Hu B, Zhang M, Yu Y
… +27 more, Liu Y, Wang J, Zhang A, Li Q, Gao Y, Li Z, Bian L, Gu Y, Zhu X, She Q, Gao X, Deng B, Fang H, Hu C, Chen Y, Chen Y, Wang X, Yin X, Zhu M, Wang L, Jiang Y, Chen J, Dai J, Ma H, Ding Y, Yan C, Jin G
Genome-wide association studies (GWASs) have identified at least 17 genetic variants associated with gastric cancer risk. However, the underlying genetic regulatory mechanisms remain poorly understood. We systematically...Genome-wide association studies (GWASs) have identified at least 17 genetic variants associated with gastric cancer risk. However, the underlying genetic regulatory mechanisms remain poorly understood. We systematically performed genome-wide analyses of expression quantitative trait loci (eQTLs), splicing QTLs (sQTLs), and alternative polyadenylation QTLs (apaQTLs) using gastric biopsy tissues from 262 Chinese individuals, and we integrated these data with GWAS results from 10,254 gastric cancer cases and 10,914 controls. We identified 4,636 eGenes, 1,422 sGenes, and 511 apaGenes, with 55.3% of sGenes and 49.5% of apaGenes being distinct from eGenes. Notably, over half of the variants associated with shared genes were unique to a specific QTL type, with these variants characterized by a wide physical separation (median distance = 25.01 kb) and weak linkage disequilibrium (median r = 0.42). Gastric cancer risk variants showed significant enrichment across all three QTL categories. Integrative transcriptome-wide association studies (TWASs) across expression, splicing, and alternative polyadenylation identified 34 genes at false discovery rate (FDR) <0.05; PSCA was implicated across all three regulatory layers. The candidates DIP2B and RMC1 were experimentally validated to promote gastric tumorigenesis both in vitro and in vivo. Functional analyses revealed that the rs11264361-T allele reduced FDPS exon 9 skipping, leading to increased expression of the full-length transcript, while the apaVariant rs7445 regulated UBE2L3 polyadenylation via ATXN2 binding, contributing to gastric cancer risk. Collectively, these results provide a comprehensive QTL resource in gastric tissues and demonstrate distinct regulatory mechanisms of eQTLs, sQTLs, and apaQTLs in gastric cancer development.
BACKGROUND: Microscopic colitis is a well-defined entity comprising two histopathological subtypes: lymphocytic colitis and collagenous colitis, which may represent different stages of the same disease. Upper gastrointes...BACKGROUND: Microscopic colitis is a well-defined entity comprising two histopathological subtypes: lymphocytic colitis and collagenous colitis, which may represent different stages of the same disease. Upper gastrointestinal involvement by a process sharing histological features with microscopic colitis appears to be much more uncommon, and its pathogenesis, clinical significance, and management remain poorly characterised in the literature, as it may be easily overlooked or mistaken for other entities. PATIENTS AND METHODS: We retrospectively reviewed a series of patients with collagenous gastritis diagnosed at a large tertiary hospital serving a population of over 500,000 inhabitants in the metropolitan area of Madrid, Spain. Between 2010 and 2023, only seven gastric biopsy specimens were diagnosed as collagenous gastritis, corresponding to five patients. RESULTS: All patients were women, aged 21-38 years. They presented with non-specific symptoms, and endoscopy revealed only mild nodularity in one case. Random gastric biopsies established the diagnosis of collagenous gastritis. None of the patients had associated collagenous colitis, collagenous enteritis or coeliac disease. Only one patient underwent long-term follow-up with sequential biopsies, which demonstrated persistent histological changes over time while the patient remained asymptomatic. CONCLUSIONS: A recent systematic review identified 101 patients with collagenous gastritis presenting with heterogenous clinical profiles and an overall favourable prognosis, even in the absence of specific treatment. It remains unclear whether collagenous gastritis represents a distinct clinicopathological entity or merely a residual histopathological finding, as there are no clear-cut clinical or endoscopic features that allow reliable suspicion of this disease.
