OBJECTIVES:Vaccinations are important for patients with immune-mediated inflammatory diseases (IMID), including multiple sclerosis (MS), inflammatory rheumatic and musculoskeletal diseases (iRMD), or inflammatory bowel diseases (IBD). However, safety concerns persist regarding potential disease worsening. This study assessed the risk of IMID worsening requiring emergency hospitalization following pneumococcal or influenza vaccination. METHODS:In this retrospective population-based cohort study, six target trial emulations with time-dependent matching were performed using claims data from the German statutory health insurance BARMER from January 2013 to December 2019. Covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS:Of 432,768 IMID patients, 9526 MS, 108,422 iRMD, and 19,238 IBD patients were included in pneumococcal trials, and 30,416 MS, 265,850 iRMD, and 53,056 IBD patients in influenza trials. No increased risk was found; instead, a trend toward risk reduction was observed. Pneumococcal trials showed HRs of 0.91 [95% CI: 0.58-1.42] for MS, 0.60 [0.38-0.94] for iRMD, and 0.89 [0.62-1.26] for IBD. The influenza trials showed similar results (MS: 0.94 [0.73-1.21]; iRMD: 0.79 [0.63-1.00]; IBD: 0.83 [0.68-1.03]). CONCLUSIONS:No evidence of increased IMID worsening requiring emergency hospitalization after pneumococcal or influenza vaccination was found, supporting the safety of immunizing these patients.

Abstract The gut microbiota communicates extensively with its host through small metabolites, such as bile acids. Primary bile acids are synthesized by the host and secreted into the intestine, where they are actively converted by the microbiota into secondary bile acids. Depending on the resulting bile acid composition, the host’s bile acid receptor, Takeda G protein–coupled receptor 5 (TGR5), is activated and mediates immune tolerance. It has been suggested that a disturbed bile acid profile in inflammatory bowel disease (IBD) might lead to inflammation via reduced activation of TGR5. Our study is the first to investigate whether bile acid-induced TGR5 activation differs between healthy individuals and patients with IBD. Bile acid profiles in stool and plasma were quantified by mass spectrometry, and TGR5 bioactivity was assessed from these profiles. In parallel, metagenomic sequencing was performed on fecal samples. We demonstrate that reduced alpha diversity in IBD is associated with a loss of microbial capacity for bile acid transformation, resulting in a significantly decreased secondary-to-primary bile acid ratio (sBA/pBA) in both stool and circulation. TGR5 bioactivity induced by bile acid profiles was substantially reduced in IBD patients, and a lower TGR5 bioactivity correlated with increased inflammatory activity.

Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) have an increased risk of infections due to immunosuppression and autoimmune disease. While vaccinations are an important preventive strategy, vaccination coverage remains insufficient in Germany. The study aimed to identify barriers and facilitators for vaccination uptake from the perspective of iRMD patients, general practitioners (GPs), and rheumatologists. We conducted semi-structured, qualitative interviews with German iRMD patients (n = 15), GPs (n = 10), and rheumatologists (n = 5). Data were analyzed using Kuckartz’s structured content analysis. The analysis focused on attitudes towards vaccination, information needs, decision-making, and perceived role distribution in care. A trust-based doctor-patient relationship and consistent, comprehensible information promoted willingness to vaccinate. Barriers included uncertainties regarding immunosuppressants, unclear responsibilities between GPs and rheumatologists, and inconsistent or conflicting medical recommendations. Patients desired a proactive approach from physicians and clearly assigned responsibilities. Physicians emphasized interprofessional exchange but stated time and structural challenges. The results underline the importance of coordinated communication and clear responsibilities in the vaccination process for iRMD patients. To increase vaccination rates among patients with iRMD, the focus should be on targeted information services, improved allocation of tasks between GPs and rheumatologists, timely scheduling of vaccinations (ideally before initiating immunosuppressive therapy), clear responsibilities for initiating and coordination of vaccination, and a structured, transparent flow of evidence-based information between specialists. The results provide a basis for the development of practical intervention strategies to increase vaccination uptake in this high-risk group. The study was registered at the German Register of Clinical Studies (DRKS): https://drks.de/search/de/trial/DRKS00031559 (Registration Date: 28.08.2023).

