{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:43:46Z","timestamp":1793317426752,"version":"4.5.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Crit Care"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as \u2018mild\u2019, \u2018moderate\u2019 or \u2018severe\u2019 based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (&lt;\u200924\u00a0h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with \u2018moderate\u2019 TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with \u2018severe\u2019 GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      The core study was registered with ClinicalTrials.gov, number\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02210221\">NCT02210221<\/jats:ext-link>\n                      , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13054-022-04079-w","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T12:45:56Z","timestamp":1659098756000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study"],"prefix":"10.1186","volume":"26","clinical-trial-number":[{"clinical-trial-number":"nct02210221","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Cecilia A. 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Available from: https:\/\/www.center-tbi.eu\/project\/ethical-approval"}],"container-title":["Critical Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13054-022-04079-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13054-022-04079-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13054-022-04079-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T02:05:29Z","timestamp":1727661929000},"score":1,"resource":{"primary":{"URL":"https:\/\/ccforum.biomedcentral.com\/articles\/10.1186\/s13054-022-04079-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["4079"],"URL":"https:\/\/doi.org\/10.1186\/s13054-022-04079-w","relation":{},"ISSN":["1364-8535"],"issn-type":[{"value":"1364-8535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,27]]},"assertion":[{"value":"20 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This sub-study was approved by the CENTER-TBI management committee. The CENTER-TBI study was conducted in accordance with all relevant laws of the European Union if directly applicable or of direct effect and all relevant laws of the country where the Recruiting sites were located, including but not limited to, the relevant privacy and data protection laws and regulations (the \u201cPrivacy Law\u201d), the relevant laws and regulations on the use of human materials, and all relevant guidance relating to clinical studies from time to time in force including, but not limited to, the ICH Harmonised Tripartite Guideline for Good Clinical Practice (CPMP\/ICH\/135\/95) (\u201cICH GCP\u201d) and the World Medical Association Declaration of Helsinki. Informed Consent by the patients or next of kin was obtained, according to the local legislations, for all patients recruited in the Core Dataset of CENTER-TBI and documented in the electronic case report form. Ethical approval for CENTER-TBI was obtained at each recruiting site. The list of sites, Ethical Committees, approval numbers and approval dates are available online [\n                      \n                      ].","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DM reports grants, personal fees and non-financial support from GlaxoSmithKline, grants and personal fees from NeuroTrauma Sciences, personal fees from Pfizer Ltd, personal fees from PressuraNeuro, grants and personal fees from Lantmannen AB, grants and personal fees from Integra, outside the submitted work. All other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"228"}}