American Journal of Gastroenterology

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.

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: 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.

Aims: Serrated lesions contribute substantially to colorectal cancer (CRC), while routine management of small distal hyperplastic polyps (HPs) assumes low risk. Surveillance guidelines nevertheless incorporate uncertainty at the HP/SSL interface and recommend shortened intervals for large serrated lesions. We tested whether fibroblast activation protein-alpha; (FAPalpha) expression by stromal fibroblasts within expert-reviewed HPs stratifies risk of subsequent neoplasia. Methods and results: In a single centre historical cohort, FAPalpha; immunohistochemistry (Abcam ab53066, 1:200) was performed on FFPE colon tissues from 64 patients (normal colon n=10; HP n=39; low grade TA n=6; high-grade TA n=4; adenocarcinoma n=5). FAPalpha positive stromal fibroblasts were quantified in 20 randomly selected fields at magnification 1000 by two blinded readers (ICC 0.93). Among 39 patients with expert reviewed index HPs and colonoscopic follow up, the endpoint was metachronous adenoma occurring in the same general colonic area as the index HP, with proximal defined as ascending colon and distal as descending colon. Follow-up colonoscopies were scheduled every 2 years for up to 10 years. ROC analysis identified an optimal threshold of [&ge;]9 FAPalpha positive fibroblasts (AUC 0.8658; sensitivity 81.25%, specificity 87.93%). FAPalpha high status (44% of HPs) was associated with shortened neoplasm free survival (log-rank p=0.0012): five-year neoplasm free survival 41% versus 91% for FAPalpha; no/low. In multivariable Cox modelling, FAPalpha high status remained independently associated with metachronous adenoma (HR 4.5, 95% CI 1.2-16.8, p=0.022). Conclusion: FAPalpha+ fibroblasts in expert-reviewed colorectal HPs identify a high-risk subgroup for metachronous adenoma, supporting stromal activation markers as a feasible pathology-anchored stratification tool.

Background & Aims: The association between upper gastrointestinal (GI) symptoms and delayed gastric emptying time (GET) is debated. This study utilized Body Surface Gastric Mapping (BSGM) and the 'Auckland Classification' BSGM phenotyping scheme to investigate whether symptom associations with GET vary across different mechanistic phenotypes. Methods: A pooled analysis was performed on two prospective datasets of 194 patients with chronic upper GI symptoms. Participants underwent simultaneous BSGM (Gastric Alimetry) and gastric emptying testing (breath test or scintigraphy). Validated time-of-test symptom profiling was recorded at 15-minute intervals using 0-10 Likert-type scales. Patients were classified: 'Spectral Abnormal' (abnormal electrophysiology), 'Sensorimotor' (symptoms correlate with gastric electrical amplitude), 'Continuous' (symptoms uncorrelated), and 'NA' (no phenotype). Results: In the analyzed cohort, 24% had delayed GET. Overall, delayed GET was associated with a higher total symptom burden (15.6 delayed vs. 8.8 normal, p=0.006; r=0.30, p<0.001), specifically postprandial fullness (p=0.004) and early satiation (p=0.015). However, associations varied significantly by phenotype. In the 'Sensorimotor' phenotype, nausea was associated with delayed GET (4.9 vs. 1.0, p=0.027; r=0.59, p=0.009), while total symptom burden was 23.3 vs. 8.4 (p=0.135). Conversely, patients with 'Continuous' or 'Spectral Abnormal' phenotypes, or who were unclassified, showed no symptom associations. Conclusions: Delayed GET is weakly associated with an increased burden of upper GI symptoms. However, gastroduodenal disorders are heterogeneous, such that phenotyping reveals this association to be exclusive to patients with a 'Sensorimotor' phenotype. These results could improve targeting of therapies that address gastric emptying.

