American Journal of Gastroenterology

Background and Study Aims Fully covered, self expandable metal stents (FCSEMS) are used to treat biliary strictures. FCSEMS with transmural side holes may facilitate cystic duct drainage to mitigate risk of cholecystitis and impact other stent-related adverse events such as migration and occlusion. This study compared rates of premature stent occlusion and acute cholecystitis among patients with biliary strictures who underwent first time placement of a FCSEMS with or without transmural side holes. Patients and Methods This was a retrospective cohort study of adults who underwent endoscopic retrograde cholangiopancreatography (ERCP) with FCSEMS between April 2022 to April 2025 for malignant or benign extrahepatic bile duct strictures. Patients were followed for a minimum of 9 months or through planned stent removal. The primary outcome was premature bile duct occlusion. The secondary outcome was acute cholecystitis among patients with an intact gallbladder. Results Among 219 patients meeting enrollment criteria, 57 (26%) had side holes. The rate of premature stent occlusion was similar with transmural side holes (12%) vs. without (11%, HR 1.02, 95% CI 0.42 2.43, p = 0.96). Among patients with an intact gallbladder (n=129), acute cholecystitis rates were similar with side holes (6%) or without (4.8%, HR 1.01, 95% CI 0.22 4.5, p = 0.99). Conclusions FCSEMS stents with side holes do not reduce rates of premature bile duct stent occlusion or acute cholecystitis compared to FCSEMS without side holes.

BackgroundThis study evaluated the safety and efficacy of primary resection and anastomosis (PRA) for colovesical fistula (CVF) of diverse etiologies and identified independent prognostic factors for oncological outcomes. MethodsWe retrospectively analyzed 112 CVF patients (2017-2024) undergoing PRA with or without a defunctioning stoma, comparing clinical outcomes across benign and malignant cohorts. ResultsBenign etiologies accounted for 33.0% (n=37) (colonic diverticulitis (n=19, 51.4%), Crohns disease (n=14, 37.8%), and iatrogenic injury (n=4, 10.8%)), all underwent PRA with partial cystectomy, achieving zero mortality and no recurrence. Malignancies (67.0%) primarily included colorectal adenocarcinoma (sigmoid colon cancer (n=44, 58.7%) or rectal cancer (n=31, 41.3%)). Within the malignant cohort, radical cystectomy (n=15) was strictly necessitated by advanced disease features, including distal tumor location and extensive bladder wall invasion (80.0% vs 36.7%, P=0.003). Consequently, this advanced cohort experienced longer operative times (589 vs. 289 min), higher blood loss (600 vs. 100 mL), increased morbidity (80.0% vs. 20.0%, P<0.001), and shorter disease-free survival (DFS) (8 vs. 20 months, P=0.008) compared to those amenable to partial cystectomy (n=60). Crucially, multivariate analysis identified perineural invasion (PNI) (HR: 3.83, 95% CI: 1.49-9.84; P=0.005) as a critical independent predictor of recurrence, reflecting the impact of tumor biology over surgical extent. ConclusionsPRA is a definitive and versatile strategy for CVF. In malignant cases, bladder-preserving strategies are oncologically viable when R0 margins are achievable. Integration of PNI status and neoadjuvant therapy was essential for refining personalized multidisciplinary management.

Background. Balanced (1:1:1) transfusion of red blood cells (RBCs), plasma, and platelets is the standard of care in trauma-induced massive haemorrhage, where early coagulopathy is a defining feature. In gastrointestinal (GI) haemorrhage this physiology is non-prominent, and whether plasma and platelets provide benefit when [&ge;] 10 RBC units are required within 24 hours is unknown. Objective. To test whether a red-blood-cell-only (RBC-only) transfusion strategy is non-inferior to a balanced (Balanced) strategy for in-hospital mortality in adults meeting massive-transfusion criteria for GI haemorrhage. Design. Single-centre retrospective cohort of 559 adult massive-transfusion encounters (536 patients; 2021-2025) with a primary admitting diagnosis of upper, lower, or unspecified GI haemorrhage. Exposures were RBC-only versus Balanced (RBCs with any plasma and/or platelets). The primary outcome was in-hospital mortality, with a pre-specified 5-percentage-point (pp) non-inferiority margin on the absolute risk difference and a 3-pp sensitivity margin. Analysis used augmented inverse-probability-of-treatment weighting (AIPTW) with bootstrap inference (2,000 resamples by patient). Five pre-specified sensitivity analyses were performed. Results. 505 encounters (90.3%) received RBC-only and 54 (9.7%) received Balanced transfusion. The AIPTW risk difference for in-hospital mortality (RBC-only - Balanced) was -19.8 pp (95% CI -68.1 - -2.2 pp). Non-inferiority was demonstrated at both the primary 5-pp and the more stringent 3-pp margins. Five pre-specified sensitivity analyses, (1) a propensity-score matched cohort, (2) a complete-case model incorporating INR, (3) a broader GI diagnosis set (n = 749), (4) a first encounter per patient restriction, and (5) E-value bound analysis were concordant with the primary estimate. Conclusion. In this propensity-score-weighted cohort of adults with massive GI haemorrhage, an RBC-only transfusion strategy was non-inferior to a balanced strategy for in-hospital mortality at both 5-pp and 3-pp margins. The findings support individualized use of plasma and platelets in GI haemorrhage rather than reflexive application of the 1:1:1 trauma protocol; prospective confirmation is warranted.

