{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:01:51Z","timestamp":1787313711240,"version":"build-2736575974"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["128235"],"award-info":[{"award-number":["128235"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005609","name":"Turun Yliopisto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005609","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Research Funding"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Out-of-hospital cardiac arrest (OHCA) carries a relatively poor prognosis and requires multimodal prognostication to guide clinical decisions. Identification of previously unrecognized metabolic routes associated with patient outcome may contribute to future biomarker discovery. In OHCA, inhaled xenon elicits neuro- and cardioprotection. However, the metabolic effects remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>In this post-hoc study of the randomised, 2-group, single-blind, phase 2 Xe-Hypotheca trial, 110 OHCA survivors were randomised 1:1 to receive targeted temperature management (TTM) at 33\u00b0C with or without inhaled xenon during 24 h. Blood samples for nuclear magnetic resonance spectroscopy metabolic profiling were drawn upon admission, at 24 and 72 h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 24 h, increased lactate, adjusted hazard-ratio 2.25, 95% CI [1.53; 3.30], p&lt;0.001, and decreased branched-chain amino acids (BCAA) leucine 0.64 [0.5; 0.82], p = 0.007, and valine 0.37 [0.22; 0.63], p = 0.003, associated with 6-month mortality. At 72 h, increased lactate 2.77 [1.76; 4.36], p&lt;0.001, and alanine 2.43 [1.56; 3.78], p = 0.001, and decreased small HDL cholesterol ester content (S-HDL-CE) 0.36 [0.19; 0.68], p = 0.021, associated with mortality. No difference was observed between xenon and control groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In OHCA patients receiving TTM with or without xenon, high lactate and alanine and decreased BCAAs and S-HDL-CE associated with increased mortality. It remains to be established whether current observations on BCAAs, and possibly alanine and lactate, could reflect neural damage via their roles in the metabolism of the neurotransmitter glutamate. Xenon did not significantly alter the measured metabolic profile, a potentially beneficial attribute in the context of compromised ICU patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Trial Registry number:<\/jats:bold>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00879892\" xlink:type=\"simple\">NCT00879892<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0304966","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T16:09:11Z","timestamp":1717517351000},"page":"e0304966","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["A metabolic profile of xenon and metabolite associations with 6-month mortality after out-of-hospital cardiac arrest: A post-hoc study of the randomised Xe-Hypotheca trial"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6679-4753","authenticated-orcid":true,"given":"Aleksi J.","family":"Nummela","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Scheinin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Perola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7547-7458","authenticated-orcid":true,"given":"Anni","family":"Joensuu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruut","family":"Laitio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Arola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Gr\u00f6nlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risto O.","family":"Roine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"B\u00e4cklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero J.","family":"Vahlberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Laitio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Xe-Hypotheca Collaboration Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"issue":"14","key":"pone.0304966.ref001","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/eurheartj\/ehu240","article-title":"Improved outcome in Sweden after out-of-hospital cardiac arrest and possible association with improvements in every link in the chain of survival","volume":"36","author":"A Stromsoe","year":"2015","journal-title":"Eur Heart J [Internet]"},{"key":"pone.0304966.ref002","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.resuscitation.2015.02.003","article-title":"Out-of-hospital cardiac arrest survival improving over time: Results from the Resuscitation Outcomes Consortium (ROC)","volume":"91","author":"MR Daya","year":"2015","journal-title":"Resuscitation [Internet]"},{"issue":"8","key":"pone.0304966.ref003","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1056\/NEJMoa003289","article-title":"Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia","volume":"346","author":"SA Bernard","year":"2002","journal-title":"N Engl J Med [Internet]"},{"issue":"8","key":"pone.0304966.ref004","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1056\/NEJMoa012689","article-title":"Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest","volume":"346","author":"M. 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