Prediction of Neurological Recovery After Cardiac Arrest Using Neurofilament Light Chain is Improved by a Proteomics-Based Multimarker Panel.
Cardiac arrest
Cardiopulmonary resuscitation
Neurofilament light chain
Prognostication
Proteomics
Journal
Neurocritical care
ISSN: 1556-0961
Titre abrégé: Neurocrit Care
Pays: United States
ID NLM: 101156086
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
20
03
2021
accepted:
19
07
2021
pubmed:
4
8
2021
medline:
14
4
2022
entrez:
3
8
2021
Statut:
ppublish
Résumé
Continuous advances in resuscitation care have increased survival, but the rate of favorable neurological outcome remains low. We have shown the usefulness of proteomics in identifying novel biomarkers to predict neurological outcome. Neurofilament light chain (NfL), a marker of axonal damage, has since emerged as a promising single marker. The aim of this study was to assess the predictive value of NfL in comparison with and in addition to our established model. NfL was measured in plasma samples drawn at 48 h after cardiac arrest using single-molecule assays. Neurological function was recorded on the cerebral performance category (CPC) scale at discharge from the intensive care unit and after 6 months. The ability to predict a dichotomized outcome (CPC 1-2 vs. 3-5) was assessed with receiver operating characteristic (ROC) curves. Seventy patients were included in this analysis, of whom 21 (30%) showed a favorable outcome (CPC 1-2), compared with 49 (70%) with an unfavorable outcome (CPC 3-5) at discharge. NfL increased from CPC 1 to 5 (16.5 pg/ml to 641 pg/ml, p < 0.001). The addition of NfL to the existing model improved it significantly (Wald test, p < 0.001), and the combination of NfL with a multimarker model showed high areas under the ROC curve (89.7% [95% confidence interval 81.7-97.7] at discharge and 93.7% [88.2-99.2] at 6 months) that were significantly greater than each model alone. The combination of NfL with other plasma and clinical markers is superior to that of either model alone and achieves high areas under the ROC curve in this relatively small sample.
Sections du résumé
BACKGROUND
Continuous advances in resuscitation care have increased survival, but the rate of favorable neurological outcome remains low. We have shown the usefulness of proteomics in identifying novel biomarkers to predict neurological outcome. Neurofilament light chain (NfL), a marker of axonal damage, has since emerged as a promising single marker. The aim of this study was to assess the predictive value of NfL in comparison with and in addition to our established model.
METHODS
NfL was measured in plasma samples drawn at 48 h after cardiac arrest using single-molecule assays. Neurological function was recorded on the cerebral performance category (CPC) scale at discharge from the intensive care unit and after 6 months. The ability to predict a dichotomized outcome (CPC 1-2 vs. 3-5) was assessed with receiver operating characteristic (ROC) curves.
RESULTS
Seventy patients were included in this analysis, of whom 21 (30%) showed a favorable outcome (CPC 1-2), compared with 49 (70%) with an unfavorable outcome (CPC 3-5) at discharge. NfL increased from CPC 1 to 5 (16.5 pg/ml to 641 pg/ml, p < 0.001). The addition of NfL to the existing model improved it significantly (Wald test, p < 0.001), and the combination of NfL with a multimarker model showed high areas under the ROC curve (89.7% [95% confidence interval 81.7-97.7] at discharge and 93.7% [88.2-99.2] at 6 months) that were significantly greater than each model alone.
CONCLUSIONS
The combination of NfL with other plasma and clinical markers is superior to that of either model alone and achieves high areas under the ROC curve in this relatively small sample.
Identifiants
pubmed: 34342833
doi: 10.1007/s12028-021-01321-1
pii: 10.1007/s12028-021-01321-1
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
434-440Informations de copyright
© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.
Références
Nehme Z, Andrew E, Bernard S, Haskins B, Smith K. Trends in survival from out-of-hospital cardiac arrests defibrillated by paramedics, first responders and bystanders. Resuscitation. 2019;143:85–91.
doi: 10.1016/j.resuscitation.2019.08.018
Buick JE, Drennan IR, Scales DC, Brooks SC, Byers A, Cheskes S, et al. Improving temporal trends in survival and neurological outcomes after out-of-hospital cardiac arrest. Circ Cardiovasc Qual Outcomes. 2018;11:e003561.
doi: 10.1161/CIRCOUTCOMES.117.003561
Golan E, Barrett K, Alali AS, Duggal A, Jichici D, Pinto R, et al. Predicting neurologic outcome after targeted temperature management for cardiac arrest: systematic review and meta-analysis. Crit Care Med. 2014;42:1919–30.
