Environmental maternal exposures and the risk of premature birth and intrauterine growth restriction: The Generation Gemelli study protocol of newborn exposome.

Background: The study of women exposures and child outcomes occurring in the first 1,000 days of life since conception enhances understanding of the relationships between environmental factors, epigenetic changes, and disease development, extending beyond childhood and spanning the entire lifespan. Generation Gemelli is a recently launched case-control study that enrolls mother-newborns pairs in one of the largest university hospitals in Italy, in order to examine the association between maternal environmental exposures and intrauterine growth restriction (IUGR) and the risk of premature birth. The study will also evaluate the association of maternal exposures and the health and growth of infants and children up to 24 months of age.

Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

Nationwide population-based infection- and vaccine-induced SARS-CoV-2 antibody seroprevalence in Germany in autumn/winter 2021/2022.

BackgroundThe first Corona Monitoring Nationwide (RKI-SOEP) study (October 2020-February 2021) found a low pre-vaccine SARS-CoV-2 antibody seroprevalence (2.1%) in the German adult population (≥ 18 years).AimThe objective of this second RKI-SOEP (RKI-SOEP-2) study in November 2021-March 2022 was to estimate the prevalence of SARS-CoV-2-specific anti-spike and/or anti-nucleocapsid (anti-N) IgG antibodies (combined seroprevalence), past infection based on infection-induced seroprevalence (anti-N), and basic immunisation (at least two antigen contacts through vaccination or infection) in individuals aged ≥ 14 years.

Ultrasound-assisted and landmark-based nusinersen delivery in spinal muscular atrophy adults: A retrospective analysis.

Introduction/purpose: Nusinersen, the first treatment approved for all spinal muscular atrophy (SMA) types, is administered intrathecally through lumbar puncture. We used ultrasound assistance or a landmark-based technique to access the lumbar intrathecal space in adult SMA patients. This study aimed to evaluate the technical success and adverse events (AEs) in such patients using either technique over a long observation period.

Type I spinal muscular atrophy and disease modifying treatments: a nationwide study in children born since 2016.

Background: The advent of disease-modifying treatments (DMT) has changed natural history in 5q Spinal muscular atrophy (SMA). The aim of this study was to report survival and functional aspects in all the Italian type I children born since 2016.

Methods: The study included all symptomatic children with type I SMA born since January 1st, 2016, when DMTs became available in Italy.

Evidentiary basis of the first regulatory qualification of a digital primary efficacy endpoint.

Stride velocity 95th centile (SV95C) is a wearable-derived endpoint representing the 5% fastest strides taken during everyday living. In July 2023, SV95C received European Medicines Agency (EMA) qualification for use as a primary endpoint in trials of patients with Duchenne muscular dystrophy (DMD) aged ≥ 4 years-becoming the first digital endpoint to receive such qualification. We present the data supporting this qualification, providing insights into the evidentiary basis of qualification as a digital clinical outcome assessment.

High Expression of SMN circ4-2b-3 in SMA I Children Treated with Nusinersen is Associated with Improved Motor Outcomes.

Spinal muscular atrophy (SMA) is a neuromuscular disorder resulting in the loss of α-motor neurons. Nusinersen is an antisense oligonucleotide administered intrathecally to SMA patients that corrects the splicing defect of SMN2. Not all SMA patients respond equally to the therapy and work is in progress to identify biomarkers that may help stratify to SMA patients.

Correction: Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging.

[This corrects the article DOI: 10.1371/journal.pone.

Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy.

Introduction: Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients' physical functioning and/or response to treatment.

Assessment of early attention in an Italian cohort of preschooler preterm children using the Early Childhood Attention Battery.

Purpose: This cross-sectional monocentric study aims to utilize the Early Childhood Attention Battery to investigate early attention patterns in young preterm children and ascertain the extent to which their attentional abilities diverge from those of term peers.

Methods: Inclusion criteria encompassed gestational age < 34 weeks, with assessments conducted between 3 and 5 years 11 months. Exclusion criteria included major brain lesions, significant motor or behavioral disorders, and intellectual functioning with IQ < 70.

