关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Biologics   Post-operative complications   Infliximab   Anti-tnf   Biological therapy   Indeterminate colitis   Vedolizumab   Ustekinumab   Certolizumab pegol   Adalimumab   alpha 4 beta 7-integrin inhibitor   Interleukin IL-12/IL-23 inhibitor  

摘要： Background: Biopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/ anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice. Methods: A systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/*** population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intraabdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle-Ottowa scale. Results: 2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNF alpha exposure while vedolizumab increased SSI and small bowel obstruction. Conclusion: Prospective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population. Crown Copyright (

关键词： Inflammatory bowel disease   DRAM1   Autophagy   Apoptosis   Intestinal inflammation   JNK  

摘要： Background and Aims DNA damage-regulated autophagy modulator 1 (DRAM1) is required for induction of autophagy and apoptosis. However, the influence of DRAM1 on the pathogenesis of inflammatory bowel disease (IBD) has not been explored. Methods DRAM1 expression was examined in the intestinal mucosa of patients with IBD and colons of colitis mice. We used a recombinant adeno-associated virus carrying small hairpain DRAM1 to knock down the DRAM1 gene to treat colitis in the mice. The effect of DRAM1 on autophagy and apoptosis of intestinal epithelial cells was explored. DRAM1-mediated interaction with the c-Jun N-terminal kinase (JNK) pathway was also examined. Results DRAM1 expression in the intestinal mucosa of the IBD patients was higher than that in the control participates. DRAM1 expression in the inflammatory cells in patients with Crohn's disease (CD) was lower than that in patients with ulcerative colitis (UC). Additionally, DRAM1 expression was correlated with the Simple Endoscopic Score for CD and the Mayo endoscopic score for UC. Serum levels of DRAM1 in the IBD group were substantially higher than those in the normal group. The knockdown of DRAM1 could alleviate colitis symptoms in mice. In in vitro experiments, knocking down DRAM1 could reduce autophagy and apoptosis levels. Mechanistically, DRAM1 may participate in the regulation of these two processes by positively regulating JNK activation. Conclusions During intestinal inflammation, the upregulation of DRAM1 may promote the activation of JNK and further aggravate intestinal epithelium damage.

关键词： Fatigue   Foecal incontinence   Inflammatory bowel disease   Pain   Qualitative   Self-management   Urgency  

摘要： Background Inflammatory bowel disease (IBD) causes inter-related symptoms of fatigue, pain and urgency which can persist in remission. Aim To understand how people with IBD experience and self-manage these symptoms and to inform the future development of an online self-management programme. Methods Using exploratory qualitative methods, we recruited participants from clinic and community settings. Focus groups, conducted across the UK, were audio-recorded and professionally transcribed. Transcripts were analysed over four rounds using framework analysis. Eight patients were consulted to agree the final structure of data and themes. Results Seven focus groups were held;five gave useable data. Twenty-six participants (15 female;ages 21-60 years;disease duration 2-40 years) with Crohn's disease (n = 10), ulcerative colitis (n = 14) and IBD-unclassified (n = 2) attended one of these five focus groups. Three core themes emerged: The Negative Impact of Symptoms, Positively Taking Control and Seeking and Receiving Support. The persistent, often stark impact of multiple co-existing symptoms on physical and emotional wellbeing can force unwanted adjustments and limitations in working, social and intimate arenas of life. Unpredictable symptoms are challenging and impact each other in negative vicious cycles. Managing diet, pacing, accepting background levels of fatigue, pain and urgency, seeking support, exercising and attending to mental wellbeing, are all perceived as helpful in self-managing symptoms. Conclusion Fatigue, pain and urgency are troublesome for patients, especially in combination, suggesting that these should be addressed simultaneously by clinicians. Participants reported several strategies for self-management, providing patient-focused evidence to inform future development of a self-management intervention programme.

摘要： Background: Increase in lipid levels associated with the treatment of inflammatory bowel disease (IBD) has previously been reported. However, it is unknown if this effect is similar for all IBD drug classes. Aim: To precisely assess the effect of different IBD drug classes on lipid profiles Methods: We performed a systematic literature search of randomised controlled trials and observational cohort studies that assessed lipid levels before and after induction (<= 10 weeks) and maintenance (>10 weeks) of IBD treatment. Data of 11 studies (1663 patients) were pooled using random effects models. The influence of patient and disease characteristics on treatment effects on total cholesterol levels was analysed in 6 studies (1211 patients) for which individual data were available, using linear mixed models. Results: A statistically significant increase in total cholesterol was observed after induction treatment with corticosteroids (+1.19 mmol/L, 95% confidence interval [CI95] +0.52 to +2.59), and tofacitinib (+0.66 mmol/L, CI95 +0.42 to +0.79), but not after anti-TNF alpha treatment (-0.11 mmol/L, CI95 -0.26 to +0.36 mmol/L). Similar differences were observed after maintenance treatment. Treatment effects were significantly related to age, but not with other factors. Lipid changes were inversely correlated with but not modified by CRP changes. Conclusions: Increase in total cholesterol levels was strongest for corticosteroids followed by tofacitinib but was not observed for anti-TNF alpha agents. Whether total cholesterol change associated with IBD treatment has an effect on cardiovascular risk requires further study.

