Adjustable intragastric balloon for treatment of obesity: a multicentre, open-label, randomised clinical trial.

BACKGROUND: Intragastric balloons are anatomy-preserving, minimally invasive obesity therapies. Enhanced tolerance and durability could help broaden clinical adoption. We investigated the safety and efficacy of an adjustable intragastric balloon (aIGB) in adults with obesity. METHODS: In this prospective, multicentre, open-label, randomised clinical trial done at seven US sites, adults aged 22-65 years with obesity were randomly assigned (2:1) to aIGB with lifestyle intervention or lifestyle intervention alone (control) for 32 weeks. Balloon volume could be increased to facilitate weight loss or decreased for tolerability. Coprimary endpoints included mean percentage total bodyweight loss and responder rate (≥5% total bodyweight loss) at 32 weeks. We used a multiple imputed intention-to-treat population analysis. This study was registered with ClinicalTrials.gov, NCT02812160. FINDINGS: Between Aug 9, 2016, and Dec 7, 2018, we randomly assigned 288 patients to aIGB (n=187 [65%]) or control (n=101 [35%]) groups. Mean total bodyweight loss at 32 weeks was 15·0% (95% CI 13·9-16·1) in the aIGB group versus 3·3% (2·0-4·6) in the control group (p<0·0001). Clinical response was observed in 171 (92%) patients in the aIGB group. Adjustments to the aIGB occurred in 145 (80%) patients for weight loss plateau or intolerance. Upward volume adjustment facilitated an additional mean 5·2% (4·5-5·8) total bodyweight loss. Downward volume adjustment allowed 21 (75%) patients in the aIGB group to complete the full duration of therapy. Intolerance caused early removal of the device in 31 (17%) patients. No micronutrient deficiencies were observed in the aIGB cohort. Device-related serious adverse events were observed in seven (4%) patients, without any deaths. INTERPRETATION: When aIGB was combined with lifestyle modification, significant weight loss was achieved and maintained for 6 months following removal. Balloon volume adjustability permitted individualised therapy, maximising weight loss and tolerance. FUNDING: Spatz Medical.

Increased Sessile Serrated Adenoma Detection Rate With Mechanical New Technology Devices: A Systematic Review and Meta-Analysis.

GOAL: This meta-analysis aims to compare the sessile-serrated adenoma detection rate (SSADR) of currently available mechanical new technology devices (NTDs) to conventional colonoscopy (CC). BACKGROUND: NTDs including Endocuff, EndoRing, G-Eye, and AmplifEYE were developed with the aim of improving adenoma detection rate by enhancing colonic mucosal visualization. Increasing awareness of the risk of sessile-serrated adenoma progression to malignancy has ushered a need to increase the detection of these characteristically flat lesions. STUDY: Embase and PubMed/Medline databases were searched from inception through January 2019 for published manuscripts or major conference abstracts reporting SSADR with Endocuff, EndoRing, G-Eye, AmplifEYE, and CC. Randomized controlled trials, high-quality case-control, cohort, and observational studies in adults with >10 subjects were included. The primary outcome was pooled SSADR odds ratio (ORs) with 95% confidence interval (95% CI) comparing CC with the NTDs. In addition, an analysis comparing each device to CC was performed. RESULTS: Of 207 citations identified, a total of 14 studies with 12,655 subjects were included in our analysis (5931 subjects with NTDs and 6724 with CC). There were 12 studies with Endocuff, 2 with EndoRing, 1 with G-EYE, and 1 with AmplifEYE. The mean age was 62.4 years and 57.5% were males. Pooled SSADR with NTDs was 12.3% as compared with 6.4% with CC, with an OR of 1.81 (95% CI: 1.6-2.0, I2: 77%). Analysis of Endocuff alone yielded an OR 1.81 (95% CI: 1.6-2.1, I2: 79%). CONCLUSION: Mechanical NTDs, notably Endocuff, are a safe and effective tool to increase the SSADR.

