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Chronic intestinal failure (CIF) is a rare but feared complication of Crohn's disease. Depending on the remaining length of the small intestine, the affected intestinal segment, and the residual bowel function, CIF can result in a wide spectrum of symptoms, from single micronutrient malabsorption to complete intestinal failure. Management of CIF has improved significantly in recent years. Advances in home-based parenteral nutrition, in particular, have translated into increased survival and improved quality of life. Nevertheless, 60% of patients are permanently reliant on parenteral nutrition. Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy. The outcomes of patients with CIF could be greatly improved by more effective prevention, understanding, and treatment. In complex cases, the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation, nutritional support, and an improved quality of life. Here, we summarize current literature on CIF and short bowel syndrome, encompassing epidemiology, pathophysiology, and advances in surgical and medical management, and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease., Competing Interests: Conflict-of-interest statement: Aksan A reports congress expenses, consultancy fees and research funding from Vifor Pharma and Immundiagnostik AG. Farrag K reports speakers’ honoraria and congress expenses from Immundiagnostik AG, Janssen Cilag GmbH; consultancy honoraria from Vifor Pharma. Blumenstein I reports consultancy honoraria from AbbVie Deutschland, Amgen GmbH, Bristol Myers Squibb, Janssen Cilag GmbH, Fresenius Kabi Deutschland, Pharmacosmos GmbH, Pfizer GmbH, Shire Deutschland GmbH, Takeda Pharma GmbH; honoraria from AbbVie Deutschland, Biogen GmbH, DGVS, Dr. Falk Pharma GmbH, Endoakademie, Ferring Arzneimittel, Fraunhofer, Fresenius Kabi Deutschland, Kompetenznetz Darmerkrankungen, MSD Sharp Dome, Mylan GmbH, Pfizer GmbH, Janssen Cilag GmbH, Shire Deutschland GmbH, Takeda Pharma GmbH. Schroeder O reports congress expenses from Abbvie, Falk, Janssen, Takeda; speakers’ honoraria from Abbvie, Falk, Janssen, Takeda, Norgine, Pfizer. Dignass A reports consultancy honoraria from Abbott, Pharmacosmos, MSD, Ferring, Janssen, Pfizer, Otsuka, Roche/Genentech, Takeda, Falk; grants from Institut für Gemeinwohl & Stiftung Leben mit Krebs; Lecturing: Falk, Ferring, MSD, Abbott, Janssen, Pfizer, Otsuka, Vifor, Stiftung Leben mit Krebs, Kompetenznetz CED, Takeda, Pharmacosmos; Manuscript preparation: Falk. Education presentations: Abbott, Pharmacosmos, Falk, Ferring. Stein J reports personal fees from Abbvie, personal fees from Dr Schär, personal fees from Falk, personal fees from Ferring, personal fees from Fresenius Kabi, personal fees from Immundiagnostik AG, personal fees from Janssen, personal fees from Medice, personal fees from MSD, personal fees from Pfizer, personal fees from Pharmacosmos, personal fees from Shire, personal fees from Shield, personal fees from Takeda, personal fees from ThermoFisher, personal fees from Vifor Pharma, from NPS, outside the submitted work., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Autoimmune enteropathy (AIE) is a rare cause of intractable diarrhea in infancy. A variant with onset in adulthood has recently been described. The immune mechanisms underlying AIE are unclear and the experience in the management of adult AIE is very limited., Case Report: A 19-year-old male patient with massive refractory diarrhea and significant weight loss was diagnosed with AIE. He did not improve with corticosteroid and azathioprine treatment and was then treated successfully with infliximab. The response to treatment was rapid and complete. Because of a severe life-threatening hypersensitivity reaction during the 4th infliximab dose, infliximab had to be discontinued and therapy with tacrolimus was initiated. A complete clinical remission has since been maintained., Conclusion: Both infliximab and tacrolimus may provide a therapeutic alternative in patients with adult refractory AIE.

Background Vedolizumab (VDZ) is a humanised monoclonal IgG1 antibody targeting α4β7 integrin. Aim To investigate the real-world efficacy of vedolizumab for the treatment of Crohn's disease ( CD) and ulcerative colitis ( UC). Methods A consecutive cohort of 212 adult IBD patients with active disease ( HBI >7/partial Mayo >4) newly receiving VDZ was prospectively recruited from 7 academic and 17 community centres. The primary endpoint was clinical remission ( CRM) ( CD HBI ≤4, UC pMayo ≤1) in week 14. Secondary endpoints included steroid-free remission ( SFCRM), clinical response ( CRS) ( HBI/pMayo score drop ≥3), vedolizumab impact on CRP, calprotectin and haemoglobin. Results Data of 97 CD (71.1% female, HBI 11) and 115 UC (42.6% female, pMayo 6) patients were analysed. Only 5.2% CD and 24.3% UC were anti- TNFα naïve. Most had extensive mucosal involvement (Montreal L3 69.1%/E3 53.9%). At week 14, 23.7% vs. 23.5% of CD vs. UC patients achieved CRM, 19.6% vs. 19.1% SFCRM and 60.8% vs. 57.4% CRS, respectively (all based on NRI). Week 14 CRM in CD was significantly associated with no history of extraintestinal manifestations ( P = 0.019), no prior adalimumab use ( P = 0.011), no hospitalisation in the past 12 months ( P = 0.015) and low HBI score ( P = 0.02) and in UC with active or previous smoking ( P = 0.044/0.028) and no anti- TNFα ( P = 0.023) use. Low HBI ( P = 0.019) and no hospitalisation in the past 12 months ( P = 0.01) predict CD CRM. The three most common AE were joint pain, acne and nasopharyngitis. Conclusion Vedolizumab is effective in routine use. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host pathogen interactions is of key interest. Methods: In this two-center, retrospective German and Hungarian cohort study, patients with Crohn’s disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed. Results: In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383). Conclusion: IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE: We and others have reported the use of tacrolimus in refractory inflammatory bowel disease (IBD). Little is known about its long-term efficacy and safety. METHODS: In this retrospective, observational single center study the charts of 53 adult patients with steroid-dependent (n = 18) or steroid-refractory (n = 35) IBD, Crohn's disease (CD) (n = 11), ulcerative colitis (UC) (n = 40), or pouchitis (PC) (n = 2) were reviewed. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in all and initially intravenously in 2 patients (0.01 mg/kg body weight per day), aiming for serum trough levels of 4–8 ng/mL. Forty-one of 53 (77.1%) patients were receiving concomitant azathioprine. The mean treatment duration was 25.2 ± 4.6 SD months (0.43–164 months). Patients were followed for a mean of 39 ± 4.1 SD months (5–164 months). Response was evaluated using a modified clinical activity index (M-CAI). RESULTS: Thirty-one UC (78%), 10 CD (90.1%), and both PC (100%) patients experienced an immediate clinical response or went into remission at 30 days. A statistically significant drop on the M-CAI was documented for UC and CD patients. Nine UC patients (22.5%) underwent colectomy between 1.6 and 41.3 months following initiation. Mean colectomy-free survival was 104.8 ± 15.5 (95% CI 74.4–135.2) months (limited to 164.4 months). Cumulative colectomy-free survival was estimated 56.5% at 43.8 months. Steroids were reduced or discontinued in 40 of 45 UC and CD patients (90%) taking steroids. Side effects included a temporary rise of creatinine (n = 4, 7.6%), tremor or paresthesias (n = 5, 9.4%), hyperkalemia (n = 1, 1.9%), hypertension (n = 1, 1.9%), and opportunistic infections (n = 2, 3.8%). CONCLUSION: Long-term tacrolimus therapy appears safe and effective in refractory IBD. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Genetic variants within DLG5 were recently reported to be associated with inflammatory bowel disease (IBD). The aim of our study was to test for allelic and haplotype associations of six DLG5 variants in 668 IBD patients from two European populations. Furthermore, we evaluated whether DLG5 variants alter gastrointestinal permeability in Crohn's disease (CD). METHODS: Six DLG5 variants (p.R30Q, p.P1371Q, p.G1066G, rs2289308, DLG_e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205). Subtyping analysis was performed in respect of CARD15 mutations and clinical characteristics. We also tested for differences within DLG5 genotypes in German CD patients with respect to gastroduodenal and intestinal permeability measured by triple-sugar-test. RESULTS: Allele as well as genotype frequencies of DLG5 variants did not differ between IBD patients and controls in either study population. Indeed, the p.R30Q polymorphism was found more frequently in controls than in patients. The distribution of DLG5 genotypes in German and Hungarian CD patients with CARD15 mutations was not different from patients without mutated CARD15. We did also not observe any association between DLG5 variants and clinical parameters. Importantly, DLG5 variants were not associated with gastroduodenal or intestinal permeability. CONCLUSIONS: We could not replicate that DLG5 is a relevant disease susceptibility gene for IBD in German or Hungarian subjects. In addition, we have no evidence that DLG5 variants are involved in altered gastrointestinal permeability in CD. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Anemia is a frequent complication in patients with inflammatory bowel disease (IBD). The optimal route for iron supplementation to replenish iron stores has not been determined so far. We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia (IDA) in patients with IBD. METHODS: A randomized, prospective, open-label, multicenter study was performed in 46 patients with anemia and transferrin saturation ≤20% and/or serum ferritin concentrations ≤20 μg/L. The intravenous group received a single dose of iron sucrose of 7 mg iron/kg body weight, followed by five 200 mg infusions for the following 5 wks. The oral group received iron sulfate 100–200 mg per day for 6 wks. RESULTS: While a comparable increase in hemoglobin was observed for both administration routes (median increase 0.25 g/L in the intravenous group vs 0.21 g/L in the oral group), only iron sucrose led to a rise in serum ferritin concentrations. Intractable gastrointestinal adverse events caused permanent study drug discontinuation in five patients (20.8%) receiving iron sulfate, whereas only one patient (4.5%) had to be withdrawn because of side effects due to iron sucrose. CONCLUSIONS: Although being equal in short-term efficacy and overall tolerability our results suggest a better gastrointestinal tolerability for iron sucrose. Larger trials are mandatory to prove a possible advantage of iron sucrose in short- and long-term efficacy as well as in tolerability over iron sulfate in the management of IDA in IBD. [ABSTRACT FROM AUTHOR]