Targeted metabolomics analysis of postoperative delirium
Abstract Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-80412-z |
| _version_ | 1819200207470985216 |
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| author | Bridget A. Tripp Simon T. Dillon Min Yuan John M. Asara Sarinnapha M. Vasunilashorn Tamara G. Fong Eran D. Metzger Sharon K. Inouye Zhongcong Xie Long H. Ngo Edward R. Marcantonio Towia A. Libermann Hasan H. Otu |
| author_facet | Bridget A. Tripp Simon T. Dillon Min Yuan John M. Asara Sarinnapha M. Vasunilashorn Tamara G. Fong Eran D. Metzger Sharon K. Inouye Zhongcong Xie Long H. Ngo Edward R. Marcantonio Towia A. Libermann Hasan H. Otu |
| author_sort | Bridget A. Tripp |
| collection | DOAJ |
| description | Abstract Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) cohort (N = 560) of patients ≥ 70 years old without dementia undergoing scheduled major non-cardiac surgery. We applied targeted mass spectrometry with internal standards and pooled controls using a nested matched case-control study preoperatively (PREOP) and on postoperative day 2 (POD2) to identify potential delirium risk and disease markers. Univariate analyses identified 37 PREOP and 53 POD2 metabolites associated with delirium and multivariate analyses achieved significant separation between the two groups with an 11-metabolite prediction model at PREOP (AUC = 83.80%). Systems biology analysis using the metabolites with differential concentrations rendered “valine, leucine, and isoleucine biosynthesis” at PREOP and “citrate cycle” at POD2 as the most significantly enriched pathways (false discovery rate < 0.05). Perturbations in energy metabolism and amino acid synthesis pathways may be associated with postoperative delirium and suggest potential mechanisms for delirium pathogenesis. Our results could lead to the development of a metabolomic delirium predictor. |
| first_indexed | 2024-12-23T03:28:34Z |
| format | Article |
| id | doaj.art-211d02c8977c44098e54809aa3d389c8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T03:28:34Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-211d02c8977c44098e54809aa3d389c82022-12-21T18:01:46ZengNature PortfolioScientific Reports2045-23222021-01-0111111310.1038/s41598-020-80412-zTargeted metabolomics analysis of postoperative deliriumBridget A. Tripp0Simon T. Dillon1Min Yuan2John M. Asara3Sarinnapha M. Vasunilashorn4Tamara G. Fong5Eran D. Metzger6Sharon K. Inouye7Zhongcong Xie8Long H. Ngo9Edward R. Marcantonio10Towia A. Libermann11Hasan H. Otu12Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Nebraska Hall E419Proteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical CenterDivision of Signal Transduction and Mass Spectrometry Core, Beth Israel Deaconess Medical CenterHarvard Medical SchoolHarvard Medical SchoolHarvard Medical SchoolDepartment of Medicine, Hebrew SeniorLifeHarvard Medical SchoolHarvard Medical SchoolHarvard Medical SchoolHarvard Medical SchoolProteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical CenterDepartment of Electrical and Computer Engineering, University of Nebraska-Lincoln, Nebraska Hall E419Abstract Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) cohort (N = 560) of patients ≥ 70 years old without dementia undergoing scheduled major non-cardiac surgery. We applied targeted mass spectrometry with internal standards and pooled controls using a nested matched case-control study preoperatively (PREOP) and on postoperative day 2 (POD2) to identify potential delirium risk and disease markers. Univariate analyses identified 37 PREOP and 53 POD2 metabolites associated with delirium and multivariate analyses achieved significant separation between the two groups with an 11-metabolite prediction model at PREOP (AUC = 83.80%). Systems biology analysis using the metabolites with differential concentrations rendered “valine, leucine, and isoleucine biosynthesis” at PREOP and “citrate cycle” at POD2 as the most significantly enriched pathways (false discovery rate < 0.05). Perturbations in energy metabolism and amino acid synthesis pathways may be associated with postoperative delirium and suggest potential mechanisms for delirium pathogenesis. Our results could lead to the development of a metabolomic delirium predictor.https://doi.org/10.1038/s41598-020-80412-z |
| spellingShingle | Bridget A. Tripp Simon T. Dillon Min Yuan John M. Asara Sarinnapha M. Vasunilashorn Tamara G. Fong Eran D. Metzger Sharon K. Inouye Zhongcong Xie Long H. Ngo Edward R. Marcantonio Towia A. Libermann Hasan H. Otu Targeted metabolomics analysis of postoperative delirium Scientific Reports |
| title | Targeted metabolomics analysis of postoperative delirium |
| title_full | Targeted metabolomics analysis of postoperative delirium |
| title_fullStr | Targeted metabolomics analysis of postoperative delirium |
| title_full_unstemmed | Targeted metabolomics analysis of postoperative delirium |
| title_short | Targeted metabolomics analysis of postoperative delirium |
| title_sort | targeted metabolomics analysis of postoperative delirium |
| url | https://doi.org/10.1038/s41598-020-80412-z |
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