nuclei test result shows that the effect mitoxantrone on formation of MnPCE was increased in dose dependent manner.
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CONCLUSION: 1µM, 2µM of naringenin has the potential to reduce the genotoxicity induced by 1µM, 2µM of mitoxantrone, thereby reducing the chances of developing secondary tumours during the therapy. P214
ACUTE LYMPHOBLASTIC HYPERDIPLOIDY
LEUKEMIA
WITH
T(9;22)
AND
HIGH
Bexy B1,Palle A 3,Fouzia N.A1, Devasia A.J1, Nisham P.N1, Korula A1, Abraham A1,,George B1, 1 Mathews V1, Poonkuzhali B1,Srivastava A1 ,Srivastava VM2 Dept of Haematology, 2 3 Cytogenetics Unit, Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore INTRODUCTION: High hyperdiploidy (HHy) with a modal chromosome number of 51~65 is associated with a favourable prognosis in acute lymphoblastic leukemia (ALL) . The t(9;22) is another ALLassociated abnormality seen in ~3 of childhood ALL and up to 30% of adult ALL with a poor prognosis. This translocation results in the formation of the BCR–ABL1 fusion gene which encodes a constitutively activated tyrosine kinase. Several secondary changes may be seen in t(9;22) ALL, notably an additional Philadelphia (Ph) chromosome, trisomies 8, 19,and 21 and the isochromosome 17q. HHy with trisomy 2 is another secondary change associated with t(9;22) ALL .This is an important category of ALL and is associated with a poor prognosis unlike other high hyperdiploid-ALL . MATERIALS AND METHODS: The study group consisted of all patients with t(9;22) ALL and high hyperdiploidy seen in the Department of Haematology between January 2003 and December 2015. G-banded karyotypes were reported in accordance with the International system for Human Cytogenetics Nomenclature (ISCN) and correlated with blood and bone marrow findings. RESULTS: Among the 1199 ALL seen during the period of study, 11 patients (0.9%) had the t(9;22) and HHy. The patients ranged from 7-50 years of age (median age 39 years). Nine were adults (82%) and eight were males (73%). The median haemoglobin was 8g/dl (4-12 g/dl), the median WBC count, 17 × 109/L (range 2-328 × 109/L) and the median platelet count, 22×109/L (range 5-113 × 109/L). The percentage of blasts in the marrow varied from 49-99. The modal chromosome number was 51~65; one patient had a second clone with near-triploidy. The additional Ph chromosome was seen in 8/11 (72%). Other chromosomal gains associated with the t(9;22) such as trisomies 8,19 and 21, were seen in 5/11 (45%), 3/11 (27%) and 8/11 (72% ) respectively.
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Trisomy 2 was present in 6/11 (54%). Other secondary changes included an additional Ph chromosome (72%), trisomies 8, 19 and 21 in 45%, 27% and 72% respectively.
CONCLUSION: The frequency of ALL with the t(9;22) and high hyperdiploidy was 0.9%. Trisomy 2 was seen in 54% of t(9;22) ALL with HHy. The most common associated abnormalities were gain of the Ph chromosome and trisomy 21 (72% each). It is important to look for the t(9;22) in HHy-ALL because of its adverse prognosis. P215
CYTOGENETIC STUDY OF THE T(6;11)(Q27;Q23) IN AML Esther J 1, Palle A 3 Abraham A2, Fouzia N.A2, Anup J Devasia2, Nisham P.N 2, Anu Korula 2, George B2, Mathews V2, Srivastava A2, Srivastava VM1. 1 Cytogenetics Unit, 2Dept of Haematology, 3Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore. INTRODUCTION & BACKGROUND: The MLL (Mixed-Lineage Leukemia or Myeloid-Lymphoid Leukemia) or KMT2A (lysine (K)specific methyltransferase 2A) gene is involved in translocations with several partner chromosomes in acute myeloid leukemia (AML). The t(6;11)(q27;q23) is one such translocation that is typically associated with AML with monocytic differentiation. This translocation results in the formation of the KMT2A/MLL T4 (MLL/AF6) fusion gene and is associated with a poor prognosis. PATIENT/ MATERIAL AND METHODS: G-banded karyotypes of the patients with the t(6;11) seen in the Department of Haematology, CMC, Vellore, were reported according to the International System for Human Cytogenetics. The period of study was from January 2003 to December 2015. Cytogenetic findings were correlated with blood and bone marrow findings. RESULTS: The t(6;11) accounted for 11/2487 (0.4 %) patients with AML. There were 10 adults and 1 child ranging from 6-65 years of age (median age 32); six were males (55%). The median hemoglobin was 9.4g/dl (range 6.5-14.2 g/dl), median WBC count, 67.5 × 109/L (range 3.4-168 ×109/L) and median platelet count, 16×109/L (range 8-157× 109/L). All 11 patients had AML with monocytic differentiation (AML M4:4, AML M5:7). Four patients (36%) had a solitary t(6;11). The remaining seven had one or more additional abnormalities. These included gain of the derivative (abnormal) chromosome 6 (27%); trisomies 8 (36 %) and 19 (27 %) and tetrasomy 21 (18%) with a complex karyotype in 36 %.