Endoscopic part-task training box scores correlate with endoscopic outcomes.

BACKGROUND: Competency in endoscopy has traditionally been based on number of procedures performed. With movement towards milestone-based accreditation, new standards of establishing competency are required. The Thompson Endoscopic Skills Trainer (TEST) is a training device previously shown to differentiate between novice and expert endoscopists. This study aims to correlate TEST scores to other markers of performance in endoscopy. METHODS: Trainees of a gastroenterology fellowship program were guided through the TEST. Their scores and sub-scores were correlated to their endoscopic metrics of performance, including adenoma detection rate, cecal intubation rate, cecal intubation time, withdrawal time, fentanyl usage, midazolam usage, pain score, overall procedure time, and performance on the ASGE Assessment of Competency in Endoscopy Tool (ACE Tool). RESULTS: The Overall Score positively correlated with the ACE Tool Total Score (r = 0.707, p = 0.010) and sub-scores (Cognitive Skills Score: r = 0.624, p = 0.030; Motor Skills Score: r = 0.756, p = 0.004), and negatively correlated with cecal intubation time (r = - 0.591, p = 0.043). The Gross Motor Score positively correlated with cecal intubation rate (r = 0.593, p = 0.042), ACE Tool Total Score (r = 0.594, p = 0.042) and Motor Skills Score (r = 0.623, p = 0.031), and negatively correlated with cecal intubation time (r = - 0.695, p = 0.012). The Fine Motor Score positively correlated with the ACE Tool Polypectomy Score (r = 0.601, p = 0.039), and negatively correlated with procedure time (r = - 0.640, p = 0.025), cecal intubation time (r = - 0.645, p = 0.024), and withdrawal time (r = - 0.629, p = 0.028). CONCLUSION: This study demonstrates that performance on the TEST correlate to endoscopic measures. Given these results, the TEST may be used in conjunction with existing assessment tools for demonstrating competency in endoscopy.

Ustekinumab Does Not Increase Risk of Adverse Events: A Meta-Analysis of Randomized Controlled Trials.

GOALS AND BACKGROUND: Ustekinumab (UST) is a monoclonal antibody inhibitor of IL-12/IL-23 approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We conducted a meta-analysis to compare rates of adverse events (AEs) in randomized controlled trials (RCTs) of UST for all indications. STUDY: A systematic search was performed of MEDLINE, Embase, and PubMed databases through November 2019. Study inclusion included RCTs comparing UST to placebo or other biologics in patients aged 18 years or older with a diagnosis of an autoimmune condition. RESULTS: Thirty RCTs with 16,068 patients were included in our analysis. Nine thousand six hundred and twenty-six subjects were included in the UST vs placebo analysis. There was no significant difference in serious or mild/moderate AEs between UST and placebo with an OR of 0.83 (95% CI 0.66, 1.05) and 1.08 (95% CI 0.99, 1.18), respectively, over a median follow-up time of 16 weeks. In a sub-analysis of CD and UC trials, no difference in serious or mild/moderate AEs in UST versus placebo was seen. CONCLUSIONS: UST was not associated with an increase in short-term risk of AEs.

