关键词： inflammation   disease activity   treatment  

摘要： In these cases, anti-TNF therapy has failed to confine gut inflammation. [...]the use of monoclonal antibodies for treatment of extra-articular manifestations may be redundant, unless other EAMs such as psoriasis or uveitis occurred in the disease course. [...]in case of predictable flare of SpA in patients displaying both diseases, the withdrawal of anti-TNF should be avoided. [...]for now, rheumatologists and gastroenterologists might have to rely on medical need programmes to treat their patients accordingly. [...]the use of vedolizumab monotherapy after loss of efficacy of anti-TNF at the level of the gut in patients displaying both SpA and IBD should be taken with caution as flares may be expected short term.

关键词： health administrative data   emergency department use   outpatient use   hospitalization   laboratory use  

摘要： Objectives To evaluate the impact of the transfer from pediatric to adult care on health services use for adolescents with inflammatory bowel disease (IBD). Study design A population-based retrospective cohort study identified all children diagnosed with IBD from 1994 to 2008 and treated by pediatric gastroenterologists in Ontario, Canada, using health administrative data. Self-controlled case series analyses compared health service use in the 2 years before and 2 years after transfer with adult gastroenterologists, with a 6-month washout period at transfer. Outcomes evaluated included IBD-specific and IBD-related hospitalizations, emergency department use, outpatient visits, and laboratory use. The relative incidence (RI) in the post-transfer period was compared with pretransfer periods using Poisson regression analysis controlling for transfer starting age. Analyses were stratified by IBD type: Crohn's disease (CD) and ulcerative colitis (UC). Results There were 536 patients included in the study (388 CD, 148 UC). Emergency department use rate was higher after transfer for both CD (RI, 2.12;95% CI, 1.53-2.93) and UC (RI, 2.34;95% CI, 1.09-5.03), as were outpatient visits (CD: RI, 1.56;95% CI, 1.42-1.72;UC: RI, 1.48;95% CI, 1.24-1.76), and laboratory investigations (CD: RI, 1.43;95% CI, 1.26-1.63;UC: 1.38;95% CI, 1.13-1.68). There was no change in the hospitalization rate (CD: RI, 0.70;95% CI, 0.42-1.18;UC: RI, 2.41;95% CI, 0.62-9.40). Conclusions Health services use in Canada increases after transfer from pediatric to adult care for outpatient visits, emergency department use, and laboratory tests, but not hospitalizations. This study has implications for the planning and budgeting of care for adolescents transitioning to adult care.

关键词： Biological therapy   Clinical predictors   Crohn's disease   Elderly   Immunomodulator   Ulcerative colitis  

摘要： Background: Real-life data on vedolizumab effectiveness in inflammatory bowel disease (IBD) are still emerging. Data on the comparative safety of the gut selective profile are of particular interest. Aims: To assess clinical outcome and safety in IBD patients treated with vedolizumab. Methods: We retrospectively collected data of patients treated with vedolizumab at eight UK hospitals (August 2014-January 2018). Clinical response and remission at 14 and 52 weeks evaluated through Physician Global Assessment (PGA) and adverse events were recorded. Possible predictors of clinical response were examined. Results: Two hundred and three IBD patients (mean treatment 16 + 8 months) were included. Of these, 135 patients (mean age 40.6 + 16.0 years;F:M 1.9:1) had CD and 68 (mean age 44.5 + 18.1 years;F:M 1:1.2) had UC. According to PGA, 106/135 (78.5%) CD and 62/68 (91.2%) UC patients (p = 0.02) had a clinical response/remission at 14 weeks, whereas 76/119 (63.9%) CD and 52/63 (82.5%) UC patients (p < 0.01) showed a sustained response or remission at 52 weeks, with a high adherence rate (97%). No predictors of clinical response were found. The cumulative incidence of infectious diseases was 11.9 per 100 person years. Conclusion: Vedolizumab is an effective therapy for inducing and maintaining remission of IBD, with better results for UC, and with a good safety profile. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica ltaliana S.r.l.

关键词： BCBSIL   Blue Cross and Blue Shield of Illinois   CD   Crohn’s disease   CDST   clinical decision support tool   EMR   electronic medical record   IBD   inflammatory bowel disease   IGG   Illinois Gastroenterology Group   IMH   Intensive Medical Home   NCM   nurse care manager   SMH   specialty medical home   UC   ulcerative colitis  

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Surgery   Pediatric   Operative complications  

摘要： Background: Pediatric inflammatory bowel disease (IBD) may be associated with a higher burden of surgery and postoperative complications. This study aimed to measure the burden in pediatric IBD over a 20-year period in a large tertiary referral center. Methods: A retrospective review was conducted of children diagnosed with IBD between 1996 and 2015, with a focus upon operative intervention (excluding endoscopy) and postoperative outcomes. Results: Of 786 IBD patients, 121/581 (20.8%) with Crohn's disease (CD) and 22/205 (10.7%) with ulcerative colitis (UC) underwent surgery during the study period. When comparing 10-year epochs for CD, median time from diagnosis to intervention decreased from 34 months to 3 months (P < 0.0001). Postoperative complications occurred in 16/121 (13%) CD patients (bowel obstruction: 10, anastomotic stricture: 4, stomal issues: 4, anastomotic leak: 1). Within the UC cohort, the median time from diagnosis to intervention decreased from 62 months to 6 months (P = 0.0019). Postoperative complications occurred in 9/22 (41%) UC patients (bowel obstruction: 7, stomal issues: 3, anastomotic stricture: 1). Compared with CD, complications were more frequent in UC patients (P = 0.004). Conclusion: Surgery and postoperative complications are common in pediatric IBD. The timing of intervention has trended towards earlier operations in both CD and UC. Level of evidence: Treatment study-level III (retrospective comparative study). Crown Copyright (C) 2018 Published by Elsevier Inc. All rights reserved.

关键词： Inflammatory bowel disease   Epstein-Barr virus   Refractory   Ulcerative colitis   Crohn Disease  

摘要： A potential role for viral infections has been implicated in inflammatory bowel disease (IBD) unresponsive to medical treatment. It is well known that Epstein-Barr virus (EBV) infection can elicit a brisk mononuclear response in the gastrointestinal tract. The aim of this study was to further evaluate the role of EBV in patients with refractory IBD and compare them with nonrefractory IBD cases. Surgically resected colonic specimens from 67 patients with refractory IBD (62 with ulcerative colitis, 3 patients with Crohn disease, and 2 patients with indeterminate colitis) were retrieved. Twelve colectomy specimens from patients with ulcerative colitis who had undergone resections for dysplasia or endometriosis were included as controls. Highly sensitive EBV-encoded small RNA1 (EBER-1) in situ hybridization was performed on a representative block from each specimen. EBER-1 reactivity was graded as absent, focal, or diffuse. EBV was detected in 60% (40/67) of patients with refractory 1BD compared with 25% (3/12) of the control group (P < .05). Focal EBER-1 positivity was present in 45% of cases of refractory 1BD compared with 25% of controls. Diffuse EBER-1 reactivity was seen in 15% of cases of refractory IBD (10/67);none of the samples from the control group contained diffuse EBER-1 positivity. There was a positive correlation between EBER positivity and depth of inflammation and mucosal ulceration in patients with refractory IBD. Our findings suggest a potential role for EBV infection in patients with refractory 1BD. (C) 2018 Elsevier Inc. All rights reserved.

关键词： ankylosing spondylitis   spondyloarthritis   anti-TNF  

摘要： Correspondence to Dr. Nicolas Richard, Division of Rheumatology, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada; ***2@*** We read with interest the article by Varkas et al 1 suggesting a temporal association between the initiation of vedolizumab (VDZ) for inflammatory bowel disease (IBD) and induction or worsening of spondyloarthritis (SpA). ADA, adalimumab; CZP, certolizumab pegol; GOL, golimumab; HLA, human leucocyte antigen; IBD, inflammatory bowel disease; IFX, infliximab;  Long-term combination therapy with anti-TNF plus vedolizumab induces and maintains remission in therapy-refractory ulcerative colitis.

