Gender disparities in advanced endoscopy fellowship.

Background and study aims Women remain underrepresented in gastroenterology, especially advanced endoscopy. Women represent 30 % of general gastroenterology fellows; yet in 2019, only 12.8 % of fellows who matched into advanced endoscopy fellowship (AEF) programs were women. Methods We administered a web-based survey to the program directors (PDs) of AEF programs that participated in the 2018-2019 American Society for Gastroenterology (ASGE) match. We assessed PD and program characteristics, in addition to perceived barriers and facilitators (scale 1-5, 5 = most important) influencing women pursuing AEF training. Results We received 38 (59.3 %) responses from 64 PDs. 15.8 % (6/38) of AEF PDs and 13.2 % (5/38) of endoscopy chiefs were women. By program, women represented 14.8 % (mean) ± 17.0 % (SD) of AEF faculty and 12.0 % (mean) ± 11.1 % (SD) of AEF trainees over the past 10 years. 47.4 % (18/38) programs reported no female advanced endoscopy faculty and 31.6 % (12/38) of programs have never had a female fellow. Percentage of female fellows was strongly associated with percentage of female AEF faculty (ß = 0.43, P  < 0.001). Inflexible hours and call (mean rank 3.3 ±â€Š1.1), exposure to fluoroscopy (2.9 ±â€Š1.1), lack of women endoscopists at national conferences/courses (2.9 ±â€Š1.1) and lack of female mentorship (2.9 ±â€Š1.0) were cited as the most important barriers to recruitment. Conclusion We utilized a survey of AEF PDs participating in the ASGE match to determine program characteristics and identify contributors to gender disparity. Women represent a minority of AEF PDs, endoscopy chiefs, advanced endoscopy faculty and AEF trainees. Our study highlights perceived barriers and facilitators to recruitment, and emphasizes the importance of having female representation in faculty, and leadership positions in endoscopy.

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.

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.

PEPCK1 Antisense Oligonucleotide Prevents Adiposity and Impairs Hepatic Glycogen Synthesis in High-Fat Male Fed Rats.

The increased hepatic gluconeogenesis in type 2 diabetes mellitus has often been ascribed to increased transcription of phosphoenolpyruvate carboxykinase 1, cystolic form (PEPCK1), although recent evidence has questioned this attribution. To assess the metabolic role of PEPCK1, we treated regular chow fed and high-fat fed (HFF) male Sprague-Dawley rats with a 2'-O-methoxyethyl chimeric antisense oligonucleotide (ASO) against PEPCK1 and compared them with control ASO-treated rats. PEPCK1 ASO effectively decreased PEPCK1 expression in the liver and white adipose tissue. In chow fed rats, PEPCK1 ASO did not alter adiposity, plasma glucose, or insulin. In contrast, PEPCK1 ASO decreased the white adipose tissue mass in HFF rats but without altering basal rates of lipolysis, de novo lipogenesis, or glyceroneogenesis in vivo. Despite the protection from adiposity, hepatic insulin sensitivity was impaired in HFF PEPCK1 ASO-treated rats. PEPCK1 ASO worsened hepatic steatosis, although without additional impairments in hepatic insulin signaling or activation of inflammatory signals in the liver. Instead, the development of hepatic insulin resistance and the decrease in hepatic glycogen synthesis during a hyperglycemic clamp was attributed to a decrease in hepatic glucokinase (GCK) expression and decreased synthesis of glycogen via the direct pathway. The decrease in GCK expression was associated with increased expression of activating transcription factor 3, a negative regulator of GCK transcription. These studies have demonstrated that PEPCK1 is integral to coordinating cellular metabolism in the liver and adipose tissue, although it does not directly effect hepatic glucose production or adipose glyceroneogenesis.

Risk of Suicide and Self-harm Is Increased After Bariatric Surgery-a Systematic Review and Meta-analysis.

