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Background: Early diagnosis is key to prevent bowel damage in inflammatory bowel disease (IBD). Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists., Aim: To identify risk factors leading to prolonged diagnostic time in a German IBD cohort., Methods: Between 2012 and 2022, 430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis. Total diagnostic time was defined as the time from symptom onset to consulting a physician (patient waiting time) and from first consultation to IBD diagnosis (physician diagnostic time). Univariate and multivariate analyses were performed to identify risk factors for each time period., Results: The total diagnostic time was significantly longer in Crohn's disease (CD) compared to ulcerative colitis (UC) patients (12.0 vs 4.0 mo; P < 0.001), mainly due to increased physician diagnostic time (5.5 vs 1.0 mo; P < 0.001). In a multivariate analysis, the predominant symptoms diarrhea ( P = 0.012) and skin lesions ( P = 0.028) as well as performed gastroscopy ( P = 0.042) were associated with longer physician diagnostic time in CD patients. In UC, fever was correlated ( P = 0.020) with shorter physician diagnostic time, while fatigue ( P = 0.011) and positive family history ( P = 0.046) were correlated with longer physician diagnostic time., Conclusion: We demonstrated that CD patients compared to UC are at risk of long diagnostic delay. Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflicts of interest related to this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aberrant CD4 + T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4 + T cell reactions in patients with Crohn's disease (CD). Yeast-responsive CD4 + T cells in CD display a cytotoxic T helper cell (T H 1 cell) phenotype and show selective expansion of T cell clones that are highly cross-reactive to several commensal, as well as food-derived, fungal species. This indicates cross-reactive T cell selection by repeated encounter with conserved fungal antigens in the context of chronic intestinal disease. Our results highlighted a role of yeasts as drivers of aberrant CD4 + T cell reactivity in patients with CD and suggest that both gut-resident fungal commensals and daily dietary intake of yeasts might contribute to chronic activation of inflammatory CD4 + T cell responses in patients with CD., (© 2023. The Author(s).)

Immunosuppressive Interleukin (IL)-10 production by pro-inflammatory CD4 + T cells is a central self-regulatory function to limit aberrant inflammation. Still, the molecular mediators controlling IL-10 expression in human CD4 + T cells are largely undefined. Here, we identify a Notch/STAT3 signaling-module as a universal molecular switch to induce IL-10 expression across human naïve and major effector CD4 + T cell subsets. IL-10 induction was transient, jointly controlled by the transcription factors Blimp-1/c-Maf and accompanied by upregulation of several co-inhibitory receptors, including LAG-3, CD49b, PD-1, TIM-3 and TIGIT. Consistent with a protective role of IL-10 in inflammatory bowel diseases (IBD), effector CD4 + T cells from Crohn's disease patients were defective in Notch/STAT3-induced IL-10 production and skewed towards an inflammatory Th1/17 cell phenotype. Collectively, our data identify a Notch/STAT3-Blimp-1/c-Maf axis as a common anti-inflammatory pathway in human CD4 + T cells, which is defective in IBD and thus may represent an attractive therapeutic target., (© 2022. The Author(s).)

