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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.

Early dropout and treatment adherence are main challenges in the treatment of children with obesity. The aim of this study was to identify factors associated with attrition and adherence to weight loss intervention program. We retrospectively reviewed the medical records of all the children who entered the program for pediatric weight loss over 5 years and retrieved demographic and clinical characteristics. Attrition and adherence were documented. Ninety-two of the 248 enrolled children (52% women, mean age 11.1 ± 3.9 years, mean body mass index 31.1 ± 7 kg/m2) dropped out (37%). Dropping out correlated with male sex, low parental education, and self-referral to the clinic ( P < .05 for all). Adherence correlated with older age and the mother’s healthy lifestyle ( P < .05 for all). Sex, parental education, and referral source may predict treatment attrition. Early recognition of children at risk of attrition may help to facilitate better care of those children.

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.

Purpose To investigate factors associated with pediatric feeding disorders (PFD) among children of parents that reported to have had feeding disorders during their own childhood compared to children with PFD with no history of parental PFD. Methods We retrospectively reviewed the medical records of children diagnosed with PFD according to the recent WHO-based definition. Demographic and clinical characteristics of children with PFD with a parental history of PFD were compared to those of children with a PFD with no history of parental PFD. Results Included were 231 children with PFD (median [interquartile range] age 10 (5.5–29) months at diagnosis, 58% boys) of whom 133 children had parents without PFD and 98 children had parents with PFD. Unexpectedly, children of parents without PFD had a higher rate of low birth weight (28% vs. 19%, respectively, p = 0.007), more delivery complications (10% vs. 2%, p = 0.006), more hospitalizations (33% vs. 17%, p = 0.004), more prescription medications (27% vs. 18%, p = 0.05), and a higher percent of gastrostomy tube use (6% vs. 0, p = 0.02). Moreover, more parents with PFD had an academic background compared with parents without PFD (72% vs. 59%, p = 0.05). There were no significant group differences in sex, history of breastfeeding, parental marital status, or type of the child's feeding disorder. Conclusions PFD among children with a parental history of PFD comprise a distinct group of patients with unique characteristics and outcomes. Since parental feeding history may explain their child's PFD in highly differing ways, treatment should be family-based and multidisciplinary.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p

Transition of care (TOC) in adolescents and young adults (AYAs) with chronic gastrointestinal disorders has received increased attention, especially in those with inflammatory bowel disease. AYAs with hereditary polyposis syndromes are a heterogeneous group of patients with overlapping and complex medical needs. These patients are particularly vulnerable because of the risk of loss of continuity of care and subsequent poor disease outcomes. The Pediatric Committee of the American College of Gastroenterology commissioned a report with recommendations on TOC in AYAs with hereditary polyposis syndromes. This report aims at achieving best practice by both pediatric and adult gastroenterologists despite the paucity of published evidence in this population reflected in the included PRISMA report. Therefore, the group extrapolated findings from the literature related to other chronic gastrointestinal disorders, and a high degree of expert consensus was scored for all recommendations. The report addresses TOC through identifying shared domains followed by specific recommendations in disease management, including models of care, providers and patient and socioeconomic factors relevant to TOC. Areas of strong emphasis include the need for early planning, flexibility in the transition process to maintain continuity during major surgical procedures, patient and family psychological readiness, liaison among team members addressing transition, and changing insurance coverage in this population.

Background The effect of biologic therapy on the incidence of inflammatory bowel disease (IBD)-related hospitalizations is controversial. The high efficacy of biologic agents is weighted against potential therapy-related adverse events, however, there are no data on the effect of biologic therapy on the indications for hospitalization in IBD. We aimed to evaluate the impact of biologic therapy on the indications and rate of hospitalization in pediatric IBD. Methods This retrospective cohort study included all children ( Results Included were 218 hospitalizations of 100 children, of whom 65 (65%) had Crohn’s disease and 35 (35%) had ulcerative colitis. The indications for hospitalization were IBD exacerbations or complications in 194 (89%) and therapy-related adverse events in 24 (11%). The patients of 56 (25.7%) hospitalizations were receiving biologic therapy. In a multivariate analysis, no correlation between therapy and indication for hospitalization was found (p = 0.829). Among children under biologic therapy, a decrease in the rate of hospitalizations from 1.09 (0.11–3.33) to 0.27 (0–0.47) per year was observed for patients that were hospitalized during 2016–2019 (p = 0.043). Conclusion Biologic therapy did not influence the indication for hospitalization, but were associated with a decrease in the rate of hospitalization during 2016–2019 in pediatric IBD.

