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Anti-tumor necrosis factor (TNF) antibodies play a major role in treating inflammatory bowel disease (IBD), both in adult and pediatric patients. While there is a large number of studies on efficacy and safety of infliximab in treating children and adolescents with ulcerative colitis (UC), data on adalimumab (ADA) are scarce. Here, we review published case reports, cohort and real-time data, as well as the first randomized trial, ENVISION I, using ADA for treating pediatric UC. Available evidence confirms good efficacy in inducing and maintaining remission in children and adolescents with UC, with even higher response rates compared to adult UC. ENVISION I showed that in UC patients responding to ADA induction therapy, almost half of the patients remained in remission after 52 weeks of therapy on high-dosing ADA (weekly administration). As already well experienced with other biologics, dosing schemes are different between pediatric and adult patients, with children often requiring higher dosing. Further data are required to better understand how to optimize ADA therapy. The present and still-growing evidence places subcutaneous (sc.) anti-TNF-medication as alternative first-line therapy also for pediatric UC. This is also reflected by the preference for sc. medication of adolescent patients allowing less frequent and autonomous drug administration. [ABSTRACT FROM AUTHOR]

Objective The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. Methods We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. Results Forty-three cases were included. IBD [mainly Crohn's disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4–15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19–56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). Conclusions This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse. [ABSTRACT FROM AUTHOR]

An observatory of sexual harassment and psychological abuse was set up at one of France's largest schools of medicine to both quantify and reduce sexual harassment or psychological abuse of medical students. Over a 2-year period, we described the evolution of sexual harassment and psychological abuse and explored for associated factors. Moreover, a qualitative analysis using an inductive approach was performed from students' verbatim. 2795 responses were collected. Sexual harassment was reported in 7% and psychological abuse in 15%, at baseline, and decreased after the observatory was set up. Women had higher odds of being a victim of sexual harassment. Older students reported less often psychological abuse and being a witness of sexual harassment. Surgery departments were associated with up to 5.7-fold increased odds of sexual harassment. Surgery and pediatrics departments were associated with a 2-fold increased odds of psychological abuse. Qualitative analysis revealed four categories: humiliation, the feeling of inferiority, sexual harassment, and manifestations of violence. During clerkships, factors associated with higher odds of sexual harassment and psychological abuse were female gender, younger age, and departments of surgery. Setting up such an observatory may contribute to reduce this burden and provide a useful tool to raise awareness. [ABSTRACT FROM AUTHOR]

