{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:04:08Z","timestamp":1790949848758,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cardiac surgery with cardiopulmonary bypass (CPB) is considered to be one of the surgical types with the highest incidence of post-operative delirium (POD). POD has been associated with a prolonged intensive care and hospital stay, long-term neurocognitive deterioration, and increased mortality. However, the specific pathogenesis of POD is still unclear. Untargeted metabolomics techniques can be used to understand the changes of serum metabolites in early POD to discover the relationship between serum metabolites and disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>The present study recruited 58 elderly patients undergoing cardiac surgery with CPB. Serum was collected within the first 24 h after surgery. The Confusion Assessment Method (CAM) and ICU-CAM assessments were used to identify patients who experienced POD. All patients with normal post-operative cognitive assessment were included in the non-POD groups. Moreover, we collected serum from 20 healthy adult volunteers. We performed untargeted analyses of post-operative serum metabolites in all surgical groups, as well as serum metabolites in healthy non-surgical adults by using liquid chromatography mass spectrometry (LC\/MS) and analyzed metabolic profiles and related metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The probability of POD after cardiac surgery were 31%. There were statistically significant differences in post-operative mechanical ventilation time, ICU stay time and post-operative hospital stay between POD and non-POD group (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). And ICU stay time was an independent risk factor for POD. The analysis revealed that a total of 51 differentially expressed metabolites (DEMs) were identified by comparing the POD and non-POD group, mostly lipids and lipid-like molecules. Three phosphatidylinositol (PI) were down-regulated in POD group, i.e., PI [18:0\/18:2 (9Z, 12Z)], PI [20:4 (8Z, 11Z, 14Z, 17Z)\/18:0], and PI [18:1 (9Z)\/20:3 (8Z, 11Z, 14Z)]. The receiver operating characteristic (ROC) curve analysis showed that three kinds of PI metabolites had the highest area under the curve (AUC), which were 0.789, 0.781, and 0.715, respectively. Correlation analysis showed that the expression of three PIs was negatively correlated with the incidence of POD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that lipid metabolism plays an important role in the serum metabolic profile of elderly patients with POD in the early post-operative period. Low serum lipid metabolic PI was associated with incidence of POD in elderly following cardiac bypass surgery, which may provide new insights into the pathogenesis of POD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2022.857902","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T01:23:55Z","timestamp":1654824235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Early Serum Metabolism Profile of Post-operative Delirium in Elderly Patients Following Cardiac Surgery With Cardiopulmonary Bypass"],"prefix":"10.3389","volume":"14","author":[{"given":"He","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ebiom.2018.10.021","article-title":"Surgery, neuroinflammation and cognitive impairment.","volume":"37","author":"Alam","year":"2018","journal-title":"EBioMedicine"},{"key":"B2","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1097\/sla.0000000000005287","article-title":"Is it time to Assess Neurological Status Before Surgery to Improve Postoperative Outcomes?","volume":"275","author":"Alam","year":"2022","journal-title":"Ann. Surg."},{"key":"B3","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1053\/j.jvca.2016.09.028","article-title":"Cognitive Outcomes After Coronary Artery Bypass Grafting.","volume":"31","author":"Bhamidipati","year":"2017","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"B4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.bbalip.2014.08.011","article-title":"Lipids in the nervous system: from biochemistry and molecular biology to patho-physiology.","volume":"1851","author":"Cermenati","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01853-x","article-title":"TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K\/Akt pathway after intracerebral hemorrhage in mice.","volume":"17","author":"Chen","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"B6","first-page":"1346","article-title":"Evaluation of the postoperative cognitive dysfunction in elderly patients with general anesthesia.","volume":"21","author":"Chi","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.ahj.2020.11.011","article-title":"Diagnosis, prevention, and management of delirium in the intensive cardiac care unit.","volume":"232","author":"Cort\u00e9s-Beringola","year":"2021","journal-title":"Am. Heart J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1097\/aln.0000000000002729","article-title":"Postoperative Delirium and Postoperative Cognitive Dysfunction: Overlap and Divergence.","volume":"131","author":"Daiello","year":"2019","journal-title":"Anesthesiology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"R33","DOI":"10.1016\/j.cub.2012.10.041","article-title":"The role of lipids in the control of autophagy.","volume":"23","author":"Dall\u2019Armi","year":"2013","journal-title":"Curr. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"30.4.1","DOI":"10.1002\/0471142727.mb3004s114","article-title":"Metabolomics by Gas Chromatography-Mass Spectrometry: combined Targeted and Untargeted Profiling.","volume":"114","author":"Fiehn","year":"2016","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.120.017275","article-title":"Risk Factors for Delirium and Cognitive Decline Following Coronary Artery Bypass Grafting Surgery: A Systematic Review and Meta-Analysis.","volume":"9","author":"Greaves","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"B12","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1093\/ageing\/afz132","article-title":"Post-operative delirium associated with metabolic alterations following hemi-arthroplasty in older patients.","volume":"49","author":"Guo","year":"2019","journal-title":"Age Ageing"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1093\/gerona\/glx001","article-title":"Preoperative Serum Metabolites Are Associated With Postoperative Delirium in Elderly Hip-Fracture Patients.","volume":"72","author":"Guo","year":"2017","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1097\/aln.0000000000001378","article-title":"Intensive Care Unit Delirium: a Review of Diagnosis, Prevention, and Treatment.","volume":"125","author":"Hayhurst","year":"2016","journal-title":"Anesthesiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.1016\/j.cellsig.2014.08.019","article-title":"The role of PI3K\/AKT\/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration.","volume":"26","author":"Heras-Sandoval","year":"2014","journal-title":"Cell Signal"},{"key":"B16","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.bja.2019.03.045","article-title":"The association between postoperative cognitive dysfunction and cerebral oximetry during cardiac surgery: a secondary analysis of a randomised trial.","volume":"123","author":"Holmgaard","year":"2019","journal-title":"Br. J. Anaesth"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19473-7","article-title":"Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer\u2019s disease.","volume":"11","author":"Huynh","year":"2020","journal-title":"Nat. Commun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.bja.2020.06.063","article-title":"Postoperative delirium: perioperative assessment, risk reduction, and management.","volume":"125","author":"Jin","year":"2020","journal-title":"Br. J. Anaesth."},{"key":"B19","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: beyond biomarkers and towards mechanisms.","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.biopsych.2014.05.006","article-title":"Alzheimer\u2019s disease risk genes and mechanisms of disease pathogenesis.","volume":"77","author":"Karch","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3109\/14017430903490981","article-title":"Inflammatory\/oxidative stress during the first week after different types of cardiac surgery.","volume":"44","author":"Karu","year":"2010","journal-title":"Scand. Cardiovasc. J."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-018-0486-8","article-title":"Unusual elevation in Entropy but not in PSI during general anesthesia: a case report.","volume":"18","author":"Kim","year":"2018","journal-title":"BMC Anesthesiol."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-020-01166-9","article-title":"Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip\/knee replacement: a prospective cohort study.","volume":"20","author":"Lin","year":"2020","journal-title":"BMC Anesthesiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1053\/j.jvca.2018.07.012","article-title":"Delirium After Cardiac Surgery and Cumulative Fluid Balance: a Case-Control Cohort Study.","volume":"33","author":"Mailhot","year":"2019","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"B25","doi-asserted-by":"crossref","first-page":"14363","DOI":"10.1523\/JNEUROSCI.3928-08.2008","article-title":"RTP801 is induced in Parkinson\u2019s disease and mediates neuron death by inhibiting Akt phosphorylation\/activation.","volume":"28","author":"Malagelada","year":"2008","journal-title":"J. Neurosci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.jagp.2013.09.005","article-title":"Neuropathogenesis of delirium: review of current etiologic