Clinical and Translational Gastroenterology最新文献

Introduction: Interleukin-13 receptor alpha 2 (IL13RA2), triggering receptor expressed on myeloid cells-1 (TREM-1), and oncostatin M (OSM) may be associated with response to tumor necrosis factor-α antagonists (TNFAs) in inflammatory bowel disease. We aimed to assess the direction of association between TNFA-induced clinical remission and IL13RA2 and TREM-1, respectively, and assess the value of combining biomarkers for identifying nonresponders.

Methods: Plasma samples from a retrospective inflammatory bowel disease cohort were collected before TNFA start. Clinical remission at 1-year, surgery, hospitalization, adverse drug events, and TNFA discontinuation were assessed. IL13RA2 and TREM-1 concentrations were compared between those with and without 1-year clinical remission. OSM data were obtained from our previous cohort. Where significant, TREM-1 and IL23RA2 thresholds associated with clinical remission at 1-year were assessed using a receiver operating characteristic analysis. Significant biomarkers were combined using a linear discriminant analysis. The performance characteristics were assessed for individual biomarkers and biomarker combinations.

Results: In Crohn's disease (CD) (n = 95) and ulcerative colitis (UC) (n = 53), higher IL13RA2 concentrations, but not TREM-1, were found among those not achieving TNFA-associated clinical remission at 1-year (IL13RA2, CD, P < 0.0001; UC, P = 0.0003). IL13RA2 thresholds, 4.554 ng/mL (CD) and 6.117 ng/mL (UC) separated those with and without clinical remission at 1-year (CD, area under the receiver-operating characteristic curve = 0.80, 95% CI = 0.71-0.90, P < 0.0001; UC, area under the receiver-operating characteristic curve = 0.79, 95% CI = 0.66-0.91, P = 0.0005). In CD, combining IL13RA2 and OSM concentrations enhanced prediction accuracy compared with either biomarker alone and increased the identification of other important clinical outcomes.

Discussion: IL13RA2, but not TREM-1, was associated with TNFA response. In CD, its prediction accuracy improves when combined with OSM.

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.

Introduction: 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 patients with CVID 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%) patients with CVID-E suffered from GI infections, while 12 (46.2%) presented concurrent liver involvement. In comparison with the rest of the cohort, patients with CVID-E 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%) patients with CVID-L concurrently exhibited CVID-E, and patients with CVID-L presented more CVID-E, splenomegaly, and a trend toward more GI cancer and GI infections. CVID-L and age at CVID diagnosis emerged as independent risk factors for mortality.

Discussion: GI and hepatic involvements are common in patients with CVID and frequently occur together. These manifestations significantly affect 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.