We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). A multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023 was performed. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient’s bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode. During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) antithrombotic users, compared to 1113/5866 (18.9%) in nonusers (p < 0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occurred in 927 (36.5%) of antithrombotic users (36.5%), compared to 795 (13.5%) of nonusers (13.5%, p < 0.00001). Both the diagnostic yield of SBCE and the rebleeding rates were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real-world setting only for a minority of patients with positive findings.
Background/Introduction: Response to Janus kinase (JAK) inhibitors in ulcerative colitis (UC) varies, and reliable pretreatment molecular markers predicting therapeutic response are lacking. We investigated mucosal gene-expression profiles before and after treatment with tofacitinib or upadacitinib to identify baseline molecular signatures associated with clinical response and treatment-related changes. Methods: Paired baseline and follow-up mucosal biopsies were obtained from 57 patients with UC receiving upadacitinib (n = 32) or tofacitinib (n = 25), alongside biopsies from 11 healthy controls. Gene expression was assessed using a targeted 84-gene RT2 Profiler PCR Array. Gene-level and biologically informed module-level analyses were performed with Benjamini–Hochberg correction, while exploratory lasso logistic-regression models were evaluated using repeated nested cross-validation. Results: At baseline, 42 of 84 genes differed significantly between subsequent responders and non-responders [False Discovery Rate (FDR) < 0.05]. The strongest response-associated genes included IL13RA1, IL12B, IL18R1, IL6, BCL6, and STAT1, whereas IL25 and SPP1 showed lower expression in responders. Ten of 11 expression modules were higher in responders. Longitudinal analyses revealed treatment-associated molecular changes in both responders and non-responders. Tofacitinib responders exhibited significant reductions in several cytokine- and JAK/STAT-related genes and modules, whereas fewer changes reached statistical significance among upadacitinib responders. The combined gene-level prediction model achieved an internally cross-validated area under the curve (AUC) of 1.000 using participant-level predictions averaged across 50 repetitions, compared with 0.889 and 1.000 for the upadacitinib- and tofacitinib-specific models, respectively. Conclusions: These findings suggest that baseline mucosal gene-expression signatures are strongly associated with subsequent response to JAK inhibition. However, the small cohort and lack of external validation limit their immediate clinical applicability. Notably, molecular changes observed in non-responders indicate that pharmacodynamic pathway modulation does not necessarily translate into clinical improvement.
Background: Dysbiosis, mucosal inflammation and increased intestinal permeability have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Objective: To evaluate the effectiveness of a sequential butyrate–probiotic administration in reducing symptoms and improving stool consistency in patients with diarrhea-predominant (IBS-D) or mixed-type IBS (IBS-M). Methods: Two hundred adult patients were allocated to intervention (n = 105) or control (n = 95). The intervention group received ColonLife formulation (Εuro-Pharma S.r.l., Torino—Italy), consisting of two distinct capsules: the first containing butyric acid and grapefruit seed extract, and the second containing microencapsulated probiotic strains together with fructooligosaccharides (FOSs). Symptom severity, quality of life and stool consistency (Bristol Stool Scale) were assessed at baseline and three follow-up visits. Results: Baseline characteristics were comparable between groups (p > 0.05). Diarrhea severity decreased significantly in the intervention group (3.78 ± 1.01 to 3.31 ± 1.21; Δ − 0.47) compared with minimal change in controls (3.71 ± 1.05 to 3.62 ± 1.14; Δ − 0.08; p = 0.015). Stool consistency improved more in the intervention group (−1.18 ± 1.46 vs. −0.64 ± 1.41; p = 0.028), with normal stools increasing from 1.0% to 65.7% versus 4.2% to 36.8% in controls (p < 0.001). The degree of change in pain scores was similar between the two groups (p > 0.05). The degree of reduction in bloating scores was also similar between groups (p > 0.05). Quality of life improved in both groups (intervention: +0.68 ± 1.43; control: +0.71 ± 1.64; both p < 0.01), with no significant difference between groups (p > 0.05). Conclusions: Sequential butyrate–probiotic administration significantly improves diarrhea, stool consistency and gastrointestinal symptoms in IBS-D and IBS-M, supporting its role as a microbiota-targeted treatment.