Abstract Background Inflammatory bowel disease (IBD) patients with Clostridiodes difficile Infection (CDI) are at increased risk of disease exacerbations, therapy escalation, colectomy, and mortality. Data on fidaxomicin use in IBD patients with CDI are very limited. We aimed to assess the effectiveness and safety of fidaxomicin for CDI and its impact on IBD outcomes in a large retrospective multicenter cohort study. Methods Adult ulcerative colitis (UC) or Crohn’s disease (CD) patients with a CDI episode (positive toxin enzyme immunoassay or polymerase chain reaction for toxigenic C. difficile) treated with fidaxomicin for at least 7 consecutive days were included. The primary outcome was CDI recurrence rate, defined as C. difficile toxin detection and treatment with any antibiotic targeting CDI or faecal microbial transplantation within 8 weeks. Secondary outcomes included sustained response rate (no CDI treatment for 12 weeks), IBD therapy escalation, colectomy, and all-cause mortality at 30, 90, and 180 days. Pre-specified and any other adverse events were collected. Results A total of 96 patients (57 CD and 39 UC) were included from 20 European IBD centers. Patient demographics, IBD, and CDI characteristics are summarized in Tables 1 and 2. Most patients (73%) were on advanced IBD therapy, and 34% on steroids. Half of the patients were hospitalized, and 15% had a severe CDI episode. Half of the patients had a prior episode of CDI (30% with one, 21% with two or more), predominantly treated with vancomycin. Most patients (86%) received a fidaxomicin standard dose regimen, while 9 received extended-pulsed dosing. CDI recurrence occurred in 10 (10%) patients, while 79 (82%) patients achieved a sustained response. Compared to CDI-experienced patients, CDI naïve patients tended to have a lower recurrence (4.3 vs 16%; p=0.06) and higher sustained response (91 vs 75%; p=0.04) rate. Induction treatment with an IBD advanced therapy was required in 22 (24%), 18 (20%), and 11 (13%) patients at 30, 90, and 180 days, respectively. No difference in terms of CDI recurrence and sustained response was identified between CD and UC patients. Patients achieving, compared to not-achieving, CDI sustained response, showed a numerically lower need for IBD therapy escalation, with 2 (12%) vs 20 (26%), at day 30. Five UC patients underwent colectomy. A 79-year-old UC patient died unrelated to IBD or CDI. Mild episodes of rash, nausea, conjunctivitis, asthenia, hypokalemia, and hypocalcemia were reported. Conclusion In this large cohort of IBD patients with CDI, fidaxomicin was effective and safe for CDI resolution, with greater effectiveness for CDI first episodes. CDI resolution might influence short-term IBD-related outcomes, although further studies are required.

