Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Catalogue of inherited autosomal recessive disorders found amongst the Roma population of Europe.

Background: The Roma population are an endogamous, genetically isolated, minority population who migrated from North-Western India to Europe from the 10th Century throughout the Byzantine period and continues to the present day. Approximately 10-12 million Romani people reside in segregated settlements in Europe, and smaller populations live in North America and China. In addition to the endogamy, they also practice consanguinity.

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.

The mechanics of congenital heart disease: from a morphological trait to the functional echocardiographic evaluation.

Advances in pediatric cardiac surgery have resulted in a recent growing epidemic of children and young adults with congenital heart diseases (CHDs). In these patients, congenital defects themselves, surgical operations and remaining lesions may alter cardiac anatomy and impact the mechanical performance of both ventricles. Cardiac function significantly influences outcomes in CHDs, necessitating regular patient follow-up to detect clinical changes and relevant risk factors.

The Role of Myeloid Cells in Thromboinflammatory Disease.

Inflammation contributes to the development of thrombosis, but the mechanistic basis for this association remains poorly understood. Innate immune responses and coagulation pathways are activated in parallel following infection or injury, and represent an important host defense mechanism to limit pathogen spread in the bloodstream. However, dysregulated proinflammatory activity is implicated in the progression of venous thromboembolism and arterial thrombosis.

Age of first self-harm act in childhood and adolescence: A scoping review protocol.

Background: Self-harm in youth is associated with adverse outcomes for many. The age of first self-harm is not often reported in the literature and there is considerable heterogeneity in how it is reported and in the methods used to estimate it. The objective of this study will be to examine the age of first self-harm act in childhood and adolescence and to identify the research methods used to assess this.

Treatment satisfaction of adult patients with moderate-to-severe atopic dermatitis treated with baricitinib in France, Germany, and the United Kingdom: results from a cross-sectional international patient survey.

Introduction: We explored patient satisfaction with baricitinib, an oral Janus kinase inhibitor, in patients with atopic dermatitis (AD) treated in routine clinical practice.

Methods: Adults with moderate-to-severe AD treated with baricitinib in clinical practice for ≥4 weeks in France, Germany, and the UK completed a one-time online survey under market research methodologies. Treatment satisfaction was assessed using a Likert scale and abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9).

Survival in a young child with out-of-hospital cardiac arrest: diagnostic dilemma and when to deviate from standard resuscitation guidelines.

A boy in early childhood presented in cardiac arrest. Care was provided out of hospital and in the emergency department as per standard paediatric resuscitation guidelines. Despite initial return of spontaneous circulation following cardiopulmonary resuscitation, two defibrillation shocks and epinephrine via intraosseous access, he had recurrent episodes of pulseless ventricular tachycardia and ventricular fibrillation.

Burnout in mental health services in Ireland during the COVID-19 pandemic.

Background: Burnout is a consequence of chronic occupational stress. Specific work-related factors may contribute to burnout experienced by those working in mental health services (MHS), many of which have increased since the COVID-19 pandemic.

Aims: To examine personal, work- and patient-related burnout among MHS staff in Ireland during the COVID-19 pandemic, and explore the impact of work-related conditions on burnout.

Börjeson-Forssman-Lehmann syndrome: delineating the clinical and allelic spectrum in 14 new families.

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported.

Pulmonary transit time as a marker of diastolic dysfunction in Takotsubo syndrome.

Aim: To evaluate the pulmonary transit time (PTT) and its derived parameters using cardiac magnetic resonance imaging (CMRI) as markers of diastolic dysfunction in Takotsubo syndrome (TS) and its relationship with transthoracic echocardiography and CMRI parameters.

Materials And Methods: Twenty-two patients with TS, who exhibited diastolic dysfunction as assessed by transthoracic echocardiography, were enrolled retrospectively and the PTT, pulmonary transit time index (PTTI), and pulmonary blood volume index (PBVI) were evaluated using first-pass CMRI. PTT was calculated as the number of cardiac cycles required for a bolus of contrast agent to move from the right ventricle (RV) to the left ventricle (LV), whereas PTTI represents the PTT interval corrected for the heart rate.

Assessment of Myocardial Function in Infants of Mothers with Gestational Diabetes Mellitus Using Deformation Imaging over the First Year of Age.

Objective: To assess serial myocardial performance and pulmonary vascular resistance (PVR) in infants of mothers with gestational diabetes mellitus (GDM) over the first year of life.

Study Design: This was a prospective, observational study. Echocardiography was performed at birth, 6 months, and 1 year of age.

Reproducibility of the EL-Khuffash PDA severity score and PDA diameter measurements in extremely preterm infants.

Background & Aim: Almost all randomised controlled trials use a Patent Ductus Arteriosus (PDA) diameter ≥ 1.5 mm as the primary criterion to ascribe haemodynamic significance to the PDA. The aim of this study was to evaluate if calculation of a PDA Severity Score (PDAsc) possessed superior intra- and inter-rater reproducibility when compared with the measurement of PDA diameter alone.

The natural history of cystic fibrosis liver disease a prospective cohort study.

Background: Our understanding of the natural history of cystic fibrosis liver disease (CFLD) is limited, leading to uncertainty for patients their families and clinicians when liver abnormalities are identified.

Aim: to determine the incidence of CFLD, identify risk factors and document the natural history of liver abnormalities in cystic fibrosis (CF).

Methods: The Irish longitudinal study of CFLD (ILSCFLD) prospectively enrolled 95% of children with CF in 2007.

Germline pathogenic variants in HNRNPU are associated with alterations in blood methylome.

HNRNPU encodes a multifunctional RNA-binding protein that plays critical roles in regulating pre-mRNA splicing, mRNA stability, and translation. Aberrant expression and dysregulation of HNRNPU have been implicated in various human diseases, including cancers and neurological disorders. We applied a next generation sequencing based assay (EPIC-NGS) to investigate genome-wide methylation profiling for >2 M CpGs for 7 individuals with a neurodevelopmental disorder associated with HNRNPU germline pathogenic loss-of-function variants.