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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.

European Crohn's Colitis Organization (ECCO) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines recommend the early use of anti-TNF biologicals in pediatric Crohn disease (CD) patients with positive predictors for poor outcome.The objective of the present study was to compare early "Top-Down" use of Adalimumab (ADA) immunomodulator/biologics-naïve patients to conventional "Step-Up" management.One hundred and twenty consecutive patients with a confirmed diagnosis of CD and treated with Adalimumab (ADA) between 2008 and 2019 were included and allocated to the ADA-Top Down (n=59) or ADA-Step Up group (n=61). The primary endpoint was prolonged steroid-/enteral nutrition-free clinical remission at 24 months, defined by a wPCDAI12.5. Clinical and biological data were collected at 12 and 24 months.At start of ADA, disease activity was comparable between the ADA-Top Down group and the ADA-Step Up group (wPCDAI=31 ± 16 versus 31.3 ± 15.2 respectively, p=0.84). At 24 months, the remission rate was significantly higher in the ADA-Top Down group (73% versus 51%, p0.01). After propensity score, the Top-Down strategy is still more effective than the Step-Up strategy in maintaining remission at 24 months (HR=0.36, 95%CI[0.15-0.87], p=0.02). Patients in the ADA-Top Down group were mainly on monotherapy compared to patients in the ADA-Step Up group (53/55 versus 28/55 respectively, p0.001). Serum levels of Adalimumab were higher in the ADA-Top Down group than in the ADA-Step Up group (12.8µg/ml±4.3 versus 10.4µg/ml±3.9 respectively, p0.01).There were no serious adverse events.Early use of ADA appears to be more effective in maintaining relapse-free remission at 2 years, while using it as monotherapy. These findings further favor the recommendation of early anti-TNF use in high-risk CD patients.

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.

The first ECCO-ESPGHAN guidelines for the medical management of pediatric Crohn disease (CD) were published in 2014. Whether their implementation, and the consequent increased use of an upfront anti-tumor necrosis factor therapy, have changed the course of the disease has not been investigated yet. We aimed at comparing the evolution of pediatric CD patients diagnosed and treated before and after 2014.Single-center retrospective study including all children diagnosed with CD from January 2010 to December 2018. Patients diagnosed between 2010 and 2014 (group 1) were compared to those diagnosed after 2014 (group 2). For each patient, at baseline and every 6-month, number of relapses, the occurrence of complication, therapy received and biological parameters were noted, as well as any endoscopic or radiologic evaluation.One hundred and fifty-four patients were included in the analysis, 78 (51%) diagnosed after 2014. The cumulative probability of a relapse-free and surgery-free course was significantly higher for patients treated according to the guidelines (log rank hazard ratio [HR] = 1,818, P = 0.003 and HR = 3,15, 95% confidence interval, P = 0.04, respectively). Mucosal healing rate was significantly higher among patients of group 2 at 1 and 2 years (P = 0.04 and P = 0.05, respectively), while no significant difference was observed for transmural healing rates, as well as for the risk of complications.The implementation of the 2014 CD guidelines appears to have a significant impact on disease outcomes, with a significantly lower risk for relapse and surgery, while no effect could be observed on the risk of developing complications.

Congenital enteropathies (CE) are a group of rare inherited diseases with a typical onset early in life. They involve defects in enterocyte structure or differentiation. They can cause a severe condition of intestinal failure (IF). The diagnostic approach is based first on clinical presentation (consanguinity, prenatal expression, polyhydramnios, early neonatal onset, aspect of stools, persistence at bowel rest, associated extra-digestive manifestations….) and histo-pathological analyses. These rare intestinal diseases cause protracted diarrhea that might resolve, for a few, with a dietetic approach. However, protracted or permanent IF may require long term parenteral nutrition and, in limited cases, intestinal transplantation. With the progresses in both clinical nutrition and genetics, many of these CE are nowadays associated with recognized gene mutations. It improved our knowledge and the understanding in the patho-physiology of these diseases, thus, leading potentially to therapeutic perspectives. These review cover most of the early onset CE and excludes the immune related diarrhea.