The current treatment goal for inflammatory bowel disease (IBD) is achievement of mucosal healing (MH). While established with biologic or azathioprine (AZA) therapies, the data on MH with methotrexate (MTX( treatment is scarce. We aimed to compare MH rate as reflected by FC in children with Crohn's disease (CD) treated with either MTX or thiopurines monotherapy.A cross-sectional multicenter study including children with CD (18 years), with documented mucosal ulcerations/erosions on their first endoscopy, who were in clinical and biochemical remission for at least 6 months on MTX or AZA/6-MP monotherapy and had fecal calprotectin (FC) measurements during remission. Clinical remission was defined as PCDAI10 and normal C-reactive-protein (CRP) level. FC100 μg/gr was used as a marker of MH. Demographic, clinical and laboratory data were retrieved from the medical charts.64 patients (41 males, age 16.6±4.2 years) were included; 36 with MTX, 26 with AZA and 2 with 6-MP treatment. The mean treatment dose was 14.0±1.8 mg/m2 for MTX, and 1.8±0.66 mg/kg for AZA, and mean therapy duration was 22 ±17.1 months. MH (FC100 μg/gr) was demonstrated in 14/36 (39%) and 18/28 (64%) of patients on MTX and AZA/6-MP therapy, respectively (p=0.04). Rates of FC300 μg/gr were comparable [27/36 (75%) MTX, 24/28 (86%) AZA/6-MP, p=0.29]. MH was associated with longer treatment duration (p=0.03).MH as reflected by FC100 μg/gr, was higher with AZA/6-MP compared to MTX treatment in pediatric CD.

Very early-onset inflammatory bowel disease (IBD) and specifically infantile-onset IBD patients, are characterized by high rates of extensive colonic involvement and decreased response rate to standard therapeutic regimens, including infliximab (IFX). We present a case series of 4 patients with infantile-onset IBD achieving clinical and biologic remission, after treatment with therapeutic drug monitoring (TDM)-guided accelerated high-dose IFX therapy. All patients were treated with accelerated high-dose IFX induction of up to 22 mg/kg. In 3 of these patients, accelerated high-dose IFX was used following failure of intensified standard dose induction. All patients achieved remission following re-induction.We suggest that children with infantile-onset IBD may require a TDM-guided accelerated high-dose IFX induction and maintenance treatment in order to achieve and maintain remission. Personalized approach in these patients is essential in order to prevent underdosing and to avoid inappropriate interpretation of treatment failure.

Little is known about the effect of prematurity on later development of celiac disease (CD). We conducted a retrospective analysis of real-world data examining the association between very low birth weight (VLBW) prematurity and later development of CD autoimmunity (CDA) in 3580 infants born between years 2000 and 2012 and their matched controls. At a median of 12 years, VLBW prematurity was negatively associated with later development of CDA with a cumulative prevalence of 5.9 per 1000 versus 10.3 per 1000 (P = 0.02), though more former VLBW premature infants were ever tested for CDA (48.5% vs 37.4%, P < 0.001). The odds ratio for developing CDA among children born preterm at VLBW was 0.57 (95% confidence interval (CI) 0.35-0.92) as compared with matched controls. There was no difference in clinical characteristics of CDA between both groups. In conclusion, VLBW preterm infants present a decreased risk for the development of CDA during childhood and adolescence.