OBJECTIVE: To evaluate the impact of high and low Body mass index (BMI) on 90-day postoperative outcomes in patients with Crohn's disease (CD). METHODS: This retrospective cohort study (2017-2019) included 271 patients u...OBJECTIVE: To evaluate the impact of high and low Body mass index (BMI) on 90-day postoperative outcomes in patients with Crohn's disease (CD). METHODS: This retrospective cohort study (2017-2019) included 271 patients undergoing abdominal surgery, categorized as underweight (BMI <18.5), normal/overweight (18.5-30), and obese (>30). Primary outcomes were 90-day overall and severe (Clavien-Dindo >2) complications and total length of stay (LOS). RESULTS: The cohort comprised 64 underweight, 189 normal/overweight, and 18 obese patients. Multivariable analysis revealed that underweight status was independently associated with higher overall complications (OR = 2.0, p = 0.045), severe complications (OR = 3.05, p = 0.018), and increased total LOS (beta = 3.43, p = 0.003). While obesity showed a trend toward higher morbidity in univariable analysis, it did not maintain independent significance after adjustment (p = 0.159). CONCLUSION: Underweight status is a significant independent predictor of poor 90-day postoperative outcomes in patients with CD, necessitating targeted preoperative nutritional optimization.
Bellec C, Augé A, L'Hermite S
… +54 more, Moirand R, Abergel A, Amstrong M, Antonini T, Anty R, Khaldi M, Baron A, Bensenane-Oussalah M, Bernal W, Bureau C, Carbonell N, Cadranel JF, Cardoso F, Carrier P, Coilly A, Conde I, Conti F, Bonadona A, Crespo G, Murad SD, Dharancy S, Duvoux C, Engelmann C, Faitot F, Francoz C, Garioud A, Gerolami R, Gigante E, Goria O, Gustot T, Hogan B, Lagin L, Lannes A, Latournerie M, de Ledinghen V, Magini G, Mateo M, Maurin A, Merli M, Meszaros M, Pageaux GP, Perignon C, Perricone G, Praktiknjo M, Reboux N, Reiberger T, Rolle V, Rosa I, Sarba R, Wartel F, Weil DV, Zanetto A, Elkrief L, Artru F
BACKGROUND & AIMS: Liver transplantation (LT) is increasingly performed in the setting of acute-on-chronic liver failure (ACLF). In this context, pre-transplant evaluation must be completed rapidly while minimizing the r...BACKGROUND & AIMS: Liver transplantation (LT) is increasingly performed in the setting of acute-on-chronic liver failure (ACLF). In this context, pre-transplant evaluation must be completed rapidly while minimizing the risk of overlooking contraindications. We aimed to describe current practices for pre-transplant assessment in patients with ACLF. METHODS: We conducted a survey across 34 European LT centers (including 16 French) and 22 French non-LT centers to assess pre-transplant evaluation practices, focusing on cardiopulmonary, addiction, oncological, and nutritional assessments. Practices were compared across three clinical scenarios: outpatients (OutPat), hospitalized decompensated patients without ACLF (Hosp), and patients with ACLF admitted to intensive care units (ACLF-ICU). In parallel, we retrospectively evaluated post-transplant outcomes in patients with cirrhosis and severe ACLF transplanted in two high-volume centers. RESULTS: Fifty-three centers (96%) responded. Cardiological stress testing was reported in 2% of ACLF-ICU patients vs. 21% of OutPat (p = 0.002) vs. 17% of Hosp patients (p = 0.008). Coronary angiography following abnormal non-invasive testing was less frequently performed in ACLF (42%) than in OutPat (76%, p = 0.0004) or Hosp patients (66%, p = 0.01). Alcohol abstinence requirements were more often decided on a case-by-case basis in patients with ACLF (62%) than in OutPat or Hosp patients. Oncological screening, including colonoscopy and ear, nose, and throat consultation, was also less frequently performed in ACLF-ICU patients. Median time from assessment initiation to listing was 7 days in ACLF-ICU vs. 45 days in OutPat and 18 days in Hosp patients (both p <0.0001). In the retrospective cohort (n = 221), patients listed after ACLF onset had a higher 1-year incidence of cardiovascular events than those listed before ACLF onset (19% vs. 9%). CONCLUSIONS: In ACLF-ICU patients, pre-transplant evaluation is markedly abbreviated, with critical gaps-particularly in cardiological assessment-highlighting the need for dedicated, evidence-based guidelines. IMPACT AND IMPLICATIONS: We sent a questionnaire to centers with an expertise in the management of patients with ACLF to assess current practices in pre-transplant evaluation in patients with ACLF admitted to an intensive care unit, as compared with patients without (outpatients and patients hospitalized in a regular ward). According to the responses from 53 centers, cardiological stress test and coronary angiography were less commonly performed as part of the pre-transplant evaluation in patients with ACLF admitted to the ICU, as well as colonoscopy and ear, nose, and throat consultation. Median timeframe from pre-LT workup initiation to listing was 7 days in patients with ACLF admitted to the ICU, which was significantly shorter than in patients without ACLF. These results suggest that pre-transplant workup is abbreviated in patients with ACLF, and might have an impact on post-transplant outcome, especially cardiovascular complications. Further dedicated studies are needed to specifically address the relation between pre-transplant workup and post-LT complications in patients with ACLF.
