Development and Validation of a Tool for Assessing Adherence to Gluten-Free Diet in Patients With Celiac Disease.

INTRODUCTION: Life-long adherence to gluten-free diet (GFD) and its assessment is essential for patients with celiac disease (CeD). We have developed and validated a tool for assessing adherence to GFD which can be used by both physicians and dietitians. METHODS: Phase 1: Development, content validation, and assessment of reliability of tool. Phase 2: Validation of tool against standard dietary evaluation (SDE) (gold standard), immunoglobulin A - anti-tissue transglutaminase antibodies (IgA anti-tTG Ab), and gluten immunogenic peptides in urine. Overall, 380 biopsy-confirmed patients with CeD (derivation cohort: n = 100 [phase 1], n = 210 [phase 2] and independent validation cohort, n = 70) were recruited. RESULTS: Of an initial 90-point questionnaire, 84 items (Celiac Disease: Compliance Assessment Test [CD-CAT.v1]) were retained after content validation and pilot testing. In phase 1, upon administering CD-CAT.v1 on 100 patients, a comprehensive 35-item tool (CD-CAT.v2; α = 0.86) was obtained after removing items with low test-retest reliability and item-rest correlation values. In phase 2, upon administering CD-CAT.v2 on 210 patients, 22 items were removed having low correlation values (R < 0.4) with SDE. Finally, a 13-item tool (CD-CAT.v3; α = 0.84) was obtained with high criterion validity with SDE ( r = 0.806, P < 0.001), moderate convergent validity with celiac disease adherence test ( r = 0.602, P = 0.007), and moderate to weak correlation with urine gluten immunogenic peptides ( r = 0.46, P = 0.001) and IgA anti-tTG Ab ( r = 0.39, P = 0.008), respectively. The final 13-item tool also strongly correlated with SDE ( r = 0.78, P < 0.001) in an independent validation cohort of 70 patients with CeD. Principal component analysis identified 3 relevant subscales with a cumulative variance of 62%. The sensitivity and specificity of CD-CAT.v3 were 80% and 91%, respectively, with an area under curve of 0.905 with SDE. The obtained cutoff score of <19 from the receiver operating characteristic curve was further categorized as 13 = excellent, 14-18 = very good, 19-28 = average, and >28 = poor adherence to GFD. DISCUSSION: CD-CAT is a new and rapid tool for monitoring dietary adherence to GFD with high sensitivity and specificity, which can be administered by both physicians and dietitians.

Hyperammonemia Secondary to 5-Fluorouracil.

5-fluorouracil (5-FU) is one of the most common adjuvant antineoplastic agents used in the treatment of localized and metastatic colon cancer. Frequent side effects of 5-FU include myelosuppression, mucositis, nausea, vomiting, and diarrhea. However, hyperammonemic encephalopathy is a rare neurologic toxicity that can occur after 5-FU chemotherapy administration. Patients with 5-FU-induced hyperammonemic encephalopathy often exhibit symptoms of altered mental status with no radiologic abnormalities or laboratory abnormalities except for significantly elevated ammonia levels with occasional lactic acidosis and respiratory alkalosis. We report a case of a patient with stage IV colon adenocarcinoma who experienced altered state of consciousness due to hyperammonemia during the administration of palliative chemotherapy with 5-FU, bevacizumab, and leucovorin. On cycle 1 day 2 of chemotherapy, the patient became drowsy and confused at home, prompting a visit to the emergency department and ultimately hospital admission. Laboratory tests revealed an elevated blood ammonia level (838 µg/dL). After an extensive negative workup, his altered state of consciousness was thought to be secondary to 5-FU-induced hyperammonemia. Upon admission, 5-FU was immediately discontinued and the patient was treated with lactulose enemas, intravenous fluids, rifaximin, and continuous renal replacement therapy with gradual recovery to baseline mental status. It is crucial for advanced practitioners to be aware of this rare side effect to ensure prompt diagnosis and maximize treatment effectiveness.

Efficacy and Safety of Percutaneous Radiological Gastrostomy (PRG) as a Rescue Measure for Enteral Feeding in Patients with Advanced Head, Neck, and Upper Digestive Malignancies.

