The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients Over an 8-day Course Using An Untargeted Approach
The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients Over an 8-day Course Using An Untargeted Approach
Abstract Metabolites are generated from critical biological functions and metabolism. This pediatric study reviewed plasma metabolites in patients suffering from multi-organ dysfunction syndrome (MODS) in the pediatric intensive care unit (PICU) using an untargeted metabolomics approach. Patients meeting criteria for MODS were screened for eligibility and consented (n=24), and blood samples were collected at baseline, 72 hours, and 8 days; control patients (n=4), were presenting for routine sedation in an outpatient setting. A sub-set of MODS patients (n=8) required additional support with veno-atrial extracorporeal membrane oxygenation (VA-ECMO) therapy. Metabolites from thawed blood plasma were determined from ion pairing reversed-phase LC-MS analysis. Chromatographic peak alignment, identification, relative quantitation, statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the PLS-DA with VIP scores above ≥2.0, 7 dynamic metabolites emerged over the 3 time points: tauro-chenodeoxycholic acid (TCDCA), hexose, p-hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferonni adjustment for repeated measures hexose and p-hydroxybenzoate were significant at one time point, or more. Kendall’s tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patient’s pathophysiology and require operator interpretation.
Lydic Todd、Leimanis-Laurens Mara L.、Gil Danny、Krohn Claire、Rajasekaran Surender、Prentice Elizabeth、Kampfshulte Andrew、Sanfilippo Dominic、Prokop Jeremy W.
Department of Physiology, Collaborative Mass Spectrometry Core Michigan State UniversityPediatric Critical Care Unit, Helen DeVos Children?ˉs Hospital||Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Life Sciences BuildingPediatric Critical Care Unit, Helen DeVos Children?ˉs Hospital||Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Life Sciences BuildingMichigan State University, College of Human MedicinePediatric Critical Care Unit, Helen DeVos Children?ˉs Hospital||Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Life Sciences Building||Spectrum HealthPediatric Critical Care Unit, Helen DeVos Children?ˉs Hospital||Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Life Sciences BuildingSpectrum HealthPediatric Critical Care Unit, Helen DeVos Children?ˉs Hospital||Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Life Sciences BuildingDepartment of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Life Sciences Building||Department of Pharmacology and Toxicology, Michigan State University
医学研究方法基础医学儿科学
blood plasmaextracorporeal membrane oxygenationmetabolitesmultiple organ dysfunction syndromepediatric intensive care unitliquid chromatography mass spectrometry
Lydic Todd,Leimanis-Laurens Mara L.,Gil Danny,Krohn Claire,Rajasekaran Surender,Prentice Elizabeth,Kampfshulte Andrew,Sanfilippo Dominic,Prokop Jeremy W..The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients Over an 8-day Course Using An Untargeted Approach[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2020.12.04.20244053.点此复制
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