BACKGROUND: Sessile serrated lesions (SSLs) account for 15% of colorectal cancers (CRCs) but detection remains difficult due to flat morphology, mucinous features, and subtle histology. AIMS: This study aimed to identify...BACKGROUND: Sessile serrated lesions (SSLs) account for 15% of colorectal cancers (CRCs) but detection remains difficult due to flat morphology, mucinous features, and subtle histology. AIMS: This study aimed to identify novel and functionally relevant biomarkers of SSLs using transcriptomic screening and multi-omics validation. METHODS: Paired SSL and normal mucosa specimens (n = 6) underwent RNA sequencing. Differentially expressed genes (DEGs) were filtered for membrane or secretory proteins and validated across TCGA and adenoma transcriptomes. Functional significance was assessed using CRISPR dependency profiling, proteotranscriptomic concordance, pharmacogenomic sensitivity, and connectivity map analysis. RESULTS: We identified 216 upregulated genes in SSLs, including 68 encoding secretory/membrane proteins that better discriminated SSLs from controls and were enriched for adhesion and neuronal signaling while suppressing TNFα-NFκB inflammatory pathways. Cross-cohort comparison revealed five overlapping candidates between SSLs and TCGA CMS1 tumors. Among them, S100P emerged as the primary biomarker candidate, showing consistent upregulation in SSLs and CMS1 tumors while remaining low in normal mucosa and conventional adenomas. TFF1 also showed RNA-level upregulation but appeared more context-dependent. S100P demonstrated strong RNA-protein concordance in CRC cell-line profiling, supporting its detectability as a biomarker candidate. Pharmacogenomic profiling of LS411N cells revealed marked sensitivity to SN-38 and fluoropyrimidines, consistent with serrated CRC vulnerabilities. Connectivity map analysis identified perturbations, including MAPK1 and histone acetyltransferase suppression, that may reverse parts of the SSL transcriptional program. CONCLUSION: These findings prioritize S100P as a promising biomarker candidate for SSLs that warrants further validation in larger cohorts and clinically applicable platforms.
BACKGROUND AND AIMS: There are limited data on hepatic recompensation in autoimmune hepatitis (AIH)-related decompensated cirrhosis. We evaluated incidence and predictors of recompensation and further decompensation, and...BACKGROUND AND AIMS: There are limited data on hepatic recompensation in autoimmune hepatitis (AIH)-related decompensated cirrhosis. We evaluated incidence and predictors of recompensation and further decompensation, and assessed the impact of recompensation on survival. METHODS: In this retrospective analysis of a prospectively maintained database, we included patients with AIH-related decompensated cirrhosis, confirmed by liver biopsy, who were treated with immunosuppression. Recompensation, defined by Baveno VII criteria (including etiological suppression), was analyzed using Fine and Gray competing-risk model with death as competing events. Secondary outcomes were all-cause mortality and further decompensation. RESULTS: Among 112 patients (71% women; mean age 41 ± 13 years), 75% had ascites, 26% had variceal bleeding, and 13% had hepatic encephalopathy; median MELD-Na and CTP scores were 15.7 and 7, respectively. Prednisolone, azathioprine, and mycophenolate mofetil were used in 89%, 62% and 21% of patients, respectively. Over a median follow-up of 29 months, 60 (54%) patients achieved recompensation. Younger age, lower CTP score, and biochemical response at 6 months independently predicted recompensation, with biochemical response being the strongest predictor (sHR 1.75, 95% CI 1.02-2.88). After recompensation, 9 (15%) patients developed further decompensation (1- and 2-year incidence of 3.4% and 8.5%), whereas among 52 non-recompensated patients, 36 (69%) developed further decompensation and 16 (31%) remained in a stable decompensated state. Recompensation was associated with reduced mortality (HR 0.22, 95% CI 0.05-0.90) compared with non-recompensated patients. CONCLUSION: Over half of treated AIH-related decompensated cirrhosis can achieve recompensation with immunosuppression, which is associated with reduced mortality. Younger age, lower CTP score, and biochemical response predict recompensation.
