American Journal of Gastroenterology

Looping is a major cause of difficult and painful insertion during unsedated colonoscopy, yet strategies are largely guided by trial and error; prolonged insertion may jeopardise completion, discourage future surveillance and is associated with lower adenoma detection. In this randomised trial of 141 patients, protocolised review of pre-existing abdominal-pelvic computed tomography (CT) anticipated colonic anatomy and shortened caecal intubation time by 136 s, while reducing pain, discomfort and operator workload and increasing willingness to repeat colonoscopy. Effects were largest in N-loop and alpha-loop configurations, which accounted for 83% of patients. Routinely acquired CT could support anatomy-informed colonoscope insertion especially when anesthesia services are limited or sedation poses an elevated risk.

Background Optimal timing for resuming direct oral anticoagulants (DOACs) after high-risk endoscopic procedures remains uncertain, and existing recommendations derive largely from expert opinion. The objective of this study was to characterize practice patterns and perceptions among endoscopists and outcome prioritization among patients with atrial fibrillation, in order to inform the design of the planned RESUME randomized trial. Methods We conducted parallel, cross-sectional surveys of practicing endoscopists and patients with atrial fibrillation using electronic questionnaires administered via Qualtrics. The endoscopist survey, distributed through the American Society for Gastrointestinal Endoscopy, assessed practice patterns, acceptability of early (postoperative day [POD] +1), intermediate (POD +3), and late (POD +5) resumption strategies, and perceptions of clinical equipoise. The patient survey, distributed through two advocacy organizations, assessed perceived confidence in existing guidance and prioritization of bleeding versus thromboembolic risk. Results A total of 201 endoscopists and 477 patients (92.5% taking a DOAC) provided evaluable responses. Endoscopists demonstrated wide variability in preferred timing of DOAC resumption after a standardized high-risk mucosal resection vignette, ranging from same-day resumption to delays beyond five days. POD +2 was the most commonly selected strategy, and most respondents rated more than one proposed RESUME trial arm as acceptable. Nearly all endoscopists (98.9%) rated a randomized trial to determine optimal timing as important. Patient preferences regarding bleeding versus stroke risk were heterogeneous and symmetrically distributed around the neutral response on a five-point ordinal scale. Preferences did not differ by prior stroke or transient ischemic attack, prior major bleeding, age, sex, or geographic region. More than half of patients (54.6%) reported being very or somewhat confident that clear guidance exists regarding DOAC resumption, despite the absence of high-quality randomized evidence informing this question. Conclusions Endoscopists demonstrate substantial practice variability and clinical equipoise, and patients demonstrate heterogeneous and balanced outcome preferences, regarding the timing of DOAC resumption after high-risk endoscopy. These findings support the ethical justification and relevance of the planned RESUME trial.

Background: Blood-based colorectal cancer (CRC) screening is a novel, less invasive screening that has the potential to improve CRC screening adherence, particularly among Black American populations, which has historically lower screening rates. We evaluated factors associated with preference for blood-based CRC screening among Black adults in church-based community settings. Methods: From October 2023 to January 2024, a cross-sectional survey was conducted over 101 adults aged 45 to 75 years at three Black churches in metropolitan Atlanta, Georgia. Demographics, CRC screening history, healthcare access, and attitudes toward blood-based CRC screening were assessed. Results: Overall, 72 participants (71.3%) preferred blood-based CRC screening. Preference was not associated with demographic or socioeconomic characteristics, screening history, or healthcare access. The most commonly reported reasons for ease of testing (83.3%), avoidance of stool collection (38.9%), avoidance of bowel preparation (36.1%), perceived fewer side effects (34.7%), and perceived lower risk (33.3%). Needle concerns were the only factor significantly associated with non-preference (p=0.034). Conclusion: Blood-based colorectal cancer screening was preferred by most Black adults and may improve CRC screening participation through greater convenience.

