BACKGROUND AND AIMS: Ileocaecal resection (ICR) is frequent in paediatric patients with Crohn's disease (pCD). Despite rates of reoperation being low, the risk of clinical or endoscopic post-operative recurrence (POR) is high; effective medical strategies to prevent POR are thus needed. The aim of this systematic review (SR) was to identify and evaluate the published literature on post-operative medical prevention of POR in pCD to draft a possible therapy guide for pCD patients undergoing ICR. METHODS: We performed an SR according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and registered it in the PROSPERO database (ID: CRD42024533855). The population, intervention, control, outcome (PICO) model was focussed on post-surgical medical prevention of POR in pCD with clearly expressed definition of recurrence (endoscopically using a standardized scoring system (e.g. Rutgeerts score) or by laboratory markers, for example, faecal calprotectin (F-CPT), C-reactive protein (CRP) or by histological findings or by clinical activity indexes [e.g. weighted paediatric Crohn's disease activity index - (w)PCDAI]. From inception until 29 February 2024, the following databases were searched: PubMed/MEDLINE, Scopus/Embase, Web of Sciences, Evidence-Based Medicine Reviews (including Cochrane), Cochrane Central Registrar of controlled Trials (CENTRAL), ClinicalTrials.gov and EudraCT. Retrieved articles were evaluated for eligibility and finally selected publications for risk of bias using ROBINS-I tool. RESULTS: Out of 811 publications identified by the search, only 5 fulfilled inclusion criteria of the SR. None of the studies fully answered our PICO question. The studies were overall of poor quality and the heterogeneity of the data did not allow us to perform meta-analysis, detailed statistical analysis or formal synthesis of data. Adverse events of post-operative medication were not described in any of the included studies. Existing guidelines of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), North American Society for Paediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), European Crohn's and Colitis Organisation (ECCO) and American Gastroenterological Association (AGA) were reviewed and paediatric therapy guide for pCD undergoing ICR was drafted with respect to recent SRs and meta-analyses in adult population and including scarce paediatric data identified by our SR. As pCD patients undergoing ICR are a high-risk population, they should not be left untreated post-operatively. Anti-tumour necrosis factor (anti-TNF) drugs should be considered as first-line therapy in the majority of patients. Non-anti-TNF biologics should be considered in case of anti-TNF failure. Regular endoscopic monitoring starting at 6 months after the surgery and supported by regular F-CPT evaluation should be used to identify early endoscopic recurrence and to escalate the treatment. CONCLUSION: Our SR revealed that there is wide variability in treatment strategies in children, and high-quality data are generally lacking. At the moment, paediatric prophylaxis of POR should be guided by available adult evidence with respect to the high-risk nature of pCD. Extensive research in pCD should be encouraged.

• MeSH
• cékum chirurgie   MeSH
• Crohnova nemoc * chirurgie   prevence a kontrola   MeSH
• dítě MeSH
• ileum chirurgie   MeSH
• lidé MeSH
• pooperační komplikace prevence a kontrola   MeSH
• recidiva * MeSH
• sekundární prevence metody   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

BACKGROUND: The duration of remission has been shown to be longer in patients initially treated with exclusive enteral nutrition (EEN) compared to corticosteroids (CS). However, no published studies required concurrent immunomodulator [6-mercaptopurine or azathioprine (AZA)] use at the time of diagnosis. AIMS: The aims of this retrospective study were to compare the duration of remission between patients initially treated with AZA in combination with CS or EEN and identify predictors of early relapse in these patients. METHODS: Data from 65 newly diagnosed children with CD in clinical remission on either EEN or CS and commencing AZA at diagnosis were included. We compared duration of remission using physician global assessment and carried out Cox regression analysis to identify predictors of early relapse. Patients were followed up to the time of first relapse or for at least 12 months. RESULTS: There were no differences in the duration of remission between patients initially treated with EEN or CS (p = 0.978). We identified younger age at diagnosis [hazard ratio (HR) 0.87, 95 CI 0.78-0.98, p = 0.016], lower height Z score at diagnosis (HR 0.61, 95 CI 0.44-0.85, p = 0.003), involvement of the upper gastrointestinal tract (HR 2.69, 95 CI 1.27-5.66, p = 0.009), and elevated platelet count at remission (HR 1.004, 95 CI 1.001-1.008, p = 0.021) as independent predictors of early relapse. CONCLUSIONS: Neither induction regime demonstrated longer duration of remission of CD in patients treated with immunomodulators since the time of diagnosis.