Background and AimsAcute pancreatitis (AP) can lead to systemic inflammatory response (SIRS), paralytic intestinal obstruction, and in severe cases, intra-abdominal hypertension (IAH), organ failure (OF), and even death. Early magnesium sulphate (MS) catharsis treatment can relieve paralytic intestinal obstruction and IAH, thus reducing the incidence of severe acute pancreatitis (SAP) as well as mortality. Methods850 patients with AP at high risk of systemic complications (potential SAP (p-SAP)) were recruited. These p-SAP patients were categorized into two groups based on the treatment they received: the routine group (RT group, standard treatment for AP) and the MS group (early MS catharsis added to standard treatment). The final cohort had an allocation ratio of 2.5:1 (RT : MS). The primary composite endpoints were clinically finally diagnosed SAP (d-SAP) and mortality. The intensive care unit (ICU) admission, OF, inflammatory factors, length of hospital stay, and hospitalization costs, etc. were also compared and analyzed. ResultsIt demonstrated that early MS catharsis treatment was highly effective in preventing patients with p-SAP of various aetiologies from deteriorating to d-SAP and reducing their mortality significantly. In addition, it significantly reduced the incidence of OFs, pancreatic necrosis, ICU admissions, CRRT utilisation, and the cost and length of stay of hospitalisation for these patients. ConclusionsIt showed that early MS catharsis had a significant therapeutic effect on p-SAP patients, which would profoundly contribute to the clinical management of AP.

BackgroundChronic gastroduodenal symptoms are challenging to diagnose and treat. Body surface gastric mapping provides non-invasive biomarkers of gastric function, but the requirement of a standard meal for postprandial assessment can be difficult for severely symptomatic patients. AimsTo assess the impact of reduced meal sizes and fasting on body surface gastric mapping metrics to determine clinical interpretability under non-standard nutritional loads. MethodsHealthy controls (n=60) underwent a 4.5-hour Gastric Alimetry test. Three age, sex, and BMI-matched groups (n=20 each) were compared: Standard Meal (482 kCal), Nutrient bar + Water (250 kcal), and Fasted (no meal). Principal Gastric Frequency, Gastric Alimetry Rhythm Index, BMI-Adjusted Amplitude, and fed:fasted Amplitude Ratio were analyzed against normative intervals. ResultsMeal status significantly affected amplitude-based metrics; the Standard Meal group exhibited higher BMI-Adjusted Amplitude (p<0.001) and fed:fasted Amplitude Ratio (p=0.001) than Fasted and Bar + Water groups. Frequency and rhythm-based metrics were resilient; Principal Gastric Frequency (p=0.245) and Gastric Alimetry Rhythm Index (p=0.336) showed no significant differences across conditions. While amplitude deviations were common in the Fasted group (20% fell below the normative range), Gastric Alimetry Rhythm Index and Principal Gastric Frequency remained within normal reference ranges for 95% of participants across all conditions. ConclusionsWhile consuming <50% of the standard meal significantly reduces gastric amplitude, gastric rhythm remains stable. Principal Gastric Frequency and Gastric Alimetry Rhythm Index function as reliable biomarkers of gastric myoelectrical function regardless of nutritional state.