Background. Anaerostipes caccae CLB101TM is a next-generation probiotic that directly produces butyrate and is hypothesized to reduce gastrointestinal symptoms by strengthening intestinal barrier integrity. Clinical evidence for A. caccae in symptomatic adult populations remains limited. Methods. Ninety-three adults were randomized 1:1 to CLB101TM ( n=47) or placebo (n=46) for 28 days. The primary outcome was safety and tolerability as assessed by the number, frequency, and severity of adverse events. Secondary outcomes were focused on exploring signals of efficacy, and included change in the Gastrointestinal Symptom Rating Scale (GSRS) composite score from baseline to Week 4. Five GSRS subcategories were additionally evaluated. Exploratory endpoints included daily self-reported GI symptoms, as well as stool and blood measures of intestinal barrier function. Results. 71 participants were evaluated for the GSRS (77.5% female, aged 42.1 SD 12 years, BMI mean 31.3 SD 3.6). No adverse events were reported in the placebo arm, while three self-limiting adverse events were associated with CLB101TM administration. CLB101TM reduced GI symptom burden versus placebo on the primary GSRS composite at Week 4 (mean change: -1.60 vs -0.90; MWU p=0.040). Two secondary subscales reached significance after FDR-BH correction: Reflux (mean change: -1.26 vs -0.30; FDR-adjusted p=0.024) and Abdominal Pain (mean change: -1.86 vs -0.83; FDR-adjusted p=0.024). Daily symptom diaries showed trends toward greater reductions in abdominal discomfort, bloating, and flatulence in the active arm at the end of study. This study population did not demonstrate signs of intestinal barrier dysfunction. Product adherence averaged 97.7%. Conclusions. CLB101TM was safe and tolerable and significantly improved overall GI symptom burden, reflux, and abdominal pain after four weeks of daily supplementation in overweight symptomatic adults. Trial Registration. The trial was approved by Sterling IRB (14583-NACraft) and registered with ClinicalTrials.gov (NCT07336615).

ABSTRACT Background and study aims: Patients on direct oral anticoagulants (DOACs) undergoing high-risk endoscopy face competing risks of bleeding and thromboembolism during peri-procedural anticoagulant interruption. We quantified peri-procedural adverse event (AE) rates and incremental healthcare costs. Patients and methods: Retrospective cohort study using the TriNetX Linked Claims database (2015-2025), a US-wide multi-payer claims network. Adults on DOAC or warfarin therapy who underwent high-risk endoscopy were included (N=2,486 unique patients; N=1,933 with linked cost data). Peri-procedural bleeding and thromboembolic events were identified using principal-diagnosis codes in acute care encounters (emergency department or inpatient) within 90 days of the index procedure. Unadjusted and multivariable-adjusted incremental 90-day costs were compared between patients with and without each AE type using generalized linear models. Results: Among 2,486 anticoagulated patients (median age 65; 61.5% male; 81% with atrial fibrillation), bleeding occurred in 18.0% at 7 days and 22.9% at 90 days. Stroke/TIA occurred in 0.5% at 7 days and 1.7% at 90 days. Each thromboembolic event cost approximately 2.5 times more than each bleeding event. Stroke/TIA added $8,874 unadjusted (p<0.001) and $5,798 adjusted (cost ratio 1.56; 95% CI 1.11-2.20; p=0.011); bleeding added $3,471 unadjusted and $3,157 adjusted (cost ratio 1.33; 95% CI 1.18-1.50; p<0.001). Patients experiencing both bleeding and subsequent stroke/TIA had the highest costs (mean $23,716). Conclusions: Peri-procedural thromboembolic events cost the healthcare system 2.5-fold more per event than bleeding, underscoring the clinical and economic importance of periprocedural DOAC management and motivating randomized evidence on optimal DOAC resumption timing strategies.

Background: Functional dyspepsia (FD) is among the most common gastrointestinal disorders worldwide and is characterized by symptoms including epigastric pain, early satiety, postprandial fullness, bloating, and upper abdominal discomfort. Itopride hydrochloride is commonly administered as 50 mg three times daily (TID). To improve convenience and potentially enhance adherence, a once-daily (OD) 150 mg extended-release formulation was developed. Phase 1 studies demonstrated bioequivalent overall exposure between the OD and TID regimens, with sustained-release characteristics and no evidence of dose dumping, supporting advancement to Phase 3. This pivotal clinical study evaluated whether itopride hydrochloride 150 mg OD is non-inferior to the established 50 mg TID regimen in improving FD symptoms over 8 weeks. Methods: This Phase 3, randomized, open-label, multicenter, active-controlled study enrolled 564 participants with FD (or chronic gastritis) to compare the efficacy and safety of itopride hydrochloride 150 mg OD versus 50 mg TID over 8 weeks. The primary endpoint was change in overall FD severity from baseline to Week 8, assessed using the Leeds Dyspepsia Questionnaire (LDQ) severity score. Secondary endpoints included symptom-specific severity, disease-specific quality of life, responder rates, treatment acceptance, and safety. Results: Clinical non-inferiority in terms of overall FD severity was demonstrated with OD treatment compared to TID. LDQ severity improved by -9.60 (95% CI -10.15, -9.05) with TID and -9.76 (95% CI -10.32, -9.19) with OD, with a between-group difference of 0.16 (95% CI -0.42, 0.74). Improvements across symptom domains and quality of life measures were comparable. Treatment acceptance favored OD (mean 4.22 vs 3.83; p < 0.001). Both regimens were well tolerated, with predominantly mild adverse events. This clinical evaluation of OD was supported by the Phase 1 results confirming that both single-dose and multiple-dose administration of itopride hydrochloride 150 mg OD provided a comparable extent of exposure to the 50 mg TID regimen, demonstrated by area under the curve (AUC) values within the 80 to125% bioequivalence range and stable pharmacokinetic profiles across fed and fasted conditions. Conclusion: The study confirmed that itopride hydrochloride 150 mg OD is non-inferior to the TID regimen for improving FD (or chronic gastritis) symptoms. The OD regimen demonstrated comparable efficacy, favorable treatment acceptance, and a positive benefit-risk profile, offering a more convenient therapeutic option for patients.

