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Targeted metabolomics analysis of postoperative delirium

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...

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Autores principales: Tripp, Bridget A., Dillon, Simon T., Yuan, Min, Asara, John M., Vasunilashorn, Sarinnapha M., Fong, Tamara G., Metzger, Eran D., Inouye, Sharon K., Xie, Zhongcong, Ngo, Long H., Marcantonio, Edward R., Libermann, Towia A., Otu, Hasan H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810737/
https://www.ncbi.nlm.nih.gov/pubmed/33452279
http://dx.doi.org/10.1038/s41598-020-80412-z
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author Tripp, Bridget A.
Dillon, Simon T.
Yuan, Min
Asara, John M.
Vasunilashorn, Sarinnapha M.
Fong, Tamara G.
Metzger, Eran D.
Inouye, Sharon K.
Xie, Zhongcong
Ngo, Long H.
Marcantonio, Edward R.
Libermann, Towia A.
Otu, Hasan H.
author_facet Tripp, Bridget A.
Dillon, Simon T.
Yuan, Min
Asara, John M.
Vasunilashorn, Sarinnapha M.
Fong, Tamara G.
Metzger, Eran D.
Inouye, Sharon K.
Xie, Zhongcong
Ngo, Long H.
Marcantonio, Edward R.
Libermann, Towia A.
Otu, Hasan H.
author_sort Tripp, Bridget A.
collection PubMed
description 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.
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spelling pubmed-78107372021-01-21 Targeted metabolomics analysis of postoperative delirium Tripp, Bridget A. Dillon, Simon T. Yuan, Min Asara, John M. Vasunilashorn, Sarinnapha M. Fong, Tamara G. Metzger, Eran D. Inouye, Sharon K. Xie, Zhongcong Ngo, Long H. Marcantonio, Edward R. Libermann, Towia A. Otu, Hasan H. Sci Rep Article 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. Nature Publishing Group UK 2021-01-15 /pmc/articles/PMC7810737/ /pubmed/33452279 http://dx.doi.org/10.1038/s41598-020-80412-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tripp, Bridget A.
Dillon, Simon T.
Yuan, Min
Asara, John M.
Vasunilashorn, Sarinnapha M.
Fong, Tamara G.
Metzger, Eran D.
Inouye, Sharon K.
Xie, Zhongcong
Ngo, Long H.
Marcantonio, Edward R.
Libermann, Towia A.
Otu, Hasan H.
Targeted metabolomics analysis of postoperative delirium
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810737/
https://www.ncbi.nlm.nih.gov/pubmed/33452279
http://dx.doi.org/10.1038/s41598-020-80412-z
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