Summary Background & aims Intestinal rehabilitation is the preferred treatment for children with short bowel syndrome (SBS) whatever the residual bowel length, and depends on the accurate management of long-term parenteral nutrition (PN). If nutritional failure develops, intestinal transplantation (ITx) should be discussed and may be life-saving. This study aimed to evaluate survival, PN dependency and nutritional status in children with neonatal very SBS on PN or after ITx, in order to define indications and timing of both treatments. Patients and methods This retrospective cross-sectional study enrolled 36 children with very SBS ( Results All the children on long-term PN (n = 16) survived with a follow-up of 17 years (9–20). Six of them were eventually weaned off PN. Twenty children underwent ITx: eight children died (40%) 29 months (0–127) after Tx. The others 12 patients were weaned off PN 73 days (13–330) after Tx. Follow-up after transplantation was 14 years (6–28). Seven out of 8 (88%) patients with a history of gastroschisis required ITx. Patients who required ITx had longer stoma duration. Conclusion Survival rate of children with very short bowel was excellent if no life-threatening complications requiring transplantation developed. Gastroschisis and delayed ostomy closure are confirmed as risk factor for nutritional failure. Intestinal rehabilitation may allow a total weaning of PN before adulthood. A follow-up by a multidisciplinary team is necessary to avoid PN complications in order to minimize indications for ITx.

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.

Background Children have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections. Aim We 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. Methods We 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. Results Prevalence 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. Conclusion Prior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

BackgroundChildren have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS).MethodsThis cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup).FindingsSARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55·6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66·9 −100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection.InterpretationPrior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.Evidence before this studyChildren seem to be less likely affected by SARS-CoV-2 infection and clinical course of COVID-19 is less severe than in adults. As those asymptomatic or mildly symptomatic children are underdiagnosed and their viral loads are comparable to those of adults, they may act as an asymptomatic reservoir for the spread of the virus. One explanation of the difference between the adult and the pediatric infectious profile might be that infection with seasonal human coronaviruses, which is very frequent from a very young age, could lead to cross protective immunity. We searched in PubMed, MedRxiv and BioRxiv for publications from inception to June 15, 2020, using the terms “COVID-19, SARS-CoV-2, children, serology, Kawasaki, Corona Virus”.Added value of this studySARS-CoV-2 mean prevalence rate was 11.7% from April 1 to June 1 and neutralizing antibodies were found in 55% of the tested seropositive children. Among patients with a Multisystem Inflammatory Syndrome, Kawasaki-like disease, 70% were SARS-CoV-2 seropositive and had neutralizing antibodies. COVID-19 and MIS attack rates, and anti-SARS-CoV-2 antibodies titres were not significantly impacted by prior seasonal coronavirus infection.Implications of all the available evidencePrior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children As antibodies against seasonal coronaviruses are very frequent and as these viruses circulate efficiently in human populations every winter, our results question to what extent the concept of herd immunity based on circulating antibodies can be applied to seasonal coronaviruses and possibly SARS-CoV-2.

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.