Objective Vedolizumab (VDZ) is effective in ulcerative colitis (UC), but its onset of action may be relatively slow during induction therapy. VSL#3TM, a high-potency multi-strain probiotic, may provide synergistic effects through microbiota modulation and immune regulation. This preliminary real-world study aimed to evaluate the efficacy and safety of VSL#3TM combined with VDZ in patients with UC. Methods Clinical data were retrospectively collected from patients with active UC who received VSL#3TM combined with VDZ for at least 12 weeks at the Second Affiliated Hospital of Zhejiang University School of Medicine in China between January 2023 and December 2024. The primary endpoints were clinical response rates at weeks 6 and 12. Secondary endpoints included clinical remission, changes in inflammatory bowel disease questionnaire (IBDQ) scores, safety assessment. Results Using PRO2 criteria, clinical response rates were 82.4% (14/17) at 6 weeks and 100.0% (17/17) at week 12, with clinical remission in 58.8% (10/17) at week 12. By Full Mayo Score, clinical response and remission at week 12 were 68.8% (11/16) and 50.0% (8/16), respectively. These response rates appeared numerically higher than those reported in published historical VDZ monotherapy studies, although direct comparisons are limited by the single-arm design. Mean IBDQ score improved from 157.3 at baseline to 174.5 at week 12 (p<0.001). The combination was well-tolerated with no serious adverse events. Fatigue, borborygmus, and arthralgia were reported in 1/17 (5.9%), 2/17 (11.8%), and 1/17 (5.9%) patients, respectively. Notably, all 3 patients with baseline history of Clostridioides difficile (CDI) positivity tested negative for both toxin and antigen at 12 weeks; one toxin-positive patient had received anti-CDI antibiotic therapy. Conclusions This preliminary real-world study suggests that VSL#3TM may enhance early clinical outcomes in patients receiving VDZ for active UC. The observed benefits may be related to complementary effects on the gut microbiota and intestinal immune responses, although these mechanisms were not directly assessed. Further larger prospective randomized controlled trials are warranted to confirm these findings.

Background: Endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), with or without the esophageal gland duct involvement (DI or NDI), has been reported in small case series, but ESD-related safety, efficacy, and outcomes remain unknown. We conducted a retrospective study of those issues in consecutive 748 patients treated at our center in China. Material and Methods: Over the study period from January 2014 to January 2019, we identified 748 eligible SESCC patients who were divided into the DI (22.6%, 169/748) and NDI (77.4%, 579/748) groups, based on histopathologic reports. Following the European and Japanese guidelines on endoscopic resection of SESCC, we investigated and statistically compared characteristics of clinicopathology and ESD-related safety, efficacy, and prognosis between DI and NDI groups. Results: The mean age of patients was 64.9 years for the cohort and significantly older in the DI (66.1) than in the NDI (64.5) group (P<0.05). There was no significant difference in smoking/alcohol abuse and comorbidity. Endoscopically, the DI group showed significantly larger tumor size and deeper invasion than the NDI group. There was no ESD-related death in the cohort. Although the en bloc resection rate was 100%, the complete and curative resection rates were significantly lower in the DI (88.2% and 61.2%, respectively) than in the NDI (96.4%, and 86.9%, respectively) group (P<0.01). ESD-related infection (0.7%) and bleeding (2.3%) rates were very low and no significant difference was found between the two groups. Only one perforation (0.1%) occurred in the NDI group. Post-ESD stenosis was 11.9% for the cohort and significantly more common in the DI (20.7%) than in the NDI (9.3%) group (P<0.01). The overall survival rate was 95.7% for the cohort and significantly lower in the NDI (94.6%) than in the DI (100.0%) group (P<0.05). However, there was no significant difference in disease-specific death, recurrence-free survival, distant metastasis, and the requirement for subsequent chemoradiation therapy and surgery between the two groups. Conclusion: In our cohort, there was no ESD-associated death; ESD-related infection and bleeding were minimal; and perforation was rare. Post-ESD stenosis was 11.9% in prevalence and successfully managed by endoscopic dilation. The overall survival rate was 95.7%. Compared to the NDI group, the DI group showed older age, larger tumor size, deeper invasion, lower complete and curative resection rates, higher prevalence of post-ESD stenosis; there was no significant difference in disease-specific death. Taken together, ESD was safe with excellent efficacy and prognosis for endoscopic resection of SESCC with or without esophageal gland duct involvement. Keywords: superficial esophageal squamous cell carcinoma, endoscopic submucosal dissection, ductal involvement, survival, postoperative stenosis.

