المؤلفون: Fierens, L, Carney, N, Novacek, G, van der Woude, CJ, Siegmund, B, Casellas, F, Borruel, N, Huberts, AS, Sonnenberg, E, Gerold, N, Primas, C, Hedin, CRH, Stamm, T, Julsgaard, M, Fiorino, G, Radice, S, Zini, MLL, Gross, E, Sander, C, Arijs, I, Vakouftsi, VR, Koltai, T, Charlafti, I, Ferrante, M

المصدر: Journal of Crohn's & colitis.

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:154670056Test

المؤلفون: Reinisch, W., Hébuterne, Xavier, Buisson, Anthony, Schreiber, S., Desreumaux, Pierre, Primas, C., Paillarse, Jean-Michel, Chevalier, G., Bonny, C.

المساهمون: Université de Lille, Inserm, CHU Lille, Centre Hospitalier Universitaire de Nice CHU Nice, Université Côte d'Azur UniCA, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte M2iSH, Service d'Hépatologie Gastro-entérologie CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes CHU Clermont-Ferrand 3IHP, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

مصطلحات موضوعية: adherent-invasive E, coli, basic science, clinical trials, Crohn's disease, experimental models and pathophysiology, FimH blocker, FimH receptor, microbiology, microbiome, sibofimloc

الوصف: Background and Aim Expression of FimH adhesin by invasive Escherichia coli in the gastrointestinal tract of patients with Crohn's disease (CD) facilitates binding to epithelial glycoproteins and release of pro-inflammatory cytokines. Sibofimloc is a first-in-class FimH blocker that showed little systemic absorption in healthy volunteers. The current study evaluated systemic absorption, safety, and effect on inflammatory biomarkers of sibofimloc in patients with CD. Methods This was an open-label, multicenter phase 1b study in adults with active CD. In part 1, two patients received a single oral dose of 3000-mg sibofimloc followed by 1500 mg b.i.d. for 13 days. In part 2, six patients received 1500-mg sibofimloc b.i.d. for 13 days. Blood was drawn for pharmacokinetic and biomarker analysis, and stool was collected for biomarker and microbiome analysis. Results Eight patients with active ileal or ileocolonic CD were enrolled into the study. Systemic sibofimloc exposure was low. Sibofimloc was well tolerated with only grade 1–2 events observed. Several pro-inflammatory biomarkers, including IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and calprotectin, were decreased in stool by end of study. Conclusions This first study of the novel FimH blocker, sibofimloc, in patients with active CD demonstrated minimal systemic exposure with good tolerance, while decreasing several inflammatory biomarkers.

العلاقة: Journal of Gastroenterology and Hepatology; J Gastroenterol Hepatol; http://hdl.handle.net/20.500.12210/100874Test

الإتاحة: https://doi.org/20.500.12210/100874Test
https://hdl.handle.net/20.500.12210/100874Test

المؤلفون: Riva, A, Primas, C, Wiekowski, M, Badalamenti, S, Reinisch, W, Busslinger, G

المصدر: Journal of Crohn's and Colitis ; volume 18, issue Supplement_1, page i302-i302 ; ISSN 1873-9946 1876-4479

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: Background Patients suffering from ulcerative colitis (UC) have reduced life qualities and an increased risk of developing cancer. Current treatment options are limited and have a ceiling effect with remission rates of ~35%. A possible reason is the multi-factorial aetiology, which are associated with an overactivation of the immune system and a dysbiosis of the gut microbiome. An important step towards a better understanding is the characterization of epithelial lesions. Their severity is classified by the Mayo score system based on their macroscopic appearance. While previous studies analysed cellular changes within the colon in UC patients, a detailed characterization of different UC-associated lesions are still missing, which is the aim of our study in collaboration with Sanofi Pharmaceuticals. Methods We recruit patients with active disease at our endoscopy unit and collect different biopsies from multiple regions within these patients to compare the reproducibility of single cell RNA sequencing (scRNAseq) results of similar appearing lesions within and between patients. For the sample preparation, we include a cellular enrichment step for immune, epithelial and stromal cells before performing 10x scRNAseq to obtain equal numbers for each cell fraction from every sampled area. Results Our cellular isolation strategy allows successful recovery of fibroblast, epithelial and immune cell fractions from each lesion. All expected epithelial cell types as previously described are detected in our dataset as well. Moreover, our experimental setup to obtain comparable numbers of fibroblasts, epithelial and immune cells enables us now to investigate cell-cell communication differences within different Mayo score lesions. For example, CXCL signal increased with the severity of macroscopic lesions and involves multiple cell types. Conclusion Our preliminary results promise exciting insights into cell-cell communications at an unprecedented depth, which identifies aberrant signalling pathway that may contribute ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjad212.0170Test
https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i302/56348309/jjad212.0170.pdfTest