theories and common pathways.","volume":"21","author":"Maldonado","year":"2013","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.neurobiolaging.2016.08.027","article-title":"Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer\u2019s and Parkinson\u2019s diseases.","volume":"49","author":"Marin","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"B28","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1093\/ejcts\/ezt637","article-title":"Oxidative stress during extracorporeal circulation.","volume":"46","author":"McDonald","year":"2014","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1111\/jgs.14238","article-title":"Associations Between Delirium and Preoperative Cerebrospinal Fluid C-Reactive Protein, Interleukin-6, and Interleukin-6 Receptor in Individuals with Acute Hip Fracture.","volume":"64","author":"Neerland","year":"2016","journal-title":"J. Am. Geriatr. Soc."},{"key":"B30","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.vph.2015.12.005","article-title":"Lipid-lowering drugs prevent neurovascular and cognitive consequences of cardiopulmonary bypass.","volume":"80","author":"Ouk","year":"2016","journal-title":"Vascul. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1097\/aln.0000000000003328","article-title":"Electroencephalogram Burst-suppression during Cardiopulmonary Bypass in Elderly Patients Mediates Postoperative Delirium.","volume":"133","author":"Pedemonte","year":"2020","journal-title":"Anesthesiology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jprot.2019.04.008","article-title":"Plasma metabolomics in early Alzheimer\u2019s disease patients diagnosed with amyloid biomarker.","volume":"200","author":"Pe\u00f1a-Bautista","year":"2019","journal-title":"J. Proteom."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8957541","article-title":"Serum Metabolomics of Early Postoperative Cognitive Dysfunction in Elderly Patients Using Liquid Chromatography and Q-TOF Mass Spectrometry.","volume":"2020","author":"Qian","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/bja\/aex053","article-title":"Association between delirium and cognitive change after cardiac surgery.","volume":"119","author":"Sau\u00ebr","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"B35","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.jalz.2017.01.020","article-title":"Metabolic network failures in Alzheimer\u2019s disease: a biochemical road map.","volume":"13","author":"Toledo","year":"2017","journal-title":"Alzheimers Dement"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1053\/j.jvca.2015.06.018","article-title":"Incidence of and Risk Factors for Delirium After Cardiac Surgery at a Quaternary Care Center: a Retrospective Cohort Study.","volume":"29","author":"Tse","year":"2015","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"B37","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/acn3.58","article-title":"Preoperative cerebrospinal fluid \u03b2-Amyloid\/Tau ratio and postoperative delirium.","volume":"1","author":"Xie","year":"2014","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00073","article-title":"The Role of Insulin\/IGF-1\/PI3K\/Akt\/GSK3\u03b2 Signaling in Parkinson\u2019s Disease Dementia.","volume":"12","author":"Yang","year":"2018","journal-title":"Front. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1007\/s11064-020-03072-5","article-title":"Estrogen Exerts Neuroprotective Effects in Vascular Dementia Rats by Suppressing Autophagy and Activating the Wnt\/\u03b2-Catenin Signaling Pathway.","volume":"45","author":"Yang","year":"2020","journal-title":"Neurochem. Res."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01050","article-title":"Neuroprotective Effects of Annexin A1 Tripeptide after Deep Hypothermic Circulatory Arrest in Rats.","volume":"8","author":"Zhang","year":"2017","journal-title":"Front. Immunol."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1211-8","article-title":"Aggf1 attenuates neuroinflammation and BBB disruption via PI3K\/Akt\/NF-\u03baB pathway after subarachnoid hemorrhage in rats.","volume":"15","author":"Zhu","year":"2018","journal-title":"J. Neuroinflam."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0000000000005041","article-title":"Inflammation Disrupts the Brain Network of Executive Function After Cardiac Surgery.","volume":"2021","author":"Zhu","year":"2021","journal-title":"Ann. Surg."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.857902\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T01:23:59Z","timestamp":1654824239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.857902\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":42,"alternative-id":["10.3389\/fnagi.2022.857902"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.857902","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]},"article-number":"857902"}}