Background Recent mouse model data demonstrate that chronic colonization with toxigenic Clostridioides difficile promotes colonic tumorigenesis via intraluminal toxin B (TcdB), its main virulence factor. In a prior multisite hospital cohort, we found that history of positive tcdB stool testing was associated with increased CRC risk in a dose-dependent manner, though limited by small sample size. We aimed to validate this association in a larger cohort with extended follow-up and greater geographic distribution using the Veterans Health Administration (VHA) Corporate Data Warehouse (CDW). Methods We conducted a retrospective cohort study among adults receiving care through the VA from 2000-2025 who underwent C. difficile testing. Data collected from the VHA CDW and National Death Index (NDI) included demographics, comorbidities, medications, CRC risk factors, and cancer incidence and death. The first C. difficile test date defined cohort entry; individuals with prior CRC were excluded. Ever C. difficile positivity was defined by a positive PCR or EIA results. The number of positive tests (episodes) was also determined to define recurrent positivity. Follow-up time ended at the first occurrence of CRC incidence or mortality, death from other causes, or censor date. Follow-up time was split for individuals who converted from negative to positive, with follow-up time updated accordingly. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) for C. difficile exposure and CRC incidence and mortality after adjustment for confounders. Tests for linear trend and tests for interaction were conducted to assess effect modification by sex and IBD status, while time-lag intervals were evaluated for 1, 3, 5, and 10 years before the outcome. Results Among 806,844 veterans with C. difficile testing, those with positive tests were more likely to be older, male, to have diabetes, to use aspirin, and to have a lower BMI than those with negative tests. Race and IBD prevalence were similar between the groups. There was no overall association between ever C. difficile positivity and CRC incidence (HR = 0.99, 95% CI 0.93-1.05). However, recurrent C. difficile positivity was associated with increased risk in a dose-response manner [2-3 episodes HR = 1.30 (95% CI 1.16-1.47), and >3 episodes HR = 1.58 (95% CI 1.17-2.14) compared to negative tests; ptrend< 0.001]. Further, ever C. difficile positivity was associated with increased CRC mortality risk (HR = 1.21, 95% CI 1.13-1.30; p < 0.001). Recurrent C. difficile positivity was associated with increased mortality risk but was particularly strong for those with >3 episodes among individuals with IBD (HR=3.84, 95% CI 1.98-7.45). In sensitivity analyses, the increased risk of CRC incidence and mortality attenuated beyond 10 years. Conclusion Prior positive C. difficile testing was associated with increased CRC incidence and mortality in a dose-dependent manner, particularly among patients with IBD. These findings extend animal model evidence, epidemiologically establishing C. difficile presence as an independent risk factor for subsequent colorectal tumorigenesis and supporting investigation into recurrent CDI, especially among patients with IBD, as a potential modifiable CRC risk factor.

Background Unplanned hospital admissions in Inflammatory Bowel Diseases (IBD) account for nearly three-quarters of IBD inpatient stays in the United Kingdom. Although costly to services and distressing for patients, research exploring experiences and potential drivers of admissions is limited. We undertook a qualitative study to explore the healthcare experiences and access needs of people with IBD who had unplanned admissions, along with their caregivers and clinicians. Methods Semi-structured interviews with 25 participants from a single tertiary IBD service in England (17 people with IBD, 3 informal caregivers, 5 clinicians) were conducted. We applied thematic framework analysis, guided by the Candidacy Framework, and worked with 2 patient and public contributors to generate final themes. Results We identified four themes: 1) Difficulties in Identifying flares and asserting severity before admission, summarised the prevailing uncertainty in identifying a flare and access to timely IBD care. 2) Navigating a disjointed healthcare system, highlighted how lack of care plans and systemic barriers can delay access. 2) Emergency care access challenges highlighted the gaps in emergency and inpatient care during flares. Whilst 4) fighting for care and individual advocacy needs, described the persistent assertion for care that may disproportionally impact access to vulnerable groups, also highlighting the importance of positive interpersonal relationships. Conclusions Individual, interpersonal and healthcare factors across the patient pathway were perceived to shape access to care in unplanned IBD admissions. Potentially reducing admissions requires proactive strategies, including the integration of patient education, monitoring tools, establishment of specialist rapid-access pathways, and formal psychological support to address barriers to access.

Background and Aims: Diet plays a critical role in managing Crohns disease (CD) inflammation. We assessed whether dietary replacement of animal protein (AnimalP) by soy-pea protein (SoyP) decreases the pro-inflammatory potential of gut microbiota and intestinal inflammation in CD patients. Design: In an open-label, randomized controlled feeding trial at University Hospitals Cleveland Medical Center, CD participants and healthy controls were randomized (1:1) to a soy-pea or animal protein diet for 7-days. Primary outcomes were the absolute difference (d7-d0) in; Crohns Disease Activity Index (CDAI) score and fecal myeloperoxidase (MPO). Secondary outcomes included fecal calprotectin (FC) and high-sensitivity C-reactive protein (hsCRP). Murine fecal transplantation experiments were performed to determine the inflammatory potential of diet-altered gut microbiota. Results: The study randomized 66 participants and 60 were included in the final analysis (n=31 CD, n=29 HC). After 7 days, CD-SoyP participants were more likely than CD-AnimalP to show reductions in HBI (RR=4.68, 95% CI: 1.22-17.98, P=0.009) and fecal MPO (RR=2.30, 95% CI: 1.04-4.85, P=0.032), with a similar directional trend for CDAI (RR=1.52, 95% CI: 0.89-2.58, P=0.135). No participants experienced worsening of CDAI. The rank-based composite CDAI-MPO score was lower in the CD-SoyP vs CD-AnimalP group (median [IQR]: 5 [4-6] vs 8 [7-9]; P=0.012). Stratified analyses showed significant reductions in fecal MPO among CD participants with lower baseline disease activity (CDAI <150; P<0.0001), but not in those with higher activity (P=0.799) Conclusion: Short-term addition of plant-based soy-pea protein within a controlled diet exerted a beneficial, anti-inflammatory effect in CD, with evidence of greater effects among participants with lower baseline disease activity. ClinicalTrials.gov, Number NCT04065048.