INTRODUCTION: With advances in surgical techniques, resectability of intrahepatic cholangiocarcinoma (ICCA) is now largely determined by oncological criteria. Distinguishing localized disease from early systemic spread r...INTRODUCTION: With advances in surgical techniques, resectability of intrahepatic cholangiocarcinoma (ICCA) is now largely determined by oncological criteria. Distinguishing localized disease from early systemic spread remains a major challenge in interdisciplinary decision-making. This study aimed to evaluate the prognostic significance of radiologically enlarged mediastinal lymph nodes (emLN) in patients with resectable ICCA. MATERIALS AND METHODS: Clinical data from all consecutive patients who underwent liver resection for ICCA between 2008 and 2018 at a single high-volume center were prospectively collected, with outcome data supplemented retrospectively. RESULTS: A total of 109 patients met the inclusion criteria and comprised the study cohort. Cross-sectional imaging identified emLN in 48 patients (44 %). Overall survival (OS) and recurrence-free survival (RFS) did not differ significantly between patients with and without emLN (OS: 29 vs. 30 months, p = 0.55; RFS: 11 months in both groups, p = 0.63). Among patients with left-sided ICCA, emLN were present in 39 cases (79.6 %), compared with 33 cases (55.0 %) in patients with right-lobe tumors (p = 0.008). CONCLUSION: This is the first study to assess the potential prognostic impact of radiologically enlarged mediastinal lymph nodes in ICCA. The presence of emLN on preoperative staging was not associated with impaired survival outcomes. Therefore, patients with resectable ICCA should be considered for curative resection irrespective of this radiological finding.
OBJECTIVE: Lung adenocarcinoma (LUAD) molecular heterogeneity limits traditional prognostic models. Given the emerging role of neural regulation (NR) in tumor progression, we aimed to delineate NR-associated cellular phe...OBJECTIVE: Lung adenocarcinoma (LUAD) molecular heterogeneity limits traditional prognostic models. Given the emerging role of neural regulation (NR) in tumor progression, we aimed to delineate NR-associated cellular phenotypes via single-cell RNA sequencing (scRNA-seq) and develop a robust machine-learning-derived signature (NR.Sig) to precisely assess prognosis and guide personalized immunotherapy. METHODS: We integrated three LUAD scRNA-seq cohorts and ten transcriptomic cohorts with immunotherapy records. Single-cell analyses (clustering, cell-cell communication, pseudotime trajectory) identified NR-enriched epithelial subpopulations. Using their prognostic marker genes, we evaluated 101 combinations from 10 machine learning algorithms via leave-one-out cross-validation. The combination yielding the highest C-index formed the NR.Sig model. Its prognostic accuracy, stability, and clinical utility in characterizing the tumor immune microenvironment (TME) and forecasting immunotherapy efficacy were comprehensively validated across multiple independent cohorts. RESULTS: "CRABP2-positive epithelial cells" were identified as a stem-like, NR-enriched malignant subpopulation correlating strongly with immune exhaustion. The random survival forest (RSF)-based NR.Sig achieved optimal modeling performance. Validation confirmed that NR.Sig high-risk patients had significantly shorter overall and progression-free survival. NR.Sig outperformed conventional clinical indicators and existing prognostic models, with FAM83A identified as the core hub gene. Crucially, high-risk scores inversely correlated with immune infiltration. Conversely, the low-risk group exhibited an "immune-hot" phenotype with enhanced cancer-immunity cycle activity and elevated checkpoint expression, translating to significantly higher immunotherapy response rates in independent clinical cohorts. CONCLUSION: By integrating scRNA-seq with an optimized machine learning framework, we developed and validated NR.Sig. This robust signature holds significant clinical translational value, serving as a precise molecular tool for LUAD risk stratification, prognostic assessment, and the guidance of personalized immunotherapy strategies.