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CONCLUSIONS: The frequency (0.4 %) of the t(6;11) in AML and the morphological findings are similar to the literature. The median age of our patients is slightly lower than what has been reported (32 years vs. 40 years). It is important to be aware of the morphological features associated with this translocation because it is a subtle abnormality which may be difficult to detect. P216
CLINICOPATHOLOGICAL CORRELATIONS OF THE DIC (9;12)(P11~12;P11~13) Manoj M1,Palle A 3,Fouzia N.A1, Devasia A.J1, Nisham P.N1, Korula A1, Abraham A1,,George B1, Mathews V1, Poonkuzhali B1,Srivastava A1 ,Srivastava VM2 1 Dept of Haematology, 2Cytogenetics Unit, 3Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore INTRODUCTION & BACKGROUND: The dicentric (9;12) is associated with acute lymphoblastic leukemia (ALL) and a favourable prognosis. This unbalanced rearrangement results in the formation of a chimeric fusion gene involving the PAX5 gene , a regulator of B cell development, on chromosome 9p13 and the ETV6 gene on 12p13; the resulting PAX5/ ETV6 fusion gene encodes a protein which is a repressor of transcription. The dic(9;12) is reported to be associated with ETV6–RUNX1 fusion which results from the cryptic t(12;21). PATIENT/ MATERIAL AND METHODS: G-banded karyotypes of ALL with the dic(9;12) seen in the Department of Haematology, CMC, Vellore from January 2003 - December 2015 were correlated with blood and bone marrow findings. RESULTS: There were 16 patients with the dic(9;12) who accounted for 1.3% of the 1199 ALL seen during the period of study. Twelve were children (up to 18 years), with a median age of 16.5 years (range: 2-49 years). Fourteen were males (88%). The median haemoglobin was 7g/dl (range 414.4 g/dl), median WBC count, 2.9 × 109/L (range 8-47 ×109/L) and median platelet count, 73 ×109/L (range 7-21 × 109/L). Bone marrow blast percentage varied from 69 -100 %; there was no morphological evidence of disease in one patient who had received treatment. Immunophenotype was available in 14 patients all of whom had pre B ALL. RT-PCR was negative for the ETV6 /RUNX1 fusion gene in all 10 patients studied. One or more additional abnormalities were seen in 11 patients (69%). These included trisomy 8 (25%) and abnormalities of chromosomes 7p and 17(three each). Of the eight with complex karyotypes, one was an adult with the t(9;22) and with gain of the derivative chromosome 22 (Ph chromosome) and trisomy 21. CONCLUSIONS:
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The frequency (1.3%) of the dic(9;12) in our ALL is similar to what has been reported in the literature. We did not find the associated ETV6/RUNX1 fusion. We had four adults with this abnormality. The association with the t(9;22) is also an unusual finding, with only one other patient being reported till date . P217
CLINICAL AND BIOCHEMICAL OUTCOME OF A COHORT OF CHILDREN DIAGNOSED WITH SUBCLINICAL HYPOTHYROIDISM IN A TERTIARY CARE CENTER IN SOUTH INDIA G Mathew & A Simon, Department of Pediatrics unit I, Christian Medical College, Vellore . INTRODUCTION: Subclinical hypothyroidism (SH)(also known as isolated thyrotropinemia) is a common biochemical diagnosis in children and its unclear natural history warrants good quality research. OBJECTIVES: Objectives were defined as (1)Description of biochemical outcome at the end of follow up period, (2)Identification of risk factors which may correlate with outcome and (3)Assessment of growth during the follow up period. DESIGN : Prospective-retrospective cohort study. MATERIALS AND METHODS: 166 children (aged 1-18 years) diagnosed to have SH of various etiologies were selected for the study after obtaining informed consent and assent. Medical records were retrospectively looked for 2 years and were followed up prospectively to a minimum period of 12 months. The biochemical and growth outcomes are analyzed with Chi square tests and described with p values (2-tailed, significance level ≤0.05). RESULTS: Total number
166(Females-54.82%)
Mean period of follow up ± SD
32.56±13.6 months
Outcomes
Hypothyroidism-10(6.02%) Physician 13(7.83%)
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decided
to
treat-
Normothyroidism-48(28.92%) Persistent subclinical hypothyroidism-95(57.23%)
P218