Children on long-term home parenteral nutrition (HPN) are at increased risk of suboptimal growth and metabolic bone disease (MBD) i.e. decreased bone mineral density (BMD). The aims of this cross-sectional study were to assess growth and bone health in children on long term HPN and to identify risk factors for MBD. Children above the age of 5 years, stable on HPN for more than 2 years were included. Medical files were reviewed retrospectively and included demographics, gestational age, birth weight and height, indication for PN, age at PN start, duration of PN, number of weekly PN infusions, weight-for-age and height-for-age (SD), body mass index (BMI, kg/m2) as well as blood and urine analyses at the time of Dual X-ray absorptiometry (DXA) measurements. All BMD values were adjusted to statural age which corresponds to the 50th percentile of height. Growth failure (height-for-age ≤ -2SD) and MBD (at least one BMD measurement ≤ -2SD) were analyzed according to the indication of PN, duration of PN and PN dependency index (PNDI) by comparing means and performing logistic regression analysis. PNDI is the ratio of non-protein energy intake in HPN to resting energy expenditure using Schofield equations. Forty children were assessed at 12.4 ± 4.5 years of age. Mean age at PN start was 1.1 ± 3.6 y (median 0.5). The indications for PN were short bowel syndrome (SBS, n = 21), chronic intestinal pseudo-obstruction syndrome (CIPOS, n = 10) and congenital enteropathies (CE, n = 9). The mean number of PN perfusions was 6 ± 1/week. PNDI was 110 ± 30%. The mean serum level of 25-OHD3 was suboptimal at 26.5 ± 9.1 ng/mL (66.2 ± 22.8 nmol/L). The mean concentrations of calcium, phosphorus, and parathyroid hormone (PTH) were in the normal ranges. Eight children (20%) had PTH levels above normal with low 25-OHD3 levels. The mean weight-for-age and height-for-age Z-scores SDS were 0.4 ± 0.9 and −0.5 ± 1.1 respectively. The actual height was lower than genetic target height (p < 0.001). The BMD Z-scores, adjusted to the 50th percentile of height, of the spine, the left femur and the whole body were: −1.1 ± 1.7, −1.2 ± 1.5 and −1.5 ± 1.8 SDS respectively. Children with CE had significantly lower BMD values than those with SBS and CIPOS (p = 0.01). Only two children had bone fractures after a mild trauma (5%). All children on long-term PN, are at risk of low BMD. High dependency on PN (PNDI>120%) and very long-term PN (>10 years) do not appear to increase the risk of growth failure nor MBD. PN-related bone fractures were rare. Close follow-up remains mandatory. • Suboptimal bone mineral density (BMD) is observed in children on long term parenteral nutrition (PN). • The prevalence of metabolic bone disease does not seem to increase with the degree of dependency to PN nor duration of PN > 10 years. • Children suffering from congenital enteropathies are at increased risk of MBD. • Children on long term PN have suboptimal levels of 25-OHD3 with no correlation to low BMD. • Bone fractures in children on long term PN are rare. [ABSTRACT FROM AUTHOR]

Aims Exclusive enteral nutrition [EEN] is as efficacious as corticosteroids [CS] to induce remission in Crohn's disease [CD], without their adverse effects. EEN seems to be more efficient than steroids to induce mucosal healing, but the underlying molecular mechanisms are only sparsely understood. We aimed in the present work to study the anti-inflammatory effects of EEN with Modulen IBD® vs CS in active paediatric CD, and to assess its modulatory effects on the intestinal microbiota as compared with steroids. Materials and Methods Nineteen patients with new-onset active CD (Harvey-Bradshaw index [HBI] >5), aged from 6 to 17 years, were included in this prospective randomised induction trial with CS [ n = 6] or EEN [ n = 13]. Patients were assessed at Weeks 0 and 8 using clinical parameters HBI, endoscopic findings (Crohn's Disease Endoscopic Index of Severity [CDEIS] score) and analysis of faecal microbiota composition. Results At 8 weeks, clinical remission [HBI <5] was achieved in 13/13 patients on EEN and 5/6 patients on steroids; the mucosal healing rate was significantly higher in the EEN [89%] compared with steroid group [17%]. There were no significant differences between groups regarding biological markers, but the intestinal microbiota profiles shifted upon EEN-induced remission to a higher proportion of Ruminococcus bacteria compared with steroid-induced remission [ p = 0.049], and with higher proportions of bacteria belonging to Clostridium in EEN-treated patients. Conclusions Both steroid and EEN induced clinical remission. However, patients with EEN-induced remission showed a higher rate of mucosal healing and this was associated with a different gut microbiota compositional shift in these children. [ABSTRACT FROM AUTHOR]

Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children. The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting "nutritional failure" which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx. [ABSTRACT FROM AUTHOR]

