Staphylococcus aureus Cardiac Device Infections - From the Vascular Viewpoint

金黄色葡萄球菌心脏装置感染 - 从血管角度

• 批准号: 10524831
• 负责人: Stacey A Maskarinec
• 金额: $ 15.62万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10524831
• 关键词: 3-Dimensional; Academic Medical Centers; Affect; Antibiotic Resistance; Automobile Driving; Award; Bacteremia; Bacterial Model; Biological; Biological Markers; Biological Models; Biology; Biomedical Engineering; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cell Communication; Characteristics; Clinical; Clinical Data; Clinical Research; Cohort Studies; Collaborations; Complication; Device Removal; Devices; Diagnosis; Disease; Economic Burden; Endothelial Cells; Endothelium; Engineering; Etiology; Excision; Faculty; Goals; Healthcare Systems; Heart Valve Prosthesis; Homeostasis; Human; Hydrogels; Immune; Immune response; In Vitro; Individual; Infection; International; Leadership; Left; Mechanics; Mentors; Methods; Modeling; Molecular; National Heart, Lung, and Blood Institute; Operative Surgical Procedures; Outcome; Pacemakers; Patients; Performance; Persons; Phenotype; Physicians; Physiological; Play; Population Analysis; Predisposition; Prevention; Prospective cohort; Published Comment; Publishing; Quality of life; Research; Research Personnel; Research Proposals; Resources; Risk; Risk Factors; Role; Sampling; Schools; Scientist; Selectins; Sepsis; Serum; Staphylococcus aureus; Staphylococcus aureus infection; Symptoms; System; Test Result; Tissue Engineering; Tissue Model; Validation; Variant; Vascular Diseases; Work; biobank; biomarker signature; cardiac device; cardiac implant; career; cell behavior; cohort; cost; cytokine; experience; fighting; follow-up; high risk; improved; in vitro Model; infection risk; mechanical properties; mechanical stimulus; microbial; mortality; novel; novel diagnostics; novel therapeutics; outcome prediction; phenotypic biomarker; prospective; response; shear stress; therapeutically effective; treatment response; working group

PROJECT SUMMARY For patients with advanced cardiovascular disease, implanted cardiac devices can significantly improve their survival and quality of life. While lifesaving, cardiac devices carry the added risk of developing a cardiac device infection (CDI), in which case the device has to be surgically removed. In many cases, patients with a CDI present with vague symptoms and undergo a number of inconclusive tests, resulting in a delay in their diagnosis. If left undiagnosed or untreated the mortality from a CDI is high. If identified early, CDIs can be treated swiftly, thereby reducing infection-related complications. Currently there are no reliable methods for early prevention or identification of CDI. Rapid and accurate CDI diagnosis is critical in cardiac device recipients who have a Staphylococcus aureus bloodstream infection, as the risk of CDI approaches 50%. Building on the candidate's published work, this research will use the singular resource of the Bloodstream Infection Biorepository to define the vascular biomarker signature associated with an individual's risk for a S. aureus-CDI. Second, the biological basis for why some, but not all patients, develop a CDI will be identified through the application of a novel in vitro model system of bacteremia, created by the candidate in collaboration with Biomedical Engineering. This project will: 1) define the biomarker signature associated with S. aureus-CDI, 2) determine how changes in vascular mechanics affect infection risk, and 3) apply a novel tissue engineered blood vessel system to identify critical endothelial-bacterial-device interactions that impact CDI risk. Results from this project will serve as a basis for follow-up R01 proposals, which will prospectively evaluate adjunctive CDI biomarker signatures among other etiologies of bloodstream infection and determine if a patient's endothelial phenotype is an independent risk factor for CDI. This project has direct relevance to the NHLBI's strategic goals and objectives of identifying phenotypic, biomarker, and molecular characteristics predictive of outcome, that when applied in clinical studies, can predict differential response to therapy in individuals. This project will also support the candidate's transition to an independent research career. This project will provide expertise and advanced skillsets in tissue engineering, vascular biology, and clinical research, all of which are necessary for the candidate's long-term career goal of identifying key factors that impact susceptibility to CDIs and developing effective therapeutic strategies for their prevention and treatment. The primary mentor for this award is Dr. Vance Fowler, an internationally recognized clinician-scientist in S. aureus bacteremia who has extensive experience as a mentor of junior faculty researchers. A complementary and diverse group of mentors will provide guidance in tissue engineering (Dr. Truskey) and vascular biology (Dr. Kontos). The candidate will use the outstanding resources and interdisciplinary working groups at Duke University Medical Center, the Pratt School of Engineering, the Duke Cardiovascular Research Center, and the Antibiotic Resistance Leadership Group to launch her career as an independent physician-scientist.

项目摘要 对于患有晚期心血管疾病的患者，植入的心脏设备可以显著改善其 生存和生活质量。在挽救生命的同时，心脏设备也带来了开发心脏设备的额外风险 感染（CDI），在这种情况下，必须通过手术取出器械。在许多情况下，CDI患者 出现模糊的症状，并进行一些不确定的测试，导致诊断延迟。 如果不及时诊断或治疗，CDI的死亡率很高。如果早期发现，CDIs可以迅速治疗， 从而减少与感染相关的并发症。目前还没有可靠的早期预防方法， 识别CDI。快速和准确的CDI诊断对于患有心脏病的心脏设备接受者至关重要。 金黄色葡萄球菌血流感染，因为CDI的风险接近50%。基于候选人的 这项研究将使用血流感染生物储存库的单一资源来定义 血管生物标志物签名与个体的S. aureus-CDI.第二，生物 将通过应用一种新的体外试验来确定为什么一些但不是所有患者发生CDI的依据。 菌血症模型系统，由候选人与生物医学工程合作创建。这个项目 将：1）定义与S相关的生物标志物特征。aureus-CDI，2）确定血管的变化 力学影响感染风险，以及3）应用新型组织工程血管系统来识别关键的 影响CDI风险的内皮-细菌-器械相互作用。该项目的结果将作为以下方面的基础： 后续R 01提案，将前瞻性评估CDI生物标志物特征， 血液感染的病因学，并确定患者的内皮表型是否是一个独立的风险 因素CDI。该项目与NHLBI的战略目标直接相关， 预测结果的表型、生物标志物和分子特征，当应用于临床研究时， 可以预测个体对治疗的不同反应。这个项目也将支持候选人的过渡 独立的研究生涯。该项目将提供组织方面的专业知识和先进技能 工程学，血管生物学和临床研究，所有这些都是候选人长期所必需的 职业目标是确定影响CDIs易感性的关键因素，并开发有效的治疗方法 预防和治疗的战略。该奖项的主要导师是万斯福勒博士， 国际公认的临床科学家在S。金黄色葡萄球菌菌血症，具有丰富的导师经验 初级研究员的名单一个互补和多样化的导师小组将提供组织指导， 工程学（Truskey博士）和血管生物学（Kontos博士）。候选人将利用优秀的资源 以及杜克大学医学中心、普拉特工程学院、 杜克心血管研究中心和抗生素耐药性领导小组将开始她的职业生涯， 一个独立的物理学家兼科学家