Introduction: Illness perceptions, the cognitive and emotional beliefs patients hold about their condition, are key determinants of patient outcomes across a range of chronic health conditions. Although well-studied in several gastrointestinal disorders, their role remains poorly characterized within patients with functional dyspepsia (FD) and chronic nausea and vomiting syndrome (CNVS). This study examined the associations between illness perceptions, gastrointestinal symptoms, mental health, and gastric electrophysiology in these patients. Methods: Patients meeting self-reported Rome IV criteria for FD and/or CNVS underwent body surface gastric mapping (BSGM) using Gastric Alimetry (Alimetry, New Zealand). The standardized protocol included a 30-minute fasting baseline, 482 kCal meal, and a 4-hour postprandial recording, with concurrent symptom logging. From the BSGM data, patients were phenotyped using established rule-based criteria via the Auckland Classification. Illness perceptions were assessed using the Brief Illness Perceptions Questionnaire alongside validated psychological and quality of life metrics. Results: The cohort included 309 patients (80% female; median age= 36, 15-88) who reported highly negative illness perceptions, which were significantly correlated with worse symptomatology, quality of life, and mental health (medium-large effect sizes). Using multivariable analysis, perceived consequences and emotional responses emerged as the most robust predictors of these patient-reported outcomes. Additionally, illness perceptions significantly mediated the relationship between mental health and gastrointestinal symptoms, with large effect sizes. Associations with gastric electrophysiology were limited to BMI-Adjusted Amplitude, which was associated with poorer perceptions of treatment control and greater emotional response to symptoms. Furthermore, the Continuous Phenotype (normal spectral activity, with continuous symptoms) was associated with worse illness perceptions, including higher perceived consequences, symptom identity, concern, and emotional response, whilst the High Frequency Phenotype was associated with lower understanding. Discussion: The way patients perceive their condition is a quantifiable aspect of the illness experience that is associated with symptom burden, mental health, and quality of life in patients with FD and CNVS. The observed associations with gastric electrophysiology suggest that illness perceptions may also vary in relation to underlying patient physiology. These findings support the consideration of illness perceptions as part of multidisciplinary assessment and management, including targeted patient education and clinical interventions to address distressing or maladaptive illness beliefs.

Introduction Patients undergoing polypectomy at colonoscopy remain at risk of metachronous neoplasia despite surveillance guided by histopathological features. Mutational profiling of adenomas, including canonical driver mutations in APC, KRAS, and TP53, may offer additional predictive value. This study aimed to determine whether mutational status in index adenomas was associated with metachronous lesion risk. Methods The INCISE cohort included patients aged 50 to 74 years who underwent polypectomy within the Scottish Bowel Screening Programme and subsequent surveillance colonoscopy within 6 years. Targeted next-generation sequencing was performed on formalin-fixed paraffin-embedded polyps. Driver mutation frequency, tumour mutational burden (TMB), and variant allele frequency (VAF) were analysed and correlated with histopathological features and metachronous outcomes using appropriate statistical models. Results A total of 895 adenomas from 723 patients were analysed. In conventional adenomas, as the number of high-risk histopathological features (size >=10mm, villous architecture, and high-grade dysplasia) increased there was a stepwise increase in the proportion of samples with a mutation in KRAS from 13% to 51% (padj<0.001) and TP53 from 8% to 35% (padj<0.001). However, neither mutation frequency (p=0.901), nor median tumour mutation burden (TMB) (2.27 vs 2.15 mut/Mb, p=0.242), in index adenomas was associated with the development of metachronous lesions. Conclusions While classical driver mutations reflect histopathological progression within adenomas, they do not predict metachronous lesion risk post-polypectomy. Targeted mutation profiling alone is insufficient for surveillance risk stratification, highlighting the need for integrated molecular approaches in this setting.

