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<PubmedArticle><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">35677835</PMID><DateRevised><Year>2023</Year><Month>09</Month><Day>16</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">2666-5204</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><PubDate><Year>2022</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Resuscitation plus</Title><ISOAbbreviation>Resusc Plus</ISOAbbreviation></Journal><ArticleTitle>Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators.</ArticleTitle><Pagination><StartPage>100258</StartPage><MedlinePgn>100258</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">100258</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.resplu.2022.100258</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="UNASSIGNED">Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation.</AbstractText><AbstractText Label="METHODS" NlmCategory="UNASSIGNED">Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys&#xae; electrochemiluminescence immunoassays on a Cobas e601 instrument.</AbstractText><AbstractText Label="RESULTS" NlmCategory="UNASSIGNED">Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="UNASSIGNED">This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.</AbstractText><CopyrightInformation>&#xa9; 2022 The Authors.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Moseby-Knappe</LastName><ForeName>Marion</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Neurology, Lund University, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Levin</LastName><ForeName>Helena</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Anaesthesiology and Intensive Care, Research and Education, Lund University, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blennow</LastName><ForeName>Kaj</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Neurochemistry, Institute of Neuroscience &amp; Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M&#xf6;lndal, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ull&#xe9;n</LastName><ForeName>Susann</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Clinical Studies Sweden - Forum South, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zetterberg</LastName><ForeName>Henrik</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Neurochemistry, Institute of Neuroscience &amp; Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M&#xf6;lndal, Sweden.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>UK Dementia Research Institute at UCL, London, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lilja</LastName><ForeName>Gisela</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Neurology, Lund University, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dankiewicz</LastName><ForeName>Josef</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Cardiology, Lund University, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jakobsen</LastName><ForeName>Janus Christian</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lagebrant</LastName><ForeName>Alice</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Neurology, Lund University, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Friberg</LastName><ForeName>Hans</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Sk&#xe5;ne University Hospital, Malm&#xf6;, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nichol</LastName><ForeName>Alistair</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>University College Dublin, Clinical Research Centre, St Vincent's University Hospital Dublin, Ireland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne. Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Intensive Care Unit, Alfred Hospital, Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ainschough</LastName><ForeName>Kate</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>University College Dublin, Clinical Research Centre, St Vincent's University Hospital Dublin, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eastwood</LastName><ForeName>Glenn M</ForeName><Initials>GM</Initials><AffiliationInfo><Affiliation>Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wise</LastName><ForeName>Matt P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thomas</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Intensive Care Unit, University Hospitals, Bristol and Weston, England, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Keeble</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Essex Cardiothoracic Centre, MSE, Basildon, Essex, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>MTRC, Anglia Ruskin School of Medicine, Chelmsford, Essex, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cariou</LastName><ForeName>Alain</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Medical Intensive Care Unit, AP-HP, Cochin Hospital, Paris, France, Paris Cit&#xe9; University, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leithner</LastName><ForeName>Christoph</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>AG Emergency and Critical Care Neurology, Campus Virchow Klinikum, Department of Neurology, Charit&#xe9; Universit&#xe4;tsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rylander</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>D&#xfc;ring</LastName><ForeName>Joachim</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Sk&#xe5;ne University Hospital, Malm&#xf6;, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>B&#x11b;lohl&#xe1;vek</LastName><ForeName>Jan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Second Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grejs</LastName><ForeName>Anders</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Borgquist</LastName><ForeName>Ola</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Department of Cardiothoracic Surgery, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Und&#xe9;n</LastName><ForeName>Johan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Malm&#xf6;, Dept. Operation and Intensive Care, Lund University, Hallands Hospital Halmstad, Halmstad, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Simon</LastName><ForeName>Maryline</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Clinical Development Department, Roche Diagnostics International AG, Rotkreuz, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rolny</LastName><ForeName>Vinzent</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Biostatistical Department, Roche Diagnostics International AG, Rotkreuz, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Piehler</LastName><ForeName>Alex</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Biostatistical Department, Roche Diagnostics International AG, Rotkreuz, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cronberg</LastName><ForeName>Tobias</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Neurology, Lund University, Sk&#xe5;ne University Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nielsen</LastName><ForeName>Niklas</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2022</Year><Month>06</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Resusc Plus</MedlineTA><NlmUniqueID>101774410</NlmUniqueID><ISSNLinking>2666-5204</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Brain injury markers</Keyword><Keyword MajorTopicYN="N">Cardiac arrest</Keyword><Keyword MajorTopicYN="N">GFAP, S100</Keyword><Keyword MajorTopicYN="N">NFL</Keyword><Keyword MajorTopicYN="N">NSE</Keyword><Keyword MajorTopicYN="N">Neurofilament light</Keyword><Keyword MajorTopicYN="N">Neuron specific enolase</Keyword><Keyword MajorTopicYN="N">Prognostication, outcome, biomarkers</Keyword><Keyword MajorTopicYN="N">Protocol</Keyword><Keyword MajorTopicYN="N">Total-tau, glial fibrially acidic protein</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2022</Year><Month>5</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2022</Year><Month>5</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2022</Year><Month>5</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2022</Year><Month>6</Month><Day>9</Day><Hour>2</Hour><Minute>23</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2022</Year><Month>6</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>6</Month><Day>10</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2022</Year><Month>6</Month><Day>2</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">35677835</ArticleId><ArticleId IdType="pmc">PMC9168690</ArticleId><ArticleId IdType="doi">10.1016/j.resplu.2022.100258</ArticleId><ArticleId IdType="pii">S2666-5204(22)00058-3</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Nolan J.P., Sandroni C., Bottiger B.W., et al. 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