关键词： Inflammatory   bowel   disease   Hepatitis   Gene   Cytosolic   isoleucine   tRNA   synthase  

摘要： BACKGROUND Aminoacyl tRNA synthetases/ligases(ARSs)are highly conserved enzymes involved in attaching amino acids to tRNA promoting protein *** deficiencies of ARSs localized to the mitochondria classically present with neuropathology,the clinical features of cytosolic ARS deficiencies are more *** have previously been associated with neonatal hepatitis,but never with early-onset inflammatory bowel *** SUMMARY A nine-year-old Bangladeshi boy presented with neonatal liver failure and deranged clotting,transaminitis and *** parents were first *** older brothers and a sister were *** patient suffered from loose stools from early infancy which became more troublesome and persistent from five years old with ten bloody motions a *** endoscopies showed persistent pancolitis,which was refractory to mesalazine,corticosteroids,azathioprine,sirolimus and anti-TNF(adalimumab)therapy,but has improved recently with subcutaneous *** Genome Sequencing revealed a novel pathogenic missense variant(c.290A>G)in the cytosolic isoleucyl-tRNA synthetase gene,leading to an amino acid substitution(***97Gly).Pathogenic variants in other genes associated with inflammatory bowel disease(IBD)(ADAM17,EGFR,FOXP3,IL10RA,IL10RB,IL21R,NCF4,STAT3)were *** assays demonstrated markedly elevated IL-2,IL-5,IL-13,IL-9 and IL-10 by the patient’s CD4+T-cells,while IL-17A,IL-17F,IFNβwere lower,and TNFαnot significantly different when compared to healthy *** This case report provides evidence that recessive mutations in cytosolic isoleucyltRNA synthetase are a novel monogenic cause of IBD,which should be considered,particularly in infants and children with a history of neonatal hepatitis and very early-onset IBD poorly responsive to treatment.

关键词： clinical   inflammatory   bowel  

摘要： In the past decade,artificial intelligence(Al)has been applied in several clinical studies to improve the medical care of patients with gastroenterological diseases,to accurately detect polyps and early cancer lesions,to facilitate the analysis of inflammatory lesions,to assess liver fibrosis,and to predict the response and clinical outcomes of medications.[1-2]Inflammatory bowel disease(IBD),comprising Crohn disease(CD)and ulcerative colitis(UC),is a prototypical complex disease that has been considered a significant healthcare burden in the healthcare system of Western countries.

关键词： Inflammatory   bowel   disease   Colorectal   cancer   Cytokines   mRNA   Interleukin-6   Th17/Treg   cells  

摘要： BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both *** may further influence the inflammation and the carcinogenesis *** To compare cytokine patterns of active IBD patients with early and advanced *** Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein *** We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD *** stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced *** protein levels of the cytokines were significantly higher in CRC patients compared to IBD *** Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC *** significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

关键词： Inflammatory bowel disease   M1 and M2 macrophages   Immune system   Inflammation   Gastrointestinal system  

摘要： Chronic inflammation of the gastrointestinal system is mediated by both the immune system activity and homeostasis, mainly through releasing of various cytokines and chemokines, as well as the transmigration of the inflammatory cells to the affected site. In between, macrophages are key mediators of the immune system, nearly located all over the gastrointestinal tract. Macrophages have vital influence on the inflammatory condition with both pro-inflammatory and anti-inflammatory functions. Their polarization status has been linked to numerous metabolic disorders such as inflammatory bowel disease (IBD). The equilibrium between the phenotypes and functions of inflammatory M1 and anti-inflammatory M2 cells is regulated by both extracellular and intracellular stimuli, determining how the disease progresses. Thereby, factors that interchange such balance in the direction of increasing M2 macrophages offer unique approaches for future management of IBD. This study reflects the novel IBD treatment targets via the immune system's pathway, reporting the latest treatments that regulate the M1/M2 macrophages distribution in a way to favor IBD.

