ABSTRACTBackgroundThe fecal immunochemical test (FIT) is widely implemented as a first‐line tool in organized colorectal cancer (CRC) screening programs, including Italy. Following a positive FIT, colonoscopy is recommended. Computer‐aided detection (CADe) systems have the potential to enhance adenoma detection, particularly in FIT‐positive populations where identifying advanced adenomas is critical for cancer prevention. This study evaluated the diagnostic performance of CADe‐assisted colonoscopy versus standard colonoscopy (SC) in a FIT‐based screening cohort.MethodsIn this multicenter, randomized controlled trial, patients with a positive FIT result were randomized to undergo either CADe‐assisted or standard colonoscopy. The primary endpoint was the advanced adenoma detection rate (AADR). Secondary endpoints included overall adenoma detection rate (ADR), adenomas per colonoscopy (APC), and mean withdrawal time (WT).ResultsOf 1077 patients enrolled, 68 were excluded due to inadequate bowel preparation, leaving 1009 patients for analysis (CADe: n = 506; SC: n = 503). AADR was comparable between the groups (21.3% vs. 20.5%, p = 0.794). However, CADe significantly improved ADR (67.6% vs. 59.8%, p = 0.012) and APC (1.82 ± 2.12 vs. 1.34 ± 1.81, p < 0.001). Mean WT was longer in the CADe group (17.10 ± 8.28 min vs. 16.13 ± 8.28 min, p = 0.016).ConclusionsIn a FIT‐based organized CRC screening setting, CADe did not enhance detection of AADR with a modest increase in withdrawal time. NCT04441580.

ABSTRACTBackground and aimsNo medications are currently approved for the prevention of recurrent acute pancreatitis. This trial evaluated whether naldemedine, a peripherally acting μ‐opioid receptor antagonist, reduces the risk of acute pancreatitis in patients with recurrent acute pancreatitis.MethodsThis was a multicentre, double‐blinded, placebo‐controlled randomised trial conducted at four Danish pancreatitis referral centres. Participants aged 18–75 years with recurrent acute pancreatitis, both with and without a diagnosis of chronic pancreatitis, were randomised to receive naldemedine 0.2 mg or a matching placebo daily for up to 12 months. The primary outcome was acute pancreatitis recurrence, defined by the revised Atlanta Criteria. Secondary outcomes included pain flares, gastrointestinal symptoms, and quality of life. At the end of follow‐up, the participant's global impression of change, safety and tolerability outcomes, new‐onset diabetes and pancreatic exocrine insufficiency were assessed.Results74 participants (mean age: 46 years; 41% female) were randomised to naldemedine (n = 36) or placebo (n = 38). During a median follow‐up time of 365 days (IQR, 352–370), participants in the naldemedine group had a numerically lower risk of acute pancreatitis compared to placebo (HR 0.54; 95% CI, 0.29–1.01; p = 0.05). No differences were observed between the groups for secondary efficacy, safety, and tolerability outcomes. Participants treated with naldemedine for at least 1 year had a lower risk of acute pancreatitis (HR 0.49; 95% CI, 0.24–0.97; p = 0.04).ConclusionsTreatment with naldemedine was safe and well‐tolerated and may reduce the risk of recurrent acute pancreatitis. A larger confirmatory trial is needed to verify these findings.Trial registrationClinicalTrials.gov Identifier: PAMORA‐RAP: NCT04966559

ABSTRACTBackgroundAcute pancreatic injury can result from blunt or sharp force trauma, often leading to serious complications. While direct pancreatic trauma is associated with high rates of infection, organ failure, and mortality, little is known about the pancreas as a potential secondary target and remote trauma organ and thereby as a booster of systemic injury.MethodsWe employed a murine model of multiple trauma and hemorrhagic shock in which the pancreas was deliberately spared from the direct trauma impact. Four hours post‐trauma, we determined systemic and local inflammatory responses, pancreatic tissue damage, pancreatic lipase (Pnlip in mice), and protease activity, and conducted proteomic profiling of the pancreas. For clinical translation, we performed a post hoc analysis of severely injured polytrauma patients, focusing on acute pancreatic involvement and its association with clinical parameters.ResultsSevere trauma in mice induced rapid systemic inflammation and significantly elevated plasma levels of Pnlip. Notably, pancreatic edema formation was observed in a subset of polytraumatized mice, accompanied by increased activity of matrix metalloproteinases Mmp2 and Mmp9. Proteomic analysis revealed an enrichment of inflammatory and cellular stress pathways in pancreatic tissue. Similarly, in polytraumatized patients, plasma pancreatic lipase (PNLIP in humans) and trypsin concentrations were elevated during the early posttraumatic period and correlated with injury patterns, systemic inflammation, coagulopathy, endotheliopathy, organ failure, and time in hospitals and intensive care units.ConclusionOur findings highlight the pancreas as a novel remote responder to severe tissue trauma, even in the absence of direct injury. This widely overlooked dimension of trauma pathophysiology has potential clinical implications. However, further research is essential (i) to unravel the mechanisms driving remote pancreatic enzyme release and (ii) to prove the causality between the pancreatic response and observed clinical parameters.