Pain in pancreatic ductal adenocarcinoma (PDAC) is associated with poor survival, but whether altered pain processing carries prognostic significance is unknown. We analyzed a prospective cohort of 143 patients with PDAC who underwent pancreatic quantitative sensory testing (PQST) after diagnosis. Patients were classified as having normal pain processing (n=84), segmental hyperalgesia (n=30), or widespread hyperalgesia (n=29). Survival was measured from the date of P-QST assessment. During follow-up, 70 deaths occurred. Widespread hyperalgesia was associated with increased mortality in unadjusted Cox analysis (HR 1.96, 95% CI 1.14,3.35) and after adjustment for age, sex, tumor stage, comorbidity, opioid treatment, and body mass index (adjusted HR 2.33, 95% CI 1.30,4.15). Segmental hyperalgesia was not associated with mortality. Kaplan Meier analysis demonstrated lower survival probability in the widespread hyperalgesia group (log rank p=0.025). These findings suggest that widespread hyperalgesia, reflecting altered central pain processing, identifies a subgroup of PDAC patients at increased risk of mortality independent of conventional clinical factors.

Background and ObjectivesThe etiology of biliary obstruction has undergone notable shifts over recent decades, yet long-term epidemiological studies addressing these changes remain scarce. With the widespread clinical adoption of endoscopic ultrasound (EUS), its role in altering diagnostic patterns warrants investigation. This study aimed to characterize the evolving disease patterns of biliary obstruction and specifically evaluate the impact of EUS adoption on driving these perceived etiological shifts over a 15-year period. MethodsThis retrospective, single-center study analyzed data from patients with biliary obstruction over a 15-year period. Time-series analysis was employed to characterize evolving disease patterns. To investigate the drivers underlying the observed trends, we applied a difference-in-differences (DID) analytical framework, uniquely treating the widespread clinical adoption of EUS as a natural experiment. Furthermore, multivariable logistic regression was utilized to identify independent predictors for malignant biliary obstruction of pancreatic origin. ResultsAmong 5,672 patients with pathological diagnoses, the disease spectrum shifted significantly toward malignant etiologies, particularly pancreatic and ampullary cancers, over the study period. The DID analysis confirmed that the broad adoption of EUS was associated with a significant relative increase in the precise diagnosis of malignancies detectable by this modality. Multivariable analysis further identified the EUS promotion era and calendar year as independent predictors for the pancreatic origin of malignancy. ConclusionsThe observed increase in pancreatic and ampullary cancers among patients with biliary obstruction is significantly associated with the enhanced diagnostic capabilities brought by EUS. This suggests that the diagnostic evolution driven by the widespread adoption of EUS, alongside potential epidemiological changes, is a major contributing factor to the perceived etiological shifts in biliary obstruction.