The accurate definition of in vivo, ex vivo and in vitro models is critical for the whole R&D process, i.e., basic research, clinical translation and reliability of results. Although many models are currently being developed, it is important to recognize the limitations and advantages of each of them. The aim of this review is to compile the most important alternatives to animal models in the fields of gastroenterology and hepatology research. A thorough comparison and understanding of each alternative model will certainly save time and money and will lead to better predictability and reliability of results for clinical translation and clinical trials. There is no single model capable of replacing the complexity of human biology. Nevertheless, it is essential to understand the fundamentals of human anatomy, physiology and disease pathophysiology to select the most appropriate model in translational research. At the same time, the appropriate model must be selected to gain a deeper understanding of the principal processes underlying human physiology and the pathology of diseases.

Zusammenfassung Die Colitis ulcerosa ist eine chronisch-entzündliche Systemerkrankung mit steigender Inzidenz und hoher Morbidität. Trotz etablierter Therapiestrategien, insbesondere der Rezidivprophylaxe mit Mesalazin, erleiden innerhalb eines Jahres etwa ein Drittel der Patientinnen und Patienten ein Rezidiv. Epidemiologische Studien zeigen eine inverse Assoziation zwischen vorausgegangener Appendektomie und Erkrankungsrisiko, was auf eine immunologische Rolle des Appendix hinweist. Vor diesem Hintergrund wurde die Appendektomie als ein potenziell krankheitsmodifizierender Ansatz postuliert. Die randomisierte ACCURE-Studie belegt im Remissionserhalt eine signifikante Reduktion der Ein-Jahres-Rezidivrate durch zusätzliche Appendektomie (36% vs. 56%; relatives Risiko 0,65; NNT=5) bei günstiger Sicherheitsbilanz. Für aktive Erkrankungen unter fortgeschrittener Therapie zeigte die nicht-randomisierte COSTA-Studie höhere steroidfreie Remissionsraten nach Appendektomie im Vergleich zu einem Wechsel auf JAK-Inhibitoren, jedoch ohne Unterschied hinsichtlich Kolektomierate. In der PASSION-Studie bei therapierefraktären Verläufen erreichten 30% ein klinisches Ansprechen; ein histologisch entzündeter Appendix war prädiktiv für Therapieerfolg. Zusammenfassend existiert randomisierte Evidenz ausschließlich für das Remissionserhaltungs-Setting. Die Appendektomie erscheint als risikoarmer, potenziell additiver Ansatz für selektionierte Patientinnen und Patienten, bedarf jedoch weiterer kontrollierter Studien mit Langzeitbeobachtung und Biomarkerstratifizierung.

Abstract Characterizing the non-pathological, exercise-induced immune-metabolic stress regulation is important for understanding physiological adaptations and distinguishing them from maladaptive responses. Because such responses are mostly studied with extensive, resource-intensive protocols, simple, standardized tests eliciting measurable immune-metabolic responses are valuable in clinical and non-clinical settings. Established field tests assess functional exercise capacity rather than providing a standardized stimulus for investigating exercise-induced immune regulation. This study examined the effects of the 1-minute sit-to-stand test (STST) on immune-metabolic stress indices and whether it elicits sufficient anaerobic stress to serve as a tool for investigating exercise-induced immunological stress responses. Capillary blood from 28 healthy adults was collected before, immediately after, and during 45 min after exercise to determine lactate, glucose, and blood cell counts; hemoconcentration correction was applied. Lactate increased significantly immediately after the STST, exceeding the anaerobic threshold (> 4 mmol/L). Leukocyte, lymphocyte, and granulocyte counts rose significantly post-exercise; leukocytes returned to baseline by 30 min, whereas granulocytes remained elevated. GLR and SII decreased significantly immediately post-exercise and increased during recovery, together with SIRI. Lactate changes correlated significantly with leukocyte, lymphocyte and granulocyte changes. Therefore, the STST represents a practical, standardized field-based model for immune-metabolic assessment with translational potential for clinical and non-clinical settings.

Abstract:Ulcerative colitis is a chronic inflammatory systemic disease with rising incidence and increased mortality. Despite established therapeutic strategies, particularly maintenance therapy with mesalazine, approximately one third of patients experience a relapse within one year. Epidemiological studies demonstrate an inverse association between prior appendectomy and the risk of developing the disease, suggesting an immunological role of the appendix. Against this background, appendectomy has been investigated as a potential disease-modifying approach. The randomized ACCURE trial demonstrated a significant reduction in the one-year relapse rate with adjunctive appendectomy in the maintenance setting (36% vs. 56%; relative risk 0.65; NNT = 5), with a favorable safety profile. In patients with active disease under advanced therapy, the non-randomized COSTA study showed higher rates of steroid-free remission after appendectomy compared with switching to a JAK inhibitor, although no difference in colectomy rates was observed. In the PASSION study of therapy-refractory disease, 30% achieved a clinical response; histologically inflamed appendices were predictive of therapeutic success. In summary, randomized evidence currently exists only for the maintenance setting. Appendectomy appears to be a low-risk, potentially additive strategy for selected patients, but further controlled studies with long-term follow-up and biomarker stratification are required.

