Fluorescence and Biomarkers in Prosthetic Joint Infection

假体关节感染中的荧光和生物标志物

基本信息

批准号：
10473529
负责人：
Matthew J Dietz
金额：
$ 15.71万
依托单位：
WEST VIRGINIA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-07 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10473529
关键词：
Address Angiography Animal Model Antibiotics Beds Bioenergetics Biological Markers Blood Vessels Caring Cell physiology Cells Clinical Colon Carcinoma Complication Data Debridement Development Diagnosis Diagnostic Dyes Educational workshop Effectiveness Environment Evaluation Faculty Failure Fluorescence Foundations Funding Glycolysis Goals Healthcare Systems Hospital Costs Human Imaging technology Immune Immunoassay Indocyanine Green Infection Inflammation Inflammatory Intervention Intravenous Joint Prosthesis Joints Knee Knee Prosthesis Knee joint Knowledge Label Lasers Learning Measures Medicare Mentors Mentorship Methods Modeling Monitor Operative Surgical Procedures Organism Orthopedics Outcome Oxidative Stress Oxygen Consumption Patient Care Patients Perfusion Positioning Attribute Postoperative Period Pre-Clinical Model Proteins Replacement Arthroplasty Research Research Personnel Research Support Sampling Sprague-Dawley Rats Surgeon Surgical wound Symptoms Tactile Techniques Testing Therapeutic Tissue Sample Tissues Training Treatment Cost Variant Vascularization Visual base career development comorbidity cost cytokine extracellular fluorescence imaging imaging probe immune activation improved improved functioning in vivo Model inflammatory milieu joint infection knee replacement arthroplasty method development mortality multidisciplinary novel novel strategies pain relief pre-clinical response septic skills standard of care success symposium technique development tool tumor

项目摘要

Abstract Total knee arthroplasty (TKA), one of the most common surgical procedures reimbursed by Medicare, provides improved function and pain relief. The most devastating complication related to this surgery is infection, also known as prosthetic joint infection (PJI). The recommended management for PJI depends on a number of factors but ideally involves a surgical debridement of the joint and surrounding tissues. Despite surgical intervention and long courses of intravenous antibiotics, the failure rate for these treatments can reach 60% which leads to multiple surgeries and significant cost to the patient and health care systems. There is a large gap in our current understanding of what constitutes an adequate debridement. The hypothesis of this proposal is that variability exists in the concentration of biomarkers, regional vascularity, and immune cell response dependent on the depth of debridement and the presence or absence of infection. Evaluation in the clinical setting and in a preclinical PJI model will allow for the development of methods to detect the adequacy of debridement and improve significant failure rates in the treatment of PJI. The proposed aims will demonstrate the variability in the tissue environment in the infected and non- infected setting. The results of this variability will be demonstrated in both clinical samples obtained from discarded surgical tissue and in a preclinical model to allow for further development of translational treatments and techniques. Preliminary results in this proposal demonstrate the ability to detect regional variations in inflammatory biomarkers, the ability to detect local vascularity via laser assisted fluorescent angiography, and the assessment of immune cell activation via extracellular flux analysis. In Aim 1, clinical samples from revision knee arthroplasties will be compared in the presence or absence of infection and according to the depth of debridement. A preclinical model will be validated with the results obtained from the clinical samples. Aim 2 will assess the regional vascular environment before and after debridement to demonstrate the alteration of perfusion as a result of infection and surgical debridement. In Aim 3, the bioenergetic profile of cells located within a tissue bed in a revision knee and a preclinical model will be defined. This information will further the understanding of the local environment of a revision knee joint and allow for comparison to a preclinical model. This ambitious research plan has been developed with the assistance and guidance of a multidisciplinary mentor team of respected investigators and leaders in their fields. The mentor team and advisory panel were selected based on longstanding relationships, known expertise, and track record of successful mentorship of junior faculty and investigators. The career development goals outlined will be achieved through didactic classes, workshops, and conferences in addition to the direct mentoring of the group. The preliminary data and training acquired will position Dr. Dietz to achieve independence with R01 funded research.

抽象的全膝关节置换术（TKA）是医疗保险报销的最常见的外科手术之一，提供改善的功能和缓解疼痛。与该手术相关的最具破坏性的并发症是感染，也称为假体关节感染 (PJI)。 PJI 的推荐管理取决于多种因素，但理想情况下涉及关节和周围组织的手术清创。尽管手术干预和长期静脉注射抗生素，这些治疗的失败率可达 60%，这会导致多次手术，给患者和医疗保健系统带来巨大成本。有一个我们目前对什么是充分清创的理解存在很大差距。对此的假设建议认为生物标志物浓度、区域血管分布和免疫细胞存在变异性反应取决于清创深度和是否存在感染。评价在临床环境和临床前 PJI 模型将允许开发检测充分性的方法清创术并显着提高 PJI 治疗的失败率。拟议的目标将证明感染者和非感染者组织环境的可变性受感染的环境。这种变异性的结果将在从以下来源获得的两个临床样本中得到证明：废弃的手术组织和临床前模型，以便进一步开发转化治疗和技术。该提案的初步结果证明了检测区域差异的能力炎症生物标志物，通过激光辅助荧光血管造影检测局部血管的能力，以及通过细胞外通量分析评估免疫细胞激活。在目标 1 中，修订中的临床样本将根据是否存在感染以及根据感染的深度对膝关节置换术进行比较清创术。临床前模型将利用从临床样本获得的结果进行验证。目标2将评估清创前后的局部血管环境，以证明感染和手术清创导致的灌注。在目标 3 中，细胞的生物能特征位于将在修正膝关节的组织床内定义临床前模型。该信息将进一步了解修正膝关节的局部环境并允许与临床前模型进行比较。这项雄心勃勃的研究计划是在专家的协助和指导下制定的多学科导师团队由各领域受人尊敬的研究人员和领导者组成。导师团队及顾问小组的选择基于长期的关系、已知的专业知识和跟踪记录对初级教师和研究人员的成功指导。概述的职业发展目标将是除了直接指导外，还通过教学课程、讲习班和会议来实现团体。获得的初步数据和培训将使 Dietz 博士能够通过 R01 实现独立资助的研究。