关键词： Crohn's disease   Ulcerative colitis   Inflammatory bowel disease   HLA-G   Inflammatory cells  

摘要： Background Since HLA-G is an immune checkpoint molecule and since Crohn's disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension. Methods HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA. Results HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P < 0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P = 0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P = 0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P < 0.0001) than in controls, but no difference was observed between diseases. Conclusions Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.

关键词： Crohn's disease   inflammatory bowel disease   paediatrics   transition   ulcerative colitis  

摘要： Objectives: Patients with paediatric inflammatory bowel disease (IBD) constitute one of the largest cohorts requiring transition from paediatric to adult services. Standardised transition care improves short and long-term patient outcomes. This study aimed to detail the current state of transition services for !BD in the United Kingdom (UK). Methods: We performed a nationwide study to ascertain current practice, facilities and resources for children and young people with IBD. Specialist paediatric IBD centres were invited to contribute data on: timing of transition/transfer of care;transition resources available including clinics, staff and patient information;planning for future improvement. Results: Twenty of 21 (95%) of invited centres responded. Over 90% of centres began the transition process below 16 years of age and all had completed transfer to adult care at 18 years of age. The proportion of patients in the transition process at individual centres varied from 10% to 50%. Joint clinics were held in every centre, with a mean of 12.9 clinics per year. Adult and paediatric gastroenterologists attended at all sites. Availability of additional team members was patchy across the UK, with dietetic, psychological and surgical attendance available in <50% centres. A structured transition tool was used in 75% of centres. Sexual health, contraception and pregnancy were discussed by <60% of teams. Conclusions: This study provides real-world clinical data on UK-wide transition services. These data can be used to develop a national strategy to complement current transition guidelines, focused on standardising services whilst allowing for local implementation.

关键词： anti-HBs   anti-TNF   aOR   CDC   CIN   CoE   CI   DTaP   GRADE   HBV   Hib   HPV   HZ   IBD   IMD   IPD   LZV   NACI   PCV13   PPSV23   QALY   RCT   RR   RZV   4vHPV   9vHPV   WHO  

摘要： BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years o

关键词： Atherosclerosis   Cardiovascular disease   Chronic inflammation   Crohn disease   Premature ASCVD   Ulcerative Colitis   Veterans  

摘要： BACKGROUND: Recent literature has shown an association between atherosclerotic cardiovascular disease and inflammatory bowel disease, potentially mediated through chronic inflammatory pathways. However, there is a paucity of data demonstrating this relationship among young patients with premature atherosclerotic cardiovascular disease. METHODS: Using data from the nationwide Veterans wIth premaTure AtheroscLerosis (VITAL) registry, we assessed the association between extremely premature and premature atherosclerotic cardiovascular disease (age at diagnosis: <40 years and <55 years, respectively) and inflammatory bowel disease. Patients were compared with age-matched controls without atherosclerotic cardiovascular disease. Multivariable regression models adjusted for traditional risk factors. RESULTS: We identified 147,600 patients and 9485 patients with premature and extremely premature atherosclerotic cardiovascular disease, respectively. Compared with controls, there was a higher prevalence of overall inflammatory bowel disease among premature (0.96% vs 0.84%;odds ratio [OR] 1.14;95% confidence interval [CI], 1.08-1.21) and extremely premature (1.36% vs 0.75%;OR 1.82;95% CI, 1.52-2.17) patients. After adjustment, these associations attenuated in both premature and extremely premature groups (OR 1.07;95% CI, 1.00-1.14 and OR 1.61;95% CI, 1.34-1.94, respectively). CONCLUSION: Inflammatory bowel disease is associated with higher odds of extremely premature atherosclerotic cardiovascular disease, especially for those age <40 years. With increasing age, this risk is attenuated by traditional cardiometabolic factors such as obesity, hypertension, diabetes, smoking, and dyslipidemia. Prospective studies are needed to assess the role of early intervention to decrease cardiovascular risk among young patients with inflammatory bowel disease. Published by Elsevier Inc.

