BACKGROUND: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN. METHODS: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing. RESULTS: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi. CONCLUSIONS: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.

• MeSH
• Crohnova nemoc * terapie   mikrobiologie   imunologie   MeSH
• dítě MeSH
• enterální výživa * metody   MeSH
• feces * mikrobiologie   chemie   MeSH
• leukocytární L1-antigenní komplex * analýza   MeSH
• leukocyty mononukleární imunologie   metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• střevní mikroflóra * MeSH
• TNF-alfa * metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIMS: We sought to define the prevalence and to characterize possible predictive factors of Crohn's disease (CD) occurring in children with ulcerative colitis (UC) after ileal pouch-anal anastomosis (IPAA). METHODS: This was a multicenter, retrospective study including 15 centers of the Porto IBD group of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Children with a confirmed diagnosis of UC undergoing colectomy with IPAA and a minimal follow up of 6 months were identified. The following data were collected: demographic data; endoscopic and histologic data; disease activity; laboratory exams; therapeutic history; indication for surgery, type, and timing; and IPAA functional outcomes and complications. In de novo CD cases, time of diagnosis, phenotype, location, and therapies were gathered. RESULTS: We identified 111 UC children undergoing IPAA from January 2008 to June 2018 (median age at colectomy: 13 years; age range: 1-18 years; female/male: 59/52). The median time from diagnosis to colectomy was 16 (range, 0-202) months. At the last follow-up, 40 (36%) of 111 children developed pouchitis. The criteria for de novo CD were met in 19(17.1%) of 111 children with a 25-month median (range, 3-61 months). At last follow-up, 12 (63.1%) of 19 were treated with biologics and in 5 (26.3%) of 19 children, the pouch was replaced with definitive ileostomy. In a multivariable logistic regression model, decreased preoperative body mass index z scores (odds ratio, 2.2; 95% confidence interval, 1.1-4.4; P = .01) resulted as the only variable associated with CD development. CONCLUSIONS: Children with UC undergoing IPAA carry a high risk of developing subsequent CD. De novo CD cases showed decreased preoperative body mass index z scores, identifying a poor nutritional status as a possible predictive factor.

• MeSH
• Crohnova nemoc * chirurgie   MeSH
• dítě MeSH
• kojenec MeSH
• kolektomie škodlivé účinky   MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• pooperační komplikace etiologie   epidemiologie   MeSH
• pouchitis * etiologie   epidemiologie   MeSH
• předškolní dítě MeSH
• proktokolektomie rekonstrukční * škodlivé účinky   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• ulcerózní kolitida * chirurgie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

• MeSH
• dospělí MeSH
• indukce remise MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• kolektomie MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• piperidiny * terapeutické užití   MeSH
• pyrimidiny * terapeutické užití   MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• ulcerózní kolitida * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease 2019 (COVID-19); thus, data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414, and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and magnitude of seroconversion, assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD. METHODS: The study included 602 IBD patients and 168 immunocompetent health care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination and 8 weeks after the vaccination. RESULTS: Of IBD patients, 82.2% were receiving biological treatment: most of them were treated with antitumor necrosis factor (TNF)-α inhibitors (48.5%), and just under half of them were treated with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The postvaccine seropositivity rate among IBD patients and controls was 97.8% vs 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared with 2 other vaccines (P < .0001) and control ChAdOx1 nCoV-19 recipients (P = .01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. The TNF-α inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with a lower postvaccination antibody response (P < .0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and 8 weeks after its completion. CONCLUSIONS: Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNF-α inhibitors with concomitant immunomodulators and show the priority of mRNA vaccines in this specific group of patients.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• ChAdOx1 nCoV-19 MeSH
• COVID-19 * prevence a kontrola   MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• imunoglobulin G MeSH
• leukocytární L1-antigenní komplex MeSH
• lidé MeSH
• methotrexát MeSH
• prospektivní studie MeSH
• protilátky virové MeSH
• SARS-CoV-2 MeSH
• TNF-alfa metabolismus   MeSH
• tvorba protilátek MeSH
• ustekinumab MeSH
• vakcína BNT162 MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Vaccine-preventable diseases and opportunistic infections in pediatric inflammatory bowel disease (IBD) are increasingly recognized issues. The aims of this study were to evaluate vaccinations, immunization status, and consequent therapeutic management in children with IBD and to analyze the differences among patients diagnosed before (Group 1) and after June 2012 (Group 2). METHODS: This was a multicenter, retrospective cohort investigation. Between July 2016 and July 2017, 430 children with IBD were enrolled in 13 centers. Diagnosis, therapeutic history, vaccinations, and immunization status screening at diagnosis and at immunosuppressant (IM)/biologic initiation and reasons for incomplete immunization were retrieved. RESULTS: Vaccination rates at diagnosis were unsatisfactory for measles, mumps, and rubella (89.3%), Haemophilus influenzae (81.9%), meningococcus C (23.5%), chickenpox (18.4%), pneumococcus (18.6%), papillomavirus (5.9%), and rotavirus (1.9%). Complete immunization was recorded in 38/430 (8.8%) children, but specific vaccines were recommended in 79/430 patients (18.6%), without differences between the 2 groups. At IM start, 22% of children were tested for Epstein-Barr virus (EBV) status, with 96.2% of EBV-naïve patients starting azathioprine, without differences between Groups 1 and 2. Screening for latent tuberculosis (TB) before start of biologics was performed in 175/190 (92.1%), with up to 9 different screening strategies and numerous inconsistencies. CONCLUSIONS: We demonstrated a poor immunization status at diagnosis in children with IBD, which was not followed by proper vaccination catch-up. EBV status before IM initiation and latent TB before biologics were not adequately assessed. Thus, the overall impact of the current guidelines seems unsatisfactory.

