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: 10656586
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10656586
• 关键词: Acute; Address; Affect; Alteplase; American; Biological; Biological Markers; Blood; Blood flow; Brain Injuries; Categories; 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; Nurses; Outcome; Participant; Pathology; Patient Self-Report; Patients; Peripheral; Phospholipid Metabolism; Plasma; Postdoctoral Fellow; Precision Health; Prospective cohort; Prospective, cohort study; Qualifying; 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; career development; cerebral artery; depressive symptoms; dietary; disability; experience; group intervention; health related quality of life; improved outcome; laboratory experience; lipid metabolism; lipidomics; nervous system disorder; 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.

项目摘要/摘要 这个K23以病人为导向的导师职业发展奖旨在提供 为萨拉·玛莎博士提供必要的指导、知识和培训，她是加州大学博士后研究员 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 医疗外资助的研究计划侧重于有针对性的干预措施以改善症状和 急性缺血性卒中幸存者的预后。急性缺血性卒中(AIS)是导致严重迟发性脑梗塞的主要原因。 美国的长期残疾。AIS的特征是由于大动脉导致的脑血流中断。 闭塞，由脑血栓引起。AIS幸存者中有一半表现出疲劳和抑郁症状， 认知缺陷，以及较差的功能和健康相关的生活质量(HRQOL)结果。最新进展 在组学方法论中，能够进行脂肪组学分析，这可能提供关于基础病理的知识 人工授精及其相关症状和结果。这项拟议的研究将解决以下方面的知识差距 血脂生物标志物与症状发展及随访6个月预后的关系 AIS和再灌流干预的作用。该职业发展奖将支持申请者的培训。 通过提供指导、课程作业、实验室培训和其他活动来实现研究目标 直接涉及内容领域的先进统计方法，用于临床纵向研究、分析 脂体生物标记物、AIS病理学、临床试验设计和职业发展。年提出的项目 该应用程序将检查脂类签名、症状、功能和HRQOL结果的方式和时间 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，n=52/各)，涉及AIS后的参与者。 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记物 这可能提供有助于识别预测性症状和认知、功能和 HRQOL结果。具体地说，该提案旨在：1)比较症状(疲劳和抑郁)， 接受和未接受治疗的AIS患者在6个月内的认知、功能和HRQOL结果 再灌注干预；2)比较AIS患者在6个月内的外周血脂水平 3)检测早期和晚期外周血脂水平及 接受和不接受治疗的患者的症状、认知、功能和HRQOL结果随时间的变化 4)探讨13种脂类与症状、认知、功能、 再灌注期(4a)远端和近端动脉血脂水平及6个月后的HRQOL结果 干预组(4b/c)AIS患者(4b)和(4c)未接受干预的AIS患者的外周血脂水平 再灌注干预。描述性统计、线性混合建模和综合多变量组学 将使用分析来实现目标1至4。