Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

Impacts of intestinal fermentation on gastroesophageal reflux disease: can the tail wag the dog?

Communication between the foregut and the hindgut is amply illustrated by the gastro-colonic reflex and the impact of constipation on gastric function. Less well studied are the effects of the small intestinal or colonic microbiome and its metabolites on motor and secretory activities in the esophagus and stomach. In the study, the authors posit that small intestinal bacterial overgrowth promotes gastroesophageal and laryngo-pharyngeal reflux and in support of this hypothesis report an amelioration of related symptoms with antibiotic and dietary therapies.

Assessing the reliability and validity of sleep assessments in patients seeking metabolic and bariatric surgery.

Background: More than 80% of patients seeking metabolic and bariatric surgery (MBS) report disturbance in sleep function. No studies have assessed the psychometric properties of sleep measures in MBS samples.

Objectives: This study assessed the reliability and validity of the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) in a large sample of patients seeking MBS.

The Bidirectional Relationship Between Sleep and Pain in Crohn's Disease: A Daily Diary Study.

Background: Pain is common in Crohn's disease (CD) even after endoscopic healing is achieved. Depression, sleep disturbances, fatigue, and worry about pain impact the pain experience. There is a bidirectional relationship between sleep and pain, though it has received minimal attention in CD.

Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2).

Objective: The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2).

Methods: In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.

Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial.

Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors may be more effective than GLP-1 receptor agonism alone in reducing body weight, but the cardiovascular (CV) effects are unknown. The authors describe the rationale and design of SYNCHRONIZE-CVOT, a phase 3, randomized, double-blind, parallel-group, event-driven, CV safety study of survodutide, a dual glucagon and GLP-1 receptor agonist, administered subcutaneously once weekly compared with placebo in adults with a body mass index ≥27 kg/m and established CV disease or chronic kidney disease, and/or at least 2 weight-related complications or risk factors for CV disease. The primary endpoint of SYNCHRONIZE-CVOT is time to first occurrence of the composite adjudicated endpoint of 5-point major adverse CV events.

Clinician perceptions on barriers and facilitators to 1-year surveillance colonoscopy completion in survivors of colorectal cancer.

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Surveillance colonoscopy is recommended 1-year after surgical resection for patients with stage I-III CRC; however, only 18%-61% of CRC survivors complete this test. This study describes clinician-identified barriers and facilitators to surveillance colonoscopy among CRC survivors.

Incidence Trends in Upper Gastrointestinal Cancer in Young Adults: A Nationwide Time-Trend Analysis Using 2001-2019 US Cancer Statistics Databases.

Introduction: Upper gastrointestinal (UGI) cancers, comprising malignancies of the esophagus, stomach, duodenum, pancreas, liver, biliary tract, and gallbladder, are the second leading cause of cancer-related mortality in the United States and are associated with significant comorbidities. Recent studies show a disproportionate rise in pancreatic and stomach cancer among young adults. This study aims to use a nationwide, population-based cohort to (i) evaluate the trend of all UGI cancer as an aggregate and (ii) examine the role of demographics, histology, and tumor stage in UGI cancer incidence among young adults.

North American Expert Consensus on the Post-procedural Care of Patients After Per-oral Endoscopic Myotomy Using a Delphi Process.

Background & Aims: There is significant variability in the immediate post-operative and long-term management of patients undergoing per-oral endoscopic myotomy (POEM), largely stemming from the lack of high-quality evidence. We aimed to establish a consensus on several important questions on the after care of post-POEM patients through a modified Delphi process.

Methods: A steering committee developed an initial questionnaire consisting of 5 domains (33 statements): post-POEM admission/discharge, indication for immediate post-POEM esophagram, peri-procedural medications and diet resumption, clinic follow-up recommendations, and post-POEM reflux surveillance and management.

Quantifying Forms and Functions of Enterohepatic Bile Acid Pools in Mice.

Backgrounds & Aims: Bile acids (BAs) are core gastrointestinal metabolites with dual functions in lipid absorption and cell signaling. BAs circulate between the liver and distal small intestine (i.e.

Barriers to Engagement with Gastrointestinal Health Management.

Background: Although behavioral interventions have been effective in gastrointestinal (GI) conditions, barriers exist in implementing these interventions into clinical practice. The majority of previously published studies have focused on workforce limitations and have not considered individual and social determinants of health (SDoH) factors that can impact engagement in GI behavioral healthcare.

Aims: To characterize barriers to engagement in appointment attendance and health management, explore individual and SDoH factors impacting GI behavioral healthcare engagement, and identify barriers that occur more often for patients with SDoH-related vulnerability (low health literacy and/or financial insecurity).

Treatment preferences in diverticulitis are common and rarely change after a clinic visit.

With the increasing prevalence of diverticulitis, professional guidelines encourage the individualization of treatment. However, the frequency of treatment preferences of both surgeons, and patients, and the resultant impact of that preference on diverticulitis management is underexplored. We reviewed 27 consecutive patient visits of 3 colorectal surgeons at our institution to evaluate factors that drove their treatment, as well as their equipoise for patient randomization into medical or surgical treatments.

History of the Interventional Pancreaticobiliary Endoscopy.

With the introduction of endoscopic retrograde cholangiopancreatography and linear endoscopic ultrasound, interventional pancreaticobiliary (PB) endoscopy has had an enormous impact in the management of pancreatic and biliary diseases. Continuous efforts to improve various devices and techniques have revolutionized these treatment modalities as viable alternatives to surgery. In recent years, trends toward combining endoscopic techniques with other modalities, such as laparoscopic and radiological interventions, for complex PB diseases have emerged using a multidisciplinary approach.

Stomach Cancer Prediction Model (SCoPM): An approach to risk stratification in a diverse U.S. population.

Background And Aims: Population-based screening for gastric cancer (GC) in low prevalence nations is not recommended. The objective of this study was to develop a risk-prediction model to identify high-risk patients who could potentially benefit from targeted screening in a racial/ethnically diverse regional US population.

Methods: We performed a retrospective cohort study from Kaiser Permanente Southern California from January 2008-June 2018 among individuals age ≥50 years.

Coronavirus HKU1 infection and development of pediatric acute liver failure with immune dysregulation phenotype.

Pediatric acute liver failure is a rare but serious complication of Coronavirus infections. Our patient is a previously healthy 8-year-old male who presented with acute liver failure in the setting of human coronavirus HKU1 (HCoV-HKU1) infection while asymptomatic from a respiratory perspective. During the hospital course, he developed acute hepatic encephalopathy and was listed for liver transplantation, but fortunately recovered remaining status 7 (inactive) on the transplant list.