Clinical and Translational Gastroenterology最新文献

Introduction: Biliary strictures present diagnostic challenges, necessitating early differentiation between benign and malignant cases. This study evaluates the diagnostic value of biliary and serum carcinoembryonic antigen (SCEA, BCEA) and carbohydrate antigen 19-9 (BCA19-9, SCA19-9) to enhance diagnostic accuracy.

Methods: A single-center retrospective cohort study enrolled 268 endoscopic retrograde cholangiopancreatography-treated patients, divided into training (n = 160) and validation (n = 108) sets. Levels of SCEA/SCA19-9 and BCEA/BCA19-9 were measured, and a combined diagnostic model was developed using receiver operating characteristic analysis and logistic regression. A meta-analysis of 7 studies assessed pooled odds ratios and heterogeneity in marker detection.

Results: BCEA and BCA19-9 levels significantly exceeded serum levels, with the combined model achieving an area under the curve of 0.921 (training) and 0.911 (validation), sensitivity 85.0%-83.3%, and specificity 83.7%-87.0%. Meta-analysis demonstrated a pooled odds ratio of 25.65, sensitivity of 95.0%, and specificity of 83.7%. CA19-9 cutoff variations had an insignificant impact, and the model improved pre-endoscopic retrograde cholangiopancreatography diagnostic accuracy by 20.7%.

Discussion: BCEA and BCA19-9 exhibit superior expression levels and diagnostic efficacy in distinguishing benign and malignant biliary strictures. The multimarker model enhances diagnostic performance, suggesting the relevance of integrating serum and biliary markers for accurate differentiation. Future studies should focus on optimizing cutoff values for enhanced diagnostic precision.

Introduction: Indomethacin is often used experimentally to induce intestinal hyperpermeability, enabling evaluation of interventions targeting barrier function.

Methods: We conducted a randomized, double-blind, placebo-controlled study (NCT05538247) in healthy volunteers to assess whether a supplement could mitigate indomethacin-induced hyperpermeability. Participants received 150 mg/d of indomethacin for 6 days, either before or during placebo/supplement administration. Permeability was measured using 13 C-mannitol and lactulose urinary excretion.

Results: Contrary to expectations, indomethacin failed to increase 13 C-mannitol excretion in either group. No meaningful elevations in serum (zonulin, claudins) or fecal (calprotectin) biomarkers were observed.

Discussion: Our findings suggest that the expected increase in intestinal permeability after indomethacin administration may not be consistently observed in healthy volunteers. These results highlight the need to carefully consider the reproducibility and sensitivity of this model in future clinical studies aiming to investigate gut barrier function.

Introduction: Celiac disease (CD) may affect quality of life (QoL), health care use, and societal costs in various ways both before and after diagnosis. However, detailed evidence remains limited about how costs and QoL change after diagnosis and which patient characteristics (e.g., symptom duration) influence those changes. The aim of this study was to evaluate CD patients' QoL and societal costs before and after diagnosis.

Methods: In this cross-sectional study, 2,691 patient-members of the Dutch Celiac Society completed a questionnaire about their life before and after diagnosis. Data collection included sociodemographic and clinical characteristics, health care use, non-health care costs, and QoL (measured using the EuroQol 5-Dimension 5-Level). Mean QoL and annual health care and societal costs were compared prediagnosis and postdiagnosis. Multivariate regression models were used to identify factors associated with QoL and costs in both periods (and difference between periods).

Results: On average, respondents recalled experiencing 4-5 symptoms before diagnosis. QoL improved significantly postdiagnosis, with greater improvements among childhood diagnoses. Annual health care and societal costs decreased by 23% and 36%, respectively, postdiagnosis, except for societal costs in those diagnosed during childhood. Age at diagnosis and the number of prediagnosis symptoms were associated with lower and higher recalled prediagnosis QoL, respectively. Number of symptoms, comorbidities, and nonadherence to a gluten-free diet were associated with lower postdiagnosis QoL.

Discussion: After CD diagnosis, QoL significantly improved and health care and societal costs decreased, except for societal costs among childhood diagnoses. These findings enhance the understanding of CD's burden and economic impact, supporting health care and policy efforts for timely CD identification.

Introduction: The risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been extensively studied; however, nonpancreatic adverse events, such as cholangitis, bleeding, and cardiopulmonary complications, are under characterized. We aimed to characterize the 30-day incidence and financial burden of nonpancreatic post-ERCP adverse events.

Methods: We performed a cross-sectional analysis using the Merative MarketScan commercial claims database from January 1, 2019 to December 31, 2021. The study included 27,482 patients who underwent 42,318 inpatient and outpatient ERCPs. Primary outcomes were post-ERCP cholangitis, bleeding, and cardiopulmonary complications within 30 days. Financial burden was measured using total direct healthcare costs and out-of-pocket costs during the 30-day period after ERCP. Multivariable logistic regression was used to identify associated risk factors and to estimate adjusted costs.

Results: Among 27,482 patients who underwent a total of 42,318 ERCPs, nonpancreatic adverse events occurred in 5.3% of cases: cholangitis in 3.6% (95% confidence interval [CI] 3.5%-3.8%), bleeding in 1.3% (95% CI 1.2%-1.4%), and cardiopulmonary complications in 1.1% (95% CI 1.0-1.3). In multivariable analysis, adverse events were more common among men and those with higher comorbidity burden. Patients with complications had significantly higher adjusted 30-day costs: cholangitis ($38,512 vs $30,881, difference $7,631), bleeding ($43,702 vs $30,918; difference $12,748), and cardiopulmonary complications ($53,649 vs $30,918; difference $22,930). Out-of-pocket costs varied by region and insurance type but exceeded $1,000 for many patients.

