关键词： 6-methylmercaptopurine   leukocytopenia   therapeutic drug monitoring   thiopurines  

摘要： Background and Aim: Thiopurines have a favorable benefit-risk ratio in the treatment of inflammatory bowel disease. A feared adverse event of thiopurine therapy is myelotoxicity, mostly occurring due to toxic concentrations of the pharmacologically active metabolites 6-thioguaninenucleotides. In oncology, myelosuppression has also been associated with elevated 6-methylmercaptopurine (6-MMP). In this case series, we provide a detailed overview of 6-MMP-induced myelotoxicity in inflammatory bowel disease patients. Methods: We retrospectively scrutinized pharmacological laboratory databases of five participating centers over a 5-year period. Patients with leukocytopenia at time of elevated 6-MMP levels (>5700pmol/8x10(8) red blood cells) were included for detailed chart review. Results: In this case series, we describe demographic, clinical, and pharmacological aspects of 24 cases of 6-MMP-induced myelotoxicity on weight-based thiopurine therapy with a median steady-state 6-MMP level of 14500pmol/8x10(8) red blood cells (range 6600-48000). All patients developed leukocytopenia (white blood cell count 2.70.9x10(9)/L) after a median period of 11weeks after initiation of thiopurine therapy (interquartile range 6-46weeks). Eighteen patients (75%) developed concurrent anemia (median hemoglobin concentration 6.9x10(9)/L), and four patients developed concurrent thrombocytopenia (median platelet count 104x10(9)/L). Leukocytopenia resolved in 20 patients (83%) within 4weeks upon altered thiopurine treatment regimen, and white blood cell count was increasing, but not yet normalized, in the remaining four patients. Conclusion: We observed that thiopurine-induced myelotoxicity also occurs because of (extremely) high 6-MMP concentrations in patients with a skewed thiopurine metabolism. Continued treatment with adapted thiopurine therapy was successful in almost all patients.

关键词： Corticosteroids   Crohn's disease   Guidelines   IBD   Immunosuppressors   Ulcerative colitis  

摘要： The two main forms of intestinal bowel disease, namely ulcerative colitis and Crohn's disease, are not curable but can be controlled by various medical therapies. The Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. The guidelines consider therapies that induce remission in patients with active disease as well as treatment regimens that maintain remission. These guidelines complement already existing guidelines from IG-IBD on the use of biological drugs in patients with inflammatory bowel diseases. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： Pediatrics   Adolescents   Inflammatory bowel disease   Crohn   Ulcerative colitis  

摘要： Inflammatory bowel disease (IBD), including Crohn disease, ulcerative colitis, and IBD-unspecified, is a chronic immune-mediated condition of the gastrointestinal tract in which the goal of treatment is to induce and maintain durable remission. In pediatrics, there is a wide spectrum of presenting symptoms, but esophagogastroduodenoscopy and colonoscopy are imperative to confirming the diagnosis. Treatment goals include achieving mucosal healing of the gastrointestinal tract, reaching growth potential, limiting medication toxicities, and optimizing quality of life for all patients.

关键词： Crohn's disease   inflammatory bowel disease   periodontal diseases   periodontitis  

摘要： Inflammatory bowel disease and periodontitis are both described as a disproportionate mucosal inflammatory response to a microbial environment in susceptible patients. Moreover, these two conditions share major environmental and lifestyle-related risk factors. Despite this intriguing pathogenic parallel, large-scale studies and basic research have only recently considered periodontal outcomes as relevant data. There are mounting and consistent arguments, from recent epidemiologic studies and animal models, that these two conditions might be related. This article is a comprehensive and critical up-to-date review of the current evidence and future prospects in understanding the biologic and epidemiologic relationships between periodontal status and inflammatory bowel disease.

关键词： hucMSCs   Inflammatory bowel disease   Macrophages   Mesenchymal stem cells 15-LOX-1  

摘要： Objective To investigate the role of human umbilical cord mesenchymal stem cells (hucMSCs) in the treatment of dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD). Results ICG-hucMSCs homed to colon tissues of IBD mice 12 h after injection. The injection of hucMSCs significantly relieved the IBD symptoms and inflammatory cell infiltration. The expression of IL-10 gene increased while those of 15-LOX-1, TNF-alpha, IL-6, IL-1 beta, and IP-10 genes decreased in colon tissues and spleens of hucMSCs-treated mice. The activation of STAT3 was inhibited in colon tissues and spleens of IBD mice that were treated with hucMSCs. In addition, the percentage of macrophages decreased in colon tissues and spleens of hucMSCs-treated IBD mice. Moreover, we provided evidence that in vitro co-culture with hucMSCs inhibited the expression of 15-LOX-1, IL-6 and p-STAT3 in mouse enterocoelia macrophages. Conclusions HucMSCs alleviate DSS-induced IBD through the modulation of 15-LOX-1 in macrophages.

关键词： TNF-alpha inhibitors   psoriasiform eruption   inflammatory bowel disease   arthritis   psoriasis   tumour necrosis factor  

摘要： Psoriasiform eruptions are a classical adverse skin reaction of tumour necrosis factor (TNF)-alpha inhibitors. The aim of this study was to identify the association between the severity or pattern of psoriasiform reactions and the underlying disease. A retrospective study was conducted between January 2012 and May 2015. Adult patients who developed psoriasiform eruptions whilst being treated with TNF alpha inhibitors were included. For each patient, 3 independent blinded dermatologists graded twice the severity of the lesions according to 6 clinical psoriasiform eruption types. Inter-and intra-individual kappa tests were performed to evaluate the robustness of the scoring system. The association between severity score levels or the pattern of reactions and the underlying disease was assessed. The severity scoring system showed good inter-and intra-observer reproducibility. Women patients treated with TNF alpha inhibitors for inflammatory bowel diseases showed a higher risk of developing severe reactions with scalp and skin-fold involvement.

关键词： Inflammatory bowel diseases   MiRNA   Intestinal epithelial barrier   Immune homeostasis   Autophagy   Diagnosis  

摘要： Inflammatory bowel diseases (IBD), mainly including Crohn's disease and ulcerative colitis, are characterized by chronic inflammation of the gastrointestinal tract. Despite improvements in detection, drug treatment and surgery, the pathogenesis of IBD has not been clarified. A number of miRNAs have been found to be involved in the initiation, development and progression of IBD, and they may have the potential to be used as biomarkers and therapeutic targets. Here, we have summarized the recent advances about the roles of miRNAs in IBD and analyzed the contribution of miRNAs to general diagnosis, differential diagnosis and activity judgment of IBD. Furthermore, we have also elaborated the promising role of miRNAs in IBD-related cancer prevention and prognosis prediction.

关键词： Biographical disruption   chronic illness   long-term illness   colitis   experience of illness   narratives   crohn's disease  

摘要： Biographical disruption and related concepts continue to be widely drawn upon in explaining how individuals experience chronic illness. Through in-depth examination of the narrative experiences of two young adults with inflammatory bowel disease (IBD), this article aims to contribute to the continuing theoretical elaboration of biographical disruption, and in turn offer new insights into how young adults experience this condition. The cases are analysed from an interaction-based, constructionist perspective, through which it is argued that the relapse-remission nature of IBD can give rise to a particular form of recurrent biographical disruption, constructed in narrative through a complex configuration of past, present and anticipated future experiences. The two young adults are found to give different meaning to this recurrent disruption in terms of its significance and consequences - whilst Samuel represents an ongoing cycle of profound disruption and biographical reinstatement, Edith normalises the cycle of disruption and its role in her ongoing biography. Therefore, moving beyond the notion of normal illness' observed in previous research literature, the concept of normal recurrent disruption' is proposed. Finally, it is argued that this recurrent biographical disruption may be experienced particularly severely in young adulthood owing to the unique pressures and expectations of this lifestage.