关键词： Crohn's disease   drug antibodies   paediatric   trough levels   ulcerative colitis  

摘要： Aim Tumour necrosis factor alpha inhibitors (anti-TNF alpha) are the main therapy for moderate to severe inflammatory bowel disease (IBD) in children. Biosimilars to the original drug infliximab are now available, but there are few reports on their real-life use. We compared the outcomes of patients treated with infliximab and its biosimilar, CT-P13. Methods We collected outcome data on anti-TNF alpha-naive patients who started infliximab in the Children's Hospital, University of Helsinki, Finland, in 2015-2016. We studied 51 paediatric patients with IBD at a median age of 12 (range 4-16): 65% had Crohn disease, 23 received the original infliximab drug and 28 received the biosimilar. During 2015, infliximab was introduced to all treatment-naive patients, and during 2016, all treatment-naive patients received the biosimilar. Results We found no statistically significant differences between the two drug products related to the outcome of the therapy during the first year. There were no significant differences in the trough levels between the treatment groups. Likewise, the proportion of patients with therapy enhancement was comparable between the two treatment groups. Conclusion The first-year therapy outcomes of infliximab and its biosimilar were comparable. There were no alarming signs of differences in safety.

摘要： Background Growth retardation is well described in childhood-onset inflammatory bowel disease (IBD). Aims To study if childhood-onset IBD is associated with reduced final adult height. Methods We identified 4201 individuals diagnosed with childhood-onset IBD 1990-2014 (Crohn's disease: n = 1640;ulcerative colitis: n = 2201 and IBD-unclassified = 360) in the Swedish National Patient Register. Results Patients with IBD attained a lower adult height compared to reference individuals (adjusted mean height difference [AMHD] -0.9 cm [95% CI -1.1 to -0.7]) and to their healthy siblings (AMHD -0.8 cm [-1.0 to -0.6]). Patients with Crohn's disease (CD) were slightly shorter than patients with ulcerative colitis (UC;-1.3 cm vs -0.6 cm). Lower adult height was more often seen in patients with pre-pubertal disease onset (AMHD -1.6 cm [-2.0 to -1.2]), and in patients with a more severe disease course (AMHD -1.9 cm, [-2.4 to -1.4]). Some 5.0% of CD and 4.3% of UC patients were classified as growth retarded vs 2.5% of matched reference individuals (OR 2.42 [95% CI 1.85-3.17] and 1.74 [1.36-2.22] respectively). Conclusion Patients with childhood-onset IBD on average attain a slightly lower adult height than their healthy peers. Adult height was more reduced in patients with pre-pubertal onset of disease and in those with a more severe disease course.

关键词： Bone mineral density   Crohn's disease   ulcerative colitis  

摘要： Inflammatory bowel disease (IBD) is a chronic inflammatory medical condition with relapses and remission. Metabolic bone disease, including osteoporosis, is associated with IBD and imparts a significant morbidity if pathologic fractures were to occur. There has been a significant amount of research that evaluated the pathophysiology and associations between IBD and osteoporosis. Although corticosteroids contribute to the risk of low bone mineral density, osteoporosis and fractures, older age, female gender, smoking, and family history of fracture have been shown to contribute. Additionally, intestinal inflammation affects bone resorption and formation through proinflammatory cytokines such as tumor necrosis factor-a, interleukin-1, and interleukin-6 further accelerating bone loss. Little information is available on standardizing screening or treatment. It is important to recognize the risk factors that are associated with IBD and osteoporosis to identify the patient population at risk and initiate treatment/prevention strategies early. Treatment can include calcium, vitamin D, or bisphosphonates. Some studies showed benefit of treating the underlying IBD to improve bone mineral density.

关键词： Crohn's disease   gender   natural history   ulcerative colitis  

摘要： Sex-based differences in inflammatory bowel disease (IBD) pathogenesis, disease course, and response to therapy have been increasingly recognized, however, not fully understood. Experimental and translational models have been leveraged to investigate hypothesized mechanisms for these observed differences, including the potential modifying role of sex hormones and sex-dependent (epi)genetic and gut microbiome changes. The primary objective of this review is to comprehensively describe sex-based differences in IBD including epidemiology, pathogenesis, phenotypic differences, therapeutic response, and outcomes.