Background: Gastrointestinal (GI) motility disorders are prevalent, impose a significant burden, and are associated with disrupted spatial propagation of bioelectrical gastric slow waves. High-resolution endoscopic gastric mapping (EGM) is an emerging minimally invasive technique for imaging gastric electrical activity; however, EGM is performed alongside standard gastroscopy and requires procedural sedation, which may interact with gastric electrical activity, distorting clinical insights. This study explored the influence of procedural sedation on EGM-recorded slow-wave activity. Methods: EGM was performed for {approx}7 min in 32 patients undergoing upper GI endoscopy at two New Zealand hospitals. Endoscopists administered procedural sedation (fentanyl and midazolam) according to best clinical practice. The relationship between slow-wave amplitude and patient characteristics was then investigated using a variety of statistical techniques. Key Results: Gastric slow waves were detected in 30 of 32 patients who underwent EGM. Symptom scores and demographic measures were comparable between sites. Fentanyl (A, 93.4 {+/-} 13.7 g vs B, 137.5 {+/-} 33.7 g, p[&le;]0.001) and midazolam (A, 5.0 {+/-} 0.9 mg vs B, 7.4 {+/-} 1.6 mg, p[&le;]0.001) doses were higher at Hospital B than Hospital A. Correspondingly, slow-wave amplitudes were lower at Hospital B than Hospital A (A, 2.33 {+/-} 1.61 mV vs B, 0.86 {+/-} 1.01 mV, p=0.004). All other slow-wave metrics were consistent between hospitals. Combined sedative dose was negatively correlated with slow-wave amplitude (p=0.037). Conclusions & Inferences: Higher procedural sedative doses are associated with lower-amplitude gastric slow-waves. Procedural sedation dose and opiate administration should be carefully considered when interpreting GI electrophysiology measurements.

Background Small common bile duct stones may pass after endoscopic sphincterotomy, but leaving the duct without attempting extraction also leaves clearance uncertain. We compared same-session stone clearance after sphincterotomy alone with clearance after sphincterotomy followed by balloon-based and/or basket extraction. Methods We conducted a single-center observational study of 203 patients with common bile duct stones 5 mm or smaller who underwent therapeutic endoscopic retrograde cholangiopancreatography. The endoscopist chose the treatment during the procedure. Forty-seven patients underwent sphincterotomy alone, and 156 underwent sphincterotomy followed by balloon-based and/or basket extraction. The primary outcome was fluoroscopically confirmed clearance during the same procedure. Intraprocedural bleeding was a secondary outcome. We calculated unadjusted risk ratios and used Fisher's exact test for sparse events. Results The mean age was 58.62 years (standard deviation 20.10), and 90 patients (44.3%) were men. Same-session clearance was documented in 21 of 47 patients (44.7%) after sphincterotomy alone and 130 of 156 (83.3%) after adjunctive extraction (risk ratio 1.87, 95% confidence interval 1.35 to 2.58; P < 0.001). A prominent ampulla was more common in the sphincterotomy-alone group (25.5% vs 10.9%; P = 0.012). Intraprocedural bleeding occurred in 2 patients after sphincterotomy alone and none after adjunctive extraction (4.3% vs 0%; Fisher's exact P = 0.053). Conclusions Adjunctive extraction was associated with a higher rate of documented same-session clearance than sphincterotomy alone. Treatment was not randomized, the groups differed at baseline, and only two bleeding events occurred. These findings therefore do not prove that adjunctive extraction is causally superior or safer. Prospective studies using standardized techniques and follow-up are needed.

