Critical Illness Polyneuropathy/Myopathy in ALI

描述（由申请人提供）： 该奖项将为Lee博士提供一个机会，使其能够在转化研究（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成为一名独立的以患者为导向的科学研究者。通过与流行病学和分子生物学课程的综合课程，与急性肺损伤（AL）生物学当地专家的合作，以及在设计，实施和解释前瞻性临床研究方面的实践经验，李博士将利用该奖项成为一名训练有素的翻译研究员，具有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，专注于急性淋巴细胞白血病的病理生物学之间的关系，包括其长期并发症，和以患者为中心的结果。本提案的主要科学目标是研究急性淋巴细胞白血病患者重症多发性神经病/肌病（CIPM）的流行病学、机制和结局。CIPM最近被证明在脓毒症中非常普遍，并且可能与危重病后以患者为中心的重要结局相关。尚未在ALL患者群体中研究CIPM。总体设计为前瞻性队列研究。将鉴定患有AL 1的患者，接受临床和电诊断评估，并收集血液和肌肉样品用于组织学、生物化学和遗传学研究。将在6个月时对受试者进行随访和访谈，以测量健康相关的生活质量。目的确定CIPM的患病率并确定其临床危险因素。目的二是研究肌球蛋白代谢产物和炎性细胞因子等标志物和介质与CIPM诊断的关系。目的三是一项遗传关联研究，其检查了ALL患者中的CIPM与影响炎症和肌肉代谢的多态性之间的关系。目的四是研究CIPM和健康相关的生活质量的影响，在急性淋巴细胞白血病幸存者。本研究将提供CIPM在ALL患者中的临床影响的重要见解，进一步加深我们对危重疾病的神经肌肉表现的生物学的理解，并创建用于未来研究的生物样品库。

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.