关键词： INFLIXIMAB   CROHN'S disease  

摘要： Linked Content This article is linked to Schmitz et al papers. To view this article visit https://***/10.1111/apt.14453.

关键词： Integrate   Patients  

摘要： Introduction IL-10R defects account for about 2.6% of patients who present with VEOIBD¹. We identified a baby with IL-10R deficiency through lack of downstream phosphorylated STAT3 *** Description A two-week old male born full term, presented to the hospital with persistent fevers and diarrhea; hospital course was complicated by failure to thrive, Enterobacter pneumonia, respiratory failure, hepatitis, persistently elevated alpha-feto protein, and colitis. Immunology was consulted to assess for immunodeficiency. History was unremarkable for infections prior to admission. Family history was notable for parental consanguinity (1st cousins). Immune work-up showed normal levels of T/B/NK cells, immunoglobulins, and lymphocyte stimulation by mitogens. Diagnosis was made through defective signaling via the IL-10 receptor by lack of phosphorylated STAT3 expression but normal signaling via IL-21. Gene sequencing confirmed a homozygous defect in the IL-10Rβ chain. He was treated with infliximab and adalimumab prior to stem cell transplant. He underwent reduced intensity conditioning and received an allogenic, mismatched, unrelated, cord, female donor stem cells. Unfortunately, he had primary graft failure. About 4 weeks after transplant, he presented with septic shock and found to have CD4 count of 138, increased to 248 at present day. The family refused repeat transplant. Currently, he is 5 years old and is alive and stable on daily prednisolone, metronidazole, and *** Binding to the heterotetrameric interleukin-10 receptor results in the activation of JAK1 and Tyk2, leading to phosphorylation of STAT3 and activation of STAT3 dependent genes². Testing for phosphorylated STAT3 expression via IL-10 and IL-21 is effective for identifying IL10R deficiency.

关键词： Bone density   Fracture risk   Inflammatory bowel disease   Meta-analysis   Osteoporosis  

摘要： Inflammatory bowel diseases (IBDs) are associated with a decreased bone mineral density, but the impact on fractures is unknown. In our study, global risk of fracture is increased for patients with IBDs versus controls. This result will help to determine the appropriate assessment with early screening and management of osteoporosis. Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), are associated with a decreased bone mineral density (BMD). However, the impact on fracture risk is unknown and data are contradictory across studies. In this systematic review and meta-analysis, we aimed to assess the risk of fracture and presence of low BMD in patients with IBDs compared to healthy controls. A systematic search of literature was conducted of MEDLINE, EMBASE, the Cochrane library and abstracts from appropriate scientific congresses. Studies were selected if they compared the incidence of fractures and/or BMD measurement by dual-energy X-ray absorptiometry in patients with IBDs and healthy sex- and age-matched controls. Data were extracted by two independent investigators. Meta-analysis was performed with the inverse variance approach to estimate pooled odds ratios (ORs) and risk ratios (RRs) with their 95% confidence intervals (CIs). Twenty-four studies met the inclusion criteria. On the basis of nine studies, global risk of fracture was increased for patients with IBDs versus controls (RR=1.38, 95% CI 1.11-1.73;p=0.005). Fracture risk with IBDs was significantly increased for vertebral fractures (OR=2.26, 95% CI 1.04-4.90;p<0.001), but not for any other site. The analysis of 16 studies evaluating BMD showed a significant decrease in mean BMD and Z-scores for IBD patients versus controls at all sites. In our meta-analysis, patients with IBDs have an increased risk of fractures, especially in the spine, and significant decreased BMD at all sites, which suggests the need for identifying high-risk individuals among this population

关键词： Inflammatory Bowel Diseases   Virus Diseases   Intestinal Diseases  

摘要： Linked Content This article is linked to de Francisco et al and Hans and Scott papers. To view these articles visit https://***/10.1111/apt.14933 and https://***/10.1111/apt.14988.

关键词： Thromboembolism   disease activity   Inflammatory Bowel Diseases   hazard ratio   Venous Thromboembolism   Hospitalization   major surgery   hospital   Patients  

摘要： Background Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism. Aims Methods To determine when patients are at high risk of thromboembolic events, including after major surgery, and to guide timing of thromboprophylaxis. Each IBD patient from Clinical Practice Research Datalink, linked with Hospital Episode Statistics, was matched to up to five non-IBD patients in this cohort study. We examined their risk of thromboembolism in hospital and within 6 weeks after leaving hospital, with or without undergoing major surgery, and while ambulant. Hazard ratios were estimated using Cox regression, with adjustment for age, sex, body mass index, smoking and history of malignancy or thromboembolism. Results Conclusions Overall 23 046 IBD patients had a thromboembolic risk 1.74-times (95% CI = 1.55-1.96) higher than 106 795 non-IBD patients. Among ambulant patients, the thromboembolic risk was raised during acute (hazard ratio = 3.94, 2.79-5.57) or chronic disease activity (3.97, 2.90-5.45) but their absolute risk remained below 5/1000 person-years. The hazard ratio for thromboembolism among in-patients not undergoing major surgery was 1.13 (0.63-2.02), compared to 2.43 (1.20-4.92) among surgical patients, with a near doubling of absolute risk associated with surgery (59.5/1000 person-years, compared with 31.1 without surgery). The absolute risk remained elevated within 6 weeks after leaving hospital (18.6/1000 person-years in IBD patients after surgery). IBD patients are at an increased risk of venous thromboembolism. Absolute risks are raised during active disease, when in hospital, and after leaving hospital following major surgery.

关键词： Epidemiology   Inflammatory bowel disease   Familial risk   Ashkenazi Jewish  

摘要： Background and AimsThe inflammatory bowel diseases (IBD) are particularly common among the Ashkenazi Jewish (AJ) population. Population-specific estimates of familial risk are important for counseling;however, relatively small cohorts of AJ IBD patients have been analyzed for familial risk to date. This study aimed to recruit a new cohort of AJ IBD patients, mainly from the UK, to determine the familial occurrence of *** total of 864 AJ IBD patients were recruited through advertisements, hospital clinics, and primary care. Participants were interviewed about their Jewish ancestry, disease phenotype, age of diagnosis, and family history of disease. Case notes were *** 864 probands comprised 506 sporadic and 358 familial cases, the latter with a total of 625 affected relatives. Of the UK cases, 40% had a positive family history with 25% having at least one affected first-degree relative. These percentages were lower among those recruited through hospital clinics and primary care (33% for all relatives and 22% among first-degree relatives). Examining all probands, the relative risk of IBD for offspring, siblings, and parents was 10.5, 7.4, and 4, respectively. Age of diagnosis was significantly lower in familial versus sporadic patients with Crohn's *** study reports familial risk estimates for a significant proportion of the AJ IBD population in the UK. The high rate of a positive family history in this cohort may reflect the greater genetic burden for IBD among AJs. These data are of value in predicting the likelihood of future recurrence of IBD in AJ families.