• Klíčová slova
• Corticosteroids, Crohn’s disease, Exclusive enteral nutrition, Follow-up, Immunosuppressive therapy, azathioprine,
• MeSH
• azathioprin aplikace a dávkování   terapeutické užití   MeSH
• Crohnova nemoc dietoterapie   farmakoterapie   MeSH
• dítě MeSH
• enterální výživa * MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azathioprin MeSH
• hormony kůry nadledvin MeSH
• imunosupresiva MeSH

Infliximab, monoclonal antibody against tumor necrosis factor alpha, is an effective agent in the therapy of Crohn's disease. Although therapy with infliximab is generally well tolerated, there is an obvious concern about the effect of this treatment on the incidence of cancer. We report a case of mucinous anorectal adenocarcinoma observed in a 39-year-old patient with long-standing Crohn's disease after therapy with two courses of infliximab. The carcinoma was discovered fortuitously after abdominoperineal resection. Despite clear margins, the tumor recurred in a few months and progressed during combination chemotherapy. Although there is currently no definitive proof of a causal link between infliximab therapy and cancer, the present observation and other reports in the literature should lead to a careful evaluation of the possibility of increased cancer risk in patients treated with this new agent.

• MeSH
• adenokarcinom chemicky indukované   patologie   chirurgie   MeSH
• Crohnova nemoc farmakoterapie   MeSH
• dospělí MeSH
• infliximab MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• nádory rekta chemicky indukované   patologie   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• infliximab MeSH
• monoklonální protilátky MeSH

BACKGROUND AND AIMS: Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA]. METHODS: Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab. RESULTS: We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test. CONCLUSIONS: Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

• Klíčová slova
• Crohn’s disease, IBD, anti-TNF, children, metabolomics, microbiome,
• MeSH
• Bacteria MeSH
• Crohnova nemoc * patologie   MeSH
• dítě MeSH
• infliximab farmakologie   terapeutické užití   MeSH
• inhibitory TNF farmakologie   terapeutické užití   MeSH
• lidé MeSH
• metabolom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• infliximab MeSH
• inhibitory TNF MeSH

OBJECTIVE: Crohn's disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy. MATERIAL AND METHODS: A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy. RESULTS: Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn's Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test). CONCLUSIONS: This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.

• MeSH
• autonomní nervový systém MeSH
• biologická terapie MeSH
• Crohnova nemoc * farmakoterapie   epidemiologie   komplikace   MeSH
• lidé MeSH
• nemoci autonomního nervového systému * MeSH
• nemoci periferního nervového systému * MeSH
• TNF-alfa terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• TNF-alfa MeSH

BACKGROUND: In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. SUMMARY: Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.

• Klíčová slova
• Anti-tumour necrosis factor, Antibodies to infliximab, Biological therapy, Infliximab levels, Paediatric,
• MeSH
• biologické markery metabolismus   MeSH
• C-reaktivní protein metabolismus   MeSH
• Crohnova nemoc krev   farmakoterapie   MeSH
• dítě MeSH
• feces chemie   MeSH
• indukce remise MeSH
• infliximab aplikace a dávkování   terapeutické užití   MeSH
• krevní sedimentace MeSH
• leukocytární L1-antigenní komplex metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• plocha pod křivkou MeSH
• ROC křivka MeSH
• terapie neúspěšná MeSH
• zánět patologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• biologické markery MeSH
• C-reaktivní protein MeSH
• infliximab MeSH
• leukocytární L1-antigenní komplex MeSH

BACKGROUND: The additional value of azathioprine concomitant treatment on infliximab pharmacokinetics in children is not well described yet. AIMS: In the present study, we aimed to describe the relationship between thiopurine metabolite levels, infliximab trough levels, anti-IFX antibody formation, and clinical and laboratory markers of disease activity in pediatric patients with Crohn's disease, and to assess non-adherence. METHODS: Data were collected prospectively during repeated visits from pediatric patients followed for Crohn's disease in two Czech pediatric inflammatory bowel disease centers between January 2016 and June 2017. Thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine) were measured by high-performance liquid chromatography. Infliximab trough levels and anti-IFX antibody serum levels were measured routinely by ELISA. The risk of loss of response to infliximab therapy was also assessed. RESULTS: A significant association between infliximab serum levels and 6-thioguanine erythrocyte levels was observed when tested as categorical variables (63 patients, 321 observations). To predict infliximab levels > 5 µg/mL, we propose a 6-thioguanine cutoff of 278 pmol/8 × 108 erythrocytes (sensitivity, 0.799; specificity, 0.347). A higher loss-of-response-to-infliximab rate (tested in a subgroup of 51 patients) was observed in patients with undetectable 6-thioguanine levels than in those with detectable levels (p = 0.026). Non-adherence to azathioprine therapy was suspected in 20% of patients. CONCLUSION: Thiopurine metabolite monitoring in pediatric patients with Crohn's disease is useful when optimizing combination therapy. Pediatric patients with undetectable 6-thioguanine levels are more likely to lose response to infliximab therapy. When targeting optimal infliximab levels, the 6-thioguanine cutoff levels in children appear to be higher than in adults.

