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.

项目总结