Objectives Neurological adverse effects (NAEs) induced by biotherapies have been reported in the literature mainly in adult patients with inflammatory bowel disease (IBD), rheumatic diseases, or psoriasis. There are scant data in children. Aims of this study are to report and describe noninfective NAE associated with anti-TNFα antibodies in pediatric IBD, and to evaluate their incidence. Methods We retrospectively collected all reports of NAE in pediatric IBD treated with anti-TNFα antibodies recorded in the French Pharmacovigilance Database. To estimate the national incidence of NAEs, we extrapolated data from the French regional inception population-based cohort EPIMAD. Results Between 2000 and 2018, 231 adverse events in pediatric IBD exposed to anti-TNFα antibodies were reported to this Database. Seventeen NAEs (7.36%) were collected: 8 severe NAE (1 demyelinating neuropathy, 1 optic neuritis, 1 acute transverse myelitis, 1 polyradiculoneuritis, 1 sensorineural hearing loss, 1 seizure, 1 stroke, and 1 glioma), 7 moderate NAE (headaches), and 2 neuropsychic events. The median delay between anti-TNFα start and NAE occurrence was 6 months (range: 13 days to 26 months). In 10 of 17 patients, anti-TNFα antibodies were stopped. Nine of 17 patients had a complete resolution (including 2 severe NAE) and 8 of 17 a partial resolution (including 6 severe NAE). We estimate the incidence of severe NAE in pediatric IBD treated with anti-TNFα antibodies at 1 case for 10,000 patients-year in France. Conclusions NAE associated with anti-TNFα antibodies in pediatric IBD are rare. In severe NAE, we recommend to discontinue anti-TNFα therapy and to consider alternative treatment.

Summary Background & aims 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. Methods 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. Results 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 Conclusions 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.

International audience; Marine was a fourteen and a half-year-old adolescent female hospitalized for an eating disorder (ED) of the anorexic type with purging behaviors. She has had a complicated life course, made up of disruptions and discontinuities, both family and school. Since the age of five, Marine had been intermittently treated in psychiatry for a diagnosis of oppositional defiant disorder. The current illness started with spontaneous and induced vomiting associated with major weight loss (body mass index, 15.27 kg m−2). The diagnosis of anorexia nervosa was established after several opinions from professionals in five Parisian university pediatric departments, where additional investigations were carried out without any somatic cause being identified. In this context, Marine was transferred to a child psychiatry unit. There, she had acute dyspnea during the insertion of a nasogastric tube. As a result, a new specialized opinion was sought from a pediatric gastroenterologist and further explorations were performed (oeso-gastroduodenal transit and manometry), leading to the conclusion to an oesophageal achalasia requiring surgical treatment. This case report highlights that the exclusion of any organic disorder should be a priority in the diagnostic assessment of an ED. Oesophageal achalasia is a rare differential diagnosis and should be considered in case of swallowing difficulties or dysphagia. Health care professionals should take care to provide appropriate somatic follow-up for patients with psychiatric disorders.

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.

AimsExclusive 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 MethodsNineteen 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.ResultsAt 8 weeks, clinical remission [HBI ConclusionsBoth 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.

International audience; It is increasingly admitted that Crohn's disease and ulcerative colitis, the two entities of inflammatory bowel disease, are initiated and reactivated by environmental factors in genetically susceptible hosts, and result from aberrant immune response to specific intestinal microbes, in the context of altered composition of intestinal microbiota, called dysbiosis. We hypothesize that the role of the gut microbiota in Crohn's disease pathogenesis is linked to early-life abnormal crosstalk with the host immune system under construction. By contrast, in ulcerative colitis, the detrimental effect of intestinal dysbiosis could occur at any time of life, due to instant environment. This hypothesis could explain why the incidence of Crohn's disease raises many years later than that of ulcerative colitis in developing countries that adopt the Western lifestyle. This would also explain why many early-life events, such as caesarean section, increased hygiene and repeated antibiotic exposure, are risk factors for subsequent development of Crohn's disease, but not ulcerative colitis.

International audience; The gut microbiota plays a key role 63 in host physiology and is an actor in inflammatory bowel disease pathogenesis. Patients with primary immunodeficiency causing intestinal inflammation have disease-specific dysbiosis.