Background. Tandem colonoscopy meta-analyses estimate adenoma miss rates, which have been used as a proxy for colonoscopy sensitivity. Doing so overstates sensitivity because it ignores lesions missed by both exams. Methods. We introduce Bayesian and frequentist approaches to estimate white-light colonoscopy (WLC) sensitivity from tandem colonoscopy meta-analyses. Neither approach assumes that the second colonoscopy is perfect. We apply both approaches to reanalyze data from a recent tandem colonoscopy meta-analysis, overall and across ten subgroups. Sensitivity analyses assess how assumptions about the relative performance of enhanced colonoscopy versus WLC affect estimates. Results. Under our Baseline specification, overall WLC sensitivity estimated by the Bayesian model was 0.54 [0.41, 0.63] (posterior mean and 95% credible interval). Sensitivity rose with lesion size: 0.49 [0.35, 0.60] for 1-5 mm adenomas, 0.64 [0.43, 0.78] for 6-9 mm adenomas and 0.84 [0.70, 0.93] for lesions 10 mm or larger. The frequentist plausible range encompassed the Bayesian estimate. The model-implied miss rate (0.35 [0.30, 0.40]) matched the original meta-analysis estimate and was stable across prior specifications. Assuming enhanced colonoscopy was perfect overstated overall sensitivity by 0.12 [0.06, 0.20]. Limitations. Tandem colonoscopy data identify the miss rate but not WLC sensitivity, so estimates depend on an external assumption about the relative performance of enhanced colonoscopy versus WLC. As a result, WLC sensitivity estimates varied with the prior specification, especially for small and flat adenomas. Conclusions. WLC sensitivity may be meaningfully lower than previously assumed in CRC screening cost-effectiveness analyses. Modelers should use colonoscopy sensitivity estimates that do not assume a second colonoscopy exam is perfect.

Background: Each year, thousands of patients are diagnosed with gastrointestinal (GI) bleeding. Many of these patients undergo colonoscopy and are subsequently diagnosed with benign or malignant colorectal neoplasms. Aim of this study is to evaluate whether patients with cardiovascular comorbidities, many of whom are on anti-platelet or anticoagulation therapy, are more likely to be diagnosed with new benign or malignant colorectal neoplasms than patients without cardiovascular comorbidities. Methods : From the 2007-2011 NIS, 802,080 primary lower GI bleed admissions (ICD-9) were identified; 283,925 had cardiovascular comorbidities. We compared patients with vs without these comorbidities for the primary outcome of new benign or malignant colorectal neoplasms. Weighted analyses accounting for the complex survey design were performed in SAS 9.4, with trends assessed using Cochran-Armitage tests and linear regression and associations with colorectal cancer stage evaluated by multinomial logistic regression (p [&le;] 0.05). Results: Between 2007-2011, the odds of malignant colorectal neoplasms increased between 49.9% and 65.3% for patients without cardiovascular comorbidities when presenting with a lower GI bleed, compared to those with cardiovascular comorbidities. Between 2007 and 2011, the most notable and statistically significant difference was observed in 2010, when patients with cardiovascular comorbidities had 10.5% higher odds of being diagnosed with benign colorectal neoplasms than those without cardiovascular comorbidities. Conclusion: Patients presenting with a lower gastrointestinal bleed without cardiovascular comorbidities were significantly more likely to be diagnosed with malignant colorectal neoplasms than those with cardiovascular comorbidities.

Background: Real-world evidence on food-as-medicine programs for irritable bowel syndrome (IBS) is scarce, and single-arm evaluations overstate improvement because of regression to the mean (RTM). We estimated change in the IBS Symptom Severity Scale (IBS-SSS, 0-500) in a multi-omics personalized digital health food-as-medicine program, unadjusted and RTM-corrected. Methods: Retrospective single-arm cohort. Of 15,933 members with a valid baseline, 2,254 had a follow-up reading and 1,683 one at least 14 days after baseline. Change at 4, 12 (primary) and 26 weeks was estimated by baseline severity stratum, unadjusted and RTM-corrected by analysis of covariance. A responder fell by at least 50 points (the minimal clinically important difference benchmark). Sensitivity analyses covered equity, inverse-probability weighting and tipping-point analyses for members without a reading in each landmark window, a negative-control stratum and medication. The association of weight loss and dietary nutrient density with symptom change was evaluated within and between members. Results: At 12 weeks (n = 430) IBS-SSS fell by 43.88 points unadjusted (95% confidence interval [CI] -52.44 to -35.32; p < 0.001) and by 47.73 RTM-corrected (-55.48 to -39.98; p < 0.001); 720 of 1,339 symptomatic members (53.8%; 95% CI 51.1 to 56.4) fell by at least 50 points. Larger improvement in more severe members persisted after RTM correction (severe stratum, n = 37: unadjusted -127.43, RTM-corrected -60.71, 95% CI -97.75 to -23.68, p = 0.001). A higher meal nutrient density was associated with lower IBS-SSS within a member's own trajectory (p = 0.018) while weight change was not (p = 0.361). Improvement was similar across groups in spite of baseline differences by age and sex: RTM-corrected 12-week change did not differ by age (p = 0.458), body-mass index (p = 0.328), sex (p = 0.749), income (p = 0.486) or ethnicity (p = 0.170). Estimates were robust to weighting for members without a reading in the landmark window (RTM-corrected estimates moved by less than 2 points), and the change of those members would have had to be 39 to 73 points worse than observed before the mean change reached zero. Baseline medication use and starting a GLP-1 receptor agonist did not explain symptom changes. Conclusions: IBS-SSS fell significantly among program participants, with steeper improvement in the more severe group, even after RTM correction. The improvement was comparable across socioeconomic characteristics, age and sex and robust to the confounders and missing-data assumptions evaluated. These associations from a self-selected single-arm cohort warrant replication in independent studies.

