Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.

Enhanced fetal hemoglobin production via dual-beneficial mutation editing of the HBG promoter in hematopoietic stem and progenitor cells for β-hemoglobinopathies.

Background: Sickle cell disease (SCD) and β-thalassemia patients with elevated gamma globin (HBG1/G2) levels exhibit mild or no symptoms. To recapitulate this natural phenomenon, the most coveted gene therapy approach is to edit the regulatory sequences of HBG1/G2 to reactivate them. By editing more than one regulatory sequence in the HBG promoter, the production of fetal hemoglobin (HbF) can be significantly increased.

Estimated Vaccine Effectiveness for Pediatric Patients With Severe Influenza, 2015-2020.

Importance: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally.

Objective: To investigate VE in children by severity of influenza illness.

Design, Setting, And Participants: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020.

Osteomyelitis and Septic Arthritis of the Upper Extremity in Pediatric Patients.

Purpose Of Review: For pediatric osteomyelitis and septic arthritis, 10-24% of cases occur in the upper extremity (UE). Due to delays in presentation and diagnosis, UE infections are often more complex and severe than infections of the lower extremity (LE). This review evaluates the literature from the past 6 years related to pediatric osteomyelitis and septic arthritis of the UE and provides a guide for professionals managing these conditions in children.

Implications of the choroid plexus in Niemann-Pick disease Type C neuropathogenesis.

Background: Niemann-Pick Disease Type C (NPC) is an ultra-rare disorder characterized by progressive psychiatric and neurologic manifestations, with late infantile, juvenile, and adolescent/adult presentations. We examined morphological properties of the choroid plexus, a protective blood-cerebrospinal fluid barrier, in NPC, and their relationship with neurodegeneration, clinical status, and circulatory markers. This study also determined whether choroid plexus morphology differentiates between NPC and more prevalent illnesses, schizophrenia (SZ) and bipolar disorder (BD), which have overlapping psychiatric symptoms with adolescent and adult-onset NPC and are associated with misdiagnosis.

repeat expansion creates the unstable folate-sensitive fragile site FRA9A.

The hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes and , is linked to multiple diseases. (GGGGCC)n expansions (Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders. Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immunostimulatory or damaged DNA is unknown.

Expanding the Scope of Narrative Medicine by Emphasizing Stories from Minoritized Communities: A Novel Facilitator Training Program.

Background: Narrative medicine (NM) emphasizes the vital role healthcare stories play in conveying patients' experiences and expanding health professionals' reflective capacity. Though predicated on inclusivity, social justice, and equality, NM programs do not tend to include communities with marginalized health narratives due to a paucity of trained facilitators.

Objective: To evaluate the impact of a novel virtual NM facilitator training intended to expand NM programming to minoritized communities.

Pediatrics ACES and related life event screener (PEARLS): translation, transcultural adaptation, and validation to Brazilian Portuguese.

Objective: Adverse Childhood Experiences (ACEs) have been associated with negative health outcomes. Screening for ACEs is crucial for improving health results, however, there is a shortage of standardized tools designed for children in Brazilian Portuguese. This study aimed to translate, culturally adapt, and validate the Pediatrics ACES and Related Life Event Screener (PEARLS) for use in Brazil.

Pediatric Clinical Influenza Disease by Type and Subtype 2015-2020: A Multicenter, Prospective Study.

Background: Previous investigations into clinical signs and symptoms associated with influenza types and subtypes have not definitively established differences in the clinical presentation or severity of influenza disease.

Methods: The study population included children 0 through 17 years old enrolled at 8 New Vaccine Surveillance Network sites between 2015 and 2020 who tested positive for influenza virus by molecular testing. Demographic and clinical data were collected for study participants via parent/guardian interview and medical chart review.

Perioperative Quality Improvement in Children's Hospitals Neonatal Consortium NICUs.