Abstract Background The best maintenance therapy after a steroid-responsive acute severe ulcerative colitis (ASUC) episode remains poorly studied and is not addressed in current guidelines. We aimed to compare the impact of different treatment strategies following hospitalization for steroid-responsive ASUC. Methods Multicentric, multinational, retrospective cohort study including patients hospitalized with ASUC, between 2010-2021, who responded to intravenous steroids (Oxford Criteria). Patients were categorized according to treatment instituted after discharge - 5ASA, immunomodulators (IMM) and advanced therapy (AT). AT was considered as the reference for comparison. Our primary outcome was a composite of time until disease progression (need for steroids, need for therapy change, new hospitalization or colectomy); secondary outcomes were each event analyzed separately. Survival analysis and multivariate cox regression were performed. Results 271 steroid-responsive patients from 19 countries were included; median-age at diagnosis was 33 (IQR 25-48) years, 49% were male, 49% had extensive colitis at diagnosis; median disease duration was 26 (IQR 3.0-92.3) months. Following hospitalization for steroid responsive ASUC, 34% of patients received 5-ASA as a maintenance therapy, 23% IMM and 43% AT. During a median follow up of 59 months (IQR 38-92), 68% had disease progression: new course of steroids was needed in 40%, therapy change in 54%, new hospitalization in 33% and colectomy in 10%. In univariate analysis, patients treated with 5-ASA had a trend towards earlier disease progression, compared to AT (HR 1.37, CI 95% 0.99-1.91, p=0.06), earlier need for steroids (HR 1.70, CI 95% 1.11-2.59, p=0.014) and therapy change (HR 1.68, CI 95% 1.15-2.43, p=0.007). In multivariate analysis, adjusting for age and disease extension at diagnosis, disease duration, use of AT prior to ASUC hospitalization, and period of hospitalization (2010-2015 vs 2016-2021), patients treated with 5-ASA had a higher risk of disease progression compared to both IMM (HR 1.50, CI 95% 1.02-2.21, p=0.041) and AT (HR 1.86, CI 95% 1.26-2.74, p=0.002) – Figure 1. No differences were seen between IMM and AT in uni- and multivariate analysis. Shorter disease duration (HR 0.99, CI 95% 0.99-0.99, p=0.007), and prior use of AT (HR 1.67, CI 95% 1.13-2.47, p=0.010) were also associated with higher risk of disease progression – Table 1. Conclusion After an episode of steroid-responsive ASUC, shorter disease duration and prior use of advanced therapy were risk factors for disease progression. Approximately 1/3 of patients was treated with 5ASA alone. This strategy was also associated with a higher risk of poor outcomes and should be avoided.

Abstract Background Crohn’s disease (CD) complicated with intra-abdominal abscess often requires surgical intervention. Image guided percutaneous drainage (PD) can help to avoid surgical interventions, however there is limited evidence on the optimal management after PD. Our study aimed to analyze the long-term outcomes of CD complicated with intra-abdominal abscess after intervention. Methods In this multicenter, multinational retrospective trial penetrating CD patients with simplex intra-abdominal abscess were enrolled and followed. Baseline was defined as the day of the first detection of simplex abdominal abscess, while follow-up period of 12-24 months was set. Patients with urgent resection were excluded. Patients were grouped based on elective surgical need during follow-up after a successful PD, while a control group of patients after resection without PD is created. Primary outcome was the abscess recurrence, while stoma rate, post procedural complications rate (<30 days), and postoperative luminal recurrence were analyzed as secondary outcomes. Logistic regression and Cox-regression models were created, while descriptive statistics, Welch’s test, and Fisher’s exact test were used to compare groups, with p-values <0.05 considered significant. Results A total of 131 CD patients from 7 countries were recruited (Table 1., 58% were male, the median age at inclusion was 31.4 [IQR25-40] years) and 74/131 patients had PD due to simplex abdominal abscess during a median follow-up of 104 (74-104) weeks. Abscess recurrence rates did not differ between groups (p=0.155, Figure 1.); however baseline SES-CD score was coupled with increased risk of recurrence (HR=1,17, 95% CI 0.993-1.389). Need for re-drainage was more common amongst PD patients (OR=0.092, 95% CI=0.012-0.732), while new stoma was created more frequently in patients without prior PD (OR=2.50, 95% CI=1.034-6.034). Postoperative luminal recurrence was similar between groups based on PD. Surgical complications were coupled with increased odds in patients without prior PD (OR=8.609, 95% CI=1.825-40.616), septic complications, perforation and new fistula formation were reported the most, while PD associated complication did not occur. Conclusion However, abscess recurrence did not differ between groups, PD prior to surgery strongly correlated with less stoma creature. Furthermore, surgical treatment of intra-abdominal abscess alone may be coupled with post procedural complications.

