Gag proteins encoded by endogenous retroviruses are required for zebrafish development.

Transposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound of TE-derived sequences repurposed for organismal function. The process by which TEs become coopted remains obscure because most cases involve ancient, transpositionally inactive elements. Reports of active TEs serving beneficial functions are scarce and often contentious due to difficulties in manipulating repetitive sequences. Here we show that recently active TEs in zebrafish encode products critical for embryonic development. Knockdown and rescue experiments demonstrate that the endogenous retrovirus family BHIKHARI-1 (Bik-1) encodes a Gag protein essential for mesoderm development. Mechanistically, Bik-1 Gag associates with the cell membrane and its ectopic expression in chicken embryos alters cell migration. Similarly, depletion of BHIKHARI-2 Gag, a relative of Bik-1, causes defects in neural crest development in zebrafish. We propose an "addiction" model to explain how active TEs can be integrated into conserved developmental processes.

Increased rate of pancreatitis in gender diverse and transgender patients on hormone therapy: a case series study.

BACKGROUND: There is limited data on the incidence of gastrointestinal-specific pathology in gender non-conforming (GNC) populations. METHODS: Retrospective analysis of pancreatitis incidence rates in transgender and GNC persons exposed and not exposed to gender-affirming hormone therapy (GAHT). RESULTS: 7 of the 1333 patients on hormone therapy had an incidence of pancreatitis. 0 of the 615 patients with no history of GAHT use developed pancreatitis. Representing a 6.96 (95% CI 2.76 to 848.78) for the development of pancreatitis in patients with exposure to GAHT therapy. CONCLUSION: Clinicians working with GNC individuals should be aware of this possible association.

Associations between income and survival in cholangiocarcinoma: A comprehensive subtype-based analysis.

Backgrounds/Aims: Socioeconomic determinants of health are incompletely characterized in cholangiocarcinoma (CCA). We assessed how socioeconomic status influences initial treatment decisions and survival outcomes in patients with CCA, additionally performing multiple sub-analyses based on anatomic location of the primary tumor. Methods: Observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results (SEER)-18 Database. In total, 5,476 patients from 2004-2015 with a CCA were separated based on median household income (MHI) into low income (< 25th percentile of MHI) and high income (> 25th percentile of MHI) groups. Seventy-three percent of patients had complete follow up data, and were included in survival analyses. Survival and treatment outcomes were calculated using R-studio. Results: When all cases of CCA were included, the high-income group was more likely than the low-income to receive surgery, chemotherapy, and local tumor destruction modalities. Initial treatment modality based on income differed significantly between tumor locations. Patients of lower income had higher overall and cancer-specific mortality at 2 and 5 years. Non-cancer mortality was similar between the groups. Survival differences identified in the overall cohort were maintained in the intrahepatic CCA subgroup. No differences between income groups were noted in cancer-specific or overall mortality for perihilar tumors, with variable differences in the distal cohort. Conclusions: Lower income was associated with higher rates of cancer-specific mortality and lower rates of surgical resection in CCA. There were significant differences in treatment selection and outcomes between intrahepatic, perihilar, and distal tumors. Population- based strategies aimed at identifying possible etiologies for these disparities are paramount to improving patient outcomes.

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Assessment of Pathology Domain-Specific Knowledge of ChatGPT and Comparison to Human Performance.

CONTEXT.­: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. OBJECTIVES.­: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. DESIGN.­: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist that recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. RESULTS.­: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. CONCLUSIONS.­: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training.

AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Rapid Clinical Practice Update (CPU) Communication is to review the available evidence and provide expert advice regarding the evolving management of patients taking GLP-1 receptor agonists prior to endoscopy. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in this field, and it reflects the experiences of the authors who are experts in bariatric medicine and/or endoscopy.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasia in close proximity to esophageal varices: a multicenter international experience.

BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients. METHODS: This multicenter retrospective study included cirrhotic patients with a history of esophageal varices with SEN located at or adjacent to the esophageal varices who underwent ESD. RESULTS: 23 patients with SEN (median lesion size 30 mm; 16 squamous cell neoplasia and seven Barrett's esophagus-related neoplasia) were included. The majority were Child-Pugh B (57 %) and had small esophageal varices (87 %). En bloc, R0, and curative resections were achieved in 22 (96 %), 21 (91 %), and 19 (83 %) of patients, respectively. Severe intraprocedural bleeding (n = 1) and delayed bleeding (n = 1) were successfully treated endoscopically. No delayed perforation, hepatic decompensation, or deaths were observed. During a median (interquartile range) follow-up of 36 (22-55) months, one case of local recurrence occurred after noncurative resection. CONCLUSION: ESD is feasible and effective for SEN located at or adjacent to esophageal varices in cirrhotic patients. Albeit, the majority of the esophageal varices in our study were small in size, when expertise is available, ESD should be considered as a viable option for such patients.

Development and initial validation of a video-based peroral endoscopic myotomy assessment tool.

BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.