NOCARDIOSIS: 10-YEAR EXPERIENCE FROM A TERTIARY MEDICAL CENTER IN SOUTH INDIA Shalabh Arora, Ronald Albert Carey, O C Abraham BACKGROUND: Studies on Nocardiosis are limited and are largely confined to specific clinical settings with immunocompromised patients. Sparsity of data coupled with a low index of suspicion outside these settings often leads to delayed diagnosis, with increased morbidity and mortality. OBJECTIVES The aim of this study was to characterize the common risk factors, patient profile, clinical course, laboratory findings, treatment and outcome of Nocardia infection in general medicine patient population over a period of ten years. METHODS In this retrospective cohort study, we reviewed the medical records of all patients diagnosed with Nocardiosis in Department of Internal Medicine at Christian Medical College Vellore, from year 2005 through 2015. RESULTS A total of 33 patients with Nocardia infection were analyzed. The majority of our patients (94%) were immunocompromised, mostly due to immunosuppressive drug therapy, HIV/AIDS, connective tissue diseases and underlying lung diseases (Table 1). In HIV infection, nocardiosis occurs in advanced disease (Median CD4 count 23/cu mm; IQR = 4/cu mm). The typical clinical presentation was that of a chronic smoldering illness, with 80% patients having fever of more than 2 weeks’ duration. Most common clinical syndrome was pleuropulmonary (58%), followed by disseminated disease (33%), while neurological (6%) and skin/soft tissue infection (3%) were unusual. Chest X-ray infiltrates consistent with Nocardia infection were detected in 27 (82%) patients and brain abscess was seen in 6 (18%) patients. 75% of the examined isolates were susceptible to trimethoprim/sulfamethoxazole; amikacin and imipenem also had high susceptibility. Most patients were treated with combinations of trimethoprim/sulfamethoxazole with imipenem or amikacin (median treatment duration 180 days). High in-hospital mortality rate (33%) was noted in our study. CONCLUSION :
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Nocardiosis is unusual in immunocompetent individuals; a meticulous search for underlying conditions is warranted. As clinical and radiological findings are non-specific, high index of clinical suspicion has significant implications in early initiation of therapy and outcomes. Table 1 Underlying condition
N
%
Immunomodulation
15
45.4
HIV infection
7
21.2
Lung diseases
7
21.2
Bronchial asthma
2
Bronchiectasis
2
Interstitial Lung Disease
2
Hypersensitivity Pneumonitis
1
Connective tissue diseases
6
Systemic Lupus Erythematosus
3
Rheumatoid arthritis
1
Reactive arthritis
1
Systemic sclerosis
1
Diabetes Mellitus
6
18.2
Chronic Kidney Disease
3
9.1
Malignancy
2
6.1
Metastatic medullary thyroid cancer
1
Carcinoma cervix
1
Carcinoma cervix
1
3
None identified
2
6.1
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18.2
P219
ECTOPIC CUSHINGS’ SYNDROME: A TEN YEAR EXPERIENCE FROM A TERTIARY CARE CENTRE IN SOUTHERN INDIA Samantha.S, Nihal Thomas, Thomas V Paul, Simon Rajaratnam, HS Asha, Birla Roy Gnanamuthu, MJ Paul Christian medical college, Vellore OBJECTIVE: Ectopic ACTH secretion is a rare cause of Cushings syndrome, seen in 5 to 10% of cases with endogenous hypercortisolemia .We describe our experience of patients with ectopic Cushings syndrome, seen over the past 10 years at a tertiary care centre in Southern India. METHODS: Inpatient and outpatient records of patients from 2006 to 2015 were retrospectively reviewed. Clinical features, details of history, biochemical values, imaging features including radiology and PET scans, management, details of follow-up and outcomes were documented. We compared the biochemical findings in these patients with findings seen in 20 consecutive patients with Cushings disease. RESULTS: A total of 21 patients were studied.The median age at presentation was 34 years. 7 patients had thymic carcinoid, 7 had bronchial carcinoid, 3 had lung malignancies, 2 had medullary carcinoma thyroid, 1 patient had a pancreatic neuroendocrine tumor. 