To describe trends and correlates of acid-suppressant therapy usage during the first year of life.A population-based cohort in a large state-mandated health fund in Israel, including members born between 2005 and 2020, was conducted. Acid-suppressant therapy initiation was defined by any purchase within the first year of life. The association between acid-suppressant therapy initiation with medical and sociodemographic characteristics was assessed via logistic regression.Among 595 860 children, acid-suppressant therapy was initiated in 22 412 (37.6 per 1000). The incidence rate increased by 2.8-fold from 18.2 per 1000 in 2005 to 51.0 per 1000 in 2020, furthermore the median age at initiation decreased. Primary care providers accounted for 74.8% of prescribing physicians in 2005 vs 96.1% in 2020, whereas the prevalence of prescribing gastroenterologists decreased from 18.8% to 2.8%. Preterm birth and small weight per gestational age were associated with acid-suppressant therapy usage, with an aOR of 4.23 (95% CI 3.59-4.99), 3.05 (95% CI 2.72-3.42), and 1.65 (95% CI 1.58-1.74) for extreme, very, and moderate preterm vs term birth and aOR 1.22 (95% CI 1.16-1.28) for small weight per gestational age. Birth order was inversely associated with acid-suppressant therapy initiation, with aOR 0.62 (95% CI 0.60-0.65) for third born vs firstborns. High socioeconomic status was linearly associated with initiation, with aOR 1.12 (95% CI 1.11-1.12) per 1-point increase on a 10-point score.Our analysis demonstrates a substantial increase in early life exposure to acid-suppressant therapy during recent years in Israel. Correlates for initiation in early life were identified to define a population for intervention to reduce potential unnecessary use.

Background: Knowledge and understanding of risk mechanisms associated with pediatric feeding disorders (PFD) remain limited. We aimed to investigate causative factors associated with PFD and their relation to specific PFD types according to the recent consensus WHO-based definition. Methods: We retrospectively reviewed the medical records of children with PFD and retrieved their demographic and clinical characteristics. Healthy age- and sex-matched children served as controls. Results: Included were 254 children with PFD [median (interquartile range) age 16.4 (9.5-33) months at diagnosis] and 108 children in the control group [median age 24.85 (14.5-28.5) months]. According to the WHO-based definition, disturbances in oral intake were predominantly related to nutritional dysfunction in 118 (46.6%), feeding skill dysfunction in 83 (32.3%), medical conditions in 42 (16.7%) and psychosocial dysfunction in 11 (4.4%). In multivariate analysis, children with PFD had a higher risk for lower socioeconomic background (PPP=0.003). There were no significant differences in any of those variables between PFD types. Conclusions: Low socioeconomic status, lack of breastfeeding, and low birth weight were significantly more frequent in children with PFD. PDF manifest as multiple dysfunctions, thus highlighting the need to offer these children and their families multidisciplinary care.

Abstract Juvenile polyposis syndrome (JPS), has diverse phenotypes. Aim: To assess mutation rate, clinical features and genotype-phenotype correlation among Israeli JPS kindreds from different ethnicities. Methods Patients’ data were extracted retrospectively from 5 centers. Results Thirty five kindreds (49 patients) were included. Thirty one (89%) Jewish [10 (32%) Ashkenazi; 9 (29%) Sephardi; 11 (35%) non-Russia former Soviet-Union countries (NRFSU), one (3%) unknown]. 40/49 individuals from 27 families underwent genetic testing. Among them 34, from 21 families (85, 78%, respectively) had a pathogenic mutation: BMPR1A n = 15 (71%), SMAD4 n = 6 families (29%). While no SMAD4 mutation was described among Jewish families from NRFSU, 7 NRFSU families carried a founder mutation comprising a large genomic deletion of BMPR1A. GI involvement was reported in 42 patients (86%): colonic polyps (n = 40, 95%, > 50 polyps n = 14, 35%) and 12 underwent colonic resection. Fourteen patients (34%) had gastric or small bowel involvement (n = 5) and 4\14 underwent gastrectomy due to polyp burden. Families from NRFSU had more gastric involvement (66.7% vs. 22.2%- Sephardic and 20%- Ashkenazi Jews; p = 0.038), with more gastric polyps (p = 0.017). Conclusions We demonstrated a high rate of mutation detection in the heterogeneous population of Israel. Patients from NRFSU with BMPR1A mutation had high rate of gastric involvement.