关键词： Lymphoma   inflammatory bowel disease   biomarker   haptoglobin   non-invasive   enteropathy  

摘要： Objectives The aim of this study was to evaluate serum haptoglobin as a biomarker to differentiate between small-cell alimentary lymphoma and inflammatory bowel disease in cats. Methods Client-owned domestic cats with and without chronic gastrointestinal signs were enrolled in the study. Serum was collected from each patient and serum haptoglobin levels were measured using ELISA. In cats with gastrointestinal signs, histopathologic evaluation of endoscopic biopsies harvested from the intestinal tract was used to separate them into inflammatory bowel disease and small-cell lymphoma cohorts. Serum haptoglobin levels were statistically analyzed and compared among the three groups: healthy cats;cats with inflammatory bowel disease;and cats with small-cell alimentary lymphoma. Results Sixty-two cats were enrolled in the study, including 20 clinically normal cats, 14 cats with small-cell alimentary lymphoma and 28 cats with inflammatory bowel disease. The mean +/- SD serum haptoglobin was 73.2 +/- 39.1 mg/dl in normal cats, 115.3 +/- 72.8 mg/dl in cats with inflammatory bowel disease and 133.1 +/- 86.1 mg/dl in cats with small-cell alimentary lymphoma. Cats with inflammatory bowel disease and lymphoma had significantly higher serum haptoglobin than controls, with P values of 0.0382 and 0.0138, respectively. There was no statistical difference between the inflammatory bowel disease and lymphoma cohorts (P = 0.4235). For every one unit increase in serum haptoglobin, the odds of gastrointestinal inflammatory disease (inflammatory bowel disease or small-cell alimentary lymphoma) increased by 1.41% (P = 0.0165). Conclusions and relevance Serum haptoglobin is a useful biomarker for distinguishing between normal cats and those with gastrointestinal inflammatory disease, but it could not significantly differentiate between inflammatory bowel disease and lymphoma. Additional studies may be beneficial in determining the prognostic significance of serum haptoglobin as it may relate

关键词： inflammatory bowel disease   paediatrics   severe acute respiratory syndrome coronavirus 2   vaccination  

摘要： In this communication, the members of the Porto group (the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN], inflammatory bowel diseases [IBD] working group) provide the current available evidence regarding vaccination of children and young adolescents with IBD against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our intent is to help provide meaningful answers to the concerns that parents and adolescents may have.

关键词： elderly   inflammation   monoclonal antibodies   pharmacokinetic‐   pharmacodynamic   population analysis  

摘要： Aims Controversies regarding infliximab treatment in elderly patients with inflammatory bowel diseases remain. We evaluated the effect of patient's age on infliximab exposure, efficacy and safety. Methods Retrospective case-control data of patients receiving infliximab induction treatment were analysed. A population pharmacokinetic model was developed to estimate individual pharmacokinetic parameters. A logistic regression model was used to investigate the effect of exposure on endoscopic remission. Repeated time-to-event models were developed to describe the hazard of safety events over time. Results A total of 104 patients (46 elderly, >= 65 years) were included. A two-compartment population pharmacokinetic model with linear elimination adequately described the data. Infliximab clearance decreased with older age, higher serum albumin, lower fat-free mass, lower C-reactive protein and absence of immunogenicity. Yet, infliximab exposure was not significantly different between elderly and nonelderly. Regardless of age, an infliximab trough concentration at week (w)14 of 15.6 mg/L was associated with a 50% probability of attaining endoscopic remission between w6 and w22. Infliximab exposure during induction treatment was not a risk factor of (severe) adverse events. The hazard of severe adverse events and malignancy increased by 2% and 7%, respectively, with increasing year of age. Concomitant immunomodulator use increased the hazard of infection by 958%, regardless of age. Conclusions Elderly patients attained infliximab exposure and endoscopic remission similarly to nonelderly patients. Therefore, the same infliximab trough concentration target can be used in therapeutic drug monitoring. The hazards of severe adverse events and malignancy increased with age, but not with infliximab exposure.

关键词： Inflammation   Inflammatory bowel disease   Microbiology  

摘要： This Perspective highlights an accumulating body of literature that outlines a direct role for oral-associated bacteria in inflammatory bowel disease pathogenesis. The authors propose a model by which oral-associated species might expand in the inflamed intestinal environment to exacerbate inflammation. Over the past two decades, the importance of the microbiota in health and disease has become evident. Pathological changes to the oral bacterial microbiota, such as those occurring during periodontal disease, are associated with multiple inflammatory conditions, including inflammatory bowel disease. However, the degree to which this association is a consequence of elevated oral inflammation or because oral bacteria can directly drive inflammation at distal sites remains under debate. In this Perspective, we propose that in inflammatory bowel disease, oral disease-associated bacteria translocate to the intestine and directly exacerbate disease. We propose a multistage model that involves pathological changes to the microbial and immune compartments of both the oral cavity and intestine. The evidence to support this hypothesis is critically evaluated and the relevance to other diseases in which oral bacteria have been implicated (including colorectal cancer and liver disease) are discussed.