A multicenter double-blind, placebo-controlled randomized trial to evaluate the safety and efficacy of bovine colostrum in the treatment of severe alcoholic hepatitis (SAH).

BACKGROUND: Severe alcoholic hepatitis (SAH) is associated with high mortality. Numerous studies and meta-analysis have reported that corticosteroids reduce the 28-day mortality in SAH, but not the 6-month mortality. Therefore, newer treatments for SAH need to be studied. A pilot study from our group had recently treated ten patients with SAH with bovine colostrum (BC) [20 g thrice in a day for 8 weeks] and prednisolone. This therapy improved the biological functions and 3-month mortality. However, as more and more data showed the failure of corticosteroids to improve the 3- and 6-month mortality, especially in patients with high mDF and MELD scores, we planned this trial to study the safety and efficacy of BC (without corticosteroids) in the treatment of SAH. METHOD: This is a multicenter, parallel, double-blind, randomized (1:1) placebo-controlled trial, which will enroll 174 patients with SAH from 5 academic centers in the India. Patients will receive freeze-dried BC or placebo by random 1:1 allocation for 4 weeks. The primary outcome measure is survival at 3 months. The secondary outcome measures are survival at 1 month, change in mDF and MELD scores, change in endotoxin and cytokines (alpha TNF, IL6, and IL8) levels, number of episodes of sepsis [pneumonia, spontaneous bacterial peritonitis (SBP), cellulitis, urinary tract infection (UTI)] from baseline to 4 weeks. DISCUSSION: This study will evaluate the safety and efficacy of bovine colostrum in improving the survival of patients with SAH. TRIAL REGISTRATION: ClinicalTrials.gov NCT02473341. Prospectively registered on June 16, 2015.

Sofosbuvir plus ribavirin in treatment-naïve patients with chronic hepatitis C virus genotype 1 or 3 infection in India.

Until 2014, pegylated interferon plus ribavirin was the recommended standard of care for the treatment of chronic hepatitis C virus (HCV) infection in India. This open-label phase 3b study, conducted across 14 sites in India between 31 March 2014 and 30 November 2015, evaluated the efficacy and safety of sofosbuvir plus ribavirin therapy among treatment-naïve patients with chronic genotype 1 or 3 HCV infection. A total of 117 patients with genotype 1 or 3 HCV infection were randomized 1:1 to receive sofosbuvir 400 mg and weight-based ribavirin (1000 or 1200 mg) daily for 16 or 24 weeks. Among those with genotype 1 infection, the primary efficacy endpoint of sustained virologic response at 12 weeks post-treatment (SVR12) was reported in 90% (95% confidence intervals [CI], 73-98) and 96% (95% CI, 82-100) of patients following 16 and 24 weeks of treatment, respectively. For patients with genotype 3 infection, SVR12 rates were 100% (95% CI, 88-100) and 93% (95% CI, 78-99) after 16 and 24 weeks of therapy, respectively. Adverse events, most of which were mild or moderate in severity, occurred in 69% and 57% of patients receiving 16 and 24 weeks of treatment, respectively. The most common treatment-emergent adverse events were asthenia, headache and cough. Only one patient in the 24-week group discontinued treatment with sofosbuvir during this study. Overall, sofosbuvir plus ribavirin therapy achieved SVR12 rates ≥90% and was well tolerated among treatment-naïve patients with chronic genotype 1 or 3 HCV infection in India.

Aggressive bougie dilatation and intralesional steroids is effective in refractory benign esophageal strictures secondary to corrosive ingestion.

Endoscopic dilatation of corrosive esophageal strictures is effective, but some patients are refractory to it and require long-term repeated dilatations. The present study was carried out to analyze whether rigorous schedule of endoscopic bougie dilatation along with intralesional injection of triamcinolone in patients refractory to endoscopic dilatation alone could decrease the number and frequency of endoscopic dilatations. The inclusion criterion for this prospective study was patients with refractory corrosive esophageal stricture of any age group. Refractory benign esophageal stricture is defined as an anatomic fibrotic esophageal restriction with inability to achieve dilatation of ≥14 mm or to maintain dilatation for 4 weeks once ≥14 mm diameter is achieved. The patients were followed up prospectively for 1 year. Patients with refractory strictures were subjected to weekly bougie dilatation (Savary-Gilliard) of the strictures along with injections of intralesional triamcinolone (40 mg/mL, 1 mL diluted in 1 mL of saline, 0.5 mL injected per quadrant of stricture) for consecutive 5 weeks, referred to as rigorous schedule. Further dilatation was done on an 'on-demand' basis. Eleven patients were enrolled for the study. Dysphagia score improved from pre-intervention score of 3.54 ± 0.52 to 0.45 ± 0.52 post-intervention (P < 0.001). The maximum dilatation achieved pre-intervention was 9.90+1.04 mm Savary-Gilliard and post-intervention significantly improved to 14.7 + 0.7 mm Savary-Gilliard (P < 0.001). The periodic dilatation index defined as number of dilatations per month also significantly improved from pre-intervention score of 2.54 ± 1.06 to post-intervention score of 0.19 + 0.13 (P < 0.001). No adverse effects were reported by the patients. Rigorous weekly schedule of bougie dilatation and intralesional triamcinolone in combination is safe and effective in achieving significant dilatation, reducing the frequency dilatations, maintaining dilatation and improving dysphagia till 1 year of follow-up.

