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: 10409652
• 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/10409652
• 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; 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; Serology; 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）中的骨骼肌病与残疾和死亡率的增加有关。没有 SSC相关的肌病的共识分类，可用于为 了解硬皮病中的肌肉疾病。我们知道有病理，血清学和结果 在定义SSC中肌病的不同子集时可能有益的异质性。我们的初步数据 证明（1）肌肉组织病理学在SSC中是异质的，（2）患有肌病的患者 结局差，尤其是心脏死亡，（3）高级MRI有强烈的信号吸收 在SSC相关的肌病中，诸如扩散加权和张量成像和T2映射之类的成像 与常规肌肉MRI相比，可能表明早期相关的变化。这个K23提案 将首先建立肌病队员（AIM 1），设计分类模式并测试其在预测长时间的效用 术语结果，例如轨迹，心肺疾病，残疾，死亡率和治疗 反应性（AIM 2），检测和量化早期疾病与晚期肌肉相关的肌肉变化 MRI（目标3）。该申请是为医学博士Julie Paik颁发的K23奖，MHS，医学助理教授 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个 在观测队列研究的背景下，领先的硬皮病肌肉疾病的临床研究者 她设计这种分类的短期目标 模式将为验证SSC的外部肌病队列的验证提供新的金标准 未来研究的框架旨在了解生物学机制并开发治疗试验 使用可测量的结果，例如定量肌肉MRI。该建议利用富人 约翰·霍普金斯硬皮病中心的资源和基础设施，最近指定的精密中心 2018年的卓越表现。她的心理团队包括Laura Hummers博士和Fredrick Wigley博士 Andrew Mammen博士是SSC和临床流行病学专家，是国际公认的 肌炎专家和Scott Zeger博士是生物统计和流行病学研究的领导者。 Paik博士有 招募了她的咨询委员会的重要成员 与该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（高级放射学成像），Laura Fayad博士（肌肉骨骼放射学），博士 Andrea Corse（肌肉组织病理学），汤姆·劳埃德（Tom Lloyd） Ami Shah博士（硬皮病转化研究）。该K23奖将使Paik博士能够获得所需的技能 要分析和开发在硬皮病中骨骼肌病的分类模式，请发展专业知识 高级肌肉MRI分析，并建立她的临床试验技能，以最终支持未来的R01提案。