Cancer Treat Res Commun
· 2026 Jul · PMID 42391655
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Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD), characterized by a unique inflammation-driven pathogenesis that distinguishes it from sporadic colorectal cancer. D...Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD), characterized by a unique inflammation-driven pathogenesis that distinguishes it from sporadic colorectal cancer. Despite advances in diagnostics and therapeutic interventions for IBD, effective preventive pharmacological treatments for CAC remain a critical unmet need. Drug discovery through the design and synthesis of novel molecules consumes considerable time and expense, especially for CAC in which no single enzyme, receptor, or gene dominates. Alternative approaches involve drug repurposing and application of natural compounds. The concurrent administration of multiple existing agents, as part of combination therapy, alongside the implementation of novel drug delivery systems such as nanocarriers, presents feasible and practical approaches for discovering effective treatments for CAC. After highlighting key molecular mechanisms in CAC pathogenesis, this review comprehensively surveys applied drug discovery approaches for CAC in preclinical studies. Our review highlights the importance of early and long-term intervention to prevent CAC, primarily by inhibiting the COX-2, STAT3, and NF-κB pathways associated with inflammation. Promising advances in CAC therapy involve the use of natural compounds and repurposed drugs, often administered in combination or through nanocarriers. These strategies aim to enhance therapeutic efficacy while minimizing toxicity.
Kalra SS, Grilli CB, Coombes BJ
… +29 more, Armasu S, Upjohn DP, Egan JB, Chen Q, Tern C, Zhang C, Rose JA, Putman R, Mcdermott G, Hsieh YL, Bublitz ML, Carmona EM, Klee EW, Lazaridis KN, Lasky-Su J, Dudbridge F, Peljto AL, Schwartz DA, Silverman EK, Allen RJ, Olson J, Walker T, Wain LV, Zamora A, Zein JG, Hunninghake GM, Ortega VE, Matthew Moll TC, Cho MH
Am J Respir Crit Care Med
· 2026 Jul · PMID 42391602
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RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic progressive pulmonary fibrosis and high mortality. Genetic markers, summarized into a polygenic risk score (PRS), associate with IPF in well-phen...RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic progressive pulmonary fibrosis and high mortality. Genetic markers, summarized into a polygenic risk score (PRS), associate with IPF in well-phenotyped research cohorts. OBJECTIVES: To evaluate the performance of the PRS using real-world data from routinely captured electronic healthcare records. METHODS: We conducted an observational study evaluating the association of a PRS for IPF with electronic healthcare record diagnosis of IPF as well as lung transplant-free survival in four independent cohorts; the Mass General Brigham Biobank (MGBB), Mayo Clinic Biobank (MCBB), Mayo Clinic Tapestry Cohort (Tapestry), and U.K. Biobank (UKBB). We used multivariable logistic regression and multivariable Cox proportional hazards models adjusting for age, gender, and principal components of ancestry. The cohorts then underwent fixed and random effects meta-analysis. MEASUREMENTS AND MAIN RESULTS: Of 37,709; 44,195; 43,202; and 447,422 participants from MGBB, MCBB, Tapestry and UKBB respectively, 1,015 (2.7%) 2,879 (6.5%), 1,310 (3.0%), and 2,742 (0.6%) participants had an IPF diagnosis. Meta-analysis demonstrated a high-risk PRS associated with IPF diagnosis, OR 2.88 (95%CI 2.41-3.44) compared to all other individuals. A high-risk PRS also associated with the composite endpoint of mortality or lung transplant among those with an IPF diagnosis, HR 1.23(95%CI 1.11-1.35) compared to all other individuals. CONCLUSIONS: A PRS can identify those at risk for an IPF diagnosis and mortality in biobank-scale data, which may have implications for clinical decisions. Further work is necessary to evaluate the utility of adding genetics in clinical settings.