Alcohol metabolism is not affected by sleeve gastrectomy.

INTRODUCTION: It has been published that patients who underwent gastric bypass surgery have impaired alcohol metabolism, predisposing them to higher rates of intoxication and DUI arrests. Yet the impact of laparoscopic sleeve gastrectomy (LSG) on alcohol metabolism and in particular the long-term effects are still unclear. We hypothesized that LSG does not alter alcohol metabolism. METHODS: A prospective cohort study of patients undergoing LSG was evaluated. Blood alcohol concentration (BAC) was extrapolated using a Breathalyzer(®). Alcohol metabolism was evaluated by determining BAC every 5 min after a single dose of alcohol (5 oz. glass of 14% v/v Malbec wine), until BAC was equal to zero. Subjects were queried about alcohol intoxication symptoms. All parameters were obtained and analyzed preoperatively and at 3 and 12 months postoperatively. RESULTS: Our study consisted of 10 patients (9 female) with a mean age of 46.6 ± 2.2 years and BMI of 43.5 ± 2.2 kg/m(2). The mean percentage excess weight loss was 39.5 ± 3.3 at 3 months and 55.6 ± 4.4 at 12 months. Peak BAC at 20 min was not different at 3 months (0.068 ± 0.007, p = 0.77) or at 12 months (0.047 ± 0.008, p = 0.19) when compared to the preoperative assessment (0.059 ± 0.014). In addition, the time to BAC equal to zero was not significantly different between baseline and the follow-up values (preoperative: 70 ± 9 min, 3 months: 95 ± 18 min, and 12 months: 57 ± 8 min, (p > 0.05). Symptoms of intoxication were not significantly different in patients before and after surgery. CONCLUSIONS: Our study suggests that LSG does not alter alcohol metabolism. Patients who undergo LSG do not have higher levels of intoxication following alcohol consumption and are therefore not prone to higher rates of DUI charges than the general public, in contrast to that previously reported following in patients who undergo gastric bypass surgery.

Mitomycin-C: 'a ray of hope' in refractory corrosive esophageal strictures.

Increasingly frequent dilation may become a self-defeating cycle in refractory stricture as recurrent trauma enhance, scar formation, and ultimately recurrence and potential worsening of the stricture. In 12 patients of caustic induced esophageal stricture, who failed to respond despite rigorous dilatation regimen for more than one year, a trial of topical mitomycin-C application to improve dilatation results was undertaken, considering the recently reported efficacy and safety of this agent. Mitomycin-C was applied for 2-3 minutes at the strictured esophageal segment after dilation with wire-guided Savary-Gilliard dilator. Patient was kept nil by mouth for 2-3 hours. After 4-6 sessions of mitomycin-C treatment, resolution of symptoms and significant improvement in dysphagia score and periodic dilatation index was seen in all 12 patients. Mitomycin-C topical application may be a useful strategy in refractory corrosive esophageal strictures and salvage patients from surgery.