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: Recreational physical activity has been shown to improve survival among colorectal cancer (CRC) patients. With a growing survivor population, it is necessary to understand whether there are survival benefits across physical activity levels and across sociodemographic and clinical features. Methods: Disparities and Cancer Epidemiology (DANCE) is a population-based cohort of CRC survivors from metro-Detroit and Louisiana. Self-reported moderate and vigorous recreational physical activity was modeled continuously and categorically as none, low (<7.5 MET-hrs/wk), and high (7.5+ MET-hrs/wk). Survival models estimated hazard ratios (HRs) for physical activity with all-cause and CRC-specific survival. Models were stratified by sociodemographic and clinical features; cross-product terms estimated interaction with physical activity. Results: Of 1,107 participants, 26.5% were inactive, 49.1% had low physical activity, and 24.5% had high physical activity. Compared to inactivity, low activity was associated with 44% higher overall survival (HR= 0.56, 95% CI: 0.42, 0.75), and high activity with 66% higher survival (HR=0.34, 95% CI: 0.22, 0.53; P-trend=0.01). Adjustment for comorbidities, quality of life, BMI, and BMI-change did not alter results. Results remained significant for CRC-specific survival (low: HR=0.65, 95% CI: 0.44, 0.96; high: HR=0.45, 95% CI: 0.25, 0.80). Associations were consistent across sociodemographic and clinical features other than BMI and race; survival benefits were larger among White survivors. Conclusion: Any recreational physical activity is associated with longer overall and CRC-specific survival, regardless of sociodemographic or clinical characteristics for the most part. Any physical activity may have survival benefits for CRC survivors, but meeting physical activity guidelines may have the greatest benefit.

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.

Background: Sleeve gastrectomy is the most frequently performed bariatric procedure worldwide but is associated with the development of de novo gastroesophageal reflux disease (GERD). Hiatal hernia has been identified as a relevant anatomical factor in postoperative reflux, although most studies evaluate it dichotomously without analyzing whether its size influences GERD risk. The aim was to evaluate the association between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy. Methods: Retrospective, single - center, observational study of patients undergoing sleeve gastrectomy at Hospital Central Norte de Petroleos Mexicanos (2018 - 2025). Demographic and clinical characteristics, endoscopic classification of hiatal hernia size (small <2 cm, medium 2.1 - 4 cm, large >4 cm), and evidence of de novo GERD were analyzed using descriptive statistics, Fisher's exact test, odds ratio (=R) estimation with 95% confidence intervals (CI), and binary logistic regression. Statistical significance was set at p<0.05. Results: Fiftysix patients were included (mean age 48.3 {+/-} 8.1 years; 67.9% male). Hiatal hernia classification was conclusive in 46 patients (82.1%): 63.0% no hernia, 4.3% small, 30.4% medium, and 2.2% large. De novo GERD occurred in 14.0% of patients without preexisting GERD (6/43). No significant association was found between hiatal hernia size and de novo GERD (Fisher p=0.515). In the reduced logistic model, neither hiatal hernia (medium/large vs. absent/small; OR 3.47; 95% CI 0.50 - 29.43; p=0.207) nor age (OR 1.02; 95% CI 0.90 - 1.13; p=0.754) was significantly associated. No evaluated factor (sex, smoking, alcohol, age) reached significance. Conclusions: In this cohort, no statistically significant association was demonstrated between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy; however, the low number of events limits the ability to exclude a clinically relevant association. These findings are compatible with a multifactorial mechanism rather than with the isolated presence of this finding. Prospective studies with larger sample sizes and standardized reflux assessment instruments are required to confirm these results.

Background: Early identification of complicated appendicitis is essential for appropriate management, yet accurate preoperative risk stratification remains challenging. Whether objective laboratory-based models can achieve predictive performance comparable to models incorporating clinical findings remains unclear. Objective: To compare clinical, laboratory-based, and combined clinical-laboratory prediction models for complicated appendicitis and to evaluate the incremental value of the Prognostic Nutritional Index (PNI). Methods: This retrospective study included 1,132 consecutive patients with acute appendicitis. Cases were classified as uncomplicated or complicated appendicitis based on pathological findings and imaging. Three multivariable logistic regression models were developed: a clinical model (Model A), a laboratory-based model (Model B), and a combined clinical-laboratory model (Model C). Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC), and AUCs were compared using DeLong's test. Results: Complicated appendicitis was identified in 341 patients (30.1%). Higher C-reactive protein, higher neutrophil percentage, and lower PNI were independent predictors of complicated appendicitis. The AUCs were 0.791 for Model A, 0.847 for Model B, and 0.857 for Model C. Model B significantly outperformed Model A (P = 0.0020), whereas no significant difference was observed between Models B and C (P = 0.0816). PNI remained an independent predictor after adjustment for conventional inflammatory markers. Conclusion: A laboratory-based prediction model incorporating PNI demonstrated discrimination comparable to that of a combined clinical-laboratory model while relying exclusively on routinely available objective laboratory parameters. These findings support laboratory-based risk stratification as a practical adjunct to clinical assessment for the early identification of complicated appendicitis.