The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15 years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041).Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome. What is Known: •Familial clustering of inflammatory bowel disease (IBD) has been reported in 5%-15% of IBD patients. •The investigation of the impact of a positive family history upon IBD characteristics and severity revealed conflicting results. What is New: •In this cohort of 325 children with IBD, 25.2% had a positive family history. •The rate of a positive family history of IBD in the pediatric IBD population is increasing. •A positive family history may have some impact upon IBD phenotype but none on IBD outcome.

Background Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augments inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White blood cells (WBCs). This reduction correlated with disease activity1. Our aim in the current study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC). Methods Fourteen CD and 11 UC patients, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and faecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (5 mg/l) and Fcal levels (250 μg/mg) in CD (21 samples) and UC patients (20 samples). Results In UC, CLOCK (p < 0.025), CRY1 (p < 0.033) and PER1 (p < 0.038) showed decreased expression when Fcal levels were >>250 μg/mg. When compared with the clinical status only BMAL1 showed reduced expression (p < 0.019). CRP levels showed no correlation with clock gene expression. In CD, CRP as well as the clinical status correlated with clock gene expression. Whereas CLOCK was reduced (p < 0.019), PER2 was induced (p < 0.005) when CRP levels were >5 mg/dl. Furthermore, CLOCK (p < 0.0005), PER1 (0.017) and PER2 (0.044) were reduced in CD patients with an active disease. However, Fcal did not correlate with clock gene expression. Conclusion Altered levels of certain clock genes were demonstrated in young CD and UC patients in relapse vs. remission and correlated with Fcal in UC patients and clinical status as well as CRP levels in CD patients. Reference

BackgroundAlterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC).MethodsHospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome.ResultsTwenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm.ConclusionPatients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408).

Background The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction. Methods Participants were children 6–17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies. Results Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group. Conclusions Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).

As a large number of cancers are caused by nonsense mutations in key genes, read-through of these mutations to restore full-length protein expression is a potential therapeutic strategy. Mutations in the adenomatous polyposis coli (APC) gene initiate the majority of both sporadic and hereditary colorectal cancers (CRC) and around 30% of these mutations are nonsense mutations. Our goal was to test the feasibility and effectiveness of APC nonsense mutation read-through as a potential chemo-preventive therapy in Familial Adenomatous Polyposis (FAP), an inherited CRC syndrome patients. Ten FAP patients harboring APC nonsense mutations were treated with the read-through inducing antibiotic erythromycin for 4 months. Endoscopic assessment of the adenomas was performed at baseline, after 4 and after 12 months. Adenoma burden was documented in terms of adenoma number, maximal polyp size and cumulative polyp size per procedure. Tissue samples were collected and subjected to molecular and genetic analyses. Our results show that in the majority of patients the treatment led to a decrease in cumulative adenoma burden, median reduction in cumulative adenoma size and median reduction in adenoma number. Molecular and genetic analyses of the adenomas revealed that the treatment led to a reduced number of somatic APC mutations, reduced cellular proliferation and restoration of APC tumor-suppressing activity. Together, our findings show that induced read-through of APC nonsense mutations leads to promising clinical results and should be further investigated to establish its therapeutic potential in FAP and sporadic CRCs harboring nonsense APC mutations.

Extraintestinal manifestations (EIM) are common complications of inflammatory bowel disease (IBD) associated with morbidity and reduced quality of life (QOL). The aim of this study was to identify and validate predictors for EIM in children with IBD. The medical records of children with IBD were retrospectively reviewed, and EIM present before diagnosis and those detected during follow-up, were recorded. One-hundred children were included, and their median age (interquartile range) was 13.9 (11.9–15.2) years. Forty-six (46%) children had EIM, including 10 (10%) whose EIM was present before diagnosis and 36 (36%) during follow-up. The most common EIMs were aphthous stomatitis (18%), arthralgia (14%), dermatologic manifestations (8%), and arthritis (6%). A body mass index in the lower or upper quartile (hazard ratio [HR] 9.30 and 23.71, respectively, p