关键词： Immunology   Infectious Diseases   Internal Medicine   Medical Microbiology  

摘要： This article is linked to Friedman et al and Horjus-Talabur Horje & van Bodegraven papers. To view these articles, visit https://***/10.1111/apt.16452 and https://***/10.1111/apt.16476

摘要： Background Knowledge of the cost of illness of inflammatory bowel disease (IBD) is essential for health policy makers worldwide. Aim To assess the cost of illness of IBD from the societal perspective taking into account time trends and geographical differences. Methods A systematic review of all population-based studies on cost of illness of IBD published in Embase, Medline, Web of Science and Google Scholar. Methodology of included studies was assessed and costs were adjusted to 2018 US dollars. Results Study methodologies differed considerably, with large differences in perspective, valuation method and population. For prevalent Crohn's disease (CD) cases in the last ten years annual healthcare costs were in Asia $4417 (range $1230-$31 161);Europe $12 439 ($7694-$15 807) and North America $17 495 ($14 454-$20 535). For ulcerative colitis (UC), these were $1606 ($309-$14 572), $7224 ($3228-$9779) and $13 559 ($13 559-$13 559). The main cost driver was medication, the cost of which increased considerably between 1985 and 2018, while outpatient and inpatient costs remained stable. IBD had a negative impact on work productivity. Annual costs of absenteeism for CD and UC were in Asia (with presenteeism) $5638 ($5638-$5638) and $4828 ($4828-$4828);Europe $2660 ($641-$5277) and $2394 ($651-$5992);North America $752 ($307-$1303) and $1443 ($85-$2350). Conclusion IBD societal cost of illness is increasing, driven by growing costs of medication, and varies considerably between continents. While biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, these costs have not declined.

关键词： 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis   dextran sulfate sodium (DSS)-induced colitis   inflammatory bowel disease (IBD)   inhibitor of apoptosis stimulating p53 protein (iASPP)   NF-kappa B  

摘要： Drugs and therapies available for the treatment of inflammatory bowel disease (IBD) are not satisfactory. Our previous study has established the inhibitor of apoptosis-stimulating p53 protein (iASPP) as an oncogenic regulator in colorectal cancer by forming a regulatory axis or feedback loop with miR-124, p53, or p63. As iASPP could target and inhibit nuclear factor kappa B (NF-kappa B) activation, in this study the role and mechanism of iASPP in IBD was investigated. The aberrant up-regulation of iASPP in IBD was subsequently confirmed, based on online data sets, clinical sample examinations and 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis mice models. TNBS or DSS stimulation successfully induced colon shortness, body weight loss, mice colon oxidative stress and inflammation. In both types of colitis mice models, iASPP over-expression improved, whereas iASPP knockdown aggravated TNBS or DSS stimulation-caused colon shortness, body weight loss and mice colon oxidative stress and inflammation. Meanwhile, in both types of colitis mice models, iASPP over-expression inhibited p65 phosphorylation and decreased the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, C-X-C motif chemokine ligand (CXCL)1 and CXCL2 in mice colons, whereas iASPP knockdown exerted opposite effects.

关键词： Inflammatory bowel disease   Lymphangiogenesis   Lymphangiectasia   Lymphadenopathy   Pathogenesis   Therapy  

摘要： Inflammatory bowel disease (IBD) is characterized by intense immune dysregulation, gut microbiota imbalance, and intestinal epithelium destruction. Among the factors that contribute to the pathogenesis of IBD, lymphatics have received less attention, hence less studied, characterized, and explored. However, in recent years, the role of the lymphatic system in gastrointestinal pathophysiology continues to be highlighted. This paper examines the implications of lymphatic changes in IBD pathogenesis related to immune cells, gut microbiota, intestinal and mesenteric epithelial barrier integrity, and progression to colorectal cancer (CRC). Therapeutic targets of lymphatics in IBD studies are also presented. Available studies indicate that lymph nodes and other secondary lymphatic tissues, provide highly specialized microenvironments for mounting effective immune responses and that lymphatic integrity plays a significant role in small intestine homeostasis, where the lymphatic vasculature effectively controls tissue edema, leukocyte exit, bacterial antigen, and inflammatory chemokine clearance. In IBD, there are functional and morphological alterations in intestinal and mesenteric lymphatic vessels (more profoundly in Crohn's disease [CD] compared to ulcerative colitis [UC]), including lymphangiogenesis, lymphangiectasia, lymphadenopathy, and lymphatic vasculature blockade, affecting not only immunity but gut microbiota and epithelial barrier integrity. While increased lymphangiogenesis is primarily associated with a good prognosis of IBD, increased lymphangiectasia, lymphadenopathy, and lymphatic vessel occlusion correlate with poor prognosis. IBD therapies that target the lymphatic system seek to increase lymphangiogenesis via induction of lymphangiogenic factors and inhibition of its antagonists. The resultant increased lymphatic flow coupled with other anti-inflammatory activities restores gut homeostasis.