Endoscopic balloon dilation for treatment of sleeve gastrectomy stenosis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Gastric stenosis is a rare but potentially serious adverse event after sleeve gastrectomy. Despite current suboptimal treatments, endoscopic balloon dilatation (EBD) has emerged as a safe and efficacious approach. The purpose of this study is to assess the overall success of EBD for sleeve gastrectomy stenosis (SGS) as first-line therapy. METHODS: MEDLINE, Embase, Web of Science, Google Scholar, and Cochrane Database were searched from inception to July 2018. The primary outcome was defined as overall success rate of clinical resolution of SGS obstructive symptoms with EBD, expressed as pooled event rate and 95% confidence interval (CI). The secondary predefined outcomes include EBD success rates for SGS in the proximal (cardia) location or mid-distal location (antrum/incisura), in early SGS (up to 3 months after laparoscopic sleeve gastrectomy), and late SGS (3 months or longer after laparoscopic sleeve gastrectomy) and success rate of cases requiring stents or salvage surgery. RESULTS: Eighteen studies encompassing 426 patients were analyzed. The average age and body mass index were 41.7 years and 40.1 kg/m2, respectively, and the average number of dilations for all cases was 1.8 per person. Overall EBD success rate was 76% (95% CI, .67-.86). EBD success rate in the proximal SGS was 90% (95% CI, 63%-98%), distal SGS was 70% (95% CI, 47%-86%), early SGS within 3 months was 59% (95% CI, 34%-79%), and late SGS after 3 months was 61% (95% CI, 41%-78%). Seventeen percent of patients underwent secondary salvage surgery, with a success rate of 91% (95% CI, 80%-96%). CONCLUSIONS: Endoscopic balloon dilation appears to be a safe and effective minimally invasive alternative to surgical revision and should be used as first-line therapy for SGS.

New technologies improve adenoma detection rate, adenoma miss rate, and polyp detection rate: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The need to increase the adenoma detection rate (ADR) for colorectal cancer screening has ushered in devices that mechanically or optically improve conventional colonoscopy. Recently, new technology devices (NTDs) have become available. We aimed to compare the ADR, polyp detection rate (PDR), and adenoma miss rate (AMR) between NTDs and conventional colonoscopy and between mechanical and optical NTDs. METHODS: MEDLINE and Embase databases were searched from inception through September 2017 for articles or abstracts reporting ADR, PDR, and AMR with NTDs. Randomized controlled trials and case-control studies with >10 subjects were included. Primary outcomes included ADR, PDR, and AMR odds ratio (OR) between conventional colonoscopy and NTDs. Secondary outcomes included cecal intubation rates, adverse events, cecal intubation time, and total colonoscopy time. RESULTS: From 141 citations, 45 studies with 20,887 subjects were eligible for ≥1 analyses. Overall, the ORs for ADR (1.35; 95% confidence interval [CI] 1.24-1.47; P < .01) and PDR (1.51; 95% CI, 1.37-1.67; P < .01) were higher with NTDs. Higher ADR (OR, 1.52 vs 1.25; P = .035) and PDR (OR, 1.63 vs 1.10; P ≤ .01) were observed with mechanical NTDs. The overall AMR with NTDs was lower compared with conventional colonoscopy (OR, .19; 95% CI, .14-.26; P < .01). Mechanical NTDs had lower AMRs compared with optical NTDs (OR, .10 vs .33; P < .01). No differences in cecal intubation rates, cecal intubation time, or total colonoscopy time were found. CONCLUSIONS: Newer endoscopic technologies are an effective option to improve ADR and PDR and decrease AMR, particularly with mechanical NTDs. No differences in operability and safety were found.

The Impact of Intragastric Balloons on Obesity-Related Co-Morbidities: A Systematic Review and Meta-Analysis.

ObjectivesTherapies less invasive than surgery and more effective than lifestyle and pharmacotherapy are needed to contend with the obesity epidemic. Intragastric balloons (IGBs) are a minimally invasive endoscopic weight loss method recently approved for use in the US. The purpose of the study is to assess the effect of IGBs on metabolic outcomes associated with obesity.MethodsMEDLINE, Embase, and Cochrane Database were searched through July 2016. Dual extraction and quality assessment of studies using Cochrane risk of bias tool were performed independently by two authors. Primary outcomes included the change from baseline in metabolic parameters. Secondary outcomes included resolution and/or improvement in metabolic co-morbidities and association with baseline parameters.Results10 randomized controlled trials (RCT) and 30 observational studies including 5,668 subjects were analyzed. There was moderate-quality evidence for improvement in most metabolic parameters in subjects assigned to IGB therapy as compared to conventional non-surgical therapy in RCTs: mean difference (MD) in fasting glucose change: -12.7 mg/dl (95% confidence interval (CI) -21.5, -4); MD in triglycerides: -19 mg/dl (95% CI -42, 3.5); MD in waist circumference: -4.1 cm (95% CI -6.9, -1.4); MD in diastolic blood pressure: -2.9 mm Hg (95% CI -4.1, -1.8). The odds ratio for diabetes resolution after IGB therapy was 1.4 (95% CI 1.3, 1.6). The rate of serious adverse events was 1.3%.ConclusionsIGBs are more effective than diet in improving obesity-related metabolic risk factors with a low rate of adverse effects, however the strength of the evidence is limited given the small number of participants and lack of long-term follow-up.