关键词： Infliximab   Infusion reaction   Very early-onset inflammatory bowel disease  

摘要： Background and Aim Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed before 6 years of age, tends to be refractory to conventional treatment for IBD. However, there have been a few reports about the usage of infliximab for VEO-IBD. This study aimed to evaluate the efficacy and safety of infliximab for VEO-IBD. Methods Medical records of a cohort of children with VEO-IBD who had received infliximab in a Japanese tertiary children's hospital were retrospectively reviewed for their disease characteristics and clinical course. Subjects were categorized into three groups for the descriptive comparison: ulcerative colitis type (UCT), non-UCT with perianal disease (NUC-PD), and non-UCT without perianal disease (NUC-NPD). Results Seventeen VEO-IBD patients (five UCT, five NUC-PD, and seven NUC-NPD) had received infliximab as their first biologic. In the UCT group, infliximab was continued over 54 weeks in two patients, and three eventually required surgery. In contrast, all patients in the NUC-PD and NUC-NPD groups followed up over 54 weeks remained on infliximab, and two of three patients and three of five patients were in remission at week 54, respectively. Infusion reactions occurred in all five UCT, three of five NUC-PD, and two of seven NUC-NPD patients;however, except for two patients with severe reactions, infliximab was continued with premedication and slow infusions. Conclusions Infliximab appeared useful for children with VEO-IBD. Children with NUC-PD and NUC-NPD responded better with less infusion reaction compared with that with UCT.

关键词： Ileal pouch-anal anastomosis   Inflammatory bowel disease   Peripouch fat   Pouch prolapse   Floppy pouch complex  

摘要： Background Pouch prolapse is a rare pouch complication which often leads to pouch failure in inflammatory bowel disease (IBD) patients. Its exact cause remains unknown. Floppy pouch complex (FPC) was defined as the presence of any one of the following pouch disorders: pouch prolapse, afferent limb syndrome (ALS), redundant loop, and pouch folding. We aimed to explore the role of peripouch fat area in the occurrence of pouch prolapse and FPC. Methods Pouch patients with available pouchoscopy and abdominal CT scans who were followed up between 2011 and 2017 in Cleveland Clinic were reviewed. Peripouch fat was measured on CT images. Results Of the 93 included patients, 31 were females;87 had J pouches and 6 had S pouches. The median duration of pouch was 8.0 (interquartile range [IQR] 5.0-16.5) years. A total of 18 cases (19.4%, 18/93) were identified as FPC, including 12 pouch prolapse, 5 ALS, 1 redundant loop, and 3 pouch folding. Patients with pouch prolapse had lower peripouch fat area (13.6 (9.3-18.5) vs. 27.6 (11.0-46.2)cm(2), P = 0.022) than those without. Patients with FPC had lower peripouch fat area (15.4 (11.4-20.6) vs. 27.6 (11.0-46.9)cm(2), P = 0.040) than those without. Univariate and multivariate analyses demonstrated that lower peripouch fat area, lower weight, and family history of IBD were independent predictors of pouch prolapse and FPC. Conclusions A lower peripouch fat area was observed in inflammatory bowel disease patients with pouch prolapse and FPC. Longitudinal studies are needed to further elucidate the role of peripouch fat in the pathogenesis of pouch prolapse and FPC.

关键词： inflammatory bowel disease   mice colitis model   miR-802   SOCS5   Th17   TNF-α  

摘要： The present study aims to reveal the detailed molecular mechanism of microRNA (miR)-802 in the progression of inflammatory bowel disease (IBD). IBD tissues were obtained from IBD patients, followed by CD4⁺ cells isolation. Then, qRT-PCR and ELISA were used to detect the expression of miR-802, suppressor of cytokine signaling 5 (SOCS5), interleukin (IL)-17A and tumor necrosis factor (TNF)-α. Transfection of miR-802 mimics and miR-802 inhibitor in CD4⁺ cells was detected by Western blot. TargetScan and luciferase reporter assay were used to detect the relationship between SOCS5 and miR-802. Finally, colitis mice model was established to verify whether miR-802 inhibitor was involved in the protective effect of colonicmucosa. ThemiR-802 was highly expressed in inflamed mucosa and PBMC cells of IBD. The highest expression of miR-802 was observed in CD4⁺ T cells based on different immune cell subsets analysis. SOCS5 was the target gene of miR-802. The mice model experiments showed that blockade of miR-802 could alleviate mice colitis. Our study suggests that up-regulation of miR-802 plays an important role in inflammatory process of IBD via targeting SOCS5. Moreover, the differentiation of Th17 and secretion of TNF-α in IBD could be stimulated by miR-802. © 2020 The Author(s).

