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.

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 [≥] 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 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 & 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.

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 & 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.

Background: Heterogeneity in symptom presentation and treatment response in irritable bowel syndrome (IBS) remains poorly understood. The gut microbiota may contribute to this variability, but its role in shaping symptom trajectories and responses to self-management interventions is unclear. Objective: To identify symptom trajectory phenotypes and determine whether gut microbiota composition and function distinguish these phenotypes and predict multidimensional responses to pain self-management interventions in young adults with IBS. Design: Ancillary data analysis from a randomized control trial (NCT03332537). Methods: Participants with longitudinal data (n = 62) were analyzed using longitudinal k-means clustering (KML) based on trajectories of measures in IBS quality of life (QOL), Brief Pain Inventory (BPI), and psychoneurological outcomes (anxiety, applied cognition, depression, fatigue, global health, positive affect, and sleep disturbance) over 12 weeks. Baseline differences between clusters were assessed with Wilcoxon rank-sum tests, and longitudinal changes were evaluated with linear mixed models. Gut microbiota composition and predicted functional pathways were compared between phenotypes. Bayesian Additive Regression Trees (BART) models were used to identify baseline microbial taxa and pathways predictive of longitudinal changes in QOL, BPI pain interference, and severity. Results: Two distinct trajectory-defined response phenotypes were identified: a Constrained Response Phenotype (Phenotype A, n = 35) and an Adaptive Multidomain Response Phenotype (Phenotype B, n = 27). At baseline, Phenotype B showed lower pain severity and interference, but higher levels of anxiety, depression, and fatigue compared to Phenotype A. Over 12 weeks, both phenotypes showed improvements in pain outcomes (all p < 0.05), but only Phenotype B demonstrated broad improvements across psychoneurological domains and QOL (all p < 0.05). Phenotype A exhibited more limited improvements and worsening in several psychoneurological domains. Gut microbiota functional pathways differed between phenotypes, including pathways related to xenobiotic degradation, amino acid metabolism, bile secretion, and immune-related processes (all raw p < 0.05), although these did not remain significant after multiple testing correction. Machine learning models identified distinct, phenotype-specific microbial predictors of intervention response. In Phenotype A, genera such as Alistipes and Sutterella were consistently identified across models, whereas in Phenotype B, predictors included Phascolarctobacterium, Collinsella, and Parabacteroides. Functional pathways also differed between phenotypes, suggesting distinct microbiome-linked mechanisms underlying symptom trajectories and responses to pain interventions. Conclusions: Young adults with IBS exhibit distinct multidimensional response phenotypes that are associated with differential clinical and microbiome profiles. Baseline gut microbiota composition and functional capacity demonstrate phenotype-specific predictive signatures of treatment response, supporting a microbiome-informed framework for stratifying patients and advancing personalized self-management strategies in IBS.

Objective To verify the reliability of a self developed bowel sound monitoring device under real biological tissue acoustic propagation conditions using a controllable sound source, and to establish quantitative evidence for its translational applicability. Methods Freshly euthanized six month old Bama miniature pigs were used as an experimental model. A high fidelity Bluetooth audio playback device was implanted into the abdominal cavity to deliver manually annotated bowel sound recordings as controllable acoustic stimuli. A self developed bowel sound monitoring device was fixed on the abdominal surface for continuous signal acquisition. Playback timestamps were defined as the ground truth, and event level matching was performed within a predefined temporal tolerance window. Four performance indicators were evaluated: (1) bowel sound acquisition and energy amplification, (2) event matching accuracy, (3) acoustic feature consistency, and (4) subjective agreement assessed by blinded auscultation from gastroenterologists with different levels of clinical experience. Results The monitoring device exhibited stable detection capability and effectively covered the full spectral range of the original signals. It significantly enhanced bowel sound energy while preserving temporal and spectral characteristics, demonstrating high consistency in time and frequency domain features. Blinded clinician assessments showed a subjective agreement rate of 88.9% between original and surface recorded bowel sound events. Conclusions Under real tissue acoustic propagation conditions, the self-developed bowel sound monitoring device reliably captures bowel sound events with high temporal accuracy, acoustic fidelity, and clinical perceptual consistency. This controllable sound source based validation provides robust technical evidence for subsequent in vivo studies and clinical translation, supporting the development of objective and continuous gastrointestinal function monitoring.

Background & Aims: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the leading cause of chronic liver disease in children. However, accurate, noninvasive diagnostic tools remain limited. Current screening methods are invasive or lack sensitivity. Breath-based volatile organic compound (VOC) analysis offers a simple approach with potential for point of care screening. This study aimed to identify and validate breath VOC signatures of pediatric MASLD. Approach & Results: We conducted a prospective IRB approved cohort study at the Childrens Hospital of Philadelphia (CHOP). Children aged between 7 and 20 years with MASLD (n=22), as defined by hepatic steatosis either by liver biopsy or imaging and 1 cardiometabolic risk factor, and a control group without MASLD (n=20) were enrolled. Breath samples were collected using a standardized protocol and analyzed by untargeted comprehensive two-dimensional gas chromatography-mass spectrometry (GCGCMS). Machine learning and unsupervised clustering were applied to identify discriminatory VOCs and assess heterogeneity. Untargeted GCGCMS analysis identified a distinct breath VOC signature in children with MASLD compared with non MASLD controls. A Random Forest model achieved a sensitivity of 73% and specificity of 65%, with AUC of 0.84. The VOC 2,4-dimethyl-1-heptene demonstrated strong diagnostic performance in the discovery cohort with a sensitivity of 85%, specificity of 77% and an AUC of 0.81. Unsupervised clustering revealed four MASLD subgroups with distinct volatile phenotypes associated with differences in liver enzymes and metabolic parameters. External validation in a second pediatric cohort confirmed reproducible reductions in o/p-xylene in subjects with MASLD. Conclusions: Pediatric MASLD is associated with a reproducible breath VOC signature identified by untargeted GCGCMS. These findings support breath analysis as a scalable, noninvasive screening and stratification tool for pediatric MASLD and warrant validation in larger, longitudinal studies.

Background: Colon capsule endoscopy (CCE) has been proposed as a non-invasive alternative to colonoscopy for colorectal cancer (CRC) screening, offering greater patient comfort and potentially reducing healthcare burden. However, its cost-effectiveness in population-based screening remains uncertain. Methods: This study used a state-transition (Markov) model to simulate lifetime outcomes of CRC screening in Denmark, Scotland, and Spain, comparing the standard pathway based on fecal immunochemical testing (FIT) followed by colonoscopy with an alternative pathway replacing colonoscopy with CCE after a positive FIT result. The model incorporated costs (2024 euros), quality-adjusted life-years (QALYs), and CRC cases avoided, applying a yearly discount rate of 3%. Deterministic sensitivity analyses explored uncertainty in capsule cost, adherence, and reinvestigation rates for non-advanced polyps. Results: Across all settings, CCE resulted in higher costs but slightly increased effectiveness and utility (mean QALYs 28.7 vs. 28.8; CRC detected 0.032-0.034 vs. 0.035-0.037 per person). Incremental cost-effectiveness ratios (ICER) ranged from 43,538EUR in Spain to 136,930EUR in Denmark per additional CRC detected. Capsule cost was the main driver of ICER variation, whereas adherence rates had minimal effect on cost-effectiveness. Changes in the prevalence of non-advanced polyps had a modest impact, except when capsule prices were high. Conclusions: Overall, replacing colonoscopy with CCE slightly increases detection and health gains at the expense of higher costs. Cost-effectiveness largely depends on capsule price and adherence. Artificial intelligence-assisted CCE interpretation may further improve diagnostic and economic performance, potentially supporting adoption in large-scale CRC screening programs.

Background: Histological examination of mucosal tissue in inflammatory bowel diseases (IBD) is a sensitive tool to measure disease activity, and histological remission is emerging as a potentially important treatment target. There are several existing histopathological indices, but they often encompass caveats such as not primarily having been designed to measure the degree of inflammation, encompassing subjective components with poor intra- and interindividual reproducibility, and requiring expert pathologists who are scarce, thus resulting in extended response times. Aim: To construct a new computerized, automated index to objectively measure histological disease activity in the ileal and colonic mucosa, applicable to both Crohn's disease (CD) and ulcerative colitis (UC). Materials and methods: Ileocolonic biopsies were collected from control subjects and patients with CD or UC. A group of CD patients was sampled before and after 12 weeks of anti-TNF therapy. Another group of CD and UC patients functioned as a small validation cohort. Epithelial cells, neutrophils, macrophages, and T cells were immunohistochemically stained, followed by digitalization of the color signal and computerized delineation of the epithelial and lamina propria compartments. The various immune cell types within the epithelium and the lamina propria, respectively, were enumerated, and the numbers were compared between control subjects and patients with CD or UC. Results: The numbers of neutrophils and macrophages in the epithelium, and neutrophils in the lamina propria, showed the highest sensitivity and specificity for distinguishing control-subject tissues from CD and UC tissues. These three parameters were thus chosen to construct a new index, named QiC3 1.0, that could separate tissues from control subjects and patients with CD or UC with high precision. It performed equally well in a small validation cohort of patients. The QiC3 index correlated well with previously described histopathological indices, fecal calprotectin, and endoscopic scores in UC, but showed worse correlation with endoscopic scores in CD and symptomatic scores. When applying the new index to tissues from CD patients before and after therapy, it showed good responsiveness, demonstrating a distinct amelioration in the microscopic inflammatory status that corresponded well to improvements in histopathological scores. Conclusion: We describe a new quantitative, computerized, automated, non-subjective, and response-sensitive immunohistological index (QiC3) for measuring disease activity in ileal and colonic mucosal biopsies, suitable for both CD and UC.