Second-generation antisense oligonucleotides against ß-catenin protect mice against diet-induced hepatic steatosis and hepatic and peripheral insulin resistance.

Although mutations in the Wnt/ß-catenin signaling pathway are linked with the metabolic syndrome and type 2 diabetes in humans, the mechanism is unclear. High-fat-fed male C57BL/6 mice were treated for 4 wk with a 2'-O-methoxyethyl chimeric antisense oligonucleotide (ASO) to decrease hepatic and adipose expression of ß-catenin. ß-Catenin mRNA decreased by ≈80% in the liver and by 70% in white adipose tissue relative to control ASO-treated mice. ß-Catenin ASO improved hepatic insulin sensitivity and increased insulin-stimulated whole body glucose metabolism, as assessed during hyperinsulinemic-euglycemic clamp in awake mice. ß-Catenin ASO altered hepatic lipid composition in high-fat-fed mice. There were reductions in hepatic triglyceride (44%, P < 0.05) and diacylglycerol content (60%, P < 0.01) but a 30% increase in ceramide content (P < 0.001). The altered lipid content was attributed to decreased expression of sn-1,2 diacylglycerol acyltransferase and mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase and an increase in serine palmitoyl transferase. The decrease in cellular diacyglycerol was associated with a 33% decrease in PKCε activation (P < 0.05) and 64% increase in Akt2 phosphorylation (P < 0.05). In summary, Reducing ß-catenin expression decreases expression of enzymes involved in hepatic fatty acid esterification, ameliorates hepatic steatosis and lipid-induced insulin resistance.

Randomized sham-controlled trials in endoscopy: a systematic review and meta-analysis of adverse events.

BACKGROUND AND AIMS: Sham procedures in endoscopy are used with the intention of controlling for placebo response, potentially allowing more precise evaluation of treatment effect. Nevertheless, this type of study may impose significant risk without potential benefit for those in the sham group. The aim of the current study was to systematically review and analyze the endoscopic literature to assess the safety of sham controls. METHODS: MEDLINE and Embase databases were searched for endoscopic sham procedures for all dates to July 2017. Only randomized controlled trials comparing an endoscopic therapy with a sham were included. Primary outcome was adverse events (AEs) categorized as mild, moderate, or severe. Results were combined using a random-effects model. Heterogeneity was assessed with the I2 statistic, and publication bias was assessed with the Egger test and funnel plots. RESULTS: Data were extracted from 34 publications (1987-2017; 100% full text), with a total of 2492 procedures (1355 treatment/1137 sham). Sham procedures involved upper endoscopy (31 studies) and ERCP (3 studies). Treatment arms included procedures with the following indications: weight loss (38.2%), GI bleeding (26.5%), GERD (20.6%), sphincter of Oddi dysfunction (8.8%), and dysphagia (6.2%). Overall percentage of severe adverse events (SAEs) in the sham group was 1.7% (19/1137). Of these, the most common SAEs in the sham groups were need for surgery/intensive care unit stay (35.3%), post-ERCP pancreatitis (23.5%), and perforation (11.8%). There was no significant difference in the odds of developing an SAE between the treatment group and the sham group (odds ratio, 1.3; 95% confidence interval [CI], 0.7-2.3). The pooled additional risk incurred from being initially randomized to the sham arm and then receiving a cross-over intervention was significant (RR, 1.33; 95% CI, 1.14-1.56; P < .001), compared with patients initially randomized to the study intervention. CONCLUSION: The frequency of AEs in endoscopic sham procedures is substantial, and patients are subjected to considerable morbidity. These results raise a serious ethical dilemma regarding the use of sham-controlled trials.