BACKGROUND & AIMS Conventional reusable endoscopes incur significant expenses in the form of purchase, maintenance, reprocessing, and disinfection. Reprocessing is frequently ineffective even following the use of high-level disinfectants (HLDs). Disposable gastroscopy might be a strategy to decrease infectious outbreaks associated with reusable endoscope. The aim of this study was to analyze and evaluate the performance, efficiency and safety in gastroscopy observation and subsequent potential EMR procedure via the disposable gastroscope in a clinical setting. METHODS Patients who required gastroscopies and met the criteria were recruited to this prospective, open-label, non-inferiority study. After obtaining the written informed content, the enrolled subjects selected themselves independently to the disposable group or reusable group. The primary measure was to evaluate the acceptable image quality and whether the disposable endoscope devices could meet the basic clinical demands with a noninferiority margin of -8%. The second measures were to analyze and evaluate the image conditions, accepted endoscopic maneuverability, efficiency and safety of observation and advanced potential EMR procedure. Appropriate statistical methods were conducted via PASS software and SAS 9.4. A two-tailed P value < 0.05 was considered statistically significant. RESULTS A total of 90 individuals (the number of those in disposable group and reusable group was both 45) were recruited to this study. The success rate of acceptable image quality via photographing iconic anatomical sites between two groups was 100.0% (45/45, 95% confidence interval (CI): 0.9213,1.0000) and the lower limit of the 95%CI (-7.8654%, 7.8654%) was larger than the noninferiority margin of -8% (Newcombe-Wilson score method). Significant differences were showed in the measures of image conditions (image acquisition, image quality, brightness, contrast and sharpness) and accepted endoscopic maneuverability (endoscopy body rigidity). No significant differences were observed in the field of knob operation, sharp angle adaptability, and the auxiliary features including air supply, water supply and suction. In terms of efficiency, the total operating time, insertion time and withdrawal time were longer in the disposable group. The En-bloc resection rate of those observed polyps and required to EMR procedure due to relatively larger diameter (5mm-15mm) was the same 100% in both groups (26/26 vs 23/23, 95%CI: 0.8713,1.0000). Nevertheless, the procedure time of EMR for each polyp was significantly longer in the disposable group. This study showed no intraoperative bleeding, delayed bleeding, perforation or other study-related adverse events among 90 patients. No dramatic fluctuations in vital signs were showed in perioperative period. CONCLUSIONS In consideration of the efficiency, efficacy and safety evaluation, the disposable gastroscopes might represent an alternative to conventional reusable gastroscopes in routine examination and endoscopic mucosal resection.

Background and Aims: Fatigue is a prevalent and disabling symptom in inflammatory bowel disease (IBD), yet its underlying biological mechanisms remain poorly understood. We aimed to characterize fatigue-associated molecular signatures in IBD patients by integrating DNA methylation and mRNA expression analyses. Methods: Peripheral blood was collected from 40 patients with Crohn's disease (CD), 29 with ulcerative colitis (UC), and 10 healthy controls. Fatigue severity was assessed continuously using the Multidimensional Fatigue Inventory (MFI). Epigenome-wide DNA methylation profiling and mRNA sequencing were performed, identifying differentially methylated regions (DMRs) and differentially expressed genes (DEGs) for active and quiescent CD and UC, adjusting for age, sex, and smoking status. Pathway enrichment analysis was performed on genes with differential methylation and expression. Results: In active CD, more severe fatigue was associated with transcriptional suppression of immune and metabolic pathways (246 DMRs; 1,090 DEGs), versus upregulation of mitochondrial and metabolic processes in quiescent CD (200 DMRs; 1,619 DEGs). In active UC, fatigue was associated with anabolic pathway upregulation and epigenetic silencing of neuroactive pathways (6,927 DMRs; 343 DEGs; 56 concordant genes). Quiescent UC showed transcriptional changes without significant epigenetic pathway enrichment (1,710 DMRs; 3,224 DEGs). Healthy controls exhibited a distinct profile spanning metabolic, immune, and neuronal pathways (8,621 DMRs; 395 DEGs). Fatigue-associated signatures were largely non-overlapping across all five groups. Conclusions: Fatigue-associated molecular profiles differed substantially by disease subtype and activity state, highlighting the biological heterogeneity of IBD-related fatigue and laying the foundation for multi-omics approaches to identify biomarkers and potential therapeutic targets.

Background and AimsSteatotic liver disease (SLD) is characterized by excessive lipid accumulation in hepatocytes, and alcohol consumption may modify the disease course, but the evidence is inclusive. This systematic review and meta-analysis aimed to holistically evaluate the impact of mild, moderate, and high levels of alcohol consumption on hepatic and extrahepatic outcomes in SLD. MethodsWe systematically searched EMBASE, MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials for relevant studies. The study outcomes included liver related events, malignancy, mortality and cardiovascular disease among adults with SLD who consumed alcohol. ResultsOf 2228 records identified, twenty-six studies comprising 466611 adults with SLD were included. High alcohol consumption was associated with an increased risk of liver-related events compared with abstinence (2.97, 95% CI 1.61-5.50; p<0.001), and a similar association was observed among alcohol drinkers overall (HR 1.93, 95% CI 1.60-2.33; p<0.001). Moderate alcohol consumption was associated with a higher incidence of malignancy (HR 1.41, 95% CI 1.13-1.78; p=0.677). In contrast, mild alcohol consumption was associated with lower all-cause mortality compared with abstinence (HR 0.88, 95% CI 0.78-0.98; p=0.001). No association was observed between alcohol consumption and cardiovascular disease incidence or hepatocellular carcinoma ConclusionsAlcohol intake may increase the risk of liver-related complications and cancer risk in individuals with SLD. Mild alcohol consumption was associated with lower all-cause mortality, and alcohol intake showed no association with cardiovascular disease incidence. Further studies are needed to clarify the dose-dependent effects of alcohol on hepatic and extrahepatic outcomes in SLD.