Mutations in interleukin-10 receptor (IL-10R) genes are one cause of very early-onset inflammatory bowel disease with perianal lesions, which can be cured by hematopoietic stem cell transplantation. Using a functional test, which assesses responsiveness of peripheral monocytes to IL-10, we identified three unrelated Portuguese patients carrying two novel IL-10RB mutations. In the three patients, sequencing of genomic DNA identified the same large deletion of exon 3 which precluded protein expression. This mutation was homozygous in two patients born from consanguineous families and heterozygous in the third patient born from unrelated parents. Microsatellite analysis of the IL10RB genomic region revealed a common haplotype in the three Portuguese families pointing to a founder deletion inherited from a common ancestor 400 years ago. In the third patient, surface expression of IL-10R was normal but signaling in response to IL-10 was impaired. Complementary DNA sequencing and next-generation sequencing of IL10RB locus with custom-made probes revealed a ≈ 6 Kb duplication encompassing the exon 6 which leads to a frameshift mutation and a loss of the TYK2-interacting Box 2 motif. Altogether, we describe two novel copy number variations in IL10RB, one with founder effect and one preserving cell surface expression but abolishing signaling. [ABSTRACT FROM AUTHOR]

Background: Infants with intestinal failure (IF) are at increased risk of malnutrition and require adapted nutrition support. Optimal weight gain during nutrition rehabilitation should occur at the velocity of statural age (adjusted to the 50th percentile of height) and not chronological age. The aim of this study was to assess the relationship between weight gain during catch-up growth, nonprotein energy intake (NPEI) provided by total parenteral nutrition (TPN), and resting energy expenditure (REE) in children with severe malnutrition due to IF.Materials and Methods: This retrospective study included all infants with severe malnutrition treated with TPN for IF between January 1, 2010, and December 31, 2013. They all had no or minimal oral intake (<10% REE). The REE was calculated using the Schofield equations.Results: Seventeen children were included (11 boys) with a mean age at TPN onset of 5 mo. They were followed for a mean duration of 39 days. On admission, body weight and height were -3.1 ± 0.9 and -3.3 ± 1.3 SD, respectively. The indications for TPN were short bowel syndrome (n = 10), congenital enteropathy (microvillous inclusion disease, n = 6) and chronic intestinal pseudo-obstruction syndrome (n = 1). After 28 days of nutrition rehabilitation with full NPEI from TPN, the observed weight gain was 110 ± 5% of optimal weight gain for statural age. The mean NPEI from TPN was 104.3 ± 8.0 kcal/kg/d. The mean ratio of NPEI over REE was 2.1 ± 0.2.Conclusion: Optimal weight gain was achieved with NPEI from TPN twice the REE in severely malnourished infants with IF. NPEI values were adequate and not excessive for age. [ABSTRACT FROM AUTHOR]

Intestinal microbiota plays a major role in the digestive physiology and in the gut homeostasy. Errors in the regulation of the cross talk between intestinal immune response and gut microbiota could lead to a pathological or uncontrolled inflammation and development of pathologies. Inflammatory Bowel diseases (IBD) are chronic intestinal disorders in which, in a genetically susceptible subject, the mucosal immune system displays an aberrant response towards luminal antigens, most probably commensal bacteria. Patients with IBD exhibit an imbalance in the composition of intestinal microbiota called "dysbiosis". Imbalance of gut microbial populations has important functional consequences and is implicated in many digestive diseases such as IBD or coeliac disease. These observations have led to an increasing number of studies, which aim to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Early onset inflammatory bowel diseases (EO-IBD) developing during the first year of life are likely to reflect inherited defects in key mechanism(s) controlling intestinal homeostasis, as recently suggested for interleukin 10 (IL10). Thus, we aimed to further elaborate the hypothesis of defective anti-inflammatory responses in patients with IBD.METHODS:The capacities of transforming growth factor β (TGFβ) and IL10 to inhibit proinflammatory cytokine production by monocyte-derived dendritic cells (MoDC) or peripheral blood cells (PBMC) was analyzed in 75 children with IBD, including 13 infants with EO-IBD (in whom autoimmune diseases or classical immunodeficiencies were ruled out). IL10 receptor-A/-B expression, STAT3 activation in response to IL6, IL10, IL21, IL22 were analyzed by FACS and western blotting. IL10RA and B genes were sequenced. The response to IL22 was tested in ileal/colonic tissue cultures. Tissue gene expression was analyzed by Taqman real-time polymerase chain reaction.RESULTS:Production of IL10 in response to bacterial motifs was normal in all IBD patients. In contrast to our original hypothesis, no defect of the anti-inflammatory potential of TGFβ and IL10 was observed in children with IBD or EO-IBD except two infants who presented with granuloma-positive colitis at 3 months of life: no response to IL10 was observed secondary to mutations in the α (p.R262C) or β (p.E141X) chain of IL10R, respectively, although a fully functional Jak-STAT3 pathway was present in both patients. When analyzing the regulation of intestinal bacterial clearance, we detected a defect in the patient with absent IL10 RB to upregulate protective transcripts in response to IL22, whereas all other EO-IBD patients, including the patient with an abnormal α chain, responded normally.CONCLUSIONS:Impaired IL10 signaling characterizes a subgroup of IBD patients, whereas the majority of children with severe IBD including EO forms normally produces and responds to IL10. Defective IL22 signaling may additionally impair intestinal epithelial clearance. Our data point out the complexity of IBD, which represent a group of distinct diseases with several pathogenetic abnormalities. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Detailed comparative assessment of procedure‐related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited.We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure‐related factors associated with FMT success in CDI.We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression.Six hundred fifty‐eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty‐seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20–3.88]), non‐severe refractory CDI (OR: 15.35, [1.94–318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11–5.67]), insufficient bowel cleansing (OR: 5.47, [1.57–20.03]) and partial FMT retention (OR: 9.97, [2.62–48.49]) were associated with CDI recurrence within 8 weeks.Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real‐life practice, whereas it had lower efficacy in severe CDI and non‐severe refractory CDI. [ABSTRACT FROM AUTHOR]