Background Percutaneous radiologic gastrostomy is an established mode of enteral feeding for nutritional support for patients with dysphagia from upper digestive tract malignancy. Its role as a rescue measure in patients with advanced malignancy, presenting with absolute dysphagia and failure of nasogastric tube insertion has not been well established. Purpose This study was performed to assess technical success and long-term outcomes of percutaneous radiologic gastrostomy (push type) for nutritional support for patients with absolute dysphagia as a last ditch nonsurgical rescue effort for enteral access. Materials and Methods This was a prospective observational study of 31 patients who underwent push-type percutaneous radiologic gastrostomy over a period of 2 years (March 2017-March 2019). The study was a part of a larger trial approved by the institutional ethics committee. Patients were followed till the removal of tube, death, or 1 year, whichever was earlier. Gastrostomy tube-related problems and complications were documented. Descriptive summary statistics were employed to analyze the success rate and complications. Results Thirty-one patients with mean age 56 years (26-78 years) including 18 males and 13 females with head and neck squamous cell cancer and esophageal cancer presenting with absolute dysphagia or significant dysphagia with failed nasogastric or endoscopic enteral access were included. Overall technical success was 93.5% (29/31), achieved in 26/31 patients with just fluoroscopy guidance and 3/5 patients with computed tomography guidance. One major (3.3%) and two minor (6.5%) complications were encountered. Five out of 29 gastrostomy tubes had to be exchanged, after a mean of 44 days (1-128 days) after insertion. Conclusion Percutaneous radiologic gastrostomy is a safe and effective intervention even as a rescue measure in patients with absolute dysphagia from advanced upper digestive tract malignancies.

Differential expression of miRNA in histological subtype of Wilms tumor.

INTRODUCTION: Wilms tumor is the most common renal malignancy in children and difficult to differentiate from other paediatric abdominal tumors radiologically, necessitating an invasive procedure for diagnosis. Previous studies have shown the potential role of miRNA as biomarkers for diagnosis, histological subtyping and prognosis. In this study, we are exploring the role of miRNA in the histological subtyping of Wilms tumor in the Indian population. MATERIALS AND METHODS: A total of 15 cases of Wilms tumor were evaluated for global miRNA expression analysis by microarray. Total RNA was extracted from fresh frozen tumor and miRNA expression analysis was performed using Agilent platform. Unsupervised clustering was done to analyse the data. RESULTS: Using unpaired student T test, top 10 significantly differentially expressed miRNA were selected which could differentiate among different histological subtypes by unsupervised hierarchical clustering and principal component analysis. The presence of necrosis, heterologous differentiation led to change in miRNA expression profile and led to a distinct cluster formation. CONCLUSIONS: A panel of 5 miRNAs (miR1, 133b, 299-3p, 499a-5p, 491-3p) could differentiate among different histological subtypes of Wilms tumor, thus avoiding an invasive procedure in children, however, further confirmation using real time PCR analysis will be needed.

A randomized pilot study to compare hair follicle cell suspensions prepared using trypsin alone versus trypsin in combination with collagenase type I for transplantation in vitiligo.

BACKGROUND: Noncultured extracted hair follicle outer root sheath cell suspension (NC-EHF-ORS-CS) is an upcoming surgical technique to treat stable vitiligo. Conventionally it employs trypsin to tap the hair follicle (HF) reservoir for autologous melanocytes and their precursors for transplantation. However, a perifollicular dermal sheath composed of type 1 collagen encases the target 'bulge' region of the HF. Adding collagenase type 1 would digest the ORS, facilitating better release of cells. AIM: To compare the repigmentation achieved using trypsin and a combination of collagenase plus trypsin, respectively, with dermabrasion alone, and to compare cell counts, viability and composition of both suspensions. METHODS: This was a randomized, double-blind, comparative, therapeutic trial, conducted as a pilot study on 22 patients with stable vitiligo. Three similar patches were randomized into three parallel treatment arms [(A) trypsin plus collagenase, (B) trypsin alone and (C) dermabrasion with vehicle alone]. Each patient's HF sample was divided and digested by the two methods, and transplanted as suspensions onto dermabraded patches, while a third dermabraded patch received the vehicle only. Suspensions were sent for laboratory analysis. Repigmentation was assessed over a follow-up of 6 months. RESULTS: There was a significant increase in cell yield and comparable viability when collagenase was added. Immunohistochemical and flow cytometry studies showed a nonsignificant increase in HMB45+ melanocytes and their precursor stem cells in group A. This trend was reflected clinically in the extent of repigmentation [group A (33.22%) > B (24.31%) > C (16.59%); P = 0.13]. Adding collagenase induced significantly higher repigmentation than dermabrasion alone (P < 0.05). CONCLUSIONS: Incorporating collagenase type I into the conventional NC-EHF-ORS-CS technique resulted in enhanced retrieval of pigment-forming cells and subsequently improved repigmentation in vitiligo.

