Clinical and Translational Gastroenterology最新文献

Introduction: Crohn's disease is associated with varying degrees of mesenteric adipose tissue (MAT) hypertrophy. The study aimed to evaluate whether MAT hypertrophy, measured by MAT volume, is associated with worse response to anti-tumor necrosis factor alpha (TNF-α) therapy in biologic-naïve patients with Crohn's disease (CD).

Methods: A cohort of consecutive patients with CD who underwent computed tomography or MRI before the start of the anti-TNF-α therapy was included. Total MAT volume, excluding large vessels, was estimated. Primary outcomes-dose intensification, surgery, and withdrawal of anti-TNF-α therapy-were evaluated at 3 and 12 months after the initiation of treatment. We performed a multivariate logistic regression model to identify MAT volume as an independent risk factor of poor response to anti-TNF-α.

Results: Fifty biologic-naïve, consecutive patients with CD were included. The median MAT volume was 559.5 cm 3 (IQR: 410.3-891.9). MAT volume was positively correlated with weight (ρ = 0.66, P < 0.001) and age (ρ = 0.5, P < 0.001). Multivariate regression model showed that higher MAT volume independently predicted a poor response to anti-TNF-α treatment, as indicated by a greater need for dose intensification of anti-TNF-α agents within 12 months (adjusted odds ratio [OR a ]: 1.36; 95% CI: 1.08-1.81; P = 0.016) and an increased risk of CD surgery within 3 months (OR a : 1.65; 95% CI: 1.08-3.05; P = 0.048).

Discussion: MAT volume predicted an increased need for anti-TNF-α dose intensification and surgery in patients with biological-naïve Crohn's disease. MAT volume could be a valuable measure for identifying patients at risk of a poor anti-TNF-α response.

Introduction: The value of esophageal baseline impedance (BI) in assessing proximal reflux and laryngopharyngeal symptoms (LPSs) is unclear.

Methods: Two hundred eighteen patients with LPS underwent 24-hour combined hypopharyngeal-esophageal impedance-pH monitoring. Proximal/distal BI was obtained, and a slope-and-intercept model of proximal BI contour was constructed.

Results: Proximal BI correlated with proximal/pharyngeal reflux (r = -0.21, P < 0.01) and reflux symptom index (r = -0.14, P = 0.08). The proximal BI contour model incorporating both the BI change (slope) and BI just below upper esophageal sphincter (intercept) outperformed models using individual BI measures in predicting proximal (Akaike information criterion: 110 vs 251-253) or pharyngeal (akaike information criterion: 32 vs 141-148) reflux.

Discussion: Proximal esophageal impedance contour predicts proximal reflux in patients with LPS.

Introduction: Anti-integrin αvβ6 (anti-αvβ6) autoantibodies serve as a diagnostic biomarker and are associated with poor prognosis in ulcerative colitis (UC). We aimed to investigate whether anti-αvβ6 autoantibody levels predict treatment outcomes of advanced therapies in patients with moderately to severely active UC.

Methods: Anti-αvβ6 autoantibody levels were measured using prospectively collected serum samples at the initiation of advanced therapies. The primary outcome was treatment persistence up to 1 year; secondary outcomes included clinical remission rates at weeks 2, 6, 14, 24, and 48, comparing low-level and high-level groups stratified by an optimal cutoff from receiver operating characteristic analysis.

Results: A total of 144 patients were analyzed (121 [84.0%] with extensive colitis and 87 [60.4%] with prior exposure to advanced therapies). The median observation period was 10 months, and treatment discontinuation occurred in 70 patients (48.6%). Treatment persistence was significantly higher in the low-level group (log-rank test, P = 0.002), and multivariable Cox analysis identified low antibody levels as the only independent predictor (hazard ratio, 1.90; 95% CI, 1.09-3.32). Clinical remission rates were consistently higher in the low-level group throughout all time points, with the greatest difference at week 6 (47.5% vs 20.0%; χ 2 test, P = 0.003). Low antibody levels remained an independent predictor of remission at all time points.

Discussion: Anti-αvβ6 autoantibodies predicted both treatment persistence and clinical remission after advanced therapies, highlighting their potential as a predictive biomarker in patients with active UC.

Introduction: Colorectal cancer 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 postcolonoscopy colorectal cancer. 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 systematized nomenclature of medicine - clinical terms. This cohort provided a large training set to develop a natural language processing 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 systematized nomenclature of medicine - clinical terms from 95,188 unstructured colonoscopy reports. The final model was assessed on an independent holdout set of 337 manually annotated procedures obtaining an area under the receiver operating characteristic curve of 0.997 (confidence interval [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 natural language processing 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: 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: Gastrointestinal graft-versus-host disease (GI-GVHD) is a serious complication of hematopoietic stem cell transplantation, with diagnosis reliant on results of endoscopic biopsy. Optimal endoscopic approaches based on symptoms remain unclear.

Methods: We conducted a retrospective cohort study of 75 adult hematopoietic stem cell transplantation recipients with GVHD and GI symptoms undergoing endoscopic biopsy at Montefiore Medical Center (2015-2023). We assessed correlations between presenting upper (UGI) or lower GI (LGI) symptoms and biopsy-proven GVHD. Statistical analyses included χ 2 tests, phi coefficients, and logistic regression adjusting for demographic confounders. A subgroup analysis compared the diagnostic yield of flexible sigmoidoscopy vs full colonoscopy.

Results: Biopsy positivity strongly correlated with symptom location: 89.5% of patients with UGI symptoms had positive upper GI biopsies, and 100% with LGI symptoms had positive lower GI biopsies. χ 2 tests showed significant associations between symptoms and biopsy positivity ( P < 0.001), with phi coefficients indicating strong correlations ( r = 0.79 UGI; r = 0.82 LGI). Logistic regression confirmed symptom location as an independent predictor of biopsy results. Among 37 patients undergoing full colonoscopy, rectosigmoid biopsies showed perfect correlation with a diagnosis of GVHD ( r = 1.0, P < 0.001) when compared with other anatomic colon biopsy sites, suggesting flexible sigmoidoscopy is a cost-effective alternative for LGI symptoms.

Discussion: Symptom-guided endoscopic evaluation in GI-GVHD yields high diagnostic accuracy. Flexible sigmoidoscopy with targeted biopsies should be considered for patients with LGI symptoms because it may reduce procedural burden and health care costs without compromising diagnostic yield. These findings support symptom-directed, anatomically targeted approaches to improve patient care and resource utilization.

Introduction: Evidence on the comparative real-world effectiveness of terlipressin vs midodrine plus octreotide (MO) for hepatorenal syndrome-acute kidney injury (HRS-AKI) in the United Kingdom and the United States is limited.

Methods: Using individual-level chart review data for patients across the United Kingdom (2013-2017) and the United States (2016-2019), an indirect treatment comparison was conducted comparing the efficacy of terlipressin (UK cohort) with MO (US cohort). Covariate balancing propensity scoring matched the cohorts on baseline serum creatinine (SCr), presence of encephalopathy and/or ascites, albumin use and duration, age, and sex. The primary endpoint was HRS reversal, defined as achieving SCr ≤1.5 mg/dL by the last day of treatment.

Results: At treatment initiation, 90.2% of UK patients received terlipressin (194/215), while 89.2% of US patients received MO (140/157). Concomitant albumin was administered in 67.9% of UK and 98.7% of US patients. In a covariate balancing propensity score-adjusted cohort, HRS reversal was achieved in 53.2% of terlipressin-treated patients (the United Kingdom, weighted effective sample size of 75) compared with 16.9% of MO-treated patients (the United States, n = 89) (adjusted mean difference (95% CI) 36.3% (22.4, 50.2), P < 0.0001). In adjusted analysis, individuals treated with terlipressin experienced an overall reduction in SCr at completion of treatment (SCr decrease 1.00 mg/dL vs increase of 0.08 mg/dL for MO-treated patients, P < 0.0001).

Discussion: HRS-AKI treatment and outcomes differ between the United Kingdom and the United States, attributed to the historical standard of care MO in the United States. In adjusted analyses, real-world use of terlipressin was more effective than MO at improving kidney function and achieving HRS-AKI reversal.

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: 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: Noncirrhotic portal hypertension (NCPH) refers to a diverse group of disorders that affects the hepatic portosinusoidal vascular system resulting in portal hypertension (PH). Unlike cirrhosis, there are no noninvasive criteria to diagnose PH and varices in NCPH.

Methods: A prospective cohort of patients with NCPH who had transjugular liver biopsy, liver stiffness (LSM) measured using transient elastography, and laboratory and imaging data were included. PH was defined by the presence of one among the following-varices on endoscopy, portosystemic collaterals, or ascites on imaging. Logistic regression was used to identify predictors. The classification tree approach was used to identify cutoff values for the stepwise decision model.

Results: Of the 59 patients, 41 (69%) had PH and 36 (62%) had varices. LSM was higher in patients with PH (11.5 kPa vs 5.7 kPa, P < 0.01) and varices (12 kPa vs 5.9 kPa, P < 0.01). Platelet count was lower in patients with PH (79 vs 218 × 10 9 /L, P < 0.01) and varices (75 vs 209 × 10 9 /L, P < 0.01). Multivariate analysis combining LSM and platelet count predicts PH (area under receiver operating characteristic 96% [91%-99%]) and varices (area under receiver operating characteristic 92% [85%-99%]). A stepwise model combining platelet 140 × 10 9 /L and LSM 7 kPa performed with a sensitivity of 100%, negative predictive value of 100%, and accuracy of 90% to detect PH. The same model performed with sensitivity of 100%, negative predictive value of 100%, and accuracy of 81% to detect varices.

Discussion: Noninvasive model combining LSM with platelet count can aid in identifying NCPH patients with PH and varices. However, this model requires validation in an independent cohort.