International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia.

Achondroplasia is the most common genetic form of short-limbed skeletal dysplasia (dwarfism). Clinical manifestations and complications can affect individuals across the lifespan, including the need for adaptations for activities of daily living, which can affect quality of life. Current international guidelines focus on symptomatic management, with little discussion regarding potential medication, as therapeutic options were limited at the time of their publication.

Characterization of a Novel Col1a1 Osteogenesis Imperfecta Mouse Model with Insights into Skeletal Phenotype, Fragility, and Therapeutic Evaluations.

Osteogenesis imperfecta (OI) is an inheritable skeletal disorder characterized by bone fragility often caused by pathogenic variants in the COL1A1 gene. Current OI mouse models with a glycine substitution in Col1a1 exhibit excessive severity, thereby limiting long-term pathophysiological analysis and drug effect assessments. To address this limitation, we constructed a novel OI mouse model mimicking a patient with OI type III.

Prognostic Impact of Primary Tumor Size in Thymic Epithelial Tumor: An NCDB-Based Study.

Background: Thymic epithelial tumor (TET) staging has been based on Masaoka-Koga systems or the 8th edition of the TNM classification, which do not use tumor size as a T descriptor. The 9th edition of the TNM classification incorporates tumor size; however, the study on which this classification is based included only 4.4% of patients from North America.

Significance and limitations of routine p16/Ki-67 immunohistochemistry as a diagnostic tool for high-grade squamous intraepithelial lesions of the uterine cervix.

Objective: To evaluate the diagnostic utility and limitations of routine p16 and Ki-67 immunohistochemistry (IHC) in detecting high-grade squamous intraepithelial lesions (HSILs) in the uterine cervix.

Methods: We reviewed 2,061 cervical biopsy records, including 271 morphologically indeterminate squamous lesions, evaluated using p16/Ki-67 IHC for HSIL detection or exclusion. HSIL was diagnosed based on p16 positivity and a high Ki-67 labeling index (Ki-LI).

Effect of Mutation Type on Ectopic Ossification Among Adult Patients With X-Linked Hypophosphatemia.

Context: Causative factors for ectopic ossifications in X-linked hypophosphatemia (XLH) remain to be elucidated.

Objective: This work aimed to investigate the genotype-phenotype correlations between the phosphate-regulating endopeptidase homologue, X-linked gene () and ectopic ossifications in XLH.

Methods: Biochemical data, spinal computed tomography scans, and x-rays of hip/knee joints were retrospectively reviewed.

Prevalence and characteristics of postoperative and nonoperative chronic hypoparathyroidism in Japan: a nationwide retrospective analysis.

Hypoparathyroidism is a rare endocrine disorder characterized by low serum calcium and elevated serum phosphorus levels. Patients who do not recover parathyroid function after surgeries or have nonsurgical causes involving congenital and metabolic diseases, require long-term use of active vitamin D and calcium supplementation as conventional therapy in Japan. This study aimed to estimate prevalence of chronic hypoparathyroidism and investigate its disease etiology, patient characteristics, and treatment in Japan, using a health insurance claim database.

Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants.

Hydrops fetalis, characterized by abnormal fluid accumulation in fetuses, presents a significant risk of stillbirth and neonatal mortality. Although the etiology of nonimmune hydrops fetalis (NIHF) is multifaceted, recent studies have highlighted genetic factors as crucial determinants. This study focused on a family with three consecutive stillbirths, each with pronounced hydrops fetalis.

Burosumab treatment of X-linked hypophosphatemia patients: interim analysis of the SUNFLOWER longitudinal, observational cohort study.

X-linked hypophosphatemia (XLH) is a genetic disease that results in excessive FGF23, chronic hypophosphatemia, and musculoskeletal abnormalities, with affected patients experiencing symptoms such as bone pain, bone deformity, fracture, and pseudofracture. Burosumab is a fully human monoclonal antibody that binds to FGF23, improving lowered serum 1,25(OH)D and phosphate levels in patients with XLH. There are insufficient data on the use of burosumab, its safety, and the outcomes of treated patients in a real-world setting.

Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model.

Background And Objective: Vosoritide is a recently approved therapy for achondroplasia, the most common form of disproportionate short stature, that has been shown to be well tolerated and effective in increasing linear growth. This study aimed to develop a population pharmacokinetic (PPK) model to characterize pharmacokinetics (PK) of vosoritide and establish a weight-band dosing regimen.

Methods: A PPK model was developed using data from five clinical trials in children with achondroplasia (aged 0.

Promising horizons in achondroplasia along with the development of new drugs.

Achondroplasia (ACH) is a representative skeletal disorder characterized by rhizomelic shortened limbs and short stature. ACH is classified as belonging to the fibroblast growth factor receptor 3 (FGFR3) group. The downstream signal transduction of FGFR3 consists of STAT1 and RAS/RAF/MEK/ERK pathways.

Comprehensive analyses of neurodevelopmental outcomes and quality of life of children with biliary atresia.

Objectives: To holistically evaluate neurodevelopmental outcomes and quality of life (QOL) of Japanese patients with biliary atresia (BA) and to investigate the factors associated with the outcomes.

Methods: This study enrolled patients with BA aged 5-18 years who visited Osaka University Hospital in 2021. Neurodevelopmental assessments were performed to evaluate intellectual ability, cognitive functions and adaptive skill levels.

Complex intrinsic abnormalities in osteoblast lineage cells of X-linked hypophosphatemia: Analysis of human iPS cell models generated by CRISPR/Cas9-mediated gene ablation.

X-linked hypophosphatemia (XLH) is caused by inactivating variants of the phosphate regulating endopeptidase homolog X-linked (PHEX) gene. Although the overproduction of fibroblast growth factor 23 (FGF23) is responsible for hypophosphatemia and impaired vitamin D metabolism, the pathogenesis of XLH remains unclear. We herein generated PHEX-knockout (KO) human induced pluripotent stem (iPS) cells by applying CRISPR/Cas9-mediated gene ablation to an iPS clone derived from a healthy male, and analyzed PHEX-KO iPS cells with deletions extending from exons 1 to 3 and frameshifts by inducing them to differentiate into the osteoblast lineage.

Severe hemothorax due to traumatic fracture of thoracic vertebra.

Background: Hemothorax occurs in approx. 0.4% of all chest injury patients, but hemothorax due to a thoracic vertebral fracture is rare.

Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Vosoritide is a recombinant C-type natriuretic peptide analogue that increases annualised growth velocity in children with achondroplasia aged 5-18 years. We aimed to assess the safety and efficacy of vosoritide in infants and children younger than 5 years.

Methods: This double-blind, randomised, placebo-controlled, phase 2 trial was done in 16 hospitals across Australia, Japan, the UK, and the USA.