1 patient had an occult source of ACTH. The most common clinical features at presentation were muscle weakness (95.2%), hyperpigmentation (90%), facial puffiness (76.1%), easy bruising (61%), edema (57%), striae (52%). Extensive acne was seen in a large number of patients(42.8%). Central obesity was seen in just 3 patients(14%). Biochemical evaluation had shown a median 8 am cortisol of 55.46mcg/dl(13.8 – 131), median 8am ACTH of 207pg/ml (31.1 to 703) and a median 24 hour urinary free cortisol of 2484 mcg(248 – 25438). Basal cortisol and ACTH levels, as well as midnight cortisol and ACTH level were markedly higher in these patients as compared to patients with Cushings disease. Twelve of the twenty one patients had developed serious infections during follow up. 9 patients had undergone surgery to address the primary lesion. However only one patient had a sustained cure on followup. CONCLUSION: In our series EAS was most commonly seen in association intrathoracic tumors in the form of bronchial or thymic carcinoid. Hyperpigmentation and proximal myopathy were seen in a large proportion of patients, while central obesity was uncommon. Prognosis depended on tumor type. Early and rapid control of hypercortisolemia is important in order to prevent serious infectious and metabolic complications.
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P220
TUMORAL CALCINOSIS OUR EXPERIENCE FROM A TERTIARY CARE CENTER Geethu Antony , Nitin Kapoor, Riddhi Das Gupta, Sahana Shetty, Thomas V Paul, Nihal Thomas Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India. BACKGROUND: Tumoral Calcinosis is a rare genetic disorder of phosphate metabolism characterized by ectopic calcification around major joints which usually occurs in the setting of either normal or high phosphorus levels(along with a normal renal function).It has been attributed to reduced bioactive levels of fibroblast growth factor(FGF23). Current therapeutic option is limited to only reducing blood phosphate levels by using phosphate binders as surgical exicision usually leads to recurrence. AIMS &OBJECTIVE: To study the clinical and biochemical profile of the patients presented with tumoral calcinosis over last 5 years at a tertiary care centre. METHODS: Clinical, biochemical, radiological and treatment data of all the patients diagnosed to have tumoral calcinosis from April 2011 to June 2016 were analysed. A total of 6 patients had a diagnosis of tumoral calcinosis. RESULTS: The mean(SD) age at presentation was 28(Âą13) years. M: F ratio was 2:4.Median duration of follow up was 18 months. Of the 6 patients, 2 were siblings. Most common joint involved was hip followed by shoulder and elbow. One patient presented with distal interphalangeal joint involvement, while another had a scalp lesion which is also considered as a rare site for ectopic calcification in this setting. All except one had high phosphate levels and were treated with phosphate binders and bisphosphonates(alendronate or zoledronic acid). Two patients were also given acetazolamide. Only one patient had surgical removal of the lesions from elbow and shoulder. The treatment outcome was variable with mild regression in 4 subjects or progression of the disease in others. CONCLUSION: The diagnosis of tumoral calcinosis is usually made with the typical radiological featuresalong with either high or normal phosphate levels. Limited number of cases have been described in literature with few therapeutic options and conservative treatment along with phosphate binders remains the main stay and surgical excision is only considered when patients are presenting with disabling symptoms.
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P221 DETERMINANTS OF WALKING ABILITY IN PATIENTS WITH TRAUMATIC PARAPLEGIA AUTHORS: DR. SHERAJ FERNANDEZ, DR. GEORGE THARION, DEPT OF PMR, CMC VELLORE. WALKING IS ONE OF THE MOST SOUGHT AFTER GOALS AMONG INDIVIDUALS FOLLOWING A TRAUMATIC SPINAL CORD INJURY. HOWEVER, ONLY LESS THAN ONE THIRD OF PATIENTS WITH SPINAL CORD INJURY ARE ABLE TO WALK AGAIN AFTER THIS LIFE CHANGING EVENT. OBJECTIVES: To determine the role of modifiable factors including cardiovascular endurance, shoulder depressor forces and body balance on walking ability among motor complete T8-L2 paraplegics, who have completed a routine rehabilitation program. METHODS: Cardiovascular endurance was determined using the rate of change of heart rate to an incremental workload by a hand cycle ergometery test. Shoulder depressor force was measured using a standard walker mounted on an electronic weighing balance. Balance was determined by measurement of postural sway produced by the participant over a Good Balance triangular force platform. The data collected was analyzed to determine whether there was a significant difference in the above variables between patients who could ambulate at least 10mts, versus those who could not do so.