Abstract Background Reproduction is an essential part of life. Our aim was to obtain a global perspective on IBD management by gastroenterologists (GIs) during preconception, pregnancy, lactation and neonatal period. Methods An anonymous survey (75 questions) was developed to investigate different aspects of clinical practice concerning the management of pregnancy and breastfeeding in patients with IBD. A national representative from each European country, USA, Latin America, Australia and New Zealand was selected to distribute the survey among their GI colleagues who treat patients with IBD (irrespectively of their experience). Results A total of 856 GIs from 36 countries participated in the survey. Among the participants, 63% had over a decade of experience as GIs, and 61% identified themselves as IBD specialist (IBDologists). The most relevant survey results and sub-analyses based on expertise are presented in tables 1 and 2. In the management of pregnant patients in remission, treatment discontinuation occurred either consistently or occasionally as follows: 20% thiopurines, 37% vedolizumab, 31% ustekinumab, and 96% small molecules. Notably, 13% did not always discontinue small molecules in patients contemplating pregnancy. Safety was the main reason for discontinuing IBD therapy during pregnancy. Contrary to the recommendations in clinical practice guidelines, many GIs avoid starting oral or rectal budesonide, anti-TNF, vedolizumab or ustekinumab during a disease flare. Further, a third of GIs would start thiopurines for a flare during pregnancy. Moreover, 13% will never perform a colonoscopy in a pregnant patient to guide decision making. Half of GIs implemented a dedicated outpatient follow-up program for pregnant patients in remission, with 87% enrolling all pregnant patients in this program. Concerning breastfeeding, 14% believed that all drugs can be used while breastfeeding. Regarding offspring’s vaccination, about 20% recommend against the administration of non-live vaccines and only 50% recommended avoiding live vaccines during the first 12 months for children exposed to anti-TNF in-utero. Among those GIs who recommended delaying vaccines in such cases, only 41% recommended testing the infant for detectable anti-TNF levels if live vaccines were required. Among the surveyed GIs, only a minority had a referral obstetrician, and only 35% referred patients with active or complicated IBD, while 45% had a referral paediatrician with expertise in IBD. Conclusion The management of IBD during pregnancy, lactation, and neonatal period is notably suboptimal, even among GIs specifically dedicated to IBD. It is crucial to address this current need and implement urgent educational measures in this area.

BACKGROUND:Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis. MATERIALS AND METHODS:This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed. RESULTS:Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn's disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis. CONCLUSIONS:Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes.

Background The gut microbiome of patients with inflammatory bowel diseases (IBD) is characterized by increased longitudinal variability. It remains unknown if this is caused by increased instability of the microbiome to external factors. We investigated the influence of osmotic diarrhea induced by bowel preparation as an external source of irritation on the gut microbiome in IBD patients and healthy comparators.

Background Faktor XIII ist ein Gerinnungsfaktor der für die Stabilisierung des Thrombus notwendig ist. Die globalen Gerinnungstests (Prothrombinzeit und partielle Thromboplastinzeit) bilden die Faktor XIII Aktivität nicht ab. Daten aus der Traumatologie und nach herzchirurgischen Eingriffen legen nahe, dass die Faktor XIII Substitution Blutungen positiv beeinflussen kann. Das Ziel der Studie war es, den Einfluss der Faktor XIII Aktivität und dessen Substitution auf den Verlauf von gastrointestinalen Blutungen zu untersuchen.

Hintergrund und Ziele Systemischen Kortikosteroide sind eine wichtige Substanzgruppe in der Behandlung der aktiven Colitis ulcerosa (CU). Das Ansprechen auf medikamentöse Therapien wie Biologika wird mutmaßlich durch das Darmmikrobiom beeinflusst. Wir untersuchten ob die Zusammensetzung und die Funktion des Mikrobioms bei Patienten mit aktiver CU auch in Zusammenhang mit dem Therapieansprechen auf Kortikosteroide steht.

Background and aims The rare cholestatic liver disease secondary sclerosing cholangitis in critically ill patients (SC-CIP) is induced by long-term intensive care treatment with invasive ventilation in patients without prior liver damage. The aim of this retrospective, single-center, investigator-initiated study was to describe the frequency and characteristics of gastrointestinal bleedings in SC-CIP.