Turk Arch Pediatr
· 2026 May · PMID 42391436
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OBJECTIVE: This study aimed to evaluate the discriminatory performance of hemogram-derived inflammatory parameters in distinguishing pediatric eosinophilic esophagitis (EoE) from symptomatic controls. To determine their...OBJECTIVE: This study aimed to evaluate the discriminatory performance of hemogram-derived inflammatory parameters in distinguishing pediatric eosinophilic esophagitis (EoE) from symptomatic controls. To determine their potential value as non-invasive tools for longitudinal monitoring, whether these markers correlate with endoscopic and histologic activity during follow-up was also assessed. METHODS: This retrospective, longitudinal study included pediatric patients who underwent upper gastrointestinal endoscopy at a tertiary pediatric gastroenterology center between August 2022 and August 2025. Children presenting with dysphagia, vomiting, or abdominal pain who had esophageal, gastric, and duodenal biopsies were evaluated. Eosinophilic esophagitis was diagnosed based on symptoms and the presence of ≥15 eosinophils per high-power field in esophageal biopsies. Symptomatic children with similar age and sex distribution without esophageal eosinophilia served as controls. Hemogram results obtained within 1 week before each endoscopy were analyzed. Hemogram-derived indices (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, derived neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index [SIRI], aggregate index of systemic inflammation, mean platelet volume-to-lymphocyte ratio, mean platelet volume-to-platelet ratio, and red cell distribution width-to-platelet ratio) were calculated. Diagnostic performance was assessed using receiver-operating characteristic analyses, and associations with endoscopic and histologic findings were examined using linear mixed-effects models. RESULTS: Children with EoE showed significantly higher absolute eosinophil counts and markedly elevated SIRI values at diagnosis compared with controls (P < .001). Systemic inflammation response index demonstrated excellent discriminatory performance, whereas most other hemogram-derived indices showed limited accuracy. During follow-up, none of the hemo- gram-derived parameters-including SIRI-correlated with endoscopic or histologic activity. CONCLUSION: Systemic inflammation response index demonstrated high discriminatory performance in distinguishing pediatric EoE from symptomatic controls, but showed no association with longitudinal disease activity. Endoscopic and histologic assessments remain essential for diagnosis and monitoring.
Daldaban Sarıca B, Kısaarslan AP, Altay D
… +1 more, Arslan D
Turk Arch Pediatr
· 2026 May · PMID 42391433
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OBJECTIVE: Rheumatologic diseases (RDs) are major comorbidities that frequently occur with inflammatory bowel disease (IBD). Rheumatologic diseases (RDs), such as juvenile spondylo-arthritis, juvenile idiopathic arthriti...OBJECTIVE: Rheumatologic diseases (RDs) are major comorbidities that frequently occur with inflammatory bowel disease (IBD). Rheumatologic diseases (RDs), such as juvenile spondylo-arthritis, juvenile idiopathic arthritis, systemic autoinflammatory diseases, vasculitis, and mixed connective tissue diseases, can affect disease activity and clinical course in patients with IBD. Therefore, it is essential to assess children with IBD for comorbid RDs. This study was conducted to evaluate the effect of rheumatologic conditions accompanying IBD on disease severity. MATERIALS AND METHODS: This study was conducted in the Pediatric Gastroenterology and Pediatric Rheumatology Departments of Erciyes University. Patients diagnosed with histopathologically confirmed IBD who were followed between November 2020 and December 2022, including those with concomitant RDs, were included. RESULTS: Forty-seven patients with IBD (ulcerative colitis (UC) and Crohn's disease (CD)), aged 14.0 (2.0-18.0) years [median, min-max], were included in the study. Twenty of 47 patients had accompanying RDs. Findings indicate that baseline disease activity for both CD and UC was higher in patients with IBD accompanied by RDs compared to those with IBD alone, both for CD and UC. In children with UC and CD, the decrease in disease activity scores in the group with concomitant RDs was found to be significantly more limited compared to those with IBD alone (P=.004 for CD; P=.006 for UC). CONCLUSION: These results emphasize the necessity for multidisciplinary management of comorbid RDs in patients with IBD, given its association with increased disease activity.
A mechanosensitive ion channel regulates liver cell proliferation after injury.A mechanosensitive ion channel regulates liver cell proliferation after injury.
Long-term success after liver transplantation (LT) is often hindered by side effects from lifelong immunosuppression (IS). Standard liver enzyme tests are poor indicators of graft inflammation or fibrosis. To address thi...Long-term success after liver transplantation (LT) is often hindered by side effects from lifelong immunosuppression (IS). Standard liver enzyme tests are poor indicators of graft inflammation or fibrosis. To address this, a program of surveillance liver biopsy (svLbx)-guided personalized IS has been implemented to inform decisions on IS minimization. This study, spanning from 2018 to 2024, extends previous short-term observations to assess the long-term impact of biopsy-guided Calcineurin Inhibitor (CNI) reduction in LT recipients, including follow-up biopsies. Patients' IS was adjusted based on svLbx findings, donor-specific antibodies, liver function, and comorbidities. Analyzing 242 LT recipients, the study compared outcomes in those whose CNI dosage was reduced (n=89) versus those whose dosage was maintained or increased (n=83). CNI reduction proved safe, with no increase in rejection, graft loss or death. Crucially, it significantly preserved kidney function (ΔeGFR: +0.5 vs. -6.5 mL/min) over a median follow-up of 47 months, even when controlling for baseline kidney function, CNI score, graft injury and time post-LT. Sequential biopsies revealed no worsening of fibrosis or inflammation, and non-invasive measures corroborated these findings. In conclusion, svLbx-guided CNI reduction safely maintains kidney function and prevents graft injury late after LT, making it a viable strategy for long-term IS minimization.
