Real-world Outcomes of Commercial Tisagenlecleucel for Children, Adolescents, and Young Adults With Acute Lymphoblastic Leukemia in Japan.

Chimeric antigen receptor (CAR) T cells are a major new treatment option for children, adolescents, and young adults (CAYA) patients with relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Therefore, accumulating evidence from real-world experiences of CAR-T outcomes in various regions worldwide is important, particularly when comparing outcomes of patients with differing medical and ethnic backgrounds. More than 5 years have passed since tisagenlecleucel was approved in Japan.

A Non-targeted Proteomics Newborn Screening Platform for Inborn Errors of Immunity.

Purpose: Newborn screening using dried blood spot (DBS) samples for the targeted measurement of metabolites and nucleic acids has made a substantial contribution to public healthcare by facilitating the detection of neonates with genetic disorders. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for inborn errors of immunity (IEIs).

Methods: DBS samples from 40 healthy newborns and eight healthy adults were subjected to non-targeted proteomics analysis using liquid chromatography-mass spectrometry after removal of the hydrophilic fraction.

Establishment and Characterization of a Novel Pleuropulmonary Blastoma Cell Line.

Purpose: Pleuropulmonary blastoma (PPB) is an infrequently encountered childhood malignant intrathoracic neoplasm associated with unfavorable clinical behavior. Since a well-characterized preclinical model is essential for developing competent agents for PPB, we aim to establish and characterize the world's first cell line of PPB, and attempt to perform the cytotoxicity assay on the PPB cell line.

Experimental Design: The index case is a 2-year-old female who developed a right thoracic tumor that was surgically removed and treated with multi-agent chemotherapy.

Pathophysiology of Hyponatremia in Preterm Infants with Relative Adrenal Insufficiency after the Early Neonatal Period.

Objective:  Preterm infants often develop relative adrenal insufficiency (RAI) not only within the early neonatal period but also beyond this period. RAI is commonly accompanied by hyponatremia, but the pathogenesis of hyponatremia with RAI has not been clarified. This study aimed to investigate the pathophysiology of hyponatremia in infants with RAI.

Efficacy of steroid therapy for improving native liver survival after pediatric acute liver failure with immune activation.

Aim: Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment.

The genomic basis of childhood T-lineage acute lymphoblastic leukaemia.

T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes.

MGMT protein expression is a reliable predictive biomarker for temozolomide-containing chemotherapy in osteosarcoma.

The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels.

A higher CD34 + cell dose correlates with better event-free survival after KIR-ligand mismatched cord blood transplantation for childhood acute myeloid leukemia.

Although killer Ig-like receptor ligands (KIR-L) mismatch has been associated with alloreactive natural killer cell activity and potent graft-versus-leukemia (GVL) effect among adults with acute myeloid leukemia (AML), its role among children with AML receiving cord blood transplantation (CBT) has not been determined. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients who were diagnosed with de novo non-M3 AML and who underwent their first CBT in remission between 2000 and 2021 at under 16 years old were included.

A de novo dominant-negative variant is associated with OTULIN-related autoinflammatory syndrome.

OTULIN-related autoinflammatory syndrome (ORAS), a severe autoinflammatory disease, is caused by biallelic pathogenic variants of OTULIN, a linear ubiquitin-specific deubiquitinating enzyme. Loss of OTULIN attenuates linear ubiquitination by inhibiting the linear ubiquitin chain assembly complex (LUBAC). Here, we report a patient who harbors two rare heterozygous variants of OTULIN (p.

Severe Bronchopulmonary Dysplasia Adversely Affects Brain Growth in Preterm Infants.

Introduction: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental outcomes of preterm infants, but its effect on brain growth in preterm infants after the neonatal period is unknown. This study aimed to evaluate the effect of severe BPD on brain growth of preterm infants from term to 18 months of corrected age (CA).

Methods: Sixty-three preterm infants (42 with severe BPD and 21 without severe BPD) who underwent magnetic resonance imaging at term equivalent age (TEA) and 18 months of CA were studied by using the Infant Brain Extraction and Analysis Toolbox (iBEAT).

HOIL-1L deficiency induces cell cycle alteration which causes immaturity of skeletal muscle and cardiomyocytes.

HOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disease-specific human induced pluripotent stem cells (hiPSCs).

Inhibition of the galactosyltransferase C1GALT1 reduces osteosarcoma cell proliferation by interfering with ERK signaling and cell cycle progression.

Novel therapeutic strategies are urgently required for osteosarcoma, given the early age at onset and persistently high mortality rate. Modern transcriptomics techniques can identify differentially expressed genes (DEGs) that may serve as biomarkers and therapeutic targets, so we screened for DEGs in osteosarcoma. We found that osteosarcoma cases could be divided into fair and poor survival groups based on gene expression profiles.

Neuropsychological outcome after frontal surgery for pediatric-onset epilepsy with focal cortical dysplasia in adolescent and young adult.

Objective: We investigated neuropsychological outcome in patients with pharmacoresistant pediatric-onset epilepsy caused by focal cortical dysplasia (FCD), who underwent frontal lobe resection during adolescence and young adulthood.

Methods: Twenty-seven patients were studied, comprising 15 patients who underwent language-dominant side resection (LDR) and 12 patients who had languagenondominant side resection (n-LDR). We evaluated intelligence (language function, arithmetic ability, working memory, processing speed, visuo-spatial reasoning), executive function, and memory in these patients before and two years after resection surgery.

Chloroquine decreases cardiac fibrosis and improves cardiac function in a mouse model of Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD), a severe degenerative skeletal and cardiac muscle disease, has a poor prognosis, and no curative treatments are available. Because decreased autophagy has been reported to contribute to skeletal muscle degeneration, therapies targeting autophagy are expected to improve skeletal muscle hypofunction. However, the role of this regulatory mechanism has not been evaluated clearly in DMD cardiomyocytes.