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OBJECTIVES: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD. METHODS: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up. RESULTS: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported. CONCLUSIONS: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.

Background Long term growth may be compromised in patients with Inflammatory Bowel Disease (IBD). The aims of the study were to evaluate the final height in a cohort of patients with pediatric-onset IBD with respect to genetic target and to determine factors influencing long-term growth. Methods This is a monocentric retrospective cohort study. All patients with diagnosed prepubertal onset IBD were enrolled. Patients were classified into two groups on the basis of the achievement of target height at time of the last follow-up. Clinical parameters were also recorded. Results 82 patients were identified: 42 with Crohn's Disease (CD) and 40 with Ulcerative Colitis (UC). The mean age at diagnosis was 11.0 (SD 4.0) years. Eighty-nine percent of patients achieved final target height. Mean difference between final and target height was -1.2 cm (SD: 5,4). No statistical significance was detected between CD and UC patients final height (p=0.16). Growth failure at the diagnosis and disease severity were the only factors associated with final height achievement failure (p=0.001 and p=0.01 respectively). Conclusions Most part of CD and UC patients achieve the target final height. Disease severity and low height at diagnosis seem to be the two best predictive factors for low final height.

Background Current data on dual biologic therapy in children are limited. This multicenter study aimed to evaluate the effectiveness and safety of dual therapy in pediatric patients with inflammatory bowel disease (IBD). Methods A retrospective study from 14 centers affiliated with the Pediatric IBD Interest and Porto Groups of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Included were children with IBD who underwent combinations of biologic agents or biologic and small molecule therapy for at least 3 months. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded. Results Sixty-two children (35 Crohn’s disease, 27 ulcerative colitis; median age 15.5 [interquartile range, 13.1-16.8] years) were included. They had all failed previous biologic therapies, and 47 (76%) failed at least 2 biologic agents. The dual therapy included an anti-tumor necrosis factor agent and vedolizumab in 30 children (48%), anti-tumor necrosis factor and ustekinumab in 21 (34%) children, vedolizumab and ustekinumab in 8 (13%) children, and tofacitinib with a biologic in 3 (5%) children. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Normalization of C-reactive protein and decrease in fecal calprotectin to Conclusions Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events.

Background Few drugs have been studied for patients with very early onset inflammatory bowel disease (VEOIBD). This study aimed to evaluate the efficacy and tolerance of thalidomide in children with VEOIBD compared with children with pediatric-onset IBD (pIBD). Methods A retrospective cohort study with a control group was conducted. Propensity score 1:1 matching was used to identify control subjects. The treatment persistence; the causes of drug withdrawal; the rate of clinical remission and mucosal healing at 1, 2, and 3 years; and adverse events (AEs) were evaluated in children with VEOIBD treated with thalidomide and compared with children with pIBD. Results Thirty-nine courses of treatment with thalidomide in VEOIBD and pIBD patients were compared. The treatment persistence at 1, 2, and 3 years was 68.2% (95% confidence interval [CI], 50.8%-80.6%), 57.0% (95% CI, 39.6%-71.1%), and 50.9% (95% CI, 33.7%-65.8%) for VEOIBD patients and 81.7% (95% CI, 65.3%-90.9%), 60.0% (95% CI, 41.7%-74.3%) and 33.0% (95% CI, 17.4%-49.5%) for pIBD patients, respectively (P = .12). A significantly higher proportion of VEOIBD patients discontinued therapy due to lack of efficacy (48.2% vs 17.2%; P = .03), while AEs were the main reason for discontinuation in pIBD patients. Clinical remission and mucosal healing rates did not significantly differ between VEOIBD and pIBD patients. A significatively lower number of VEOIBD patients experienced AEs compared with pIBD patients (14 [35.9%] vs 30 [76.9%]; P = .0005). Conclusions Thalidomide is an effective and tolerated treatment in children with VEOIBD. Discontinuation due to lack of efficacy is more frequent, but AEs are less common than in children with pIBD.

Coeliac disease is an immune-mediated systemic disease that affects 1% of the population and it is caused by the ingestion of gluten in genetically predisposed subjects. Clinical manifestations and intestinal damage completely resolve once gluten is excluded from the diet, therefore the precocity of diagnosis is of primary relevance. Although considerable progress has been made in recent years, the wide spectrum of clinical manifestations still causes diagnostic delay. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) has recently published an update of the guidelines providing tools to optimize diagnostic skills. This work aims to summarize the main topics of the new guidelines through illustrative clinical cases.