doi: 10.1097/CCM.0000000000000335
Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: post-resuscitation care. Resuscitation. 2021;161:220–69.
doi: 10.1016/j.resuscitation.2021.02.012
Mulder M, Gibbs HG, Smith SW, Dhaliwal R, Scott NL, Sprenkle MD, et al. Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia*. Crit Care Med. 2014;42:2493–9.
doi: 10.1097/CCM.0000000000000540
Zellner T, Gärtner R, Schopohl J, Angstwurm M. NSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest. Resuscitation. 2013;84:1382–6.
doi: 10.1016/j.resuscitation.2013.03.021
Distelmaier K, Muqaku B, Wurm R, Arfsten H, Seidel S, Kovacs GG, et al. Proteomics-enriched prediction model for poor neurologic outcome in cardiac arrest survivors. Crit Care Med. 2020;48:167–75.
doi: 10.1097/CCM.0000000000004105
Aaronson RM, Graven KK, Tucci M, McDonald RJ, Farber HW. Non-neuronal enolase is an endothelial hypoxic stress protein. J Biol Chem. 1995;270:27752–7.
doi: 10.1074/jbc.270.46.27752
Cao G, Xing J, Xiao X, Liou AKF, Gao Y, Yin X-M, et al. Critical role of calpain I in mitochondrial release of apoptosis-inducing factor in ischemic neuronal injury. J Neurosci. 2007;27:9278–93.
doi: 10.1523/JNEUROSCI.2826-07.2007
Madineni A, Alhadidi Q, Shah ZA. Cofilin inhibition restores neuronal cell death in oxygen–glucose deprivation model of ischemia. Mol Neurobiol. 2016;53:867–78.
doi: 10.1007/s12035-014-9056-3
Liu T, Daniels CK, Cao S. Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential. Pharmacol Ther. 2012;136:354–74.
doi: 10.1016/j.pharmthera.2012.08.014
Moseby-Knappe M, Mattsson N, Nielsen N, Zetterberg H, Blennow K, Dankiewicz J, et al. Serum neurofilament light chain for prognosis of outcome after cardiac arrest. JAMA Neurol. 2019;76:64–71.
doi: 10.1001/jamaneurol.2018.3223
Hviid CVB, Knudsen CS, Parkner T. Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand J Clin Lab Investig. 2020;80:291–5.
doi: 10.1080/00365513.2020.1730434
Donnino MW, Andersen LW, Berg KM, Reynolds JC, Nolan JP, Morley PT, et al. Temperature management after cardiac arrest: an advisory statement by the advanced life support task force of the international liaison committee on resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Circulation. 2015;132:2448–56.
doi: 10.1161/CIR.0000000000000313
Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VRM, Deakin CD, et al. European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care. Intensive Care Med. 2015;41:2039–56.
doi: 10.1007/s00134-015-4051-3
Ondracek AS, Hofbauer TM, Wurm R, Arfsten H, Seidl V, Früh A, et al. Imbalance between plasma double-stranded DNA and deoxyribonuclease activity predicts mortality after out-of-hospital cardiac arrest. Resuscitation. 2020;151:26–32.
doi: 10.1016/j.resuscitation.2020.03.006
Früh A, Goliasch G, Wurm R, Arfsten H, Seidel S, Galli L, et al. Gastric regurgitation predicts neurological outcome in out-of-hospital cardiac arrest survivors. Eur J Intern Med. 2020. https://doi.org/10.1016/j.ejim.2020.08.010 .
doi: 10.1016/j.ejim.2020.08.010
pubmed: 32839077
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.
doi: 10.1056/NEJMoa012689
Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L, et al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol. 2010;28:595–9.
doi: 10.1038/nbt.1641
van Buuren S, Groothuis-Oudshoorn K. Mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45:1–67.
doi: 10.18637/jss.v045.i03
DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.
doi: 10.2307/2531595
Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J-C, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform. 2011;12:77.
doi: 10.1186/1471-2105-12-77
Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3:32–5.
doi: 10.1002/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3
Hunziker S, Quinto A, Ramin-Wright M, Becker C, Beck K, Vincent A, et al. Serum neurofilament measurement improves clinical risk scores for outcome prediction after cardiac arrest: results of a prospective study. Crit Care. 2021;25:32.
doi: 10.1186/s13054-021-03459-y
Wihersaari L, Ashton NJ, Reinikainen M, Jakkula P, Pettilä V, Hästbacka J, et al. Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial. Intensive Care Med. 2021;47:39–48.
doi: 10.1007/s00134-020-06218-9