Environmental factors, particularly diet, are the focus of current research as potential triggers of inflammatory bowel disease (IBD). Epidemiological cohort data showing a rapid increase of IBD in western countries and the emergence of IBD in developing countries paralleling the introduction of a western diet are indirect arguments linking food and food behaviour to intestinal inflammation. The successful use of exclusive enteral nutrition (EEN), now considered as first-line induction therapy for paediatric Crohn's disease (CD), is the strongest argument for a link between diet and IBD. Mechanistic studies revealed that EEN impacts intestinal microbiota composition and together with the exclusion of potentially harmful food ingredients this allows the control of intestinal inflammation and induces mucosal healing. However, the exclusivity character of EEN is a major drawback. Based on the data of EEN, the search for more tolerable and still effective diets has begun. Recent reports on the new CD exclusion diet (CDED), CD-TREAT, as well as the specific carbohydrate diet (SCD) provide the first promising results, further underlining the potential of diet to control inflammation in patients with CD by excluding certain food components. Ongoing research is trying to combine nutritional interventions with analyses of intestinal microbiota and their metabolic functions with the aim of correcting the intestinal dysbiosis that characterizes IBD. This research is promising and gives new hope to patients that have been looking for decades for nutritional interventions with the aim of stabilizing their disease course. There might even be potential for disease prevention in high-risk patients by excluding potentially harmful food components. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Caused by biallelic mutations of the gene encoding the transcription factor RFX6 , the rare Mitchell-Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, duodenal atresia, and severe chronic diarrhea. So far, sixteen cases have been reported, all with a poor prognosis. This study discusses the multidisciplinary intensive clinical management of 4 new cases of MRS that survived over the first 2 years of life. Moreover, it demonstrates how the mutations impair the RFX6 function., Methods: Clinical records were analyzed and described in detail. The functional impact of two RFX6 R181W and RFX6 V506G variants was assessed by measuring their ability to transactivate insulin transcription and genes that encode the L-type calcium channels required for normal pancreatic beta-cell function., Results: All four patients were small for gestational age (SGA) and prenatally diagnosed with duodenal atresia. They presented with neonatal diabetes early in life and were treated with intravenous insulin therapy before switching to subcutaneous insulin pump therapy. All patients faced recurrent hypoglycemic episodes, exacerbated when parenteral nutrition (PN) was disconnected. A sensor-augmented insulin pump therapy with a predictive low-glucose suspension system was installed with good results. One patient had a homozygous c.1517T>G (p.Val506Gly) mutation, two patients had a homozygous p.Arg181Trp mutation, and one patient presented with new compound heterozygosity. The RFX6 V506G and RFX6 R181W mutations failed to transactivate the expression of insulin and genes that encode L-type calcium channel subunits required for normal pancreatic beta-cell function., Conclusions/interpretation: Multidisciplinary and intensive disease management improved the clinical outcomes in four patients with MRS, including adjustment of parenteral/oral nutrition progression and advanced diabetes technologies. A better understanding of RFX6 function, in both intestine and pancreas cells, may break ground in new therapies, particularly regarding the use of drugs that modulate the enteroendocrine system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Passone, Vermillac, Staels, Besancon, Kariyawasam, Godot, Lambe, Talbotec, Girard, Chardot, Berteloot, Hachem, Lapillonne, Poidvin, Storey, Neve, Stan, Dugelay, Fauret-Amsellem, Capri, Cavé, Ybarra, Chandra, Scharfmann, Bismuth, Polak, Carel, Pigneur and Beltrand.)