Background: Gastric cancer surveillance in CDH1 pathogenic variant carriers is challenging, as predictors of localized (stage T1a) and advanced (stage >T1a) signet ring cell carcinoma (SRCC) are not well defined. We established the Group of investigAtors STriving toward Research In CDH1 (GASTRIC) consortium to identify clinicopathological factors associated with localized and advanced SRCC. Methods: A retrospective observational study (1998-2025) of CDH1 carriers across twelve academic centers was performed. Clinical, endoscopic, and pathological data were compared between carriers with and without SRCC on endoscopy, and between those with advanced versus localized or no cancer on gastrectomy specimens. Results: Overall, 390 CDH1 carriers from 235 families were included. Presence of SRCCs on endoscopy was significantly associated with thickened folds, nodularity, masses, and intestinal metaplasia, while gastritis was negatively associated. Of 196 carriers (52.4%) undergoing gastrectomy, 11 (5.6%) had advanced cancers, 10(90.9%) of which showed endoscopic abnormalities. Identification of SRCC on baseline endoscopy was the most sensitive feature for advanced disease (0.81) but had moderate specificity (0.74), whereas masses and thickened folds were highly specific (0.99 and 0.96, respectively) but less sensitive. Negative predictive values were high (0.94-1.0), while positive predictive values were modest (0.13-0.66). On multivariate analysis, masses and SRCC foci on baseline endoscopy were independent predictors of advanced disease. Conclusion: Among CDH1 carriers, absence of endoscopic findings was reassuring, whereas significance of detected endoscopic and pathological abnormalities was less certain. Advanced cancer occurred in a small number of carriers, with endoscopic abnormalities in nearly all cases. Endoscopic surveillance might be an alternative to surgery in carriers without worrisome mucosal findings.

Background and ObjectivesBariatric surgery is a highly effective obesity treatment, yet it may predispose individuals to alcohol-related liver injury. While altered ethanol metabolism following procedures like Roux-en-Y gastric bypass (RYGB) is well described, the long-term hepatic consequences, particularly the risk of portal hypertension in patients who develop alcohol-related hepatitis (AH,) remain poorly defined. MethodsUsing the TriNetX US Collaborative Network, we identified adult patients diagnosed with AH or alcohol-related cirrhosis. We compared outcomes between patients with a history of RYGB or sleeve gastrectomy (SG) who subsequently developed AH (Bariatric+AH group) and those with AH and no history of bariatric surgery (AH-only group). Propensity score matching was performed on over 44 demographic, clinical, and laboratory variables. Cox proportional hazards models and Kaplan-Meier survival curves were used to estimate the risk of clinically significant portal hypertension (PH) events, liver transplantation, and all-cause mortality at three-, five-, and seven-year follow-ups. ResultsAfter matching, 772 patients were included in each cohort. At 7 years post-index event, the Bariatric + AH group exhibited a significantly higher risk of PH-related complications compared to the AH-only group (HR 1.519; 95% CI, 1.15-2.005; p = 0.003). No significant differences were observed in liver transplantation (HR 1.412; 95% CI, 0.850-2.346; p = 0.181) or all-cause mortality (HR 1.085; 95% CI, 0.904-1.303; p = 0.381). These findings were consistent across all follow-up intervals. ConclusionBariatric surgery is associated with an increased long-term risk of portal hypertension in patients who develop alcohol-related hepatitis despite similar mortality and transplantation rates. These findings underscore the need for targeted postoperative counseling, liver-focused surveillance strategies, and integration of hepatologic risk assessment into metabolic surgery care pathways.