The complete and reliable documentation of endoscopic findings make up the crucial foundation for the treatment of patients with inflammatory bowel diseases such as Crohn´s disease and ulcerative colitis. These findings are, on the one hand, a prerequisite for therapeutic decisions and, on the other hand, important as a tool for assessing the response to ongoing treatments. Endoscopic reports should, therefore, be recorded according to standardized criteria to ensure that the findings of different endoscopists can be adequately compared and that changes in the course of the disease can be traced back. In consideration of these necessities, fifteen members of the Imaging Working Group of the German Kompetenznetz Darmerkrankungen have created a position paper proposing a structure and specifications for the documentation of endoscopic exams. In addition to the formal report structure, the recommendations address a large number of attributes of acute and chronic inflammatory alterations as well as endoscopically detectable complications, which are explained in detail and illustrated using exemplary images. In addition, more frequently used endoscopic activity indices are presented and their use in everyday clinical practice is discussed., Competing Interests: CS erhielt Beratungshonorare von AbbVie, Biogen, Ewopharma, Janssen-Cilag, MSD Sharp & Dohme, Pfizer und Takeda, AbbVie, Berlin Chemie, Biogen, Ewopharma, Dr. Falk, Janssen-Cilag, med update, Merckle, MSD Sharp & Dohme, Norgine, Novartis, Pfizer, Shire, Shield Therapeutics und Takeda sowie Forschungsunterstützung von AbbVie, Olympus und Pentax. OB erhielt Beratungshonorare von AbbVie, AMGEN, Hexal, Immundiagnostik, Dr. Falk Pharma, FERRING Arzneimittel, Janssen-Cilag, MSD Sharp & Dohme, Shield Therapeutics, Takeda Pharma, Tillotts Pharma sowie Referentenhonorare von AbbVie, Astellas Pharma, Biogen, Bristol-Myers Squibb, Dr. Falk Pharma, FERRING Arzneimittel, Janssen-Cilag, MSD Sharp & Dohme, Pfizer Pharma, Takeda Pharma. DCB hat keine Interessenkonflikte angegeben. MG erhielt Berater- bzw. Vortragshonorare von Janssen, Falk, MSD, Galapagos, AbbVie und Takeda. OD hat keine Interessenkonflikte angegeben. TK erhielt Beratungs- und Vortragshonorare von AbbVie, Allmiral, Arena Pharmaceuticals, Celgene/BMS, Celltrion, Ferring, Falk, Gilead Sciences, Galapagos, Janssen, Medtronic, Mundipharma, MSD, Pfizer, Shire, Sterna Biologicals, Takeda, Tillotts Pharma, JL hat folgende Verbindungen zu Unternehmen offenzulegen (Forschungsunterstützung: Vortragshonorar Berater/Gutachtertätigkeit) Medizinverlage Stuttgart; Celgene GmbH, Falk Foundation, Ferring Arzneimittel GmbH; Repha GmbH biologische Arzneimittel, Steigerwald Arzneimittelwerke GmbH, Sanofi, Dr. Willmar Schwabe; TechLab. JMa erhielt Beraterhonorar von AbbVie, Janssen-Cilag, Pharmacosmos und Takeda sowie Referentenhonorar und Reisekostenerstattungen von AbbVie, Cellgene, Falk Foundation, Ferring, Fujifilm, Janssen-Cilag, MSD, Pfizer und Takeda. WM erhielt Beratungshonorare von AbbVie, Amgen, Hexal, Janssen, MSD, Pfizer, Synformulas, Takeda, Vortragshonorare und Reiseunterstützung von AbbVie, alanta health service, Almirall, Aptalis, biogen, Falk, Gilead, Janssen, Pfizer, MSD, Takeda, Tillots, Vifor, Honorare für Studien von AbbVie, Janssen, MSD, Pfizer, Takeda. Er gibt Tätigkeiten in öffentlich-rechtlichen Gremien an als Mitglied der Vertreterversammlung der Landesärztekammer Saarland, der Beratungskommission der Prüfungsstelle für das Saarland, des beratenden Fachausschusses Fachärzte der KV Saarland, des Landesausschusses der Ärzte und Krankenkassen sowie des erweiterten Landesausschusses Saarland. Er ist abhängig beschäftigt im Konzern der alanta health group GmbH, Hamburg, und hält Aktien der Firmen AbbVie und Gilead. JMu macht folgende Angaben: Kooperationsvertrag mit Pentax, Vortragstätigkeiten für Pentax und Olympus, Vortragstätigkeiten für Helios Deutschland. MR erhielt Vortragshonorare von AbbVie, Janssen-Cilag und Ovesco. Der Arbeitgeber von AS erhielt Honorare für Vortrags- oder Beratungstätigkeit von AbbVie, Biogen, Cellgene, Falk Foundation, Pfizer, Janssen-Cilag, MSD, Pfizer und Takeda. TK erhielt Beratungshonorare von AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Hospira, Mundipharma, Dr. Falk Pharma GmbH, Gilead, Janssen, MSD Sharp & Dome GmbH, Novartis, Roche, Takeda Pharma GmbH und UCB sowie Referentenhonorare von AbbVie, Dr. Falk Pharma GmbH, Ferring Arzneimittel GmbH, MSD Sharp & Dome GmbH, Pfizer, Roche, Takeda Pharma GmbH und UCB. DW gibt Vortrags- und/oder Beratertätigkeiten für die Firmen AbbVie, Takeda, Janssen, MSD, Ferring, Celgene, Pharmacosmos, Celltrion, Tillotts Pharma und Falk Pharma an. RA hat folgende Verbindungen zu Unternehmen offenzulegen (Beratendes Gremium oder Komitee; Referententätigkeit; Beratungstätigkeit; Forschungsförderung): AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Cellgene, Celltrion Healthcare, Dr. Falk Pharma, Ferring, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa Pharmaceuticals, MSD Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche Pharma, Samsung Bioepsis, Takeda Pharma, Tillotts Pharma AG., (Thieme. All rights reserved.)