PURPOSE: Even in the absence of active inflammation, patients with inflammatory bowel diseases (IBD) frequently report symptoms consistent with irritable bowel syndrome (IBS), which may lead to restrictive dietary patter...PURPOSE: Even in the absence of active inflammation, patients with inflammatory bowel diseases (IBD) frequently report symptoms consistent with irritable bowel syndrome (IBS), which may lead to restrictive dietary patterns and ultimately increase the risk of avoidant/restrictive food intake disorder (ARFID). The aim was to evaluate the prevalence of patients at risk of ARFID among individuals with quiescent IBD and IBS-type symptoms, and to evaluate its association with the FODMAP intake. METHODS: A cross-sectional study was conducted on adult IBD patients followed in a tertiary Belgian center whose recent work-up showed endoscopic and biological remission as per STRIDE II criteria. Self-administered questionnaires (NIAS-Fr, SCOFF-F, FFQ-FODMAP-BE, GAD-7, PHQ-9, IBS SSS, PRO-2, HBI) were completed remotely via REDCap. Univariate and multivariate logistic regressions were performed, with the significant threshold fixed at 5%. RESULTS: Sixty-two patients were enrolled (65% female, 66% Crohn's disease, mean age 39 ± 14 years). Overall, 16 patients (26%) were screened positive for ARFID risk. Among these 16 patients, the distribution across subscales (picky eater, small appetite, fear of eating) was as follows: 63% (10/16) fulfilled one subscale, 31% (5/16) fulfilled two subscales, 6% (1/16) fulfilled all three. Higher IBS symptom severity was associated with a higher risk of positive screening for ARFID. In a multivariate logistic regression model, positive screening for risk of ARFID was associated with mild FODMAP consumption (FFQ-FODMAP-BE < 1.80) and anxiety. CONCLUSION: One in four patients with quiescent IBD has a positive screening for ARFID. Anxiety and low FODMAP intakes are associated with positive screening.
PURPOSE: Endoscopic resection (ER) has gradually emerged as an optional treatment method for non-ampullary duodenal lesions (NADLs); however, this procedure is associated with technical challenges and a notable risk of a...PURPOSE: Endoscopic resection (ER) has gradually emerged as an optional treatment method for non-ampullary duodenal lesions (NADLs); however, this procedure is associated with technical challenges and a notable risk of adverse events (AEs). The present study aimed to evaluate the efficacy and safety of ER for NADLs in a real-world clinical setting. METHODS: This was a retrospective observational study. Patients who received ER for NADLs were consecutively enrolled between January 2012 and December 2024. A total of 262 patients with a median (interquartile range) follow-up period of 24.0 (12.0-48.0) months were included, comprising 178 with epithelial lesions and 84 with subepithelial lesions. Patient demographics, clinical characteristics, and treatment outcomes were systematically documented and compared. Additionally, the associations between clinical variables and the occurrence of AEs were also analyzed. RESULTS: The en bloc and complete resection rates were 88.8% and 84.3%, respectively, for epithelial lesions and 88.1% and 86.9%, respectively, for subepithelial lesions. Lesions located in the duodenal junction (odds ratio [OR] 8.97; 95% confidence interval [CI] 1.92-41.98) and clipping closure (OR 0.39; 95% CI 0.17-0.87) were identified as independent predictors of AEs in the epithelial lesion group, whereas intraoperative perforation (OR 12.32; 95% CI 2.03-74.60) and size of defect (OR 3.34; 95% CI 1.46-7.63) were identified in the subepithelial group. CONCLUSION: ER is a relatively effective and safe therapeutic approach for NADLs in real-world practice, with a controllable risk of AEs and a low recurrence rate. Clinicians should pay more attention to postprocedural care for patients with duodenal junction lesions, intraoperative perforation, or large defects.