AGA Clinical Practice Update on Gastric Peroral Endoscopic Myotomy for Gastroparesis: Commentary.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding cognitive, procedural, and post-procedural aspects of performing gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are advanced endoscopists with expertise in treating patients by performing third-space endoscopy and gastric peroral endoscopic myotomy.

Socioeconomic Disparities Affect Outcomes in Early-Stage Esophageal Adenocarcinoma: A SEER Analysis.

BACKGROUND & AIMS: Socioeconomic determinants of health are understudied in early stage esophageal adenocarcinoma. We aimed to assess how socioeconomic status influences initial treatment decisions and survival outcomes in patients with T1a esophageal adenocarcinoma. METHODS: We performed an observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results-18 database. A total of 1526 patients from 2004 to 2015 with a primary T1aN0M0 esophageal adenocarcinoma were subdivided into 3 socioeconomic tertiles based on their median household income. Endoscopic trends over time, rates of endoscopic and surgical treatment, 2- and 5-year overall survival, cancer-specific mortality, and non-cancer-specific mortality were calculated. Statistical analysis was performed using R-studio. RESULTS: Patients within the lowest median household income tertile ($20,000-$54,390) were associated with higher cancer-specific mortality at 2 years (P < .01) and 5 years (P < .02), and lower overall survival at 2 and 5 years (P < .01) compared with patients in higher income tertiles. Patients with a higher income had a decreased hazard ratio for cancer-specific mortality (hazard ratio, 0.66; 95% CI, 0.45-0.99) in a multivariate Cox proportional hazards regression model. Patients within the higher income tertile were more likely to receive endoscopic intervention (P < .001), which was associated with improved cancer-specific mortality compared with patients who received primary surgical intervention (P = .001). The South had lower rates of endoscopy compared with other regions. CONCLUSIONS: Lower median household income was associated with higher rates of cancer-specific mortality and lower rates of endoscopic resection in T1aN0M0 esophageal adenocarcinoma. Population-based strategies aimed at identifying and rectifying possible etiologies for these socioeconomic and geographic disparities are paramount to improving patient outcomes in early esophageal cancer.

ACG Clinical Guideline: Diagnosis and Management of Biliary Strictures.

A biliary stricture is an abnormal narrowing in the ductal drainage system of the liver that can result in clinically and physiologically relevant obstruction to the flow of bile. The most common and ominous etiology is malignancy, underscoring the importance of a high index of suspicion in the evaluation of this condition. The goals of care in patients with a biliary stricture are confirming or excluding malignancy (diagnosis) and reestablishing flow of bile to the duodenum (drainage); the approach to diagnosis and drainage varies according to anatomic location (extrahepatic vs perihilar). For extrahepatic strictures, endoscopic ultrasound-guided tissue acquisition is highly accurate and has become the diagnostic mainstay. In contrast, the diagnosis of perihilar strictures remains a challenge. Similarly, the drainage of extrahepatic strictures tends to be more straightforward and safer and less controversial than that of perihilar strictures. Recent evidence has provided some clarity in multiple important areas pertaining to biliary strictures, whereas several remaining controversies require additional research. The goal of this guideline is to provide practicing clinicians with the most evidence-based guidance on the approach to patients with extrahepatic and perihilar strictures, focusing on diagnosis and drainage.

Endoscopic Sleeve Gastroplasty: A Safe Bariatric Intervention for Class III Obesity (BMI > 40).

PURPOSE: Endoscopic sleeve gastroplasty (ESG) is primarily offered to patients with class I and II obesity (BMI 30-40), although there are no guidelines specifying applicability. There is little data comparing ESG to bariatric surgery in patients with class III obesity (BMI > 40). This study evaluates the short-term safety of ESG compared to sleeve gastrectomy (SG) and gastric bypass (RYGB) in patients with class III obesity. METHODS: We retrospectively analyzed over 500,000 patients who underwent ESG, SG, and RNYGB from 2016 to 2020 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. ESG patients were stratified by BMI to compare outcomes between class I and II versus class III obese patients. Class III obese patients who underwent ESG were also propensity matched to SG and RNYGB patients for matched comparisons. Primary outcomes included adverse events (AE), readmissions, re-operations, and re-interventions within 30 days. Secondary outcomes included procedure time, length of stay (LOS), and total body weight loss (%TBWL) at 30 days. RESULTS: Among ESG patients, those with BMI > 40 had no difference in AE, readmissions, or re-interventions versus patients with BMI 30-40 (p > 0.05), while achieving greater %TBWL at 30 days (p < 0.05). In comparison to surgery, ESG had similar AE to SG and less than RNYGB, while producing comparable %TBWL to SG and RNYGB at 30 days. CONCLUSIONS: The feasibility and safety of ESG in patients with class III obesity are comparable to patients with class I and II obesity. Additionally, the safety of ESG in patients with class III obesity is comparable to SG and safer than RYGB. Endoscopic sleeve gastroplasty: a safe bariatric intervention for class III obesity (BMI > 40).

Comparison of endoscopic sleeve gastroplasty versus surgical sleeve gastrectomy: a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database analysis.

