ILAE neonatal seizure framework to aide in determining etiology.

Objective: To employ the neonatal seizure framework developed by the International League Against Epilepsy (ILAE) Neonatal Task force to assess its usefulness in determining the etiology of neonatal seizures.

Methods: The members of the ILAE Neonatal Task Force evaluated 157 seizures from 146 neonates to determine internal validity and associations between semiology and a specific etiology.

Results: Provoked neonatal electrographic and electroclinical seizures were due to multiple etiologies.

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q Biosynthesis Disorders.

Background And Objectives: Disorders of coenzyme Q (CoQ) biosynthesis comprise a group of 11 clinically and genetically heterogeneous rare primary mitochondrial diseases. We sought to delineate clinical, biochemical, and neuroimaging features of these disorders, together with outcomes after oral CoQ supplementation and the utility of peripheral blood mononuclear cell (PBMNC) CoQ levels in monitoring therapy.

Methods: This was a retrospective cohort study, registered as an audit at a specialist pediatric hospital (Registration Number: 3318) of 14 patients with genetically confirmed CoQ biosynthesis deficiency, including 13 previously unreported cases.

A Systematic Review and Meta-Analysis of Conditioned Pain Modulation in Children and Young People with Chronic Pain.

Background/objectives: Conditioned pain modulation (CPM) is a psychophysical experimental measure of the endogenous pain inhibitory pathway in humans, wherein one pain stimulus (the conditioning stimulus) is used to inhibit an individual's perception of a second painful (test) stimulus. Research provides evidence of impaired endogenous inhibitory pain responses in adults with chronic pain. CPM is now increasingly applied in paediatric research and clinical practice.

What does a consent conversation for whole genome sequencing look like in the NHS Genomic Medicine Service? An observational study.

Patient choice consent for whole genome sequencing (WGS) through the Genomic Medicine Service in England covers consent to diagnostic testing and an invitation to the National Genomic Research Library (NGRL). Little is known about what consent conversations for WGS look like in practice. We audio-recorded and analysed the content and structure of consent appointments (n = 26) between healthcare professionals (HCPs) and parents of children with rare disease across seven NHS Trusts.

Cost-effectiveness of high flow nasal cannula therapy versus continuous positive airway pressure for non-invasive respiratory support in paediatric critical care.

Background: High flow nasal cannula therapy (HFNC) and continuous positive airway pressure (CPAP) are two widely used modes of non-invasive respiratory support in paediatric critical care units. The FIRST-ABC randomised controlled trials (RCTs) evaluated the clinical and cost-effectiveness of HFNC compared with CPAP in two distinct critical care populations: acutely ill children ('step-up' RCT) and extubated children ('step-down' RCT). Clinical effectiveness findings (time to liberation from all forms of respiratory support) showed that HFNC was non-inferior to CPAP in the step-up RCT, but failed to meet non-inferiority criteria in the step-down RCT.

Parental Somatic Mosaicism Detected During Prenatal Diagnosis.

Objective: Accurate recurrence risks are essential for genomic counselling and parental reproductive choices. Historically, Sanger sequencing was used to test parental samples, which has a limited sensitivity of ∼ 10% for detecting somatic mosaicism. Next generation sequencing (NGS) methods, utilised for non-invasive prenatal diagnosis (NIPD) and trio prenatal exome sequencing in our laboratory, have greater sensitivity.

Air-Bone Gap in Meniere's Disease: A Case Series and Literature Review.

Background/objectives: An air-bone gap (ABG) on audiometry is usually secondary to a conductive hearing loss. However, persistent and repeatable ABGs on audiometry in the absence of external or middle ear pathology is thought to arise from inner ear disorders including Meniere's Disease (MD). In this paper, we aim to showcase this interesting finding occurring in MD with an associated literature review.

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

Tumour mimics in paediatric neuroimaging.

Distinguishing tumours from other conditions is a primary challenge in paediatric neuro-radiology. This paper aims to describe mimics, which are non-neoplastic conditions that have features similar to a neoplastic process caused by a non-neoplastic entity, and chameleons, which are uncommon presentations of brain tumours that are mistaken for other diagnoses. By doing so, we aim to raise awareness of these conditions and prevent inappropriate investigations or treatment in children.

