Clinical and Translational Gastroenterology最新文献

Background: Colorectal cancer (CRC) is a highly prevalent cancer type worldwide. The global aging population situation is severe. Research on the disease burden of CRC among the 65+ elderly population, especially the risk factors, is still insufficient. Studies based on the GBD database can guide screening and prevention strategies.

Methods: As part of the 2021 GBD Study, we estimated the incidence, mortality, and disability-adjusted life years (DALYs) of CRC by sex and geographic location in the 65+ population, as well as the number of DALYs due to CRC-related risk factors.

Results: In 2021, diet low in whole grains (ASDR, 290.11 [117.98 to 440.48] per 100000), diet low in milk (ASDR, 239.69 [64.75 to 399.12] per 100000), diet high in red meat (ASDR, 239.02 [-0.08 to 486.82] per 100000) were the top 3 risk factors contributing to ASDR for both sexes combined globally. From 1990 to 2021, the ASDR for CRC attributable to 10 risk factors decreased for both sexes combined except high body-mass index (AAPC, 0.10[ 0.02 to 0.18]).

Conclusions: Over the past decade, the AAPC of ASIR, ASMR, and ASDR of CRC cases among people aged 65 and above globally has shown a downward trend overall, but the burden pattern varies by SDI quintile and GBD region, with an upward trend in middle to low SDI regions. There are differences in the incidence, mortality, and major risk factors of CRC in different regions. Reducing the prevalence of related risk factors is key to reducing CRC DALYs.

Objectives: Patients with decompensated cirrhosis have a high symptom burden and poor outcomes. Collaborative care models that provide coordinated, personalized care could improve outcomes. In this pilot randomized trial, we tested a cirrhosis-centric collaborative care model: the Cirrhosis Medical Home (CMH).

Methods: A single-center pilot randomized trial enrolling 40 hospitalized adults with decompensated cirrhosis randomized 1:1 to CMH or usual care. CMH involved 6 months of post-discharge individualized care. Primary outcomes were feasibility-based (enrollment, retention, data completeness). Secondary outcomes at 3 and 6 months included quality of life (SF-36) and healthcare utilization.

Results: Of 205 patients screened, 40 were enrolled. Of the 20 patients randomized to CMH, 13 received post-discharge CMH follow-up. At 3 months, 19 died or had a transplant, 9 were lost to follow-up, and 12 completed the SF-36. At 6 months, an additional 4 died or were lost to follow-up, and 8 completed the SF-36. In intention-to-treat analysis at 3 months, CMH did not improve quality of life. In per-protocol analysis at 3 months, CMH improved physical functioning (delta +15 vs -10, p=0.015), energy/fatigue (+20 vs -5, p=0.02), and physical component score (+5.5 vs -5.0, p=0.009). High mortality and readmission rates were seen in both arms but without significant differences.

Conclusions: Enrollment and retention in a randomized trial of the CMH for post-hospitalization management of decompensated cirrhosis is challenging, and patient-reported outcome assessment is limited by high rates of mortality, transplant, and loss to follow-up. These data can be used to inform future design and testing of health services interventions for this population.

Objective: Gut microbiome-modulating therapies are potential strategies for managing liver cirrhosis (LC), yet head-to-head comparisons to determine the optimal intervention are lacking. This study aimed to evaluate and rank the therapeutic efficacy of these therapies on liver function and disease progression in patients with LC.

Methods: We searched major databases (PubMed, Web of Science, Embase, Cochrane Library) for randomized controlled trials (RCTs) published from January 1, 2000, to December 30, 2024. Interventions included probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) versus placebo or standard care. Primary outcomes were hepatic function indicators; secondary outcomes included inflammatory markers. Data were analyzed using random-effects frequentist network meta-analyses. The study was registered on PROSPERO (CRD420251000506).

Results: Seventeen studies comprising 1051 individuals were included. Synbiotics demonstrated the most significant efficacy among all interventions, showing superior reduction in blood ammonia levels compared to placebo (Mean Difference (MD): -5.57), probiotics, and prebiotics. Prebiotics showed significant differences in lowering endotoxin levels compared to placebo (MD: -3.29) and probiotics. Furthermore, relative to placebo, prebiotics significantly reduced tumor necrosis factor-alpha (MD: -2.30) and interleukin-6 levels (MD: -4.60).

Conclusions: This network meta-analysis advances current knowledge by establishing an evidence-based hierarchy of efficacy. Synbiotics are most effective for reducing blood ammonia, whereas prebiotics demonstrate superior efficacy in lowering endotoxin and inflammatory markers. These results support a personalized therapeutic approach: prioritizing synbiotics for patients with hyperammonemia, and prebiotics for those characterized by systemic inflammation. Future high-quality RCTs are needed to standardize specific strain combinations.

Aims: This study aimed to investigate the oral-cecal transit time (OCTT) and its correlation with small intestinal dysbiosis in cirrhotic patients with minimal hepatic encephalopathy (MHE) and co-existing small intestinal bacterial overgrowth (SIBO).

Methods: We enrolled 110 patients with a confirmed diagnosis of cirrhosis admitted to the Department of Gastroenterology at The Affiliated Hospital of Qingdao University between December 2021 and December 2023. The lactulose hydrogen breath test (LHBT) was utilized to diagnose SIBO and to measure OCTT. Patients were stratified into three cohorts: a SIBO(+) MHE group, a SIBO(-) MHE group, and a non-MHE group. Duodenal mucosal biopsies were collected from a subset of 26 cirrhotic patients and 5 healthy controls for microbial analysis.