RESULTS: 45% of the patients were able to achieve functional ambulation. Walkers had better cardiovascular endurance than non-walkers as evidenced by higher 'mean work load' achieved at lower heart rates. Statistically significant differences in heart rate were noted at work loads of above 110 watts. The overall slope of change in heart rate with incremental work load was lower among walkers by 1.09 units (95% CI: 0.12, 2.07, p =0.028) indicating better exercise tolerance. There was no statistically significant difference in shoulder depressor forces and body balance between the two groups of walkers and non walkers. CONCLUSION: The findings suggest that better cardiovascular endurance can lead to improved walking ability among T8-L2 paraplegics post rehabilitation.
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P222
AUTONOMIC NEUROPATHY IN DIABETIC WITH AND WITHOUT NEUROPATHY AND CHRONIC CHARCOT FOOT BACK-GROUND AND OBJECTIVE: Autonomic Neuropathy is an important contributing factor for the development of foot ulcer. This study was designed to assess the prevalence and pattern of autonomic neuropathy in patients with diabetic with and without neuropathy and chronic Charcot foot. SUBJECTS, MATERIALS AND METHODS: This is a cross-sectional study designed to evaluate autonomic function in 74 patients with Type -2 diabetes mellitus which include 24 patients with Charcot foot (Group-A) , 22 patients with diabetic neuropathy (group –B )include and 28 patients without neuropathy (Group –C) include. Both sympathetic and parasympathetic autonomic function was assessed using a personal Computer based Cardiac autonomic neuropathy (CANS-504) analyzer. RESULTS: The mean age, duration of diabetes and HbA1c levels were comparable between the 3 groups. In patients with Charcot foot, 13 (54.16%) had combined autonomic neuropathy, 25% had isolated sympathetic autonomic neuropathy and single test parasympathetic abnormality - E: I ratio on breathing was detected in 4(16%) and 30:15 RR ratio on standing in 11 (45.8%) of patients. The prevalence of combined autonomic neuropathy in diabetic neuropathic group was found to be similar 12(54.56%) to that of Charcot foot group, however the prevalence was 10 (35.7%) in diabetic group. Among all study groups, the 30:15 RR ratio on standing and diastolic BP changes with sustained handgrip were found to be the most common parasympathetic and sympathetic tests abnormality respectively.
CONCLUSION: Autonomic neuropathy was found to be more common in patients with Charcot foot and in patients with diabetes neuropathy. This study highlights that patients with neuropathy without Charcot should be screen for autonomic neuropathy.
P223
COMPARISON OF BOTH LOBES OF THYROID FOLLOWING THYROIDECTOMY IN LOW RISK DIFFERENTIATED THYROID CANCER.
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Justin Benjamin, Julie Hephzibah, David Mathew, Nylla Shanthly, Regi Oommen Department Of Nuclear Medicine, Christian Medical College, Vellore. INTRODUCTION: In low risk differentiated thyroid carcinoma (DTC), the appropriate surgical procedure in terms of hemi/total thyroidectomy, has been an area of debate and controversial unsolved issue. In the background of this, several studies have stated that a hemi-thyroidectomy is sufficient in these patients. This finding has also been endorsed and recommended by the latest ATA 2015 guidelines that thyroid lobectomy alone may be sufficient in initial treatment for low-risk papillary and follicular carcinomas. In the background of this we felt the necessity to look at our own data and see the relevance of this finding. AIM: To assess the relevance of total thyroidectomy and compare histology of both the lobes and also profile of follow-up in low risk DTC patients. MATERIALS & METHODS: We retrospectively analyzed the histopathological reports of 400 patients with differentiated thyroid cancer who underwent radioactive iodine ablation following total/completion thyroidectomy in CMC from 2008 to 2014. Patients with low risk features (primary tumor <4 cm in diameter, no extrathyroidal extension and no nodal metastases) were 100 and these were analysed. RESULTS : Out of the 100 patients, 26 patients were detected to have tumour in both lobes. 18 patients were detected to have microcarcinomas in the other lobe. 56 patients were detected to be free of tumour in the other lobe. Therefore 44% of the patients were found to have tumour in the other lobe which implied that total thyroidectomy was beneficial as compared to hemithyroidectomy alone, in low risk patients. Of these 100 patients, only 3 patients were subjected to repeat ablation. In the follow up of these patients with a minimum of 1 year and maximum of 7 years, it was found that 13% had residual at 6 months of follow-up and 9% patients had persistent residual at one year follow-up and 4% continued to have residual uptake even after 3 years of follow-up. CONCLUSION: The role of total thyroidectomy in low risk DTC patients as first line of treatment cannot be underestimated, as a significant number of patients were found to have tumour in the contralateral lobe as well, which would have otherwise been overlooked if the guideline of just the lobectomy would have been strictly followed in these patients. As all these patients were subjected to radio-iodine therapy, only 13% of these patients were found to have residual in the 6 month follow-up. This also enabled us to have a hassle free follow-up.
