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Abstract
Postmortem metabolomics holds promise for identifying crucial biological markers relevant to death investigations and clinical scenarios. We aimed to assess its applicability in diagnosing hypothermia, a condition lacking definitive biomarkers. Our retrospective analysis involved 1095 postmortem femoral blood samples, including 150 hypothermia cases, 278 matched controls, and 667 randomly selected test cases, analyzed using UHPLC-QTOF mass spectrometry. The model demonstrated robustness with an R2 and Q2 value of 0.73 and 0.68, achieving 94% classification accuracy, 92% sensitivity, and 96% specificity. Discriminative metabolite patterns, including acylcarnitines, stress hormones, and NAD metabolites, along with identified pathways, suggest that metabolomics analysis can be helpful to diagnose fatal hypothermia. Exposure to cold seems to trigger a stress response in the body, increasing cortisol production to maintain core temperature, possibly explaining the observed upregulation of cortisol levels and alterations in metabolic markers related to renal function. In addition, thermogenesis seems to increase metabolism in brown adipose tissue, contributing to changes in nicotinamide metabolism and elevated levels of ketone bodies and acylcarnitines, these findings highlight the effectiveness of UHPLC-QTOF mass spectrometry, multivariate analysis, and pathway identification of postmortem samples in identifying metabolite markers with forensic and clinical significance. The discovered patterns may offer valuable clinical insights and diagnostic markers, emphasizing the broader potential of postmortem metabolomics in understanding critical states or diseases.
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1 National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden (GRID:grid.419160.b) (ISNI:0000 0004 0476 3080)
2 Karolinska Institute, Forensic Medicine Laboratory, Department of Oncology-Pathology, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); University of Oulu, Department of Forensic Medicine, Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873)
3 RIKEN SPring-8 Center, Forensic Science Group, Photon Science Research Division, Sayo-Gun, Japan (GRID:grid.472717.0)
4 National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden (GRID:grid.419160.b) (ISNI:0000 0004 0476 3080); Linköping University, Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping, Sweden (GRID:grid.5640.7) (ISNI:0000 0001 2162 9922)
5 Karolinska Institute, Forensic Medicine Laboratory, Department of Oncology-Pathology, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)