Vineet Kumar Kamal

Association of TNF-α-(308(GG)), IL-10(-819(TT)), IL-10(-1082(GG)) and IL-1R1(+1970(CC)) genotypes with the susceptibility and progression of leprosy in North Indian population.

Leprosy is an infectious disease caused by M. leprae. We analyzed 48 cytokine polymorphisms in 13 (pro as well as anti-inflammatory) cytokine genes using PCR-SSP assay in 102 leprosy patients and 120 healthy controls with intent to find out a link between cytokine polymorphisms and disease susceptibility. TNF-α (-308) GG, IL-10 (-819) TT, IL-10 (-1082) GG and IL1R (+1970) CC genotypes are found to be predominant (p=0.01, p=0.02, p=0.0001 and p=0.001, respectively) in both tuberculoid as well as lepromatous leprosy patients. This observation suggests these genotypes as play the central role(s) in the progression of disease. CBA assay demonstrates the varied serum concentration of these cytokines with respect to their genotypes. The above genotypes appeared as high producer genotypes in our study. Even in presence of high produce genotypes, TNF-α level are found to be affected/masked by the presence of IL-10 in leprosy patients. Expressional masking of TNF-α is associated with the expression of IL-10 in these patients. This is one the negative impact of SNP-SNP interaction in leprosy patients. Therefore, we can conclude that cytokine gene polymorphisms determine the predisposition to the leprosy progression.

Compliance to Therapy—Elderly Head and Neck Carcinoma Patients

Background Treatment compliance of elderly patients to intensive multi-modality cancer therapy can be challenging and has not been adequately addressed in developing countries. The present study evaluated compliance of elderly head and neck carcinomas patients to cancer-directed therapy. Methods Forty-seven elderly HNSCC patients were evaluated in the present study. Patients were assessed as per stage and site of disease, general condition, performance status, and any pre-existing co-morbidities. Compliance was defined as patients who were able to complete cancer therapy as intended at primary clinic. Non-compliance to therapy was stratified as early, mid- and late-course non-compliance. Statistical analysis was done using STATA 9.1 software, chi-square/Fischer’s exact test to see strength of association between two categorical variables that could possibly affect compliance in elderly patients. Results Sixty-eight per cent of elderly patients were subjected to radical treatment, majority (42/47) presented in loco-regionally advanced stage (III–IV), most common site of malignancy was oropharynx (21/47). Sixty-two per cent of elderly HNSCC patients were compliance to cancer therapy. Median overall treatment time for patients subjected to radical radiation therapy was 52 (range 47–99) days, and for radical surgery and adjuvant radiotherapy was 109 (95–190) days. Compliance to therapy for elderly HNSCC patients was not significantly associated with advanced stage, poor general condition, intent of treatment or presence of co-morbidity. As regards to non-compliance, majority (14/18) of elderly patients showed mid-course treatment non-compliance. Conclusions Nearly two-thirds of elderly head and neck carcinoma patients were compliant to cancer-directed therapy.

Gene copy number alteration profile and its clinical correlation in B-cell acute lymphoblastic leukemia.

Abstract The genes related to B-cell development are frequently altered in B-cell acute lymphoblastic leukemia (B-ALL). One hundred sixty-two newly diagnosed B-ALL cases, median age 8.5 years (2 months–67 years), were prospectively analyzed for copy number alterations (CNAs) in CDKN2A/B, IKZF1, PAX5, RB1, ETV6, BTG1, EBF1, and pseudoautosomal region genes (CRLF2, CSF2RA, IL3RA) using multiplex ligation-dependent probe amplification. The CNAs were detected in 114 (70.4%) cases; most commonly affected genes being CDKN2A/B-55 (34%), PAX5-51 (31.5%), and IKZF1-43 (26.5%). IKZF1 and RB1 deletions correlated with higher induction failure. Patients classified as good-risk, according to the integrated CNA profile and cytogenetic criteria, had lower induction failure [5 (8.6%) vs. 20 (25.3%); p = 0.012]. Those classified as good-risk, based on CNA profile irrespective of cytogenetics, also showed lower induction failure [6 (9.4%) vs. 19 (26%); p = 0.012]. The CNA profile identified patients with better induction outcome and has a potential role in better risk stratification of B-ALL.

