Leveraging biomarkers of traumatic brain injury in adults to assess pediatric neurocritical illness

利用成人创伤性脑损伤的生物标志物评估儿科神经危重疾病

• 批准号: 9768508
• 负责人: Melania Maria Bembea
• 金额: $ 19.48万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768508
• 关键词: Acute Brain Injuries; Address; Admission activity; Adult; Age; Astrocytes; Axon; Bedside Testings; Biological Markers; Brain; Brain Injuries; Brain-Derived Neurotrophic Factor; CCL2 gene; CKB gene; Cardiac Surgery procedures; Cardiopulmonary Bypass; Caring; Categories; Cause of Death; Cerebrum; Cessation of life; Child; Childhood; Childhood Injury; Classification; Clinical; Critical Care; Critically ill children; Data; Detection; Devices; Diagnosis; Diagnostic; Disease; Drops; Enrollment; Evaluation; Extracorporeal Membrane Oxygenation; Failure; Future; Gelatinase B; Glial Fibrillary Acidic Protein; Goals; Heart Arrest; Hospital Mortality; Hospitals; Hyperthermia; Hypoglycemia; Hypotension; Hypoxia; Hypoxic Brain Damage; Inflammatory; Injury; Intervention; Intracranial Hemorrhages; Intracranial Hypertension; Measures; Medical; Methods; Modernization; Monitor; Morbidity - disease rate; Nervous System Trauma; Neurologic; Neuron-Specific Enolase; Neurons; Operative Surgical Procedures; Outcome; Participant; Patients; Pediatric Intensive Care Units; Pharmacology; Phenotype; Plasma; Population; Predictive Value; Proteins; Randomized Controlled Trials; Risk; Risk stratification; Sampling; Seizures; Severities; Severity of illness; Status Epilepticus; Stroke; Survivors; System; Testing; Therapeutic; Time; Traumatic Brain Injury; UCHL1 gene; United States; VSNL1 gene; VWF gene; animal data; base; biobank; biomarker panel; cohort; data registry; design; disability; embolic stroke; functional disability; functional status; insight; mortality; natural hypothermia; neurodevelopment; neurogranin; neuroimaging; neurological recovery; novel; point of care; pre-clinical; prevent; prospective test; repository; response; tau Proteins; tool

PROJECT SUMMARY Approximately 230,000-480,000 children are admitted to Pediatric Intensive Care Units (PICU) annually in the United States. Of these children, 16% present with neurocritical illness. Neurocritical conditions range from traumatic brain injury (TBI), stroke, seizures and status epilepticus, to hypoxic brain injury following cardiac arrest. While overall PICU mortality has declined significantly from 11% in the 1980s to 1.3%-5% in the contemporary era, mortality in children with neurocritical illness is as high as 12%, with highest mortality following cardiac arrest (24%). Brain injury and neurological system failure represent the proximal cause of death for 65% of all deaths in the PICU, with 14% of children acquiring brain injuries during their PICU stay. Among all PICU survivors, children with neurocritical illness also have higher rates of decline in neurofunctional status (7.3%) at the time of discharge vs baseline, compared to the general PICU population (4.8%). Thus, modern neurocritical care focuses on monitoring neurologic functional status and preventing secondary injuries that exacerbate the initial injury and worsen long-term outcomes (e.g., hypotension, hypoglycemia, hyperthermia, hypoxia, intracranial hypertension, or seizures). We currently lack valid tools for timely evaluation of the severity of the initial brain injury, for monitoring of secondary neurologic injury, and for risk stratification and outcome classification early in the PICU course of critically ill children. Inability to adequately classify and select study participants for targeted interventions is a well described problem in critical care studies. The overall goal of this proposal is to design a point-of-care plasma brain injury biomarker panel for pediatric neurocritical illness with a 30 minute time-to-results, using biomarkers that have been validated in adult populations. We hypothesize that point-of-care testing of brain injury biomarkers will allow for timely identification of patients who would benefit the most from neuroprotective interventions needing rapid initiation for optimal efficacy, and could then be used to monitor cerebral response to such interventions. As unique combinations of biomarkers are likely to be superior for each condition, we will use an already existing well phenotyped PICU cohort and plasma repository, and a comprehensive point-of-care panel of 14 brain injury biomarkers developed for adult TBI by Meso Scale Diagnostics (MSD, Rockville, MD). We will address our overall goal in the following specific aims: (1) Determine the sensitivity of a novel platform for detection of plasma brain injury biomarkers in children admitted to the PICU with clinical neurologic injury; and (2) Determine the extent to which circulating levels of brain injury biomarkers during PICU admission predict A) mortality before hospital discharge, B) neurologic disability at hospital discharge, and C) association with abnormalities on neuroimaging. If sensitivity of injury and predictive value for outcomes are confirmed, the point-of-care device developed for adult TBI will be tested prospectively in future pediatric bedside studies.

项目总结 每年约有230,000-48,000名儿童进入儿科重症监护病房(PICU)。 美国。在这些儿童中，16%患有神经危重疾病。神经危重状况的范围从 创伤性脑损伤、中风、癫痫发作和癫痫持续状态，到心脏手术后缺氧性脑损伤 逮捕。虽然PICU的总体死亡率从20世纪80年代的11%显着下降到2005年的1.3%-5% 当代，患有神经危重疾病的儿童死亡率高达12%，最高死亡率仅次于 心脏骤停(24%)。脑损伤和神经系统衰竭是65%的人死亡的近端原因 在PICU的所有死亡中，有14%的儿童在PICU期间患上了脑损伤。在所有PICU中 幸存者、患有神经危重疾病的儿童的神经功能状态下降率也较高(7.3%) 出院时间与基线相比，与普通PICU人口(4.8%)相比。因此，现代神经危急症 护理的重点是监测神经功能状态，防止继发性损伤加剧 最初的损伤和恶化的长期结果(如低血压、低血糖、体温过高、缺氧、 颅内压增高，或癫痫)。我们目前缺乏有效的工具来及时评估 最初的脑损伤，用于监测继发性神经损伤，并用于风险分层和结果 危重患儿PICU病程早期分类。无法对研究进行适当的分类和选择 在重症监护研究中，有针对性的干预措施的参与者是一个很好描述的问题。这个项目的总体目标是 建议设计一种治疗儿童神经危重疾病的护理点血浆脑损伤生物标志物小组 30分钟结果，使用已在成人人群中验证的生物标记物。我们假设 脑损伤生物标志物的护理点测试将允许及时识别哪些患者将受益于 大多数来自神经保护干预，需要快速启动以获得最佳效果，然后可以用于 监测大脑对此类干预的反应。因为生物标志物的独特组合可能会更好 对于每种情况，我们将使用已经存在的表型良好的PICU队列和血浆存储库，以及 由14项脑损伤生物标志物组成的综合护理小组采用MESO量表为成人颅脑损伤开发 诊断(MSD，罗克维尔，马里兰州)。我们将在以下具体目标中解决我们的总目标：(1)确定 PICU患儿血浆脑损伤生物标志物检测平台的敏感性 临床神经损伤；以及(2)确定脑损伤生物标志物循环水平的程度 在PICU入院期间，预测A)出院前的死亡率，B)在医院的神经残疾 C)与神经影像异常有关。如果损伤的敏感性和预测价值 结果得到确认，为成人脑外伤开发的护理点设备将在未来进行前瞻性测试 儿科床边研究。