Acetic acid versus radiofrequency ablation for the treatment of hepatocellular carcinoma: A randomized controlled trial.

PURPOSE: The purpose of this prospective study was to compare the efficacy of percutaneous acetic acid (PAAI) to that of radiofrequency ablation (RFA) in the treatment of small (≤5cm) hepatocellular carcinoma (HCC) using a randomized trial. MATERIAL AND METHODS: Consecutive patients with small HCC underwent clinical, biochemical, and imaging evaluation. Those fulfilling the inclusion criteria (Child's A/B cirrhosis, less than 5 HCC nodules, HCC nodules≤5cm diameter, no extrahepatic disease, patent portal vein, normal coagulation profile with informed consent) were randomly assigned to receive RFA or PAAI. Tumor response and survival rate were estimated. Non-inferiority margin of 10% difference was taken for effectivity of PAAI compared to RFA. RESULTS: Of the 86 patients screened, 55 patients with 67 HCC nodules were included. There were 40 men and 15 women with a mean age of 54.3±10.5 (SD) years (range: 28-71years). Of these, 26 patients had PAAI and 29 had RFA. The clinical, demographic and imaging profiles of the two groups were similar. Complete response was non-inferior to RFA [PAAI 75% and RFA 83.3%, difference 8.3% CI (-12.5% to 29.2%)]. Lower limit of this 95% CI (-12.5%) was lower than the 10% non-inferiority margin difference (8.3%). Survival rates were similar at 12months (PAAI, 81.6% vs. RFA, 71.9%; P=0.68) and at 30months (PAAI, 54.4% vs. RFA, 52%; P=0.50). CONCLUSION: PAAI and RFA have similar efficacy in treating small HCC. PAAI could thus be a cost-effective alternative in situations where RFA is either unavailable or unaffordable.

Symphytum officinale augments osteogenesis in human bone marrow-derived mesenchymal stem cells in vitro as they differentiate into osteoblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Mesenchymal stem cells (MSCs) are multipotent stem cells possessing regenerative potential. Symphytum officinale (SO) is a medicinal plant and in homoeopathic literature, believed to accelerate bone healing. AIM OF THE STUDY: This study aimed to determine if homoeopathic doses of SO could augment osteogenesis in MSCs as they differentiate into osteoblasts in vitro. MATERIALS AND METHODS: Bone marrow samples were obtained from patients who underwent bone grafting procedures (n = 15). MSCs were isolated, expanded and characterized by flow cytometry (CD90, CD105). Cytotoxicity of SO was evaluated by MTT assay. Osteogenic differentiation was induced in MSCs with ß-glycerophosphate, ascorbic acid and dexamethasone over 2 weeks. Different homoeopathic doses of SO (MT, 3C, 6C, 12C and 30C) were added to the basic differentiation medium (BDM) and efficiency of MSCs differentiating into osteoblasts were measured by evaluating expression of Osteocalcin using flow cytometry, and alkaline phosphatase activity using ELISA. Gene expression analyses for osteoblast markers (Runx-2, Osteopontin and Osteocalcin) were evaluated in differentiated osteoblasts using qPCR. RESULTS: Flow cytometry (CD90, CD105) detected MSCs isolated from bone marrow (93-98%). MTT assay showed that the selected doses of SO did not induce any cytotoxicity in MSCs (24 hours). The efficiency of osteogenic differentiation (2 weeks) for different doses of Symphytum officinale was determined by flow cytometry (n = 10) for osteoblast marker, Osteocalcin, and most doses of Symphytum officinale enhanced osteogenesis. Interestingly, gene expression analysis for Runx-2 (n = 10), Osteopontin (n = 10), Osteocalcin (n = 10) and alkaline phosphatase activity (n = 8) also showed increased osteogenesis with the addition of Symphytum officinale to BDM, specially mother tincture. CONCLUSIONS: Our findings suggest that homoeopathic dose (specially mother tincture) of Symphytum officinale has the potential to enhance osteogenesis.

Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial.

AIM: To determine equivalence of modified gemcitabine and oxaliplatin compared with gemcitabine and cisplatin in unresectable gallbladder cancer (GBC). Primary end-point was overall survival (OS). METHODS: Open label, prospective, randomised phase III equivalence study. Inclusion criteria included histologically proven unresectable GBC, 18 years or older, adequate organ functions and Eastern Cooperative Oncology Group ≤2. SAMPLE SIZE: 108 patients were required in each arm to have an equivalence margin of ±2 months with power of 80%. TREATMENT: Modified gemcitabine and oxaliplatin (mGemOx)-gemcitabine 900 mg/m2, oxaliplatin 80 mg/m2, maximum 6 cycles; gemcitabine + cisplatin (CisGem)-gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, maximum 8 cycles, all day 1 and 8 every 3 weeks. RESULTS: Two hundred sixty subjects were recruited between February 2011 and July 2015. Two hundred forty-three patients (119, mGemOx and 124, CisGem) received at least 1 dose and analysed for safety and efficacy (modified intention to treat). Median OS was 8·5 months for whole group (95% confidence interval [CI]: 7·9-9·1). Median OS in mGemOx was 9 months and 8·3 months in CisGem; p = 0·057 (hazard ratio = 0·78; 95% CI = 0·60-1·02). Restricted mean OS for follow-up limited to 30 months was 11·2 months (95% CI: 9·8-12·6) in mGemOx and 10·4 months (95% CI: 9·1-11·7) in CisGem. Difference of the mean was 0·8 months with 95% CI, exceeding 2 months (-1·1 to 2·7), hence rejecting equivalence. Peripheral neuropathy, thrombocytopaenia in mGemOx and nephrotoxicity was higher with CisGem. CONCLUSION: This trial failed to show equivalence of eight cycles of CisGem to six cycles of mGemOx. Numerically OS was better with mGemOx. Toxicities were different. The trial was not powered to answer superiority. CLINICAL TRIAL REGISTRATION: CTRI/2010/091/001406.

Rectal Carriage of Carbapenem-Resistant Enterobacteriaceae: A Menace to Highly Vulnerable Patients.

BACKGROUND: Bloodstream infection (BSI) due to carbapenem-resistant enterobacteriaceae (CRE) is the leading cause of morbidity and mortality in patients with hematological malignancy. These patients receive chemotherapy during treatment, which lead to severe mucositis of gastrointestinal tract and myelosuppression. It was hypothesized that the gut colonizer translocate into the blood circulation causing BSI. Colonization rate with CRE among these patients in India is unknown. AIM: This study aims to determine the carriage rate of CRE in cancer patients. SETTING AND DESIGN: A prospective study was conducted in a tertiary care hospital of India. MATERIALS AND METHODS: Rectal swab of 93 patients were collected and processed as per the Center for Disease Control and Prevention protocol for detection of CRE. The isolate CREs were identified by standard phenotypic tests and confirmed for carbapenem resistance by disk diffusion test using carbapenem disk (imipenem, meropenem, doripenem, and ertapenem), Carba-NP test and modified Hodge test. Resistant to any of the carbapenem disc is considered as CRE. RESULTS: A total of 86 isolates were detected from 93 patients. Seventy-six isolates were identified as CRE, and 10 isolates were Gram-positive cocci and other Gram-negative bacilli. Acute myeloid leukemia was the most common clinical presentation followed by acute lymphoid leukemia. Thirty-nine out of 93 patients were on chemotherapy. Sixty-seven out of 76 isolates of CRE were observed positive for carbapenemase production by Carba-NP test. CONCLUSION: This study highlights very high rate of CRE carriage among the hematological malignancy patients; who are highly vulnerable to infection. This confirms the need of infection control prevention activities among the hematological malignancy patients.

Breast mass characterization using shear wave elastography and ultrasound.