Nutritional risk factors and status of serum 25(OH)D levels in patients with breast cancer: A case control study in India.

To study the nutritional risk factors and status of serum 25(OH)D levels in patients with breast cancer. A total of 100 women (cases) with confirmed breast cancer (BC) matched with equal number of healthy females (controls) of similar age and socioeconomic status (SES) were included in study. Controls included were nonbreast cancer patients who accompanied the patients to a tertiary care hospital. All the subjects (cases and controls) were administered a questionnaires to collect data on socioeconomic status, dietary pattern and the frequency of food consumption using a validated food frequency questionnaire. Anthropometric assessment was done for waist and hip circumference to calculate waist to hip ratio (WHR). Non fasting blood samples were collected for serum 25-hydroxyvitamin D [25(OH)D] levels estimation using chemiluminescent immunoassay technique and total serum calcium levels by colorimetric assay technique. Serum 25(OH)D and total calcium levels were expressed in ng/ml and mg/dl. Vitamin D deficiency was defined as per the guidelines set by United States Endocrine Society. The mean age of cases and controls was 45±9 and 46±10 years respectively. On multivariate analysis, an inverse association with BC was found for less frequency of fruits consumption with an adjusted (ORs, 95% CI) (2.7, 0.5-15.7) respectively. Mushroom intake was inversely associated with risk of BC (ORs, 95% CI) (5.6, 1.9-16.6). Saturated fat intake and high WHR were significantly associated with high risk of BC with adjusted ORs, 95% CI of (3.4, 1.4-8.1) and (5, 1.4-17). A significant association (p<0.05) was found between low serum 25(OH)D levels and the risk of BC with adjusted ORs, 95% CI of (2.5, 0.9-7.4). Majority of the patients with BC were suffering from vitamin D deficiency. Dietary intake of mushrooms containing vitamin D naturally was found to be associated with decreased risk of breast cancer. A significant association was found between low serum 25(OH)D levels (<20ng/ml) with the risk of BC. Obesity as a consequence of nutritional risk factors determined by higher WHR was found to be significantly associated with the risk of BC.

Epidemiology, clinical characteristics and outcomes of traumatic brain injury: Evidences from integrated level 1 trauma center in India

Introduction: Traumatic brain injury (TBI) is a leading cause of mortality, morbidity, disability, and socioeconomic losses in the Indian subcontinent. However, for policymaking and research, there is a lack of reliable and larger data in our settings. Aims and Objectives: To evaluate and describe the epidemiological, clinical characteristics, and outcomes of patients with TBI in a Level 1 Trauma Center in India. Materials and Methods: In this retrospective study, all patients with moderate or severe TBI, based on emergency department Glasgow Coma Scale, admitted to neurosurgery Intensive Care Unit (ICU) during May 2010–July 2012 were evaluated to provide detailed information on TBI-related variables and outcomes using descriptive statistics. Results: Among the 1527 patients with moderate or severe TBI patients with mean age 32.15 ± 16.76 years (range: 1–90) and male:female ratio 6.5:1, 1281 (83.89%) had severe TBI. The majority of cases took place in the age group of 21–40 years (50.24%) with the most common mode of injury as road traffic accidents (RTAs) (64.96%). Surgical intervention (craniotomy) was done in 49.12% of patients. About 34.58% (n = 528) patients died in hospital, and 67.21% (n = 701) had unfavorable outcome at 6 months. Conclusions: This is the first study of its kind from the Indian subcontinent that gives data on the admission characteristics, mortality, and 6 months outcome of such patients. Most of the injuries occurred due to RTAs, more common among the economic productive age groups and mostly in males with a high rate of mortality and unfavorable outcome.