BackgroundTryptophan (Trp) metabolism is a central immunometabolic axis in inflammatory bowel disease (IBD) and has been linked to inflammatory activity and immune regulation. While individual Trp metabolites have been associated with disease severity and treatment response, systems-level frameworks to define metabolic subtypes in IBD are lacking. ObjectiveTo identify reproducible Trp-related metabolic subtypes ("metabotypes") in IBD and assess their association with disease activity, clinical outcomes, and early disease development. DesignWe applied unsupervised clustering to serum concentrations of 16 Trp-related metabolites in a discovery cohort of patients with IBD undergoing biologic induction therapy (n=134). Metabotypes were validated in three independent IBD cohorts (total n>2,800), a healthy reference population, and a prospective cohort of first-degree relatives at risk for Crohns disease. Associations with disease activity, longitudinal outcomes, and metabolic pathways were assessed using multivariable regression and survival analysis. ResultsFour reproducible metabotypes with distinct metabolite profiles were identified across cohorts: Low Kyna, High Kyna, High Quin, and Balanced. Low Kyna and High Quin metabotypes were consistently associated with increased inflammatory activity and adverse clinical outcomes, including increased risk of treatment escalation and disease progression. Pathway-level analyses revealed alterations in NAD-related, lipid, and amino acid pathways between inflammatory metabotypes. A metabotype resembling inflammatory disease states was enriched in individuals who later developed Crohns disease in a prospective pre-disease cohort. ConclusionTrp-linked metabotypes define reproducible immunometabolic states in IBD that associate with disease activity and clinical outcomes and may precede disease onset. These findings provide a framework for metabolic stratification and biomarker-guided clinical trials targeting immunometabolic pathways. What is already known on this topicTryptophan metabolism through the kynurenine pathway is a central immunometabolic axis in inflammatory bowel disease (IBD) and has been linked to inflammatory activity and immune regulation. Individual tryptophan metabolites have been associated with disease severity and treatment response, but their clinical utility for patient stratification remains limited. Systems-level approaches to define clinically meaningful metabolic subtypes in IBD are lacking. What this study addsWe identify four reproducible tryptophan-related metabolic subtypes ("metabotypes") that are consistently associated with disease activity across multiple independent IBD cohorts. Inflammation-associated metabotypes show distinct pathway-level alterations, including differences in NAD-related metabolism and broader metabolic programs. A metabotype resembling inflammatory disease states is detectable before clinical diagnosis in individuals who later develop Crohns disease. How this study might affect research, practice or policyMetabotype-based classification provides a framework for molecular stratification of patients in mechanistic studies and clinical trials targeting immunometabolic pathways. This approach may support biomarker-guided monitoring of disease activity and disease progression in IBD. Identification of preclinical metabolic states highlights the potential of metabolomics for early disease detection and prevention-oriented research strategies.

BackgroundVedolizumab, a gut-selective anti-integrin therapy, is effective in IBD, but response rates remain variable. Conventional clinical and biochemical markers, including C-reactive protein and faecal calprotectin, have limited predictive value. Although recent transcriptomic studies have implicated T-cell-related signatures in predicting vedolizumab response, these findings lack validation across independent cohorts. MethodsWe analyzed pre-treatment transcriptomic profiles from whole blood and T-cell subsets across five independent cohorts comprising 100 patients with UC and CD. The primary outcome was clinical response. Secondary outcomes included clinical and biochemical remission. ResultsAmong the 100 patients, 61 were responders and 39 non-responders, with no significant baseline clinical differences. Gene set enrichment analyses revealed downregulation of interferon alpha and gamma signalling in responders baseline blood samples, a finding validated across independent cohorts. Downregulated interferon signalling at baseline was also observed in patients who achieved clinical and biochemical remission. To build a predictive model, an adaptive elastic net logistic regression model was applied to baseline whole-blood RNA-sequencing data. The classifier achieved an AUC of 1.0 in training, 0.71-0.83 in UC validation cohorts, and 0.64-1.0 in CD cohorts. Reduced interferon signalling was observed across CD4{square} and CD8{square} T-cell subsets, including regulatory T cells, suggesting a broad immune signature rather than cell-type specificity. ConclusionsDownregulated interferon signalling in peripheral blood prior to treatment is a reproducible molecular signature predictive of vedolizumab response and biochemical remission. Whole-blood transcriptomics revealed a robust interferon-axis signal that predicted vedolizumab response across independent cohorts, with stronger performance in UC than CD. Given heterogeneous clinical endpoints and assessment windows, these data provide proof-of-concept that warrants validation with standardised, endoscopy-based outcomes.

Background: Jejunal diverticulitis is an uncommon but increasingly recognized cause of acute abdomen. It can present with a range of CT findings, including peridiverticular inflammation, bowel wall thickening, and fecalized small bowel content, with perforation or abscess occurring as complications in roughly 6% of cases. Case reports note varied presentations with jejunal and ileal involvement, treatment ranging from nonoperative management with antibiotics to urgent surgical intervention. Though rare, small bowel diverticulitis, particularly involving the jejunum, can result in significant morbidity, including peritonitis and sepsis, requiring heightened clinical suspicion in elderly or immunocompromised patients. Methods: We conducted a single center retrospective review of patients diagnosed with jejunal diverticulitis in a single academic center's Emergency General Surgery registry between December 2017 and December 2024. Of 42 patients initially identified, 34 had confirmed diagnoses on chart review. Data abstracted included age, sex, imaging modality, presence of perforation, serial physical exams, lab values (CBC, lactate), ICU admission, length of stay (LOS), antibiotic duration, operative status and timing, distance of residence from our institution, disposition after index admission, and readmission within one year. Results: Of the 34 confirmed cases, 24 (71%) were perforated: 2 presented with small bowel obstruction, 16 with abscesses and/or contained perforations, and 1 with both. 19 of the 24 perforated patients required operative intervention: 9 proceeded directly to the OR, 3 on hospital day one, and 2 as late as hospital day six. Among non-operative patients treated with antibiotics alone, the average LOS was 6 days (range: 2-23). Two patients were readmitted within one year: neither had undergone surgery during their index admission and neither were related to their index admission. Overall, three patients died: two during the index admission (both perforated and operated on) and one on readmission. Conclusion: Compared to the 6% complication rate reported in prior literature, our series demonstrates a notably higher rate of perforation (71%) among patients diagnosed with jejunal diverticulitis. Operative intervention was common, though a subset of patients was successfully managed non-operatively with antibiotics. Mortality was limited to patients with significant comorbidities and complex presentations. These findings underscore the heterogeneity in presentation and outcomes and highlight the need for a standardized approach. Development of practice guidelines incorporating clinical, radiographic, and laboratory parameters may improve diagnostic accuracy and guide timely, evidence-based management of this rare but serious condition.

