Skeletal Myopathy in Systemic Sclerosis: Devising a Classification Schema Predictive of Outcomes

系统性硬化症中的骨骼肌病：设计预测结果的分类模式

• 批准号: 9892505
• 负责人: Julie Jisun Paik
• 金额: $ 15.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9892505
• 关键词: Address; Advisory Committees; Age; Algorithms; Biological; Biological Process; Biopsy; Cardiac Death; Cessation of life; Chronic; Classification; Clinical; Clinical Investigator; Clinical Trials; Cohort Studies; Consensus; Creatine Kinase; Data; Development; Diagnostic radiologic examination; Diffusion Magnetic Resonance Imaging; Disease; Early identification; Edema; Electromyography; Enrollment; Fatty acid glycerol esters; Fibrosis; Foundations; Future; Gender; Goals; Gold; Heterogeneity; Histologic; Histopathology; Image; Imaging Techniques; Incidence; Inclusion Body Myositis; Individual; Inflammation; Inflammation Process; Inflammatory; Infrastructure; International; Intramuscular; Knowledge; Laboratories; Logistic Regressions; Magnetic Resonance Imaging; Manuals; Maps; Measurable; Measures; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Methodology; Methods; Modeling; Muscle; Muscle Weakness; Musculoskeletal; Myopathy; Myositis; Necrosis; Outcome; Outcome Measure; Pathogenesis; Pathologic; Patients; Pattern; Phenotype; Prediction of Response to Therapy; Prospective cohort; Protocols documentation; Pulmonary Heart Disease; Radiology Specialty; Research; Resources; Retrospective Studies; Rheumatology; Sampling Biases; Scleroderma; Serologic tests; Serological; Signal Transduction; Skeletal Muscle; Systemic Scleroderma; Techniques; Testing; Therapeutic; Therapeutic Trials; Translational Research; Universities; Validation; career; clinical development; clinical epidemiology; clinically significant; cohort; diffusion weighted; disability; disorder control; epidemiology study; high risk; illness length; imaging biomarker; interest; member; mortality; muscle form; muscle strength; novel; outcome prediction; predictive marker; professor; prospective; quantitative imaging; radiological imaging; random forest; recruit; skeletal; skills; treatment response; uptake

PROJECT SUMMARY Skeletal myopathy in systemic sclerosis (SSc) is associated with increased disability and mortality. There is no consensus classification of SSc-associated myopathy that can be utilized to lay the groundwork for understanding muscle disease in scleroderma. We know that there is pathological, serological, and outcome heterogeneity that may be informative in defining distinct subsets of myopathy in SSc. Our preliminary data demonstrate that (1) muscle histopathology is heterogeneous in SSc, (2) patients with a fibrosing myopathy have poor outcomes, in particular cardiac death, and (3) there is intense signal uptake on advanced MRI imaging such as diffusion weighted and tensor imaging and T2 mapping in SSc-associated myopathy which may indicate early disease related changes when compared to conventional muscle MRI. This K23 proposal will first establish a Myopathy cohort (Aim 1), devise a classification schema and test its utility in predicting long term outcomes such as trajectory, cardiopulmonary disease, disability, mortality, and treatment responsiveness(Aim 2), and detect and quantify early disease related muscle changes on advanced muscle MRI (Aim 3). This application is for a K23 award for Julie Paik, MD, MHS, Assistant Professor of Medicine in the Division of Rheumatology at the Johns Hopkins University. Her long term career goal is to become a leading clinical investigator in scleroderma muscle disease in the context of observational cohort studies, state of the art imaging biomarkers, and clinical trial methodology. Her short term goal of devising this classification schema will provide a new gold standard for the validation of external myopathy cohorts in SSc and lay the framework for future studies directed at understanding biological mechanism and developing a therapeutic trial using measurable outcomes such as quantitative muscle MRI. This proposal takes advantage of the rich resources and infrastructure at the Johns Hopkins Scleroderma Center, a recently designated Precision Center of Excellence in 2018. Her mentoring team includes Dr. Laura Hummers and Dr. Fredrick Wigley, both renowned experts in SSc and clinical epidemiology, Dr. Andrew Mammen is an internationally recognized myositis expert, and Dr. Scott Zeger a leader in bio statistical and epidemiological research. Dr. Paik has recruited vital members to her Advisory Committee, composed of mentors and collaborators who have specific expertise relevant to the proposal and are fully supportive of Dr. Paik’s research and career goals. These include Dr. Michael Jacobs (advanced radiological imaging), Dr. Laura Fayad (musculoskeletal radiology), Dr. Andrea Corse (muscle histopathology), Dr. Tom Lloyd (classification schemas in inclusion body myositis), and Dr. Ami Shah (scleroderma translational research). This K23 award will allow Dr. Paik to gain the skills needed to analyze and develop a classification schema of skeletal myopathy in scleroderma, develop expertise in advanced muscle MRI analysis, and build her clinical trial skill set to ultimately support a future R01 proposal.

项目摘要 系统性硬化症（SSc）中的骨骼肌病变与残疾和死亡率增加相关。没有 SSc相关肌病的共识分类，可用于为 了解硬皮病中的肌肉疾病我们知道，有病理学，血清学，和结果 这可能是在定义SSc中肌病的不同子集方面提供信息的异质性。我们的初步数据 表明（1）SSc的肌肉组织病理学是异质性的，（2）纤维化肌病患者 预后差，特别是心源性死亡，（3）在高级MRI上有强烈的信号摄取 成像，如扩散加权和张量成像和T2映射在Ssc相关肌病， 与常规肌肉MRI相比，可能提示早期疾病相关变化。K23提案 我将首先建立一个肌病队列（目标1），设计一个分类方案，并测试其在预测长期 长期结局，如轨迹、心肺疾病、残疾、死亡率和治疗 反应性（目标2），并检测和量化晚期肌肉的早期疾病相关肌肉变化 MRI（目标3）。此应用程序是一个K23奖朱莉白，医学博士，MHS，医学助理教授，在 约翰·霍普金斯大学风湿病学系。她的长期职业目标是成为一名 在观察性队列研究的背景下，硬皮病肌肉疾病的主要临床研究者 现有技术的成像生物标志物和临床试验方法。她设计这种分类的短期目标是 该方案将为SSc外部肌病队列的验证提供一个新的金标准， 未来研究的框架，旨在了解生物学机制和开发治疗试验 使用可测量的结果，如定量肌肉MRI。这个提议利用了富人 约翰霍普金斯硬皮病中心的资源和基础设施，最近被指定为精密中心 2018年的卓越。她的指导团队包括Laura Hummers博士和Fredrick Wigley博士 著名的SSc和临床流行病学专家，Andrew Mammen博士是国际公认的 他是肌炎专家，Scott Zeger博士是生物统计学和流行病学研究的领导者。白博士 她的顾问委员会招募了重要成员，由导师和合作者组成，他们有具体的 我们将提供与提案相关的专业知识，并完全支持Paik博士的研究和职业目标。这些 包括Michael Jacobs博士（高级放射成像）、Laura Fayad博士（肌肉骨骼放射学）、 Andrea科塞（肌肉组织病理学）、Tom Lloyd博士（包涵体肌炎的分类模式）和 博士Ami Shah（硬皮病转化研究）。这个K23奖将使白博士获得所需的技能 分析和制定硬皮病骨骼肌病变的分类方案， 高级肌肉MRI分析，并建立她的临床试验技能集，以最终支持未来的R01提案。