Prognostic models for prediction of outcomes after traumatic brain injury based on patients admission characteristics

Abstract Objective: To identify the best performing prognostic model using admission characteristics to predict mortality at 30 days and functioning outcome at 6-months post-admission in patients with moderate or severe brain injury. Methods: Using a retrospective database (n = 1466 patients) of a tertiary trauma care centre, three different models were developed using logistic regression methods for predicting mortality and functioning outcome. The performance of the models was assessed in terms of discrimination and calibration. The models were validated using split sample method. For facilitating clinical usefulness, score charts were derived from the regression models. Results: The variables motor score, hypotension, pupillary reactivity, age, creatinine level, limb movement (hemiparesis), and tSAH/IVH were found to be the most predictive independent prognostic factors of both mortality and functioning outcome. For both the outcomes, discriminative ability of the three prognostic models was excellent in the development dataset (AUC = 0.845–-0.905) as well as the validation data set (AUC = 0.836–0.880). Calibration in the validation data set for model-2 was good (H-L test p-value > 0.05); however, for model-1 and model-3, it was poor (H-L test p-value < 0.05). Conclusion: For clinical decision-making, model-2 is recommended on the basis of good performance in predicting outcomes in patients with moderate or severe TBI in India and other similar countries.

Evaluation of circulating haematopoietic progenitor cells in patients with Trauma Haemorrhagic shock and its correlation with outcomes.

Background: Haemorrhagic shock accounts up to 50% of early trauma deaths. Hematopoietic failure has been observed in experimental animals and human following shock and injury. One of the facets of bone marrow failure is multiple organ dysfunction syndrome and is commonly seen in patients recovering from severe trauma and hemorrhagic shock. Bone Marrow (BM) dysfunction is associated with mobilization of hematopoietic progenitor cells (HPCs) into peripheral blood. Present study explored the association of peripheral blood hematopoietic progenitor cells (HPCs) with mortality in trauma haemorrhagic shock patients (T/HS). Materials and Methods: Prospective cohort studies of patients presenting within 8 hrs of injury with T/HS to the Department of Emergency Medicine, Jai Prakash Narayan Apex Trauma Center, All India Institute of Medical Sciences were recruited. Peripheral blood samples were collected in each patient for measurement of peripheral blood HPCs. Peripheral blood progenitor cell (PBPC) quantification was performed by measuring HPCs counts using the haematology analyzer (Sysmex XE-2100). Clinical and laboratory data were prospectively collected after consent. Ethical approval was taken and data was analysed by Stata 11.2. Results: 39 patients with trauma hemorrhagic shock and 30 normal healthy controls were recruited. HPCs were significantly higher (P < 0.001) in the T/HS as compared to control. Among study group, 14 patients died within 24 h. at the hospital admission, and found HPCs concentrations were highly significant (<0.001) in non-survivors (n = 14) when compared with survivors (n = 25) among T/HS patients. Conclusions: Our studies suggest the peripheral blood HPCs may be early prognostic marker for mortality among patients who presented with trauma hemorrhagic shock on admission. But the exact molecular mechanism and signalling pathway involved in the change of the behaviour of bone marrow microenvironment is still unclear.

