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Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures

结合蛋白质组生物标志物特征的创伤性脑损伤后低风险表型的预测因子

基本信息

批准号：
9975580
负责人：
Holly Elaine Hinson
金额：
$ 18.91万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9975580
关键词：
Accounting Acute Acute Brain Injuries Admission activity Age Benign Biological Markers Blood Blood Vessels Brain Injuries Cause of Death Cell Adhesion Molecules Classification Clinical Clinical Data Clinical Research Clinical Trials Complement Complex Data Deterioration Development Disease model Enrollment Event Exclusion Criteria Glasgow Outcome Scale Goals Head Health Sciences Heterogeneity Holly Hour Image Immune Immune response Injury Interleukin-6 Intervention Intracranial Hemorrhages Ion Transport Magnetic Resonance Imaging Mass Spectrum Analysis Measurable Measures Mediator of activation protein Mentors Metabolism Methods Modeling Molecular Nervous System Trauma Neurologic Neurologist Oregon Outcome Outcome Measure Patient Care Patient Selection Patient risk Patients Peripheral Phenotype Population Proteins Proteomics ROC Curve Randomized Controlled Clinical Trials Research Project Grants Risk Risk stratification Series Signaling Protein Specific qualifier value Structure TBI treatment Technology Testing Therapeutic Clinical Trial Tranexamic Acid Traumatic Brain Injury Universities Vascular Cell Adhesion Molecule-1 analog base blood-based biomarker clinical phenotype clinical risk clinically actionable cohort cytokine digital effective therapy high dimensionality immunoregulation improved inclusion criteria innovation insight mortality multidisciplinary novel patient oriented research patient stratification peripheral blood placebo group predictive modeling programs prospective proteomic signature response sensor single molecule skills supervised learning

项目摘要

PROJECT SUMMARY Traumatic brain injury (TBI) is a leading cause of death in the US, and treatment options are limited. Therapeutic clinical trials in TBI have yielded disappointing results owing in part to the difficulty in accounting for clinically important heterogeneity within TBI. Early delivery of therapy is essential after TBI to reduce secondary brain injury, but unrestricted treatment of all brain injuries could be harmful. TBI stimulates a complex cascade of immunologic responses, both centrally and peripherally. These peripheral immune responses to TBI could serve as an early sensor of risk phenotype given the rapid, readily measurable response in the blood. An improved ability to risk-stratify patients on admission will streamline patient selection for aggressive interventions—such as invasive neuromonitoring—versus selection of those patients who can safely be observed reducing potential harms. Holly E Hinson, MD MCR is a Neurologist and Neurointensivist at Oregon Health and Science University where she cares for patients with severe acute brain injury. The objective of this application is to develop supervised learning models of actionable short- and long-term outcomes post-TBI and to interrogate if pre-specified immunoregulatory proteins add predictive power to the models over clinical features alone. Her central hypothesis is that immunoregulatory proteomic signatures improve our ability to classify a low-risk clinical phenotype after TBI. Dr. Hinson’s preliminary data suggest peripheral cytokine levels are associated with actionable clinical events acutely after TBI. The project employs a highly-sensitive, single molecule immunoarray (SIMOA) to detect immunoregulatory proteins complemented with an unbiased proteomic approach utilizing global discovery mass spectrometry. She will develop and assess a series of models incorporating proteomic signatures to classify: acute progressive intracranial hemorrhage (Aim 1A), acute neurologic deterioration (Aim 1B), and long-term outcomes measured by the 6-month Glasgow Outcome Scale (Aim 2). She will develop these models in a well-defined, clinical trial population (development set), and test their ability to correctly classify outcome in an independent, prospectively enrolled cohort at OHSU (test set). Under a multidisciplinary team of expert mentors, the project will generate new insights into low-risk phenotype recognition and outcome classification after acute TBI. The proposed patient-oriented research project will be enhanced by a structured didactic program in the principles of predictive modeling and patient phenotyping (including proteomics), which will provide Dr. Hinson with the critical skills she will need to conduct independent, innovative translational clinical research in the field of neurotrauma.

项目总结