Bleeding phenotype according to factor level in 825 children with nonsevere hemophilia: data from the PedNet cohort.

Background: Information on bleeding phenotype in nonsevere hemophilia may be used to determine target factor levels for prophylaxis or gene therapy in severe hemophilia.

Objectives: To assess the association between endogenous factor level and bleeding phenotype in children with nonsevere (factor [F]VIII/FIX activity 1%-25%) hemophilia A (HA) and B without prophylaxis.

Methods: Data on annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), and onset of bleeding were extracted from the international PedNet cohort including children born since 2000.

Genome Sequencing for Cases Unsolved by Exome Sequencing: Identifying a Single-Exon Deletion in TBCK in a Case from 30 Years Ago.

In patients with neurodevelopmental disorders (NDDs), exome sequencing (ES), the diagnostic gold standard, reveals an underlying monogenic condition in only approximately 40% of cases. We report the case of a female patient with profound NDD who died 30 years ago at the age of 3 years and for whom genome sequencing (GS) now identified a single-exon deletion in previously missed by ExomeDepth, the copy number variation (CNV) detection algorithm in ES.Deoxyribonucleic acid (DNA) was extracted from frozen muscle tissue of the index patient and the parents' blood.

Interleukin-10 enhances recruitment of immune cells in the neonatal mouse model of obstructive nephropathy.

Urinary tract obstruction during renal development leads to inflammation, leukocyte infiltration, tubular cell death, and interstitial fibrosis. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, produced mainly by monocytes/macrophages and regulatory T-cells. IL-10 inhibits innate and adaptive immune responses.

Factors influencing the success and complications of intraosseous access in pediatric patients-a prospective nationwide surveillance study in Germany.

Background: Vascular access is essential for the efficient treatment of critically ill children, but it can be difficult to obtain. Our study was conducted to analyze the feasibility and short-term safety of intraosseous access (IO) use as well as factors influencing its success and the incidence of complications in pediatric emergencies and resuscitation. This dataset of systematically documented intraosseous access attempts constitutes one of the largest published in the literature.

TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy.

Urinary tract obstruction during renal development leads to inflammation, tubular apoptosis, and interstitial fibrosis. Toll like receptors (TLRs) expressed on leukocytes, myofibroblasts and renal cells play a central role in acute inflammation. TLR2 is activated by endogenous danger signals in the kidney; its contribution to renal injury in early life is still a controversial topic.

Impaired Neurodevelopment in Children with 5q-SMA - 2 Years After Newborn Screening.

Objective: Numerous studies have consistently found that reduced SMN protein expression does not severely affect cognitive function in SMA patients. However, the average intelligence quotient of SMA patients has ranged above to below average in different studies. The cognitive development of SMA patients identified through newborn screening remains largely unknown.

Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration.

By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel.

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process.

Background: Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage.

Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes.

The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, taking use of the hereditary podocytopathy Alport syndrome (AS) as a model disease for any CKD. Urine samples originated from the prospective randomized, controlled EARLY PRO-TECT Alport trial (NCT01485978).

Kidney concentrating capacity in children with autosomal recessive polycystic kidney disease is linked to glomerular filtration and hypertension.

Background: Impaired kidney concentration capacity is present in half of the patients with autosomal dominant polycystic kidney disease (ADPKD). The kidney concentrating capacity was further impaired within the animal model of autosomal recessive polycystic kidney disease (ARPKD). To date, only one small study has investigated it in children having ARPKD.

BK Viremia and Changes in Estimated Glomerular Filtration Rate in Children and Young Adults after Hematopoietic Cell Transplantation.

Kidney disease in allogeneic hematopoietic cell transplantation (HCT) recipients is associated with increased mortality rates. BK virus (BKV) viremia has been associated with kidney dysfunction in pediatric HCT recipients; however, few studies have investigated longer-term kidney outcomes in association with BKV in this population. Here we assessed the relationship between BK viremia and changes in estimated glomerular filtration rate (eGFR) in children in the first year post-HCT.

Chronic Kidney Disease in Boys with Posterior Urethral Valves-Pathogenesis, Prognosis and Management.

Posterior urethral valves (PUV) are the most common form of lower urinary tract obstructions (LUTO). The valves can be surgically corrected postnatally; however, the impairment of kidney and bladder development is irreversible and has lifelong implications. Chronic kidney disease (CKD) and bladder dysfunction are frequent problems.

A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy.

Background: Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.

Antimicrobial Use in Pediatric Oncology and Hematology: Protocol for a Multicenter Point-Prevalence Study With Qualitative Expert Panel Assessment.

Background: Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking.

Relationship between impaired BMP signalling and clinical risk factors at early-stage vascular injury in the preterm infant.

Introduction: Chronic lung disease, that is, bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and develops as a consequence of the misguided formation of the gas-exchange area undergoing prenatal and postnatal injury. Subsequent vascular disease and its progression into pulmonary arterial hypertension critically determines long-term outcome in the BPD infant but lacks identification of early, disease-defining changes.

Methods: We link impaired bone morphogenetic protein (BMP) signalling to the earliest onset of vascular pathology in the human preterm lung and delineate the specific effects of the most prevalent prenatal and postnatal clinical risk factors for lung injury mimicking clinically relevant conditions in a multilayered animal model using wild-type and transgenic neonatal mice.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.