Background & Aims: ACLF is defined differently by APASL (acute hepatic dysfunction) and by organ failure-based frameworks including EASL-CLIF and the recently developed A-TANGO score. Whether these definitions identify competing populations or sequential stages of the same syndrome remains unresolved, with direct implications for the timing of intervention. We tested whether APASL-defined ACLF can be integrated into the A-TANGO framework to identify a clinically actionable patient population. Methods: 4,024 patients hospitalised with acute decompensation of cirrhosis in a multicentre cohort were classified simultaneously by APASL and A-TANGO criteria. Mortality, progression to A-TANGO ACLF among A-TANGO-negative patients, and reversal of ACLF were assessed using Fine-Gray competing-risk models with death as a competing event. EASL-CLIF analyses were performed as sensitivity analyses. Results: A-TANGO-negative/APASL-positive patients comprised 8.7% of the cohort and had higher 90-day mortality than A-TANGO-negative/APASL-negative patients (22.3% vs 14.4%, p=0.001), despite similar 28-day mortality. Once A-TANGO ACLF was established, 28-day mortality was high irrespective of APASL status (45.4% in APASL-positive and 56.0% in APASL-negative patients). Among A-TANGO-negative patients, 53.5% of APASL-positive vs 27.9% of APASL-negative patients progressed to A-TANGO ACLF within 28 days, with APASL positivity independently predicting progression (adjusted sHR: 2.30, 95%CI: 1.90-2.77). Within A-TANGO-negative/APASL-negative patients an A-TANGO OF score [&ge;]8 independently enriched for progression (52% vs 19%). A-TANGO reversal occurred in 17.1% and was independently reduced by APASL positivity (adjusted sHR: 0.756, 95%CI: 0.586-0.975), while APASL reversal was rare (4.0%). EASL-CLIF sensitivity analyses were directionally consistent. Conclusions: APASL-defined ACLF does not compete with A-TANGO; it occupies an upstream position on the same disease trajectory. A-TANGO-negative/APASL-positive patients and A-TANGO-negative/APASL-negative patients with A-TANGO OF [&ge;]8 represent complementary pre-ACLF populations suitable for prevention trials and enrichment strategies.

Irritable Bowel Syndrome (IBS) is a highly prevalent, commonly diagnosed gastrointestinal disorder of gut-brain interaction (DGBI) that causes substantial physical, psychological, and financial burden. The role of abnormal motility and altered autonomic nervous system function, and their interplay, remains to be fully understood. Here we present a non-invasive method using body surface electrical recordings to concurrently quantify meal-response colonic motility and heart rate variability (HRV). We demonstrate the practical utility of this new technique in a pilot study comparing colonic motility and autonomic nervous system (ANS) function in IBS patients (n=14) and healthy controls (HC; n = 22). The study protocol included a 2-3 hr body-surface electrical recording with 60-90 minutes each of pre- and post- meal epochs. Colonic motility was markedly increased in the subset of IBS patients experiencing moderate-to-severe symptoms during the study, compared to IBS no or mild symptom groups and healthy controls. HRV metrics in IBS patients showed substantial baseline shifts with decreased vagal and increased sympathetic input, with blunted autonomic meal responses compared to HC. Newly introduced dynamic trajectory maps revealed pronounced colon motility-vagal dysregulation in high symptom IBS patients but not mild or no symptom groups. These results indicate altered autonomic-motility interaction as a potential mechanism of symptom genesis in IBS patients. This technology platform offers an easy-to-apply, non-invasive tool for larger scale investigations of gut and autonomic nervous system function in healthy and gastrointestinal disease cohorts.