Lewy body dementia promotion by air pollutants.

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. In this work, we showed in a cohort of 56.5 million individuals across the United States that fine particulate matter (PM) exposure raises LBD risk.

Genomic sequencing technologies for rare disease in mainstream healthcare: the current state of implementation.

Genomic sequencing technologies, which include both exome and genome sequencing, as well as panels or targeted analyses using genome-wide approaches, are being implemented across healthcare. Implementation, however, varies greatly by application and jurisdiction, with a diversity of approaches being employed around the world. This review aims to summarise the current state of implementation of genomic testing in mainstream healthcare for the detection of rare disease throughout the lifespan.

Management of bilateral vocal fold paralysis in children.

Purpose Of Review: Bilateral vocal fold paralysis (BVFP) is a complex condition with a range of aetiologies and clinical presentations. Whilst spontaneous improvement may occur in a significant number of cases (48-70%), in the absence of recovery, multiple operations have been used to improve the airway. This review aims to analyse recent literature surrounding the management of BVFP and discuss changes in practice.

Long COVID in children and young people: then and now.

Purpose Of Review: On 11 March 2020, the WHO characterized COVID-19 as a pandemic. A clinical case definition for post-COVID-19 condition in children and adolescents by expert consensus was agreed by the WHO in 2023. It is now 5 years since the WHO declared a pandemic, and this review aims to summarize key advances in our understanding of long COVID over those 5 years.

Core outcome sets for pediatric perioperative research: An international stakeholder engagement exercise and consensus report from the Pediatric Perioperative Outcomes Group.

Background: Identifying the outcomes that matter in clinical research is important, especially those that matter to patients and their parents/guardians. Consistency in outcome reporting enables meaningful assessments of interventions and facilitates comparison of results across trials. The aim of this study was to develop core outcome sets for pediatric perioperative research.

Mosaic disorders affecting pigmentation - part 2: how to make a genetic diagnosis.

Mosaic disorders affecting pigmentation are a large group of different rare diseases which present with hypo- and/or hyper-pigmented birthmarks. These can carry associated risks such as involvement of other organ systems, a predisposition to cancer, and the possibility of transmission to future offspring as germline disease. This review draws on the clinical and genetic discoveries of the last decade to discuss how to make a genetic diagnosis in mosaic disorders affecting pigmentation.

Housing tenure and early-life acute lower respiratory tract infection admissions in two national Scottish birth cohorts.

Introduction: Early-life acute lower respiratory tract infections (LRTIs) have been associated with subsequent wheezing, asthma and mortality. Despite infants and young children spending much of their time at home, the association of housing circumstances, including housing ownership status, on acute LRTI hospital admissions is not well explored.

Objective: To assess the association between housing tenure and the odds of hospital admission for acute LRTIs in children aged <2 years in Scotland.

Pigmented Birthmarks and Spinal Neurofibromas in KRAS Mosaicism-Not to Be Confused With NF1.

We report a child presenting with pigmentary skin lesions and spinal neurofibromas who was diagnosed molecularly with KRAS mosaicism. We review the previous literature of two cases of congenital skin lesions and neurofibromas and spinal nerve root hypertrophy caused by KRAS variants and highlight this presentation as an important differential diagnosis for neurofibromatosis.

Neonatal seizures: Advances in diagnosis and management.

The International League Against Epilepsy (ILAE) created the ILAE Neonatal Task Force that classified neonatal seizures, defined neonatal epilepsy syndromes, and specified treatment guidelines. These frameworks, in addition to improved access to genetic testing and other recent advances, have revolutionized the diagnosis and management of neonatal seizures. PLAIN LANGUAGE SUMMARY: Neonatal seizures, occurring within the first 4 weeks of life, present unique challenges due to the immature neonatal brain.

Atlas of amnion development during the first trimester of human pregnancy.

The amnion is a critical extra-embryonic structure that supports foetal development, yet its ontogeny remains poorly defined. Here, using single-cell transcriptomics, we identified major cell types and subtypes in the human amnion across the first trimester of pregnancy, broadly categorized into epithelial, mesenchymal and macrophage lineages. We uncovered epithelial-mesenchymal and epithelial-immune transitions, highlighting dynamic remodelling during early pregnancy.

Segmental macular hyperpigmentation: new genes, new clinical implications.

Background: Segmental macular hyperpigmentation (SMH) is macular hyperpigmentation in a defined developmental pattern, presenting at birth or in the early years. The only known cause of this phenotype has been mosaicism in gene GNAS, as part of McCune-Albright syndrome. It is unknown how often GNAS mosaicism is the cause of SMH presenting to Dermatology, or whether there are other genetic causes for the phenotype with different clinical implications.

Mosaic disorders affecting pigmentation - part 1: how to make a clinical diagnosis.

Mosaic disorders affecting pigmentation are a large group of different rare diseases which present with hypo- and/or hyper-pigmented birthmarks. These can carry associated risks such as involvement of other organ systems, a predisposition to cancer, and the possibility of transmission to future offspring as germline disease. However, clinical diagnosis of these conditions has been notoriously difficult, due not only to the rarity of the conditions, but to the similarity of their cutaneous signs and the massive intra-disease variability intrinsic to their pathogenetic mechanism.

Choosing biologic therapy in children with severe asthma.