Background and AimsThe role of hepcidin in inflammatory bowel disease [IBD] in children with anaemia is poorly understood. However, it has been shown that vitamin D suppresses hepcidin expression. We aimed to assess serum hepcidin levels and the effect of vitamin D treatment on those levels in newly diagnosed IBD paediatric patients.MethodsEighty-five children were prospectively recruited in the Dana-Dwek Children’s Hospital [40 newly diagnosed IBD, 45 healthy controls, 47% female, mean age 13.5 ± 3.4 years]. Blood samples for measurement of interleukin 6 [IL-6], C-reactive protein [CRP], hepcidin, iron parameters and 25-hydroxyvitamin D [25-(OH)-D] levels were obtained at baseline. Patients with mild-to-moderate signs and symptoms of IBD were treated with 4000 units of vitamin D daily for 2 weeks, after which the blood tests were repeated.ResultsBasal hepcidin, IL-6, CRP and platelet counts were significantly higher, and haemoglobin, serum iron and transferrin levels were significantly lower in the IBD children compared to controls [p < 0.001]. Eighteen patients completed 2 weeks of treatment with vitamin D. Following treatment, serum 25-(OH)-D concentrations increased by 40% [from 22.5 to 32.5 ng/mL], and serum hepcidin, CRP and ferritin levels decreased by 81%, 81% and 40% [from 33.9 to 6.7 ng/mL, from 23.9 to 4.7 mg/L, and from 27 to 16 ng/mL, respectively] [p ≤ 0.001].ConclusionSerum hepcidin levels were significantly higher in IBD paediatric patients compared to controls. Following vitamin D treatment, serum hepcidin concentration decreased significantly. These findings suggest a potential role for vitamin D in treating anaemia in IBD children.ClinicalTrials.gov numberNCT03145896

Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps, and characteristic mucocutaneous freckling. Development of small bowel intestinal polyps may lead to intussusception in children may require emergency laparotomy with potential loss of bowel. Gastrointestinal polyps may lead to bleeding and anemia. This European Society for Paediatric Gastroenterology Hepatology and Nutrition position paper provides a guide for diagnosis, assessment, and management of PJS in children and adolescents and guidance on avoiding complications from PJS or from the endoscopic procedures performed on these patients.This is the first position paper regarding PJS published by European Society for Paediatric Gastroenterology Hepatology and Nutrition. Literature from PubMed, Medline, and Embase was reviewed and in the absence of evidence, recommendations reflect the opinion of pediatric and adult experts involved in the care of polyposis syndromes. Because many of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, some of the recommendations are based on expert opinion. This position paper will be helpful in the appropriate management and timing of procedures in children and adolescents with PJS.

Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, characterized by the development of hundreds to thousands of adenomas in the colorectum, with implications in children and adolescents. Almost all adult patients will develop colorectal cancer if they are not identified and treated early enough. Identifying and screening for FAP commences in adolescence. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the adenomatous polyposis (APC) gene. This European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) position paper provides a guide for diagnosis, assessment, and management of FAP in children and adolescents.This is the first position paper regarding FAP published by ESPGHAN. Literature from PubMed, Medline, and Embase was reviewed and in the absence of evidence, recommendations reflect the opinion of paediatric and adult experts involved in the care of polyposis syndromes. Because many of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, these of the recommendations are supported on expert opinion. This position paper will instruct on the appropriate management and timing of procedures in children and adolescents with FAP.

Objective: Combinations of antitumor necrosis factor alpha (TNFα) and immunomodulators may be indicated in high-risk inflammatory bowel disease patients. Our aims were to compare disease course between children that did and did not step down to anti-TNFα monotherapy and to define risk factors for complicated disease course after stepping down. Methods: A retrospective review of the medical records of consecutive children who were treated with combination therapy. Results: Of 64 children, 32 continued combination therapy while the others stepped down to monotherapy (median duration of 6 months [range 6–10]). Children that stepped down had a trend of lower anti-TNFα levels (median [interquartile range] of 2.4 [1–4.2] µg/mL) compared to those that did not step down (4.5 [2.2–6.23] µg/mL, p = 0.065). Children with Crohn’s disease that stepped down had a significantly higher risk for disease exacerbation, hospital admission, and operation (p < 0.025). Univariate analysis revealed that penetrating phenotype, upper gastrointestinal involvement, higher disease activity at diagnosis, and lower anti-TNFα levels under combination therapy were predictors for complicated course after stepping down. Conclusion: Stepping down to anti-TNFα monotherapy may be related to lower anti-TNFα levels and to a more complicated disease course thereafter. Predictors for a complicated course were identified.