Low anastomotic stricture rate after Roux-en-Y gastric bypass using a 21-mm circular stapling device.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) has been established as a safe and effective procedure for morbid obesity management. Amongst some of the postoperative complications are gastrojejunal (GJ) anastomotic strictures, with an incidence of 3 to 27 % in some series. This study evaluates the incidence of GJ strictures using a 21-mm circular stapling device and its response to treatment with endoscopic balloon dilation. METHODS: A retrospective chart review was conducted of patients who underwent LRYGB between January 2007 and September 2010. We used our previously published technique of retrocolic, retrogastric Roux-en-Y bypass, using a 21-mm circular stapler to construct the gastrojejunostomy. Postoperatively, patients with persistent food intolerance underwent an endoscopy. Those found to have a GJ stricture (defined as inability to pass the endoscope beyond he anastomotic site) underwent pneumatic dilation with a 12-mm balloon. RESULTS: A total of 338 patients underwent LRYGB. Median follow-up was 57.6 weeks (8-137). Twenty-two patients underwent an endoscopy due to food intolerance. Sixteen patients (4.7 %, 16/338) were identified with GJ stricture and received at least one endoscopic dilation. The other six patients had a normal endoscopic evaluation. GJ strictures presented at an average of 35 days (13 to 90 days) postoperatively. Four patients underwent two endoscopic interventions, and one underwent three endoscopic interventions. CONCLUSIONS: We hereby demonstrate that the construction of GJ anastomosis with a 21-mm circular stapler is associated with a low stricture rate using our standardized technique. Strictures are amenable to balloon dilatation with subsequent long-term resolution of symptoms.

Laparoscopic gastric bypass for the adolescent patient: long-term results.

BACKGROUND: Obesity is a major public health problem in the developed world. The National Survey of Children's Health 2003 estimated around 17 million children in the USA to be overweight, making this a significantly alarming disease in the young population. Findings from the Third National Health and Nutrition Examination Survey demonstrated at least 30 % of overweight adolescents to be suffering from the metabolic syndrome. Combined metabolic and restrictive bariatric operations have been shown to improve or resolve these various comorbidities, and surgical therapy is recommended as a part of a multidisciplinary approach to the treatment of morbid obesity in adults. Data in the adolescent population are sparse. METHODS: This is a retrospective, descriptive study of prospectively collected data over 10 years. Twenty-five adolescents between the ages of 14 and 18 years underwent laparoscopic Roux-en-Y gastric bypass (RYGBP) using a standard technique by a single surgeon with follow-up of at least 5 years. RESULTS: Twenty of the 25 patients were available for follow-up from 5 to 10 years after their operation. Average BMI preop/postop was 45.7/28.6 kg/m(2). Average percentage of excess body weight loss was 77.7 %. Average BMI change was 17.1. CONCLUSION: Our long-term data demonstrate that laparoscopic RYGBP is a safe and effective operation for morbidly obese adolescents, in the proper setting. We advocate that surgical intervention be recommended for this population using the same NIH guidelines used for adults.

Greater white and grey matter changes associated with early cannabis use in adolescent-onset schizophrenia (AOS).

BACKGROUND: Cannabis use is associated with a higher risk of schizophrenia, however, its specific long-term effect on the structure of the brain of adolescent-onset schizophrenic patients remains unclear. AIMS: To study cognitive and structural (grey and white matter) changes in patients with adolescent-onset schizophrenia (AOS) with early cannabis use (CAN+ve) (more than 3 times/week for at least 6 months) and without cannabis use (CAN-ve) versus controls. METHOD: An optimised voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) MRI study of 32 adolescents with DSM IV schizophrenia-16 CAN+ve and 16 CAN-ve, and 28 healthy adolescents. RESULTS: Compared to CAN-ve subjects, CAN+ve subjects showed GM density loss in temporal fusiform gyrus, parahippocampal gyrus, ventral striatum, right middle temporal gyrus, insular cortex, precuneus, right paracingulate gyrus, dorsolateral prefrontal cortex, left postcentral gyrus, lateral occipital cortex and cerebellum. Similar group comparison showed decreased fractional anisotropy (FA) in particular in brain stem, internal capsule, corona radiata, superior and inferior longitudinal fasciculus in CAN+ve patients. No cognitive differences were apparent between CAN+ve and CAN-ve subjects, and both were impaired relative to controls. CONCLUSION: Cannabis use in early adolescence increases WM and GM deficits in AOS, but does not appear to increase the cognitive deficit associated with this illness.

Transcallosal resection of hypothalamic hamartoma for gelastic epilepsy.

INTRODUCTION: Hypothalamic hamartomas (HHs) are commonly associated with severe epilepsy resistant to anticonvulsant therapy. Historically, surgical resection of HHs resulted in considerable morbidity. DISCUSSION: Two series of patients who successfully underwent resection using a transcallosal approach have now been published; we report the first UK experience of this technique in a series of five patients with HHs and gelastic epilepsy resistant to anticonvulsant therapy. Patients were assessed pre- and postoperatively for seizure activity, endocrine function, ophthalmology, and neurocognitive function. Two patients had precocious puberty and all had evidence of developmental delay and behavioral problems. Postoperatively, all children experienced at least a 50% reduction in seizure frequency with abolition of major seizure types; one child remains seizure-free. One child developed a mild postoperative right hemiparesis and one developed transient diabetes insipidus. CONCLUSION: There were no adverse developmental effects of surgery. Transcallosal resection of HHs ameliorates resistant epilepsy syndromes associated with HH.

