Endoscopy and Anesthesia Outcomes Associated with Glucagon-Like Peptide-1 Receptor Agonist use in Patients Undergoing Outpatient Upper Endoscopy.

Background And Aims: Glucagon-like peptide-1 receptor agonists (GLP1RAs) can cause delayed gastric emptying, raising concern for retained gastric contents (RGCs) during endoscopy and adverse anesthesia events. We aimed to determine associations between GLP1RA and endoscopy and anesthesia outcomes.

Methods: This single-center retrospective cohort study examined patients prescribed GLP1RA who underwent outpatient endoscopy stratified by exposure at the time of endoscopy.

The unexpected role of GIP in transforming obesity treatment.

Despite sharing incretin activity with glucagon-like peptide 1 (GLP-1), the development of gastric inhibitory polypeptide (GIP)-based drugs has been hindered by the minor effects of native GIP on appetite and body weight and genetic studies associating loss-of-function with reduced obesity. Yet, pharmacologically optimized GIP-based molecules have demonstrated profound weight lowering benefits of GIPR agonism when combined with GLP-1-based therapies, which has re-energized deeper exploration of the molecular mechanisms and downstream signaling of GIPR. Interestingly, both GIPR agonism and antagonism offer metabolic benefits, leading to differing viewpoints on how to target GIPR therapeutically.

Aspirin is associated with a reduced incidence of liver disease in men.

Background: The hepatoprotective effects of aspirin have been observed in individuals with viral hepatitis; however, its impact on the general population remains uncertain. Understanding the association between aspirin use and the development of liver diseases is crucial for optimizing preventive strategies.

Methods: We identified individuals with aspirin use in the UK Biobank and the Penn Medicine Biobank, as well as propensity-score-matched controls.

Large-scale identification of undiagnosed hepatic steatosis using natural language processing.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity in people with and without diabetes, but it is underdiagnosed, posing challenges for research and clinical management. Here, we determine if natural language processing (NLP) of data in the electronic health record (EHR) could identify undiagnosed patients with hepatic steatosis based on pathology and radiology reports.

Methods: A rule-based NLP algorithm was built using a Linguamatics literature text mining tool to search 2.

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality.

Importance: Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed.

Objective: To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population.

Design, Setting, And Participants: This cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020.

A phenotypic approach to obesity treatment.

Obesity is a chronic disease that increases morbidity and mortality and adversely affects quality of life. The rapid rise of obesity has outpaced the development and deployment of effective therapeutic interventions, thereby creating a global health crisis. The presentation, complications, and response to obesity treatments vary, yet lifestyle modification, which is the foundational therapeutic intervention for obesity, is often "one size fits all.

A coding variant in the microsomal triglyceride transfer protein reduces both hepatic steatosis and plasma lipids.

Background: Genetic inactivation and pharmacologic inhibition of the microsomal triglyceride transfer protein (MTP; gene name MTTP) inhibits hepatic secretion of VLDL, thereby reducing serum lipids and apoB at the expense of increasing hepatic steatosis.

Aim: To examine the effects of missense variants in MTTP on hepatic and circulating lipids.

Methods: We analysed the association of MTTP missense variants with metabolic, hepatic and clinical phenotypes in the Penn Medicine Biobank (PMBB; n = 37,960) and the UKBiobank (UKB; n = 451,444).

Dietary Vitamin E Intake Is Associated With a Reduced Risk of Developing Digestive Diseases and Nonalcoholic Fatty Liver Disease.

Introduction: Vitamin E supplementation is recommended for the treatment of nonalcoholic fatty liver disease (NAFLD) for nondiabetic patients, but its preventative effects are unclear.

Methods: We assessed dietary vitamin E intake with disease phenotypes and evaluated vitamin E levels with the development of NAFLD.

Results: Data from >210,000 participants demonstrate that increased dietary vitamin E associates with reduced rates of several gastrointestinal diseases and reduced overall mortality.

Systematic Review and Meta-Analysis: Efficacy of Vancomycin Taper and Pulse Regimens in Clostridioides difficile Infection.

Background: Vancomycin is the drug of choice for treating infection (CDI). We compare CDI resolution with vancomycin taper, pulse, and taper-and-pulse regimens.

Methods: We searched for Medline, Embase, Cochrane, and Scopus through October 9, 2020.

A genome-first approach to mortality and metabolic phenotypes in p.Ala165Thr (rs2642438) heterozygotes and homozygotes.

Background: A coding variant in (rs2642438; p.Ala165Thr) was recently associated with protection from cirrhosis in European individuals. However, its impact on overall and cause-specific mortality remained elusive.

Physical activity is associated with reduced risk of liver disease in the prospective UK Biobank cohort.

Background & Aims: Previous studies have identified physical activity as an important lifestyle factor in the pathogenesis of chronic liver diseases (CLD). However, most studies were short in follow-up, and based on self-reported activity. Moreover, it is unknown whether physical activity affects the risk of liver disease development in the general population.

Ileo-colonic delivery of conjugated bile acids improves glucose homeostasis via colonic GLP-1-producing enteroendocrine cells in human obesity and diabetes.

Background: The bile acid (BA) pathway plays a role in regulation of food intake and glucose metabolism, based mainly on findings in animal models. Our aim was to determine whether the BA pathway is altered and correctable in human obesity and diabetes.

Methods: We conducted 3 investigations: 1) BA receptor pathways were studied in NCI-H716 enteroendocrine cell (EEC) line, whole human colonic mucosal tissue and in human colonic EEC isolated by Fluorescence-activated Cell Sorting (ex vivo) from endoscopically-obtained biopsies colon mucosa; 2) We characterized the BA pathway in 307 participants by measuring during fasting and postprandial levels of FGF19, 7αC4 and serum BA; 3) In a placebo-controlled, double-blind, randomised, 28-day trial, we studied the effect of ileo-colonic delivery of conjugated BAs (IC-CBAS) on glucose metabolism, incretins, and lipids, in participants with obesity and diabetes.

Cell-free DNA testing: future applications in gastroenterology and hepatology.

The application of next-generation sequencing in clinical practice is increasing as accuracy and interpretation have improved and the cost continues to decline rapidly. Cell-free DNA is a unique source for next-generation sequencing that could change routine clinical practice in gastroenterology and hepatology. Testing of cell-free DNA in blood and fecal samples is an easy, rapid, and noninvasive method to assess for premalignant, malignant, metabolic, infectious, inflammatory, and autoimmune gastrointestinal and liver diseases.

Rho GTPases: Anti- or pro-neoplastic targets?

Rho GTPases are critical signal transducers of multiple pathways. They have been proposed to be useful anti-neoplastic targets for over two decades, especially in Ras-driven cancers. Until recently, however, few in vivo studies had been carried out to test this premise.

Loss of RhoA Exacerbates, Rather Than Dampens, Oncogenic K-Ras Induced Lung Adenoma Formation in Mice.

Numerous cellular studies have indicated that RhoA signaling is required for oncogenic Ras-induced transformation, suggesting that RhoA is a useful target in Ras induced neoplasia. However, to date very limited data exist to genetically attribute RhoA function to Ras-mediated tumorigenesis in mammalian models. In order to assess whether RhoA is required for K-Ras-induced lung cancer initiation, we utilized the K-RasG12D Lox-Stop-Lox murine lung cancer model in combination with a conditional RhoAflox/flox and RhoC-/- knockout mouse models.

The prevalence of BRCA1 mutations among young women with triple-negative breast cancer.

Background: Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer.

Germline RAP80 mutations and susceptibility to breast cancer.

Most of the breast cancer susceptibility genes identified to date are involved in DNA repair, including BRCA1, BRCA2, PALB2, CHEK2 and BRIP1. RAP80 works upstream of BRCA1 and is essential for the localization of BRCA1 to the site of damaged DNA. To investigate whether or not RAP80 is also a breast cancer susceptibility gene, we sequenced the entire exonic regions of RAP80 in the germline DNA of 152 women with familial breast cancer, who were previously found to be negative for BRCA1 and BRCA2 mutations.

Germline BRCA2 mutations and the risk of esophageal squamous cell carcinoma.

The incidence of esophageal squamous cell carcinoma (ESCC) is very high among the Turkmen population of Iran. Family studies suggest a genetic component to the disease. Turkmen are ethnically homogenous and are well suited for genetic studies.