Purpose Despite the substantial health and socioeconomic burden of Post-COVID condition (PCC), no disease-modifying therapy has been established, largely because of clinical heterogeneity and incompletely understood pathophysiology. Major national and international funding initiatives have been launched in response. Hundreds of interventional trials have investigated PCC, yet patients and their treating physicians largely rely on non-evidence-based treatment options in clinical practice. Methods Here we quantify the overlap between the registered trial landscape and patient-led practice. We deduplicated 854 registry records (ClinicalTrials.gov, DRKS, EU-CTR; snapshot 16 July 2026) into 714 unique interventional trials. Interventions were categorised as pharmacological or supportive/non-pharmacological, and endpoints as symptom-oriented or mechanism-oriented according to their therapeutic objective. Results Only 51 of 714 trials (7.1%) tested any of the 29 patient-guide treatments; 20 were active. Post-exertional malaise, the cardinal symptom of the ME/CFS-like phenotype, was captured in 57 trials but was a (co-)primary endpoint in only eight. Ten guide treatments - the first-line repertoire for autonomic dysfunction, mast-cell stabilisers, and several repurposed neuro-modulators - had no registered trial in any registry, and the German registry DRKS contributed no guide-relevant trial. Registered evidence concentrated instead on SARS-CoV-2 antivirals, immunoglobulins and hyperbaric oxygen. Only three of the eight trials with PEM as a (co-)primary endpoint tested an intervention directed at a proposed driver of PEM; none addressed microvascular or bioenergetic mechanisms. Conclusion The registered landscape emphasises symptomatic treatment. There is a substantial unmet need for well-powered, mechanism-based, disease-modifying trials with biomarker-driven designs and objective, exertion-based endpoints.

Die ärztliche Weiterbildung ist essenziell für eine qualitativ hochwertige Gesundheitsversorgung, da sie theoretisches Wissen in eigenständige klinische Handlungskompetenz überführt sowie dadurch Patientensicherheit und Behandlungsqualität gewährleistet. Die Weiterbildung zur Fachärztin bzw. zum Facharzt für Innere Medizin und Gastroenterologie basiert in Deutschland auf der Muster-Weiterbildungsordnung (MWBO) der Bundesärztekammer, deren Umsetzung durch die Landesärztekammern (LÄK) erfolgt. Trotz bundesweiter inhaltlicher Vorgaben bestehen regionale Unterschiede in Organisation und Durchführung. Die Weiterbildung umfasst derzeit 6 Jahre mit verpflichtenden Rotationen in Notaufnahme, Intensivmedizin und weiteren internistischen Bereichen sowie in spezifischen gastroenterologischen Kompetenzen, insbesondere in Endoskopie und Hepatologie. Zukünftige Herausforderungen ergeben sich v. a. durch die Krankenhausreform, die eine Reduktion von Weiterbildungsstandorten und damit Einschränkungen der Weiterbildungskapazitäten erwarten lässt. Gleichzeitig nimmt die Spezialisierung innerhalb der Gastroenterologie weiter zu, wodurch neue Konzepte für interventionelle Qualifikationen diskutiert werden, etwa Schwerpunktweiterbildungen oder flexible, zertifikatsbasierte Fortbildungsmodelle der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). Zudem wird die ambulante Weiterbildung in Zusammenarbeit mit niedergelassenen Gastroenterologen künftig an Bedeutung gewinnen. Entscheidend bleibt eine strukturierte, sektorenübergreifende und ausreichend finanzierte Weiterbildung, um langfristig eine flächendeckende und qualitativ hochwertige gastroenterologische Versorgung sicherzustellen.