PURPOSE: To evaluate the role of SWE in characterizing breast masses and ascertain whether additional use of SWE to ultrasound for evaluating BI-RADS 3 and 4a masses could help reduce long-term follow-up and unnecessary biopsies of these suspicious breast masses. MATERIALS AND METHODS: This prospective, cross-sectional study was performed between June 2013 and November 2014. All enrolled patients underwent clinical breast examination, ultrasound, SWE and ultrasound-guided core biopsy of the breast mass. Breast Imaging Reporting and Data System (BI-RAD) categories were assigned to breast masses. For qualitative and quantitative variables of SWE, cut-off values for differentiation between benign and malignant breast masses were estimated. Modified BIRADS' (up/downgrading of BIRADS category) was done for BI-RADS 3/4a masses by combining individual SWE parameters and ultrasound findings. Sensitivity, specificity, positive and negative predictive value of modified BI-RADS' and ultrasound BI-RADS were compared. RESULTS: A total of 119 women (mean age, 42.3±13.6 [SD] years; range: 13-87 years) with a single breast mass each were enrolled. Histopathologically, 57/119 (48%) breast masses were benign and 62 (52%) were malignant. On ultrasound, 42 breast masses were BI-RADS3 and 77 were BI-RADS 4 (4a, n=10; 4b, n=24; 4c, n=43) leading to 96.8% sensitivity and 70.2% specificity. On SWE, benign breast masses were oval/round, homogenous/reasonably homogenous, blue/green with lower elasticity values and malignant breast masses were irregular, inhomogeneous, red/orange with high elasticity values. On modified BI-RADS' using E-color and E-mean/E-max, specificity improved to 78.9% and 75.4% respectively. CONCLUSION: Addition of SWE to ultrasound improves characterization of BI-RADS 3 and 4a masses. E-max, E-mean and E-color are the most useful SWE parameters to differentiate between malignant and benign breast masses.

Operable Oral Tongue Squamous Cell Cancer: 15 Years Experience at a Tertiary Care Center in North India.

The aim of the present study was to provide insight into various demographic, clinical, and management profile of Indian patients with oral tongue squamous cell cancer (OTSCC). All the OTSCC patients who had undergone surgical treatment during 1995 to 2010 at a tertiary care center in North India were considered for the present study. The details of the patients were retrieved from a prospectively maintained computerized database. A total of 124 patients were included in the present study. Mean age of the patients was 50.4 ± 12.0 years. Lateral border of the tongue was the most common sub-site involved in 110 (88.7%) patients. Neck nodes were clinically palpable in 56.4% patients. Hemiglossectomy and anterior partial glossectomy were common surgical procedure undertaken in 57.2 and 25.8% patients. Negative resection margin was achieved in 97.5% patients. Pathological neck metastasis was seen in 40.3% patients. Occult neck metastasis was present in 25.9% patients among clinical N0 neck. At a mean follow-up of 29.8 months (SD 3.1), 20.1% developed disease relapse and 4.0% patients developed second primaries. Kaplan-Meier analysis estimated a 5-year disease-free survival of 81.5% and a 5 years overall survival of 78.6%. Cox proportional regression analysis predicted tumor size and number of positive nodes to be independent predictive variables for disease recurrence. Quality controlled surgery, coupled with adjuvant treatment when required, provides a safe and effective treatment of OTSCC with a good disease-free survival and loco-regional control.

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease.

BACKGROUND: As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. METHODS: A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. RESULTS: A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. CONCLUSIONS: Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

Evaluation of tumor response to intra-arterial chemoembolization of hepatocellular carcinoma: Comparison of contrast-enhanced ultrasound with multiphase computed tomography.

PURPOSE: To compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) with that of multiphase computed tomography (CT) in the evaluation of tumor response to transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Fifty patients (41 men, 9 women; mean age, 53 years±12.5 [SD]) with a total of 70 HCCs (mean size, 5cm±3 [SD]) were evaluated. Post-TACE therapeutic assessment of HCC was done at 4 weeks. Patients with TACE done earlier and reporting with suspicion for recurrence were also included. Patients with hepatic masses seen on ultrasound were enrolled and subjected to CEUS, multiphase CT and magnetic resonance imaging (MRI). Hyperenhancing area at the tumor site on arterial phase of CEUS/multiphase CT/MRI was termed as residual disease (RD), the patterns of which were described on CEUS. Diagnostic accuracies of CEUS and MPCT were compared to that of MRI that was used as the reference standard. RESULTS: CEUS detected RD in 43/70 HCCs (61%). RD had a heterogeneous pattern in 22/43 HCCs (51%). Sensitivities of CEUS and multiphase CT were 94% (34/36; 95% CI: 81-99%) and 50% (18/36; 95% CI: 33-67%) respectively. Significant difference in sensitivity was found between CEUS and multiphase CT (P=0.0001). CEUS and multiphase CT had 100% specificity (95% CI: 83-100%). CONCLUSION: CEUS is a useful technique for detecting RD in HCC after TACE. For long term surveillance, CEUS should be complemented with multiphase CT/MRI for a comprehensive evaluation.

Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer.

BACKGROUND/AIMS: Recent data suggest that the incidence of ulcerative colitis (UC) related colorectal cancer (CRC) in India is similar to that of West. The optimum method for surveillance is still a debate. Surveillance with random biopsies has been the standard of care, but is a tedious process. We therefore undertook this study to assess the yield of random biopsy in dysplasia surveillance. METHODS: Between March 2014 and July 2015, patients of UC attending the Inflammatory Bowel Disease clinic at the All India Institute of Medical Sciences with high risk factors for CRC like duration of disease >15 years and pancolitis, family history of CRC, primary sclerosing cholangitis underwent surveillance colonoscopy for dysplasia. Four quadrant random biopsies at 10 cm intervals were taken (33 biopsies). Two pathologists examined specimens for dysplasia, and the yield of dysplasia was calculated. RESULTS: Twenty-eight patients were included. Twenty-six of these had pancolitis with a duration of disease greater than 15 years, and two patients had associated primary sclerosing cholangis. No patient had a family history of CRC. The mean age at onset of disease was 28.89±8.73 years and the duration of disease was 19.00±8.78 years. Eighteen patients (64.28%) were males. A total of 924 biopsies were taken. None of the biopsies revealed any evidence of dysplasia, and 7/924 (0.7%) were indefinite for dysplasia. CONCLUSIONS: Random biopsy for surveillance in longstanding extensive colitis has a low yield for dysplasia and does not suffice for screening. Newer techniques such as chromoendoscopy-guided biopsies need greater adoption.

Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity.

BACKGROUND & OBJECTIVES: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). METHODS: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. RESULTS: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2FNx015/FNx017 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). INTERPRETATION & CONCLUSIONS: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

Psychological Barriers to Tobacco Cessation in Indian Buprenorphine-Naloxone Maintained Patients: A Pilot Study.

CONTEXT: The prevalence of smoking in opioid agonist treatment programmes remains high, leading to significant tobacco related health hazards and mortality. This is the first study from India addressing tobacco cessation and related barriers among recipients of buprenorphine-naloxone maintenance treatment. AIMS: The purpose of the study was to investigate Indian buprenorphine-naloxone maintained patients' willingness to quit tobacco use, to determine its possible association with demographic, agonist maintenance treatment, tobacco use related variables and personal health and risk perceptions related to health hazards associated with tobacco use. SETTINGS AND DESIGN: The study was cross-sectional, observational. It was conducted in the out-patient department of a national level de-addiction centre in India. MATERIALS AND METHODS: Fifty-five males on buprenorphine-naloxone treatment were assessed using Tobacco Use Characteristics, Fagerstrom Test for Nicotine Dependence (FTND and FTND-ST), Readiness to Change questionnaire (RCQ), Smoker's Perceived Health Risk Evaluation (SPHERE), Importance of Intervention scale and a semi-structured questionnaire. STATISTICAL ANALYSIS: Descriptive statistics, Kruskal-Wallis Chi-square test, Spearman rank order correlation, paired-t test, ANOVA (STATA 9.2 statistical package). RESULTS: Around 65.4% of the subjects were smokers, 9% were using smokeless tobacco only whereas 25.6% were using both. Mean duration of tobacco use was 20 ± 1.5 years. Only 20% had past quit attempts. Only 24% were in action phase of change. Personal health and risk perceptions were poor and only 61.62% considered intervention tobacco smoking cessation important. CONCLUSIONS: Higher severity of nicotine dependence, low perception of harm from tobacco warrant immediate attention and need for on-site treatment opportunity.

Topical Oil Application and Trans-Epidermal Water Loss in Preterm Very Low Birth Weight Infants-A Randomized Trial.