Tuberculosis (TB) continues to represent a major global health concern, particularly in high-burden countries such as India. In patients with cirrhosis, TB presents a distinct clinical challenge owing to cirrhosis-associ...Tuberculosis (TB) continues to represent a major global health concern, particularly in high-burden countries such as India. In patients with cirrhosis, TB presents a distinct clinical challenge owing to cirrhosis-associated immune dysfunction and impaired bacterial clearance, which increase susceptibility to both primary infection as well as reactivation of latent disease. Additionally, cirrhosis alters the classical clinical presentation and radiological findings of TB, thereby contributing to diagnostic ambiguity. Conventionally, tuberculin skin test and interferon-gamma release assays, demonstrate reduced reliability in the setting of immune dysregulation. Typical radiological findings may be absent, and advanced imaging modalities such as PET-CT may offer additional diagnostic value when standard imaging techniques such as chest radiography, ultrasonography, or computed tomography fail to reveal characteristic abnormalities. Invasive diagnostic approaches, including cytology or tissue biopsy, remain the gold standard for definitive confirmation. Therapeutic management is particularly complex, as first-line anti-tubercular agents such as isoniazid, rifampicin, and pyrazinamide possess significant hepatotoxic potential and may precipitate hepatic decompensation. Consequently, treatment strategies must be individualized according to Child-Turcotte-Pugh or MELD scores, with careful balancing of effective TB control against the risk of drug-induced liver injury. Close biochemical monitoring and cautious drug reintroduction are essential. Future directions should focus on the development of safer therapeutic regimens, incorporation of novel agents with lower hepatotoxic potential, application of pharmacogenomic-guided treatment approaches, and formulation of consensus guidelines specifically tailored to this high-risk population. This review aims to comprehensively describe the epidemiology, underlying pathophysiological mechanisms, diagnostic complexities, and therapeutic considerations of tuberculosis in patients with cirrhosis.
BACKGROUND AND AIMS: Ultra-processed food (UPF) is increasingly consumed worldwide and may influence gut microbial ecology relevant to inflammatory bowel disease (IBD). However, patient-level multi-omics data remains sca...BACKGROUND AND AIMS: Ultra-processed food (UPF) is increasingly consumed worldwide and may influence gut microbial ecology relevant to inflammatory bowel disease (IBD). However, patient-level multi-omics data remains scarce. We investigated whether habitual UPF intake is associated with specific microbiota and metabolite profiles in Korean patients with IBD. METHODS: Dietary intake was assessed using a validated food frequency questionnaire, and food was categorized by the NOVA system. UPF intake was expressed as percent of energy, and 313 patients were stratified into UPF low (Q1-Q2) and UPF high (Q3-Q4). Fecal samples of 174 patients underwent 16S rRNA sequencing and untargeted metabolomics. Microbiome differences were tested using PERMANOVA for beta-diversity and Mann-Whitney U tests for taxa. Differential metabolites were defined by p < 0.05 and |fold change|≥ 1.5, followed by Reactome enrichment with FDR correction. Correlations among microbiota, metabolites, and UPF subgroups were examined using Spearman tests with Benjamini-Hochberg adjustment. Associations between UPF intake and clinical characteristics were analyzed using Spearman tests, η from ANOVA and point-biserial correlation. RESULTS: Microbial beta-diversity differed significantly between UPF low and UPF high participants. UPF high participants showed expansion of pro-inflammatory pathobionts (Escherichia-Shigella, Proteus, Parasutterella, Enterococcus, Fusobacterium, and Clostridium innocuum group) and depletion of anti-inflammatory commensals (Faecalibacterium, Butyricicoccus, Lachnospiraceae ND3007 group, and Bifidobacterium). Metabolomic profiling revealed enrichment of inflammatory pathways (phospholipid metabolism, eNOS/NO signaling, mitochondrial β-oxidation, FMO3-mediated TMA to TMAO, tryptophan catabolism) and reduction of anti-inflammatory metabolites (AHR ligands, BAAT-conjugated bile acids). Integrated analyses demonstrated significant correlations between dysbiotic taxa and inflammatory metabolites. Among NOVA-defined UPF subgroups, sugar-sweetened beverages, ready-to-eat dishes, and packaged snacks and confectioneries showed the strongest associations with these adverse signatures. Analysis of clinical characteristics showed trends between total UPF intake and inflammatory markers (WBC, CRP, fecal calprotectin), and association with upper gastrointestinal tract involvement in patients with CD. Subgroup analysis showed that sugar-sweetened beverage intake was significantly associated with CRP elevation and upper gastrointestinal involvement in patients with CD. CONCLUSIONS: In IBD, higher UPF intake, particularly from specific NOVA-defined subgroups, is associated with gut dysbiosis and a pro-inflammatory metabolome, which in turn correlates with unfavorable clinical characteristics. These findings provide patient-based multi-omics evidence and underscore clinically relevant dietary targets for IBD management.
