关键词： Inflammatory bowel diseases   Infliximab   ANTI-TNFα   Lymphoma   Adolescent   Young adult  

摘要： Background Inflammatory bowel diseases (IBD) are often treated with anti-tumor necrosis factor alpha (anti-TNF alpha) medications. Concomitant treatment of IBD with anti-TNF alpha agents and immunomodulators appears to be associated with an increased risk for lymphoma. Methods Patients who developed lymphoma while on monotherapy with an anti-TNF alpha agent were identified at three centers. Institutional Review Board approval was obtained. Results Five adolescents and young adult patients with pediatric-onset IBD who were treated with infliximab (IFX) without exposure to thiopurines were subsequently diagnosed with lymphoma. Three of the five patients had bone involvement at presentation. Epstein-Barr virus was positive in 2 cases. Median time from diagnosis of IBD and exposure to IFX prior to diagnosis of lymphoma was 5 and 4.3 years, respectively. Conclusions This case series reports long-term follow-up for young patients with IBD who were treated with IFX monotherapy and developed lymphoma. Three of the five patients had bone involvement. In general, the risk of lymphoma following exposure to anti-TNF alpha medications alone remains low, but the incidence of primary bone lymphomas in IBD has not been reported. Studies examining longer exposure times may be needed to determine the true lymphoma risk in patients treated with IFX monotherapy.

关键词： Biological Agents   Crohn's Disease   Pregnancy Outcome   Ulcerative Colitis  

摘要： BACKGROUND & AIMS: Biologics are used routinely in pregnant women with inflammatory bowel disease (IBD), but large-scale data reporting adverse pregnancy outcomes among biologic users are lacking. We sought to estimate the prevalence of adverse pregnancy outcomes in women with IBD on biologic therapies. METHODS: We searched major databases from inception to June 2020 for studies estimating the prevalence of adverse pregnancy outcomes in IBD when using biologics (anti-tumor necrosis factor [TNF], anti-integrins, and anticytokines). Prevalence and relative risk (RR) were pooled using a random-effects model. RESULTS: Forty-eight studies were included in the meta-analysis comprising 6963 patients. Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% (95% CI, 6%-10%;I-2 = 87.4%) for early pregnancy loss, 9% (95% CI, 7%-11%;I-2 = 89.9%) for preterm birth, 0% (95% CI, 0%-0%;I-2 = 0%) for stillbirth, 8% (95% CI, 5%-10%;I-2 = 87.0%) for low birth weight, and 1% (95% CI, 1%-2%;I-2 = 78.3%) for congenital malformations. These rates are comparable with those published in the general population. In subgroup analyses of a small number of studies, the prevalence of early pregnancy loss and preterm birth were higher in vedolizumab vs anti-TNF users. Meta-regression did not show an association of disease activity or concomitant thiopurine on adverse outcomes. Continued TNF inhibitor use during the third trimester was not associated with risk of preterm birth (RR, 1.41;95% CI, 0.77-2.60;I-2 = 0%), low birth weight (RR, 1.32;95% CI, 0.80-2.18;I-2 = 0%), or congenital malformations (RR, 1.28;95% CI, 0.47-3.49;I-2 = 0%). CONCLUSIONS: Adverse pregnancy outcomes among pregnant IBD women using biologics are comparable with that of the general population.

关键词： hypoxia-inducible factor-1 alpha (HIF-1 alpha)   immune cell   inflammatory bowel disease (IBD)   intestinal epithelial cell (IEC)  

摘要： Inflammatory bowel disease (IBD) develops as a result of a combination of genetic predisposition, dysbiosis of the gut microbiota, and environmental influences, which is mainly represented by ulcerative colitis (UC) and Crohn's disease (CD). IBDs can result in inflammatory hypoxia by causing intestinal inflammation and vascular damage. The hypoxia-inducible factor 1-alpha (HIF-1 alpha), as a transcription factor, can regulate the cellular adaptation to low oxygen levels and support the development and function of the gut barrier. HIF-alpha plays its functions through translocating into the nucleus, dimerizing with HIF-1 beta, and binding to hypoxia-responsive elements of HIF-1 target genes. So far, most studies have addressed the function of HIF-1 alpha in murine models of IBD. In this review, we aim to outline the major roles of HIF-1 alpha in the IBD.

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

摘要： In recent years, therapeutic agents affecting the immune system have been largely implemented in the treatment of various hematological, rheumatological and dermatological disorders. Their clinical use has offered important benefits for affected patients and has also ameliorated clinical outcome and prognosis in many cases. Nonetheless, as any treatment, the use of these drugs may be associated with side effects. One of the target organs in such cases is the gastrointestinal tract. In particular, the exacerbation or the onset of inflammatory bowel disease (IBD) in treated patients is not infrequent, although the mechanism of action of these agents may be different. In this review we will focus on the use of therapeutic agents affecting the immune system and the development or exacerbation of IBD, with a mention on the possible underlying pathogenetic mechanisms.

