Critical Illness Polyneuropathy/Myopathy in ALI

描述(由申请人提供)： 这一奖项将为Lee博士提供一个机会，让他在转化研究(临床流行病学专注于将基础科学进展转化为临床实践)和遗传流行病学领域发展成为一名独立的、以患者为中心的科学调查员。通过综合课程设置、流行病学和分子生物学课程、与当地急性肺损伤生物学(ALL)专家的合作，以及设计、实施和解释前瞻性临床研究的实践经验，Lee博士将利用这一奖项成为一名训练有素的翻译研究员，具备将实验室研究纳入临床研究所需的技能。这将导致一个成功的独立研究生涯，专注于ALL的病理生物学，包括其长期并发症与以患者为中心的结果之间的关系。这项建议的主要科学目标是研究急性淋巴细胞白血病(ALL)患者危重疾病多发性神经病/肌病(CIPM)的流行病学、机制和结果。CIPM最近被证明在脓毒症中高度流行，并可能与危重疾病后以患者为中心的重要预后有关。CIPM尚未在所有患者中进行研究。总体设计为前瞻性队列研究。ALL患者将被确认，接受临床和电诊断评估，并采集血液和肌肉样本进行组织学、生化和遗传学研究。受试者将在6个月后接受跟踪和访谈，以衡量与健康相关的生活质量。目的一是确定慢性盆腔炎的患病率和临床危险因素。目的二是研究包括肌球蛋白代谢产物和炎性细胞因子在内的标志物和介质与CIPM诊断的关系。目的三是一项基因关联研究，研究所有患者CIPM与影响炎症和肌肉代谢的基因多态的关系。目的四是研究CIPM对所有幸存者健康相关生活质量的影响。这项研究将为CIPM对ALL患者的临床影响提供重要的见解，进一步加深我们对危重疾病神经肌肉表现的生物学的理解，并创建一个生物样本库用于未来的研究。

DESCRIPTION (provided by applicant): This award will provide an opportunity for Dr. Lee to develop as an independent patient-oriented scientific investigator in the field of translational investigation (clinical epidemiology focused on translating basic science advances to clinical practice) and genetic epidemiology. Through an integrated curriculum with coursework in epidemiology and molecular biology, collaboration with local experts in the biology of acute lung injury (ALl), and practical experience in designing, conducting and interpreting a prospective clinical study, Dr. Lee will use this award to become a well-trained translational investigator with the skills needed to incorporate laboratory studies into clinical research. This will lead to a successful independent research career focused on the relationship between the pathobiology of ALl, including its long term complications, and patient-centered outcomes. The primary scientific goal of this proposal is to study the epidemiology, mechanism and outcomes of critical illness polyneuropathy/myopathy (CIPM) in patients with ALl. CIPM has been recently been shown to be highly prevalent in sepsis, and may be associated with important patient-centered outcomes after critical illness. CIPM has not been studied in a population of ALl patients. The overall design is a prospective cohort study. Patients with ALl will be identified, receive clinical and electrodiagnostic evaluations, and have blood and muscle samples collected for histologic, biochemical and genetic studies. Subjects will be followed and interviewed at 6 months to measure health-related quality of life. Aim One will determine prevalence of CIPM and identify its clinical risk factors. Aim Two is a study of the association of markers and mediators, including myosin metabolites and inflammatory cytokines, with diagnosis of CIPM. Aim Three is a genetic association study that examines the relationship between CIPM in ALl patients and polymorphisms that affect inflammation and muscle metabolism. Aim Four is a study of the influence of CIPM and health-related quality of life in ALl survivors. This study will provide important insights into the clinical impact of CIPM in patients with ALl, further our under-standing about the biology of neuromuscular manifestations of critical illness, and create a repository of biologic samples to be used for future investigations.