PURPOSE: The objective of this study was to evaluate how gender, academic rank, and race/ethnicity impact general industry payments for pediatric and adult gastroenterologists before and after the COVID-19 pandemic. METH...PURPOSE: The objective of this study was to evaluate how gender, academic rank, and race/ethnicity impact general industry payments for pediatric and adult gastroenterologists before and after the COVID-19 pandemic. METHODS: This is a retrospective cross-sectional study using data from Open Payments for pediatric and adult gastroenterologists from 2015, 2019, and 2021. Given concerns for the effect of academic rank, gastroenterologists at top-ranking pediatric and adult gastroenterology institutions were paired with data from Open Payments during analysis as well. Summary statistics regarding payments by gender, race/ethnicity, academic rank, and amount of payment were described. Furthermore, the effect of gender and race/ethnicity on the total sum of general payments was tested with a logistic regression model; within the top-ranking institutions, rank was added to this model. RESULTS: Our findings show that women received lower median payments across all subgroups. Even after adjusting for confounding factors of race/ethnicity and academic rank, gender disparities persisted, with men 1.5 to 2 times as likely to receive higher numbers of payments. CONCLUSIONS: Analyses must continue to evaluate disparities and allow for continued advancements toward gender payment equity.
BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cir...BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase ≥ 2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I = 75.6%, τ = 0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I = 0%, τ = 0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I = 70.2%, τ = 0.561) in MASH F3, with significant differences between stages (p = 0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.
While the exact cause of inflammatory bowel disease (IBD) remains unclear, interactions among several complex mechanisms are thought to contribute to its pathogenesis. One such factor is diet, which has recently been inv...While the exact cause of inflammatory bowel disease (IBD) remains unclear, interactions among several complex mechanisms are thought to contribute to its pathogenesis. One such factor is diet, which has recently been investigated for its role in both IBD pathogenesis and treatment. This review examines the evidence regarding diet, nutrition support, and dietary supplements for managing IBD. The diets discussed include low fiber/residue, Crohn's Disease exclusion, Specific Carbohydrate, Mediterranean, Anti-Inflammatory, Autoimmune Protocol, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), lactose-free, and gluten-free diets. Nutrition support options include enteral nutrition, partial enteral nutrition, and parenteral nutrition. These modalities can be considered in specific situations, such as perioperative nutrition, protein-calorie malnutrition, and induction of remission. Dietary supplements studied for managing IBD include prebiotics, probiotics, vitamin D, omega-3 fatty acids, polyphenols, and aloe vera, which may be beneficial in managing IBD. Some challenges to consider in the dietary management of IBD include food avoidance, food insecurity, and cultural practices. When contemplating initiating one of these options, input from a multidisciplinary gastroenterology team should be considered.
