Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe-results from the PED-MERMAIDS multicentre case-control study.

BACKGROUND: Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation. METHODS: 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets. RESULTS: RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses. CONCLUSION: RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent.

Metabolomics applied in neonatology.

Over the past two decades, host-response biomarkers have been extensively used by clinicians for a better understanding of normal biological processes, the complexity and severity of illnesses, or pharmacological responses to therapeutic intervention. A myriad of information can be drawn from the gender, age, dietary intake and the disease history of an individual. These biomarkers may be promising for the complete phenotyping of a cell, tissue or an organism. In neonatology, these molecular markers may help in prediction of disease severity and its outcome, thus allowing personalized interventions. In this Review, existing data in the literature on metabolites in plasma, urine and maternal milk that may offer a unique insight into the host's dynamic behavior in different neonatal conditions will be examined.

Research in human resuscitation: what we learn from animals.

AIM: It was not until the 18th century that scientists throughout Europe established humane societies to develop resuscitation techniques and to keep registries of successful and unsuccessful cases. Since then, the science and art of cardiopulmonary resuscitation have flourished, multiple international organizations were found, and guidelines are proposed every 5 years in an everlasting attempt to improve the outcome of cardiac arrest victims. The aim of this article is to present the role of animal models in resuscitation research. METHODS: A comprehensive search in PubMed, CINAHL, Cochrane Library, and Scopus databases was performed. RESULTS: Mice, rats, and swine have been established as experimental models for conducting resuscitation research. The choice of the animal model is not a simple task, as there are multiple parameters that have to be considered when designing an experiment. CONCLUSION: Animal models are used extensively in resuscitation research and possess a central role in the effort towards a better understanding of the underlying mechanisms. However, experimental results should always be cautiously extrapolated in humans.

Metabolomics in the developing human being.

Metabolomics is based on the detailed analysis of metabolites and represents a unique chemical fingerprint of an organism. This approach allows assessing the dynamic behavior of biologic systems with multiple network interactions among individual components. The field of metabolic profiling has rapidly developed over the last decade, with successful applications in various research areas including toxicology, disease diagnosis and classification, pharmacology, and nutrition. This article provides a comprehensive account of existing data in the literature from animal and clinical studies on the use of metabolomics for improved understanding of medical conditions affecting the neonate and the developing human being.

The use of sildenafil in the treatment of persistent pulmonary hypertension of the newborn: a review of the literature.

Persistent pulmonary hypertension of the newborn (PPHN) is a serious and potentially fatal condition, characterized by hypoxemia due to increased pulmonary vascular resistance (PVR) with resultant shunting of pulmonary blood to the systemic circulation. Inhaled nitric oxide (iNO) has been considered a revolutionary treatment of PPHN. Data show that the use of iNO has reduced the need of ECMO in neonates with severe PPHN, while in moderate PPHN, iNO administration has been associated with a significant decrease in ventilatory support and prevented progression to severe PPHN. Not all neonates respond to iNO therapy though, and phosphodiesterase (PDE) inhibitors with their potent vasodilator properties have evolved as an alternative therapy or as an adjunct to the treatment of PPHN with iNO. There are ten families of PDE isoenzymes. PDE 5 is particularly prevalent in vascular smooth muscle (VSM) and PDE 5 inhibitors, such as sildenafil, have been used in clinical practice. This review provides a comprehensive account of existing data in the literature, from animal and clinical studies, on the use of sildenafil for the treatment of PPHN. Sildenafil may also have a role as a single mode of therapy, since in resource-limited settings the cost of iNO is a serious concern.

The potential role of erythropoietin as a pleiotropic agent in post-cardiac arrest syndrome.

Sudden cardiac arrest is a leading cause of death worldwide with survival rates still remaining suboptimal. Unfortunately, most cardiac arrest patients, who achieve return of spontaneous circulation (ROSC), develop a multi-faceted post-cardiac arrest syndrome, including post-cardiac arrest brain injury, myocardial dysfunction, and systemic ischemia/reperfusion response. Erythropoietin (EPO), the principal hematopoietic hormone regulating erythropoiesis, exhibits diverse cellular effects in nonhematopoietic tissues. Due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, as well as its angiogenic action, EPO plays a role in neuroprotection and cardioprotection. In this regard, EPO represents a promising agent in the cardiac arrest setting, based on a therapeutic strategy that focuses on the post-resuscitation phase. This review aims to provide a comprehensive account of EPO's role in the treatment of each individual component of post-cardiac arrest syndrome.