关键词： cytokine   immunity   TNBS  

摘要： RESEARCH HIGHLIGHT Ulcerative colitis and Crohn’s disease are the two major forms of inflammatory bowel disease(IBD)in humans.1 Chronic human IBD,such as Crohn’s disease,is characterized by features such as intestinal infiltration of immune cells,inflammatory cytokine milieu,intestinal fibrosis and weight loss among others,that lead to chronic and spontaneously recurring intestinal inflammation.2 Several mouse models of IBD have been used by researchers to understand the diverse aspects related to human IBD.1,2 For example,the mouse model of intra-rectal administration of the haptenating agent,2,4,6-trinitrobenzene sulfonic acid(TNBS),which induces mucosal immunity to colonic immunogenic proteins in the host,recapitulates key immunological responses observed in Crohn’s disease,such as cytokine secretion patterns,intestinal fibrosis,and immune intolerance.2 The innate immune response is critical to initiate the cytokines production that prime T-cell differentiation in the TNBS *** polarized T-cell responses are hallmarks of IBD and in the TNBS model T_(H)1 and T_(H)17-cell responses predominate as is observed with the signature cytokine secretion profile of IL12/IFNγand IL23/IL17,respectively.

关键词： Anemia   Crohn's disease   Inflammatory bowel disease   Ulcerative colitis  

摘要： Background: Tumor necrosis factor-alpha (TNF-alpha) is involved in inducing inflammatory anemia. The potential effect of anti-TNF-alpha agents on anemia in inflammatory bowel diseases (IBD) is still unknown. Methods: Analytical data and disease characteristics from 362 IBD patients [271 CD/91UC) treated with anti-TNF-alpha drugs were retrospectively collected. Effects on disease activity, blood markers and prevalence of anemia were assessed after 6 and 12 months of therapy. Results: 29.3% patients presented anemia at baseline, and significantly reduced to 14.4% and 7.8% after 6 and 12 months of therapy, respectively. Mean +/- SD Hb levels increased significantly at month 6, and this increase was sustained at 12 months. Serum markers of iron metabolism increased significantly compared to baseline, as disease activity measured by C-reactive protein (CRP) was reduced. All these effects were observed independently for CD and UC, and were independent of iron supplementation during treatment. Anemia at baseline (OR 4.09;95%CI 1.98-8.45) and elevated CRP (OR 3.45;95CI 1.29-9.22) were independently associated with risk of persistent anemia, as well as iron replacement during therapy (OR 4.36;95%CI 2.07-9.16). Conclusions: Controlling disease activity with anti-TNF-alpha therapy significantly and independently associated with resolution of anemia in IBD, with no relevant role for iron replacement therapy. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： Adalimumab   Drug survival   Inflammatory bowel disease   Infliximab   Medicine-withdrawal   Therapeutic drug monitoring  

摘要： Background Conventional therapy of inflammatory bowel disease with traditional immunosuppressant medication is increasingly being replaced by biological agents. However, the response to these biological agents may be lost over time, with discontinuation being a marker of loss of effectiveness. There are few published reports on the treatment drug survival of infliximab and adalimumab in patients with inflammatory bowel disease. Objective This study compared the drug survival of infliximab versus adalimumab as first- and second-line treatments, identified factors associated with drug survival, and described reasons for treatment withdrawal. Setting A pharmacy department of a university hospital in Spain. Method A retrospective single-centre cohort study of all patients with inflammatory bowel disease treated with biological agents between 2008 and 2017 at a regional referral hospital. The primary outcome was drug survival and associated factors during a follow-up of 52 months. Main outcome measure Drug survival of infliximab versus adalimumab. Results One hundred thirty-four patients with inflammatory bowel disease (73.9% Crohn's disease and 26.1% ulcerative colitis) were treated with biological therapy. The overall mean drug survival of first-line treatment with an anti-tumour necrosis factor agent was 18.6 months (SD 14.9), with mean values of 20.2 months (SD 16.6) for adalimumab and 17.1 months (SD 13.1) for infliximab. As a second-line treatment, the drug survival of anti-tumour necrosis factor agents was 17.9 months (SD 15.6), with mean values of 22.9 months (SD 17.1) for adalimumab and 12.5 months (SD 11.7) for infliximab. The difference in time to discontinuation at 52 months of follow-up between the infliximab and adalimumab subgroups, as either first- or second-line treatment, was not statistically significant (p = 0.547 and p = 0.676, respectively). Therapeutic drug monitoring was the only factor associated with greater drug survival in first-line treatment

