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dc.contributor.authorWhitehouse, Daniel P
dc.contributor.authorMonteiro, Miguel
dc.contributor.authorCzeiter, Endre
dc.contributor.authorVyvere, Thijs Vande
dc.contributor.authorValerio, Fernanda
dc.contributor.authorYe, Zheng
dc.contributor.authorAmrein, Krisztina
dc.contributor.authorKamnitsas, Konstantinos
dc.contributor.authorXu, Haiyan
dc.contributor.authorYang, Zhihui
dc.contributor.authorVerheyden, Jan
dc.contributor.authorDas, Tilak
dc.contributor.authorKornaropoulos, Evgenios N
dc.contributor.authorSteyerberg, Ewout
dc.contributor.authorMaas, Andrew IR
dc.contributor.authorWang, Kevin KW
dc.contributor.authorBüki, András
dc.contributor.authorGlocker, Ben
dc.contributor.authorMenon, David K
dc.contributor.authorNewcombe, Virginia
dc.contributor.authorCENTER-TBI Participants and Investigators
dc.date.accessioned2022-02-02T14:17:58Z
dc.date.available2022-02-02T14:17:58Z
dc.date.issued2021-12-24
dc.identifier.issn2352-3964
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333558
dc.description.abstractBACKGROUND: We aimed to understand the relationship between serum biomarker concentration and lesion type and volume found on computed tomography (CT) following all severities of TBI. METHODS: Concentrations of six serum biomarkers (GFAP, NFL, NSE, S100B, t-tau and UCH-L1) were measured in samples obtained <24 hours post-injury from 2869 patients with all severities of TBI, enrolled in the CENTER-TBI prospective cohort study (NCT02210221). Imaging phenotypes were defined as intraparenchymal haemorrhage (IPH), oedema, subdural haematoma (SDH), extradural haematoma (EDH), traumatic subarachnoid haemorrhage (tSAH), diffuse axonal injury (DAI), and intraventricular haemorrhage (IVH). Multivariable polynomial regression was performed to examine the association between biomarker levels and both distinct lesion types and lesion volumes. Hierarchical clustering was used to explore imaging phenotypes; and principal component analysis and k-means clustering of acute biomarker concentrations to explore patterns of biomarker clustering. FINDINGS: 2869 patient were included, 68% (n=1946) male with a median age of 49 years (range 2-96). All severities of TBI (mild, moderate and severe) were included for analysis with majority (n=1946, 68%) having a mild injury (GCS 13-15). Patients with severe diffuse injury (Marshall III/IV) showed significantly higher levels of all measured biomarkers, with the exception of NFL, than patients with focal mass lesions (Marshall grades V/VI). Patients with either DAI+IVH or SDH+IPH+tSAH, had significantly higher biomarker concentrations than patients with EDH. Higher biomarker concentrations were associated with greater volume of IPH (GFAP, S100B, t-tau;adj r2 range:0·48-0·49; p<0·05), oedema (GFAP, NFL, NSE, t-tau, UCH-L1;adj r2 range:0·44-0·44; p<0·01), IVH (S100B;adj r2 range:0.48-0.49; p<0.05), Unsupervised k-means biomarker clustering revealed two clusters explaining 83·9% of variance, with phenotyping characteristics related to clinical injury severity. INTERPRETATION: Interpretation: Biomarker concentration within 24 hours of TBI is primarily related to severity of injury and intracranial disease burden, rather than pathoanatomical type of injury. FUNDING: CENTER-TBI is funded by the European Union 7th Framework programme (EC grant 602150).
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleRelationship of admission blood proteomic biomarkers levels to lesion type and lesion burden in traumatic brain injury: A CENTER-TBI study.
dc.typeArticle
dc.publisher.departmentDepartment of Medicine
dc.date.updated2021-12-24T14:07:03Z
prism.endingPage103777
prism.number103777
prism.publicationDate2022
prism.publicationNameEBioMedicine
prism.startingPage103777
prism.volume75
dc.identifier.doi10.17863/CAM.80978
dcterms.dateAccepted2021-12-10
rioxxterms.versionofrecord10.1016/j.ebiom.2021.103777
rioxxterms.versionVoR
dc.contributor.orcidNewcombe, Virginia [0000-0001-6044-9035]
dc.identifier.eissn2352-3964
rioxxterms.typeJournal Article/Review
pubs.funder-project-idAcademy of Medical Sciences (unknown)
cam.depositDate2021-12-24
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International