• MeSH
• azathioprin terapeutické užití   MeSH
• biologické markery MeSH
• Crohnova nemoc farmakoterapie   MeSH
• dítě MeSH
• imunologické faktory terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• longitudinální studie MeSH
• merkaptopurin analogy a deriváty   analýza   MeSH
• mladiství MeSH
• prospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Názvy látek
• 6-methylthiopurine MeSH Prohlížeč
• azathioprin MeSH
• biologické markery MeSH
• imunologické faktory MeSH
• infliximab MeSH
• merkaptopurin MeSH

Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

• Klíčová slova
• Crohn's disease, Guidelines, Medical therapy, Pediatric,
• MeSH
• adalimumab MeSH
• algoritmy MeSH
• antibakteriální látky terapeutické užití   MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• azathioprin terapeutické užití   MeSH
• Crohnova nemoc terapie   MeSH
• dítě MeSH
• enterální výživa * MeSH
• hormony kůry nadledvin škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• indukce remise metody   MeSH
• infliximab MeSH
• kyseliny aminosalicylové terapeutické užití   MeSH
• lidé MeSH
• merkaptopurin terapeutické užití   MeSH
• methotrexát terapeutické užití   MeSH
• mladiství MeSH
• monoklonální protilátky terapeutické užití   MeSH
• thalidomid terapeutické užití   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• udržovací chemoterapie metody   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• Názvy látek
• adalimumab MeSH
• antibakteriální látky MeSH
• antiflogistika nesteroidní MeSH
• azathioprin MeSH
• hormony kůry nadledvin MeSH
• humanizované monoklonální protilátky MeSH
• imunosupresiva MeSH
• infliximab MeSH
• kyseliny aminosalicylové MeSH
• merkaptopurin MeSH
• methotrexát MeSH
• monoklonální protilátky MeSH
• thalidomid MeSH
• TNF-alfa MeSH

The rise of fistulae in Crohn's disease has been classed with the disorder complications, although it is a possible component of natural development of the so-called A type (De Dombal classification) or aggressive-perforating type (Greenstein's classification) of this idiopathic intestinal inflammation. Fistulae are accompanying colic localization of Crohn's disease in 20%, ileocolic affection in 40%, where 35% of them are perianal fistulae, and about 34% entero-enteral or entero-cutaneous ones. Other complications (urogenital tract, biliary tract) are mentioned infrequently in literature. Besides surgical approaches in the therapy, dominant post in the conservative area is taken up by an antitumor necrotizing factor, antibiotics and immunosuppressives whose position is, however, the most problematic although the literature references about the effectiveness of azathioprine, 6-mercaptopurine, cyclosporine, tacrolime and methotrexate have had nearly 25-years tradition. The authors present their own experience with applying a combination of cyclosporine, azathioprine in the treatment of perianal fistulae in a set of 21 patients from the period of 1995-2000. In their opinion, the therapy success is limited especially by early starting the treatment (11 cases of effective therapy) and choosing a resolute method that is, according to them, sequential immunosuppression. (Tab. 2, Ref. 32.)

• MeSH
• azathioprin terapeutické užití   MeSH
• Crohnova nemoc komplikace   farmakoterapie   MeSH
• cyklosporin aplikace a dávkování   MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• kožní píštěl komplikace   farmakoterapie   MeSH
• lidé MeSH
• střevní píštěle komplikace   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• azathioprin MeSH
• cyklosporin MeSH
• imunosupresiva MeSH

• MeSH
• Crohnova nemoc komplikace   farmakoterapie   MeSH
• dospělí MeSH
• hormony kůry nadledvin škodlivé účinky   MeSH
• kosti a kostní tkáň metabolismus   MeSH
• lidé MeSH
• metabolické nemoci kostí etiologie   prevence a kontrola   MeSH
• minerály metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormony kůry nadledvin MeSH
• minerály MeSH