Results: Among the 110 cirrhotic patients, the prevalence of MHE was 53.6% (59/110). Within the MHE cohort, the prevalence of SIBO was 71.19% (42/59). The SIBO(+) MHE group exhibited a significantly prolonged OCTT compared to both the non-MHE group (P<0.05) and the SIBO(-) MHE group (P<0.05). At the phylum level, Proteobacteria, Firmicutes, and Bacteroidetes were the most dominant taxa. At the genus level, Rothia, Streptococcus, Escherichia, Actinomyces, Prevotella, and Pseudomonas predominated. Significant differences in the small intestinal microbiota composition were found between the SIBO-MHE group and the other two cirrhotic groups (P<0.05). Patients with prolonged OCTT showed a greater relative abundance of Bacteroides, Streptococcus, Bacillus, Lactobacillus, Alphaproteobacteria, and Prevotella.

Conclusion: Cirrhotic patients with SIBO(+) MHE demonstrate a prolonged OCTT compared to their counterparts without SIBO, indicating significant gastrointestinal dysmotility.

Background and aim: While several dietary factors like high salt intake are linked to progression of Gastric intestinal metaplasia (GIM) to gastric cancer (GC) in high-risk countries, their effect on GIM progression in Western populations remains less clear. This study investigates the influence of dietary factors on GIM progression in a Western population.

Methods: The PROREGAL study (2009-2024) is a prospective cohort study of GIM patients undergoing surveillance. The Operative Link on Gastric Intestinal Metaplasia (OLGIM) criteria determined GIM stage, with an increase in OLGIM stage reflecting disease progression. Data on family history, medication use, and diet were collected through self-reported questionnaire and by medical records. Multivariate logistic regression was used to identify risk factors for disease progression.

Results: A total of 312 GIM patients were included (median age 61 years, 50.3% male, median follow-up 54 months, IQR 36). Progression occurred in 112 patients (35.9%), with six patients (1.9%) developing high-grade dysplasia or GC. High dietary salt consumption (OR 1.67; 95% CI 1.05-2.68, P=0.04), meat ≥6 servings per week (OR 1.25; 95% CI 1.07-1.46, P=0.004) smoking (OR 1.76; 95%CI 1.04-2.68), autoimmune gastritis (OR 2.49; 95%CI 1.04-5.83) and having a positive first-degree family member with GC (OR 2.01; 95%CI 1.20-3.52) were significantly associated with GIM progression. Fish consumption, alcohol intake, and previous H. pylori infection showed no significant association with GIM progression.

Conclusion: Increased consumption of meat and salt is significantly associated with GIM progression, suggesting that dietary risk factors for GIM progression are similar in low- and high-incidence countries.

Introduction: Fecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI). Adverse reactions to FMT occur early, and cellular immune responses after FMT may contribute to effects and reactions. We compared early changes in peripheral immune cell subsets and clinical outcomes in patients with rCDI who received either FMT and antibiotics or antibiotics alone in a randomized trial.

Methods: Thirty-five patients with rCDI were randomized to vancomycin and FMT (n = 20) or vancomycin alone (n = 15). Blood samples were drawn before (wk0) and 1 week (wk1) after treatment. In 3 additional patients, blood samples were drawn before and 24 hours and wk1 after FMT. Adaptive and innate immune cell subsets and gut-homing memory (CD45RO + integrinβ7 + ) and effector (CD45RO - integrinβ7 + ) T cells were analyzed by flow cytometry.

Results: FMT induced subtle changes in immune cell subsets with no clear pattern from wk0 to wk1. The Treg fraction tended to decrease after FMT, and a similar decrease at 24 hours indicated rapid T regulatory cells dynamics. Natural killer T (NKT) cells increased during the first 24 hours and returned to baseline level at wk1. Regardless of FMT, patients with clinical resolution from rCDI had a decrease in nonclassical monocytes and a shift in gut-homing memory to effector cells at wk1.

Discussion: In rCDI, FMT induced subtle and transient dynamics in peripheral immune cell subsets. T regulatory cells and NKT cells seemed responsive and should be further studied. Cure of Clostridioides difficile infection may be associated with an increase in circulating gut-homing T cells.

Introduction: We sought to perform the first validation of the American Society for Gastrointestinal Endoscopy (ASGE) complexity grades for EGD, colonoscopy, ERCP, and EUS.

Methods: We used Pearson's correlation coefficients to measure the correlation between complexity grades and both work relative value units (wRVUs) and malpractice RVUs (mRVUs) obtained from the Centers for Medicare and Medicaid Services.

Results: There was moderate to strong positive correlation between complexity grades and both wRVU and mRVU for a range of EGD, colonoscopy and EUS procedures. This was not observed for ERCP procedures, with many RVU values remaining low for even the most complex ERCP cases.

Conclusions: The ASGE's endoscopic complexity grading system for EGD, colonoscopy and EUS appears to correlate reasonably well with other recognized metrics of complexity and risk. The complexity levels for ERCP may be valid, but there is poor correlation with how these procedures are valued by Medicare.

Abstract: The increasing global burden of digestive diseases, coupled with the complexity of their pathogenesis, underscores the urgent need for in-depth research into precise organ-specific therapies. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a crucial innate immune signaling axis, has garnered considerable attention for its roles in immune defense, inflammation regulation, tumorigenesis, and tissue homeostasis. In this review, we outline common digestive diseases linked to the cGAS-STING pathway, elucidate its mechanistic contributions to these conditions, and provide a detailed analysis of how targeting this signaling axis may influence disease progression. We hope this review will offer a theoretical foundation for developing novel therapeutics and innovative treatment strategies for digestive diseases, thereby contributing to improved clinical outcomes.