Lipidomics in Acute Ischemic Stroke: Relationship to Symptoms and Outcomes

急性缺血性中风的脂质组学：与症状和结果的关系

• 批准号: 10443198
• 负责人: Sarah R Martha
• 金额: $ 17.61万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10443198
• 关键词: Acute; Address; Affect; Alteplase; American; Area; Biological; Biological Markers; Blood; Blood flow; Brain Injuries; Cell membrane; Ceramides; Cerebral Thrombus; Cerebrovascular Circulation; Cholesterol; Clinical Research; Clinical Trials Design; Cognitive; Cognitive deficits; Data; Development; Distal; Enrollment; Exhibits; Extramural Activities; Fatigue; Funding; Goals; Hospitals; Hour; Hydrolysis; Hypoxia; Impaired cognition; Infarction; Infiltration; Inflammation; Inflammation Mediators; Intervention; Ischemic Stroke; K-Series Research Career Programs; Knowledge; Lead; Lipids; Longitudinal Studies; Measures; Mechanics; Mentors; Mentorship; Methodology; Mission; Modeling; Neurologic; Nurses; Outcome; Participant; Pathology; Patient Self-Report; Patients; Peripheral; Phospholipid Metabolism; Plasma; Postdoctoral Fellow; Precision Health; Prospective cohort; Prospective cohort study; Reperfusion Therapy; Research; Research Personnel; Research Project Grants; Role; Sampling; School Nursing; Scientist; Severities; Sphingomyelins; Statistical Methods; Symptoms; Thrombectomy; Thrombus; Time; Training; United States; Universities; Washington; artery occlusion; associated symptom; biomarker development; career development; cerebral artery; depressive symptoms; dietary; disability; experience; group intervention; health related quality of life; improved outcome; laboratory experience; lipid metabolism; lipidomics; novel; patient oriented; programs; statistics; stroke patient; stroke recovery; stroke survivor; symptomatic improvement

PROJECT SUMMARY/ABSTRACT The purpose of this K23 Mentored Patient-Oriented Career Development Award is to provide the necessary mentorship, knowledge, and training to Dr. Sarah Martha, a post-doctoral fellow at the University of Washington School of Nursing. The long-term goal of Dr. Martha is to independently develop and lead an extramurally-funded program of research focused on targeted interventions to improve symptoms and outcomes in acute ischemic stroke survivors. Acute ischemic stroke (AIS) is the leading cause of severe long- term disability in the US. AIS is characterized by the disruption of cerebral blood flow due to large arterial occlusion, caused by a cerebral thrombus. Half of AIS survivors exhibit fatigue and depressive symptoms, cognitive deficits, and poorer functional and health-related quality of life (HRQOL) outcomes. Recent advances in omics methodology enables lipidomic profiling, which may provide knowledge of the underlying pathology of AIS and its associated symptoms and outcomes. This proposed research will address a gap in knowledge in the relationship between lipid biomarkers, development of symptoms and outcomes in the 6 months following AIS and the role of reperfusion intervention. This career development award will support the applicants training and research goals through the provision of mentorship, coursework, laboratory training, and other activities directly relevant to the content areas of advanced statistical methods for longitudinal clinical research, analysis of lipidomic biomarkers, AIS pathology, clinical trial design, and career development. The project proposed in this application will examine how and when lipidomic signatures, symptoms, functional and HRQOL outcomes change after AIS, and what influence, if any, reperfusion interventions have on these changes. The applicant proposes a prospective cohort (2 groups, n=52/each), longitudinal study involving participants following AIS. The research project proposed in the application will analyze arterial and peripheral plasma lipid biomarkers that may provide lipidomic signatures useful in identifying predictive symptoms and cognitive, functional, and HRQOL outcomes. Specifically, the proposal aims are to: 1) Compare symptoms (fatigue and depressive), cognitive, functional, and HRQOL outcomes over 6 months between AIS patients who did and did not receive reperfusion intervention; 2) Compare peripheral plasma lipid levels over 6 months between AIS patients who did and did not receive reperfusion intervention; 3) Examine early and late peripheral plasma lipid levels and symptoms, cognitive, functional, and HRQOL outcomes over time in patients who do and do not receive reperfusion intervention; 4) Explore the relationships of 13 lipid classes with symptoms, cognitive, functional, and HRQOL outcomes over 6 months in (4a) distal and proximal arterial plasma lipid levels in reperfusion intervention group (4b/c) peripheral plasma lipid levels in AIS patients (4b) who did and (4c) did not receive reperfusion intervention. Descriptive statistics, linear mixed modeling, and integrative multivariate omics analysis will be used to achieve aims 1 through 4.

项目总结/摘要 这个K23指导以患者为导向的职业发展奖的目的是提供 必要的指导，知识和培训博士莎拉玛莎，博士后研究员在大学 华盛顿护理学院。玛莎博士的长期目标是独立开发和领导一个 一项由校外资助的研究计划，重点是有针对性的干预措施，以改善症状， 急性缺血性卒中幸存者的结局。急性缺血性卒中（AIS）是严重的长期- 残疾人在美国。AIS的特征是由于大动脉阻塞导致脑血流中断。 由脑血栓引起的闭塞。一半的AIS幸存者表现出疲劳和抑郁症状， 认知缺陷，以及功能和健康相关生活质量（HRQOL）结果较差。最新进展 在组学方法学中，脂质组学分析可以提供关于糖尿病的潜在病理学的知识。 AIS及其相关症状和结果。这项拟议的研究将解决知识差距， 脂质生物标志物之间的关系，症状的发展和6个月后的结果 AIS和再灌注干预的作用。该职业发展奖将支持申请人的培训 通过提供指导、课程、实验室培训和其他活动， 直接相关的内容领域的先进统计方法进行纵向临床研究，分析 脂质组学生物标志物、AIS病理学、临床试验设计和职业发展。该项目在 该应用程序将检查脂质组学特征、症状、功能和HRQOL结果如何以及何时发生 AIS后的变化，以及再灌注干预对这些变化的影响（如果有的话）。申请人 提出了一项前瞻性队列研究（2组，每组n=52），涉及AIS后受试者的纵向研究。 申请中提出的研究项目将分析动脉和外周血浆脂质生物标志物 其可以提供可用于识别预测性症状和认知、功能和 HRQOL结局。具体而言，该提案的目的是：1）比较症状（疲劳和抑郁）， 接受和未接受治疗的AIS患者之间6个月内的认知、功能和HRQOL结局 再灌注干预; 2）比较AIS患者6个月内的外周血浆脂质水平， 接受和未接受再灌注干预; 3）检查早期和晚期外周血浆脂质水平， 接受和未接受治疗的患者随时间推移的症状、认知、功能和HRQOL结局 探讨13种血脂水平与症状、认知、功能、 （4a）再灌注时远端和近端动脉血脂水平的6个月和HRQOL结局 干预组（4 b/c）AIS患者（4 b）和（4c）未接受治疗的外周血浆脂质水平 再灌注干预描述性统计、线性混合模型和整合多变量组学 分析将用于实现目标1至4。