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P224
COMPARISON OF PULSE OXIMETRIC SATURATION (Spo2) / FRACTION OF INSPIRED OXYGEN(Fio2) (SF) RATIO AND THE PARTIAL PRESSURE OF OXYGEN (Pao2) / Fio2 (PF) RATIO IN CRITICALLY ILL CHILDREN REQUIRING RESPIRATORY SUPPORT IN A TERTIARY CARE CENTRE IN SOUTH INDIA. Shajin T* , Pragatheesh , Jolly Chandran, Kala Ebenezer, Ebor Jacob James Paediatric Intensive Care Unit, Dept. of Paediatrics, CMC, Vellore INTRODUCTION: Acute Respiratory Distress syndrome is one among the important cause of respiratory morbidity and mortality in children. Early diagnosis and appropriate treatment of this condition is very important. PF ratio (PaO2/FiO2), obtained from arterial blood gas(ABG) is used to diagnose and monitor children with ARDS. ABG involves an invasive procedure to obtain arterial blood which is a difficult technique and also increases the risk of infection to the children. A simple , non invasive method to assess the respiratory staus of a critically ill child is necessary, hence the study was done. AIMS: 1. To correlate the relationship between PF ratio and SF ratio in critically ill children requiring respiratory support. 2. To determine cutoff value for SF ratio in relation to PF ratio to diagnose ARDS 3. To analyze the relationship between Oxygenation index(OI) and Oxygenation Saturation index(OSI). METHODOLOGY: Two arterial blood gases were done among the recruited children, from which PaO2 was measured and the corresponding Spo2 and FiO2 administered were noted to calculate the PF and SF ratio. ROC curve is plotted with SF ratio and PF ratio to obtain the cut off value. RESULTS:
SF ratio < 180 correlated with PF ratio < 300 with 70% sensitivity, 65% specificity and PPV of 80.9%, NPV of 57.3%. SF ratio < 180 correlates well with OI >4 with AUC of 0.7048, 95% CI (0.607 to 0.808) OI >4 relates with OSI >5 in discriminating children with ARDS, AUC 0.8 with 95% CI (0.8457 to 0.949)
CONCLUSION: Our study proved a good correlation between SF ratio and PF ratio. SF ratio <180 can be reliably used as a surrogate marker for PF ratio in assessing the severity of respiratory status and to categorize ARDS in children in the absence of arterial blood gas.
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P225
AN OPEN LABEL RANDOMIZED CONTROL TRIAL TO COMPARE WEIGHT GAIN OF VERY LOW BIRTH WEIGHT BABIES WITH OR WITHOUT ADDITION OF COCONUT OIL TO BREAST MILK. Authors: Sumitha Arun, Niranjan Thomas, Manish Kumar Department of Neonatology, Christian Medical College, Vellore. INTRODUCTION: Very low birth weight babies are prone to extrauterine growth retardation on breast milk alone. Though adding human milk fortifier is recommended, cost constraints and lack of availability is a limitation. So it’s a practice to add coconut oil to breast milk to establish adequate weight gain. Here we postulate that the supplementation of oral coconut oil will result in improved weight gain but will alter body composition in terms of total body fat percentage. OBJECTIVES: To compare weight gain of very low birth weight babies with and without coconut oil to breast milk.
