James Swain

The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity

BACKGROUND Saline-filled intragastric balloon devices are reversible endoscopic devices designed to occupy stomach volume and reduce food intake. OBJECTIVE To evaluate the safety and effectiveness of a dual balloon system plus diet and exercise in the treatment of obesity compared to diet and exercise alone. SETTING Academic and community practice, United States. METHODS Participants (n = 326) with body mass index (BMI) 30-40 kg/m(2) were randomized to endoscopic DBS treatment plus diet and exercise (DUO, n = 187) or sham endoscopy plus diet and exercise alone (DIET, n = 139). Co-primary endpoints were a between-group comparison of percent excess weight loss (%EWL) and DUO subject responder rate, both at 24 weeks. Thereafter DUO patients had the DBS retrieved followed by 24 additional weeks of counseling; DIET patients were offered DBS treatment. RESULTS Mean BMI was 35.4. Both primary endpoints were met. DUO weight loss was over twice that of DIET. DUO patients had significantly greater %EWL at 24 weeks (25.1% intent-to-treat (ITT), 27.9% completed cases (CC, n = 167) compared with DIET patients (11.3% ITT, P = .004, 12.3% CC, n = 126). DUO patients significantly exceeded a 35% response rate (49.1% ITT, P<.001, 54.5% CC) for weight loss dichotomized at 25%EWL. Accommodative symptoms abated rapidly with support and medication. Balloon deflation occurred in 6% without migrations. Early retrieval for nonulcer intolerance occurred in 9%. Gastric ulcers were observed; a minor device change led to significantly reduced ulcer size and frequency (10%). CONCLUSION The DBS was significantly more effective than diet and exercise in causing weight loss with a low adverse event profile.

Effect of Reversible Intermittent Intra-abdominal Vagal Nerve Blockade on Morbid Obesity The ReCharge Randomized Clinical Trial

IMPORTANCE Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01327976.

Differential expression of lumican and fatty acid binding protein-1: New insights into the histologic spectrum of nonalcoholic fatty liver disease†

The basis of hepatocellular injury and progressive fibrosis in a subset of patients with nonalcoholic fatty liver disease (NAFLD) is poorly understood. We sought to identify hepatic proteins that are differentially abundant across the histologic spectrum of NAFLD. Hepatic protein abundance was measured in liver samples from four groups (n = 10 each) of obese (body mass index >30 kg/m2) patients: (1) obese normal group (normal liver histology), (2) simple steatosis (SS), (3) nonalcoholic steatohepatitis (NASH)‐mild (steatohepatitis with fibrosis stage 0‐1), and (4) NASH‐progressive (steatohepatitis with fibrosis stage 2‐4). Hepatic peptides were analyzed on an API Qstar XL quadrupole time‐of‐flight mass spectrometer using Analyst QS software. Linear trends tests were performed and used to screen for differential abundance. Nine known proteins were expressed with differential abundance between study groups. For seven proteins differential abundance is likely to have been on the basis increased hepatic lipid content and/or inflammation. Lumican, a 40‐kDa keratin sulfate proteoglycan that regulates collagen fibril assembly and activates transforming growth factor‐beta and smooth muscle actin, was expressed similarly in obese normal and SS but was overexpressed in a progressive manner in NASH‐mild versus SS (124%, P < 0.001), NASH‐progressive versus NASH‐mild (156%, P < 0.001) and NASH‐progressive versus obese normal (178%, P < 0.001). Fatty acid binding protein‐1 (FABP‐1), which is protective against the detergent effects of excess free fatty acids, facilitates intracellular free fatty acid transport and is an important ligand for peroxisome proliferator‐activated receptor–mediated transcription, was overexpressed in SS when compared to the obese normal group (128%, P < 0.001), but was paradoxically underexpressed in NASH‐mild versus SS (73%, P < 0.001), NASH‐progressive versus NASH‐mild (81%, P < 0.001), and NASH‐progressive versus obese normal (59%, P < 0.001). Conclusion: Histologically progressive NAFLD is associated with overexpression of lumican, an important mediator of fibrosis in nonhepatic tissues, whereas FABP‐1 is paradoxically underexpressed in NASH, suggesting a new potential mechanism of lipotoxicity in NAFLD. Further studies are needed to determine the biologic basis of lumican and/or FABP‐1 dysregulation in NAFLD. (HEPATOLOGY 2009;49:1375–1384.)

Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: an endocrine signature for advanced fibrosis in obese patients.

Liver‐related clinical consequences of non‐alcoholic fatty liver disease (NAFLD) are seen only in the minority of patients with advanced fibrosis. The aim of our study was to generate insight into a potential endocrine basis of steatohepatitis with advanced fibrosis in NAFLD.

Bariatric Surgery in Patients With Cirrhosis With and Without Portal Hypertension: A Single-Center Experience

OBJECTIVE To assess safety and outcomes (metabolic and liver) of bariatric surgery in patients with cirrhosis with or without portal hypertension. PATIENTS AND METHODS This study is a retrospective review of 14 patients with Childs A cirrhosis with or without portal hypertension who were prospectively enrolled from February 23, 2009, through November 9, 2011, with 6- to 24-month follow-up after bariatric surgery (11 patients underwent sleeve gastrectomy [78.6%] and 3 gastric bypass [21.4%]). Four patients had portal hypertension detected by esophagogastroduodenoscopy. RESULTS The mean patient age was 55.5 years, and 10 of 14 patients were women. The mean weight decreased from 125±18 to 94±17 at 1 year (P<.001) and 93±17 kg at 2 years (P<.001) postsurgery. The prevalence of diabetes decreased from 10 of 14 patients to 4 of 12 (P=.01) and 1 of 6 (P=.02) at 1 and 2 years postsurgery. The frequency of dyslipidemia and hypertension decreased but was not statistically significant; however, the number of medications required to control them decreased. Hepatic steatosis was detected by perioperative liver biopsy in 13 of 14 patients (5%-30% steatosis in 6 patients, 31%-60% in 6, and >60% in 1). At 1 year postsurgery, only 1 of 8 patients who underwent follow-up ultrasound imaging showed evidence of steatosis. The bilirubin level was above 2 mg/dL in 1 patient at 1 year postsurgery. One patient had encephalopathy at 2 years postsurgery. None of the patients developed peri- or postoperative bleeding or surgical complications. CONCLUSION Bariatric surgery in patients with compensated cirrhosis even with mild portal hypertension is well tolerated and safe with minimal risk of postoperative complications if performed in a large referral center. This population can experience the beneficial effects of weight loss and improved metabolic syndrome, as well as reduced hepatic steatosis.

Manometric components of the lower esophageal double hump.

Background/Aims: The lower esophageal sphincter manometry of patients with hiatal hernia often displays a double hump configuration. It seems that this is due to gastric herniation above the high-pressure zone of the crura. This study examines this manometric phenomenon in patients with hiatal hernia and relates it to the lower esophageal antireflux barrier. Methods: Manometric and 24-hour pH studies of 68 consecutive patients with suspected gastroesophageal reflux disease were analyzed to obtain information regarding the double hump and acid reflux. Results: The findings of a manometric double hump correlated well with the presence of a hiatal hernia of >5 cm. The overall length of the sphincter complex was greater in patients with a double hump, but the length below the respiratory inversion point was constant. Resting pressures at the respiratory inversion point were significantly lower than those measured at either high-pressure zone. The location of the respiratory inversion point was seen most commonly at the superior margin of the distal high-pressure zone. Double hump patients with a negative acid reflux score were found to have higher pressures in the distal high-pressure zone than those patients with acid reflux. Conclusions: The two high-pressure zones comprising the manometric double hump represent the crural and muscular components of the lower esophageal sphincter. Descriptive information regarding the double hump phenomenon is given, and the importance of the crural component of the lower esophageal sphincter in preventing acid reflux is stressed.

