Clinical and Translational Gastroenterology最新文献

Introduction: Women with endometriosis have a higher risk of developing inflammatory bowel diseases (IBD). This study aimed to better understanding the impact of endometriosis on the course of IBD.

Methods: We conducted a retrospective cohort study in 18 French and Belgian IBD centers between June 2022 and March 2023. Any patient with both conditions was eligible for inclusion. They were randomly matched to 1 or 2 patients with IBD without endometriosis. The impact on IBD progression was assessed using a composite severity criterion including intestinal damage or need for bowel surgery.

Results: Overall, 207 patients with both conditions (149 Crohn's disease (CD); 58 ulcerative colitis (UC)) were matched to 409 patients with IBD alone. The median follow-up duration for IBD was 10 years [5.75-17]. No difference was observed between the two groups regarding CD location, disease phenotype, and anoperineal involvement. Proctitis were more frequent in patients with UC and endometriosis. IBD patients with endometriosis were significantly less exposed to immunosuppressants (UC p<0.01; CD p<0.001) and biologics (UC p<0.01; CD p<0.001). CD patients with endometriosis had a less severe disease course compared to patients without endometriosis (HR=0.68; 95%CI 0.50-0.92; p=0.011). UC patients with endometriosis had not a significant different disease course compared to patients without endometriosis (HR=1.73; 95%CI 0.74-4.00; p=0.20). These results were similar in the subgroup of patients with endometriosis treated surgically.

Conclusions: Endometriosis does not negatively influence the course of IBD, patients with CD even have a less severe progression. Patients were significantly less exposed to immunosuppressants and biologics.

Introduction: Esophageal motility disorders (EMDs) are common in clinical practice, with a high symptomatic burden and significant impact on the patients' quality of life. High-resolution esophageal manometry (HREM) is the gold standard for the evaluation of functional esophageal disorders. The Chicago Classification offers a standardized approach to HREM. However, HREM remains a complex procedure, both in data analysis and in accessibility. This study aimed to develop and validate machine learning (ML) models to detect EMDs according to the Chicago Classification.

Methods: We retrospectively analyzed 618 HREM examinations from 3 centers (Spain and the United States) using 2 recording systems. Labels were assigned by expert consensus as either disorder present or absent for 2 categories: esophagogastric junction outflow disorders and peristalsis disorders. Several ML models were trained and evaluated. ML classifiers were developed using an 80/20 patient-level stratified split for training/validation and testing. Model selection was guided by internal evaluation through repeated 10-fold cross-validation. Model performance was assessed by accuracy and area under the receiver-operating characteristic curve (AUC-ROC).

Results: The GradientBoostingClassifier model outperformed the remaining ML models with an accuracy of 0.942 ± 0.015 and an AUC-ROC of 0.921 ± 0.041 for identifying disorders of esophagogastric junction outflow. The xGBClassifier model detected disorders of peristalsis with an accuracy of 0.809 ± 0.029 and an AUC-ROC of 0.871 ± 0.027. Performance was consistent across repeated validations, demonstrating model robustness and generalization.

Discussion: This multicenter, multidevice study demonstrates that ML models can accurately detect EMDs in HREM. Artificial intelligence-driven HREM may improve diagnosis by standardizing interpretation and reducing interobserver variability.

Introduction: Esophagogastric varices (EGV) are known to correlate with a poorer prognosis in patients with liver cirrhosis or hepatocellular carcinoma. However, their clinical significance in patients with cholangiocarcinoma (CCA) remains unknown. The aim of this study was to investigate the impact of EGV on the outcomes of patients with CCA.

Methods: This retrospective study enrolled 923 consecutive treatment-naive patients diagnosed with CCA between January 2013 and December 2023. Among these, 321 patients received esophagogastroduodenoscopy at the time of CCA diagnosis. The primary end point was to assess the impact of EGV on overall survival (OS) in patients with CCA, whereas the secondary end point was to identify the predictive factors for the occurrence of EGV.

Results: Of the patients analyzed, 47 (14.6%) were diagnosed with EGV by esophagogastroduodenoscopy. Among these, 39 patients did not receive primary prophylaxis for EGV bleeding and were classified as the EGV group, whereas the remaining 274 patients (85.4%) formed the non-EGV group. The median OS was shorter in the EGV group than that in the non-EGV group (182 vs 357 days, P = 0.009). Multivariate analyses identified the presence of EGV as an independent risk factor of poorer OS (hazard ratio 1.823, confidence interval 1.248-2.663, P = 0.002). Besides, fibrosis-4 scores >2.67 and albumin-bilirubin grades >1 were predictive factors for EGV occurrence.

Discussion: While the prevalence of concurrent EGV in patients with CCA was relatively low, its presence was associated with a poorer prognosis. The fibrosis-4 scores and albumin-bilirubin grades predicted the occurrence of EGV.

Background: Up to one third of the patients diagnosed with common variable immunodeficiency (CVID) may develop gastrointestinal (GI) and hepatic manifestations. This study aimed to evaluate the prognostic significance of enteropathy and liver disease in patients with CVID.

