Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Epigenetic Drift Is Involved in the Efficacy of HBV Vaccination.

: HBV infections can lead to serious liver complications that can have fatal consequences. In 2022, around 1.1 million individuals died from HBV-related cirrhosis and hepatocellular carcinoma.

Development of a New Score Based on Image Defined Risk Factors to Standardize Surgical Risk in Neuroblastoma Resection - A SIOPEN Collaborative Study.

Background And Aims: Image Defined Risk Factors (IDRFs) assess surgical risk in neuroblastoma (NB) and guide neoadjuvant therapy. Despite chemotherapy IDRFs may persist in 70 % of cases. Several studies have suggested that not all IDRFs hold equal significance and that the presence of an IDRF does not inherently signify unresectability.

Trends of hip arthroscopy in Italy show an increase over the years: A nationwide study from 2001 to 2016.

Purpose: Hip arthroscopy has gained popularity among orthopaedic procedures over the last decade. The present study aims to evaluate the trends of hip arthroscopy procedures in Italy analysing data recorded by the Italian Ministry of Health, reporting demographics, length of hospitalisation (LOS), diagnosis and the economic impact of the procedure.

Methods: The National Hospital Discharge records reported by the Italian Ministry of Health were used, analysing the data regarding hip arthroscopy procedures performed in Italy between 2001 and 2016.

A Case Report of 10q24.32 Microduplication Associated with Split Hand/Foot Malformation (SHFM) in Prenatal Diagnosis.

Split Hand/Foot Malformation (SHFM) is a rare congenital disorder often linked to genetic duplications that disrupt normal limb development. Here, we present a novel case of SHFM associated with a 10q24.32 microduplication, identified through prenatal diagnosis.

Unveiling genetic insights: Array-CGH and WES discoveries in a cohort of 122 children with essential autism spectrum disorder.

Background: Autistic Spectrum Disorder (ASD) is a neurodevelopmental disorder with a strong genetic component and high heterogeneity. Essential ASD refers to patients who do not have other comorbidities. This study aimed to investigate the genetic basis of essential ASD using whole exome sequencing (WES) and array-comparative genomic hybridization (array-CGH).

Reappraisal of soft tissue myoepithelial tumors by DNA methylation profiling reveals an epigenetically distinct group of mostly fusion-driven neoplasms.

Soft tissue myoepithelial tumors (METs) are diagnostically challenging tumors that require careful histologic and immunohistochemical characterization for accurate classification. Nearly half of METs show recurrent EWSR1 or FUS gene rearrangements with a diverse set of fusion partners. The diversity of fusion partners and lack of known driver abnormalities in many cases raises the question of whether METs represent a uniformly distinct tumor entity.

Biomarkers of vaccine safety and efficacy in vulnerable populations: Lessons from the fourth international precision vaccines conference.

Vaccination has been a cornerstone of public health, substantially reducing the global burden of infectious diseases, notably evident during the COVID-19 pandemic caused by SARS-CoV-2. However, vulnerable populations (VPs), including those in extreme age groups and those with underlying health conditions, have borne a disproportionate burden of morbidity and mortality from infectious diseases. Understanding vaccine immunogenicity in these populations is crucial for developing effective vaccines.

Fever management in children and insights into fever of unknown origin: a survey among Italian pediatricians.

Background: Fever is a common symptom in children, but despite existing guidelines, pediatricians may not fully apply recommendations. Fever of Unknown Origin (FUO) is generally referred to as an unexplained prolonged fever. However, a standardized FUO definition and management is missing.

Multi-year enzyme expression in patients with mucopolysaccharidosis type VI after liver-directed gene therapy.

Background: Mucopolysaccharidosis type VI (MPS VI) is due to a deficiency of the lysosomal enzyme arylsulfatase B (ARSB) that results in multi-organ accumulation of glycosaminoglycans (GAGs). Limitations of current treatments prompted the development of a liver-directed gene therapy clinical trial for MPS VI.

Methods: We report the long-term follow-up of patients with MPS VI who discontinued enzyme replacement therapy (ERT) and received a single intravenous infusion of high-dose (6 × 10 genome copies/kg) recombinant adeno-associated virus serotype 8 (AAV8) vector expressing ARSB under the control of a liver-specific promoter (ClinicalTrials.

Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype β-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial.

Background: Transfusion-dependent β-thalassaemia (TDT) is a severe disease, resulting in lifelong blood transfusions, iron overload, and associated complications. Betibeglogene autotemcel (beti-cel) gene therapy uses autologous haematopoietic stem and progenitor cells (HSPCs) transduced with BB305 lentiviral vector to enable transfusion independence.

Methods: HGB-212 was a non-randomised, multicentre, single-arm, open-label, phase 3 study of beti-cel in patients with TDT conducted at eight centres in France, Germany, Greece, Italy, the UK, and the USA.

Lymphatic Disorder Management in Pediatric Patients With Congenital Heart Disease in European Pediatric Cardiology Centers: Current Status, Disparities, and Future Considerations.

Background: Lymphatic disorders such as protein-losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pediatric cardiology centers.

Brain malformations and seizures by impaired chaperonin function of TRiC.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures.

Development and validation of a pediatric internationally agreed ultrasound knee synovitis protocol (PIUS-knee) by the PReS imaging working party.

Objectives: To identify an optimal pediatric musculoskeletal ultrasound (MSUS) protocol for the detection of knee arthritis in patients with juvenile idiopathic arthritis (JIA) including a comparison with existing protocols. Secondary aims were to correlate MSUS-identified B-Mode (BM) and Power Doppler-Mode (PD) synovitis with clinical findings.

Methods: Consecutive JIA patients with confirmed knee arthritis after clinical examination underwent a thorough MSUS study protocol which included views identified and consented by the Pediatric Rheumatology european Society (PReS) Imaging Working Party for the detection of synovitis.

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.

EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease.

Unlabelled: Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are considered the same disease, but a common approach for diagnosis and management is still missing.

Methods: In May 2022, EULAR and PReS endorsed a proposal for a joint task force (TF) to develop recommendations for the diagnosis and management of sJIA and AOSD. The TF agreed during a first meeting to address four topics: similarity between sJIA and AOSD, diagnostic biomarkers, therapeutic targets and strategies and complications including macrophage activation syndrome (MAS).

Efficacy and safety of therapies for Still's disease and macrophage activation syndrome (MAS): a systematic review informing the EULAR/PReS guidelines for the management of Still's disease.

Objectives: To analyse the efficacy and safety of treatments for Still's disease and macrophage activation syndrome (MAS).

Methods: Medline, Embase and Cochrane Library were searched for clinical trials (randomised, randomised controlled trial (RCT), controlled and clinical controlled trial (CCT)), observational studies (retrospective, longitudinal observational retrospective (LOR), prospective and longitudinal observational prospective (LOP)) and systematic reviews (SRs), in which the populations studied were patients with Still's disease and MAS. The intervention was any pharmacological treatment (approved or under evaluation) versus any comparator drug or placebo, and as outcomes, any relevant efficacy and safety event.