Syndromic (phenotypic) diarrhea in early infancy

Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000–400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (≤ 1 month in most cases) and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti), aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature

Gastro-entérologie Pédiatrique

info:eu-repo/semantics/publishe

Efficacy of infliximab in pediatric Crohn's disease: A randomized multicenter open-label trial comparing scheduled to on demand maintenance therapy

Background: Infliximab (IFX) is efficacious in inducing remission in severe forms of pediatric Crohn's disease (CD). Adult studies indicate that IFX is also safe and well tolerated as maintenance therapy. The present study aimed to evaluate in a prospective manner the efficacy and safety of IFX as maintenance therapy of severe pediatric CD comparing scheduled and "on demand" treatment strategies. Methods: Forty children with CD (nonpenetrating, nonstricturing as well as penetrating forms, mean age: 13.9 ± 2.2 years) with a severe flare-up (Harvey-Bradshaw Index [HBI] ≥ 5, erythrocyte sedimentation rate [ESR] > 20 mm/h) despite well-conducted immunomodulator therapy (n = 36 azathioprine, n = 1 mercaptopurine, n = 3 methotrexate) combined with steroids were included in this randomized, multicenter, open-label study. Three IFX infusions (5 mg/kg) were administered at week (W)0/W2/ W6. At W10, clinical remission (HBI < 5) and steroid withdrawal were analyzed and IFX responders were randomized to maintenance therapy over 1 year: group A, scheduled every 2 months; group B, "on demand" on relapse. Results: In all, 34/40 children came into remission during IFX induction therapy (HBI: 6.7 ± 2.5 (WO) vs. 1.1 ± 1.5 (W10); P < 0.001). At the end of phase 2, 15/18 (83%) patients were in remission in group A compared to 8/13 (61%) children in group B (P < 0.01), with a mean HBI of 0.5 versus 3.2 points (group A versus B, P = 0.011). In group A, 3/13 (23.1%) children experienced a relapse compared to 11/12 (92%) children in group B. No severe adverse event occurred during this trial. Conclusions: IFX is well tolerated and safe as maintenance therapy for pediatric CD, with a clear advantage when used on a scheduled 2-month basis compared to an "on demand" basis. Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A critical appraisal of current management practices for infant regurgitation - Recommendations of a working party

Regurgitation is a common manifestation in infants below the age of 1 year and a frequent reason of counselling of general practitioners and paediatricians. Current management starts with postural and dietary measures, followed by antacids and prokinetics. Recent issues such as an increased risk of sudden infant death in the prone sleeping position and persistent occult gastro-oesophageal reflux in a subset of infants receiving milk thickeners or thickened 'anti-regurgitation formula' challenge the established approach. Therefore, the clinical practices for management of infant regurgitation have been critically evaluated with respect to their efficacy, safety and practical implications. The updated recommendations reached by the working party on the management of infant regurgigation contain five phases: (1A) parental reassurance; (1B) milk-thickening agents; (2) prokinetics; (3) positional therapy as an adjuvant therapy; (4A) H2-blockers; (4B) proton pump inhibitors; (5) surgery.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Current concepts and issues in the management of regurgitation of infants: A reappraisal: Management guidelines from a working party

Regurgitation in infants is a common problem. Recent issues, such as the increased risk of sudden infant death in the prone sleeping position, the finding of persisting occult gastro-oesophageal reflux with feed thickeners, and the increasing awareness of the cost-benefit ratio of medications may challenge the currently recommended management approach. A round table was organized to elaborate on the impact of (i) the pro supine sleeping campaigns in relation to sudden infant death and (ii) advancement in medical treatment on therapeutic strategies in regurgitating infants. The participants were opinion leaders from Europe and North America (Belgium, Canada, France, UK, Italy, Switzerland and The Netherlands). The importance of parental reassurance is stressed. As a consequence of the supine sleeping campaigns aiming to decrease the incidence of sudden infant death syndrome, the "prone elevated sleeping position" is no longer advised as a first-line therapeutic approach, although it is still recommended in "complicated reflux". It is emphasized that milk thickeners are an adequate therapeutic tool for regurgitation, but not in reflux disease. According to the literature, the efficacy of (alginate-)antacids, although very popular in some countries, is questionable. These recommendations will be of interest to first-line paediatricians, since about 40% of their patients, according to the literature, present because of regurgitation.SCOPUS: re.jFLWNAinfo:eu-repo/semantics/publishe

