Clinical and Translational Gastroenterology最新文献

Introduction: Eosinophilic gastritis (EoG) is commonly missed because of limited biopsy collection and failure to request tissue eosinophil counts on gastric biopsies. Continued efforts to identify less invasive biomarkers to improve diagnosis and disease monitoring have resulted in little success. We studied gastric fluids and serum in EoG and control patients to determine whether less invasive inflammatory markers can predict active EoG disease.

Methods: By Luminex MAGPIX, we measured cytokines, chemokines, and matrix metalloproteinases biomarkers from gastric fluids collected during routine upper endoscopy and serum from patients with active EoG (n = 20), active eosinophilic esophagitis (EoE) (n = 21), and non-eosinophilic gastrointestinal disease controls (n = 19). Comparison of biomarker concentrations among patients and predictive modeling for EoG status were performed.

Results: Twenty-six biomarker in gastric fluids and 6 biomarkers in serum were significantly elevated in active EoG compared with active EoE and non-eosinophilic gastrointestinal disease controls. Tree-based model, eXtreme Gradient Boosting, identified important biomarkers in both gastric fluids and serum predictive of EoG.

Discussion: We successfully measured inflammatory markers in gastric secretions. Th2-mediated cytokines were elevated in gastric secretions in EoG, differentiating them from EoE and expanding our understanding of inflammation in EoG. Notably, our results are the first to implicate matrix metalloproteinases in the EoG inflammatory process. Importantly, we found that gastric secretions can discern patients with active gastric eosinophilia involvement. Modeling identified 9 markers that predicted EoG with an area under the curve of 0.86. With further validation, gastric fluids could be used as an easy test to screen EoG by identify patients who would benefit from histopathologic enumeration of eosinophils on biopsies.

Introduction: Eosinophilic colitis (EoC) currently has limited options to induce histologic and clinical remission. Dupilumab is a human monoclonal antibody against the interleukin-4 receptor ɑ subunit effective in eosinophilic esophagitis (EoE) and other non-EoE eosinophilic gastrointestinal disorders.

Methods: We conducted a retrospective chart review to assess the histoclinical response of patients with EoC treated with dupilumab.

Results: Of 4 included patients, all 4 improved histologically, with 3 patients attaining histologic remission. All patients' symptom scores significantly improved, and 1 patient was asymptomatic on dupilumab.

Discussion: This retrospective case series provides preliminary evidence that dupilumab may be an effective treatment option for EoC.

Introduction: Chronic hepatitis B (CHB) is a widespread liver infection caused by hepatitis B virus, affecting 296 million people globally. The disease often progresses to severe conditions such as cirrhosis, hepatocellular carcinoma, and liver failure. The aim of this study was to evaluate the global, regional, and national burden of CHB-related cirrhosis from 1990 to 2021 and projected the disease development from 2022 to 2050.

Methods: In this study, data from the Global Burden of Disease 2021 database were used to analyze the global burden of CHB-related cirrhosis. Metrics such as incidence, prevalence, deaths, disability-adjusted life-years (DALYs), years lived with disability, and years of life lost were examined. Descriptive analysis explored the burden distribution by sex, age, Sociodemographic Index levels, and country in 1990 and 2021. Trend analysis used estimated annual percentage change to assess changes in age-standardized rates over time. The Autoregressive Integrated Moving Average model and the exponential smoothing model were applied to predict future trends.

Results: In 2021, CHB-related cirrhosis caused 4.8 million incident cases, 432,000 deaths, and 13.9 million DALYs globally, with decreasing trends in age-standardized incidence rate, age-standardized mortality rate, and age-standardized DALYs rate since 1990. Men exhibited higher burdens than women. Age-specific analysis revealed the highest age-standardized incidence rate in those aged younger than 5 years and the highest age-standardized mortality rate in the 85-89 years age group. Regionally, the greatest burden was observed in low Sociodemographic Index areas, with Sierra Leone and Egypt showing the highest rates. Projections indicate stable mortality but declining incidence and slightly increasing DALYs globally by 2050, with minor sex-specific variations.

Discussion: The 2021 Global Burden of Disease Study highlights progress in reducing CHB-related cirrhosis. Targeted efforts and lessons from successful interventions are essential to further alleviate this burden and improve outcomes worldwide.

Introduction: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that gradually progresses, making early diagnosis and treatment challenging. Reliable biomarkers could enhance diagnostic accuracy and therapeutic development.