Background and study aims: Endoscopic assessment of ulcerative colitis (UC) is central to clinical decision-making however remains subjective and limited in characterisation of disease distribution. Artificial intelligence (AI) enables analysis of entire endoscopic examination, rather than relying on selected views. We aimed to develop and validate a deep learning model for automated assessment of UC severity from full-length endoscopic videos, introducing spatial representation of inflammation (Continuous Disease Score, CDS), and assess histological correlation. Patients and methods: Full-length endoscopy videos from adult patients with UC undergoing colonoscopy or flexible sigmoidoscopy were analysed; isolated proctitis was excluded. Videos were segmented and annotated using Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Activity (UCEIS). A deep learning model was trained for frame-level quality control and severity prediction, enabling analysis of full-length videos. Performance was evaluated using quadratic weighted kappa (QWK) and Cohen's kappa, with patient-level separation between datasets. CDS was derived from UCEIS predictions to quantify cumulative inflammatory burden, spatial extent of disease and histological prediction. Results: A total of 67 videos from 59 patients were included. The model demonstrated agreement for remission classification (MES=0 {kappa} 0.76; UCEIS[&le;]1 {kappa} 0.84). CDS enabled quantification of inflammatory burden and revealed spatial heterogeneity not reflected in categorical scores. Agreement with histology was strong (AUROC 0.84-0.87). Conclusions: AI-based analysis enables automated assessment of UC activity from full-length endoscopic videos, including remission detection and estimation of histological healing. CDS provides continuous characterisation of inflammatory burden and disease extent beyond conventional categorical scores, with potential to support more standardised assessment in clinical trials and practice.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is often diagnosed months to years after symptoms begin, and diagnostic delay is associated with complications. We tested whether longitudinal machine learning using electronic health record (EHR) data can identify incident IBD before diagnosis, and quantified lead time and deployment burden. METHODS: We studied adults with an IBD-compatible symptom, sign, or finding at UCSF (2012-2024). Incident cases were confirmed by structured filtering and validated large language model note review. We trained a state space model (Mamba) and comparators on pre-diagnostic EHR data, excluding diagnostic-workup features, and assessed discrimination at 6- and 12-month landmarks. We externally tested Mamba without recalibration at ZSFG, a safety-net hospital serving a demographically and socioeconomically distinct population, and simulated diagnosis-code-only deployment at UCSF. RESULTS: Six months after presentation, among patients still undiagnosed (67% of UCSF test cases), Mamba achieved an AUROC of 0.969 (95% CI, 0.928-0.999) at UCSF and 0.965 (0.952-0.976) at ZSFG. Median lead time was 20 months at UCSF and 15 months at ZSFG. Among future cases with an initially normal colonoscopy (N=32) or a histological finding of acute inflammation without chronicity (N=63), the model flagged 84% and 89% of these patients, respectively, before those procedures, indicating the potential for pre-diagnostic detection. Among 358,886 symptomatic patients not used for training (60 incident cases), the diagnosis-code-only model achieved an AUROC of 0.926; reviewing 20 alerts/month identified 34 cases (PPV, 1.09%; 64-fold above baseline). CONCLUSIONS: Longitudinal machine learning can identify increased IBD risk months to years before diagnosis and may define a population for prospective studies of early IBD biology. Prospective evaluation should determine whether earlier identification reduces diagnostic delay.