Kaur R, van Diepen K, Raiesdana S
… +10 more, Chappell KD, Ajibulu L, Gozdzik M, Halloran B, Hoentjen F, Kroeker KI, Peerani F, Prado CM, Kao D, Wong K
UNLABELLED: The role of diet in the management of inflammatory bowel disease (IBD) is increasingly recognized with recent guidelines providing specific dietary recommendations. Although mobile health apps targeting diet...UNLABELLED: The role of diet in the management of inflammatory bowel disease (IBD) is increasingly recognized with recent guidelines providing specific dietary recommendations. Although mobile health apps targeting diet and lifestyle habits in IBD are emerging, few are designed for self-management or have been formally evaluated for effectiveness. We have co-designed a diet guidance and tracking app (MyIBDDiet) with and for patients with IBD with the aim of improving overall diet profile. We will be conducting a 60-day single-centre pilot randomized trial of 40 IBD patients randomized in 1:1 ratio to MyIBDDiet app or usual care. Participants in the usual care group will crossover to the MyIBDDiet app group after 30 days. Primary outcome is usability assessed using a mixed method quantitative [Theoretical Framework of Acceptability (TFA), mHealth App Usability Questionnaire (MAUQ)], and qualitative approach (semi-structured interviews). Secondary outcomes include clinical efficacy evaluated by change in diet quality [Mini-EAT questionnaire, Automated Self-administered 24-Hour Dietary Assessment Tool (ASA-24), Healthy Eating Index (HEI), Mediterranean Diet Serving Score (MDSS)], changes in biomarkers of processed food intake (spot urine sodium and chloride), changes in IBD disease activity [Patient Reported Outcome (PRO2 and PRO3), C-reactive protein, fecal calprotectin], changes in quality of life [EuroQol-5 Dimension (EQ-5D), Short Inflammatory Bowel Disease Questionnaire (SIBDQ)] and safety. Exploratory outcomes include changes in fecal microbiome and serum and fecal metabolome. Additional quantitative data will be collected from the digital analytics of MyIBDDiet app. The pilot data generated will inform the design of an adequately powered randomized trial and future mobile app development and evaluation by providing a framework for evaluation of clinical effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06683105. Registered on 8 November 2024.
BACKGROUND AND AIMS: The impact of hospital rurality and weekend admission on outcomes in decompensated cirrhosis remains unclear. Studies suggest mixed effects of weekend admission on mortality and increased mortality i...BACKGROUND AND AIMS: The impact of hospital rurality and weekend admission on outcomes in decompensated cirrhosis remains unclear. Studies suggest mixed effects of weekend admission on mortality and increased mortality in rural hospital admissions for decompensated cirrhosis. This study evaluated the influence of hospital rurality, weekend admission, and their interaction on outcomes in decompensated cirrhosis from 2016 to 2020. METHODS: A cross-sectional analysis of the National Inpatient Sample (NIS) assessed in-hospital mortality (primary outcome), likelihood of specific procedures (esophagogastroduodenoscopy, paracentesis, TIPS, hemodialysis), and time to first procedure. Regression models adjusted for demographics, liver disease etiology, clinical severity (APR-DRG mortality risk), and other factors. RESULTS: Among 11,845,223 hospitalizations, rural hospitalizations were linked to lower in-hospital mortality (OR: 0.84; 95% CI: 0.80-0.86) and higher transfer rates for severe cases (7.2% vs. 2.8%, p < 0.001). Weekend admissions showed a statistically significant but only modest reduction in mortality odds (OR: 0.99; 95% CI: 0.975-0.998). No significant interaction existed between rurality and weekend admission regarding mortality. Rural hospitals showed lower odds of performing procedures (95% CIs < 1), though time to procedure was comparable, except for earlier hemodialysis (-1.35 days; 95% CI: -2.59 to -0.11). Weekend admissions did not significantly impact procedure rates, except for paracentesis (OR: 0.94; 95% CI: 0.88-0.99). CONCLUSIONS: Using a national cohort of hospitalized patients with decompensated cirrhosis, we showed that rural hospitals exhibited lower in-hospital mortality, fewer procedures, and higher transfer rates, and that weekend admissions showed only a minimal, clinically insignificant reduction in mortality, irrespective of hospital rurality.