Methods: This study analyzed 3 publicly available gene expression data sets from the Gene Expression Omnibus database: GSE119600 (90 patients with PBC and 47 healthy controls), GSE159676 (12 PBC patients and 6 controls), and GSE61260 (11 patients with PBC and 38 controls). To identify genes closely linked to PBC, we applied machine learning techniques, including Least Absolute Shrinkage and Selection Operator, Support Vector Machine-Recursive Feature Elimination, and random forest. We subsequently conducted gene set enrichment and immune cell infiltration analyses to investigate their biological significance. IN addition, potential drug interactions were explored through the Drug Gene Interaction Database, and a competing endogenous RNA regulatory network was developed to examine gene regulation. Finally, the expression of selected genes was validated through multiplex immunofluorescence staining of liver tissue samples from patients with PBC.

Results: We identified proteasome subunit beta 7, TRAF family member associated nuclear factor kappa-light-chain-enhancer of activated B cells activator Albumin (TANK)-binding kinase 1, solute carrier family 29 member 1, and natural killer cell receptor 2B4 as key genes associated with PBC; these genes were significantly enriched in immune-related pathways and strongly correlated with immune regulation. Drug target prediction indicated that some genes could interact with existing immunomodulators or anticancer drugs. Competing endogenous RNA network analysis revealed that TANK-binding kinase 1, solute carrier family 29 member 1, and natural killer cell receptor 2B4 interact with multiple miRNAs and long noncoding RNAs, potentially regulating the immune microenvironment of PBC through noncoding RNA mechanisms. Immunofluorescence staining confirmed that these genes were highly expressed in liver tissues from patients with PBC.

Discussion: By integrating machine learning and functional analyses, this study identified 4 genes that may serve as potential biomarkers for PBC. Their involvement in immune regulation suggests possible applications in both diagnosis and therapy. Further studies are necessary to explore their clinical relevance and therapeutic potential.

Introduction: Artificial intelligence (AI) has the potential to improve adenoma detection rates (ADRs) during colonoscopy, but the efficacy of various AI-assisted systems remains unclear. To evaluate and compare the effectiveness of different AI-assisted systems for detecting colorectal neoplasia during colonoscopy.

Methods: A systematic literature search of PubMed, Scopus, and Google Scholar databases was conducted up to March 4, 2025, to identify randomized controlled trials comparing AI-assisted colonoscopy with conventional colonoscopy. The analysis included AI systems such as GI Genius (Medtronic, Dublin, Ireland), CAD EYE (Fujifilm, Tokyo, Japan), ENDOANGEL, EndoScreener, and EndoAID. The primary outcome was ADR, analyzed using random-effects models to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Surface under the cumulative ranking curve (SUCRA) rankings and subgroup analyses were also performed.

Results: Seventeen randomized controlled trials with 10,547 participants were included. ENDOANGEL showed the highest efficacy (OR 1.84, 95% CI 1.50-2.30; SUCRA 0.9), followed by EndoAID (OR 1.64, 95% CI 1.20-2.26; SUCRA 0.7). CAD EYE and GI Genius were similarly ranked (OR 1.46 and 1.45, respectively). EndoScreener was ranked just above the control group (OR 1.37, 95% CI 1.20-1.56; SUCRA 0.4).

Discussion: AI-assisted colonoscopy systems showed improved ADR detection rates compared with traditional colonoscopy. These results suggest that artificial intelligence may help enhance detection during colonoscopy procedures; however, additional large-scale studies are needed to confirm these findings.

Introduction: The Donor Risk Index (DRI) is a widely used liver transplant allograft risk model but does not account for the increasing adoption of machine perfusion (MP).

Methods: Using Bayesian updating, we incorporated MP into the DRI framework (DRI-MP). A Bayesian proportional hazards model with informative priors derived from the original DRI was applied to Organ Procurement and Transplantation Network data from January 2022 to June 2024. Model performance was assessed using Harrell Concordance-statistic, calibration plots, and Brier scores.

Results: DRI-MP, defined as DRI × 0.7 for MP cases, improved 90-day graft survival discrimination (Harrell Concordance-statistic: = 0.546 vs 0.535, P = 0.040), while maintaining robust calibration.

Discussion: The Bayesian-updated DRI-MP modestly improves donor risk discrimination, reflecting contemporary transplant practice and providing an implementable tool with continuity from the original DRI.

Introduction: Individuals with a family history (FH) of colorectal cancer (CRC) are at increased risk of CRC. We aimed to assess the objective role and subjective perception of risk factors of colorectal neoplasia within this high-risk group.

Methods: Questionnaire and screening colonoscopy results were obtained from individuals aged 40-54 years with a reported FH of CRC in a first-degree relative in a multicenter cross-sectional study in Germany. Descriptive statistics characterized the cohort and distribution of risk factors. Multivariable logistic regression was used to derive adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) to evaluate factors associated with colorectal neoplasia and with subjectively perceived increased CRC-risk.