Omalizumab, a monoclonal antibody targeting IgE, was the first biologic therapy approved in 2003 for treating severe, allergen-driven, therapy-resistant asthma. Since then, many new biologics have been approved for use in children, targeting specific pathways, including anti-interleukin (IL)-5 (mepolizumab), IL-5 receptor (benralizumab), IL-4/IL-13 receptor (dupilumab), and thymic stromal lymphopoietin (TSLP) (tezepelumab). As the portfolio of biologics with diverse targets continues to expand, it has brought additional challenges to clinical practice.

Prediction cardiovascular deterioration in a paediatric intensive care unit (PicEWS): a machine learning modelling study of routinely collected health-care data.

Background: Paediatric intensive care medicine uses fine granular clinical data that describe substantial patient instability to make high-consequence decisions. However, these decisions are also hindered by clinical experts' ability to interpret longitudinal data along with recent and gradual changes in the vital sign data. Machine learning aided decisions can improve the identification of patient deterioration.

Caregiver experiences during their child's medical imaging examinations and potential preparatory interventions: A mixed methods systematic review.

Introduction: Caregivers are vital in supporting children during medical imaging tests, helping reduce anxiety and improve outcomes. However, caregivers often face stress and uncertainty, which can hinder their ability to provide effective support. This systematic review explores caregiver experiences and evaluates preparatory interventions aimed at improving these experiences.

Pediatric-type diffuse low-grade gliomas with MYB alterations: Neuroimaging of the Diffuse astrocytomas, or -altered.

Background And Purpose: Diffuse astrocytoma, MYB or MYBL1-altered is a new tumor type in the family of Pediatric-type diffuse low-grade gliomas and genetically related to angiocentric glioma. Imaging features of Diffuse astrocytoma, MYB or MYBL1-altered are less well known. During our clinical work, we identified a relatively characteristic imaging pattern in a subset of our patients consisting of a large, diffuse hemispheric tumor with displaced central vessels which we termed the "fireworks sign".

Somatic mosaicism in patients with "mutation-negative" CAPS: insights from a single centre UK cohort.

Introduction: Knowledge about mosaicism in cryopyrin-associated periodic syndromes (CAPS) has expanded significantly with the use of next generation sequencing technologies. The aim of this study was to assess the contribution of mosaicism in a paediatric cohort of patients with a clinical diagnosis of CAPS and no mutations identified through conventional DNA sequencing.

Methods: Mosaicism was assessed by amplicon-based deep sequencing (ADS) on DNA extracted from different tissues overtime.

Morbidity in children with major kidney anomalies: a European population-based study.

Unlabelled: Knowledge about the prognosis for children born with congenital anomalies is important for counselling parents after a prenatal diagnosis. Nine population-based European Congenital Anomaly registries provided data on all children born 1995-2014 diagnosed with congenital hydronephrosis, multicystic kidney disease (MCKD), or posterior urethral valves (PUV) and on reference children from the same populations. Data up to 2015 on prescriptions, hospital diagnosis, and surgical procedures up to the 10th birthday were obtained by linkage to prescription and hospital databases.

Effect of pubertal induction with combined gonadotropin therapy on testes development and spermatogenesis in males with gonadotropin deficiency: a cohort study.

Study Question: Are recombinant FSH (rFSH) and hCG effective therapies for promoting testicular growth and spermatogenesis in male adolescents and young adults with gonadotropin deficiency?

Summary Answer: Combined gonadotropin therapy is effective in inducing puberty and promoting spermatogenesis in male adolescents and young adults with gonadotropin deficiency and has the potential to improve adult outcomes relating to both fertility and quality of life.

What Is Known Already: Deficiency of pituitary gonadotropins (LH and FSH) due to hypogonadotropic hypogonadism (HH) can result in poor testicular development, low testicular volumes, micropenis and cryptorchidism. Inadequate hormonal replacement can lead to long-term issues, including subfertility or infertility, and reduced quality of life.

Monitoring the emergence of resistance with sotrovimab in immunocompromised patients with COVID-19: LUNAR study.

Objectives: To assess outcomes in sotrovimab-treated immunocompromised patients in the United Kingdom.

Methods: Multicenter, prospective, observational, descriptive study in immunocompromised, non-hospitalized adults infected with SARS-CoV-2 who received intravenous sotrovimab 500 mg as standard-of-care (July 1, 2022-June 30, 2023; Omicron predominance). Virology analyses included determination of SARS-CoV-2 viral load, spike sequencing, and determination of amino-acid substitutions in the spike protein and sotrovimab epitope.

FGF14 repeat length and mosaic interruptions: modifiers of spinocerebellar ataxia 27B?

Deep intronic FGF14 repeat expansions have been identified as a frequent genetic cause of late-onset cerebellar ataxias, explaining up to 30% of patients. Interruptions between repeats have previously been identified to impact the penetrance in other repeat expansion disorders. Repeat interruptions within FGF14 have yet to be characterized in detail.

The relationship between early life course air pollution exposure and general health in adolescence in the United Kingdom.

Air pollution is associated with health in childhood. However, there is limited evidence on sensitive periods during the first 18 years of life. Data were drawn from the Millennium Cohort Study, a large and nationally representative cohort born in 2000/2002.