Background and Aims: Bile acid malabsorption (BAM)-associated diarrhea is an important clinical issue in patients with Crohn's disease (CD). We analyzed the efficacy and safety of the bile acid sequestrant colesevelam for treatment of BAM-associated diarrhea in CD patients in a randomized, double-blind, placebo-controlled study., Methods: The primary endpoint was the proportion of patients with >30% reduction of liquid stools/day from baseline to termination visit at week 4. Secondary endpoints were reduction of the number of liquid stools/day, improvement of stool consistency and quality of life., Results: 26 patients were analyzed in the intention-to-treat (ITT) analysis. The primary endpoint was reached by 10 patients (69.7%) in the colesevelam group compared to 3 patients (27.3%) in the placebo group (risk difference RD=.394, 95%CI:[-0.012; 0.706]; P=.0566). In the per-protocol analysis (n=22), the risk difference was statistically significant (RD=.470, 95%CI:[0.018; 0.788], P(H0: RD=0)=0.0364; 95% CI:[1.3;54.7]). Regarding secondary endpoints, in the ITT population colesevelam-treated patients had a significant reduction of liquid stools/day at week 4 (median 5.0 to 2.0; P=0.01), while patients treated with placebo had no significant reduction (median 4.0 to 3.0; P=0.42). Significantly more patients in the colesevelam group had improvement of stool consistency of at least one level in the Bristol stool chart, as compared to the placebo group (P=0.003)., Conclusions: We found significant differences in favor for colesevelam treatment compared to placebo treatment for CD patients with BAM regarding the reduction of the number of liquid stools/day and stool consistency. ClinicalTrials.gov number: NCT01203254., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Management of Clostridium difficile infection in patients with flaring inflammatory bowel disease (IBD) has not been optimized. We investigated the effects of combination therapy with antibiotics and immunomodulators in patients with IBD and C difficile infection., Methods: We analyzed data from 155 patients (59% with ulcerative colitis [UC]) from a retrospective, European Crohn's and Colitis organization, multi-center study comparing outcome of hospitalized IBD patients with C difficile infection who were treated with antibiotics (n = 51) or antibiotics and immunomodulators (n = 104). The primary composite outcome was death or colectomy within 3 months of admission, in-hospital megacolon, bowel perforation, hemodynamic shock, or respiratory failure., Results: The primary outcome occurred in 12% of patients given the combination treatment vs none of the patients given antibiotics alone (P = .01). UC, abdominal tenderness, or severe bloody diarrhea was more common among patients that received the combined therapy. However, multivariate analysis revealed that only the combination therapy maintained a trend for an independent association with the primary outcome (likelihood ratio = 11.9; CI, 0.9-157; P = .06). Treatment with 2 or 3 immunomodulators was correlated with the primary outcome, independent of disease severity at presentation (odds ratio [OR] = 17; CI, 3.2-91; P < .01). Acid-suppressing medications increased the risk of C difficile relapse (OR = 3.8; CI, 1.1-12.9; P = .03), whereas recent hospitalization correlated with increased rate of C difficile persistence (OR = 8; CI, 2.1-29; P = .002)., Conclusions: Patients with IBD that also have C difficile infection are frequently treated with a combination of antibiotics and immunomodulators. However, this combination tends to associate with a worse outcome than antibiotic therapy alone. Prospective controlled trials are urgently needed to optimize the management of these challenging patients.