关键词： Crohn's disease   Ulcerative colitis   Enteral nutrition   Parenteral nutrition   Inflammatory bowel disease   Nutritional therapy  

摘要： The present guideline is the first of a new series of "practical guidelines" based on more detailed scientific guidelines produced by ESPEN during the last few years. The guidelines have been shortened and now include flow charts that connect the individual recommendations to logical care pathways and allow rapid navigation through the guideline. The purpose of the present practical guideline is to provide an easy-to-use tool to guide nutritional support and primary nutritional therapy in inflammatory bowel disease (IBD). The guideline is aimed at professionals working in clinical practice, either in hospitals or in outpatient medicine, and treating patients with IBD. In 40 recommendations, general aspects of care in patients with IBD, and specific aspects during active disease and in remission are addressed. All recommendations are equipped with evidence grades, consensus rates, short commentaries and links to cited literature. (C) 2019 The Author(s). Published by Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

摘要： Background Clinical application of therapeutic drug monitoring (TDM) to optimise anti-TNF therapies in patients with IBD depends upon target ranges. Aims To review methodology used to determine therapeutic ranges and critically compare and contrast its application to infliximab and adalimumab. Methods A systematic review was performed, and relevant literature was summarised and critically examined. Results Upper limits of the therapeutic range are determined by toxicity, a plateau response and cost. Lower limits are determined by optimal concentration on the target of action in vitro and/or in vivo, or by correlation of drug levels with clinical efficacy using area-under-receiver-operator-curve (AUROC) analysis. In 43 studies, there were huge variations in time at which infliximab and adalimumab levels were measured, the end-points used (clinical remission to mucosal healing), the clinical setting (active disease vs maintenance phase) and the reason for TDM (proactive vs reactive). In the maintenance phase for infliximab, lower trough limits 2.8-5.7 mu g/mL are reported depending upon end-points used, with consistent AUROC 0.68-0.77. Adalimumab TDM targets are even less consistent with a lower limit 5.9-11.8 mu g/mL (AUROC 0.66-0.83) in some studies, but no cut-off can be identified that is significantly associated with outcome in others, related to inherent pharmacokinetic and pharmacodynamic differences, and heterogeneity of study design. Conclusions Evidence for exposure-response relationship is stronger for infliximab than adalimumab. Due to heterogeneity in settings for drug level measurements, therapeutic ranges vary. These factors need to be taken into account when interpreting the evidence and extending this to therapeutic strategies for IBD patients.

关键词： inflammatory bowel disease   mucosal healing   pediatrics   vedolizumab  

摘要： Background: Vedolizumab (VDZ) is effective for treating both adult and pediatric onset inflammatory bowel disease (IBD). Clinical outcomes, however, have been reported to be superior in patients naive to anti-tumor necrosis factor (TNF). With the growing interest in endoscopic endpoints, we aimed to describe rates of mucosal healing in pediatric patients being treated with VDZ and examine the influence of anti-TNF on outcomes. Methods: We conducted a retrospective review of all IBD patients <= 21 years of age who initiated VDZ and underwent endoscopy. Primary outcome was mucosal healing (composite of endoscopic [SES-CD] and Mayo score UC) and histological remission [Nancy index-UC and Crohn disease (CD) histologic activity]. Descriptive statistics summarized the data. Comparisons were made for endpoints based on anti-TNF exposure using univariate testing. Results: Sixty-eight patients were included in the final analysis;35 with UC and 33 with CD. Thirty-two patients (22 UC and 10 CD) were anti-TNF-naive and 36 patients (13 UC and 23 CD) were anti-TNF-exposed. The median duration on VDZ before endoscopic assessment was 49 (IQR 32-73) weeks. A total of 38% (25/66) of patients met the primary outcome of mucosal healing and did not differ between anti-TNF-naive or anti-TNF-exposed. Endoscopic remission was achieved by 51% with significantly more anti-TNF naive patients reaching this endpoint (66% vs 40%,P = 0.03). Histologic remission was achieved by 42% of patients with a nonsignificant trend towards improved histologic remission rates in anti-TNF-naive patients (52% vs 33%,P = 0.13). Conclusions: VDZ is associated with mucosal healing in pediatric IBD. Anti-TNF exposure significantly impacted endoscopic remission, but not histologic remission in children on VDZ.

关键词： Crohn's disease   ulcerative colitis   arginase (ARG)   nitric oxide synthase (NOS)   arginine N-methyltransferase (PRMT)   dimethylarginine dimethylaminohydrolase (DDAH)   asymmetric dimethylarginine (ADMA)   symmetric dimethylarginine (SDMA)   L-citrulline   dimethylamine (DMA)  

摘要： L-arginine/nitric oxide pathway in Crohn's disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 mu M) compared to controls (157 and 0.494 mu M) and active-UC (164 and 0.52 mu M). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 mu M) and active-UC (65.9 and 73.9 mu M) compared to controls (42.7 and 50.4 mu M). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted.

摘要： Inflammatory bowel diseases is a group of inflammatory diseases. The pathogenesis of diseases is multifactorial, which may include a Western-type diet. Diseases occur with periods of recurrence and remission. Many factors can have a beneficial effect on reducing the frequency of recurrence and prolonging the remission period. Such ingredients include dietary fibre, mono- and polyunsaturated fatty acids, certain vitamins (D, C, and E), flavonoids, and minerals such as zinc and selenium. Properly selected nutrition might be an integral part of the treatment of patients with Crohn's disease or ulcerative colitis.

关键词： Biomarker   Dog   Inflammatory bowel disease   microRNAs  

摘要： Background Canine inflammatory bowel disease (IBD) is a group of chronic gastrointestinal (GI) disorders of still largely unknown etiology. Canine IBD diagnosis is time-consuming and costly as other diseases with similar signs should be initially excluded. In human IBD microRNA (miR) expression changes have been reported in GI mucosa and blood. Thus, there is a possibility that miRs may provide insight into disease pathogenesis, diagnosis and even treatment of canine IBD. The aim of this study was to determine the colonic mucosal and serum relative expression of a miRs panel in dogs with large intestinal IBD and healthy control dogs. Results Compared to healthy control dogs, dogs with large intestinal IBD showed significantly increased relative expression of miR-16, miR-21, miR-122 and miR-147 in the colonic mucosa and serum, while the relative expression of miR-185, miR-192 and miR-223 was significantly decreased. Relative expression of miR-146a was significantly increased only in the serum of dogs with large intestinal IBD. Furthermore, serum miR-192 and miR-223 relative expression correlated to disease activity and endoscopic score, respectively. Conclusion Our data suggest the existence of dysregulated miRs expression patterns in canine IBD and support the potential future use of serum miRs as useful noninvasive biomarkers.

关键词： Immunogenetics   Immunological deficiency syndromes   Inflammatory bowel disease   Medical genetics  

摘要： Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in similar to 70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls;P<4x10(-10)), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls;P<5x10(-10)). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

关键词： Anemia   iron metabolism   gastrointestinal diseasesreticulocyte hemoglobin   hypochromic cells  

摘要： Anemia due to lack of iron (absolute or functional deficiency) is a common complication of inflammatory bowel disease (IBD). We investigated the potential utility of reticulocyte hemoglobin content (Ret-He) and percentage of hypochromic red cells (Hypo-He) in the assessment of erythropoiesis. We recruited 123 anemic outpatients with IBD. Biochemical tests for iron deficiency were carried out. Full blood counts were performed on a XN 20 system (Sysmex Diagnostics). Differences among groups were studied using analysis of variance and post-hoc tests, considering p < .05 to be significant. Receiver operating characteristic analysis was used to assess the diagnostic performance of Ret-He and Hypo-He for detecting iron-deficient erythropoiesis. The gold standard used for diagnosing iron deficiency was soluble transferrin receptor (sTfR), with a cut-off of >52 nmol/L. Overall, 60 patients had iron deficiency anemia (IDA), 27 anemia of chronic disease (ACD) and 36 mixed ACD + IDA. Ret-He showed the best performance, with an area under curve (AUC) of 0.858 (95% CI 0.816-0.952), considering a cut-off of 30.0 pg, sensitivity of 76.8% and specificity of 99.8% (vs. AUC 0.727 [95% CI 0.624-0.814], considering a cut-off of 4.0%, sensitivity 72.0% and specificity 72.5% for Hypo-He). Ret-He and Hypo-He can be used to assess iron supply for erythropoiesis in patients with IBD, to evaluate long-term (Hypo-He) and short-term (Ret-He) periods.

关键词： pneumococcal vaccination   immunogenicity   inflammatory bowel disease   immunosuppressive therapy  

摘要： Background: Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear. Methods: We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4-8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration >= 1.3 mu g/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone >10 mg/day, thiopurines, methotrexate);(2) anti-tumor necrosis factor agents;(3) combination therapy;and (4) no treatment with immunosuppressive agents (control group). Results: One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1-3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13-.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29]). Conclusions: Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy.

关键词： invasive pneumococcal disease   pneumococcal conjugate vaccine   pneumococcal polysaccharide vaccine   inflammatory bowel disease   immunization   immunogenicity  

摘要： The article focuses on Inflammatory bowel disease (IBD) in the U.S. Topic include providers and patients with IBD would benefit from knowing if sequential pneumococcal vaccination is effective in preventing pneumococcal diseases; and understanding the immunogenicity of the sequential pneumococcal vaccination strategy among patients who are using immunosuppressant medications.