Effect of Intragastric Balloons on Liver Enzymes: A Systematic Review and Meta-Analysis.

BACKGROUND: Intragastric balloons (IGBs) are safe and effective in inducing weight loss in obese patients. The objective of this study was to review and analyze the available data of the effect of IGB on markers of nonalcoholic fatty liver disease (NAFLD) and liver enzymes. METHODS: Searches were performed of MEDLINE and Embase databases from inception through January 2016. Study inclusion criteria were the following: ≥5 overweight or obese adult patients undergoing intragastric balloon placement, with liver tests [alanine aminotransferase (ALT) or gamma-glutamyl transpeptidase (GGT)] or markers of NAFLD (e.g., imaging, biopsy) reported before balloon insertion and after balloon removal at 6 months. RESULTS: Nine observational studies and one randomized trial were identified. ALT decreased by -10.02 U/l (95 % CI, -13.2, -6.8), GGT decreased by -9.82 U/l (95 % CI, -12.9, -6.8), and BMI decreased by -4.98 kg/m(2) (-5.6, -4.4) with IGB therapy. Hepatic steatosis improved from baseline after 6 months of balloon therapy by magnetic resonance imaging (fat fraction, 16.7 ± 10.9-7.6 ± 9.8, p = 0.003), ultrasound (severe liver steatosis, 52-4 %, p < 0.0001). Histological NAFLD activity score was lower after 6 months of IGB versus control with sham endoscopy and diet (2 ± 0.75 vs. 4 ± 2.25, p = 0.03). CONCLUSION: The use of intragastric balloon decreases liver enzymes and is potentially an effective short-term treatment for NAFLD as part of a multidisciplinary approach. Larger, more rigorous trials are needed to confirm the effect of IGBs on NAFLD.

Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) and insulin resistance have recently been found to be associated with increased plasma concentrations of apolipoprotein CIII (APOC3) in humans carrying single nucleotide polymorphisms within the insulin response element of the APOC3 gene. To examine whether increased expression of APOC3 would predispose mice to NAFLD and hepatic insulin resistance, human APOC3 overexpressing (ApoC3Tg) mice were metabolically phenotyped following either a regular chow or high-fat diet (HFD). After HFD feeding, ApoC3Tg mice had increased hepatic triglyceride accumulation, which was associated with cellular ballooning and inflammatory changes. ApoC3Tg mice also manifested severe hepatic insulin resistance assessed by a hyperinsulinemic-euglycemic clamp, which could mostly be attributed to increased hepatic diacylglycerol content, protein kinase C-ϵ activation, and decreased insulin-stimulated Akt2 activity. Increased hepatic triglyceride content in the HFD-fed ApoC3Tg mice could be attributed to a ≈ 70% increase in hepatic triglyceride uptake and ≈ 50% reduction hepatic triglyceride secretion. CONCLUSION: These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance.

Acute Liver Failure Secondary to Remdesivir in the Treatment of COVID-19.

Remdesivir has been the mainstay of coronavirus disease 2019 treatment since the start of the severe acute respiratory syndrome coronavirus 2 pandemic. Despite its growing use, safety data are limited. We present the case of an elderly man with obesity and coronavirus disease 2019 who developed acute liver failure after initiation of remdesivir. This report broadens our knowledge of the side effect profile of remdesivir and discusses potential risk factors and an approach to remdesivir-induced liver failure. Our case also highlights the importance of monitoring hepatic function after initiation of therapy with remdesivir.

The impact of anthropometric parameters on colorectal cancer prognosis: A systematic review and meta-analysis.