supplemention of
STUDY DESIGN: Randomised control study
METHODS: Very low birth weight babies on 100ml/kg/day of breast milk was included in the study. Babies were stratified according to weight for gestational age into appropriate for gestational age (AGA) and small for gestational age (SGA) and randomized into 2 groups where intervention arm was given coconut oil added to breast milk and the control arm group was given breast milk alone. Coconut oil was given till 40 corrected weeks. The two groups were compared for weight gain, length and head circumference till 1.8kg or till discharge whichever was earlier. Fat mass expressed as percentage of total body mass of the two groups were compared by Dual Energy Xray Absorptiometry (DEXA) scans done at 40 weeks corrected gestational age. The two groups were also be compared for skin fold thickness, sepsis, feed intolerance and NEC. RESULTS: The two groups did not differ with respect to baseline characteristics. Weight gain was 22.34+/4.7 vs 22.54+-3.2 gram/day in the coconut oil group and control group respectively(p value=0.87). Total body fat percentage as measured by DEXA scan was increased in the coconut oil group(26.05+-4.4%) as compared to the breast milk alone group(24.4+-4.0%) but did not
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reach statistical significance. Subscapular skin fold thickness was significantly more in the coconut oil group as compared to control(p=0.02). CONCLUSION: The study did not show significant difference in weight gain after addition of coconut oil to breast milk in very low birth weight babies. There was a trend of increase in total body fat in the coconut oil group but it did not reach statistical significance. Subscapular skin fold thickness was significantly more in the coconut oil group. Further studies with larger sample size powered to detect the lack of weight difference after adding coconut oil is required. P226
THE (F)UTILITY OF TESTING FOR ANTI THROMBOPOEITIN RECEPTOR ANTIBODY PROFILING IN LUPUS RELATED THROMBOCYTOPENIA Arvind G1, ,Jayakanthan K1, Hindhumathi Mohan1 Mahasampath Gowri2, Arpana Palle 3, John Mathew1, Debashish Danda1 1 Department of Rheumatology, Christian Medical College, Vellore 2 Department of Biostatistics,Christian Medical College, Vellore 3Department of Immunohematology and Transfusion Medicine, Christian Medical College, Vellore
BACKGROUND: Thrombocytopenia occurs in 7-30 % SLE patients. Anti Thrombopoetin receptor antibody (Anti TPO-R Ab) has been reported to be present in 12% lupus related thrombocytopenia is associated with decreased platelet production, megakaryocyte hypoplasia and poorer treatment response. Objective- To study the relation of Anti TPO- R Ab in lupus related thrombocytopenia with respect to bone marrow megakaryocyte density and treatment response at 3 months (defined by manual platelet count >1,00,000/mm3) METHODS: 45 SLE patients satisfying the SLICC/ACR criteria with manual platelet count<1,00,000/mm3 not attributable to any other cause were enrolled in the study. Their demographics, clinical and laboratory parameters along with treatment details were noted. Sera from these SLE patients were tested for Anti TPO –R Ab (Qualitative ELISA ,CUSABIO China) RESULTS : Median manual platelet count was 30,000/mm3 (10,000-90,000 mm3) and Anti TPO- R Ab was positive in 8/45 (17.77%) patients. Bone Marrow Megakaryocyte density was normal/increased in 27/45 (53.33%)patients, decreased in 2/45 (4.44%) patients and not available in 16/45(35.56%) patients. Anti TPO- R Ab was seen in 1/29(3.45%) patients with bone marrow hypoplasia compared to 7/29(24.14%) patients with normal bone marrow (p-0.101). Anti TPO-R Ab was positive in 2/8 (25%) patients without treatment response compared to 6/35 (17.14%)
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patients with treatment response (p-0.606). Median manual platelet count was 56,250/mm3(30,000-75,000) vs 30,000/mm3 (10,000-90,000) in Anti TPO-R Ab positive and negative patients respectively (p-0.02). Anti TPO-R Ab positivity was not significantly associated with life threatening bleeding events or lupus related serological parameters. CONCLUSION: Our study, unlike previous studies, shows that Anti TPO-R Ab in Lupus related thrombocytopenia patients did not predict a lower platelet count, bone marrow megakaryocyte hypoplasia or poor treatment response P227