CARD15/NOD2 Mutational Analysis and Genotype-Phenotype Correlation in 612 Patients with Inflammatory Bowel Disease

CARD15/NOD2 encodes a protein involved in bacterial recognition by monocytes. Mutations in CARD15 have recently been found in patients with Crohn disease (CD), a chronic inflammatory condition of the digestive tract. Here, we report the mutational analyses of CARD15 in 453 patients with CD, including 166 sporadic and 287 familial cases, 159 patients with ulcerative colitis (UC), and 103 healthy control subjects. Of 67 sequence variations identified, 9 had an allele frequency >5% in patients with CD. Six of them were considered to be polymorphisms, and three (R702W, G908R, and 1007fs) were confirmed to be independently associated with susceptibility to CD. Also considered as potential disease-causing mutations (DCMs) were 27 rare additional mutations. The three main variants (R702W, G908R, and 1007fs) represented 32%, 18%, and 31%, respectively, of the total CD mutations, whereas the total of the 27 rare mutations represented 19% of DCMs. Altogether, 93% of the mutations were located in the distal third of the gene. No mutations were found to be associated with UC. In contrast, 50% of patients with CD carried at least one DCM, including 17% who had a double mutation. This observation confirmed the gene-dosage effect in CD. The patients with double-dose mutations were characterized by a younger age at onset (16.9 years vs. 19.8 years; P=.01), a more frequent stricturing phenotype (53% vs. 28%; P=.00003; odds ratio 2.92), and a less frequent colonic involvement (43% vs. 62%; P=.003; odds ratio 0.44) than were seen in those patients who had no mutation. The severity of the disease and extraintestinal manifestations were not different for any of the CARD15 genotypes. The proportion of familial and sporadic cases and the proportion of patients with smoking habits were similar in the groups of patients with CD with or without mutation. These findings provide tools for a DNA-based test of susceptibility and for genetic counseling in inflammatory bowel disease

Heterodyne and direct detection wind lidar developed at ONERA

In this paper, we present the two wind lidar architectures developed at ONERA: the heterodyne lidar which analyzes the backscattering of particles and the direct detection lidar using a QMZ which analyzes the backscattering of molecules. In both cases, solutions have been developed to be able to embark them on an airplane: fiber laser, robust receiver, robust general architecture. Both technologies could provide interesting comparative measurements for AEOLUS calibration/validation campaigns: the heterodyne configuration allows precise measurements on the lower part of the atmosphere while the QMZ configuration allows reaching up to at an altitude of 20 km. In addition, regarding the developments made for molecular lidar, the UV fiber laser and the monolithic QMZ receiver could be excellent solutions for the next generation of Aeolus to reduce costs, improve data quality and lidar durability.Dans cet article, nous présentons les deux architectures de lidar éolien développées à l'ONERA : le lidar hétérodyne qui analyse la rétrodiffusion des particules et le lidar à détection directe utilisant un QMZ qui analyse la rétrodiffusion des molécules. Dans les deux cas, des solutions ont été développées pour pouvoir les embarquer dans un avion : laser à fibre, récepteur robuste, architecture générale robuste. Les deux technologies pourraient fournir des mesures comparatives intéressantes pour les campagnes d'étalonnage/validation AEOLUS : la configuration hétérodyne permet des mesures précises sur la partie inférieure de l'atmosphère tandis que la configuration QMZ permet d'atteindre jusqu'à 20 km d'altitude. De plus, concernant les développements réalisés pour le lidar moléculaire, le laser à fibre UV et le récepteur QMZ monolithique pourraient être d'excellentes solutions pour la prochaine génération d'Aeolus afin de réduire les coûts, d'améliorer la qualité des données et la durabilité du lidar