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection.MethodsWe set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections.ResultsPrevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children.ConclusionPrior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

Background and study aims  The real burden of urgent endoscopy in children has not been studied yet. Our aim was to evaluate the need for urgent endoscopy in children. Patients and methods  Information was collected about all the calls that were received during the 24 hour on-call shift for pediatric endoscopy in the region of Ile-de-France (12.1 million inhabitants) during a 6 months period (February-July 2017). Results  A total of 237 calls (19 calls/y/100,000 children) were collected regarding children of an average age of 3.2 years (range 2 days-18 years). Most of the calls (68 %) were for foreign body ingestions. Gastroscopy was required in 32 % of children: 24 % of those calling for foreign body ingestion, 48 % for gastrointestinal bleeding, 63 % for caustic ingestions ( P  = 0.01). The average time between the call and the urgent endoscopy were below the international recommendations for each situation. Conclusions  Calling the endoscopist seems to have become a recurrent practice, although in most cases, urgent endoscopy did not appear necessary, especially for foreign body ingestion. This organization of pediatric endoscopy on call was able to guarantee the performance of urgent endoscopy in adequate timing for a highly populated region., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Glycogenosis type Ib (GSD1B) causes not only hypoglycemia but also infections and "Crohn's disease like" inflammatory bowel disease (IBD) that can significantly impair patient's quality of life. We retrospectively evaluated infectious and digestive complications in 9 French patients (3 girls, 6 boys) diagnosed at 0.8 years on average, with a mean follow-up of 19.1 years. Infections occurred earlier than IBD, at mean ages of 1.7 and 3.8 years, respectively. The number of acute hospitalizations was 0.7/year due to infectious (0.4/year) or digestive symptoms (0.4/year). Clinical presentations allowed separating patients into mild ( n  = 5) and severe ( n  = 4) intestinal involvement. Patients in the severe group had more serious digestive symptoms but also earlier neutropenia (median 0.3 vs. 1.5 years, p  =0 .046) with a tendency to a lower neutrophil count (NC) during follow-up, and a higher number of acute hospitalizations (median 1.3/year vs. 0.2/year, p  =0 .014) due to digestive symptoms (median 0.6/year vs. 0.05/year, p  = 0,012) and infections (median 0.8/year vs. 0.2/year, p =0 .014). Treatments included G-CSF and cotrimoxazole ( n  = 7), 5-aminosalicylic acid ( n  = 2), and a polymeric solution enriched in the anti-inflammatory cytokine TGF-β ( n  = 4, "severe" group), and immunomodulatory treatment ( n  = 1). In conclusion, infections and IBD are rare but severe complications in GSD1B. Neutropenia tended to be more prevalent in the severe IBD group than in the mild IBD group. Dietetic treatment with specific anti-inflammatory solutions seems particularly appropriate in these patients., Competing Interests: FR has received speaker fees from: Shering-Plough, Nestlé, MeadJohnson, Ferring, MSD, Johnson & Johnson, Centocor, AbbVie; serves as a board member for: SAC:DEVELOP (Johnson & Johnson), and has been invited to MSD France, Nestlé Nutrition Institute, Nestlé Health Science, Danone, MeadJohnson; TAKEDA, CELLGENE, BIOGENE, ARKOPHARMA. The other authors have no conflicts of interest., (© 2020 The Authors.)

