Identificazione in vivo di biomarcatori di vie metaboliche nell’uomo con tecniche di spettrometria di massa ad alta risoluzione

This doctoral thesis will explore the use of different high-resolution mass spectrometry techniques to identify and quantify disease biomarkers and metabolic pathway biomarkers in pediatric patients. Mass spectrometry is an essential tool in translational medicine, enabling precise and detailed analysis of complex biological compounds, such as proteins, lipids, and metabolites, which can serve as disease indicators or key elements in physiological and pathological responses. Specifically, various concrete applications of these techniques will be discussed, focusing on relevant pediatric clinical issues. The first application will involve the study of lung inflammation in children with congenital heart disease undergoing corrective surgery with cardiopulmonary bypass. In this context, mass spectrometry will be employed to identify specific inflammation biomarkers and to track the changes induced by extracorporeal circulation on lung surfactant composition. The second application will focus on the use of mass spectrometry with isotopic enrichment techniques to study the placental transfer of DHA (docosahexaenoic acid). The last application of mass spectrometry will involve the use of untargeted metabolomics for the analysis of plasma and urine from children with congenital heart disease undergoing corrective surgery with extracorporeal circulation. This will allow us to identify altered metabolic pathways in acute brain injury, improve patient management during and after surgery, and prevent long-term complications. The overall goal of this study is to apply high-resolution mass spectrometry techniques to measure and characterize different disease biomarkers in pediatric populations, and to identify different phenotypes within the same pathology. This approach will move towards increasingly personalized medicine, where therapies can be tailored to the specific biological characteristics of each patient, thereby improving treatment effectiveness and reducing the risk of complications.