OBJECTIVE: Topical emollient application reduces trans-epidermal water loss (TEWL) in preterm neonates. Coconut oil used traditionally for infant massage in India has not been evaluated for the same. PATIENTS AND METHODS: Very low birth weight (VLBW) neonates were randomized at 12 h of age to Oil (n = 37) or Control (n = 37) groups. Oil group neonates received twice-daily coconut oil application without massage, and Control group received standard care. TEWL was measured every 12 h using an evaporimeter till Day 7 when skin swabs were obtained for bacterial growth and skin condition was assessed using a validated score. RESULTS: Birth weight (g; mean ± SD: 1213 + 214 vs. 1164 + 208, p = 0.31), gestation [week; median (interquartile range): 32 (31-33) vs. 32 (29-33), p = 0.10] and other baseline variables were comparable. TEWL was significantly reduced (g/m(2)/h, mean difference: -6.80, 95% confidence interval: -3.48, -10.15; p < 0.01) with better skin condition and lower bacterial growth in the Oil group (20% vs. 60%, p < 0.01). CONCLUSION: Coconut oil application reduced TEWL without increasing skin colonization in VLBW neonates. CLINICAL TRIALS REGISTRATION: NCT01758068.

Correlation Between Retropalatal Collapse as Observed During Muller's Maneuver to Severity of OSA.

Objective of the study was to evaluate the reliability of Muller's maneuver (MM) with the severity of obstructive sleep apnea (OSA) at the retropalatal level. Case series of 58 adult patients diagnosed to have OSA. Sleep apnoea clinic in a tertiary referral center in south India. Fifty-eight adult OSA patients underwent outpatient based MM under local anaesthesia. Collapse of hypopharynx and the retroglossal regions were assessed during a maximal inspiratory effort against the closed mouth and sealed nose (reverse valsalva). Correlation co efficient was used to compare MM grade with apnea-hypopnea index (AHI) scores. Severity of OSA based on AHI scores were compared with the results of Muller's maneuver at the retropalatal level. The correlation coefficient was 0.213, hence no correlation was found, p value was 0.019, which was not statistically significant. MM is an useful tool for evaluation of upper airway collapse. The advantages include simplicity, cost-effectiveness, relatively easy to perform, thorough evaluation of upper airway. The pitfalls of the procedure includes the subjectiveness of the procedure and the fact that it is performed on awake patients and therefore remains an indirect estimation of obstruction that occurs during sleep. In our study, we did not find correlation between the severity of OSA based on the AHI scores and the collapse at the retropalate level assessed by the Muller's maneuver.

Incidence and risk factors of hepatocellular carcinoma in patients with hepatic venous outflow tract obstruction.

BACKGROUND: Frequency of hepatocellular carcinoma (HCC) in hepatic venous outflow tract obstruction (HVOTO) is unclear and risk factors in HVOTO associated with HCC are unknown. AIM: To assess the incidence of HCC and to identify risk factors for HCC in primary HVOTO. METHODS: In the consecutive primary HVOTO patients evaluated between 1989 to 2013, the incidence of HCC among HVOTO was assessed in a retrospective cohort study and identification of the risk factors for HCC in HVOTO patients done by a case-control study. RESULTS: Of the 421 HVOTO patients, 8 had HCC at presentation (prevalence 1.9%). Another 8 of the remaining 413 developed HCC during 2076.2 person-years follow-up (mean 5.03 + 4.65 years, range 0.08-20 years). The cumulative incidence of HCC was 3.5% (95% CI 1.28-9.2%) at 10 years. The case-control study included 16 HCC as cases and remaining 405 as controls. Controls were predominantly males (M:F - 230:175), mean age 29 ± 10.3 years. Cases were predominantly females with an older age of 36.2 ± 11.4 years (P < 0.01, OR = 1.06, CI 1.0-1.10%). Presence of cirrhosis (P < 0.001), combined inferior vena cava (IVC) and hepatic vein (HV) block (P < 0.03, OR = 5.58, CI 1.43-25.30%) and long-segment IVC block (P < 0.02, OR = 6.50, CI 1.32-32.0%) were significantly higher among cases than controls. CONCLUSIONS: Hepatic venous outflow tract obstruction is a risk factor for HCC. The cumulative incidence of HCC in HVOTO is low and progressively increases over time. Those with liver cirrhosis, combined IVC and HV block and long-segment IVC block are at risk to develop HCC and need active surveillance.