Methods: We conducted a retrospective study including all consecutive adult CVID patients followed in a tertiary care center in Spain from January 1990 to January 2023. A diagnosis of CVID-associated enteropathy (CVID-E) and CVID-associated liver involvement (CVID-L) was established when objective clinical, endoscopic, histologic, radiologic or hemodynamic findings were present. Relevant prognostic outcomes and their risk factors were studied, including survival, GI infections and GI cancer.

Results: Eighty-nine patients with confirmed CVID were included, 26 of them (29.2%) had CVID-E and 23 (25.8%) had CVID-L. Nineteen (73.1%) of CVID-E patients suffered from GI infections, while 12 (46.2%) presented concurrent liver involvement. In comparison with the rest of the cohort, CVID-E patients had more frequently liver involvement, GI infections, and GI cancer. Multivariate analysis identified CVID-E as an independent risk factor for GI infections. Twelve (52,2%) of CVID-L patients concurrently exhibited CVID-E, and CVID-L patients presented more CVID-associated enteropathy, splenomegaly, and a trend towards more GI cancer and GI infections. CVID-L and age at CVID diagnosis emerged as independent risk factors for mortality.

Conclusion: Gastrointestinal and hepatic involvements are common in patients with CVID, and frequently occur together. These manifestations significantly impact the disease course, increasing the risk of GI infections, GI malignancy, and, in the case of liver disease, mortality.

Introduction: Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis. Barrett's esophagus (BE) is a critical precursor of EAC. Patients with BE undergo endoscopic surveillance to monitor disease progression although only a small fraction develop EAC. These procedures are invasive and have limited accuracy in predicting BE progression. We evaluated the utility of an 8-protein mass spectrometry panel in predicting progression in patients with BE.

Methods: Eighty untreated controls and 20 cases were selected from our institutional tissue registry. Quantitative mass-spectrometry was performed on microdissected tissue sections. Data were split into 80% training and 20% test sets. We used Least Absolute Shrinkage and Selection Operator-regularized regression to train a logistic classifier on training data. Classifier performance was evaluated in test data.

Results: Ninety-two samples had sufficient tissue for mass spectrometry analysis (18 progressors, 74 nonprogressors). The multivariable regression model produced a sensitivity of 100% and a specificity of 39% in the overall cohort, with AUCs of 0.75 and 0.89 in the overall and test cohorts, respectively. Cox proportional hazards time-to-progression (TTP) showed a hazard ratio of 66.1 (95% CI 7.79-561, P = 0.00012) for the model prediction.

Discussion: The promising performance of the model generated here suggests that the test may aid in selecting patients most likely to benefit from active BE surveillance. Moreover, the association of this model's prediction with time-to-progression may offer decision support for management of patients likely to progress quickly. These results support continued development of this proteomic panel as a risk stratification tool for patients with BE.

Introduction: Clinically relevant esophagogastric junction metrics on functional lumen imaging probe (FLIP) in postfundoplication patients remain unclear.

Methods: Sixty-three symptomatic postfundoplication patients underwent FLIP, barium esophagram, and high-resolution manometry. Logistic regressions and receiver-operating characteristic curves for distensibility index (DI) at 60 mL and maximal diameter were generated to predict impaired clearance.

Results: Maximal diameter (odds ratio: 0.77, confidence interval: 0.62-0.96, P = 0.02, area under receiver-operating characteristic curve = 0.73), but not DI, independently predicted impaired clearance. Diameter >16.5 mm achieved >90% sensitivity for normal clearance; DI < 2.0 mm 2 /mm Hg and diameter <8 mm were >90% specific for impaired clearance.

Discussion: Maximal diameter on postfundoplication FLIP predicts impaired clearance and discriminates better than DI.

Introduction: Chitinase-3-like protein 1 (CHI3L1) is a glycoprotein involved in inflammation and fibrosis, but its association with nonalcoholic fatty liver disease (NAFLD) remains unclear. This study investigated the association between serum CHI3L1 levels and the risk of severe NAFLD in a large prospective cohort.

Methods: A prospective cohort study was conducted using UK Biobank data from 50,334 participants. Serum CHI3L1 levels were measured at baseline. Severe NAFLD cases were identified using hospital records. Cox proportional hazards models evaluated the association between CHI3L1 levels and severe NAFLD risk. Restricted cubic spline analysis assessed potential nonlinearity. Subgroup and mediation analyses were conducted to explore effect modifiers and underlying pathways.

Results: Over a median follow-up of 16 years, 766 severe NAFLD cases were identified. Higher CHI3L1 levels were significantly associated with increased severe NAFLD risk (hazard ratio 1.45, 95% confidence interval 1.34-1.58, P < 0.001). Restricted cubic spline analysis revealed a linear positive association without evidence of nonlinearity. Stratified analyses showed consistent associations across subgroups, with no significant interactions. Mediation analysis identified high-density lipoprotein cholesterol and alanine aminotransferase as partial mediators, explaining 6.38% and 2.86% of the total effect, respectively, whereas the direct effect of CHI3L1 remained dominant.

Discussion: Elevated CHI3L1 levels are associated with an increased risk of severe NAFLD. These findings suggest that CHI3L1 may serve as a novel biomarker and potential contributor to NAFLD progression, offering insights into the inflammatory and metabolic mechanisms underlying the disease.