关键词： Crohn's disease   CT scan   Emergency department   Ulcerative colitis  

摘要： Background: Management of inflammatory bowel diseases (IBD) in the emergency department is often suboptimal. Aims: To develop a national consensus checklist of indicators to facilitate decision-making in emergency departments concerning hospitalisation and referral for abdominopelvic computed tomography (CT). Methods: A Delphi survey was used to obtain consensus on a checklist of clinical and biological variables. 119 healthcare professionals experienced in treating IBD were invited to participate. Panellists were provided with a literature survey and invited to agree or disagree with items on a prototype checklist. Two successive rounds of voting were organised. Results: The prototype checklist included fifteen clinical or laboratory indicators for hospitalisation or CT. Four indicators were not retained in the Delphi process and four additional indicators added. The final indicators retained were: abdominal signs/symptoms of disease exacerbation, intravenous morphine titration, fever, vomiting, dehydration, recent intestinal surgery, ano-perineal abscess, bowel obstruction, haemodynamic instability, anaemia, acute kidney failure and elevated C-reactive protein. Consensus for the retained indicators was >88%. Conclusions: Use of this consensus checklist for the management of IBD in the emergency department may help improve standards of care and thus reduce the burden of these diseases. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： PIG-A assay   azathioprine   micronuclei   gene mutation   human population  

摘要： The rodent Pig-a assay has been used extensively as a potential regulatory assay for evaluating the in vivo mutagenicity of test substances. Although the assay can be conducted in different mammalian species, there have been only a few reports describing its use in humans, and rarely in genotoxicant-exposed human populations. In this study, PIG-A mutation frequencies (MFs) were evaluated in 36 azathioprine (AZA;human carcinogen)-treated inflammatory bowel disease (IBD) patients and 36 healthy volunteers. IBD patients exhibited a slight but statistically higher MF (6.10 +/- 4.44 x 10(-6)) than healthy volunteers (4.97 +/- 2.74 x 10(-6)) (P = 0.0489). The estimated relative risk for the exposed patients was 1.22 which indicated that AZA is a risk factor for inducing PIG-A mutation. However, the PIG-A MF showed no associations with AZA treatment duration or total AZA exposure. In addition, we performed the cytokinesis-block micronucleus test on the same samples. The frequencies of micronuclei (MN) and nuclear buds (NBUD) in IBD patients (MN: 4.70 +/- 2.86 parts per thousand;NBUD: 1.89 +/- 0.95 parts per thousand) were significantly higher than in healthy volunteers (MN: 1.47 +/- 0.77 parts per thousand, P < 0.001;NBUD: 0.90 +/- 0.58 parts per thousand, P = 0.004). MN frequency also had significant correlations with AZA treatment duration (P = 0.011) and total AZA exposure (P = 0.018). Our findings indicate that AZA-treated IBD patients have only a marginally significant increase in PIG-A MF;in contrast, a much stronger AZA-associated increase in genotoxicity was detected with the lymphocyte MN assay. Environ. Mol. Mutagen. 2019. (c) 2019 Wiley Periodicals, Inc.

关键词： Inflammatory   Bowel   Crohn's   Colitis   Microbiota   Gut  

摘要： Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease that can involve any part of the gastrointestinal tract. It includes two main disorders: Crohn's disease (CD) and Ulcerative colitis (UC). CD and UC often share a similar clinical presentation;however, they affect distinct parts of the GI Tract with a different gut wall inflammatory extent. Ultimately, IBD seems to emanate from an uncontrollably continuous inflammatory process arising against the intestinal microbiome in a genetically susceptible individual. It is a multifactorial disease stemming from the impact of both environmental and genetic components on the intestinal microbiome. Furthermore, IBD genetics has gained a lot of attention. Around 200 loci were identified as imparting an increased risk for IBD. Few of them were heavily investigated and determined as highly linked to IBD. These genes, as discussed below, include NOD2, ATG16L1, IRGM, LRRK2, PTPN2, IL23R, Il10, Il10RA, Il10RB, CDH1 and HNF4 alpha among others. Consequently, the incorporation of a genetic panel covering these key genes would markedly enhance the diagnosis and evaluation of IBD.