Lipid mediators (LM), formed from polyunsaturated fatty acids (PUFA) through cyclooxygenase- and lipoxygenase (LOX)-dependent pathways, contribute to all stages of inflammation and are thus valuable targets for drugs that intervene with inflammatory diseases. Novel pharmacotherapeutic concepts attempt to support LM class-switching from pro-inflammatory 5-LOX-derived leukotrienes and cyclooxygenase-derived prostaglandins towards omega-3-PUFA-based specialized pro-resolving mediators (SPM), which accomplishes resolution of inflammation. Rosemary (Rosmarinus officinalis, contained in Canephron® N) and its bioactive components carnosic acid (CA) and carnosol (CS) suppress pro-inflammatory prostaglandin and leukotriene formation, but neither the impact of rosemary/Canephron® N nor of CA and CS on the biosynthesis of 15-LOX-derived SPM has been investigated yet. Here, we studied whether BNO 2103 (a mixture of pulverized rosemary leaves, centaury herb, and lovage root contained in Canephron® N), and its bioactive components CA and CS could promote LM class-switching from pro-inflammatory towards pro-resolving LM in human monocyte-derived macrophages (MDM), as well as in primary peritoneal macrophages from patients with liver cirrhosis ex vivo. BNO 2103, CA, and CS efficiently suppressed pro-inflammatory leukotriene and prostaglandin formation in activated human inflammatory macrophages while activating 15-LOX to enhance SPM production in pro-resolving M2-MDMs. Intriguingly, these LM class-switching activities exerted by CA are Ca2 +-independent and further boosted by concomitant supply of omega-3 PUFA with synergistic elevation of SPM and their precursors. Together, CA and CS from rosemary act as LM class-switching agents that suppress pro-inflammatory signaling but strongly promote pro-resolving LM, supporting the potential of rosemary-based phytotherapeutic drugs like Canephron® N for use in resolution pharmacology.

Pyoderma gangrenosum (PG) is a rare but challenging extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), affecting 6–48% of IBD patients. This retrospective study analyzes affected patients and evaluates therapeutic strategies for both IBD remission and PG resolution. A multicenter retrospective analysis was conducted on patients with IBD and PG in 8 tertiary centers in Germany and Austria. Demographic data, prior therapies, surgeries, treatment of PG were collected, and treatment responses assessed. The cohort included 50 patients (median age: 43 years; 68% female). Crohn’s disease (CD) was present in 58%, ulcerative colitis (UC) in 42%. Fifty percent of patients had prior surgery, 68% having an intestinal stoma. 48% were experienced to biologic therapy, predominantly anti-TNF therapy (83%). PG mainly affected the lower extremities (52%) and peristomal areas (24%). Systemic steroids were used in 52% of patients and led to PG resolution in only 12%. Anti-TNF therapy was the main approach, used in 68% of patients, with resolution achieved in 80%. Calcineurin inhibitors were given to 26% of patients and induced resolution in 38%. Three of six non-responders were successfully switched to infliximab. Overall PG resolution was achieved in 80%, correlating with IBD remission in 78%. The median time to PG resolution was five months. Anti-TNF therapy was an effective treatment for PG in IBD patients, even in those with prior non-response to calcineurin inhibitors. Systemic steroids showed low response rates. PG healing mostly aligned with IBD remission, underlining the need for tailored long-term therapy.

SARS-CoV-2 disrupts the choroid plexus (ChP) epithelium by binding to the ACE-2 receptor, causing blood cerebrospinal fluid barrier leakage and permitting interleukin (IL)-6 and pathogens into the brain, subsequently leading to demyelination, white matter (WM) damage in long COVID, and clinical worsening. The role of the ChP in long COVID and its relationships to WM integrity, IL-6, clinical symptoms, and ACEIs/ARBs medications remains unclear. Fifty-two long COVID individuals, 21 COVID-19 survivors, and 26 healthy controls (HCs) completed Montgomery-Asberg Depression Rating Scale (MADRS), Montreal Cognitive Assessment (MoCA) and interleukin (IL) -6 assessments. Manually segmented ChP volume and global free water corrected WM integrity was compared among groups, and consideration of ACE inhibition on the ChP was examined. Partial correlations explored relationships among ChP volume, IL-6, fractional anisotropy tissue (FAt), and symptoms. ChP changes were also assessed at baseline and after one year. Long COVID individuals showed higher MADRS (p < 0.001), lower MOCA score (p < 0.001), and smaller ChP volume (p = 0.02) among groups. Larger ChP volume was significantly correlated to higher IL-6 levels (r = 0.478, p = 0.005) in long COVID. No ChP volume differences were found over time in the long COVID group or HCs that transitioned to COVID-19 survivors. COVID-19 survivors had larger ChP volume at follow-up compared to baseline (p = 0.04). The smaller ChP in long COVID seems to involve persistent but low-grade blood-CSF barrier dysfunction and epithelial stress. IL-6 levels may affect ChP permeability and suggest ongoing neuroinflammation in the long COVID group.