Background Gallstones are one of the most common gastrointestinal conditions closely associated with metabolic dysfunction. The metabolic dysfunction - associated fibrosis - 5 (MAF -5) score has been established as a non - invasive indicator for assessing liver fibrosis in individuals with metabolic abnormalities. However, comprehensive large - scale research examining the correlation between the MAF-5 score and gallstone occurrence remains limited. This study seeks to clarify the link between the MAF-5 score and gallstone prevalence using nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Methods This study examined data from 15,560 NHANES 2017-2020 participants aged 20 years or older, ensuring complete records for MAF-5 scores and gallstone status. Gallstone presence was identified through self-reported physician diagnoses. To assess the relationship between MAF-5 scores and gallstone prevalence, weighted logistic regression models were applied, adjusting for demographic characteristics, lifestyle factors, and health conditions. Subgroup analyses were conducted to evaluate the stability of this association and detect possible interactions. Sensitivity analyses were performed by excluding extreme values ({+/-}3SD) to assess result robustness. Furthermore, MAF-5 scores were divided into quartiles to investigate gallstone prevalence trends, and a restricted cubic spline (RCS) model was employed to visualize response patterns. Results A total of 15,560 participants met the inclusion criteria, with 747 in the gallstone group and 6,367 in the non-gallstone group. MAF-5 scores were significantly higher in the gallstone group (P < 0.001). After adjusting for multiple covariates, each unit increase in MAF-5 score correlated with a 14% higher gallstone prevalence (OR = 1.14, 95% CI: 1.06-1.23). Quartile-based analysis indicated that individuals in the highest MAF-5 quartile had a 2.12-fold higher prevalence of gallstones than those in the lowest quartile (OR = 2.12, 95% CI: 1.13-3.98). RCS analysis confirmed a linear association between MAF-5 scores and gallstone prevalence. Subgroup analyses showed this association remained stable across age, sex, and racial/ethnic groups, with no significant interactions. Sensitivity analyses, excluding extreme values ({+/-}3SD), reinforced the reliability of these findings (OR = 1.15, 95% CI: 1.04-1.28). Conclusion The MAF-5 score is significantly and positively associated with gallstone prevalence, independent of demographic and lifestyle confounders. These findings indicate that the MAF-5 score may be a useful tool for assessing gallstone prevalence in individuals with metabolic dysfunction, offering valuable insights for early screening and targeted health management strategies. Keywords: Gallstones, MAF-5 score, Metabolic dysfunction, NHANES, Liver fibrosis.

Background Conversion surgery for stage IV gastric cancer is supported by a pooled overall survival hazard ratio of 0.36 (95% confidence interval 0.32-0.40) and, in the largest international cohort, median survival of 36.7 versus 12.5-13.8 months on chemotherapy. Survival is measured from diagnosis; the median diagnosis-to-gastrectomy interval is 124 days, which patients must survive to be counted surgical. Methods We simulated cohorts of 3,177 stage IV gastric cancer patients from published parameters: background median survival 14.5 months; median diagnosis-to-surgery interval 124 days (category-specific 92-174 days). Surgery had no effect (true hazard ratio 1.00 by construction). Data were analysed as the literature analyses them (exposure fixed at baseline, follow-up from diagnosis), and by time-varying Cox and landmark analysis. Confounding by indication was added in a second scenario. Results Under immortal time bias alone the naive analysis returned a hazard ratio of 0.794 (95% simulation interval 0.743-0.851), median survival 16.8 versus 12.8 months. Time-varying Cox recovered 1.000 and landmark analysis 1.000-1.004. Bias scaled with the interval: 0.849 at 92 days, 0.715 at 174 days. Adding confounding, the naive estimate fell to 0.601 (0.560-0.644) at strength 0.5 and 0.356 (0.323-0.385) at strength 1.5, overlapping the published estimate; median survival 21.9 versus 8.7 months. Correcting immortal time alone left residual bias (hazard ratio 0.439). Conclusions The reported survival advantage of conversion surgery is reproducible where the operation does nothing; published estimates cannot distinguish benefit from bias. Resolving this requires individual patient data analysed with methods that assign person-time correctly, or completion of JCOG2301.