Passive Smoking and Breast Cancer - a Suspicious Link

BACKGROUND Breast cancer is the most common malignancy of women in the world. The disease is caused by infectious and non-infectious, environmental and lifestyle factors. Tobacco smoke has been one of the most widely studied environmental factors with possible relevance to breast cancer. The purpose of this study was to assess the impact of tobacco smoking in breast cancer patients in a hospital based cohort and to establish prognostic implications if any. MATERIALS AND METHODS A retrospective audit of 100 women with pathological diagnosis of invasive breast cancer was included in this study. The verbal questionnaire elicited information on current and previous history of exposure to smoking in addition to active smoking. All analyses were adjusted for potential confounders, including stage at presentation, alcohol intake, hormonal replacement therapy, oral contraceptive intake, obesity and menopausal status. RESULTS The mean age at presentation of breast cancer was 51.4 ± 10.86 years. Mean age of presentation was 53.1±11.5 and 45.7±11.9 years in never smokers and passive smokers, respectively. Age at presentation varied widely in patients exposed to tobacco smoke for >10 years in childhood from 40.3± 12.0 years to 47.7± 13.9 in patients exposed for > 20 years as adults. Among passive smokers, 60.9% were premenopausal and 39.1% of patients were postmenopausal. In never smokers, 71.4% were post menopausal. Expression of receptors in non-smokers vs passive smokers was comparable with no significant differences. Metastatic potential in lung parenchyma was slightly elevated in passive smokers as compared to never smokers although statistically non-significant. CONCLUSIONS An inverse relationship exists between the intensity and duration of smoking and the age at presentation and poor prognostic factors. The results strongly suggest efforts should be taken to prevent smoking, encourage quitting and restrict exposure to second hand smoke in India.

Contralateral breast cancer: a clinico-pathological study of second primaries in opposite breasts after treatment of breast malignancy.

BACKGROUND Breast cancer is by far the most frequent cancer of women (23 % of all cancers), ranking second overall when both sexes are considered together. Contralateral breast cancer (CBC) is becoming an important public health issue because of the increased incidence of primary breast cancer and improved survival. The present communication concerns a study to evaluate the role of various clinico-pathological factors on the occurrence of contralateral breast cancer. MATERIALS AND METHODS A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. The diagnosis of CBC was confirmed on histopathology report. Relative risk with 95%CI was calculated for different risk factors of contralateral breast cancer development. RESULTS CBC was found in 24 (4.5%) out of 532 patients. Mean age of presentation was 43.2 years. Family history of breast cancer was found in 37.5% of the patients. There was statistically significant higher rate (83.3%) of CBC in patients in age group of 20-40 years with RR=11.3 (95% CI: 1.4, 89.4, p=0.006) seen in 20-30 years and RR=10.8 (95% CI:1.5-79.6, p=0.002) in 30-40 years as compared to older age of 60-70 years. Risk of development was higher in premenopausal women (RR=8.6, 95% CI: 3.5-21.3, p≤0.001). Women with family history of breast cancer had highest rate (20.9%) of CBC (RR=5.4, 95% CI: 2.5-11.6, p≤0.001). Use of hormonal therapy in hormone receptor positive patients was protective factor in occurrence of CBC but not significant (RR=0.7, 95% CI: 0.3-1.5, p=0.333). CONCLUSIONS Younger age, premenopausal status, and presence of family history were found to be significant risk factors for the development of CBC. Use of hormonal therapy in hormone receptor positive patients might be protective against occurrence of CBC but did not reach significance.

Molecular genetic profile in BCR-ABL1 negative pediatric B-cell acute lymphoblastic leukemia can further refine outcome prediction in addition to that by end-induction minimal residual disease detection

Abstract The recently proposed molecular genetic criteria promise improved risk-prediction in B-cell acute lymphoblastic leukemia (B-ALL). This study assesses their utility in BCR-ABL1 negative pediatric B-ALL, particularly with respect to end-induction minimal residual disease (MRD). The DNA was analyzed for copy number alterations in CDKN2A/B, PAX5, IKZF1, and other genes. Seventy-six cases with median age 7 years (2 months–18 years) included MRD-positive (24; 32%), and MRD negative-standard (20; 26%), intermediate (20; 26%), & high risk (12;16%) cases. The risk classification was based on age, initial total leukocyte count, central nervous system involvement, cytogenetics, day 8 prednisolone response and MRD status after induction chemotherapy. The genetic profile based on Moorman’s criteria identified two subgroups with different event free survival (EFS) (0.77 vs. 0.38; p = .045) and overall survival (OS) (0.90 vs. 0.30; p = .037) in the MRD-negative intermediate-risk group. The genetic profile also separated two subgroups with different EFS (0.75 vs. 0.41; p = .036) in the MRD-positive group, however the OS was not different (0.75 vs. 0.57; p = .293).