Background and Aims: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment., Methods: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally., Results: Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES., Conclusions: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD., (© The Author(s) 2018. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Infants with intestinal failure (IF) are at increased risk of malnutrition and require adapted nutrition support. Optimal weight gain during nutrition rehabilitation should occur at the velocity of statural age (adjusted to the 50 th percentile of height) and not chronological age. The aim of this study was to assess the relationship between weight gain during catch-up growth, nonprotein energy intake (NPEI) provided by total parenteral nutrition (TPN), and resting energy expenditure (REE) in children with severe malnutrition due to IF., Materials and Methods: This retrospective study included all infants with severe malnutrition treated with TPN for IF between January 1, 2010, and December 31, 2013. They all had no or minimal oral intake (<10% REE). The REE was calculated using the Schofield equations., Results: Seventeen children were included (11 boys) with a mean age at TPN onset of 5 mo. They were followed for a mean duration of 39 days. On admission, body weight and height were -3.1 ± 0.9 and -3.3 ± 1.3 SD, respectively. The indications for TPN were short bowel syndrome (n = 10), congenital enteropathy (microvillous inclusion disease, n = 6) and chronic intestinal pseudo-obstruction syndrome (n = 1). After 28 days of nutrition rehabilitation with full NPEI from TPN, the observed weight gain was 110 ± 5% of optimal weight gain for statural age. The mean NPEI from TPN was 104.3 ± 8.0 kcal/kg/d. The mean ratio of NPEI over REE was 2.1 ± 0.2., Conclusion: Optimal weight gain was achieved with NPEI from TPN twice the REE in severely malnourished infants with IF. NPEI values were adequate and not excessive for age., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Specific features of childhood-onset inflammatory bowel diseases. The incidence of pediatric-onset inflammatory bowel diseases (PIBD) is increasing in developed countries for several decades. Pediatric-onset of the disease is a factor of severity, due to a higher activity and a longer evolution of the disease. IBD presents as two major forms, Crohn's disease (CD) potentially affecting all parts of the gastrointestinal tract, and ulcerative colitis (UC), which is restricted to the colon and rectum. Exclusive enteral nutrition is the recommended first-choice induction therapy in luminal CD, allowing symptoms remission, mucosal healing and catch-up growth. The use of an immunosuppressive maintenance therapy is frequently required. Biological therapies may be used as first-line therapy in severe cases, or in case of failure of thiopurines. In mild to moderate forms of UC, salicylates retain an important role while the use of thiopurines or biological should be considered in severe forms of disease. The use of surgery is sometimes required, usually earlier in PIBD than in adult IBD patients., Competing Interests: H. Lengliné déclare avoir été prise en charge l’occasion de déplacements pour congrès par AbbVie. B. Pigneur déclare n’avoir aucun lien d’intérêts. F. Ruemmele déclare des interventions ponctuelles (conférences, conseils scientifiques) pour Schering-Plough, Nestlé Nutrition Institute et Nestlé Health Science, Mead Johnson, Ferring, Falk, MSD, Janssen, Centocor, Danone, Biocodex.