CLINICAL AND RENAL PROFILE OF VOLUNTARY KIDNEY DONORS – A COHORT STUDY FROM A TERTIARY CARE CENTER.IN INDIA Sumeet SD, Santosh V, Anna TV, Vinoi GD, Anjali M, Suceena A, Shibu J, Shailesh K, Tamilarasi V., Christian Medical College, Vellore, Tamilnadu, India. BACKGROUND: At present, renal transplant is the best modality of treatment for the end stage renal disease. Living donor transplantation is favoured over deceased donor transplant, in view of better outcomes and shorter waiting period. In a systematic review by AX Garg et al(2006), In 12% of donors GFR reduced to 30 and 59 ml/min (per 1.73 m2) and 12% developed proteinuria on follow up. AIM OF THE STUDY: To study the clinical and renal profile of the voluntary kidney donors who underwent donor nephrectomy from 2006 Jan to 2007 Dec at the baseline and on follow up. METHODS : We studied all the donors who underwent donor nephrectomy in our institute from Jan 2006 to Dec 2007. Their baseline clinical and renal profiles were analyzed. They were followed up to study the trend of renal functions, proteinuria, blood pressure, blood sugars and lipid profile. In total 167 live donor renal transplants were done during that period of 2 years. Baseline and follow up data for all the consecutive patients was collected and analysed. RESULTS : Total number of patients having living related transplant in the year Jan 2006 to Dec 2007 were 167. Mean period of follow up was 3 years and 1 month (+ 3.3, with range of 1 month to 10 years). Average age of donor at the time of donation is 40.9 yrs (+11.5). The mean serum creatinine of the donors pre-donation was 0.86 mg (+0.15) and post-donation was 1.16 (+0.45). The mean 24 hr urine protein pre-donation is 0.065 g/day (+0.035) and post donation is 0.189 g/ day (+0.502). Donors having proteinuria more than 150 mg/24hr were 16%. The incidence of
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diabetes in the donors was 4.1% on follow up and more so in older donors. Hypertension was seen in 13.6% of the donors on follow up. 1 patient had AKI requiring hemodialysis. 1 patient underwent renal biopsy for dysfunction which showed Foamy vacuolisation suggestive of Fabrys disease. CONCLUSIONS: Voluntary kidney donors form a healthy cohort due to their rigorous pre-selection. But there will be risk always for the renal dysfunction. But as adverse rate is less, we must continue to advocate living related kidney transplant whenever possible. P228
POST TRANSPLANT ERYTHROCYTOSIS- EXPERIENCE FROM A TERTIARY CARE CENTER IN SOUTH INDIA Sandip P, Santosh V, Suceena A, Anna T V, Shibu J, Harish R P, Sailesh K T, Sumeet S, V Tamilarasi , Department of Nephrology, CMC, Vellore, Tamil Nadu, India BACKGROUND: PTE is defined as persistently elevated hematocrit > 51% or Hb > 17g%. The prevalence is 1015% and usually it occurs 6 to 24 months after transplant. The defined predisposing factors are male gender, presence of native kidney, post-transplant RAS, extent of allograft function. Though the exact pathogenesis is not deciphered, the combined trophic effect of multiple interrelated erythropoietic factors which create a state ‘tertiary hypererythropoietinemia’ is the most probable explanation. Essentially the erythropoietin level remains within normal limit. The most dreaded complication is thromboembolic event which can be found in up to 10-30% of patients. The most effective and safe therapeutic modality is inactivation of renin-angiotensin system, though other options like theophylline can be tried. AIM: To evaluate the prevalence, contributing factors and response to therapy of post transplant erythrocytosis (PTE) in renal transplant patients in a tertiary care center in South India. MATERIALS & METHODS: This retrospective study was conducted in post renal transplant patients in CMC, Vellore. The transplant records of all post transplant patients from January 2012 to December 2013 with at least 12months of follow up were studied. Patients in whom Hb exceeds 17 g% or haematocrit exceeds 51% were classified as PTE. Those who lost follow up before 12months were excluded. RESULTS & CONCLUSION: Out of 147 renal allograft recipients 12.9% were found to have PTE after a mean interval of 9 to 11.5 months post transplant. Patients with PTE were mostly males (M:F=17:2) and had better graft function as judged by eGFR(71.5+1.2 ml/min in PTE vs 58+8.4 ml/min in non PTE
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group).Surprisingly acute rejection episodes were higher in PTE group than non PTE group(42% vs 32%), which is statistically significant. Most patients(90%) with PTE were treated with Losartan whereas 10% patients received theophyllin. Phlebotomy was offered to 42% patients. Transplant renal artery stenosis(TRAS) was found in 3 patients which were managed conservatively. During follow up 40% of the patients were recovered. None of the patients had major thrombotic complications
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