المؤلفون: Maurer, J, Pokryszka, J, Wisniowski, K, Schreiner, P, Primas, C, Kazemi-Shirazi, L, Dabsch, S, Schweiger, K C, Dejaco, C, Neumann, L, Reinisch, W, Novacek, G

المصدر: Journal of Crohn's and Colitis ; volume 18, issue Supplement_1, page i2105-i2106 ; ISSN 1873-9946 1876-4479

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: Background Smoking is the best-known environmental risk factor for poor outcome of Crohn’s disease (CD). Since smoking cessation improves the prognosis of CD, patients are encouraged to quit smoking. This study aimed to assess the smoking behaviour among CD patients and explore changes after diagnosis of CD. Methods This is a retrospective single tertiary center cohort study of 1267 patients with CD with a median follow-up of 16.8 years (IQR - 18.3) whose characteristics are recorded via a validated data software (IBDIS, Inflammatory Bowel Disease Information System). Smoking behaviour was categorized into never smokers, current smokers, and ex-smokers (those who quit smoking at any point). The primary objective was smoking cessation during follow-up. The probability of smoking was calculated for those CD patients who smoked at the time of diagnosis of CD by means of Kaplan-Meier estimates. Statistical analyses were conducted using R software, employing log-rank tests for estimating differences with a significance level of alpha = 0.05. Results In total 1,128 CD patients with a complete data set were analysed (Table 1). 161 (14.2%) patients started and stopped smoking prior to diagnosis of CD. At the time of diagnosis, 541 patients (47.9%) were smokers, and 239 (44.2%) of them quit smoking during follow up. The median time from CD diagnosis to cessation for the 239 patients who were smokers at the time of diagnosis and subsequently quit was 8.6 years (IQR - 10.6 years). 80 patients (7%) started smoking after diagnosis, with 50 of these patients quitting thereafter. The probability of smoking in those CD patients who smoked at the time of diagnosis decreased over time to 0.96 (95% CI 0.95-0.98) at 1yr, 0.85 (95% CI 0.83-0.89) at 5 yrs, 0.71 (95% CI 0.67-0.76) at 10 yrs, and 0.52 (95% CI 0.47-0.57) at 20 yrs after diagnosis for the entire cohort with no significant difference between genders (p=0.76) (Figure 1a). Patients who were diagnosed 2010 and later (n=182) were more likely to stop smoking than ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjad212.1310Test
https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i2105/56351002/jjad212.1310.pdfTest

المؤلفون: Primas, C, Waldhör, T, Kozbial, K, Dawoud, C, Riss, S, Reinisch, W, Niapri, M, Kutschera, M, Kazemi-Shirazi, L, Reinisch, S, Dabsch, S, Pedarnig, N, Angermann, H, Novacek, G

المصدر: Journal of Crohn's and Colitis ; volume 16, issue Supplement_1, page i304-i305 ; ISSN 1873-9946 1876-4479

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: Background Crohn’s disease (CD) is associated with a high risk of intestinal complications such as stricture, fistula and abscess formation, as well as perianal disease, frequently requiring surgical procedures and intestinal stoma formation. The aim of the present study was to evaluate the prevalence as well as predictors for surgical stoma formation in CD patients. Methods This is a retrospective single tertiary center cohort study of 1157 patients with CD with a median follow-up of 15 years whose characteristics (Table 1) are recorded via a validated data software (IBDIS, Inflammatory Bowel Disease Information System). The primary objective was the assessment of risk factors for intestinal stoma formation during follow-up. The probability of stoma-free survival was calculated for the entire patient population and for subgroups defined by their time of diagnosis (-1999, 2000–2009, 2010-), location and behavior of disease, presence of perianal disease (ever), gender, and smoking habits by means of Kaplan-Meier estimates. Results 135 (11.7%) patients with intestinal stomas [78 (57.8%) ileostomies and 57 (42.2%) colostomies] were registered. The probability of stoma-free survival after 5, 10, and 20 years was 95.9%, 91.8%, and 85.5%, respectively. Stoma formation surgery was elective in 51 (37.8%) cases, emergency in 49 (36.3%) and unknown in the others (25.9%). The most common indications were perianal disease [(n=34; 25.2%), internal fistula/abscess [n=25 (18.5%)], postoperative complications [n=21 (15.6%)], stricture [n=11 (8.1%)], and refractory to treatment [n=10 (7.4%)]. The probability of stoma-free survival was significantly lower in patients with perianal disease (p<0.0001) (Figure 1), colon involvement (p<0.0001) (Figure 2), and penetrating disease behavior (p<0.0001) (Figure 3). Time of diagnosis, gender, and smoking habit were not significantly associated with stoma-free survival. In 73 (54.1%) patients a restorative surgery for intestinal continuity was performed. ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjab232.391Test
https://academic.oup.com/ecco-jcc/article-pdf/16/Supplement_1/i304/42250835/jjab232.391.pdfTest

المؤلفون: Kutschera, M, Primas, C, Reinisch, S, Novacek, G, Kim, S H, Lee, S H, Lee, J H, Reinisch, W, Mould, D R

المصدر: Journal of Crohn's and Colitis ; volume 15, issue Supplement_1, page S108-S109 ; ISSN 1873-9946 1876-4479

الوصف: Background Treating patients with biologics like infliximab (IFX), may cause the formation of antidrug antibodies (ADA). ADA are associated with faster drug clearance, reduced treatment efficacy and increased risk of infusion-related side effects. The aim of this study is to identify possible predictors for ADA-formation. Methods A time to first detection of ADA model was developed by using data from a Phase 3 clinical trial of biosimilar CT-P13 and originator infliximab comparing efficacy and safety in moderately to severely active Crohn’s disease (CD). We analyzed data from 220 patients initiating IFX. Seven subjects with ADA present at baseline were discarded. The following baseline covariates were evaluated in this analysis: age, weight, first estimated drug clearance, disease duration, dose, sex and concomitant immune-modulators. Continuous covariates were divided into lower quartile, inter-quartile range, and upper quartile bins. Kaplan-Meier survivor estimates were plotted by bin. The data was then modeled parametrically with NONMEM by constructing a full model which was further refined using the Wald’s Approximation Method algorithm. Hazard ratios and probability of ADA at time points of interest were calculated for significant covariates. Results Initial IFX clearance, concomitant immunomodulators and IFX dose were identified as being statistically significant predictors of the time to first ADA. The model suggested that the hazard of ADA increases by 61% for every increase on 0.1 L/day in clearance, it decreases by 41% with concomitant administration of immunomodulators and decreases by 29% for every increase in dose of 100 mg. Thus, for a patient with initial IFX clearance of 0.2 L/day, no immunomodulators and a dose of 328 mg, the average time to first ADA is 374 days (range 221–451). If clearance is 0.4 L/day under the same conditions, then ADA onset is 144.5 days (range 90–216). Increasing the starting dose to 428 mg would improve the time to onset to 203 days (range 110–337). Again, under ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjab073.113Test
http://academic.oup.com/ecco-jcc/article-pdf/15/Supplement_1/S108/38319142/jjab073.113.pdfTest