Metabolic dysfunction-associated steatohepatitis (MASH) is now recognized as the leading cause of cirrhosis, an important risk factor for hepatocellular carcinoma, and a growing indication for liver transplantation. The...Metabolic dysfunction-associated steatohepatitis (MASH) is now recognized as the leading cause of cirrhosis, an important risk factor for hepatocellular carcinoma, and a growing indication for liver transplantation. The U.S. Food and Drug Administration has recently approved two agents for the treatment of MASH in adults who have progressed to moderate-to-advanced hepatic fibrosis: resmetirom and semaglutide. Resmetirom is an oral, once-daily selective thyroid hormone receptor-β agonist that reduces steatohepatitis, promotes fibrosis regression, and improves atherogenic lipid particles. Semaglutide, a once-weekly subcutaneous glucagon-like peptide-1 receptor agonist, was originally approved for diabetes but has also demonstrated efficacy in treating MASH and hepatic fibrosis, while also exerting favorable effects on cardiometabolic risk profiles. As both agents are now considered first-line, clinicians face the challenge of selecting the optimal treatment. This review analyzes the pivotal data from the MAESTRO-NASH and ESSENCE trials to compare their contraindications, side effects, and clinical benefits, providing a practical framework for individualizing MASH treatment.
BACKGROUND AND AIMS: Hypertriglyceridemia-induced acute pancreatitis is associated with high triglyceride levels and may lead to significant clinical complications. Rapid TG-lowering strategies, including insulin, therap...BACKGROUND AND AIMS: Hypertriglyceridemia-induced acute pancreatitis is associated with high triglyceride levels and may lead to significant clinical complications. Rapid TG-lowering strategies, including insulin, therapeutic plasma exchange (TPE), heparin, hemofiltration, and conservative management, are used in clinical practice; however, their comparative efficacy and impact on clinical outcomes remain uncertain. METHODS: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration (CRD420251239674), we searched PubMed, Embase, Web of Science, Scopus, CINAHL, Google Scholar, and Cochrane. Primary outcomes included TG reduction, C-reactive protein (CRP), length of stay, mortality, and organ failure. Secondary outcomes included renal and respiratory failure. Random-effects network meta-analyses estimated mean differences or relative risks with 95% confidence intervals; treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA). Predefined sensitivity analyses were conducted according to study design (RCTs) and risk of bias (ROB). RESULTS: Across predominantly observational evidence, no intervention demonstrated statistically significant superiority over insulin-based therapy for mortality, organ failure, or length of stay, and no consistent clinical benefit was observed despite differences in biochemical TG reduction. Although some interventions showed relatively favorable SUCRA rankings across selected outcomes, these findings were not consistently supported by statistically significant or high-certainty evidence. In RCT-restricted analyses, therapeutic plasma exchange (TPE) significantly reduced TG levels versus insulin (MD - 620.0; p = 0.03) and CRP versus conservative therapy (MD - 0.80; p < 0.01), while insulin plus heparin was associated with shorter hospital stay (MD - 1.60 days; p < 0.01). However, faster triglyceride reduction did not consistently translate into improved mortality, organ failure, ICU-related outcomes, or length of stay. CONCLUSION: Despite improvements in biochemical markers, the clinical significance of rapid TG reduction in HTG-AP remains uncertain, as these effects were not consistently associated with improvements in mortality, organ failure, ICU-related outcomes, or hospital length of stay. Given that most available evidence was derived from nonrandomized studies and that the certainty of evidence was predominantly low or very low, adequately powered randomized controlled trials are needed to determine whether accelerated triglyceride lowering improves clinically meaningful patient outcomes.
BACKGROUND: In 2020, the U.S. Multi-Society Task Force (USMSTF) extended the surveillance interval for patients with 1-2 small (< 10 mm) tubular adenomas from 5-10 years to 7-10 years following a high-quality baseline co...BACKGROUND: In 2020, the U.S. Multi-Society Task Force (USMSTF) extended the surveillance interval for patients with 1-2 small (< 10 mm) tubular adenomas from 5-10 years to 7-10 years following a high-quality baseline colonoscopy. Whether longer intervals affect polyp yield at repeat colonoscopy remains unclear. METHODS: From 9,300 patients who underwent colonoscopy in 2015 within the MedStar Health system, we identified individuals with 1-2 small tubular adenomas who subsequently completed surveillance colonoscopy. Patients were identified using ICD-10 codes and manual chart review. Extracted variables included demographics, BMI, smoking status, NSAID use, race/ethnicity, family history of colorectal cancer (CRC), Boston Bowel Preparation Score, withdrawal time, pathology results, and surveillance interval. Patients were stratified into two groups: < 7 years vs ≥ 7 years between baseline and repeat colonoscopy. Primary outcomes were the detection of any polyp and neoplastic polyps (precancerous, advanced adenoma, SSL etc.). Group differences were evaluated using Wilcoxon rank-sum and Fisher's exact tests. RESULTS: A total of 399 patients met the inclusion criteria (326 < 7 years; 73 ≥ 7 years). Median follow-up time was 4.4 years vs 8.0 years, respectively (p < 0.001). Baseline characteristics-including age, gender, race/ethnicity, BMI, smoking status, NSAID use, and family history of CRC-were similar between groups, with no statistically significant differences (all p > 0.05). Procedure quality indicators such as Boston Bowel Preparation Score and withdrawal time, were also comparable. At repeat colonoscopy, patients with ≥ 7-year intervals had numerically higher rates of any polyp detection (67% vs 57%; p = 0.15) and neoplastic polyps (55% vs 48%; p = 0.30), though these differences were not statistically significant. CONCLUSIONS: Among patients with 1-2 small, low-risk tubular adenomas, extending the surveillance colonoscopy interval to ≥ 7 years did not significantly increase the detection of neoplastic polyps compared with earlier surveillance. Given the similar baseline characteristics and quality metrics between interval groups, these findings support the safety of the 2020 USMSTF recommendation for a 7-10 year surveillance interval. Larger studies may clarify whether delayed surveillance meaningfully affects advanced neoplasia risk.
PURPOSE: Underlying bioelectrical slow waves are critical for regulating gastric motility, and abnormal spatiotemporal slow-wave dysrhythmias are associated with a range of gastrointestinal disorders. However, the defini...PURPOSE: Underlying bioelectrical slow waves are critical for regulating gastric motility, and abnormal spatiotemporal slow-wave dysrhythmias are associated with a range of gastrointestinal disorders. However, the definition and role of the morphology of gastric slow-wave signals have remained limited. This study aimed to define gastric slow-wave morphology in cases of health and disease. METHODS: Data were repurposed from a study where, following ethical approval, a control cohort ( ) and a pathological cohort of patients with chronic unexplained nausea and vomiting (CUNV; ) underwent intra-operative high-resolution serosal electrical mapping (96-256 electrodes, 4.0-5.2 mm spacing). Slow waves were identified using validated software, and spatiotemporally averaged waveforms were compared between cohorts. These waveforms were replicated in a computational model of gastric slow-wave propagation to explore potential functional implications. RESULTS: The slow-wave morphology of the CUNV cohort exhibited a more gradual recovery stroke compared to controls, which manifested as an increase in the normalized recovery stroke area [0.206 (95% CI 0.169-0.247) vs. 0.134 (95% CI 0.106-0.166); ]. Computational modeling showed that these morphological differences could drive spatial slow-wave dysrhythmias. Considering the evident functional importance of gastric slow-wave morphology, we highlighted the three typical morphological features: (1) rapid, brief upstroke, (2) downstroke, and (3) biphasic recovery stroke. CONCLUSIONS: Altogether, this study presents a physiological basis of gastric slow-wave morphology in health and disease and lays a foundation for the standardization of future slow-wave morphology research.