Infants admitted to NICUs in children's hospitals represent a different population than those in a traditional birth hospital. The patients in a children's hospital NICU often have the most complex neonatal diagnoses and are cared for by various subspecialists. The Children's Hospitals Neonatal Consortium is a collaborative of more than 40 NICUs that collect data and perform quality improvement (QI) work across the United States and Canada.

Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions.

More than 50 years have elapsed since the association of human leukocyte antigens (HLA) with type 1 diabetes (T1D) was first reported. Since then, methods for identification of HLA have progressed from cell based to DNA based, and the number of recognized HLA variants has grown from a few to tens of thousands. Current genotyping methodology allows for exact identification of all HLA-encoding genes in an individual's genome, with statistical analysis methods evolving to digest the enormous amount of data that can be produced at an astonishing rate.

Pediatric Cervical Spine Trauma: Injury Patterns, Diagnosis, and Treatment.

Background: Traumatic injuries to the cervical spine or spinal cord are uncommon pathologies in the pediatric population. As injury severity is disproportionately higher among children due to significant risk for debilitating long-term disability, traumatic spinal fractures in children raise greater clinical concern than comparable injuries in adults.

Summary: Unlike adults, children possess unique features such as incomplete ossification of vertebrae, synchondroses, pseudo-subluxation, horizontal alignment of ligaments, and absence of lordosis, which results in greater mobility and flexibility in the pediatric spine.

Genetic variants associated with white blood cell count amongst individuals with sickle cell disease.

Background: Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-globin gene that leads to sickling of erythrocytes. Several studies have shown that absolute neutrophil count is strongly associated with clinical severity of SCD, suggesting an apparent role of white blood cells (WBC) in SCD pathology. However, the mechanism by which genetic variants lead to WBC count differences in SCD patients remains unclear.

Evaluation of early treatment with intravenous idursulfase and intrathecal idursulfase-IT on cognitive function in siblings with neuronopathic mucopolysaccharidosis II.

Mucopolysaccharidosis II (MPS II; Hunter syndrome; OMIM 309900) is a rare, X-linked, heterogeneous lysosomal storage disease. Approximately two-thirds of patients develop cognitive impairment, which is difficult to assess in clinical trials, partly owing to the variable nature of cognitive impairment. Analyzing data from siblings can help to minimize this heterogeneity.

Insurance Status, Language, and Access to Care for Pediatric Anterior Cruciate Ligament Injury.

Background: Patients with public insurance (PUBs) face more difficulty obtaining orthopaedic appointments and have longer wait times than privately insured patients (PVTs). These delays are associated with greater injury severity at the time of surgery, which affects sports injuries such as anterior cruciate ligament tears where early surgical stabilization leads to better outcomes. Additionally, previous evidence showed that patients with limited English proficiency often must rely on informal translation services, such as family members or friends, to communicate with their orthopaedic surgeons, which may represent a disparity in the care provided.

Travel Time to Treating Center is Associated With Diagnostic Delay in Pediatric Inflammatory Bowel Disease.

Background & Aims: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD.

Methods: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 United States sites from 2019 to 2022.

Diagnostic Validation of the Updated Pediatric Sepsis Biomarker Risk II for Acute Kidney Injury Prediction Model in Pediatric Septic Shock.

Objectives: We previously derived the updated Pediatric Sepsis Biomarker Risk for Acute Kidney Injury (PERSEVERE-II AKI) prediction model, which had robust diagnostic test characteristics for severe AKI on day 3 (D3 severe AKI) of septic shock. We now sought to validate this model in an independent cohort of children to the one in which the model was developed.

Design: A secondary analysis of a multicenter, prospective, observational study carried out from January 2019 to December 2022.

Perspectives of pediatric oncologists on referral for CAR-T therapy: a mixed methods pilot study.

Background: Receipt of chimeric antigen receptor T-cell (CAR-T) therapy at an institution different from the primary oncologist's institution is a complex, multistep process. Referral by oncologists plays an important role in the process but may be susceptible to bias.

Methods: Oncologists who previously referred patients for CAR-T therapy at 5 pediatric hospitals were sent surveys by email exploring their CAR-T referral practices.