Quality of life and nutritional status in alcohol addicts and patients with chronic liver disease.

OBJECTIVE: The aim of the study was to assess and compare the nutritional status and quality of life in chronic liver disease (alcoholic and non-alcoholic) patients and alcohol addicts. METHODS: Patients with alcoholic liver disease (n=41), nonalcoholic liver disease (n=40), alcohol addicts (n=25) without liver disease and healthy controls (n=25) were randomly selected. Nutritional status was assessed using anthropometric measurements viz. skin fold thickness, arm muscle circumference and area. Biochemical estimations included liver function tests. Food intake was assessed using 48 hour recall and macro-nutrient intake was calculated. Quality of life was assessed using the SF-36 questionnaire. RESULTS: The mean value of mid-arm muscle area was significantly lower in patients from the non-alcoholic liver disease group when compared with the other 2 groups (p= 0.0). Body fat store depletion was significantly lower in the alcohol addict group when set against the alcoholic liver disease and non-alcoholic liver disease groups (p= 0.0). The mean percentages of ideal calories (p= 0.0) and proteins (p= 0.0) were significantly higher in alcohol addicts but no significant differences in the mean percentage of fat intake (p= 0.1) was observed. The frequency of macro-nutrient deficiency was highest in the non-alcoholic liver disease group (p= 0.0). Ethanol consumption was not significantly different between alcohol addicts and patients suffering from alcoholic liver disease (p=0.06). Patients with liver disease (irrespective of aetiology) scored significantly lower on the quality of life scale when compared to alcohol addicts. CONCLUSIONS: Malnutrition is more frequent and severe in patients suffering from chronic liver disease in comparison to alcohol addicts. The health status is significantly poorer in patients suffering from alcoholic liver disease. Alcohol does not seem to play a primary role in the pathogenesis of liver disease and malnutrition.

Achalasia cardia: A study of 113 patients managed with indigenous dilator.

BACKGROUND: Endoscopic dilatation of achalasia cardia is an effective nonsurgical management option. It requires costly pneumatic dilators which are used under fluoroscopic guidance. This study assesses the efficacy and safety of an indigenous pneumatic dilator used without fluoroscopic guidance. METHODS: Over a period of eleven years, 113 patients (69M, 44F) ofachalasia cardia underwent dilatation with indigenous pneumatic dilators without fluoroscopic guidance. The dilatation was performed under endoscopic vision. RESULTS: The procedure was successful in all patients. After six weeks following dilatation, there was significant improvement in the mean dysphagia score 3.63 + 0.61 to 0.53 + 0.93 (P<0.01). The response was still significant (0.78 + 1.03, P <0.05) at the end of one year. Excellent response with single dilatation was seen in 70.7% patients. After two dilatation sessions 92% of patients showed an excellent response. One patient had perforation. There was no mortality. CONCLUSION: Pneumatic dilatation under endoscopic vision without fluoroscopic assistance with the indigenous dilator is very effective and safe for short term treatment of achalasia carida.

Magnetic loop basket: a "two-in-one" instrument.

BACKGROUND AND STUDY AIMS: Ingested coins are the most common foreign bodies encountered in the upper gastrointestinal tract in India and if they remain in the stomach for more than 5 days they need to be removed. Ferromagnetic retrieval instruments only work if the coins are ferromagnetic; and it is difficult to maneuver a loop basket in the fundus of the stomach. A magnetic loop basket was designed in an effort to overcome these difficulties and we assessed its feasibility, safety, and effectiveness in the removal of coins from the fundus of the stomach. PATIENTS AND METHODS: Twenty patients with a history of ingested coins were scheduled for removal of the coins using the magnetic loop basket. The time taken, complications, and failure rates were recorded. RESULTS: Twelve ferromagnetic coins were removed in a mean time of 60 seconds (range 30 - 90 seconds) and eight non-ferromagnetic coins were removed in a mean time of 150 seconds (range 90 - 180 seconds) without any failures or complications. CONCLUSION: The magnetic loop basket is a safe, effective, and quick method for removing both ferromagnetic and non-ferromagnetic metallic coins.