Abstract Background : Helicobacter pylori infection remains a significant public health concern and a leading cause of peptic ulcer disease (PUD). This organism colonizes the gastric mucosa and often remains asymptomatic until complications develop. Despite its global prevalence, the magnitude and association between H. pylori infection and PUD are not well established in many community settings, including Dar es Salaam. This study aimed to determine the fecal prevalence of H. pylori, risk factors, and the correlation between H. pylori and PUD in adults clinically suspected of PUD in Dar es Salaam Communities, 2025. Methodology: A cross-sectional, community-based study was conducted among 390 adults clinically suspected of having PUD in Dar es Salaam over a two-month data-collection period (April-June 2025). Sociodemographic, environmental, behavioral, and clinical data were collected using structured questionnaires, and stool samples were analyzed for Helicobacter pylori antigen using standard methods. The primary outcome was Helicobacter pylori infection status, while the secondary outcome was associated risk factors and their correlation with clinical suspicion of PUD. Data were analyzed using SPSS version 25, with categorical variables expressed in frequencies and percentages. Associations were assessed using chi-square tests and multivariable logistic regression, with results reported as adjusted odds ratios and 95% confidence intervals. Spearmans rank correlation was used to assess the relationship between H.pylori infection and clinical suspicion of PUD. Of the 400 adults enrolled,390(97.5%) provided complete data and were included in the analysis Results: Of 390 participants, 252 (64.6%) were female, and the mean age was 36.9 {+/-} 15.7 years. A total of 161 individuals (41.3%) tested positive for H. pylori. Higher Infection rates were observed among adults aged 40-49 years (46.7%), singles (44.6%), those consuming tap water (46.9%), residents of crowded area//s (43.2%), and individuals who consumed alcohol and smoked (50.4% and 44.5%, respectively). Only the source of drinking water showed a significant association with H. pylori infection. A positive correlation was observed between H. pylori infection and clinically suspected PUD. Conclusion: H.pylori infection was common among adults clinically suspected of PUD in the Dar es Salaam communities. The use of tap water for drinking was identified as the most significant risk factor. These findings highlight the need for routine community-based screening and public health interventions to improve water safety and reduce transmission. Future studies should employ longitudinal designs to establish causal relationships between H. pylori infection, behavioral risk factors, and clinical outcomes.

Malnutrition is common in Crohns disease (CD), and its assessment requires multiple tools. Comprehensive evaluation of nutritional status in a population with CD, predominantly characterized by metabolic phenotype, was inadequately reported. This study evaluated the nutritional status of CD patients using anthropometric, clinical, and biochemical measures and compared patients with active disease with those in remission. This cross-sectional study included 127 adults with CD: 63 with active disease and 64 in remission. Disease activity was classified using the Crohns Disease Activity Index, the Simple Endoscopic Score for Crohns Disease, and magnetic resonance enterography. Nutritional assessment included body mass index (BMI), mid-upper arm circumference, calf circumference, triceps skinfold thickness, mid-arm muscle circumference, Mini Nutritional Assessment-Short Form (MNA-SF), and biochemical markers including hemoglobin, serum iron, folate, vitamin B12, albumin, and zinc. Malnutrition was defined using the Global Leadership Initiative on Malnutrition criteria. Overall, 47.2% of participants were malnourished. Malnutrition was significantly more frequent in active disease than in remission (81.0% vs. 14.1%, P<0.001). Patients with active CD had lower anthropometric indices, MNA-SF score, hemoglobin, serum iron, albumin, and zinc (all P<0.001), whereas folate and vitamin B12 did not differ significantly. BMI showed positive correlations with other anthropometric measures and MNA-SF score (r=0.854-0.914, all P<0.001), whereas correlations with biochemical parameters were weaker and disappeared after subgroup stratification. Overall, the findings indicate that malnutrition is highly prevalent in CD, particularly during active disease. Anthropometric measures and MNA-SF were strongly concordant, whereas biochemical markers were less consistent, supporting a multidimensional nutritional assessment approach in CD.