Treatment of spinal muscular atrophy.

Purpose Of Review: The aim of the review was to provide an overview of safety and efficacy of the available treatments including information from both clinical trials and real-world data. Additional information form ongoing studies using other approaches than increasing SMN protein are also reported.

Recent Findings: In the last 3 years, there have been over 24 studies reporting safety and the impact of the available drugs on different aspects of function, including respiratory and bulbar function.

Safety and efficacy of viltolarsen in ambulatory and nonambulatory males with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by mutations in the dystrophin gene, causing motor and pulmonary function decline. Viltolarsen is indicated for patients with dystrophin gene mutations amenable to exon 53 skipping. Here, we report safety, motor function, and the first pulmonary function results from the open-label, phase II Galactic53 trial of viltolarsen (NCT04956289).

Association between Reported Sleep Disorders and Behavioral Issues in Children with Myotonic Dystrophy Type 1-Results from a Retrospective Analysis in Italy.

Sleep disorders have been poorly described in congenital (CDM) and childhood (ChDM) myotonic dystrophy despite being highly burdensome. The aims of this study were to explore sleep disorders in a cohort of Italian CDM and ChDM and to assess their association with motor and respiratory function and disease-specific cognitive and behavioral assessments. This was an observational multicenter study.

Lung Recruitment Before Surfactant Administration in Extremely Preterm Neonates: 2-Year Follow-Up of a Randomized Clinical Trial.

Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes.

Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units.

Design, Setting, And Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy.

Upper limb function changes over 12 months in untreated SMA II and III individuals: an item-level analysis using the Revised Upper Limb Module.

The Revised upper limb module (RULM) has been increasingly used in clinical trials and in clinical settings. The aim of this study was to use the 'shift analysis' to assess the patterns of lost or gained abilities for each item on the RULM in an untreated cohort, stratified by SMA type, age, SMN2 copy number, and motor functional status. The analysis was performed on 222 12-month paired assessments from 129 individuals (115 assessment from type II and 107 from type III) who had at least two assessments at yearly intervals.

Proteomics profiling and machine learning in nusinersen-treated patients with spinal muscular atrophy.

Aim: The availability of disease-modifying therapies and newborn screening programs for spinal muscular atrophy (SMA) has generated an urgent need for reliable prognostic biomarkers to classify patients according to disease severity. We aim to identify cerebrospinal fluid (CSF) prognostic protein biomarkers in CSF samples of SMA patients collected at baseline (T0), and to describe proteomic profile changes and biological pathways influenced by nusinersen before the sixth nusinersen infusion (T302).

Methods: In this multicenter retrospective longitudinal study, we employed an untargeted liquid chromatography mass spectrometry (LC-MS)-based proteomic approach on CSF samples collected from 61 SMA patients treated with nusinersen (SMA1 n=19, SMA2 n=19, SMA3 n=23) at T0 at T302.

Ultrasound assisted versus landmark based intrathecal administration of nusinersen in adults with spinal muscular atrophy disease: A randomized trial.

Introduction/aims: Nusinersen intrathecal administration can be challenging in spinal muscular atrophy (SMA) adults. We aimed to determine if the ultrasound (US)-assistance reduces the number of needle attempts and needle redirections needed for intrathecal drug administration and its impact on the procedure time, the incidence of adverse events (AEs), and patient satisfaction in these patients.

Methods: Fifty-eight patients aged 18 years and older scheduled for intrathecal nusinersen injection were enrolled and randomized (1:1 ratio) into Group 1 (nusinersen infusion with US-assisted technique) or Group 2 (nusinersen infusion with landmark-based technique).

Effectiveness of Nusinersen in Adolescents and Adults with Spinal Muscular Atrophy: Systematic Review and Meta-analysis.

Introduction: Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of nusinersen in adolescents and adults with SMA in clinical practice.

Methods: Our search included papers published 12/23/2016 through 07/01/2022 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months' data on ≥ 1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)].