ABSTRACTBackgroundHypomorphic variants of sucrase‐isomaltase (SI) have been associated with irritable bowel syndrome (IBS) in adults, but how their presence influences therapeutic outcomes is uncertain.AimsTo investigate the frequency of sucrase‐isomaltase hypomorphic variants in patients with IBS and their association with short‐ and long‐term outcomes after initiation of a FODMAP diet.MethodsClinical outcomes in patients with IBS were retrospectively examined at mean 7.1 (range 2.5–13.4) years after being educated on a FODMAP diet by a gastrointestinal dietitian and their current food intake (Comprehensive Nutrition Assessment Questionnaire) and gastrointestinal symptoms were documented at interview. DNA extracted from whole blood samples was analysed with the Illumina Global Screening Array for sucrase‐isomaltase hypomorphic variants.ResultsOf 72 participants (62% female, median age 59 years), 54% had at least one hypomorphic variant of which 85% were single‐carriers. On adjusted binary logistic regression analysis, no differences were noted across SI hypomorphic genotypic groups for retrospective analysis of initial response to a FODMAP diet or long‐term symptom control. Current dietary intakes of sucrose or starch were not different between non‐carriers and carriers, were directly related to FODMAP intake and did not differ in carriers according to adequacy of symptom control. Findings in those with diarrhoea‐predominant IBS (n = 29) were similar to the those in the whole group. Too few double‐carriers (n = 6) precluded the definition of associations.ConclusionsThe presence of single sucrase‐isomaltase hypomorphic variants is common but was not associated with short‐ or long‐term outcomes or dietary intake for patients with IBS who were taught a FODMAP diet.

ABSTRACTEndoscopic ultrasound‐guided biliary drainage (EUS‐BD) has evolved from a rescue therapy into a viable alternative to endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous drainage for distal malignant biliary obstruction (dMBO). Among the available techniques, EUS‐guided choledochoduodenostomy (EUS‐CDS) has become the preferred approach, supported by expanding evidence, and wider adoption beyond expert centres. EUS‐guided hepaticogastrostomy (EUS‐HGS) currently retains a role in high‐volume centres and in patients with combined biliary and duodenal obstruction, while other approaches, including EUS‐guided gallbladder drainage, antegrade stenting, and rendezvous procedures, are applied selectively due to limited evidence or narrower applicability. This review summarizes the current role of EUS‐BD in dMBO, with emphasis on EUS‐CDS. Technical and clinical considerations, training requirements, and remaining challenges are discussed, and future perspectives are outlined, focusing on device innovation and patient‐centred outcomes to guide safe and structured integration of EUS‐BD into clinical practice.

ABSTRACTBackgroundMetabolic dysfunction‐associated steatotic liver disease (MASLD) has been linked to an increased risk of serious infection, but the impact of in utero exposure to maternal MASLD on the risk of infection in offspring remains unknown.MethodsThis nationwide cohort study included all singleton live born offspring exposed in utero to maternal biopsy‐proven MASLD (1992–2017) in Sweden. Offspring born to mothers with MASLD (N = 239) were matched with up to five reference offspring (N = 1131) of mothers without MASLD by maternal age at delivery, calendar year of delivery, and parity. We used multivariable Cox regression to estimate adjusted hazard ratios (aHRs) for incident serious infection up until 2023. Results were also stratified by maternal histological severity of MASLD (simple steatosis vs. severe MASLD including steatohepatitis, any stage of liver fibrosis or cirrhosis).ResultsOver a median of 16.7 years of follow‐up, 56 incident serious infections occurred in MASLD offspring (incidence rate [IR] 15.8/1000 person‐years) and 140 incident serious infections occurred in reference offspring (IR 7.4/1000 person‐years), which corresponded to an aHR of 1.81 (95% CI 1.23–2.68). The aHRs for incident serious infection were similar to offspring of mothers with simple steatosis and severe MASLD (1.97 vs. 1.70). This association was primarily explained by early‐life infections (1‐year aHR 3.11, 95% CI 1.74–5.58), with severe MASLD potentially being a major factor in the observed association during the first year. Results remained consistent across subgroups.DiscussionMaternal MASLD, even simple steatosis, is associated with a higher hazard of serious offspring infection, highlighting the need for closer monitoring.

ABSTRACTBackground and Study AimsMotorized spiral enteroscopy (MSE) was introduced as a major advancement in small‐bowel enteroscopy, enabling higher complete enteroscopy rates with shorter procedure times. However, after a fatal adverse event (AE) involving severe esophageal injury, the device was withdrawn from the market in July 2023. This raised questions about whether earlier safety signals were missed.MethodsWe conducted a systematic review and meta‐analysis comparing MSE with balloon‐based enteroscopy (double‐balloon [DBE] and single‐balloon enteroscopy [SBE], analyzed together). Outcomes included overall AEs, serious AEs (SAEs), and data collection quality. Results from the German PowerSpiral Registry were included, comprising 647 MSE procedures in 523 patients (January 2020–July 2023) before registry closure following device withdrawal.ResultsThirteen MSE studies (including the registry) and 55 DBE/SBE studies were analyzed, totaling 12,559 enteroscopies (2024 MSE; 10,535 DBE/SBE). MSE showed significantly higher rates of AEs (10.8% vs. 1.6%) and SAEs (1.5% vs. 0.4%). Procedure‐related SAEs were also more frequent with MSE (1.1% vs. 0.3%). Esophageal injury (0.10% vs. 0.009%) and intestinal perforation (0.5% vs. 0.1%) occurred more often with MSE, whereas acute pancreatitis (0.05% vs. 0.27%) and esophageal perforation (0% vs. 0.02%) were more common with DBE/SBE. AE reporting for MSE was detailed, but structured follow‐up and reliable case tracking were inconsistent.ConclusionsMSE was associated with higher AE and SAE rates than balloon enteroscopy. These findings highlight the need for cautious adoption, rigorous safety monitoring, and more robust AE reporting when introducing innovative endoscopic technologies.Study RegistrationThe prospective and retrospective cohort studies were registered in the German Registry of Clinical Studies (DRKS), namely DRKS00026990 and DRKS00028571