BACKGROUND AND AIMS: Endoscopic sleeve gastroplasty (ESG) is an incisionless, transoral, restrictive bariatric procedure designed to imitate sleeve gastrectomy (SG). Comparative studies and large-scale population-based data are limited. Additionally, no studies have examined the impact of race on outcomes after ESG. This study aims to compare short-term outcomes of ESG with SG and evaluate racial effects on short-term outcomes after ESG. METHODS: We retrospectively analyzed over 600,000 patients in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database from 2016 to 2020. We compared occurrences of adverse events (AEs), readmissions, reoperations, and reinterventions within 30 days after procedures. Multivariate regression evaluated the impact of patient factors, including race, on AEs. RESULTS: A total of 6054 patients underwent ESG and 597,463 underwent SG. AEs were low after both procedures with no significant difference in major AEs (SG vs ESG: 1.1% vs 1.4%; P > .05). However, patients undergoing ESG had more readmissions (3.8% vs 2.6%), reoperations (1.4% vs .8%), and reinterventions (2.8% vs .7%) within 30 days (P < .05). Race was not significantly associated with AEs after ESG, with black race associated with a higher risk of AEs in SG. CONCLUSIONS: ESG demonstrates a comparable major AE rate with SG. Race did not impact short-term AEs after ESG. Further prospective studies long-term studies are needed to compare ESG with SG.

Impact of Proceduralist Specialty on Outcomes Following Endoscopic Sleeve Gastroplasty.

PURPOSE: Endoscopic sleeve gastroplasty (ESG) is a novel minimally invasive weight loss procedure designed to mimic gastric volume reduction of surgical sleeve gastrectomy. Currently, both bariatric surgeons and gastroenterologists perform ESG, and early reports suggest that ESG is safe and effective for weight loss. However, as gastroenterologists and bariatric surgeons have variations in training backgrounds, it is important to evaluate for potential differences in clinical outcomes. To date, there are no studies comparing the impact of proceduralist specialization on outcomes of ESG. This study aims to assess whether proceduralist specialization impacts short-term safety and efficacy after ESG. METHODS: We retrospectively analyzed over 6,000 patients who underwent ESG from 2016 to 2020 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. ESG patients were stratified into two groups depending on the specialty of the physician performing the procedure, and propensity matched using baseline patient characteristics. We primarily compared adverse events (AE), readmissions, re-operations, and re-interventions within 30 days after procedure. Secondary outcomes included procedure time, length of stay (LOS), early weight loss, and emergency department (ED) visits after procedure. RESULTS: There was no difference in AE in ESG performed by gastroenterologists and bariatric surgeons. ESG performed by bariatric surgeons demonstrated a trend towards higher rate of re-operations within 30 days. ESG performed by gastroenterologists had more ED visits but did not lead to higher rate of re-intervention. LOS was shorter in ESG performed by gastroenterologists, but procedure time was longer. CONCLUSIONS: ESG is safely performed by both gastroenterologists and bariatric surgeons.

AGA White Paper: Challenges and Gaps in Innovation for the Performance of Colonoscopy for Screening and Surveillance of Colorectal Cancer.

In 2018, the American Gastroenterological Association's Center for GI Innovation and Technology convened a consensus conference, entitled "Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes." The conference participants, which included more than 60 experts in colorectal cancer, considered recent improvements in colorectal cancer screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes.

Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.

Background and study aims In patients with inflammatory bowel disease (IBD), endoscopically visible lesions with distinct borders can be considered for endoscopic resection. The role of endoscopic submucosal dissection (ESD) for these lesions is not well defined because of a paucity of data. We aimed to evaluate the outcomes of colorectal ESD of dysplastic lesions in patients with IBD across centers in the United States. Patients and methods This was a retrospective analysis of consecutive patients with IBD who were referred for ESD of dysplastic colorectal lesions at nine centers. The primary endpoints were the rates of en bloc resection and complete (R0) resection. The secondary endpoints were the rates of adverse events and lesion recurrence. Results A total of 45 dysplastic lesions (median size 30mm, interquartile range [IQR] 23 to 42 mm) in 41 patients were included. Submucosal fibrosis was observed in 73 %. En bloc resection was achieved in 43 of 45 lesions (96 %) and R0 resection in 34 of 45 lesions (76 %). Intraprocedural perforation occurred in one patient (2.4 %) and was treated successfully with clip placement. Delayed bleeding occurred in four patients (9.8 %). No severe intraprocedural bleeding or delayed perforation occurred. During a median follow-up of 18 months (IQR 13 to 37 months), local recurrence occurred in one case (2.6 %). Metachronous lesions were identified in 11 patients (31 %). Conclusions ESD, when performed by experts, is safe and effective for large, dysplastic colorectal lesions in patients with IBD. Despite the high prevalence of submucosal fibrosis, en bloc resection was achieved in nearly all patients with IBD undergoing ESD. Careful endoscopic surveillance is necessary to monitor for local recurrence and metachronous lesions after ESD.