Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest.
Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest.
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DOI：
10.1001/jamanetworkopen.2022.30518
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发表时间：
2022-09-01
影响因子：
13.8
通讯作者：
Fabio, Anthony
中科院分区：
文献类型：
--
作者：
Fink, Ericka L.;Kochanek, Patrick M.;Panigrahy, Ashok;Beers, Sue R.;Berger, Rachel P.;Bayir, Hulya;Pineda, Jose;Newth, Christopher;Topjian, Alexis A.;Press, Craig A.;Maddux, Aline B.;Willyerd, Frederick;Hunt, Elizabeth A.;Siems, Ashley;Chung, Melissa G.;Smith, Lincoln;Wenger, Jesse;Doughty, Lesley;Diddle, J. Wesley;Patregnani, Jason;Piantino, Juan;Walson, Karen Hallermeier;Balakrishnan, Binod;Meyer, Michael T.;Friess, Stuart;Maloney, David;Rubin, Pamela;Haller, Tamara L.;Treble-Barna, Amery;Wang, Chunyan;Clark, Robert R. S. B.;Fabio, Anthony
儿童心脏骤停后1年早期血脑损伤生物标志物是否与不良预后相关？在这项对120名心脏骤停后复苏的儿童进行的队列研究中，4种脑损伤生物标志物（胶质纤维酸性蛋白、泛素羧基末端酯酶L1、神经丝光和tau）的血液浓度与1年的不良预后相关。这些发现表明，临床使用的基于血液的脑损伤生物标志物可能有助于儿童心脏骤停后的早期预后评估。家庭和临床医生有有限的有效工具来帮助估计儿童心脏骤停后早期的长期结果。基于血液的脑特异性生物标志物可能是帮助评估结果的有用工具。分析儿童心脏骤停1年后血基脑损伤生物标志物浓度与预后的关系。儿童心脏骤停后的个性化结局多中心前瞻性队列研究于2017年5月16日至2020年8月19日在美国14个学术转诊中心的儿科重症监护室进行，主要研究者对1年的结果进行盲法研究。该研究包括120名年龄在48小时至17岁之间的儿童，他们在心脏骤停后复苏，心脏骤停前儿童大脑表现类别评分为1至3分，并在心脏骤停后入住重症监护病房。心脏骤停。主要转归是心脏骤停后1年的不良转归（死亡或生存，根据Vineland适应行为量表，第三版，评分<70分）。在心脏骤停后第1 ~ 3天测定血液样本中的胶质纤维酸性蛋白（GFAP）、泛素羧基末端酯酶L1 （UCH-L1）、神经丝光（NfL）和tau浓度。采用多变量logistic回归和受试者工作特征曲线下面积（AUROC）分析来检验每种生物标志物与第1至3天预后的相关性。在120名有主要结局数据的儿童中，中位（IQR）年龄为1.0（0-8.5）岁；男性71例，占59.2%。亚裔5例（4.2%），黑人19例（15.8%），白人81例（67.5%），未知种族15例（12.5%）；在110名有种族数据的儿童中，11名（10.0%）为西班牙裔，99名（90.0%）为非西班牙裔。总体而言，70名儿童（58.3%）预后良好，50名儿童（41.7%）预后不良，包括43例死亡。在心脏骤停后的第1 - 3天，所有4种测量的生物标志物的浓度在1年的不利结果与有利结果的儿童中较高。协变量调整后，第1天（调整优势比[aOR]， 5.91, 95% CI, 1.82-19.19）、第2天（aOR, 11.88, 95% CI, 3.82-36.92）和第3天（aOR, 10.22, 95% CI, 3.14-33.33）的NfL浓度；第2天（aOR, 11.27, 95% CI, 3.00-42.36）和第3天（aOR, 7.56, 95% CI, 2.11-27.09） UCH-L1浓度；第2天（aOR, 2.31, 95% CI, 1.19-4.48）和第3天（aOR, 2.19, 95% CI, 1.19-4.03） GFAP浓度；第1天（aOR, 2.44; 95% CI, 1.14-5.25）、第2天（aOR, 2.28; 95% CI, 1.31-3.97）和第3天（aOR, 2.04; 95% CI, 1.16-3.57）的tau浓度与不良结果相关。在第2天，添加NfL的AUROC模型显著高于未添加NfL的AUROC模型(AUROC, 0.932 [95% CI, 0.877-0.987]比0.871 [95% CI, 0.793-0.949]；02)和第3天（AUROC, 0.921 [95% CI, 0.857-0.986] vs 0.870 [95% CI, 0.786-0.953]; P = 0.03）。在这项队列研究中，基于血液的脑损伤生物标志物，特别是NfL，与儿童心脏骤停后1年的不利结果相关。需要进一步评估生物标志物与1年后神经发育结果之间关联的准确性。本队列研究评估了心脏骤停后复苏的儿童血液脑损伤生物标志物浓度与1年预后之间的关系。
Are early blood-based brain injury biomarkers associated with an unfavorable outcome 1 year after pediatric cardiac arrest? In this cohort study of 120 children who were resuscitated after cardiac arrest, blood concentrations of 4 brain injury biomarkers (glial fibrillary acidic protein, ubiquitin carboxyl-terminal esterase L1, neurofilament light, and tau) were associated with unfavorable outcomes at 1 year. These findings suggest that blood-based brain injury biomarkers for clinical use may aid in early outcome assessment after pediatric cardiac arrest. Families and clinicians have limited validated tools available to assist in estimating long-term outcomes early after pediatric cardiac arrest. Blood-based brain-specific biomarkers may be helpful tools to aid in outcome assessment. To analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest. The Personalizing Outcomes After Child Cardiac Arrest multicenter prospective cohort study was conducted in pediatric intensive care units at 14 academic referral centers in the US between May 16, 2017, and August 19, 2020, with the primary investigators blinded to 1-year outcomes. The study included 120 children aged 48 hours to 17 years who were resuscitated after cardiac arrest, had pre–cardiac arrest Pediatric Cerebral Performance Category scores of 1 to 3 points, and were admitted to an intensive care unit after cardiac arrest. Cardiac arrest. The primary outcome was an unfavorable outcome (death or survival with a Vineland Adaptive Behavior Scales, third edition, score of <70 points) at 1 year after cardiac arrest. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCH-L1), neurofilament light (NfL), and tau concentrations were measured in blood samples from days 1 to 3 after cardiac arrest. Multivariate logistic regression and area under the receiver operating characteristic curve (AUROC) analyses were performed to examine the association of each biomarker with outcomes on days 1 to 3. Among 120 children with primary outcome data available, the median (IQR) age was 1.0 (0-8.5) year; 71 children (59.2%) were male. A total of 5 children (4.2%) were Asian, 19 (15.8%) were Black, 81 (67.5%) were White, and 15 (12.5%) were of unknown race; among 110 children with data on ethnicity, 11 (10.0%) were Hispanic, and 99 (90.0%) were non-Hispanic. Overall, 70 children (58.3%) had a favorable outcome, and 50 children (41.7%) had an unfavorable outcome, including 43 deaths. On days 1 to 3 after cardiac arrest, concentrations of all 4 measured biomarkers were higher in children with an unfavorable vs a favorable outcome at 1 year. After covariate adjustment, NfL concentrations on day 1 (adjusted odds ratio [aOR], 5.91; 95% CI, 1.82-19.19), day 2 (aOR, 11.88; 95% CI, 3.82-36.92), and day 3 (aOR, 10.22; 95% CI, 3.14-33.33); UCH-L1 concentrations on day 2 (aOR, 11.27; 95% CI, 3.00-42.36) and day 3 (aOR, 7.56; 95% CI, 2.11-27.09); GFAP concentrations on day 2 (aOR, 2.31; 95% CI, 1.19-4.48) and day 3 (aOR, 2.19; 95% CI, 1.19-4.03); and tau concentrations on day 1 (aOR, 2.44; 95% CI, 1.14-5.25), day 2 (aOR, 2.28; 95% CI, 1.31-3.97), and day 3 (aOR, 2.04; 95% CI, 1.16-3.57) were associated with an unfavorable outcome. The AUROC models were significantly higher with vs without the addition of NfL on day 2 (AUROC, 0.932 [95% CI, 0.877-0.987] vs 0.871 [95% CI, 0.793-0.949]; P = .02) and day 3 (AUROC, 0.921 [95% CI, 0.857-0.986] vs 0.870 [95% CI, 0.786-0.953]; P = .03). In this cohort study, blood-based brain injury biomarkers, especially NfL, were associated with an unfavorable outcome at 1 year after pediatric cardiac arrest. Additional evaluation of the accuracy of the association between biomarkers and neurodevelopmental outcomes beyond 1 year is needed. This cohort study assesses the association between blood-based brain injury biomarker concentrations and 1-year outcomes among children who were resuscitated after cardiac arrest.
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影响因子：
6.5
作者：
Fink EL;Berger RP;Clark RS;Watson RS;Angus DC;Panigrahy A;Richichi R;Callaway CW;Bell MJ;Mondello S;Hayes RL;Kochanek PM
通讯作者：
Kochanek PM
影响因子：
120.7
作者：
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通讯作者：
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48
作者：
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通讯作者：
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影响因子：
9.9
作者：
Chalela, JA;Wolf, RL;Kasner, SE
通讯作者：
Kasner, SE
影响因子：
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作者：
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通讯作者：
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