المؤلفون: Zoller, H, Wolf, M, Blumenstein, I, Primas, C, Lindgren, S, Thomsen, L L, Reinisch, W, Iqbal, T

المصدر: Journal of Crohn's and Colitis ; volume 15, issue Supplement_1, page S121-S121 ; ISSN 1873-9946 1876-4479

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: Background Intravenous iron can correct iron deficiency anaemia (IDA) in inflammatory bowel disease (IBD). Certain formulations are associated with hypophosphatemia, but this has not previously been investigated in a randomised clinical trial in IBD. The aim of this randomised, double-blind trial was to compare the risk of hypophosphatemia with ferric derisomaltose/iron isomaltoside 1000 (FDI) vs ferric carboxymaltose (FCM) in patients with IDA due to IBD. Methods Adults with IBD and IDA (haemoglobin [Hb] <13g/dL; s-ferritin ≤100ng/mL) who were unsuitable for oral iron treatment were recruited at outpatient clinics in 5 European countries. Patients were randomised 1:1 to FDI or FCM (1000mg at baseline and 500 or 1000mg at Week 5 based on weight and iron need at baseline). The primary endpoint was the incidence of hypophosphatemia (s-phosphate <2.0mg/dL) from baseline to Week 5. Additional endpoints included biomarkers of bone and mineral metabolism, Hb concentrations, fatigue score, and adverse events (AEs). Results Of 97 patients enrolled (mean age 42.1 years; 52.6% female; 39.2% Crohn’s disease; 60.8% ulcerative colitis), 48 received FDI and 49 FCM. The incidence of hypophosphatemia was significantly lower for FDI than FCM (8.3% vs. 51.0%; p<0.0001). After the first dose, biomarker responses (least squares mean change from baseline) were significantly less pronounced after FDI than FCM: s-phosphate decreased less with FDI than FCM, with a nadir at Week 1 (FDI, -0.49mg/dL; FCM, -1.33mg/dL; p<0.0001); urinary fractional excretion of phosphate increased less at Week 1 (FDI, 2.58%; FCM, 9.22%; p=0.0021); intact fibroblast growth factor 23 increased markedly over the first day only with FCM (FDI, -8.54pg/mL; FCM, 149.31pg/mL; p<0.0001); 1,25-dihydroxyvitamin D decreased less with FDI than FCM, with a nadir at Week 1 (FDI, -16.39pg/mL; FCM, -30.83pg/mL; p<0.0001); parathyroid hormone increased only in the FCM group, with a peak at Week 2 (FDI, -2.22pg/mL; FCM, ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjab073.128Test
http://academic.oup.com/ecco-jcc/article-pdf/15/Supplement_1/S121/38317186/jjab073.128.pdfTest

المؤلفون: Hartl, C, Novacek, G, Reinisch, S, Saciri, A, Reinisch, W, Primas, C, Maier, H

المصدر: Journal of Crohn's and Colitis ; volume 15, issue Supplement_1, page S497-S497 ; ISSN 1873-9946 1876-4479

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: Background Dermatological affections are common in patients with inflammatory bowel disease (IBD). We aimed to assess if skin examination prior to initiation of biologics in IBD patients would detect relevant skin diseases, such as skin malignancies, which could influence treatment as well as management. Methods In this ongoing cohort study we included IBD patients of the Dept. of Gastroenterology and Hepatology of the Medical University of Vienna with indication for biological treatment. Consultants of Dermatology performed a complete dermatological screening prior to initiation of therapy. We recorded all pathological findings, although the focus of this study is on certain dermatoses of high impact (melanoma, non-melanoma skin cancer, hidradenitis suppurativa, pyoderma gangrenosum, erythema nodosum and warts). Furthermore, we used a detailed questionnaire comprised of family history, medication and personal history of IBD. In cases of diagnostic uncertainties we confirmed our differential diagnosis by histopathological and further diagnostic investigations. The descriptive results are given as absolute numbers and percentages. Results 431 patients were included, 322 patients (74.7%) with Crohn’s disease, 103 (23.9%) with ulcerative colitis and 6 (1.4%) with inflammatory bowel disease unclassified. Melanoma was diagnosed in 3 out of 431 patients (0.7%). Non-melanoma skin cancer was detected in 22 patients (5.2%). Pyoderma gangrenosum, hidradenitis suppurativa and erythema nodosum were present in 5 (1.2%), 12 (2.8%), and 3 (0.7%) patients, respectively. We found viral warts in 73 patients (16.9%). 88 patients (20.4%) received further diagnostic investigations and 302 patients (70.1%) dermatological treatment for the detected skin diseases. Conclusion Dermatological screening prior to initiation of treatment with biologics can identify IBD patients with skin malignancies and other high-impact skin diseases. This may influence further IBD treatment as well as management decisions. We conclude that prior ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjab076.641Test
http://academic.oup.com/ecco-jcc/article-pdf/15/Supplement_1/S497/38320484/jjab076.641.pdfTest

