Impact du dépistage néonatal de la mucoviscidose sur l'état de santé des patients atteints par la maladie (comparaison d'une cohorte de patients mucovisicdosiques bretons dépistés avec une cohorte de patients non dépistés de Loire-Atlantique Vendée)

En 2001, une étude comparait une population de patients nés en Bretagne dont le diagnostic de la mucoviscidose avait été fait après dépistage néonatal avec des patients nés à la même époque en Loire-Atlantique dont le diagnostic avait été fait sur point d'appel. Etaient observés de meilleurs statut nutritionnel, score radiologique de Brasfield et score de Shwachman chez les patients dépistés. 12 ans après, nous avons comparé ces deux mêmes cohortes pour vérifier si les bénéfices du dépistage néonatal perduraient à plus long terme. Nous retrouvons toujours une amélioration du statut nutritionnel qui persiste jusqu'à l'adolescence, et également un délai retardé de colonisation chronique au Pseudomonas aeruginosa. Par contre, nous ne mettons pas en évidence de différence significative sur la fonction respiratoire, probablement du fait de nombreux autres facteurs confondants influençant la fonction respiratoire. Il persiste donc un bénéfice certain au dépistage néonatal de la mucoviscidose avec une amélioration de l'état nutritionnel des patients qui se confirme sur le long terme. L'autre principal intérêt du dépistage fut la création des Centres de Ressources et de Compétences de la Mucoviscidose et l'harmonisation des pratiques, confirmée par la comparaison des pratiques médicales au sein de nos deux cohortes, qui a largement contribué à l'amélioration de la santé des patients atteints.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

A quality improvement program for adolescents with cystic fibrosis: focus on psychosocial skills

Abstract Background The two pediatric cystic fibrosis centers (CFCs) in Paris (Robert Debré) and Nantes, France, have been developing therapeutic patient education (TPE) programs since 2006 and have been engaged in the pilot phase of the quality improvement program (QIP) named the Hospital Program to Improve Outcomes and Expertise in Cystic Fibrosis (PHARE-M) since 2011. The objective was to improve the FEV1 of the cohort of adolescents to prepare them for their optimal transition to an adult CFC. Methods The two CFCs formed a multidisciplinary quality team and used the analysis of causes of insufficient respiratory function taking into account the adolescents’ psychosocial factors. At the Nantes CFC, the approach was centered on adolescents’ body image and their motivation to take care of themselves by assigning specific aspects of patient follow-up to each professional in the team. At R. Debré, an individual cause-and-effect diagram identified for each patient the medical and psychosocial factors that could account for insufficient respiratory function. Personalized actions were offered to each patient. Results In 2014, the median FEV1 (Forced Expiratory Volume in 1 Second) of the adolescent cohort exceeds 90% at the 2 CFCs (Nantes and R. Debré). Between 2011 and 2014 both centers improved their ranking for FEV1% in adolescents in the Registry histograms. At R. Debré, the personalized process allowed to reinforce equality of care, offering to all the opportunity to benefit from TPE sessions and coaching with an adapted physical activity teacher. The psychologist developed a specific tool to support the patient-centered process. Conclusion The link between TPE and QIP was strong at our two centers enhancing patient centered care and targeting an optimal transition to an adult program

A step towards precision medicine in management of severe transient polyhydramnios: MAGED2 variant

International audienc

French national cohort of neuroendocrine cell hyperplasia of infancy (FRENCHI) study: diagnosis and initial management

International audienc

Long-term evolution of neuroendocrine cell hyperplasia of infancy: the FRENCHI findings

International audienc

Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway

International audiencePrimary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping similar to 2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung

Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

International audienceRationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results: Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended