Preventing Recurrence of Crohn's Disease Post-Ileocaecal Surgery in Paediatric Patients: A Therapy Guide Based on Systematic Review of the Evidence.

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.

Infant formulas for the treatment of functional gastrointestinal disorders: A position paper of the ESPGHAN Nutrition Committee.

Functional gastrointestinal disorders (FGID), such as infant regurgitation, infant colic, and functional constipation, are common and typically physiological phenomena during the early months of an infant's life and account for frequent consultations with pediatricians. Various infant formulas are marketed for their management and are frequently given by parents to infants before a medical consultation. However, the evidence supporting their effectiveness is limited and some have altered nutritional compositions when compared to standard formulas. Thus, these products should only be used under medical supervision and upon medical advice. Marketing and over-the-counter sales do not ensure proper medical guidance and supervision. The aim of this position paper is to review the current evidence regarding the safety and efficacy of formulas specifically formulated for addressing regurgitation, colic, and constipation, recognized as FGID. The objective is to provide guidance for clinical management based on the highest quality of available evidence. A wide search using Pubmed, MEDLINE, EMBASE and Cochrane Database of Systematic Reviews was performed including the MESH terms infant formula, colic, constipation, regurgitation, reflux, palmitate, lactase, lactose, magnesium, hydrolyzed protein, prebiotics or probiotics. 752 papers were identified and screened. Finally, 72 papers were included in the paper. In the absence of evidence, recommendations reflect the authors' combined expert opinion. Final consensus was obtained by multiple e-mail exchange and meetings of the Nutrition Committee. (1) For breastfed infants experiencing FGID such as regurgitation, colic, or constipation, transitioning from breastfeeding to commercial formulas is not recommended. (2) In general, whether an infant is breastfed or formula-fed, it's crucial to reassure parents that FGIDs are normal and typically do not necessitate treatment or change to a special formula. (3) Thickened formulas, often termed anti-reflux formulas, may be considered in specific cases of regurgitation. (4) The usage of specialized formulas for infants with colic is not advised due to a lack of clinical evidence. (5) In the case of constipation in infants, the use of formulas enriched with high ß-palmitate and increased magnesium content may be considered to soften the stool. Generally, there is limited evidence supporting the use of specialized formulas for FGID. Breastfeeding should never be discontinued in favor of formula feeding.

STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Functional studies associate novel DUOX2 gene variants detected in heterozygosity to Crohn's disease.

PURPOSE: Crohn's disease is a chronic gastrointestinal inflammatory disease with possible extraintestinal symptoms. There are predisposing genetic factors and even monogenic variants of the disorder. One of the possible genetic factors are variants of the DUOX2 gene. The protein product of the DUOX2 gene is a dual oxidase enzyme producing H2O2 in the bowel. Reduced H2O2 levels impact mucosal homeostasis and contribute to the development of inflammatory bowel disease. Thus far, only 19 patients with IBD with the DUOX2 variants have been described. METHODS: Here we present a case report of an adolescent female diagnosed at eleven years of age with IBD that was subsequently reclassified as Crohn's disease. She was treated with immunosuppressants and biological therapy but experienced additional complications. Her peripheral blood lymphocyte DNA was studied using massive parallel sequencing. Detected variants were functionally studied. RESULTS: Whole exome sequencing found two novel DUOX2 gene variants: a de novo variant c.3646C>T; p.R1216W and a maternally inherited variant c.3391G>A; p.A1131T which were initially classified as variants of unknown significance. However, follow-up functional studies demonstrated that both DUOX2 variants led to impaired H2O2 generation, which led to their reclassification to the likely pathogenic class according to the ACMG.net. Therefore, we conclude that these variants are causative for the disease. CONCLUSIONS: Identifying novel variants in patients with Crohn's disease and their families is important for precision medicine approaches and understanding of the pathogenesis of likely "monogenic" rare forms of inflammatory bowel disease.

Precision nutrition in pediatric IBD: A position paper from the ESPGHAN special interest group for basic science and translational research, the IBD Porto group, and allied health professionals.

Stratified and precision nutrition refers to disease management or prevention of disease onset, based on dietary interventions tailored to a person's characteristics, biology, gut microbiome, and environmental exposures. Such treatment models may lead to more effective management of inflammatory bowel disease (IBD) and reduce risk of disease development. This societal position paper aimed to report advances made in stratified and precision nutritional therapy in IBD. Following a structured literature search, limited to human studies, we identified four relevant themes: (a) nutritional epidemiology for risk prediction of IBD development, (b) food-based dietary interventions in IBD, (c) exclusive enteral nutrition (EEN) for Crohn's disease (CD) management, and (d) pre- and probiotics for IBD management. There is scarce literature upon which we can make recommendations for precision or stratified dietary therapy for IBD, both for risk of disease development and disease management. Certain single-nucleotide polymorphisms related to polyunsaturated fatty acid (PUFA) metabolism may modify the effect dietary PUFA have in increasing the risk of IBD development. Non-colonic CD, mild-to-moderate CD, and high microbiota richness may predict success of EEN and may be used both for prediction of treatment continuation, but also for early cessation in nonresponders. There is currently insufficient evidence to make recommendations for precision or stratified dietary therapy for patients with established IBD. Despite the great interest in stratified and precision nutrition, we currently lack data to support conclusive recommendations. Replication of early findings by independent research groups and within structured clinical interventions is required.

Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

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.

Sustainability of biologic treatment in paediatric patients with Crohn's disease: population-based registry analysis.

BACKGROUND: We aimed to evaluate the predictors of sustainability of biologic drugs for paediatric patients with Crohn's disease (CD). METHODS: The Czech National Prospective Registry of Biologic and Targeted Therapy of Inflammatory Bowel Disease (CREdIT) was used to identify the biologic treatment courses in paediatric patients with CD. Mixed-effects Cox models and propensity score analyses were employed to evaluate predictors of treatment sustainability. RESULTS: Among the 558 observations of 473 patients, 264 were treated with adalimumab (47%), 240 with infliximab (43%), 41 with ustekinumab (7%), and 13 with vedolizumab (2%). Multivariable analysis revealed higher discontinuation risk with infliximab compared to adalimumab (HR = 0.600, 95%CI 0.389-0.926), both overall and in first-line treatment (HR = 0.302, 95%CI 0.103-0.890). Infliximab versus adalimumab was associated with shorter time to escalation (HR = 0.094, 95%CI 0.043-0.203). Propensity-score analysis demonstrated lower sustainability of infliximab (HR = 0.563, 95%CI 1.159-2.725). The time since diagnosis to treatment initiation (HR = 0.852, 95%CI 0.781-0.926) was the most important predictor. Baseline immunosuppressive therapy prolonged sustainability with infliximab (HR = 2.899, 95%CI 1.311-6.410). CONCLUSIONS: Given the results suggesting shorter sustainability, the need for earlier intensification and thus higher drug exposure, and the greater need for immunosuppression with infliximab than with adalimumab, the choice of these drugs cannot be considered completely equitable. IMPACT: Our study identified predictors of sustainability of biologic treatment in paediatric patients with Crohn's disease, including adalimumab (versus infliximab), early initiation of biologic treatment, and normalised baseline haemoglobin levels. Infliximab treatment was associated with earlier intensification, higher drug exposure, and a greater need for immunosuppression. Parents and patients should be fully informed of the disadvantages of intravenous infliximab versus adalimumab during the decision-making process. This study emphasises the importance of not delaying the initiation of biologic therapy in paediatric patients with Crohn's disease.

De Novo Crohn's Disease in Children With Ulcerative Colitis Undergoing Ileal Pouch-Anal Anastomosis: A Multicenter, Retrospective Study From the Pediatric IBD Porto Group of the ESPGHAN.

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.

This is the largest European study describing the prevalence of Crohn's disease (CD) development in children with ulcerative colitis undergoing subtotal colectomy with ileal pouch­anal anastomosis. Children affected by ulcerative colitis carry a higher risk when compared with adults to develop de novo CD after surgery. On the other hand, the multivariate analysis identified decreased values of preoperative body mass index z scores as a possible predictor of new-onset CD.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 2: Long-Term Follow-Up on Home Parenteral Nutrition.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications, and on possible surgical and medical management to increase intestinal absorption.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 1: From Intestinal Resection to Home Discharge.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. The first part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN.

Postvaccination Immunogenicity of BNT162b2 SARS-CoV-2 Vaccine and Its Predictors in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: We prospectively compared the postvaccination immunity to messenger ribonucleic acid BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine of our pediatric patients over 12 years old with inflammatory bowel disease (IBD) to that of healthy controls and looked for predictors of its robustness. METHODS: Anti-receptor binding domain, anti-spike S2, and anti-nucleocapsid immunoglobin-G (IgG) and immunoglobin-A levels were measured in 139 pediatric patients with IBD [65 fully vaccinated (2 doses), median age 16.3, interquartile range (IQR) 15.2-17.8 years, median time from vaccination (IQR) 61.0 (42.0-80.0) days] and 1744 controls (46, 37-57 years) using microblot array. RESULTS: All IBD and control patients developed positive anti-receptor binding domain IgG antibodies at comparable titers. The proportion of observations with positive anti-spike S2 IgG was higher in patients with IBD than in controls [63% vs 21%, odds ratio 2.99 (1.51-5.90)], as was its titer [median (IQR) 485 (92-922) vs 79 [33-180] IU/mL]. Anti-receptor binding domain and anti-spike S2 IgG levels were associated with IBD status. We found an association between anti-spike S2 IgG levels and time since vaccination (ß -4.85, 95% CI -7.14 to 2.71, P = 0.0001), history of SARS-CoV-2 polymerase chain reaction positivity (206.76, 95% CI 39.93-374.05, P = 0.0213), and anti-tumor necrosis factor treatment (-239.68, 95% CI -396.44-83.55, P = 0.0047). Forty-three percent of patients reported vaccination side effects (mostly mild). Forty-six percent of observations with positive anti-nucleocapsid IgG had a history of SARS-CoV-2 infection. CONCLUSIONS: Patients with IBD produced higher levels of postvaccination anti-spike S2 antibodies than controls. Previous SARS-CoV-2 infection is associated with higher production of postvaccination antibodies and anti-tumor necrosis factor treatment with lower production.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Serum and Mucosal CD30 in Pediatric Inflammatory Bowel Diseases: Useful Biomarker for Diagnosis and Disease Activity Monitoring?

BACKGROUND: Inflammatory bowel diseases (IBD) frequently manifest in pediatric age, but may have atypical clinical, histological and laboratory features. Their underlying immune pathophysiology is incompletely understood, rendering quick diagnosis followed by tailored therapy difficult. The tumor necrosis factor superfamily receptor CD30 has been proposed as a potential marker of ulcerative colitis (UC) and has also been associated with elevated Th2 helper T cells. METHODS: A cohort of pediatric patients with UC and Crohn's disease (CD) was evaluated for serum soluble CD30 (sCD30) using ELISA and expression of CD30 and subpopulations of Th1/Th2/Th17 lymphocytes in the gastrointestinal mucosa using flow cytometry (FCM). The dataset is supported by endoscopic and microscopic activity of the disease and basic laboratory markers of inflammation. RESULTS: The cohort consisted of 102 observations from 94 patients. sCD30 levels did not differ between patients with CD or UC. However, sCD30 levels correlated with levels of CRP, ESR, fecal calprotectin and albumin and also with clinical activity of the disease in patients with both UC and CD. FCM was not helpful in evaluation of mucosal CD30, which was lowly expressed and not associated with the diagnosis or disease activity. We show augmented Th2 and Th1/17 response in terminal ileum and right-sided colon and decreased Th1/17 response in left-sided colon of UC patients. T lymphocyte subsets were also affected by anti-TNF treatment and patients' age. CONCLUSIONS: Neither sCD30 nor mucosal CD30 expression was helpful in differentiating between UC and CD. sCD30 seems to reflect a degree of systemic inflammation and clinical activity in IBD.

Prediction of thiopurine failure in pediatric Crohn's disease: pediatric IBD Porto group of ESPGHAN.

BACKGROUND: Maintaining of remission early in the disease course of Crohn's disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy. METHODS: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse. RESULTS: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031). CONCLUSIONS: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision. IMPACT: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.

Two phenotypes of chronic recurrent multifocal osteomyelitis with different patterns of bone involvement.

INTRODUCTION: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoinflammatory bone disorder with predominantly paediatric onset. Children present with multifocal osteolytic lesions accompanied by bone pain and soft tissue swelling. Patients often exhibit extraosseous co-morbidities such as psoriasis, inflammatory bowel disease, and arthritis. OBJECTIVES: Comparison of children with two different phenotypes of CRMO defined by presence or absence of extraosseous co-morbidities. METHODS: Children diagnosed with CRMO at the Motol University Hospital between 2010 and 2020 were retrospectively reviewed, and according to the absence or presence of extraosseous manifestations divided into two cohorts - bone limited CRMO and complex CRMO. The two groups were compared in terms of demographic data, age at disease onset, number and site of bone lesions, laboratory biomarker values, and need of escalation to a second-line therapy. RESULTS: Thirty-seven children (30 female, 7 male) with confirmed CRMO were included in the analysis. The mean age at disease onset was 10 years. All but 3 patients presented with multifocal disease. Twenty-three children (62%) had at least one extraosseous manifestation (13 sacroiliitis, 8 inflammatory bowel disease, 6 skin disease [acne, pustulosis, or psoriasis], 7 arthritis). Complex CRMO was associated with a significantly higher ESR rate (p = 0.0064) and CRP level (p = 0.018). The groups did not differ in number of foci or in age at disease onset. Bone lesion distribution differed between the two groups with significantly more frequent involvement of clavicle (p = 0.011) and pelvis (p = 0.038) in patients with complex CRMO. Children with complex CRMO more often needed escalation of therapy to DMARDs and biologic agents. CONCLUSION: Our data suggest that CRMO affecting solely the skeleton has milder course compared to complex CRMO with extraskeletal features. Further studies are needed to explore the clinical as well as the patient reported outcomes and promote individually tailored therapeutic strategies in both CRMO phenotypes.