BACKGROUND: Bariatric surgery is endorsed by multiple societies as the most effective treatment for obesity. Psychosocial functioning has also been noted to improve for most patients after bariatric surgery. However, some studies have shown an increase in post-operative suicide risk. The aim of this study was to review the published literature and evaluate the association of bariatric surgery with suicide events and suicide/self-harm attempts in patients who have undergone weight loss surgery. METHODS: MEDLINE and Embase were searched from inception through January 2018 for retrospective or prospective studies reporting mortality outcomes and self-harm or suicide rates after bariatric procedures. The primary outcome was the pooled event rate with 95% confidence interval (95% CI) for suicide. Secondary outcomes were suicide/self-harm attempts after bariatric surgery compared to same population prior to surgery and to matched control subjects, with the respective calculated odds ratios (OR) and 95% CI. RESULTS: From 227 citations, 32 studies with 148,643 subjects were eligible for inclusion. The patients were predominantly females (76.9%). Roux-en-Y gastric bypass (RYGB) was the most commonly performed procedure (58.9%). The post-bariatric suicide event rate was 2.7/1000 patients (95% CI 0.0019-0.0038), while the suicide/self-harm attempt event rate was 17/1000 patients (95% CI 0.01-0.03). The self-harm/suicide attempt risk was higher after bariatric surgery within the same population with OR of 1.9 (95% CI 1.23-2.95), and compared to matched control subjects, OR 3.8 (95% CI, 2.19-6.59). CONCLUSIONS: Post-bariatric surgery patients had higher self-harm/suicide attempt risk compared to age-, sex-, and BMI-matched controls. Various pre- and post-surgical psychosocial, pharmacokinetic, physiologic, and medical factors may be involved.

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.

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.

Effectiveness of intragastric balloon for obesity: A systematic review and meta-analysis based on randomized control trials.

BACKGROUND: Obesity has become a worldwide epidemic, and many methods are currently used to reduce obesity. This systematic review shows the effectiveness of the intragastric balloon (IGB) method compared to the sham/diet (s/d) method. OBJECTIVE: To demonstrate the effectiveness of the IGB method compared to the s/d method. SETTING: Hospital das Clinicas da Universidade de São Paulo, Brazil, Public Hospital. METHODS: After searching MEDLINE, Embase, Cochrane, Lilacs, Scopus, and CINAHL, only enrolled randomized control trials comparing IGB/diet with s/d were analyzed. For qualitative analysis, 12 studies were selected, and 9 of these were acceptable for quantitative analysis. RESULTS: The IGB/diet is more effective than s/d when comparing body mass index (BMI) loss with a mean difference of 1.1 kg/m(2) by the Student's t test and 1.41 kg/m(2) by the meta-analysis, with significant differences in both. It is also more effective in weight loss (WL), with a mean difference of 2 kg by the Student's t test and 3.55 kg by the meta-analysis. In the qualitative analysis of % excess WL (%EWL), the mean %EWL is 14.0% in favor of the IGB group compared to the s/d group by the Student's t test; however, no significant difference was found between these groups by quantitative analysis. CONCLUSION: Based on randomized control trial data alone, IGB>400 mL is more effective than sham/diet in achieving BMI loss, WL, and %EWL.

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.

Treatment of Nonalcoholic Fatty Liver Disease: The Role of Medical, Surgical, and Endoscopic Weight Loss.

Nonalcoholic fatty liver disease (NAFLD) represents a rapidly growing cause of chronic liver disease in the United States and is associated with significant morbidity and mortality, including progression to liver cirrhosis and hepatocellular carcinoma. NAFLD comprises a spectrum of liver conditions, ranging from simple steatosis to steatosis with inflammation (steatohepatitis) and progressive fibrosis. Weight loss represents a first line therapeutic modality for the management of NAFLD. Herein, we review the evidence base for medical, surgical, and endoscopic approaches to weight loss and their potential impact on the natural history of NAFLD.

Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler.

Nonalcoholic fatty liver disease (NAFLD) affects one in three Americans and is a major predisposing condition for the metabolic syndrome and type 2 diabetes (T2D). We examined whether a functionally liver-targeted derivative of 2,4-dinitrophenol (DNP), DNP-methyl ether (DNPME), could safely decrease hypertriglyceridemia, NAFLD, and insulin resistance without systemic toxicities. Treatment with DNPME reversed hypertriglyceridemia, fatty liver, and whole-body insulin resistance in high-fat-fed rats and decreased hyperglycemia in a rat model of T2D with a wide therapeutic index. The reversal of liver and muscle insulin resistance was associated with reductions in tissue diacylglycerol content and reductions in protein kinase C epsilon (PKCε) and PKCθ activity in liver and muscle, respectively. These results demonstrate that the beneficial effects of DNP on hypertriglyceridemia, fatty liver, and insulin resistance can be dissociated from systemic toxicities and suggest the potential utility of liver-targeted mitochondrial uncoupling agents for the treatment of hypertriglyceridemia, NAFLD, metabolic syndrome, and T2D.