Background: Black patients and individuals with low socioeconomic status (SES) face significant disparities in accessing curative therapies for hepatocellular carcinoma (HCC), including liver transplantation. This study aimed to develop provider-co-created intervention prototypes in response to patient-identified barriers and recommendations. Methods: A human-centered design session with hepatology and transplant providers at a large academic medical center was conducted. Prior to the session, participants were presented with barriers and preliminary solutions identified through an earlier human-centered design session with Black and low-SES patients. Using structured ideation methods, including brainwriting, challenge mapping, and concept voting, providers co-created intervention prototypes. Final concepts were synthesized from patient insights, provider input, and design methods using affinity diagramming and concept modeling. Results: Nine providers participated in the session. They focused on three key areas for intervention: inefficiencies in transplant pre-evaluation, inadequate social support, and information overload. Solutions included: (1) a structured triage pathway to standardize referrals and reduce delays; (2) a peer navigator model to guide patients through the transplant process; and (3) a multimodal transplant education roadmap to improve comprehension and engagement. These prototypes addressed both patient- and system-level barriers. Conclusions: Protypes developed through provider-led design, grounded in patient-identified barriers and co-created ideas, can yield actionable, scalable strategies to advance equity in HCC care. Future work will refine these prototypes through patient feedback and pilot them in clinical settings.

Background One in four surgical patients carries a drug allergy label, of which an estimated 90% are incorrect. Avoidance of first-choice drug therapies may lead to worse postoperative outcomes. We sought to determine the nature and extent of any association between drug allergy labels and postoperative complications. Methods A multicentre observational study in 21 NHS hospitals. Eligible patients were 18 years or older, undergoing common surgical procedures: primary hip or knee replacement; internal fixation of closed long bone fracture; colorectal resection; trans-urethral resection of prostate or bladder tumour; caesarean section; hysterectomy. Exclusion criteria: use of antibiotics in the two weeks prior to surgery, previous participation in the study. Primary outcome was postoperative complications within 30 days following surgery, a composite outcome comprising: all postoperative infections, anastomotic leak, acute respiratory distress syndrome, myocardial infarction, postoperative bleed, pulmonary embolism, stroke, antimicrobial side effects, death. Results Among 13,646 patients, 3924 (29%) carried greater than or equal to1 drug allergy labels. Labelled patients were more likely to develop postoperative complications (989/3924 (25%) vs 1926/9722 (20%); OR 1.21 [1.10-1.34]; p<0.001). They were more likely to develop surgical site infections (337/3924 (9%) vs 760/9722 (8%); OR 1.19 [1.03 -1.38]; p<0.018), and any postoperative infection (750/3924 (19%) vs 1472/9722 (15%); OR 1.24 [1.11-1.38] p<0.001). Labelled patients experienced increased risk of allergic drug reactions (31/3924 (0.01%) vs 29/9722 (<0.01%); OR 3.00 [1.77-5.09]; p<0.001), but no increase in mortality. Conclusions Drug allergy labels are common, but often incorrect. Labelled patients experience worse postoperative outcomes, including infective and non-infective complications and increased risk of allergic drug reactions. Trial registration Registered with ISRCTN registry, ISRCTN15775657.

Background: African Americans (AA) experience disproportionate burden of colorectal cancer (CRC). Dysregulation of the Wingless-related integration site (WNT) pathways contributes to tumor progression, yet their prognostic roles in FOLFOX-treated CRC among AA patients remain understudied. Methods: We analyzed 2,562 CRC cases stratified by ancestry, age at onset, and FOLFOX treatment using Fisher's exact, chi-square, and Kaplan-Meier analyses from AACR Project GENIE and cBioPortal databases. To enhance data integration and interpretation, we applied AI-HOPE and AI-HOPE-WNT, conversational artificial intelligence (AI) platforms designed to integrate clinical, genomic, and treatment data through natural language-driven queries. Results: Overall survival analyses showed that early-onset CRC (EOCRC) AA patients treated with FOLFOX who had WNT pathway alterations experienced significantly better survival (p = 0.035). WNT pathway alterations were less frequent in late-onset AA patients treated with FOLFOX compared to those not treated (80% vs. 92%; p = 0.05). Conclusions: Chemotherapy exposure may influence pathway-specific mutation frequencies across ancestry and disease stage. AI-enabled integrative analyses highlight the potential of conversational AI platforms to accelerate biomarker discovery and reveal ancestry- and treatment-specific vulnerabilities in CRC.