Discussion: Nonpancreatic ERCP adverse events occur in over 5% of cases and can impose a substantial financial burden on both healthcare systems and patients.

Introduction: Colorectal cancer (CRC) remains a leading cause of cancer associated death in the United States and colonoscopy the primary screening strategy for prevention. Rates of adenomatous and serrated neoplasia detection are inversely associated with post-colonoscopy CRC. This crucial quality metric depends on accurate ascertainment of colorectal neoplasia findings from both endoscopy and histopathology records. We aimed to assess the feasibility of a random forest machine learning model to rapidly and accurately categorize colorectal neoplasia from electronic health record data.

Methods: A retrospective cohort study compared neoplasia detection rates among individuals undergoing colonoscopy at a large academic institution to develop a rule-based algorithm to categorize colorectal neoplasia from endoscopy reports and pathology SNOMED II codes. This cohort provided a large training set to develop a natural language processing (NLP) system using a random forest approach to automatically classify unstructured pathology findings into adenoma, serrated, or advanced neoplasms. This system was manually validated through an independent holdout set.

Results: The training set comprised 35,953 unstructured pathology reports with matched SNOWMED II codes from 95,188 unstructured colonoscopy reports. The final model was assessed on an independent holdout set of 337 manually annotated procedures obtaining an AUC of 0.997 (CI 0.994 - 1), 0.99 (CI 0.98-1), and 0.99 (CI 0.98-0.99) for prediction of adenoma, serrated, and advanced lesions respectively.

Discussion: The random forest-based hybrid NLP system for classification of colonoscopy results was both accurate and explainable. NLP combined with effective machine learning algorithms can provide a scalable strategy for colonoscopy quality monitoring.

Introduction: Mucosal exposure devices (MEDs) and computer-aided detection (CADe) systems may both improve adenoma detection through distinct mechanisms: expanding mucosal visualization and highlighting lesions, respectively. This study investigated the efficacy of combining CADe-assisted colonoscopy with a MED compared to CADe-assisted colonoscopy alone.

Methods: This international, multicenter, prospective, non-randomized, single-arm study (NTC05220345) was conducted at three centers that also participated in the previous DISCOVERY II randomized controlled trial, comparing CADe-assisted with conventional colonoscopy. Patients referred for diagnostic, non-fecal immunochemical test screening, or surveillance colonoscopy and underwent CADe-assisted colonoscopy (DISCOVERY™, PENTAX Medical) with a MED using an integrated inflatable balloon (G-EYE™, PENTAX Medical). The primary outcome was adenoma detection rate (ADR); secondary outcomes included sessile serrated lesion detection rate (SSLDR) and withdrawal time without interventions. Outcomes were compared to historical controls of the CADe-arm of the DISCOVERY II study.

Results: Of 196 enrolled participants, 182 were included in the final analysis and compared with 250 participants from the historical CADe-arm. ADR was 47.3% in the CADe + MED-group vs. 38.4% in the CADe-group (p=.066; absolute difference: 8.9%, 95% CI: -0.6-18.3). Mixed-effects logistic regression model adjusting for clustering and confounders calculated an odds ratio of 1.16 (95% CI: 0.74-1.81). Median withdrawal time was slightly longer with CADe + MED compared to CADe-only (10.0 vs. 9.2 minutes, p=.004), while SSLDR was not significantly different (12.6% vs. 18.4%, p=.11).

Conclusions: In this study using historical controls, CADe-assisted colonoscopy combined with a MED did not significantly increase ADR compared to CADe alone, suggesting limited synergistic benefit.

Introduction: Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are first-line nucleos(t)ide analogs (NA) for chronic hepatitis B (CHB). Real-world monitoring of patients on these agents and their comparative renal safety remain poorly characterized. We evaluated guideline-adherent monitoring practices and compared renal dysfunction risk across ETV, TDF, and TAF.

Methods: We retrospectively analyzed patients with CHB who initiated ETV, TDF, or TAF between 2012 and 2022. Levels of serum alanine aminotransferase, total bilirubin, albumin, serum creatinine, hepatitis B virus DNA, and abdominal sonograms were assessed every 6 months during the 36 months of NA treatment. Incidence rates and adjusted hazard ratios (HRs) for renal dysfunction were estimated by Cox regression.

Results: Of the 2,155 enrolled patients, 65.8% received ETV, 23.1% received TDF, and 11.1% underwent TAF. Alanine aminotransferase was monitored in >90% across all groups; other tests (bilirubin, albumin, creatinine, hepatitis B virus DNA, sonogram) were performed in only 20%-80%. After multivariable adjustment, TDF (HR 1.41; 95% confidence interval 0.95-2.08) and TAF (HR 0.91; 95% confidence interval 0.52-2.18) showed no significant difference in renal dysfunction risk vs ETV. Independent predictors of increased renal risk included older age, higher Charlson comorbidity index, fibrosis-4 score, and diuretic use, whereas elevated serum albumin levels were associated with a lower risk.

Discussion: In this real-world cohort, adherence to recommended monitoring for patients with CHB on NAs was suboptimal. ETV, TDF, and TAF demonstrated comparable renal safety profiles over 3 years.

Introduction: Women with endometriosis have a higher risk of developing inflammatory bowel diseases (IBDs). 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 2 groups regarding CD location, disease phenotype, and anoperineal involvement. Proctitis were more frequent in patients with UC and endometriosis. Patients with IBD 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). Patients with CD with endometriosis had a less severe disease course compared with patients without endometriosis (hazard ratio 0.68, 95% confidence interval 0.50-0.92, P = 0.011). Patients with UC with endometriosis had not a significant different disease course compared with patients without endometriosis (hazard ratio 1.73, 95% confidence interval 0.74-4.00, P = 0.20). These results were similar in the subgroup of patients with endometriosis treated surgically.

Discussion: 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: 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.