Sore knee - why and when to call a cardiologist.

A young girl received a diagnosis of septic arthritis of the knee unresponsive to standard medical and surgical treatment. We report the patient's clinical journey with clinical commentary throughout, underlying the importance of differential diagnosis that may open several scenarios and a different final diagnosis accordingly. Finally, we will discuss the treatment and management of the patient's final diagnosis.

Paediatric heart failure - understanding the pathophysiology and the current role of cardiac biomarkers in clinical practice.

INTRODUCTION: Paediatric heart failure is a common clinical syndrome that may be experienced by children with congenital heart disease (CHD) and/or cardiomyopathy. It is characterised by clinical signs/symptoms which reflect the underlying pathophysiology based on one of three main clinical states: Pulmonary over-circulation, pressure overload, and ventricular failure. Current diagnosis relies on clinical assessment and echocardiogram imaging as cardiac biomarkers has been predominantly scientific to date. This review provides a comprehensive overview of paediatric heart failure pathophysiology and considers the available evidence for cardiac biomarkers in this setting. METHODS: A literature review was completed using MEDLINE ALL, EMBASE, and PubMed on 10th November, 2022. Search terms included biomarkers, heart failure, heart defects, congenital heart disease, fontan circulation, single ventricle circulation, cardiomyopathy, and child. This allowed the identification of individual cardiac biomarkers which are the focus of this review. These included NT-proBNP, MR-proANP, MR-proADM, troponin, sST2, galectin 3, and growth differentiation factor-15. RESULTS: Paediatric studies have established reference ranges for NT-proBNP and troponin for children with structurally normal hearts. Of all the biomarkers reviewed, NT-proBNP appears to correlate most closely with symptoms of heart failure and ventricular dysfunction on echocardiogram. However, there remains limited longitudinal data for NT-proBNP, and no validated reference ranges for patients with CHD and/or cardiomyopathy. None of the other biomarkers reviewed were consistently superior to NT-proBNP. CONCLUSION: Further large paediatric studies of patients with heart failure are needed to validate NT-proBNP in CHD and to evaluate the role of novel biomarkers in specific types of CHD, e.g. single ventricle physiology.

How to interpret cardiac biomarkers in children?

Cardiac biomarkers are used as first-line diagnostic tools in suspected myocardial injury and heart failure in adult patients. Their use in paediatric patients has been limited by variability caused by age, gender and the presence of an underlying congenital cardiac condition. There are established reference ranges for both NT-proBNP and troponin in healthy children, but these cannot be applied to all paediatric patients because of limited large studies focusing on children with congenital heart disease and/or cardiomyopathy.This article will focus on the pathophysiology of myocardial injury and heart failure in children and the subsequent cardiac biomarker correlation. It will explain how to interpret the biomarker assay levels obtained for both troponin and NT-proBNP and highlights the importance of a clear clinical question prior to requesting a cardiac biomarker assay level.Clinical cases outline scenarios that may prompt consideration of biomarker analysis in children and aims to equip the reader with an understanding of how to interpret the results.

Validating clinical practice guidelines for the management of febrile infants presenting to the emergency department in the UK and Ireland.

OBJECTIVE: To report the performance of clinical practice guidelines (CPG) in the diagnosis of serious/invasive bacterial infections (SBI/IBI) in infants presenting with a fever to emergency care in the UK and Ireland. Two CPGs were from the National Institutes for Health and Care Excellence (NICE guidelines NG51 and NG143) and one was from the British Society for Antimicrobial Chemotherapy (BSAC). DESIGN: Retrospective multicentre cohort study. PATIENTS: Febrile infants aged 90 days or less attending between the 31 August 2018 to 1 September 2019. MAIN OUTCOME MEASURES: The sensitivity, specificity and predictive values of CPGs in identifying SBI and IBI. SETTING: Six paediatric Emergency Departments in the UK/Ireland. RESULTS: 555 participants were included in the analysis. The median age was 53 days (IQR 32 to 70), 447 (81%) underwent blood testing and 421 (76%) received parenteral antibiotics. There were five participants with bacterial meningitis (1%), seven with bacteraemia (1%) and 66 (12%) with urinary tract infections. The NICE NG51 CPG was the most sensitive: 1.00 (95% CI 0.95 to 1.00). This was significantly more sensitive than NICE NG143: 0.91 (95% CI 0.82 to 0.96, p=0.0233) and BSAC: 0.82 (95% 0.72 to 0.90, p=0.0005). NICE NG51 was the least specific 0.0 (95% CI 0.0 to 0.01), and this was significantly lower than the NICE NG143: 0.09 (95% CI 0.07 to 0.12, p<0.0001) and BSAC: 0.14 (95% CI 0.1 to 0.17, p<0.0001). CONCLUSION: None of the studied CPGs demonstrated ideal performance characteristics. CPGs should be improved to guide initial clinical decision making. TRIAL REGISTRATION NUMBER: NCT04196192.

Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study.

BACKGROUND: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection. DESIGN: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2-15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. RESULTS: 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). DISCUSSION: Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity. TRIAL REGISTRATION NUMBER: NCT0434740.

Seroprevalence of SARS-CoV-2 antibodies in children of United Kingdom healthcare workers: a prospective multicentre cohort study protocol.

BACKGROUND: A novel coronavirus SARS-CoV-2 has been responsible for a worldwide pandemic. Children typically have very mild, or no, symptoms of infection. This makes estimations of seroprevalence in children difficult. Research is therefore required to determine the seroprevalence of SARS-CoV-2 antibodies in children. The primary objective of this study is to report the seroprevalence of SARS-CoV-2 IgM and/or IgG antibodies in healthy children at baseline, 2 months and 6 months. This is the only longitudinal UK study of seroprevalence in an exclusively paediatric population. Determining the changing seroprevalence is of vital public health importance and can help inform decisions around the lifting of paediatric specific social distancing measures such as school closures and the cancellation of routine paediatric hospital services. METHODS AND ANALYSIS: 1000 healthy children of healthcare workers aged between 2 and 15 years will be recruited from five UK sites (Belfast, Cardiff, Glasgow, London and Manchester). The children will undergo phlebotomy at baseline, 2 months and 6 months to measure IgM and/or IgG positivity to SARS-CoV-2. A sample size of 675 patients is required to detect a 5% change in seroprevalence at each time point assuming an alpha of 0.05 and a beta of 0.2. Adjusted probabilities for the presence of IgG and/or IgM antibodies and of SARS-CoV-2 infection will be reported using logistic regression models where appropriate. ETHICS AND DISSEMINATION: Ethical approval was obtained from the London - Chelsea Research Ethics Committee (REC Reference-20/HRA/1731) and the Belfast Health & Social Care Trust Research Governance (Reference 19147TW-SW). Results of this study will be made available as preprints and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT0434740; Results.