The coronavirus disease 2019 (COVID-19) pandemic caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents most often with mild clinical symptoms, but the severe forms are of major concern.1 SARS-CoV-2 enters human cells via the angiotensin-converting enzyme 2 receptor, expressed on epithelial and endothelial cells.2 Because the highest angiotensin-converting enzyme 2 expression is in the terminal ileum and colon, and up-regulated further during inflammation, and many COVID-19 patients experience gastrointestinal symptoms, longitudinal data are necessary to determine whether inflammatory bowel disease (IBD) patients are at risk for severe or complicated COVID-19. A recent analysis in IBD patients from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry showed older age, steroid medication, and comorbidities as risk factors for severe evolution, and the same study showed that the 29 IBD patients younger than age 20 had only mild disease courses.3 This report describes the disease course of COVID-19 in an expanded sample of pediatric IBD patients from 2 international databases.

International audience; Inflammatory bowel disease (IBD) is due to an aberrant immune response toward luminal antigens, probably commensal bacteria, in genetically susceptible subjects and is also influenced by environmental factors. An imbalanced intestinal microbiota known as “dysbiosis,” characterized by an increased proportion of pro-inflammatory microorganisms and a decreased proportion of anti-inflammatory microorganisms, has been repeatedly observed in IBD and is now recognized as a key factor in the gut inflammatory process. Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option in IBD. The goal of FMT in IBD is not only to correct the dysbiosis, but also to restore a normal dialog between the host immune system and the microbiota. Data are still scarce, but the results of the first studies suggest that FMT could be a promising therapy in IBD. More studies are needed to define the best indications, optimal timing, frequency, mode of delivery, and the optimal donor for each patient.

The aim of the present study was to describe the indications for home parenteral nutrition (HPN) in children with primary digestive diseases and to identify factors associated with weaning off.All the children initially discharged on HPN between January 1, 2000, and December 31, 2009, for chronic intestinal failure (IF) were included. The associations between clinical factors and weaning off of HPN were assessed using a multivariable Cox regression model.Among the 151 children (boys = 58%) included in this study, 98 (65%) presented with short bowel syndrome (SBS), 17 (11%) with digestive neuromuscular disorders, 14 (9%) with mucosal diseases, 13 (9%) with inflammatory bowel disease, and 9 (6%) with other primary digestive diseases. The probability of survival was ∼100%. At the end of the follow-up, the probability for weaning off of HPN was 0.73 (95% confidence interval 0.54-0.84) but varied according to the underlying cause of IF (for example, SBS and inflammatory bowel disease had a better prognosis). The median time until weaning off was 21 months (95% confidence interval 18-38 months). Unfavourable prognostic factors for weaning off of HPN included a bowel remnant of40 cm, the presence of50% of the colon, and daily lipid intakes1.5 g · kg · day. Underlying disease was also associated with weaning off.HPN is a safe therapeutic option for children with chronic IF requiring long-term nutritional management. Prognostic factors for weaning off of HPN were identified, and they highlight the relevance of SBS anatomy and parenteral nutrition caloric intake. The outcome of children on HPN was primarily dependent on the underlying disease.

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.

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.Particularités des maladies inflammatoires chroniques intestinales chez l’enfant. L’incidence des maladies inflammatoires chroniques intestinales (MICI) à début pédiatrique augmente de façon importante dans les pays développés depuis plusieurs décennies. Le début pendant l’enfance est un facteur de gravité, en raison d’une plus grande activité de la maladie et d’une durée d’évolution plus longue. Il existe deux formes principales de MICI, la maladie de Crohn qui peut atteindre toutes les parties du tube digestif et la rectocolite hémorragique qui est restreinte au côlon et au rectum. La nutrition entérale exclusive est le traitement d’induction de premier choix de la maladie de Crohn, permettant en dehors de la résolution des symptômes digestifs et de la cicatrisation muqueuse d’obtenir une croissance de rattrapage, le retard de croissance étant parfois sévère. Le recours à un traitement d’entretien par immunosuppresseurs est le plus souvent nécessaire. L’utilisation des biothérapies se fait, soit en première intention dans les formes sévères, soit en cas d’échec des thiopurines. Dans la rectocolite hémorragique de forme mineure à modérée, les salicylés gardent un rôle important tandis que le recours aux thiopurines ou aux biothérapies est réservé aux formes plus sévères. La tolérance de ces traitements doit être surveillée au long cours. Le recours à une intervention chirurgicale est parfois nécessaire, de façon plus précoce chez l’enfant que chez l’adulte.