Implementation of a National Prenatal Exome Sequencing Service in England: Cost-Effectiveness Analysis.

Objective: Prenatal exome sequencing (pES) for diagnosing fetal structural anomalies commenced in the English National Health Service (NHS) in 2020. We evaluated cost-effectiveness to the healthcare system, and costs to families, of pES in addition to standard testing, compared to standard testing alone.

Design: A cost-effectiveness analysis combining costs, outcomes, parent and professional interview and professional survey data.

A spatial human thymus cell atlas mapped to a continuous tissue axis.

T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation and selection. In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the microanatomical underpinnings of this process in pre- and early postnatal stages, we established a quantitative morphological framework for the thymus-the Cortico-Medullary Axis-and used it to perform a spatially resolved analysis.

Quantified small bowel motility assessment on magnetic resonance enterography in paediatric inflammatory bowel disease - does it reflect clinical response?

Background: Quantified small bowel motility assessment using cine magnetic resonance enterography (MRE) has shown promise as a biomarker in adult inflammatory bowel disease. Whether quantified motility corresponds to treatment response in paediatric inflammatory bowel disease is unknown.

Objective: To test whether changes in motility reflect response.

Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency.

The importance of calcium (Ca2+) as a second messenger in T cell signaling is exemplified by genetic deficiencies of STIM1 and ORAI1, which abolish store-operated Ca2+ entry (SOCE) resulting in combined immunodeficiency (CID). We report five unrelated patients with de novo missense variants in ITPR3, encoding a subunit of the inositol 1,4,5-trisphosphate receptor (IP3R), which forms a Ca2+ channel in the endoplasmic reticulum (ER) membrane responsible for the release of ER Ca2+ required to trigger SOCE, and for Ca2+ transfer to other organelles. The patients presented with CID, abnormal T cell Ca2+ homeostasis, incompletely penetrant ectodermal dysplasia, and multisystem disease.

Pediatric to Adult Transition in Solid Organ Transplant Recipients: A Systematic Review of Existing Transition Programs.

Background: Pediatric organ transplantation is the primary treatment for end-organ failure. Improving medication adherence and healthcare compliance can decrease healthcare burdens, graft rejection, morbidity, and mortality. Adolescents commonly struggle with non-adherence, necessitating a smooth transition to adult care.

Mental healthcare in paediatric epilepsy clinics: implementation by non-mental health professionals.

Objectives: Research has shown that children with epilepsy often experience mental health disorders but face barriers to effective care. One solution is to train healthcare professionals within paediatric epilepsy services to deliver psychological interventions. The aim of this paper was to examine aspects of treatment integrity of the 'Mental Health Interventions for Children with Epilepsy' (MICE) treatment, a modular cognitive behavioural therapy intervention for anxiety, depression and behavioural difficulties in childhood epilepsy.

Hypothalamic obesity: from basic mechanisms to clinical perspectives.

Despite the diverse nature of obesity, there is compelling genetic, clinical, and experimental evidence that endorses the important contribution of brain circuits to this condition. The hypothalamus contains major regulatory circuits for bodyweight homoeostasis, the deregulation of which can lead to obesity. Although functional perturbation of hypothalamic pathways could lie at the basis of common forms of obesity, the term hypothalamic obesity has been created to define those rare forms of severe obesity where a clear hypothalamic substrate can be identified, either of genetic or acquired origin.

Outcomes of X-Linked Agammaglobulinaemia Patients.

Background: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications.

Healthcare utilisation and costs associated with poor access to diagnosis and treatment for children and young people with tic disorders.

Background: There are no specific national guidelines in England to guide healthcare professionals in how to assess or treat young people with tic disorders. Access to evidence-based treatment, including behavioural therapy, is of limited availability.

Objectives: This study examined the economic impact on services arising from a lack of access to appropriate healthcare services for young people with tic disorders, alongside the impact on school attendance.