Déminéralisation osseuse en période péri-pubertaire chez les patients atteints de maladie inflammatoire chronique de l'intestin (prévalence et facteurs de risque)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude de la relation concentration - effet de l'infliximab et de la conséquence de l'arrêt d'une immunosuppression dans une cohorte de patients pédiatriques avec maladie inflammatoire chronique intestinale

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Modeling Immunization To Infliximab in Children With Crohn’s Disease Using Population Pharmacokinetics: A Pilot Study

International audienceBackground - Antidrug antibodies (ADAs) dramatically increase infliximab clearance and are responsible for underexposure to the drug, leading to treatment failure. This pilot study aimed at developing a population pharmacokinetic model to detect and describe an early increase in infliximab clearance due to ADA. Methods - Twenty children with Crohn's disease (CD) were followed for 1 year or until treatment failure. Infliximab trough concentration, ADA, C-reactive protein (CRP), and Paediatric Crohn's Disease Activity Index (PCDAI) were recorded at each visit. A time-varying clearance population pharmacokinetic model was built to detect and describe an increase in infliximab clearance, independent from ADA testing. Factors associated with clearance variation and the relationships between infliximab concentrations, clearance variation, and clinical response were investigated. Results - The model detected important increases in clearance in 4 patients. These patients had suboptimal early response, with higher mean PCDAI (P = 0.0086) and CRP (P = 0.028) compared with other patients. Two of them had detectable ADA. Clearance increase as described by the model and lower infliximab trough concentration at week 2 were associated with poorer outcomes in a multivariate Cox model (P = 0.001 and P = 0.0048, respectively). Conclusions - Being able to detect an increase in infliximab clearance, this model could allow the early detection of immunization to infliximab and therefore could help with dose adjustment in patients with CD. Moreover, the results suggest that clearance variations could be used as a predictive marker of clinical response. These findings need to be confirmed in a larger cohort, however, and predictive factors of clearance increase have to be investigated

Impact of the Methylene Bridge Substitution in Chelating NHC‐Phosphine Mn(I) Catalyst for Ketone Hydrogenation

International audienceSystematic modification of the chelating NHC‐phosphine ligand (NHC = N ‐heterocyclic carbene) in highly efficient ketone hydrogenation Mn(I) catalyst fac ‐[(Ph 2 PCH 2 NHC)Mn(CO) 3 Br] has been performed and the catalytic activity of the resulting complexes was evaluated using acetophenone as a benchmark substrate. While the variation of phosphine and NHC moieties led to inferior results than for a parent system, the incorporation of a phenyl substituent into the ligand methylene bridge improved catalytic performance by ca . 3 times providing maximal TON values in the range of 15000–20000. Mechanistic investigation combining experimental and computational studies allowed to rationalize this beneficial effect as an enhanced stabilization of reaction intermediates including anionic hydride species fac ‐[(Ph 2 PC(Ph)NHC)Mn(CO) 3 H] − playing a crucial role in the hydrogenation process. These results highlight the interest of such carbon bridge substitution strategy being rarely employed in the design of chemically non‐innocent ligands

Feeding disorders in children with oesophageal atresia: a cross-sectional study

International audienceIntroduction With advances in surgical and neonatal care, the survival of patients with oesophageal atresia (OA) has improved over time. Whereas a number of OA-related conditions (delayed primary anastomosis, anastomotic stricture and oesophageal dysmotility) may have an impact on feeding development and although children with OA experience several oral aversive events, paediatric feeding disorders (PFD) remain poorly described in this population. The primary aim of our study was to describe PFD in children born with OA, using a standardised scale. The secondary aim was to determine conditions associated with PFD. Methods The Feeding Disorders in Children with Oesophageal Atresia Study is a national cohort study based on the OA registry from the French National Network. Parents of children born with OA between 2013 and 2016 in one of the 22 participating centres were asked to complete the French version of the Montreal Children’s Hospital Feeding Scale. Results Of the 248 eligible children, 145 children, with a median age of 2.3 years (Q1–Q3 1.8–2.9, min–max 1.1–4.0 years), were included. Sixty-one children (42%) developed PFD; 13% were tube-fed (n=19). Almost 40% of children with PFD failed to thrive (n=23). The presence of chronic respiratory symptoms was associated with the development of PFD. Ten children with PFD (16%) had no other condition or OA-related complication. Conclusion PFD are common in children with OA, and there is no typical profile of patients at risk of PFD. Therefore, all children with OA require a systematic screening for PFD that could improve the care and outcomes of patients, especially in terms of growth

Corrigendum to: Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study

International audienc

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study

International audienceAn 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 adapt treatment