Background The main cause of intestinal failure is short bowel syndrome (SBS). The management goal for children with SBS is to promote intestinal adaptation while preserving growth and development with the use of parenteral nutrition (PN). Objectives This study evaluated the intestinal absorption rate in children with SBS, focusing on the role of the remnant colon. In addition, the relation between intestinal absorption rate, citrulline concentration, and small bowel length was studied. Methods Thirty-two children with SBS on PN were included. They were divided into 3 groups according to the European Society for Clinical Nutrition and Metabolism (ESPEN) anatomical classification system: type 1 SBS (n = 9), type 2 (n = 13), and type 3 (n = 10). Intestinal absorption rate was assessed by a stool balance analysis of a 3-d collection of stools. Plasma citrulline concentrations were measured and the level of PN dependency was calculated. Results The total energy absorption rate did not differ significantly between the 3 groups: 68% (61-79% ) for type 1, 60% (40-77%) for type 2, and 60% (40-77%) for type 3 ( P = 0.45). Children with type 2 or 3 SBS had significantly shorter small bowel length than children with type 1: 28 cm (19-36 cm) and 16 cm (2-29 cm), respectively, compared with 60 cm (45-78 cm) ( P = 0.04). Plasma citrulline concentrations were lower in type 3 SBS but not significantly different: 15 µmol/L (11-25 µmol/L) in type 1, 14 µmol/L (7-21 µmol/L) in type 2 , and 9 µmol/L (6-14 µmol/L) in type 3 ( P = 0.141). A multivariate analysis confirmed the role of the remnant colon in providing additional energy absorption. Conclusion This study demonstrated the importance of the colon as a salvage organ in children with SBS. Plasma citrulline concentrations should be interpreted according to the type of SBS. Efforts should focus on conservative surgery, early re-establishment of a colon in continuity, and preserving the intestinal microbiota.

Tension pneumoperitoneum is a relatively rare occurrence in the pediatric population. However, tension pneumoperitoneum is associated with significant morbidity and mortality if it is not promptly diagnosed and treated. A 5-year-old girl was admitted to emergency department with abdominal pain. She was in shock, and the radiograph film of the abdomen revealed a voluminous tension pneumoperitoneum. Aggressive fluid challenges were performed in intensive care followed by urgent laparotomy. Primary abdominal compartment due to trapped gas caused a decreased venous return and visceral perfusion. In the absence of hemodynamic improvement after vascular filling, needle decompression was performed before surgery.

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 50This 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.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.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.

Introduction et but de l’etude Les enfants en nutrition parenterale a domicile (NPAD) ont un risque accru d’osteopathie metabolique (OM) avec une carence en 25-hydroxyvitamine D3 (25-OH D3), une croissance sub-optimale et une diminution de la densite minerale osseuse (DMO). L’indice de dependance a la nutrition parenterale (IDNP) est le ratio entre l’apport energetique non proteique et la depense energetique de repos calculee en utilisant les equations de Schofield. Le but de notre etude etait d’identifier les facteurs associes a l’OM. Materiel et methodes Les enfants âges de plus de 5 ans en NPAD depuis plus de 2 ans ont ete inclus. Un bilan biologique (sang et urine) et une osteodensitometrie ont ete effectues lors d’une consultation specialisee. Les Z-scores de DMO ont ete ajustes a l’âge statural (50e percentile de taille) pour tenir compte du retard statural. Resultats et analyse statistique Ont ete inclus 40 enfants âges de 12,4 ± 4,5 ans en NPAD pour grele court (GC, n = 21), syndrome de pseudo-obstruction intestinale chronique (POIC, n = 10) et enteropathies congenitales (EC, n = 9) (dysplasie epitheliale et syndrome tricho-hepato-enterique). L’âge moyen de debut de la NPAD etait de 1,1 ± 3,6 ans. Le nombre moyen de perfusions etait de 6 ± 1/semaine. Les concentrations seriques moyennes de calcium et phosphore etaient respectivement de 2,3 ± 0,1 et 1,4 ± 0,3 mmol/L. Les taux seriques moyens de 25-OH D3 et PTH etaient de 26,5 ± 9,1 ng/mL (normal : 30–60) et 39,3 ± 18,6 ng/L (normal : 10–55 ng/L) respectivement. Huit enfants (20 %) avaient une hyperparathyroidie et un taux de 25-OH D3 inferieur a la normale. Seize enfants (40 %) avaient une valeur normale de 25-OH D3. Les Z-scores moyens de poids et de taille etaient de 0,4 ± 0,9 et −0,5 ± 1,1 DS respectivement. La taille des enfants etait significativement inferieure a leur taille cible genetique (p 1,2) n’etait pas superieure aux enfants moins dependants de la NPAD (IDNP Conclusion Les enfants en NPAD prolongee et en particulier ceux ayant une EC sont a risque d’OM. Le niveau de dependance a la NPAD ne semble pas influencer la severite de l’OM. Les fractures osseuses sont rares. Un suivi etroit clinique et biologique est indispensable.

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.

International audience; BACKGROUND: Epidemiologic data suggest that smoking increases the risk and the severity of Crohn's disease (CD), although it may protect patients with ulcerative colitis (UC). To investigate this paradox, we evaluated the effect of cigarette smoke in the function of blood mononuclear cells from healthy subjects and patients with CD or UC in flare up. METHODS: The production of mediators associated with inflammation but also with protective functions was evaluated by enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), following either in vivo or in vitro exposure to cigarette smoke. RESULTS: We found that mononuclear cells from smokers with CD were functionally impaired. These cells secreted lower levels of chemokines and cytokines as compared with nonsmoker counterparts, whereas healthy smokers or smokers with UC were not affected. Similar findings were noted after in vitro exposure to cigarette smoke extract. In addition, cells from patients with CD who smoke presented a defective sensitivity to antiinflammatory or antioxidant protection, and particularly synthesized lower levels of cytoprotective Hsp70. The effects observed were not due to diminished cell viability. Our experiments suggest that cigarette smoke-related responses were largely dependent on oxidative stress generated, and not on the nicotine component. CONCLUSIONS: Overall, our data point out the presence of biological differences between blood mononuclear cells from patients with CD and UC toward cigarette smoke that might support its opposite role in both diseases. (Inflamm Bowel Dis 2011;).

Summary Background Nutritional therapy has an established role as induction therapy in paediatric Crohn’s disease. However, compliance is the main difficulty and may be greatly influenced by the administration route. Aim To analyse the efficiency of exclusive nutrition to induce remission in children with Crohn’s disease comparing fractionated oral vs. continuous enteral feeding. Methods The medical records of 106 patients treated by exclusive nutritional therapy [Modulen IBD (R)] by either oral or continuous enteral route were reviewed retrospectively. Comparative analyses of remission rates, changes in anthropometry, Paediatric Crohn’s disease Activity Index (PCDAI), laboratory indices and compliance rates were performed. Results On exclusive enteral nutrition, at 8 weeks, 34/45 patients achieved remission in the oral group (75% on intention-to-treat analysis) and 52/61 (85%) in the enteral nutrition group (P = 0.157). All patients showed a significant decrease in disease severity assessed by PCDAI (P