BACKGROUND & AIMS: Our study aims to clarify the relationship between weight parameters and colorectal cancer outcomes. METHODS: NCBI, Embase, Cochrane, and Web of Science were searched from inception to December 2019. Studies reporting colorectal cancer (CRC) mortality, recurrence, disease-free survival, overall survival, overall mortality stratified by pre-diagnosis BMI or post-diagnosis weight change, were included in the analysis. Random effects analysis was performed for all outcomes, with heterogeneity assessed by the I2 statistic. RESULTS: Our meta-analysis included 45 studies encompassing 607,266 patients. Obesity was associated with increased odds of overall mortality and CRC-specific mortality compared to normal weight (p < 0.001). Patients with underweight BMI had increased odds of CRC-specific mortality compared to normal BMI but were not significantly different from obese BMI. CONCLUSIONS: Obese and underweight BMI are associated with increased CRC-specific and overall mortality compared to normal BMI. Long term prognosis was similar for patients with obese and underweight BMI.

The Impact of Bariatric Surgery Compared to Metformin Therapy on Pregnancy Outcomes in Patients with Polycystic Ovarian Syndrome: a Systematic Review and Meta-analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a leading cause of infertility among women of reproductive age. The interplay between hyperinsulinemia and obesity results in many of the reproductive and hormonal changes seen in PCOS including abnormal menses, infertility, and pregnancy loss. While bariatric surgery has been found to be an effective treatment strategy for morbid obesity, its role in the management of PCOS-related infertility compared to standard therapy (metformin) is less clear. AIMS: To assess the impact of bariatric surgery on pregnancy outcomes in women with PCOS compared to metformin therapy in a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, PubMed, and Google Scholar were searched from inception to August 2019. Studies that reported quantitative data on pregnancy outcomes on women of reproductive age with PCOS with at least a 3-month follow-up and a minimum of 5 or more sample size were included. The primary outcome was pregnancy rate, expressed as an event rate and 95% confidence interval (95% CI). RESULTS: Ten studies with a total of 587 patients were included in the final analyses (Metformin: 5 studies, n = 192; Bariatric surgery (BS): 5 studies (2 Roux-en-Y gastric bypass, 2 sleeve gastrectomy, 1 Roux-en-Y gastric bypass + sleeve gastrectomy), n = 186). The average time to follow-up was 18.25 months (range 3-36) with a shorter time to follow-up in the metformin group compared to the bariatric surgery group (Metformin: 11.2 vs BS: 24.5 months). While metformin increased the likelihood of pregnancy compared to placebo or non-surgical interventions (OR = 3.08, 95% CI 1.29-7.37, p = 0.01), the pregnancy rate after bariatric surgery was greater than metformin (34.9%, 95% CI 0.20-0.53 vs 17.1%, 95% CI 0.12-0.23, p = 0.026 for the difference). Additionally, there was a trend to a greater improvement in menstrual irregularity in the bariatric group compared to the metformin group with a reduction of 92% in the bariatric cohort compared to a reduction of 54% in the metformin cohort, but the data was limited. CONCLUSION: Bariatric surgery appears to be a more effective treatment strategy for patients with PCOS and class 3 obesity compared to metformin alone. Women with PCOS and infertility should consider bariatric surgery for weight loss and improvement in pregnancy outcomes.

Intragastric Balloon Improves Steatohepatitis and Fibrosis.

Obesity is a major risk factor for nonalcoholic steatohepatitis (NASH). Although weight loss has been shown to reverse histologic features of NASH, lifestyle intervention alone is often challenging and unfeasible. In this case report, we discuss the effects of intragastric balloon (IGB) therapy on steatosis, fibrosis, and portal pressures. We also demonstrate that improvement in histologic features persist at least 6 months after IGB removal. Although there are little data thus far to support IGB therapy in the treatment of NASH, our case provides evidence of the potential benefit of IGB on improving metabolic parameters and markers of liver fibrosis.