Abstract Background Anti-TNF therapy is still the most frequently used first-line biologic treatment in inflammatory bowel disease (IBD). This study aimed to determine length of treatment persistence and to describe reasons for discontinuation of first-line anti-TNF therapy used in the standard care of IBD patients. Methods A single-center, real-world, retrospective study including IBD patients (Crohn’s disease (CD), ulcerative colitis (UC), IBD unclassified (IBD-U)), who received an anti-TNF therapy in the last 20 years at the study center, was conducted. Length of first-line anti-TNF therapy, differences in treatment duration between infliximab (IFX) and adalimumab (ADA) and between CD and UC, reasons for discontinuation, side effects leading to cessation, treatment following first-line anti-TNF therapy, rates of surgery and death, and factors being associated with treatment failure were assessed. Results 586 patients were identified as having received first-line anti-TNF therapy at the study center. 48 patients were excluded due to shortness of available data. 538 patients (CD: 367, UC: 147, IBD-U: 24) with a median follow-up of 8.1 years were included in the analysis. Median (IQR) treatment persistence was 21.0 (6.0, 57.0) months in the total cohort. Treatment withdrawal arose frequently (40%) within the first year of therapy and treatment persistence was longer in CD compared to UC (CD: 27.0 (8.0, 71.0) months, UC: 11.0 (3.0, 34) months, p<0.001). Treatment failure (51%) and side effects (24%) were the most commonly noticed reasons for withdrawal from therapy. 14% withdrew from therapy due to remission. The diagnosis of UC, female sex, the absence of prior intestinal resections, lower hemoglobin and albumin levels at anti-TNF initiation predicted treatment failure. Patients with CD continued ADA treatment longer than IFX treatment (ADA: (40.5 (14.2, 80.5) months, IFX: 18.0 (4.8, 65.0) months, p<0.001). Within the follow-up period, 17% of UC patients underwent colectomy and 34% of CD patients had at least one intestinal resection after start of first-line anti-TNF therapy. 2% of all patients died due to various reasons. Conclusion Treatment persistence of first-line anti-TNF therapy is limited in IBD patients due to a large proportion of treatment failures and side effects.

Einleitung Protonenpumpenhemmer (PPI), oder umgangssprachlich auch,Magenschutz“ genannt, sind eine unverzichtbare therapeutische Maßnahme in der Gastroenterologie. Trotz allgemein guter Verträglichkeit, treten vor allem bei längerer Einnahme Nebenwirkungen auf, die teilweise mit den einhergehenden Veränderungen des Darmmikrobioms verbunden sind. Der Frage, inwiefern Probiotika die Veränderungen im Mikrobiom und somit das Nebenwirkungsprofil von PPI reduzieren können, wurde in dieser Studie nachgegangen.

Einleitung Obwohl IgG4 nur einen geringen Anteil der Serum-Immunglobuline ausmacht und bei immunologischen Mechanismen eine untergeordnete Rolle spielt, steigt die Prävalenz der IgG4- assoziierten Erkrankungen. Nahezu alle Organe können betroffen sein, wobei ein Befall der Speiseröhre selten auftritt. Anhand eines rezenten Falls berichten wir über die Schwierigkeiten der Diagnosestellung sowie der Therapie.