Introduction et but de l’etude La nutrition parenterale (NP) est la base de la prise en charge de l’insuffisance intestinale. Le but de cette etude est d’analyser, sur une periode de 14 ans, les indications de la NP a domicile (NPAD) des enfants et d’evaluer les resultats en fonction du diagnostic. Materiel et methodes Etude retrospective incluant tous les enfants suivis par le centre agree de NPAD de l’hopital Necker–Enfants-Malades entre le 1er janvier 2000 et le 31 decembre 2013. Resultats Deux cent cinquante et un enfants ont ete inclus dont 217 (86 %) avaient une pathologie primitive digestive. L’âge moyen de debut de la NP etait de 0,7 ± 0,3 ans pour une duree de 1,9 ± 0,4 ans. L’indication majeure de la NPAD etait la grele courte (59 %) : volvulus (17 %), enterocolite ulcero-necrosante (12 %), laparoschisis (12 %), maladie de Hirschsprung (10 %) et atresie du grele (6 %). Les autres causes digestives etaient les enteropathies congenitales (10 %) notamment l’atrophie microvillositaire et la dysplasie epitheliale, les pseudo-obstructions intestinales chroniques (POIC, 9 %) et les maladies inflammatoires du tube digestif (5 %). Les pathologies extra-digestives etaient principalement secondaires au deficit immunitaire (10 %). A la fin de l’etude, 56 % des enfants etaient sevres de la NP, 8 % ont ete transplantes et 10 % etaient decedes. Les complications majeures de la NP etaient les infections liees au catheter (ILC, 1,7 pour 1000 jours de catheter) et les manifestations hepatiques secondaires a l’insuffisance intestinale (51 enfants, 20 % de la cohorte). Les enfants ayant une enteropathie congenitale avaient le taux le plus eleve de perturbation du bilan hepatique (44 % du sous-groupe). Pas de ralentissement de la croissance chez les enfants ayant une grele court et evalues a 6 mois du sevrage de la NP. Conclusion Compares a l’etude realisee par le centre entre 1980 et 2000, la duree de NP jusqu’au sevrage, le taux de mortalite et l’intervalle de temps jusqu’au changement du catheter sont inferieurs. Pas de difference significative dans l’incidence des complications hepatiques secondaires. L’incidence globale des ILC a augmente notamment a Staphylococcus aureus. Cependant, l’incidence diminue depuis l’introduction de la taurolidine en 2012.

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.

International audience; Background Crohn’s disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined.Methods Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Anti-inflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice.Results The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-κB pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice.Conclusions A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.

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.

Azathioprine (AZA), a prodrug of 6-mercaptopurine, is prescribed in evolving forms of inflammatory bowel disease (IBD), affecting predominantly White adolescents and young adults. Thiopurine S-methyltransferase (TPMT) catabolizes AZA and its genetic polymorphism affects the balance between active 6-thioguanine nucleotides (6-TGN) intracellular concentrations [recommended target 235–400 pmol per 8 × 108 red blood cells (RBC)] and hepatotoxic 6-methylmercaptopurine ribonucleotides (6-MMP) [1]. Three polymorphisms (TPMT*2, *3B, *3C; rs1800462, rs1800460, rs1142345, respectively) account for >95% of variant alleles, but additional rare variants are described (TPMT*1S to TPMT*25) [2]. Approximately 90% of Whites are extensive metabolizers with two wild-type TPMT alleles, 6–11% are intermediate metabolizers and 0.2–0.6% are TPMT-deficient patients, exposed to severe myelotoxicity as they accumulate high 6-TGN concentrations under AZA conventional doses [3]. This case reports a pancytopenia under AZA treatment for IBD. As 6-TGN and 6-MMP concentrations and TPMT genotype based on the three predominant polymorphisms were discordant, we conducted additional genetic analysis and identified a new, never described TPMT mutation affecting TPMT activity.

Inflammatory bowel diseases (IBD) are an aberrant immune reaction most likely against the intestinal microbiota in genetically determined high-risk individuals. Several recent studies have highlighted