• MeSH
• Crohnova nemoc farmakoterapie   imunologie   MeSH
• dítě MeSH
• dodržování směrnic MeSH
• idiopatické střevní záněty farmakoterapie   imunologie   MeSH
• imunosupresiva škodlivé účinky   MeSH
• infekce virem Epsteina-Barrové prevence a kontrola   MeSH
• latentní tuberkulóza prevence a kontrola   MeSH
• lidé MeSH
• Mycobacterium tuberculosis MeSH
• očkovací schéma MeSH
• oportunní infekce imunologie   prevence a kontrola   MeSH
• retrospektivní studie MeSH
• ulcerózní kolitida farmakoterapie   imunologie   MeSH
• vakcinace normy   statistika a číselné údaje   MeSH
• virus Epsteinův-Barrové MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Prevalence of inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gut, has been on the rise in recent years-not only in the adult population but also especially in pediatric patients. Despite the absence of curative treatments, current therapeutic options are able to achieve long-term remission in a significant proportion of cases. To this end, however, there is a need for biomarkers enabling accurate diagnosis, prognosis, and prediction of response to therapies to facilitate a more individualized approach to pediatric IBD patients. In recent years, evidence has continued to evolve concerning noncoding RNAs (ncRNAs) and their roles as integral factors in key immune-related cellular pathways. Specific deregulation patterns of ncRNAs have been linked to pathogenesis of various diseases, including pediatric IBD. In this article, we provide an overview of current knowledge on ncRNAs, their altered expression profiles in pediatric IBD patients, and how these are emerging as potentially valuable clinical biomarkers as we enter an era of personalized medicine.

• MeSH
• biologické markery analýza   MeSH
• Crohnova nemoc genetika   MeSH
• dítě MeSH
• genetické markery genetika   MeSH
• idiopatické střevní záněty genetika   MeSH
• individualizovaná medicína trendy   MeSH
• lidé MeSH
• nekódující RNA analýza   MeSH
• signální transdukce genetika   MeSH
• transkriptom MeSH
• ulcerózní kolitida genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• úvodní články MeSH

BACKGROUND: Evidence of the impact of in utero exposure to anti-tumor necrosis factor (TNF)-alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers' inflammatory bowel disease (IBD) on long-term postnatal development of exposed children. METHODS: We included consecutive children (≥12 months of age) born to mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians' offices. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefined questionnaire. RESULTS: Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no significant difference in infectious complications within the first year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosuppressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the first year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98). CONCLUSIONS: Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women.

• MeSH
• adalimumab aplikace a dávkování   MeSH
• dítě MeSH
• gastrointestinální látky aplikace a dávkování   MeSH
• idiopatické střevní záněty farmakoterapie   imunologie   MeSH
• infliximab aplikace a dávkování   MeSH
• kohortové studie MeSH
• kojenec MeSH
• komplikace těhotenství diagnóza   farmakoterapie   imunologie   MeSH
• lidé MeSH
• matky MeSH
• následné studie MeSH
• předškolní dítě MeSH
• prognóza MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• zpožděný efekt prenatální expozice farmakoterapie   imunologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Background: Extraintestinal manifestations (EIM) have been associated with more severe course of inflammatory bowel disease. The aim was to study the frequency of EIM in pediatric- and elderly-onset Crohn's disease (CD) and the factors associated with EIM and their impact on long-term disease outcome. Methods: Pediatric- (age at diagnosis younger than 17 years) and elderly-onset CD patients (age at diagnosis 60 years or older) from a prospective population-based registry (EPIMAD) were recruited. Data on EIM and clinical factors at diagnosis and at maximal follow-up were collected. Results: We included 535 pediatric- and 370 elderly-onset patients (median age 14.5 and 69.9 years; median follow-up 11.1 and 5.9 years). Extraintestinal manifestations presented in 23.5% of childhood-onset and 4.9% of elderly-onset individuals at diagnosis, while in 29.8% and 5.9% of patients, EIM developed newly during the follow-up (hazard ration [HR] 4.4, 95% CI, 2.7-7.0, P < 0.001). The most frequently involved organ in both age cohorts, either at diagnosis or during disease course, were joints (pediatric: 11.2% and 22.6%; elderly: 3.2% and 3.5%, respectively) followed by skin (pediatric: 15.9% and 13.6%; elderly: 2.7% and 2.7%, respectively). Extraintestinal manifestations at diagnosis were associated with increased risk for corticosteroids (HR 1.42, 95% CI, 1.14-1.78 and HR 3.38, 95% CI, 1.88-6.08) and immunosuppressive therapy (HR 1.30, 95% CI, 1.02-1.65 and HR 4.24, 95% CI, 1.91-9.42), in both age populations. Conclusions: Extraintestinal manifestations occurred at lower frequency in elderly-onset compared with pediatric-onset patients. In both age populations, presence of EIM at diagnosis independently increased the need for corticosteroid and immunosuppressive treatment.

• MeSH
• Crohnova nemoc diagnóza   farmakoterapie   epidemiologie   MeSH
• dítě MeSH
• incidence MeSH
• kožní nemoci patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• nemoci kloubů patofyziologie   MeSH
• oční nemoci patofyziologie   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Francie MeSH

BACKGROUND: The outcome of patients with Crohn's disease who failed anti-tumor necrosis factor alpha (anti-TNFα) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNFα agent postoperatively. METHODS: Pediatric patients with Crohn's disease who underwent intestinal resection and were treated with anti-TNFα agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNFα pharmacodynamic failure and those with no preoperative anti-TNFα treatment. RESULTS: A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNFα initiation was 8 months (interquartile range 4-14 months). At the time of postoperative anti-TNFα initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNFα treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNFα treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNFα treatment. CONCLUSIONS: Pediatric patients with Crohn's disease who failed anti-TNFα therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNFα naive patients.

• MeSH
• Crohnova nemoc terapie   MeSH
• gastrointestinální látky aplikace a dávkování   MeSH
• indukce remise metody   MeSH
• kolektomie metody   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• mladiství MeSH
• pooperační období MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Inflammatory bowel diseases (IBD) are associated with altered bone health and increased risk for fractures. Vitamin D deficiency is frequently found in IBD; however, the effect of vitamin D supplementation on bone health of children with IBD is poorly understood. We aimed to observe the changes in volumetric bone density and dynamic muscle functions after vitamin D substitution in a cohort of pediatric patients with IBD. METHODS: This was a prospective observational study of 55 patients (aged 5-19 years) with IBD. Bone quality was assessed using peripheral quantitative computed tomography and muscle functions by jumping mechanography at baseline and after a median of 13.8 (interquartile range, 12.0-16.0) months of daily substitution of 2000 IU of cholecalciferol. RESULTS: Median serum levels of 25-hydroxyvitamin D increased from 58 nmol/L at the baseline visit to 85 nmol/L at the last follow-up visit (P < 0.001); no signs of overdose were reported. The Z-scores of trabecular bone mineral density, cortical bone cross-sectional area, and maximal muscle power improved significantly during the follow-up period (+0.5, P = 0.001, +0.3, P = 0.002 and +0.5, P = 0.002, respectively). Cholecalciferol substitution was positively associated with trabecular bone mineral density and maximal muscle power (estimates 0.26, 95% confidence interval 0.14-0.37, P < 0.0001 and 0.60, 95% confidence interval 0.32-0.85, P < 0.0001, respectively) but not with the Strength-Strain Index or maximal muscle force (Fmax). CONCLUSIONS: We observed an improvement in bone and muscle parameters after cholecalciferol substitution in pediatric patients with IBD. Therefore, vitamin D substitution can be considered in such patients.

• MeSH
• cholekalciferol aplikace a dávkování   MeSH
• dítě MeSH
• idiopatické střevní záněty patofyziologie   terapie   MeSH
• inhibitory kostní resorpce aplikace a dávkování   MeSH
• kostní denzita účinky léků   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• potravní doplňky * MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• svalová síla účinky léků   MeSH
• trabekulární kostní tkáň účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH