Graft harvest as a model of tendon injury; Trajectory of recovery and clinical outcomes

移植物收获作为肌腱损伤的模型；

基本信息

批准号：
10417618
负责人：
Andrew L Sprague
金额：
$ 12.7万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10417618
关键词：
Address Adoption Animal Model Area Autologous Transplantation Basic Science Biology Clinic Clinical Clinical Research Clinical Trials Cumulative Trauma Disorders Data Development Development Plans Evaluation Goals Harvest Hip Osteoarthritis Human Impairment Injury Intervention Investigation Isometric Exercise Knee Osteoarthritis Knowledge Lateral Lead Lower Extremity Measures Mentorship Methods Modeling Multicenter Studies Operative Surgical Procedures Outcome Outcome Measure Pain Participant Patient Outcomes Assessments Patients Performance Property Prospective cohort study Proxy Quality of life Randomized Recovery Recurrence Rehabilitation therapy Research Research Activity Residual state Resolution Risk Scientist Severities Site Societies Speed Standardization Structure Study models Symptoms Tendon Injuries Tendon structure Testing Thick Time Tissues Training Treatment Effectiveness Treatment outcome Ultrasonography Universities anterior cruciate ligament reconstruction base career clinical examination clinical practice cohort design dosage elastography experience healing high risk improved innovation mechanical properties preservation prevent prospective quadriceps muscle sedentary tendon development tendon graft therapy design treatment optimization unethical

项目摘要

PROJECT SUMMARY/ABSTRACT My career goal is to bridge the gap between tendon basic science and clinical research to optimize treatment of tendon injuries, using individualized load and recovery prescription. To achieve this goal and fill gaps in my experience, I have designed a development plan which will provide training and mentorship in administration of clinical trials and large multicenter studies, applying and interpreting mixed-effects models, and understanding of tissue biology. The research activities will provide complimentary experience and pilot data to establish myself as an independent clinician-scientist. Rationale: Healthy tendon function is critical to preserving quality of life. Overuse tendon injuries are rampant across society, occurring at a rate exceeding hip and knee osteoarthritis combined. These injuries impact the structural and mechanical properties of the tendon, which reduces tendon function, lower extremity performance, participation in daily activities, and ultimately, quality of life. Treatments for tendon injuries are designed to promote tendon remodeling, with the goal of restoring structure, mechanical properties, and tendon function. However, pain is the primary measure used to assess treatment effectiveness in clinical settings, which is a poor measure of tendon remodeling. Thus, clinicians are using interventions without the ability to determine whether the application is appropriate, increasing the risk of residual impairments and injury recurrence. This gap between research and the clinic is due to a poor understanding of tendon tissue changes in humans and their clinical implications. Changes in tendon structure and mechanical properties precedes the development of symptoms, making it difficult to capture pre-injury values of these properties. Without pre-injury values, it has not been possible to determine the degree of change due to injury, the expected trajectory of recovery, or how these changes relate to clinical outcomes. The tendon graft harvest site may provide a new model for studying tendon injuries, providing the opportunity to capture pre-harvest measures of structural and mechanical properties. Specific Aims: (1) To identify changes in graft site structure after graft harvest. (2) To identify changes in graft site mechanical properties after graft harvest. (3) To determine the association between changes in graft site structural and mechanical properties with clinical outcomes after graft harvest. Methods: This will be an ancillary, single-site, prospective cohort study of participants in the STABILITY 2 Trial at the University of Pittsburgh, which aims to identify optimal graft choice in patients at high risk of failed anterior cruciate ligament reconstruction (ACLR). Evaluations will be completed pre-surgery, and 6 weeks, 3-, 6-, 12- and 24-months after ACLR with a patellar or quadriceps tendon graft to evaluate changes in graft site structural and mechanical properties, quadriceps muscle performance, tendon pain, and lower extremity function. These measures will be combined with existing outcomes from the STABILITY 2 Trial to obtain a complete picture of participants’ clinical status. Clinical Impact: Findings will improve our understanding of tendon healing, provide a new model for testing interventions, and accelerate the adoption of suitable outcome measures for tendon injury. Long-term, this may prevent residual impairments in tendon function and restore participation in daily activities and quality of life.

项目概要/摘要我的职业目标是弥合肌腱基础科学和临床研究之间的差距，以优化肌腱的治疗为了实现这一目标并填补我的经验空白，我采用了个性化的负荷和恢复处方。设计了一项发展计划，该计划将提供临床试验和大型临床试验管理方面的培训和指导多中心研究、应用和解释混合效应模型以及对组织生物学的理解。活动将提供免费的经验和试点数据，使我自己成为一名独立的临床医生科学家。理由：健康的肌腱功能对于保持生活质量至关重要。过度使用肌腱损伤在各地都很普遍。这些损伤的发生率超过了髋关节和膝关节骨关节炎的总和。肌腱的机械性能，会降低功能、下肢性能、参与日常活动肌腱损伤的治疗旨在促进肌腱重塑，并最终提高生活质量。恢复结构、机械性能和肌腱功能的目标然而，疼痛是主要的措施。评估临床环境中的治疗效果，这是肌腱重塑的一个糟糕的衡量标准。在无法确定应用是否合适的情况下使用干预措施，增加了残留的风险研究和临床之间的这种差距是由于对肌腱的了解不足造成的。人类的组织变化及其临床意义先于肌腱结构和机械性能的变化。症状的发展，使得在没有受伤前的情况下很难捕获这些属性的受伤前值。值，无法确定由于受伤而发生的变化程度、预期的恢复轨迹，或这些变化与临床结果有何关系。肌腱移植物采集部位可能为研究肌腱提供新模型。损伤，提供了捕获结构和机械性能的收获前测量值的机会。具体目的： (1) 确定移植物收获后移植部位结构的变化 (2) 确定移植部位的变化。 (3) 确定移植部位结构变化与机械性能与移植物收获后的临床结果。方法：这将是一项针对 STABILITY 2 试验参与者的辅助、单中心、前瞻性队列研究。匹兹堡大学，旨在最佳地确定前交叉失败高风险患者的移植选择韧带重建 (ACLR) 评估将在术前以及术后 6 周、3、6、12 和 24 个月完成。 ACLR 与髌骨或股四头肌腱移植物一起评估移植部位结构和机械性能的变化，股四头肌的肌肉表现、肌腱疼痛和下肢功能将与这些测量相结合。 STABILITY 2 试验的现有结果，以获得参与者临床状态的完整情况。临床影响：研究结果将提高我们对肌腱愈合的理解，提供测试干预措施的新模型，并加速针对肌腱损伤采取适当的结果措施，这可以防止残留。肌腱功能受损并恢复日常活动参与和生活质量。