Heart rate variability (HRV), a marker of the parasympathetic vagal activity, was reportedly significantly lower in patients with inflammatory bowel disease (IBD) compared to healthy controls. The aim of this study was to evaluate HRV as a predictor of clinical outcomes in pediatric IBD.This was a prospective study. Children (12-18 years of age) with IBD were prospectively recruited. Each patient underwent two 10-min HRV measurements by means of a photoplethysmograph finger sensor. The square root of the mean squared differences of successive R-R pulse intervals (RMSSD), an indirect index of vagal activity, was calculated. Clinical data, including demographic variables, disease activity and course, medications, and laboratory results were collected during a follow-up of 12 months. The relation between RMSSD and clinical outcomes was examined, adjusting for confounders.A total of 34 children with IBD were included. Patients in clinical remission had a significantly higher RMSSD compared to patients with active disease (67.72 ± 27.81 versus 45.76 ± 22.04, respectively, P = 0.022). A multivariate analysis revealed that a higher RMSSD was a significant and independent predictor of lower risk of IBD exacerbation (odds ratio = 0.941, 95% confidence interval 0.887-0.998, p = 0.044).HRV correlates with IBD activity and may also serve as an independent predictor of disease exacerbation in pediatric IBD.

ObjectivesCeliac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients, and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation.MethodsWe conducted a prospective-observational study of all newly-diagnosed pediatric celiac patients, between August 2016 – April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics and blood test results were recorded at diagnosis and at three, six and twelve months of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l.ResultsOf 125 newly-diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3xULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD- 3.4) vs 7.3 (SD- 3.7) years, p

OBJECTIVES Inflammatory bowel disease (IBD) has a high impact on nutritional status. Sarcopenia is related to higher risk of surgery and rescue therapy in adults with IBD; however, comparable data in pediatric populations are scarce. We evaluated muscle mass as a predictor of disease outcome in pediatric IBD. METHODS All pediatric IBD patients who underwent magnetic resonance enterography (MRE) during 2008 to 2019 were included. Muscle mass was assessed by measuring the area of the psoas muscle at the upper level of L3 on MRE. The psoas area divided by the body surface area (BSA) yielded the psoas index. Clinical and radiological data, including disease location, activity, course, and medications were documented. The control group included non-IBD children who underwent an MR imaging study. RESULTS We enrolled 101 IBD patients, 69 (68.3%) with Crohn disease (CD) and 32 (31.7%) with ulcerative colitis (UC) (mean age 15.03 ± 3.27 years). The psoas index was significantly lower in the IBD patients compared with the 87 controls (326 vs 528, respectively, P

OBJECTIVES Both the inflammatory burden of Crohn disease (CD) and corticosteroids have a negative effect on bone density. Exclusive enteral nutrition (EEN) avoids corticosteroids and promotes endoscopic healing. We aimed to explore the effect of nutritional therapy on bone health in pediatric CD. METHODS This was a planned sub-study of a clinical trial enrolling children with new-onset mild-moderate CD. Children were randomized to either 6 weeks EEN followed by 6 weeks 25% partial enteral nutrition (PEN) or 6 weeks of 50% PEN with a CD exclusion diet followed by 6 weeks of 25% PEN with exclusion diet. Bone formation and resorption were measured at baseline, week 12 and week 24 by serum C-Propeptide of Type I Procollagen (CICP) and type I Collagen N-Telopeptide (NTX), respectively. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) scan at baseline and week 24. RESULTS Median CICP improved from 130 ng/mL (106-189) at baseline to 223 (143-258) at week 12 and 193 (143-252) at week 24 (P = 0.016 for both, n = 29 children). Median NTX remained unchanged (P = 0.45 and P = 0.45). Thirty-six children had DXA scans performed at diagnosis; 81% and 33% had z scores of

OBJECTIVES The impact of pediatric-onset inflammatory bowel disease (IBD) on growth is debated. We aimed to investigate the effect of IBD on anthropometric measures at young adulthood. METHODS Children diagnosed with Crohn disease (CD) or ulcerative colitis (UC) (2005-2019) were identified in a national database along with matched non-IBD controls. RESULTS Overall, 2229 IBD cases (68% CD) were matched to 4338 controls. Only females with CD differed in final height from controls (z scores: -0.37 ± 1.09 vs -0.25 ± 1.06, respectively; P = 0.01), corresponding to a mean difference of 0.7 ± 0.2 cm (all females) and 1.2 ± 0.3 cm in females diagnosed

OBJECTIVES Spinal muscular atrophy (SMA) is a genetic motor neuron disorder characterized by progressive muscle atrophy. Our aims were to evaluate the impact of nutritional intervention and nusinersen therapy on the nutritional status of SMA patients. STUDY DESIGN This prospective study included all children and young adults (

AIM More normal weight and overweight children are currently diagnosed with celiac disease (CD). We aimed to describe the relation between body mass index (BMI) and the clinical characteristics of paediatric CD and to determine the effect of a gluten-free diet (GFD) on BMI. METHODS Data on all children diagnosed with CD during 7/2010-7/2019 with documented anthropometric data at diagnosis were retrospectively analysed. The children were divided into three groups according to BMI status at diagnosis: underweight, normal weight and overweight (BMIs 85%, respectively). RESULTS Of the 236 children [median age 7.87 (4.91-11) years] included in the study, 24 (10.1%) were underweight at diagnosis and 32 (13.6%) were overweight. Diarrhoea as the presenting symptom was significantly more common in the overweight group (p = 0.012), while short stature was more common in the underweight group (p = 0.002). Following a GFD had no significant effect on the children's BMI during a median follow-up of 15.7 (0-85) months, but there was a significant shift of patients between the BMI categories (p

This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 wk after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (ICC; downregulation of transmembrane member 16A (TMEM16A) and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to a decrease in final body weight, suggesting less effective nutrient absorption. The purpose of this study was to evaluate the mechanisms of intestinal motility in a rat model of short bowel syndrome (SBS). Rats were divided into three groups: Sham rats underwent bowel transection; SBS-NSI rats underwent a 75% bowel resection and presented with normal intestinal size (NSI) at euthanasia and hypermotility patterns; SBS-DYS showed dysmotile (DYS) enlarged intestine and inhibited motility patterns. Animals were euthanized after 2 wk. Illumina's digital gene expression (DGE) analysis was used to determine the intestinal motility-related gene expression profiling in mucosal samples. Intestinal motility-related and ICC genes and protein expression in intestinal muscle layer were determined using real-time PCR, Western blotting, and immunohistochemistry. Gastrointestinal tract motility was studied by microcomputer tomography. From 10 Ca(2+) signaling pathway-related genes, six genes in jejunum and seven genes in ileum were downregulated in SBS vs. Sham animals. Downregulation of TMEM16A mRNA and protein was confirmed by real-time PCR. Rapid intestinal transit time in SBS-NSI rats correlated with a mild decrease in TMEM16A, c-kit, and vimentin mRNA and protein expression (vs/. Sham animals). SBS-DYS rats demonstrated enlarged intestinal loops and delayed small intestinal emptying (on imaging studies) that were correlated with marked downregulation in TMEM16A, c-kit, vimentin, and ghrelin mRNA and protein levels compared with the other two groups. In conclusion, 2 wk following massive bowel resection in rats, impaired intestinal motility was associated with decreased vimentin and ghrelin gene and protein levels as well as loss of ICC (c-kit and TMEM16A). NEW & NOTEWORTHY This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 weeks after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (downregulation of TMEM 16A, and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to decrease in final body weight, suggesting less effective nutrient absorption.

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients p p n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56).Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged What is Known? •Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year. What is New? •The majority of young PIBD (