Background and Aims: Vibration-controlled transient elastography (VCTE) and two-dimensional shear-wave elastography (2D-SWE) are used to assess liver stiffness in metabolic dysfunction-associated steatotic liver disease (MASLD); patients may be assessed by different methods over time. Because 2D-SWE fibrosis cut-offs are not uniformly validated and no biopsy or magnetic resonance elastography reference is available, we asked whether switching methods moves patients across decision thresholds. We evaluated agreement and decision-threshold interchangeability between VCTE and 2D-SWE in MASLD with obesity. Methods: In a retrospective cross-sectional agreement study at a tertiary-care center, 317 consecutive adults with MASLD underwent same-day VCTE (FibroScan) and GE LOGIQ E9/E10 2D-SWE. Continuous agreement was assessed by Bland-Altman analysis; the categorical analysis compared binary clinical decision thresholds (VCTE [&ge;]8.0/[&ge;]10.0 kPa; 2D-SWE [&ge;]7.204/[&ge;]8.060 kPa) using Cohen {kappa} and McNemar tests. Prespecified sensitivity analyses and a post-hoc recalibration were performed; VCTE served as operational reference. Results: VCTE yielded higher values (geometric mean VCTE/2D-SWE ratio, 1.23; ratio limits of agreement, 0.64 2.40; intraclass correlation coefficient, 0.41). At the lower threshold, 71 of 117 VCTE-positive patients (61%) were below the 2D-SWE threshold versus 5 of 200 (2.5%) reclassified upward (agreement 76.0%; {kappa} 0.417; P<.001); the upper threshold was similar (38 of 63, 60%, vs 8 of 254, 3.1%). Discordance persisted across cut-offs; agreement worsened descriptively across BMI strata. Recalibration removed the directional asymmetry but not the discordance (agreement unchanged, 76.0%). Conclusions: In MASLD patients, switching from VCTE to 2D-SWE reclassified decision-threshold status in ~60% of VCTE-positive patients; recalibration removed the directional bias but not the disagreement. Follow-up should use the same elastography modality and, when possible, the same platform.

Background & AimsWe previously developed multiple machine-learning and regression-based risk prediction models using retrospective electronic health records (EHR) to estimate near-term risk of pancreatic cancer (PC). This pilot study aimed to assess the feasibility of an early detection strategy combining initial EHR-based risk prediction with downstream imaging and blood-based testing. MethodsThis prospective study included adults aged 50-84 years with an estimated [&ge;]1% 18-month risk of PC, identified between January 2021 and March 2023 using four previously validated models. Patients with a history or active suspicion of PC were excluded. Participants completed cross-sectional imaging and CA19-9 labs at baseline and again at 18 months. Outcomes included enrollment rates, test completion rate, and burden of incidental findings. ResultsOf 1,251 eligible patients, 102 (8.2%) enrolled (median age 69 years [IQR 62-75]; 58% women; 48% Hispanic, 34% White, 11% Black, and 7% Asian). At baseline, 89 (87%) completed imaging and 98 (96%) completed CA19-9. At 18 months, 79% completed both imaging and CA19-9. Ten (10%) participants underwent additional clinical evaluations triggered by imaging findings. Evaluations included an endoscopic ultrasound, renal imaging, and FibroScan. CA19-9 results were normal in most participants, though 18% had elevated levels at baseline. ConclusionsReal-time EHR-based ML algorithms can be combined with blood- and imaging-based surveillance for early detection of PC with acceptable burden of incidental findings. However, improved patient engagement is a key aspect that will need to be addressed in order to successfully scale an AI-guided strategy for early detection.

Background/Objectives Tooth loss may impair masticatory function, potentially affecting gastrointestinal health. This study examined the association between clinically examined tooth loss and abnormal bowel habits among US adults. Methods This cross-sectional study used NHANES 2005-2010 data. Adults aged [&ge;]20 with clinical oral examination (OHX) and Bristol Stool Scale (BSS) data were included. Missing teeth (0-28) were categorized as 0, 1-5, 6-10, 11-27, and 28. The primary outcome was abnormal bowel habits (BSS 1-2 or 6-7 vs. 3-5); secondary outcomes included constipation, diarrhea, and fecal incontinence symptoms. Survey-weighted logistic regression with progressive covariate adjustment was used, with Benjamini-Hochberg FDR correction for secondary outcomes. Results Among 9,988 participants (14.5% prevalence), the P-for-trend for abnormal bowel habits was significant (OR = 1.015, 95% CI: 1.006-1.024, P = 0.001), corroborated by omnibus Wald (P = 0.006) and restricted cubic spline analyses (P = 0.019). Complete edentulism was associated with 1.5-fold higher odds (OR = 1.545, P = 0.006). Constipation survived FDR correction (FDR-adjusted P = 0.032). Results were robust across most of five sensitivity analyses, with modest attenuation noted after denture use adjustment in a restricted subset. Conclusions Tooth loss was significantly associated with abnormal bowel habits, with constipation surviving FDR correction. These findings support the oral-gut axis hypothesis and highlight the importance of maintaining natural dentition for gastrointestinal health.