Hôpital Necker-Enfants Malades

To quantify the transplacental transfer of aciclovir at an amount equivalent to 2 g of valaciclovir corresponding to the fractionated dosing regimen given four times daily used to reduce congenital cytomegalovirus (CMV) transmission and to treat the CMV-infected fetus. Experimental exvivo study. Dual closed-loop perfusion of isolated human placental cotyledons. Placentas collected at term. Placental transfer was assessed using the dual closed-loop exvivo perfusion. Aciclovir was perfused in the maternal compartment at a concentration corresponding to the oral dose of 2 g of valaciclovir taken every 6 h (8 g/day). Samples from maternal and fetal compartments were collected at regular intervals over a 3-h period. Aciclovir concentrations were measured using chromatographic techniques. The transfer rate was calculated as the ratio of the number of moles of fetal aciclovir to the number of fetal and maternal moles at 3 h. Nine perfusion experiments met the criteria for success and could be used for interpretation. The mean transplacental transfer rate of aciclovir was 17.4% (SD: 7.8%). With a single 2 g dose, fetal exposure to aciclovir remained below the IC50 for CMV. The transplacental transfer of aciclovir is low. Despite aciclovir's low molecular weight and hydrophilicity, moderate plasma protein binding and rapid renal elimination may limit placental availability, and the observed transfer was lower than expected for passive diffusion, suggesting involvement of facilitated uptake or efflux mechanisms. These results support the current rationale for high-dose valaciclovir regimens in pregnancy and suggest a potential role for transporter-mediated drug transfer.

Chronic kidney disease and its most severe complication, end-stage renal disease (ESRD), represents an estimated financial burden of €4.4billion in 2021 in France. Therapeutic patient education (TPE) improves ESRD management and health outcomes. This study explored whether providing access to an interactive web-based TPE platform with community features was cost-effective. A within-trial cost-utility analysis was carried out over an 18 months horizon, using data from the PIC-R (Plateforme Interactive Communautaire-dialyse et transplantation Rénale) trial. ESRD or post-transplant patients were randomized 1:1:1 to a control group with no specific TPE program (Control), an intervention group with online TPE (e-TPE) and an intervention group with online TPE coupled with community features such as a patient forum and a chatroom with both patients and health care professionals (e-TPE + chat). The outcome measure was the cost per quality-adjusted life-year (QALY) and per year of full capability (YFC). Both intention-to-treat (ITT) and per protocol (PP) analyses were conducted, and missing data were handled using multiple imputation and selection models. Sensitivity analyses were performed. Among the 815 patients assessed for eligibility across 12 French centres, a total of 549 patients were included in the economic analysis: 186 in the Control group, 189 in the e-TPE group and 174 in the e-TPE + chat group. The e-TPE group demonstrated cost savings and slightly higher QALYs compared to the control group, making e-TPE dominant. Conversely, the e-TPE + chat intervention resulted in higher costs without substantial effectiveness gains, making it not cost-effective. e-TPE was deemed cost-effective for ESRD patients, while e-TPE + chat was not. Web-based platforms improve ESRD management when targeted to likely users.

The increasing global prevalence of myopia represents a major public health concern. This perspective article aligns with the research theme of the special issue on Interventional Modalities for the Prevention and Management of Childhood Myopia. In progressive myopia, the goal is to implement reliable early-life strategies to control myopia and reduce the risk of high myopia. We propose the PREC framework (Prevent, Recognize, Evaluate, and Control) for childhood myopia. Each component is detailed to support individualized myopia management. However, further evidence is required to establish robust guidelines and optimize management strategies, particularly for non-isolated myopia.

NDUFAF6 encodes a mitochondrial complex I assembly factor essential for the proper biogenesis and stability of the nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH)–ubiquinone oxidoreductase complex. Pathogenic variants in NDUFAF6 have been increasingly recognized as a cause of mitochondrial disease, particularly Leigh syndrome, a severe neurodegenerative disorder characterized by bilateral symmetrical lesions in the central nervous system. To date, fewer than 50 patients with NDUFAF6-related mitochondrial disease have been reported, displaying a broad phenotypic spectrum ranging from early-onset neurodevelopmental regression to milder, more chronic presentations. The molecular mechanisms underlying these phenotypes are linked to impaired complex I assembly and reduced enzymatic activity, highlighting the critical role of NDUFAF6 in mitochondrial function.Here we present a cohort of 27 patients (14 males and 13 females) from 18 families harbouring biallelic variants in the NDUFAF6 gene. The patient’s mean age was 9.15 ± 8.30 years (range: 4 weeks to 25 years); 12 patients (37%) had died by the time the data were collected for this article. The clinical presentation showed wide phenotypic variability, from mild to severe psychomotor regression (74%) most commonly before the age of 5 years, hypotonia (22%), movement disorders (30%), and hypertonia (15%). Bilateral striatal necrosis lesions were the most characteristic features on cranial MRI (67%) although white matter abnormalities were also noted (15%), occasionally accompanied by cystic formations, suggestive of early neurodevelopmental anomalies.Genomic sequencing was applied, leading to the identification of 19 distinct variants in the NDUFAF6 gene, including nine novel variants not previously reported and either absent or extremely rare in public population databases. Functional studies confirmed the pathogenicity of these variants, demonstrating a deleterious effect on NDUFAF6 protein expression and a consequent impairment in complex I assembly and stability.To date, this represents the largest reported cohort of patients with NDUFAF6-associated mitochondrial disease. Our findings provide a comprehensive overview of clinical characteristics—including age of symptom onset, phenotypic variability, and patient outcomes—aiming to improve prognostic information and facilitate genetic counselling in clinical practice.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Focused abbreviated survey technique (FAST) brain magnetic resonance imaging (MRI) (i.e., sedation-free abbreviated MRI) is progressively being implemented in the daily clinical practice of multiple pediatric institutions for neuroimaging assessment of children presenting with neurological disorders. To survey current awareness, imaging practices, and perception of members of the European Society of Pediatric Radiology (ESPR) regarding pediatric FAST brain MRI. A survey consisting of seven questions related to FAST brain MRI was distributed electronically to all ESPR members. A total of 64 responses from 27 different countries (17 of which were European) were received, corresponding to a 4% response rate. Among responders, 68% were full-time pediatric radiologists and the great majority (94%) were aware of current clinical use of FAST brain MRI in the pediatric setting. Moreover, 83% already apply this imaging approach in daily work activity, more commonly for a few years (85%). The most cited advantage for adopting this imaging approach was radiation risk reduction (95%). Major reported obstacles to routine implementation were technical/human resource limitations (63%), potential medicolegal implications (55%), and lower image quality reducing diagnostic accuracy (53%). Diverse protocols are used, including utilization of inhouse/custom developed solutions (68%) or one of multiple commercially available/published protocols (17%), or both (15%). Near all participants (97%) expressed desire for formal consensus recommendations from the ESPR on the topic. Despite widespread knowledge and high clinical adoption rate of pediatric FAST brain MRI among participants, clinical indications/protocols remain variable and some barriers persist in the daily practice, highlighting the need for evidence-based consensus-driven guidelines.