PACSIN2 variants are associated with gastrointestinal effects of thiopurines and thiopurine methyltransferase activity through an uncharacterized mechanism that is postulated to involve autophagy. This study aims to clarify the role of PACSIN2 in autophagy and in thiopurine cytotoxicity in leukemic and intestinal models. Higher autophagy and lower PACSIN2 levels were observed in inflamed compared with non-inflamed colon biopsies of inflammatory bowel disease pediatric patients at diagnosis. PACSIN2 was identified as an inhibitor of autophagy, putatively through inhibition of autophagosome formation by a protein–protein interaction with LC3-II, mediated by a LIR motif. Moreover, PACSIN2 resulted a modulator of mercaptopurine-induced cytotoxicity in intestinal cells, suggesting that PACSIN2-regulated autophagy levels might influence thiopurine sensitivity. However, PACSIN2 modulates cellular thiopurine methyltransferase activity via mechanisms distinct from its modulation of autophagy.

Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single‐nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.

Foreign bodies or caustic ingestion is a frequent occurrence in children and can result in significant morbidity. Managing these conditions requires different levels of experience and expertise. An en-doscopy is often necessary but an incorrect use of this procedure is common. Indications and timing of endoscopy mainly depends on the clinical conditions of the child, the type of object and its posi-tion or the type of substance. The Italian Society of Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP) together with the Italian Association of Gastroenterologists and Hospital En-doscopists (AIGO) has produced the first Italian guidelines for the management of the ingestion of foreign and caustic bodies in children.

Objectives and study There is a large interobserver variability in evaluating mucosal lesions of inflammatory bowel disease (IBD), especially in pediatric patients. This multicenter prospective observational study aims to evaluate interobserver agreement (IOA) among pediatric endoscopists in assigning validated IBD endoscopic scores in children. Methods Fifteen videos of follow-up ileocolonoscopies in children with IBD were recorded and selected as cases. Eleven pediatric endoscopists from different centers blindly evaluated all videos and calculated scores: either Ulcerative Colitis Endoscopic Index of Severity (UCEIS) or Simple Endoscopic Score for Crohn Disease (SES-CD). Scores from all reviewers were compared in order to calculate IOA for general videos and specific sections. Scores from an expert adult reader were used to calculate possible reviewer's characteristics affecting scores' reliability. Results Intraclass correlation was 0.298 (95% confidence interval [CI]: 0.13-0.55) for ulcerative colitis (UC) and 0.266 (0.11-0.52) for Crohn disease (CD). When a disease activity categorization was adopted (remission, mild, moderate, severe activity) Fleiss kappa coefficient was 0.408 (0.29-0.53) for UC and 0.552 (0.43-0.73) for CD. When stratified by item, vascular pattern of UC was the most reliable item IC: 0.624 (0.321-0.854). In multivariable analysis, none of the reviewer's characteristics affected the readers' errors. Conclusions This multicenter study shows low agreement among pediatric endoscopists in evaluating endoscopic scores in children with IBD. By using disease activity categorization, agreement slightly increased, mostly for CD. All readers showed a low-grade concordance with the expert adult gastroenterologist's evaluations. Future-specific training programs should be considered to increase IOA in using IBD endoscopic activity scores.

The aim of the study was to investigate the burden of mental health problems in children and adolescents admitted to a pediatric ward with physical complaints. We conducted a retrospective study, considering all patients admitted to the pediatric ward of the IRCCS Burlo Garofolo, Trieste, Italy, between January 2015 and September 2016. We selected all patients, from 5 to 17 years old, who were admitted with physical complaints and were discharged with a diagnosis suggestive of a mental health problem: somatic symptom disorder, anxiety disorder, depressive disorder, factious disorders. For every patient, we collected demographic features, medical characteristics, health care services utilization, length of hospital stay, and after discharge referral. We selected 1456 patients; of these, 101 (6.9%) revealed a mental health problem. The median duration of symptoms was 5 months (IQR 1.5-12), and pain was the main reported symptom (69%). Of the 101 patients, 23 (23%) were affected by a previously documented chronic organic disease. Somatic symptom disorder was the most common diagnosis. In 69/78 patients (88%), a loss of social contacts emerged; 49/95 patients frequenting school (51%) had chronic school absenteeism in the previous school year.Conclusion: A considerable proportion of patients admitted to a pediatric ward with physical complaints have mental health problems. What is Known: • It has been suggested that mental health problems in children and adolescents are increasing and frequently burden on pediatric healthcare services, but how they impact on a general pediatric ward is not clear. What is New: • Among 1456 patients admitted to a general pediatric ward with physical symptoms, 101 patients (6.9%) had a mental health problem. Among them, pain was the most commonly reported symptom and somatic symptom disorder was the commonly reported diagnosis.