Results: Among 922 participants, 220 (23.9%) were diagnosed with colorectal neoplasia, 63 (6.8%) of these being advanced lesions. Strong associations with advanced neoplasia were observed for obesity (aOR 2.44, 95% CI 1.12-5.22), smoking (aOR 1.47, 95% CI 1.14-1.88 per 10-pack-years) and physical activity <45 minutes per day (aOR 2.51, 95% CI 1.11-5.25). For smoking and physical activity, but not for obesity, similar associations were also seen with any colorectal neoplasia. No associations were seen with number and age at diagnosis of affected family members. By contrast, the latter factors, but none of the behavioral factors were strongly associated with subjectively perceived CRC-risk.

Discussion: Within a cohort of individuals aged 40-54 years with a FH of CRC, obesity, smoking, and lack of physical activity represented the most prominent modifiable risk factors for the development of advanced colorectal neoplasia but did not significantly impact risk perception in these high-risk participants.

Introduction: Gastroesophageal reflux is common in respiratory disease, but the interplay between gastrointestinal mechanisms that expose individuals to reflux and potentially aspiration, and lung mechanics and function remain incompletely understood. Our aim was to investigate this in patients with chronic obstructive pulmonary disease (COPD) and non-idiopathic pulmonary fibrosis (IPF) interstitial lung disease (non-IPF ILD), and compare with our published findings in IPF.

Methods: Fifty-seven patients with COPD (aged: 34-75 years) and 64 with non-IPF ILD (22-75 years) who underwent high-resolution impedance manometry and 24-hour pH impedance together with pulmonary function assessment were compared with 35 IPF patients (51-84 years).

Results: COPD patients were less likely to exhibit ineffective esophageal motility (IEM) and/or absent contractility ( P = 0.009; P = 0.028), and tended to exhibit esophagogastric junction outflow obstruction (EGJOO) and/or hypercontractility ( P = 0.09, P = 0.14) than IPF and non-IPF ILD patients. Notably, integrated relaxation pressure correlated with esophageal length index (ELI) ( P = 0.048) and inspiratory LESP ( P = 0.003), with latter 2 correlating with each other ( P < 0.001). EGJOO patients tended to have fewer proximal reflux events and reduced pulmonary function, with the latter inversely correlating with ELI ( P < 0.05). Non-IPF ILD patients were less likely to exhibit EGJOO than COPD patients ( P = 0.27), and less likely to exhibit IEM ( P = 0.07) than IPF patients. However, those with IEM or EGJOO exhibited greater proportions of reflux events reaching the proximal esophagus than those with normal motility ( P < 0.03), which in contrast to IPF, seemed not to associate with worse pulmonary function.

Discussion: Associations between esophageal motility, and lung mechanics and function, and consequently reflux, are very disease-specific.

Introduction: The gut microbiome in Crohn's disease (CD) shows variability and conflicting associations with disease activity. We aimed to assess microbial and clinical trajectories in newly diagnosed CD (ndCD) over 1 year.

Methods: This prospective longitudinal inception cohort study followed treatment-naive patients with ndCD for 1 year. The primary outcome was sustained corticosteroid-free clinical remission (CSFR) after 1 year. Paired fecal samples were collected at diagnosis and 1 year later, analyzed using bacterial 16S rRNA gene high-throughput sequencing. Microbial composition changes were compared between baseline and 1-year follow-up and between biologics-treated and conservatively managed patients. Fecal samples from healthy volunteers served as controls.

Results: Seventy-three patients participated; 64.4% achieved sustained CSFR after 1 year. During follow-up, 60.3% had moderate-to-severe disease activity and received biologics (95.5% anti-tumor necrosis factor), whereas 39.7% were managed conservatively. Significant microbial improvements, including increased Shannon diversity and decreased microbial dysbiosis index, were observed only in patients achieving sustained CSFR (both P < 0.001). Biologic-treated patients had more disrupted baseline microbiome composition than conservatively managed ones (Shannon, P = 0.04; microbial dysbiosis index, P = 0.03); they showed significant microbial improvement regardless of clinical success, shifting toward a healthier microbiome profile. Changes in clinical outcomes over 1 year correlated with microbial alterations.

Discussion: Over 1 year, treatment-naive patients with ndCD showed microbial improvements paralleling clinical outcomes, with shifts toward a healthier state. Biologic therapy enhanced microbial profiles, likely due to greater baseline disruption in these patients. These findings suggest that the microbiome is a marker of inflammation and a modifiable factor in CD management.