Pediatric endoscopy training across Europe: a survey of the ESPGHAN National Societies Network 2016-2019.

Background and study aims The ability to perform endoscopy procedures safely and effectively is a key aspect of quality clinical care in Pediatric Gastroenterology, Hepatology and Nutrition (PGHN). The aim of this survey, which was part of a global survey on PGHN training in Europe, was to assess endoscopy training opportunities provided across Europe. Methods Responses to standardized questions related to endoscopy training were collected from training centers across Europe through the presidents/representatives of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition National Societies from June 2016 to December 2019. Results A total of 100 training centers from 19 countries participated in the survey. In 57 centers, the endoscopy suit was attached to the PGHN center, while in 23, pediatric endoscopies were performed in adult endoscopy facilities. Ninety percent of centers reported the availability of specialized endoscopy nurses and 96 % of pediatric anesthetists. Pediatric endoscopies were performed by PGHN specialists in 55 centers, while 31 centers reported the involvement of an adult endoscopist and 14 of a pediatric surgeon. Dividing the number of procedures performed at the training center by the number of trainees, ≤ 20 upper, lower, or therapeutic endoscopies per trainee per year were reported by 0 %, 23 %, and 56 % of centers, respectively, whereas ≤ 5 wireless capsule endoscopies per trainee per year by 75 %. Only one country (United Kingdom) required separate certification of competency in endoscopy. Conclusions Differences and deficiencies in infrastructure, staffing, and procedural volume, as well as in endoscopy competency assessment and certification, were identified among European PGHN training centers limiting training opportunities in pediatric endoscopy.

Training in pediatric neurogastroenterology and motility across Europe: a survey of the ESPGHAN National Societies Network 2016-2019.

Background: Pediatric gastrointestinal motility disorders present significant challenges for diagnosis and management, emphasizing the need for appropriate training in Pediatric Neurogastroenterology and Motility (PNGM). The aim of this survey, part of a comprehensive survey on training in pediatric gastroenterology, hepatology and nutrition, was to evaluate training related to PNGM across European training centers. Method: Standardized questionnaires were collected from training centers through the National Societies Network of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), from June 2016 to December 2019. Results: In total, 100 training centers from 19 countries participated in the survey. Dedicated PNGM clinics were available in 22 centers; pH-monitoring in 60; pH/impedance in 66; standard manometry in 37; and high-resolution manometry in 33. If all motility studies were performed partially or fully by the trainees, the median (range) annual numbers/per trainee were as follows: pH-monitoring 30 (1-500); pH/impedance 17 (1-131); standard manometries 10 (1-150); and high-resolution manometries 8 (1-75). The motility assessment was performed by pediatric gastroenterologists (43 centers); adult gastroenterologists (10 centers); pediatric surgeons (5 centers); and both pediatric gastroenterologists and pediatric surgeons (9 centers). Annual numbers ≤10 for pH-monitoring, pH/impedance, standard manometries and high-resolution manometries were reported by 7 (12%), 15 (23%), 11 (30%) and 14 (42%) centers, respectively. Conclusions: Significant differences exist in PNGM-related infrastructure, staff and procedural volumes at training centers across Europe. ESPGHAN and the National Societies should take initiatives to ensure the acquisition of competence in PNGM-related knowledge and skills, and develop strategies for assessment and accreditation.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic-AG6486.pdf.

Association of training standards in pediatric gastroenterology, hepatology and nutrition in European training centers with formal national recognition of the subspecialty: a survey of the ESPGHAN National Societies Network 2016-2019.

Background: This survey evaluated the effects of the recognition of pediatric gastroenterology, hepatology and nutrition (PGHN) on European PGHN training centers. Method: Standardized questionnaires were collected from training centers via the presidents/representatives of the National Societies Network of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, from June 2016 to December 2019. Results: A total of 100 training centers from 19 countries participated in the survey: 55 from 12 countries where PGHN is formally recognized (Group 1) and 45 from 7 countries where it is not (Group 2). Training centers in Group 2 were less likely to have an integrated endoscopy suite, a written training curriculum and a training lead (P=0.059, P<0.001 and P=0.012, respectively). Trainees in Group 2 were less likely to be exposed to an adequate number of diagnostic endoscopies, while no differences were found in relation to liver biopsies. Half of the training centers in both Groups do not have dedicated beds for PGHN patients, while in 64% and 58%, respectively, trainees do not participate in on-call programs for PGHN emergencies. Research training is mandatory in 26% of the centers. The duration of training, as well as the assessment and accreditation policies, vary between countries. Conclusions: This study has revealed significant discrepancies and gaps in infrastructure and training programs, training leadership, and assessment of training and certification across European training centers in PGHN. Strategies to support the recognition of PGHN and to standardize and improve training conditions should be developed and implemented.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic_AG-6496.pdf.