Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of obesity in adults and are now gaining attention in pediatric populations facing a dramatic rise of obesity prevalence and related comorbidities. In addition to weight loss, their role extends to cardiometabolic effects and improvements of kidney function. Liraglutide and semaglutide have demonstrated clinically meaningful efficacy in adolescents, leading to FDA and EMA approvals for patients >= 12 years. Ongoing trials are being conducted to combine GLP-1 analogues with other effective molecules or with bariatric surgery. Current evidence on safety most frequently highlights gastrointestinal adverse events, with no consistent impact on growth or pubertal development reported to date. Psychosocial dimensions, including stigma, mental health risks, and potential disordered eating, together with economic barriers and disparities in access, require careful consideration and effort s to be overcome. Implementing intensive lifestyle interventions is mandatory, including nutritional education, physical activity promotion, and family-based behavioral strategies, to support long-term weight management and address the broader determinants of health. Preliminary studies suggest complementary roles for GLP-1RAs alongside metabolic bariatric surgery in selected high-risk patients. Long-term data on safety and multidisciplinary approaches are required to define the optimal integration of pharmacotherapy into comprehensive, family-centered pediatric obesity care models. ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
Background and aims: Recent data suggest a role for the gut microbiome in the development of hepatocellular carcinoma. We investigated associations of gut microbiome abundances and concentrations of circulating bacteria-associated metabolites with hepatocellular carcinoma using Mendelian randomisation. Methods: Two-sample Mendelian randomisation was conducted using summary statistics from release 11 of FinnGen (609 cases and 473,046 controls) and The North American Hepatocellular Cancer Epidemiology Consortium (1872 cases and 2907 controls). Inverse variance-weighted analyses were performed as well as several sensitivity analyses. Results: In the FinnGen analyses, acetoacetate, ascorbate and asparagine were nominally associated with decreased risk. Alanine, hippuric acid and taurocholic acid were nominally associated with increased risk. The Barnesiella, Catenibacterium, Enterorhabdus and Eubacterium oxidoreducens genera were nominally associated with increased risk. Escherichia-Shigella was nominally associated with decreased risk. In the North American Hepatocellular Cancer Epidemiology Consortium analyses, the circulating bacteriaassociated metabolites taurochenodeoxycholic acid and threonate were nominally associated with decreased risk. Five genera were nominally associated with increased risk; Eubacterium rectale group, Hungatella, Sellimonas and the unknown genus 10 0 0 0 05472. Conclusion: These results, based on genetically predicted gut microbiome characteristics and circulating gut bacteria-related metabolite concentrations, suggest a putative causal role in hepatic carcinogenesis. (c) 2026 The Author(s). Published by Elsevier B.V. on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
Background and Aims: Despite concerns regarding its safety and the incidence of adverse events (AEs), EUSguided through-the-needle biopsy (EUS-TTNB) has emerged as a promising diagnostic tool. This study evaluated the clinical effectiveness of EUS-TTNB, assessed procedural AEs, and categorized risks based on predictive factors using recursive partitioning analysis (RPA). Methods: This retrospective study included 301 patients who underwent EUS-TTNB at Asan Medical Center, Seoul, South Korea, using permutation-based accuracy and RPA. Results: EUS-TTNB exhibited high diagnostic adequacy (80.3%, 241/301), showed strong histologic concordance among surgically resected cases (87.5%, 42/48), and led to changes in diagnosis and management in 16.3% of cases (49/301). AEs occurred in 20.9% of cases, with acute pancreatitis being the most common (15%, 45/301). Multivariable analysis identified intraductal papillary mucinous neoplasm (IPMN) (odds ratio [OR], 2.24; 95% CI, 1.26-3.98; P = .006) and complete cyst aspiration (OR, 0.50; 95% CI, 0.28-0.90; P = .02) as significant risk factors for AEs. In RPA, a random forest model and permutation-based accuracy were used to create 3 risk categories: low (AE rate: 11.9%, non-IPMN with complete cyst aspiration or >= 4 through-the-needle biopsies); high (AE rate: 37.0%, IPMN with age >= 70 or without complete cyst aspiration); and moderate (AE rate: 20.6%, not classified as low or high risk). Conclusions: EUS-TTNB demonstrated notable clinical utility in revising diagnoses and influencing therapeutic decisions but poses a considerable risk of AEs. By applying this risk categorization model with careful consideration and patient selection, its clinical utility may be enhanced. (Gastrointest Endosc 2026;104:416-24.)
Background and Aims: Colorectal endoscopic submucosal dissection (ESD) is an effective curative technique for superficial colorectal lesions but remains technically demanding, with variable procedure times. This study aimed to develop and validate a preprocedure predictive model for colorectal ESD duration in the era of traction-assisted strategies. Methods: We retrospectively analyzed prospectively collected data from patients who underwent colorectal ESD at Edouard Herriot Hospital (Lyon, France). The derivation cohort included 423 cases (January-December 2024), and an independent temporal validation cohort included 148 cases (January-May 2025). A generalized linear model with a gamma distribution and log-link function identified independent preprocedural predictors of ESD duration. Variables were selected on the basis of univariate significance and the Akaike information crite rion. Model calibration and discrimination were assessed using R2, mean absolute error, and classification accuracy at predefined thresholds (60, 90, and 120 minutes). A point-based score (Lyon ESD Dissection score, [LEDS]) and nomogram were derived from model coefficients. Results: Median procedure time in the derivation cohort was 50 minutes (IQR, 30-90). Independent predictors of ESD duration included dissection speed of endoscopists, lesion location (flexures, appendix, cecum, and ileocecal valve), predicted lesion size, and suspected fibrosis (all P < .05). The LEDS provides a direct estimation of the expected procedure time in minutes based on these variables, showing a strong correlation between predicted and observed durations (R2 = 0.52). Classification accuracy was 76.1%, 82.2%, and 88.1% for thresholds of 60, 90, and 120 minutes, respectively. Validation confirmed good performance (R2 = 0.48) with 91.8% accuracy for procedures >120 minutes. Conclusions: This validated preprocedure scoring system accurately predicts colorectal ESD duration, especially for longer procedures. It may facilitate scheduling, optimize resource use, and improve workflow in endoscopy units.
