{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T14:30:45Z","timestamp":1792765845467,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with sepsis-associated delirium (SAD) show severe neurological impairment, often require an intensive care unit (ICU) stay and have a high risk of mortality. Hence, useful biomarkers for early detection of SAD are urgently needed. Extracellular vesicles (EVs) and their cargo are known to maintain normal physiology but also have been linked to numerous disease states. Here, we sought to identify differentially expressed proteins in plasma EVs from SAD patients as potential biomarkers for SAD. Plasma EVs from 11 SAD patients and 11 age-matched septic patients without delirium (non-SAD) were isolated by differential centrifugation, characterized by nanoparticle tracking analysis, transmission electron microscopy and Western blot analysis. Differential EV protein expression was determined by mass spectrometry and the resulting proteomes were characterized by Gene Ontology term and between-group statistics. As preliminary results because of the small group size, five distinct proteins showed significantly different expression pattern between SAD and non-SAD patients (p \u2264 0.05). In SAD patients, upregulated proteins included paraoxonase-1 (PON1), thrombospondin 1 (THBS1), and full fibrinogen gamma chain (FGG), whereas downregulated proteins comprised immunoglobulin (IgHV3) and complement subcomponent (C1QC). Thus, plasma EVs of SAD patients show significant changes in the expression of distinct proteins involved in immune system regulation and blood coagulation as well as in lipid metabolism in this pilot study. They might be a potential indicator for to the pathogenesis of SAD and thus warrant further examination as potential biomarkers, but further research is needed to expand on these findings in longitudinal study designs with larger samples and comprehensive polymodal data collection.<\/jats:p>","DOI":"10.3390\/ijms242115781","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T12:50:42Z","timestamp":1698670242000},"page":"15781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Extracellular Vesicles as Possible Plasma Markers and Mediators in Patients with Sepsis-Associated Delirium\u2014A Pilot Study"],"prefix":"10.3390","volume":"24","author":[{"given":"Konstanze","family":"Plaschke","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-2783","authenticated-orcid":false,"given":"Mascha O.","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"H\u00f6lle","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-6535","authenticated-orcid":false,"given":"Maik","family":"von der Forst","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Christian","family":"Wolf","sequence":"additional","affiliation":[{"name":"Center for Psychosocial Medicine, Department of General Psychiatry, University Hospital Heidelberg, Vossstra\u00dfe 4, 69115 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Kopitz","sequence":"additional","affiliation":[{"name":"Department of Applied Tumor Biology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0606-7818","authenticated-orcid":false,"given":"Johannes","family":"Gebert","sequence":"additional","affiliation":[{"name":"Department of Applied Tumor Biology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1055\/s-0041-100391","article-title":"Pathophysiology of sepsis","volume":"50","author":"Uhle","year":"2015","journal-title":"Anasthesiol. 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