BACKGROUND: Spontaneous passage of common bile duct stones (CBDSs) may render endoscopic retrograde cholangiopancreatography (ERCP) unnecessary. Although predictors of passage have been described, most prior studies were...BACKGROUND: Spontaneous passage of common bile duct stones (CBDSs) may render endoscopic retrograde cholangiopancreatography (ERCP) unnecessary. Although predictors of passage have been described, most prior studies were limited by a small number of events, and the impact of spontaneous passage on post-ERCP complications remains under-investigated. This study aimed to identify clinical predictors of spontaneous passage and evaluate its association with post-ERCP complications. METHODS: We conducted a retrospective cohort study of patients diagnosed with CBDSs who underwent endoscopic ultrasonography (EUS) or ERCP at a tertiary referral center. Spontaneous passage was defined as the absence of stones confirmed during the procedure. Multivariable risk regression was used to identify predictors of passage and to assess the association between spontaneous passage and post-ERCP complications. RESULTS: Spontaneous passage was observed in 113 of 404 patients (28%). Independent predictors of spontaneous passage included younger age (RR 0.88 per 10 years; 95% CI 0.81-0.96), smaller CBDS size (RR 0.78 per 1 mm; 95% CI 0.71-0.85), and single CBDS (RR 1.64; 95% CI 1.04-2.61). Regarding complications, post-ERCP pancreatitis (PEP) occurred more frequently in patients with spontaneous passage compared to those without (16.5% vs 7.6%, P = 0.01). After adjusting for relevant confounders, including procedural factors, spontaneous passage remained an independent risk factor for PEP (RR 2.48, 95% CI 1.25-4.92). CONCLUSIONS: Spontaneous passage of CBDSs is an independent risk factor for PEP. Younger age, smaller stone size, and a single stone are significant predictors of passage. These findings suggest that pre-procedural risk stratification and non-invasive confirmation of ductal clearance may be beneficial in selecting appropriate candidates, potentially reducing unnecessary ERCP and associated complications.
Zhou Z, Trost SG, Ryde GC
… +16 more, Parra-Soto S, Fang Z, Xu C, Lu Y, Wang K, Du M, Li Z, Lv Y, Gill JMR, Gray SR, Celis-Morales C, Gunter MJ, Giovannucci E, Pell JP, Song M, Ho FK
BACKGROUND: Current sedentary behavior (SB) guidelines primarily emphasize total time spent sedentary. We explored differences between interrupted and prolonged SB in relation to a range of cancer outcomes. METHODS AND F...BACKGROUND: Current sedentary behavior (SB) guidelines primarily emphasize total time spent sedentary. We explored differences between interrupted and prolonged SB in relation to a range of cancer outcomes. METHODS AND FINDINGS: This study included 91,292 UK Biobank participants with valid accelerometer data. Participants were followed for a median of 12.38 years (interquartile range 11.56-13.15 years). A two-step approach based on a random forest model was used to classify SB. Multivariable Cox proportional hazards models were applied to overall incident cancers and cancer deaths, plus obesity-related and type-2 diabetes-related cancers, and 23 site-specific cancers. Models were adjusted for demographic, socioeconomic, lifestyle, dietary, and health-status factors, including age, ethnicity, deprivation, education, smoking, alcohol intake, diet, and morbidity count. Isotemporal substitution models were used to estimate the associated cancer risk when replacing prolonged SB with intermittent SB, or physical activity (PA). After adjusting for sociodemographic and lifestyle factors, each additional hour of prolonged SB was associated with a higher risk of overall cancer mortality (hazard ratio [HR] HR1hour 1.09; 95% confidence interval [CI] [1.06, 1.11]; p < 0.001). Replacing 1 hour per day of prolonged SB with light PA (HRLPA 0.88; 95% CI [0.79, 0.99]; p = 0.033) was associated with lower risk of overall cancer mortality. Similarly, replacing 30 min per day of prolonged SB with moderate PA (HRMPA 0.92; 95% CI [0.86, 0.99]; p = 0.024) was associated with a lower risk of overall cancer mortality. The main methodological limitations were observational design, residual confounding, healthy volunteer bias, and measurement imprecision due to having only 7 days of accelerometer wear. CONCLUSION: Cancer risk associated with SB is specific to prolonged SB. Replacing prolonged SB physical activity is associated with lower cancer risk.