المؤلفون: Bokemeyer, B, Kaiser, C, Primas, C, Novacek, G, Biedermann, L, Seibold, F, Tappe, U, Bettenworth, D, Graw, J, Hartmann, P, Plachta-Danielzik, S, Schultz, C

المصدر: Journal of Crohn's and Colitis ; volume 15, issue Supplement_1, page S310-S313 ; ISSN 1873-9946 1876-4479

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: Background IBD-care may be challenging and benefits from a multidisciplinary, cross-sectoral treatment approach and active patient involvement. However, occasionally there is a lack of patients′ empowerment and additionally, a necessity for the optimisation of physicians′ treatment is apparent. Furthermore, there is a deficiency in evidence regarding the effectiveness of structured care approaches (“managed care”) on patient-related outcomes (PROs). Therefore, our study aims to evaluate the potential of managed care programmes for IBD patients. Methods EASEIBD is a cross-border study conducted by IBD-DACH, an IBD working group in Germany (D), Austria (A) and Switzerland (Ch). Within the DACH-region, a cross-sectional survey of patients and physicians from IBD hospital-outpatient departments and gastroenterology practices was carried out. The questionnaire evaluated the effect of instruments and contextual factors of IBD-care with regard to quality of life (QoL). Additionally, the effects of “managed care” instruments were examined while considering centre-related structural characteristics. The analysis was performed using a multivariate multilevel regression model, controlled by various physician and patient characteristics. Results 2536 IBD-patients from 66 centres (643 IBD-patients/quarter; 31% hospital out-patient departments) were consecutively enrolled in EASEIBD (centres/IBD-pat.: D-52/1735; A-10/647; Ch-4/154). Overall, patient satisfaction (77-84%) (Fig. 1) as well as perceived quality of care (82-87%) (Fig. 2) was high and comparable in the descriptive analysis between German, Austrian and Swiss IBD-patients. Statistically significant differences were only found in single characteristics, e.g. in quality of life (EQ5D-VAS) (p=0.004) (Fig. 3). However, these do not appear clinically relevant with regard to the absolute values. In the entire DACH-region there were detectable effects of elements representing structural quality and assessments of the centres, with regard to the perceived quality ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjab076.404Test
http://academic.oup.com/ecco-jcc/article-pdf/15/Supplement_1/S310/38319124/jjab076.404.pdfTest

المؤلفون: Primas, C., Waldhör, T., Wisniowski, K., Dawoud, C., Riss, S., Reinisch, W., Niapier, M., Kutschera, M., Kazemi-Shirazi, L., Reinisch, S., Dabsch, S., Pedarnig, N., Angermann, H., Novacek, G.

المصدر: Zeitschrift für Gastroenterologie ; 56. Jahrestagung & 33. Fortbildungskurs der Österreichischen Gesellschaft für Gastroenterologie & Hepatologie – ÖGGH & ˶Pre˵ Symposium der young ÖGGH ; ISSN 1439-7803

الإتاحة: https://doi.org/10.1055/s-0043-1769021Test