Phenotype and endotype based treatment of preschool wheeze.

INTRODUCTION: Preschool wheeze (PSW) is a significant public health issue, with a high presentation rate to emergency departments, recurrent symptoms, and severe exacerbations. A heterogenous condition, PSW comprises several phenotypes that may relate to a range of pathobiological mechanisms. However, treating PSW remains largely generalized to inhaled corticosteroids and a short acting beta agonist, guided by symptom-based labels that often do not reflect underlying pathways of disease. AREAS COVERED: We review the observable features and characteristics used to ascribe phenotypes in children with PSW and available pathobiological evidence to identify possible endotypes. These are considered in the context of treatment options and future research directions. The role of machine learning (ML) and modern analytical techniques to identify patterns of disease that distinguish phenotypes is also explored. EXPERT OPINION: Distinct clusters (phenotypes) of severe PSW are characterized by different underlying mechanisms, some shared and some unique. ML-based methodologies applied to clinical, biomarker, and environmental data can help design tools to differentiate children with PSW that continues into adulthood, from those in whom wheezing resolves, identifying mechanisms underpinning persistence and resolution. This may help identify novel therapeutic targets, inform mechanistic studies, and serve as a foundation for stratification in future interventional therapeutic trials.

How to interpret urine toxicology tests.

A 13-year-old girl presents to the emergency department for the second time with an unresponsive episode. She has a GCS (Glasgow Coma Scale) score of 11 on arrival and all other observations are normal. The story is unclear, but there are ongoing safeguarding concerns and the family are known to social services. All investigations are normal. After a period of observation on the ward, her GCS returns to normal and she appears well. Both on the first presentation and this presentation ingestion of a toxin was suspected. However, this was denied by the patient and urine toxicology screen was negative. Does this rule out toxin ingestion? Will this change your management?

Mitral valve replacement in neonatal endocarditis: time to discuss prevention strategies for Group B streptococcus disease.

Group B streptococcus (GBS) is recognised as one of the leading organisms in early-onset neonatal sepsis but is also a cause of late-onset GBS septicaemia, meningitis and rarely, infective endocarditis (IE). We report a case of a healthy term neonate who developed GBS septicaemia and meningitis having presented with parental concern and poor feeding. Subsequent identification and treatment of GBS resulted in the requirement for long-line intravascular access in order to administer antibiotic therapy. One week later, after repeated parental concern and symptoms of shortness of breath, the neonate presented to Accident and Emergency and subsequently a Paediatric Cardiorespiratory Intensive Care Unit where emergency resuscitation procedures were required and diagnosis of severe IE affecting the mitral valve was made. Mitral valve replacement was complicated with significant morbidity and prolonged hospitalisation. An innovative procedure to insert a Melody valve was successful.