Background Exclusive enteral nutrition (EEN) is the first choice to induce remission and promote mucosal healing in pediatric Crohn’s disease (CD). However, full adherence to EEN treatment may be problematic for children with CD. Methods The goal of the current multicenter retrospective study was to define predictive factors of nonadherence to treatment and nonremission at the end of induction treatment. Those data together were analyzed with the ultimate goal of trying to define an individualized induction treatment for children with CD. Results Three hundred seventy-six children with CD from 14 IBD pediatric referral centers were enrolled in the study. The rate of EEN adherence was 89%. Colonic involvement and fecal calprotectin >600 μg/g at diagnosis were found to be associated with a reduced EEN adherence. Exclusive enteral nutrition administered for 8 weeks was effective for inducing clinical remission in 67% of the total cohort. Factors determining lower remission rates were age >15 years and Pediatric Crohn’s Disease Activity Index >50. Conclusion Although EEN is extremely effective in promoting disease remission, several patients’ related factors may adversely impact EEN adherence and response. Personalized treatments should be proposed that weigh benefits and risks based on the patient’s disease location, phenotype, and disease activity and aim to promote a rapid control of inflammation to reduce long-term bowel damage.

Introduction: The present study aimed at evaluating Italian epidemiological trends of pediatric inflammatory bowel diseases (IBD) over the period 2009–2018. Materials and methods: Data from 1969 patients enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition Registry, by 49 pediatric IBD centers throughout the country, were analyzed, comparing three different time intervals (2009–2012, 2013–2015, 2016–2018). Results: The number of new IBD diagnoses ranged from 175 to 219 per year, evenly distributed over the examined period of time. From 2009 to 2018, the minimal incidence ranged from 1.59 to 2.04 /105 inhabitants aged < 18 years, with an overall slight predominance of ulcerative colitis (UC) over Crohn's disease (CD) (ratio: 1.1). Mean diagnostic delay was 6.8 months for CD and 4.1 months for UC, with a significant reduction for CD when comparing the three-time intervals (p =0.008). The most frequent disease locations according to the Paris classification were ileocolonic for CD (41.3%) and pancolitis for UC (54.6%). Conclusions: The minimal incidence rate in Italy seems to have stabilized over the last two decades, even if it has increased when compared to previous reports. UC is still slightly more prevalent than CD in our country. Diagnostic delay significantly decreased for CD, reflecting an improved diagnostic capacity.

Patients with Crohn's disease (CD) usually undergo magnetic resonance enterography (MRE) for evaluating small bowel involvement. Musculoskeletal symptoms are the most frequent extraintestinal manifestation in inflammatory bowel diseases, especially in CD, with sacroiliitis at imaging occurring in about 6-46% of patients and possibly correlating with axial spondyloarthritis. The primary study aim was to assess the prevalence of sacroiliitis in adult and pediatric patients with CD performing an MRE. We also evaluated the inter-rater agreement for MRE sacroiliitis and the association between sacroiliitis and patients' clinical data.We retrospectively identified 100 adult and 30 pediatric patients diagnosed with CD who performed an MRE between December 2012 and May 2020 in three inflammatory bowel disease centers. Two radiologists assessed the prevalence of sacroiliitis at MRE. We evaluated the inter-rater agreement for sacroiliitis with Cohen's kappa and intraclass correlation coefficient statistics and assessed the correlation between sacroiliitis and demographic, clinical, and endoscopic data (Chi-square and Fisher's tests).The prevalence of sacroiliitis at MRE was 20% in adults and 6.7% in pediatric patients. The inter-rater agreement for sacroiliitis was substantial (k = 0.62, p 0.001) in the adults and moderate (k = 0.46, p = 0.011) in the pediatric cohort. Age ≥ 50 years and the time between CD diagnosis and MRE (≥ 86.5 months) were significantly associated with sacroiliitis in adult patients (p = 0.049 and p = 0.038, respectively).Sacroiliitis is a frequent and reliable abnormality at MRE in adult patients with CD, associated with the age of the patients ≥ 50 years and CD duration.

Patients with inflammatory bowel disease (IBD) may have diet-related beliefs that lead to restrictive dietary behaviours. This study aimed to evaluate dietary beliefs in young patients with IBD and their parents and the presence of restrictive behaviours.A questionnaire regarding dietary beliefs was administered to IBD patients aged 8-17 years and their parents. A Food Frequency Questionnaire was administered to patients with IBD and a peer control group.Seventy-five patients and 105 parents were interviewed. Twenty-seven (36%) patients and 39 (37.1%) parents believed that dietary modifications could control the IBD course.Twenty-five (33.0%) patients and 33 (33.0%) parents believe that some dietary components can prevent relapse or improve symptoms (mainly abdominal pain and diarrhoea), while 36 (48%) patients and 60 (60.0%) parents believe that some foods can induce or worsen symptoms during an IBD flare.Patients believe that milk, dairy, fried and spicy foods, sweets and carbonated drinks could have a negative effect on IBD while fruits, vegetables and rice could have a positive impact. Parents believe that fruits and vegetables have a negative effect.Responses did not differ among patients classified according to IBD phenotype, activity status, or current therapies.Compared to controls, young patients with IBD have reduced daily consumption of milk, lunch meat, raw and cooked vegetables.About one-third of paediatric patients with IBD and their parents have dietary beliefs that lead to restrictive dietary behaviours.

Diseases affecting the immune system, such as inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and acute lymphoblastic leukemia (ALL), are pathological conditions affecting the pediatric population and are often associated with alterations in the intestinal microbiota, such as a decrease in bacterial diversity. Growing evidence suggests that gut microbiota can interfere with chemotherapeutic and immunosuppressant drugs, used in the treatment of these diseases, reducing or facilitating drug efficacy. In particular, the effect of intestinal microflora through translocation, immunomodulation, metabolism, enzymatic degradation, and reduction of bacterial diversity seems to be one of the reasons of interindividual variability in the therapeutic response. Although the extent of the role of intestinal microflora in chemotherapy and immunosuppression remains still unresolved, current evidence on bacterial compositional shifts will be taken in consideration together with clinical response to drugs for a better and personalized therapy. This review is focused on the effect of the intestinal microbiota on the efficacy of pharmacological therapy of agents used to treat IBD, JIA, and ALL.

Data on the epidemiology and risk factors for pouchitis following restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) in pediatric patients with ulcerative colitis (UC) are scarce.To determine incidence, risk factors and clinical outcome of pouchitis following IPAA in children.This multicenter, retrospective cohort study, included all pediatric UC patients who underwent colectomy and IPAA from January 2010 to December 2016.Eighty-five patients were enrolled. During a median post-surgical period of 24.8 (range: 1.0-72.0) months following IPAA, 38 (44.7%) patients developed pouchitis, including 6 (15.8%) who developed chronic pouchitis. Kaplan-Meier survival estimates of the cumulative probability for pouchitis were 14.6% at 1 year and 27.3% and 51.5% at 2 and 5 years, respectively. Multiple Cox regression model showed that older age at colectomy (hazard ratio, HR: 0.89, p = 0.008) was a protective factor, whereas chronic active colitis as indication for surgery (HR: 4.45, p 0.001), and a 3-stage IPAA (HR: 2.86, p = 0.028) increased the risk for pouchitis.Long-term risk for pouchitis is significantly high in pediatric-onset UC after IPAA. Younger age at colectomy, chronic active colitis as indication for surgery and 3-stage IPAA may increase the risk for pouchitis.

This retrospective five-year experience shows that the access to the Emergency room for foreign body ingestion decreased in 2020 during the lockdown period. Altogether 21.3% of cases were hospitalized and 13.4% underwent endoscopy.

Objectives To investigate the compliance to the gluten-free diet in a cohort of adult celiac patients 20 years after the diagnosis, received in childhood through a mass screening. Methods This is an observational historic cohort follow-up study. It was carried out at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. Two matched cohorts of adult celiac patients, diagnosed in childhood through a mass screening or for symptoms were enrolled. Adherence to the gluten free-diet and development of autoimmune diseases were investigated through a questionnaire administrated in the course of a phone interview.The primary study outcome was the adherence to the gluten-free diet, measured through the Biagi questionnaire, in the two cohorts of celiac patients. Results We contacted 25 patients (mean age 28 yrs, 19 females) diagnosed with screening and 34 patients (mean age 25 yrs, 26 females) diagnosed in the same period for symptoms. After 20 years, in the cohort diagnosed with screening and in the cohort diagnosed for symptoms the adherence to the gluten-free diet was optimal in 14 (56%) and 26 (81%), improvable in 5 (20%) and 3 (9%), inadequate in 6 (24%) and 3 (9%), respectively. In the two cohorts, 4 patients (16%) and 6 patients (18%) developed other autoimmune diseases. Conclusions 20 years after the diagnosis, near half of the patients diagnosed in a mass screening, does not have an optimal adherence to the gluten-free diet and a remarkable proportion of them have developed another autoimmune disease.

To investigate the coping strategies of a group of adolescents with somatic symptom disorder compared to non-somatic symptom disorder peers during the COVID-19 related lockdown.This cross-sectional study is the second part of a previously published study showing an improved trend in depression and anxiety in a group of patients with somatic symptom disorder compared to non-somatic symptom disorder peers. An anonymous semi-structured survey was distributed to two groups of Italian adolescents to measure the impact of quarantine on their daily life and coping strategies.We recruited 115 adolescents, 58 (50.4%) mean age 15.3, with a recent diagnosis of somatic symptom disorder and 57 (49.6%) mean age 15.8, control peers.The aim of this study was to detect differences in coping strategies and relationships with parents and peers, during the lockdown period in a group of adolescents with somatic symptom disorder and low disease burden when compared with a non-somatic symptom disorder group.The relationship with parents significantly worsened in 4 (6.9%) of adolescents with somatic symptom disorder compared to 12 (21.1%) adolescents in the non-somatic symptom disorder group (p = 0.048). The relationship with peers significantly improved in 13 (22.4%) of adolescents with symptom disorder versus 3 (5.3%) of peers of the non- somatic symptom disorder group (p = 0.013).Adolescents with somatic symptom disorder with a low burden of physical symptoms experienced less deterioration in their relationships with parents and peers than the non-somatic symptom disorder group.

Objectives: Anti-tumor necrosis factor antibodies have led to a revolution in the treatment of inflammatory bowel diseases (IBD); however, a sizable proportion of patients does not respond to therapy. There is increasing evidence suggesting that treatment failure may be classified as mechanistic (pharmacodynamic), pharmacokinetic, or immune-mediated. Data regarding the contribution of these factors in children with IBD treated with infliximab (IFX) are still incomplete. The aim was to assess the causes of treatment failure in a prospective cohort of pediatric patients treated with IFX. Methods: This observational study considered 49 pediatric (median age 14.4) IBD patients (34 Crohn disease, 15 ulcerative colitis) treated with IFX. Serum samples were collected at 6, 14, 22 and 54 weeks, before IFX infusions. IFX and anti-infliximab antibodies (AIA) were measured using enzyme linked immunosorbent assays. Disease activity was determined by Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index. Results: Clinical remission, defined as a clinical score 3.11 μg/mL emerged as the strongest predictor of sustained clinical remission. AIA concentrations were correlated inversely with IFX concentrations and directly with adverse reactions. Conclusions: Most cases of therapeutic failure were associated with low serum drug levels. IFX trough levels at the end of induction are associated with sustained long-term response.

Background: IBD management has been significantly affected during the COVID-19 lockdown with potential clinical issues. Aims: The aim of this study was to analyse the impact of COVID-19 pandemic on the Italian paediatric IBD cohort. Methods: This was a multicentre, retrospective, cohort investigation including 21 different Italian IBD referral centres. An electronic data collection was performed among the participating centres including: clinical characteristics of IBD patients, number of COVID-19 cases and clinical outcomes, disease management during the lockdown and the previous 9 weeks. Results: 2291 children affected by IBD were enrolled. We experienced a significant reduction of the hospital admissions [604/2291 (26.3%) vs 1281/2291 (55.9%); p < 0.001]. More specifically, we observed a reduction of hospitalizations for new diagnosis (from n = 44 to n = 27) and endoscopic re-evaluations (from n = 46 to n = 8). Hospitalization for relapses and surgical procedures remained substantially unchanged. Biologic infusions did not significantly vary [393/2291 (17.1%) vs 368/2291 (16%); p = 0.3]. Telemedicine services for children with IBD were activated in 52.3% of the centres. In 42/2291(1.8%) children immunosuppressive therapies were adapted due to the concurrent COVID-19 pandemic. Conclusion: Due to the several limitations of the lockdown, cares for children with IBD have been kept to minimal standards, giving priorities to the urgencies and to biologics’ infusions and implementing telemedicine services.

Supplemental material, sj-docx-1-bbi-10.1177_11779322211055285 for Genetic Variants Assessing Crohn���s Disease Pattern in Pediatric Inflammatory Bowel Disease Patients by a Clinical Exome Survey by Dago Dougba Noel, Pinelli Marinella, Giacomelli Mauro, Serena Ilaria Tripodi, Alessia Pin, Arrigo Serena, Bramuzzo Matteo, Fuoti Maurizio Giuseppe, Alvisi Patrizia, Calza Stefano, Alberto Tommasini and Badolato Raffaele in Bioinformatics and Biology Insights

Background Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. Methods This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. Results Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97–8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn’s disease and CeD than in patients with Crohn’s disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13–33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). Conclusions Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.

The case of a 12-year-old boy with diffuse arthralgia initially misdiagnosed as systemic onset juvenile idiopathic arthritis is described. The diagnosis of Crohn disease was eventually posed based on high faecal calprotectin level and suggestive ultrasound abdominal images. The authors underline how Crohn disease may present without abdominal symptoms.

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Background Nutrition is involved in several aspects of pediatric IBD, ranging from disease etiology to induction and maintenance of disease. Presence of nutritional deficiencies can influence clinical outcomes and affect the immune system, growth and sexual maturation in children. Few studies assessed the dietary intake of IBD’s pediatric patients and investigated whether their dietary intakes meet the recommended daily allowances (RDA). Methods Children and adolescents with a diagnosis of IBD (> 1 year) and healthy controls (age and gender matched) were prospectively enrolled in 5 pediatric Italian IBD units. Daily dietary intake in the previous 6 months was assessed using a Food Frequency Questionnaire (FFQ). Energy intake (EI) and macro and micronutrients intakes were compared to the national RDA (LARN) and EI to the predicted total energy expenditure (TEE) based on the Schofield equation. Adherence to the Mediterranean diet was measured through the KIDMED score. Clinical and auxological data were recorded Results 110 IBD subjects and 110 controls (median age±SD: 14,6 ±2,2 and 13,8±2,8 years, p= 0,45) were enrolled. Weight and height z-scores were significantly lower in IBD compared to controls (p= 0,0005 and p=0,036).Weight, height and BMI z-score did not differ between CD and UC. EI (Kcal/day), the EI/RDA ratio (%) and the EI/TEE ratio (%) were significantly lower in IBD compared to the controls (1893 vs 2068 kcal/day, p= 0,009; 71,5% vs 84,7%, p< 0,0001; 79,8% vs 90,8%, p=0,007). When distributing patients by clinical disease activity, the TEE was lower in patients with active disease compared to patients in remission (1850 vs 1915; p=0,039). A significant correlation was not found between age, gender, type of disease, disease activity, and EI/RDA % and EI/TEE %. Total protein and fat intake were lower in children with IBD compared to controls. Conversely the total carbohydrate intake did not differ between IBD patients and controls (median 289,8 vs 311,7 gr/day, p= 0,077) while the percentage of carbohydrate to EI was higher (CHO % : 61 vs 58; p=0,012). Total charbohydrates intake was significantly lower in patients with active disease compared to patients in remission (265.7 vs 294.3 gr/day; p=0,002). IBD patients reported a lower intake of the main dietary micronutrients compared to controls. A poor adherence to the Mediterranean diet was more frequent in IBD children (37.2% vs 22.7%, p= 0,013). Conclusion The diet of Italian children and adolescents with IBD differs substantially from the general pediatric population and frequently does not meet the RDA. Our data suggest the need of an accurate evaluation of the dietary intake and nutritional status in order to prevent nutritional deficiencies and promote health.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2, spreading in Italy during the first months of 2020, abruptly changed the way of practicing medicine in this country. As a consequence of the lockdown, the diagnostic and therapeutic management of paediatric chronic conditions, such as inflammatory bowel disease (IBD) has been affected. During the peak of COVID-19 pandemic, elective visits, endoscopies and infusions have been postponed, with potential clinical and psychological impact on disease course and a high likelihood of increasing waiting lists. While slowly moving back towards normality, clinicians need to recognize the best ways to care for patients with IBD, carefully avoiding risk factors for new potential epidemic outbreaks. In this uncertain scenario until the development and spread of COVID-19 vaccine, it is necessary to continue to operate with caution. Hereby we provide useful indications for a safer and gradual restarting of routine clinical activities after COVID-19 peak in Italy.