Inflammatory bowel disorders (IBD) are characterized by chronic and recurrent inflammatory reactions of the intestinal mucosa resulting in progressing ulcerating lesions. Research over the past decade clearly identified in patients with Crohn's disease (CD) a marked dysregulation of the intestinal microbiome (dysbiosis) as one trigger factor in these inflammatory processes, particularly in patients with a high genetic risk. When treating patients with CD, most drugs aim to control the inflammatory process (either by inhibiting inflammatory pathways or by reducing the activity of immune cells). Given the importance of the disturbed interaction between the microbiota and the host immune system, there might be a different therapeutic approach in targeting directly the intestinal microflora. There are good data to believe that the use of exclusive enteral nutrition (EEN) is one such option. Historically, enteral nutrition (EN) was used as supplemental nutritional therapy in CD patients with planned resection surgery. This treatment option showed unexpected and very powerful anti-inflammatory effects, and it was rapidly introduced as induction therapy for active CD. Several clinical trials and case series confirmed the efficacy of EN to induce remission in approximately 80% of patients equaling the potential of steroids. It is well established that EN has this strong anti-inflammatory potential only when given on an exclusive basis, without any additional food. This raises major compliance issues, probably one of the reasons why it is less used in adult patients. A recent study demonstrated that EEN has a specific effect on the intestinal microbiota, which is markedly different from steroid-induced remission, while all patients obtained complete clinical remission. These observations give a first basis for the understanding of the impact of EEN on dysbiosis in patients with CD., (2014 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Objective: Early-onset inflammatory bowel disease starting within the first months of life could be due to a particular genetic defect. We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution., Design: Ten patients with early-onset inflammatory bowel disease with confirmed mutations in IL10, IL10RA, or IL10RB genes were characterized on clinical, endoscopic-histological, immunobiological, and radiological findings. Functional assays to confirm defective responses to IL10 were performed on peripheral blood mononuclear cells., Results: A functional defect in IL10 signaling was confirmed in all IL10R patients tested. Disease started with severe diarrhea within the first 12 weeks in all patients. All infants showed Crohn's disease-like ulcerations limited to the colon with marked perianal inflammation (fissures, abscess, and fistula); disease progression to the small bowel occurred in only 1 patient. Four of the 10 patients had granulomata on histology, and all patients showed Crohn's disease-like mesenteric infiltration on imaging. Disease pattern was indistinguishable between IL10R alpha or beta chain or IL10 defects; autoimmunity was not observed. Mutations in IL10 were more frequently associated with bacterial and viral infections. Patients responded partially to treatment with steroids or anti-tumor necrosis factor drugs, whereas hematopoietic stem cell transplantation proved efficacious., Conclusion: The importance of the IL10 pathway within the colonic mucosa is highlighted by the development of severe colitis within a few weeks in infants with mutations in IL10, IL10RA, or IL10RB. Immunosuppression failed to correct the defect in this pathway, which seems to be a key to controlling inflammation in the colon.

Background: Idiopathic central precocious puberty (CPP) is rare in boys. The aim was to to analyze the presentation and evaluate the frequency of familial factor in boys with idiopathic CPP., Material/methods: Data for 28 boys seen consecutively by the same physician for idiopathic CPP were analyzed., Results: Puberty started after seven years in all the boys. The associations were intrauterine growth retardation in two, one of whom had Silver Russell syndrome, bilateral retinal degeneration (one case), epilepsy (one case), cryptorchidism (two cases), and inguinal hernia (two cases). All patients had normal basal plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The LH/FSH peaks ratio after a gonadotropin hormone-releasing hormone (GnRH) test was <2 in 8/26 and plasma testosterone <0.5 ng/ml in 5/28. Familial early puberty was found in 12 cases (40%). Familial and non-familial forms had similar characteristics, except that body mass index was greater in the familial form (P<0.04). Plasma testosterone of one patient, whose mother had menstruated at 11 years, remained >1 ng/ml despite shortening the interval between GnRH analogue injections., Conclusions: Puberty started after seven years in all cases of idiopathic CPP, suggesting that pubertal onset before this age suggests organic CPP. Almost half the cases had familial early puberty.