关键词： Wet-milling   Colitis   Pluronic F127   Budesonide   Trinitrobenzenesulfonic acid (TNBS)  

摘要： Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder that affects more than 1 million individuals in the USA. Local therapy with enema formulations, such as micronized budesonide (Entocort(center dot).), is a common strategy for treating patients with distally active IBD. However, we hypothesize that micronized particulates are too large to effectively penetrate colorectal mucus, limiting the extent of drug delivery to affected tissues prior to clearance. Here, we describe the development of a budesonide nanosuspension (NS) with the appropriate surface coating and size to enhance penetration of colorectal mucus and ulcerated colorectal tissues. We demonstrate that model fluorescent polystyrene (PS) particles similar to 200 rim in size with a muco-inert Pluronic F127 coating provide enhanced mucosal distribution and tissue penetration in mice with trinitrobenzenesulfonic acid (TNBS)-induced IBD compared to model 2 mu m PS particles coated with polyvinylpyrollidone (PVP), the stabilizer used in the clinical micronized budesonide formulation. We then used a wet-milling process to develop a budesonide NS formulation with a muco-inert Pluronic F127 coating (particle size similar to 230 nm), as well as a budesonide microsuspension (MS) stabilized with PVP (particle size similar to 2 mu m). Using an acute TNBS mouse model of IBD, we show that daily budesonide NS enema treatment resulted in a significant reduction in the macroscopic (decreased colon weight) and microscopic (histology score) symptoms of IBD compared to untreated controls or mice treated daily with the budesonide MS enema. Further, we show that the budesonide NS enema treated mice had a significantly reduced number of inflammatory macrophages and IL-beta producing CD11b + cells in colon tissue compared to untreated controls or mice treated with the budesonide MS enema. We conclude that the nano-size and muco-inert coating allowed for enhanced local delivery of budesonide, and t

关键词： Crohn's disease (CD)   Ulcerative colitis (UC)   REG family genes   Transcription  

摘要： The pathophysiology of inflammatory bowel disease (IBD) reflects a balance between mucosal injury and reparative mechanisms. Some regenerating gene (Reg) family members have been reported to be expressed in Crohn's disease (CD) and ulcerative colitis (UC) and to be involved as proliferative mucosal factors in IBD. However, expression of all the REG family genes in IBD is still unclear. Here, we analyzed expression of all the REG family genes (REG I alpha, REG I beta, REG III, HIP/PAP, and REG IV) in biopsy specimens of UC and CD by real-time RT-PCR. REG I alpha, REG I beta, and REG IV genes were overexpressed in CD samples. REG IV gene was also overexpressed in UC samples. We further analyzed the expression mechanisms of REG I alpha, REG I beta, and REG IV genes in LS-174T and HT-29 human colonic epithelial cells. The expression of REG I alpha was significantly induced by IL-6 or IL-22, and REG I beta was induced by IL-22. Deletion analyses revealed that three regions (- 220 similar to- 211, - 179 similar to- 156, and - 146 similar to- 130) in REG I alpha and the region (-274 similar to- 260) in REG I beta promoter were responsible for the activation by IL-22/IL-6. The promoters contain consensus transcription factor binding sequences for MZF1, RTEF1/TEAD4, and STAT3 in REG I alpha, and HLTF/FOXN2F in REG I beta, respectively. The introduction of siRNA for MZF1, RTEF1/TEAD4, STAT3, and HLTF/FOXN2F abolished the transcription of REG I alpha and REG I beta. The gene activation mechanisms of REG I alpha/REG I beta may play a role in colon mucosal regeneration in IBD.