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.

Studies from northern Europe indicate that patients with primary sclerosing cholangitis (PSC) are predominantly males and often have ulcerative colitis (UC) and increased risk of colorectal cancer (CRC). To evaluate the epidemiological and clinical features and natural history of PSC in Greece, a southern European country. In the HERACLIS-PSC study, consecutive patients with PSC-IBD followed at Greek inflammatory bowel disease (IBD) centers were included and compared to data from consecutive patients with PSC-only followed at a Greek liver center. Among PSC-IBD patients (n=112, males:56%), 62.5% had UC (pancolitis:76%), 35.7% Crohn's disease and 1.8% indeterminate colitis. PSC was diagnosed at a younger age in PSC-IBD than PSC-only patients (n=39; males:54%) (32±15 vs 40±15 years; p=0.007), while the two groups did not differ significantly in gender, extrahepatic bile duct involvement, or development of cirrhosis, cholangiocarcinoma or CRC, although CRC occurred only in PSC-IBD (n=8). Transplant-free survival was higher in PSC-IBD than PSC-only (5-/10-year:95%/87% vs 85%/77%; p=0.021), while older age at PSC diagnosis and cirrhosis development were independently associated with lower transplant-free survival. In Greece, PSC-IBD patients are usually males with UC, in whom PSC is diagnosed at a younger age demonstrating better transplant-free survival, compared to PSC-only.

Background and aims: Tofacitinib has been approved for the treatment of patients with moderate-to-severe ulcerative colitis independently of prior therapies. We aimed to assess the efficacy and safety of tofacitinib in biologic-naive patients. Methods: This was a retrospective analysis of prospectively collected data extracted from the notes of patients with moderate-to-severe ulcerative colitis naive to advanced therapies, who were treated with tofacitinib [10 mg twice daily (b.i.d.) for 8 or 16 weeks followed by a 5 mg b.i.d. maintenance dose] in six Greek Hospitals, who had a follow-up of at least 26 weeks after treatment initiation. Results: Overall, 48 patients were included. Clinical response was seen in 30 (62.5%) and 32 (66.6%) patients at week 8 and 16, respectively. Clinical remission, corticosteroid-free clinical remission, biochemical response, and endoscopic remission at week 26 was observed in 26 (54.2%), 26 (54.2%), 28 (60.8%), and 29 (60.4%) patients, respectively. No major adverse events or infections were recorded. Conclusion: In this retrospective ongoing cohort study, tofacitinib demonstrated clinical response at weeks 8 and 16 in more than 60% and steroid-free clinical remission at week 26 in more than 50% of biologic-naive patients with moderate-to-severe ulcerative colitis with a good safety profile, indicating that tofacitinib is an effective first-line treatment for this group of patients.

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 and Objectives: Ozanimod is approved for the treatment of ulcerative colitis (UC). The aim of the present study was to evaluate the clinical, biochemical, and endoscopic outcomes. Materials and Methods: This was a retrospective, multicenter, cohort study. Clinical, biochemical, endoscopic, and safety data were collected from medical records. Τhe primary outcome was clinical response at week 12. Secondary outcomes included clinical remission, endoscopic improvement and remission, biochemical outcomes, treatment persistence, and safety. Clinical outcomes were assessed at weeks 12 and 48, while treatment persistence was evaluated over the complete 48-week follow-up period, using Kaplan–Meier analysis. Clinical response was defined as a ≥30% reduction in partial Mayo score and remission as a partial Mayo score < 3, with no individual sub-score > 1 and a rectal bleeding sub-score of 0. Clinical response and remission were primarily assessed using an observed-case approach, with an additional sensitivity analysis classifying discontinuations due to lack of efficacy as treatment failures. Results: A total of 79 patients were included (62.0% male; median age 44 years, IQR 31–56). Prior biologic exposure was recorded in 29.1%, and 64.6% were previously exposed to oral corticosteroids. Among patients with available clinical assessment at week 12 (n = 62), clinical response and clinical remission were achieved in 77.4% and 71.0%, respectively. Among patients with available data at week 12 (n = 32), endoscopic improvement was observed in 65.6%, while endoscopic remission was achieved in 15.6%. At week 48, among 26 evaluable patients, clinical response and remission rates were 96.2% and 84.6%, respectively; when discontinuations due to lack of efficacy were considered treatment failures, the corresponding rates were 52.1% and 45.8%. Treatment persistence did not differ significantly according to overall prior biologic exposure, whereas previous vedolizumab exposure was associated with lower treatment persistence over the week 48 follow-up (log-rank p = 0.037). In multivariable Cox regression, previous vedolizumab exposure remained associated with an increased hazard of treatment discontinuation (adjusted HR 3.07, 95% CI 1.23–7.67; p = 0.016). Adverse events were reported in 13.9% of patients. Conclusions: Ozanimod demonstrated good efficacy and a favorable safety profile in patients with moderate UC.

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.