{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:23:38Z","timestamp":1786123418543,"version":"build-2736575974"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Delirium after cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. In this study, we aimed to identify protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>SomaScan analysis of 1305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (preoperative baseline timepoint [PREOP]) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the Enzyme-Linked Lectin Assay (ELLA) multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Of the 115 patients, 21 (18.3%) developed delirium after surgery. The SomaScan proteome screening evidenced differential expression of 115 and 85 proteins in delirious patients compared to nondelirious preoperatively and at POD2, respectively (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .05). Following biological and methodological criteria, 12 biomarker candidates (Tukey\u2019s fold change [|tFC|] &gt;1.4, Benjamini-Hochberg [BH]-\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01) were selected for ELLA multiplex validation. Statistical analyses of model fit resulted in the combination of age, sex, and 3 proteins (angiopoietin-2; C-C motif chemokine 5; and metalloproteinase inhibitor 1; area under the curve [AUC] = 0.829) as the best performing predictive model for delirium. Analyses of pathways showed that delirium-associated proteins are involved in inflammation, glial dysfunction, vascularization, and hemostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our results support the identification of patients at higher risk of developing delirium after cardiac surgery using a multivariable model that combines demographic and physiological features, also bringing light to the role of immune and vascular dysregulation as underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1213\/ane.0000000000007293","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T13:03:32Z","timestamp":1732021412000},"page":"476-487","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Multivariable Predictive Model of Postoperative Delirium in Cardiac Surgery Patients: Proteomic and Demographic Contributions"],"prefix":"10.1213","volume":"140","author":[{"given":"Maria C. B.","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvi","family":"Khera","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan H.","family":"Otu","sequence":"additional","affiliation":[{"name":"University of Nebraska, Lincoln, Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon T.","family":"Dillon","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, Massachusetts"},{"name":"Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics, and Systems Biology Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Shanker","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Weill Cornell Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Gu","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, Massachusetts"},{"name":"Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics, and Systems Biology Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoojin","family":"Jung","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long H.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward R.","family":"Marcantonio","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of General Medicine, 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