Double-blind randomised studies investigating faecal microbiota transplantation (FMT) in chronic active ulcerative colitis (UC) have shown promising results so far. Factors influencing the efficacy of FMT in UC still remain unclear. FMT protocols for the treatment of UC patients vary in dose, frequency, route of application and donor stool preparation and might thus influence remission rates. The aim of this analysis was to find clinical predictors for non-response to FMT in UC. 54 patients suffering from chronic active ulcerative colitis were treated with repeated FMT (5 times every second week) using the same protocol with the exception of donor stool preparation. Thirty patients (mean age 37 y ± 9) were treated with frozen donor stool (mixed with sodium chloride and glycerol, stored at −80°C) and 24 patients (mean age 43 y ± 14) with freshly prepared donor stool (not older than 6 h). Remission and response were determined by total Mayo score (TMS) before FMT and at Day 90. Clinical response was defined as a decrease of ≥3 points in TMS from baseline, along with either a decrease of >1 point in the rectal bleeding subscore or the absolute rectal bleeding subscore of 0 or 1. Remission was defined as a TMS <2 and an endoscopic subscore of 0 or 1. Clinical data as well as blood and stool analysis were assessed at any time point and potential predictors for non-response were calculated using regression analysis. At baseline patients had a total Mayo score of 9.0 ± 2.0 and an endoscopic subscore of 2.5 ± 1.0. 65% of patients had failed previous biologic therapy and 70% previous immunosuppressive treatment. In total 59% of patients responded to FMT, 24% achieved remission while 41% showed no response. The mean total Mayo score dropped to 5.3 ± 3.2 at Day 90. Non-response to biologics (hazard ratio (HR): 0.23 (95% CI 0.06–0.85), p: 0.03), a total Mayo score before FMT ≥9 (HR: 0.26 (95% CI 0.07–0.95), p: 0.04) and a high endoscopic subscore before FMT (HR: 0.27 (0.10–0.69, p < 0.01) were associated with lower remission rates. There was no significant difference in decrease of TMS (p = 0.51) or in remission and response rates (p = 0.97), respectively in patients receiving fresh or frozen donor stool at Day 90. Failure to previous biologic treatment as well as a high total Mayo score and a high endoscopic subscore are associated with lower remission rates to FMT in chronic active ulcerative colitis.

The gut is hypothesised to play an important role in the development and progression of sepsis. It is however unknown whether the gut microbiome and the gut barrier function is already altered early in sepsis development and whether it is possible to modulate the microbiome in early sepsis. Therefore, a randomised, double blind, placebo-controlled pilot study to examine the alterations of the microbiome and the gut barrier in early sepsis and the influence of a concomitant probiotic intervention on dysbiosis at this early stage of the disease was conducted. Patients with early sepsis, defined as fulfilling the sepsis definition from the 2012 Surviving Sepsis Campaign guidelines but without signs of organ failure, received multispecies probiotic (Winclove 607 based on Omnibiotic® 10 AAD) for 28 days. Gut microbiome composition, function, gut barrier and bacterial translocation were studied. Patients with early sepsis had a significantly lower structural and functional alpha diversity, clustered differently and showed structural alterations on all taxonomic levels. Gut permeability was unaltered but endotoxin, endotoxin binding proteins and peptidoglycans were elevated in early sepsis patients compared to controls. Probiotic intervention successfully increased probiotic strains in stool and led to an improvement of functional diversity. Microbiome composition and function are altered in early sepsis. Probiotic intervention successfully modulates the microbiome and is therefore a promising tool for early intervention in sepsis.

Anhand doppelblinder, randomisierter Studien konnte kürzlich die Überlegenheit der fäkalen Mikrobiota-Transplantation (FMT) im Vergleich zu Placebo bei der Behandlung der aktiver Colitis ulcerosa (CU) gezeigt werden. Durch unterschiedliche Ergebnisse bei verschiedenen FMT-Protokollen sind jedoch hierfür noch viele Fragen offen. Die Verwendung von gefrorenem Spenderstuhl zur FMT bei Clostridium difficile-Infektionen hat sich als genauso wirksam erwiesen wie frischer Spenderstuhl. Das Ziel dieser Studie war es, die klinische Wirksamkeit von gefrorenem Stuhl für die FMT auch bei Colitis ulcerosa zu untersuchen.

Objectives: We report on a large prospective, multicentre clinical investigation on inter-and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. Methods: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. Results: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/ 448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. Conclusions: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalT02122,98 identifier: NCT02925091). C. Bilgilier, Clin Microbiol Infect 2018;24:267. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Die Kolonisationsresistenz bezeichnet die Fähigkeit einer mikrobiellen Gemeinschaft, die Ansiedlung von krankheitserregenden Bakterien zur verhindern. Mikrobielle Diversität und das Fehlen von Entzündung sind Indikatoren einer erhaltenen Kolonisationsresistenz. Das Ziel dieser Studie war es, Diversität und entzündliche Aktivität des Stuhlmikrobioms bei PatientInnen mit Leberzirrhose zu untersuchen.