BACKGROUND: There are limited data regarding the impact of body mass index (BMI) on pharmacokinetics in patients with inflammatory bowel disease (IBD) treated with vedolizumab (VDZ) or ustekinumab (UST). The aim of the s...BACKGROUND: There are limited data regarding the impact of body mass index (BMI) on pharmacokinetics in patients with inflammatory bowel disease (IBD) treated with vedolizumab (VDZ) or ustekinumab (UST). The aim of the study was to investigate the association of BMI with VDZ and UST concentrations in IBD. METHODS: This single-center, retrospective study included consecutive patients with IBD who received intravenous (iv) VDZ or UST and underwent therapeutic drug monitoring (TDM) from November 2016 to March 2023. We assessed the correlation of BMI with drug concentrations using Spearman's rank test. RESULTS: The study population consisted of 170 patients; 89 (52%) patients received iv VDZ [44% Crohn's disease (CD)] and 81 received UST (81% CD). There was an inverse correlation of baseline BMI [ρ: -0.321; 95% confidence interval (CI) -0.534 to -0.070; P = .011] and BMI at first TDM (ρ: -0.253; 95% CI, -0.462 to -0.018; P = .031) with UST concentration at first TDM. Regarding the latter, subgroup analyses revealed that this correlation referred only to patients with Crohn's disease (CD) (ρ: -0.293; 95% CI, -0.515 to -0.035; P = .023) or patients with IBD on standard UST dosing (ρ: -0.369; 95% CI, -0.616 to -0.055; P = .019). In contrast, there was no correlation of BMI with VDZ concentrations. Multivariable linear regression analysis identified higher BMI at first TDM as an independent variable associated with lower UST concentrations (B: -0.408; 95% CI, -0.930 to -0.217; P = .002). CONCLUSION: This study demonstrated an inverse correlation between BMI and UST concentrations in patients with CD or patients with IBD on standard UST dosing, suggesting the need for closer TDM and dose adjustments to ensure optimal drug exposure in these patients with higher BMI.
Pugliese N, Jamialahmadi O, Cesaro A
… +4 more, Flagiello V, Mancina RM, Aghemo A, Romeo S
United European Gastroenterol J
· 2026 Jul · PMID 42390998
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BACKGROUND: Fatty pancreas is a metabolically active ectopic fat depot, but its cardiometabolic implications have been assessed using heterogeneous thresholds. We investigated the association of fatty pancreas, quantifie...BACKGROUND: Fatty pancreas is a metabolically active ectopic fat depot, but its cardiometabolic implications have been assessed using heterogeneous thresholds. We investigated the association of fatty pancreas, quantified using MRI-derived proton density fat fraction (PDFF) and categorised according to 2026 international consensus thresholds, with prevalent and incident type 2 diabetes (T2D), chronic kidney disease (CKD) and major adverse cardiovascular events (MACE). METHODS: We analysed 19,255 European-ancestry participants from the UK Biobank imaging sub-study. Pancreatic PDFF was categorised as normal (< 6%), mild (6 to < 16%) and moderate-to-severe fatty pancreas (≥ 16%). Outcomes were ascertained through national health records. Associations were estimated using multivariable logistic regression and Cox models, adjusted for age, sex, BMI-defined obesity, elevated MRI-derived visceral adipose tissue and outcome-specific covariates. RESULTS: Moderate-to-severe fatty pancreas was associated with prevalent and incident T2D (OR 3.25, 95% CI 2.49-4.27; p < 0.001; HR 2.72, 1.66-4.46; p < 0.001), incident CKD (HR 1.82, 1.29-2.57; p < 0.001), and prevalent and incident MACE (OR 1.26, 1.04-1.56; p = 0.022; HR 1.30, 1.02-1.66; p = 0.034). Mild fatty pancreas was associated with incident T2D (HR 2.19, 1.40-3.42; p < 0.001) and incident MACE (HR 1.29, 1.06-1.59; p = 0.013). Each 5% increase in pancreatic PDFF was associated with higher odds and hazard of T2D (OR 1.16, 1.12-1.21; HR 1.17, 1.09-1.25; both p < 0.001). CONCLUSIONS: Fatty pancreas was independently associated with prevalent and incident T2D, incident CKD and, more modestly, with MACE. These findings position fatty pancreas within the cardiovascular-kidney-metabolic continuum and support the clinical relevance of consensus-based PDFF thresholds for cardiometabolic risk assessment in European-ancestry populations.