关键词： zinc deficiency   practical guideline   taste disorder   inflammatory bowel disease   chronic liver diseases  

摘要： Zinc deficiency is common in Japan, yet awareness on this disorder is lacking. The Japanese Society of Clinical Nutrition recently issued the Japan's Practical Guideline for Zinc Deficiency 2018 setting forth criteria for diagnosing zinc deficiency, i.e., (a) one or more symptoms of zinc deficiency or low serum alkaline phosphatase, (b) ruling out other diseases, (c) low serum zinc, and (d) alleviation of symptoms upon zinc administration. Serum zinc <60 mu g/dL and 60-80 mu g/dL indicate zinc deficiency and marginal deficiency, respectively. Zinc deficiency symptoms vary and include dermatitis and taste disorders among others. Zinc administration improves taste in 50-82% of patients suffering from taste disorders (a common symptom of zinc deficiency). Effects of zinc administration do not appear immediately, and therapy should be continued for at least three months. Zinc deficiency often accompanies various diseases and conditions. Here, we focus on inflammatory bowel diseases and liver cirrhosis. As zinc deficiency enhances intestinal inflammation via macrophage activation, we discuss the pathological mechanism for inflammation and zinc deficiency in the context of IBD. Zinc deficiency can also lead to a nitrogen metabolic disorder in patients with liver cirrhosis. Zinc supplementation can improve not only the ammonia metabolism, but also the protein metabolism. We also discuss directions for future studies of zinc deficiency.

关键词： Bone density   inflammatory bowel disease   trabecular bone score  

摘要： Introduction: Trabecular bone score (TBS) is a textural index that evaluates bone microarchitecture of the lumbar spine. Our aim was to assess TBS in children with inflammatory bowel diseases and to evaluate correlations with clinical, laboratory and densitometric variables. Methods: A retrospective study of TBS and areal bone mineral density measurements by dual-energy X-ray absorptiometry (DXA) of children with either Crohn?s disease (CD) or ulcerative colitis (UC). Bone mineral apparent density was calculated for size adjustment. TBS Z-score for each child were calculated based on data from a healthy population of similar age and gender distribution. Variables significantly associated with TBS were included in stepwise linear regression models to examine independent predictors of TBS. Results: Fifty patients (age at DXA scan 13.8 ? 3.0 years, 29 males) were included. No significant differences were observed between the patients with CD and UC, in age at diagnosis, age at DXA scan and disease duration. The mean TBS of patients with CD (n = 35) was lower than of patients with UC (n =15): 1.340 ? 0.080 vs 1.395 ? 0.092, p = 0.040. The mean TBS Z-score of patients with CD, -0.443 ? 0.788, was significantly lower than expected in healthy children (p = 0.002), while the mean TBS Zscore of patients with UC, 0.231 ? 0.685, was similar to that of healthy children (p = 0.212). In the stepwise linear regression analysis, BMI Z-score at diagnosis, phosphorus level at diagnosis and age at the time of the DXA scan were significant independent predictors of TBS (r2 = 0.604;0 = 0.037, 95% confidence interval (CI) for 0 0.022-0.051, p < 0.001;0= 0.045, 95% CI: 0.017-0.073, p = 0.002;and 0= 0.031, 95% CI: 0.005-0.021, p < 0.002, respectively). Conclusions: TBS is significantly reduced in pediatric patients with CD but not in patients with UC. This finding likely reflects the effect of CD on bone microarchitecture.

关键词： Inflammatory bowel disease   Ulcerative colitis   Crohn disease   PET   Computed tomography   PET/CT   FDG   MR imaging  

摘要： FDG-PET/CT has potential in inflammatory bowel disease. The literature generally presents good sensitivity and specificity in various settings. At present, the most promising roles are assessment of early treatment response and stricture characterization, whereas general use in the initial diagnostic workup should be reserved for equivocal cases for the time being. However, it is challenging to image the moving and physiologically active bowel with FDG, and available literature is far from ideal. Thus, several issues remain unclarified, and further data are needed to make firm conclusions on the role of FDG and PET/CT in inflammatory bowel disease.