Use of Video Capsule Endoscopy in the Setting of Recurrent Subacute Small-Bowel Obstruction

HYPOTHESIS Video capsule endoscopy (VCE) can be used to diagnose subacute intestinal obstruction in patients with otherwise negative imaging studies. PATIENTS AND METHODS Nine patients with symptoms consistent with intermittent small-bowel obstruction who received a VCE and ultimately required surgical intervention. RESULTS Patients were identified who had symptoms consistent with subacute bowel obstruction and a negative diagnostic work-up prior to VCE. All 9 patients underwent several radiologic and endoscopic examinations with no clear etiology for their symptoms. Ultimately, in every case, a stricture or mass was found to be the cause of the obstruction at either the time of VCE or exploratory laparotomy/laparoscopy. CONCLUSIONS Patients can have a small-bowel stricture or mass that can cause symptoms of subacute small-bowel obstruction. Diagnosis of the lesion may be difficult in these patients and can often result in multiple nondiagnostic radiologic and endoscopic examinations. VCE can be helpful in finding these lesions, leading to surgical resection of the diseased bowel and a cure for the patients signs and symptoms.

Recurrent Wernicke Encephalopathy in an Adolescent Female Following Laparoscopic Gastric Bypass Surgery

In the past 30 years, the prevalence of obesity in American adolescents has more than tripled. In the midst of this epidemic, the number of morbidly obese adolescents who have undergone gastric bypass surgery has also drastically increased. Wernicke encephalopathy (WE) is a known consequence of Roux-en-Y gastric bypass (RYGB) that is well described in the adult literature. Single episodes of WE have been reported in only a few adolescents who have undergone RYGB. Herein we describe an adolescent female who developed recurrent episodes of WE within 1 year of undergoing laparoscopic RYGB.

Inflammatory characteristics of adipose tissue collected by surgical excision vs needle aspiration

Subcutaneous adipose tissue can be obtained for research during an elective, clinically indicated operation by standard surgical excision approaches and by needle aspiration in pure research settings. Whether measurements of inflammatory markers and cells from tissues collected in these two different ways are comparable is debatable. We sought to determine whether these two techniques yield systematically different results for measurements of inflammation, cellular senescence and adipose tissue composition. Twelve subjects undergoing surgery participated. At the time of surgery abdominal subcutaneous adipose tissue from adjacent sites was removed by excision and needle aspiration. Stromovascular cell composition (flow cytometry), the number of senescent cells (senescence-associated-β-galactosidase staining) and interleukin (IL)-6, IL-1, TNF-α and MCP1 mRNA (reverse transcription-PCR) were measured in each sample. We found no statistically significant differences between the two sample-collection approaches for any of the parameters measured. We conclude that these two methods of obtaining adipose tissue do not systematically differ in the results of cytokine mRNA content, cellular senescence or stromovascular cell composition.

Randomized sham-controlled trial of the 6-month swallowable gas-filled intragastric balloon system for weight loss

BACKGROUND Obesity is a significant health problem and additional therapies are needed to improve obesity treatment. OBJECTIVE Determine the efficacy and safety of a 6-month swallowable gas-filled intragastric balloon system for weight loss. SETTING Fifteen academic and private practice centers in the United States. METHODS This was a double-blind, randomized sham-controlled trial of the swallowable gas-filled intragastric balloon system plus lifestyle therapy compared with lifestyle therapy alone for weight loss at 6 months in participants aged 22 to 60 years with body mass index 30 to 40 kg/m2, across 15 sites in the United States. The following endpoints were included: difference in percent total weight loss in treatment group versus control group was >2.1%, and a responder rate of >35% in the treatment group. RESULTS Three hundred eighty-seven patients swallowed at least 1 capsule. Of participants, 93.3% completed all 24 weeks of blinded study testing. Nonserious adverse events occurred in 91.1% of patients, but only .4% were severe. One bleeding ulcer and 1 balloon deflation occurred. In analysis of patients who completed treatment, the treatment and control groups achieved 7.1 ± 5.0% and 3.6 ± 5.1% total weight loss, respectively, and a mean difference of 3.5% (P = .0085). Total weight loss in treatment and control groups were 7.1 ± 5.3 and 3.6 ± 5.1 kg (P < .0001), and body mass index change in the treatment and control groups were 2.5 ± 1.8 and 1.3 ± 1.8 kg/m2 (P < .0001), respectively. The responder rate in the treatment group was 66.7% (P < .0001). Weight loss maintenance in the treatment group was 88.5% at 48 weeks. CONCLUSIONS Treatment with lifestyle therapy and the 6-month swallowable gas-filled intragastric balloon system was safe and resulted in twice as much weight loss compared with a sham control, with high weight loss maintenance at 48 weeks.