关键词： adult   enteral nutrition   inflammatory bowel disease   minerals   trace elements   parenteral nutrition   vitamins   weight loss  

摘要： Background Very early-onset inflammatory bowel disease (VEO-IBD) secondary to interleukin 10 receptor A (IL-10RA) mutations has aggressive disease courses with increased nutrition needs compared with those in other monogenic forms of IBD. Presentation A male patient was hospitalized when he was 18 days old for bloody diarrhea, which was diagnosed as Crohn's disease at 6 months old. He showed failure to thrive (FTT) and worsening inflammation while receiving enteral nutrition (EN) and standard IBD treatment. He was hospitalized in 2016, at 28 years old, for a Crohn's flare when sequencing confirmed a heterozygous mutation in IL10-RA. His weight and plasma micronutrient levels improved when he transitioned to parenteral nutrition (PN). He was initiated on anakinra while awaiting hematopoietic stem cell transplant, with substantial decrease in inflammation. He was able to gain weight, initiate an oral diet, and decrease his PN requirement. Conclusion Our patient experienced progressive FTT while receiving EN. VEO-IBD incidence is rising, and its diagnosis is often delayed. Therefore, prompt recognition with treatment initiation is essential to improving nutrition outcomes in this patient population. Further investigation is warranted to determine whether these patients would benefit from early initiation of PN.

关键词： Thiopurines   Pediatrics   Inflammatory bowel disease   Adverse events   Metabolites  

摘要： Background In the recent era of growing availability of biological agents, the role of thiopurines needs to be reassessed with the focus on toxicity. Aims We assessed the incidence and predictive factors of thiopurine-induced adverse events (AE) resulting in therapy cessation in pediatric inflammatory bowel disease (IBD), related to thiopurine metabolites and biochemical abnormalities, and determined overall drug survival. Methods We performed a retrospective, single-center study of children diagnosed with IBD between 2000 and 2019 and treated with thiopurine therapy. The incidence of AE and overall drug survival of thiopurines were evaluated using the Kaplan-Meier method. Correlations between thiopurine metabolites and biochemical tests were computed using Spearman's correlation coefficient. Results Of 391 patients with IBD, 233 patients (162 Crohn's disease, 62 ulcerative colitis, and 9 IBD-unclassified) were prescribed thiopurines (230 azathioprine and 3 mercaptopurine), of whom 50 patients (22%) discontinued treatment, at least temporary, due to thiopurine-induced AE (median follow-up 20.7 months). Twenty-six patients (52%) were rechallenged and 18 of them (70%) tolerated this. Sixteen patients (6%) switched to a second thiopurine agent after azathioprine intolerance and 10 of them (63%) tolerated this. No predictive factors for development of AE could be identified. Concentrations of 6-thioguanine nucleotides (6-TGN) were significantly correlated with white blood cell and neutrophil count, 6-methylmercaptopurine (6-MMP) concentrations with alanine aminotransferase and gamma-glutamyltranspeptidase. Conclusions Approximately 20% of pediatric patients with IBD discontinued thiopurine treatment due to AE. A rechallenge or switch to mercaptopurine is an effective strategy after development of AE. Concentrations of 6-TGN and 6-MMP are associated with biochemical abnormalities.

关键词： adalimumab   antibodies   anti-TNF   immunomodulators   infliximab  

摘要： Background: Evidence regarding the risk of immunogenicity in patients with inflammatory bowel disease (IBD) who switched anti-tumor necrosis factor alpha (anti-TNF alpha) therapies to a subsequent anti-TNF alpha (either infliximab or adalimumab) is conflicting. We aimed to assess the risk of consecutive immunogenicity to anti-TNF alpha in a large cohort of patients. Methods: This was a multicenter retrospective study. Medical records of adult and pediatric IBD switchers who had pharmacokinetic data for both agents between 2014 and 2020 were retrieved. Data including age, sex, disease type, duration of therapies, and concomitant use of immunomodulators (IMMs) were recorded. Results: Overall, 164 patients were included [52% female;88% Crohn's disease;mean age = 24.4 +/- 14.6 years;108 (66%) switched from infliximab to adalimumab and 56 (34%) vice versa];120 (73.1%) patients switched due to an immunogenic failure. Among patients switching therapy from infliximab to adalimumab due to an immunogenic failure immunogenicity to infliximab was significantly associated with consecutive immunogenicity to adalimumab (p = 0.026). Forthy four out of 120 patients (36.6%) with an immunogenic failure to the first anti-TNF alpha started an IMM with the second anti-TNF alpha. This combination with IMM was not associated with reduction of consecutive immunogenicity (p = 0.31), but it was associated with longer drug retention (p = 0.007). Multivariate analysis demonstrated that older age at second anti-TNF alpha, adjusted to the chronology of therapy and sex, was associated with increased immunogenicity to the second anti-TNF alpha. Conclusion: Patients with IBD who switch from infliximab to adalimumab following an immunogenic failure are at increased risk for consecutive immunogenicity to adalimumab. IMM use after a switch prolongs drug retention.

关键词： Gastroenterology   Hepatology   Oncology   Transplant Surgery   Biochemistry   general  

关键词： Gastroenterology   Hepatology   Oncology   Transplant Surgery   Biochemistry   general