Prevalence of ICU-Acquired Myopathy in Patients with Alcohol Use Disorders

摘要 酒精使用在美国很常见，高达7%的美国人符合诊断标准 酒精使用障碍(AUD)。澳元是健康状况不佳的重要风险因素，多达150万澳元 AUD患者每年都需要重症监护。然而，人们对澳元的整体影响知之甚少。 关于重症监护病房(ICU)的生存。肌肉萎缩是糖尿病最常见的器官表现。 酗酒，并导致呼吸损害。然而，到目前为止，还没有研究调查 肌肉疾病对AUD患者呼吸衰竭预后的影响。目前，诊断为 神经肌肉功能障碍(NMD)依赖于电生理(EP)测试和肌肉的结合 活组织检查，这两种方法在常规ICU护理中往往是不切实际的。最近的数据表明，对 肌肉特异性microRNAs(MyomiRs)可以准确地反映正在进行的肌肉发生。我们假设这个特定的 MyomiRs可能为酒精相关的肌肉损伤提供一个容易测量的、特异的生物标志物，可能 鉴别急性呼吸衰竭(ARF)患者的酒精相关肌肉疾病和NMD。我们 假设酒精是呼吸衰竭患者NMD的独立危险因素 循环myomiRs(c-myomiRs)、miR-1、-133a/133b、-206可准确识别AUD的肌肉损伤 ARF患者。为了验证这一假设，受试者将接受一系列的EP测试和肌肉超声波检查 (目标1)确定与酒精有关的肌肉疾病的流行情况和发生的NMD。受试者将经历一系列 C-miRNA测定(AIM 3)，随后在机械治疗第7天进行经皮肌活检 换气以确定肌肉和循环miRNA表达之间的一致性。最后，这一点 将对队列进行纵向跟踪(目标2)，进行功能测试和详细的酒精评估，网址为 出院，住院后2周和6个月，以确定酒精的长期影响- 相关肌肉疾病对功能损害的影响。这些评估将为申请者提供培训 在1)肌肉损伤的病理生理学和肌肉修复的调节，2)微创 评估肌肉质量和功能的技术，3)识别肌肉损伤的分子技术， (4)AUD综合评价方法。这将使申请者更倾向于她 表达了成为研究酒精相关长期影响的独立调查者的目标 肌肉疾病的危重疾病。

ABSTRACT Alcohol use is common in the United States with up to 7% of Americans meeting diagnostic criteria for alcohol use disorder (AUD). AUD is a significant risk factor for poor health outcomes and up to 1.5 million AUD patients require intensive care annually. However, little is known regarding the overall impact of AUD on intensive care unit (ICU) survivorship. Muscle wasting is the most common organ manifestation of alcohol abuse and contributes to respiratory compromise. Yet, no studies to date have investigated the impact of muscle disease on outcomes from respiratory failure in AUD patients. Currently, the diagnosis of neuromuscular dysfunction (NMD) relies on a combination of electrophysiology (EP) testing and muscle biopsy, both of which are often impractical in routine ICU care. Recent data suggest that measurement of muscle specific microRNAs (myomiRs) may accurately reflect ongoing myogenesis. We posit that specific myomiRs might provide an easily measurable, specific biomarker for alcohol-related muscle injury that may differentiate alcohol-related muscle disease and NMD in patients with acute respiratory failure (ARF). We hypothesize that alcohol is an independent risk factor for NMD in respiratory failure patients and that circulating myomiRs (c-myomiRs), miR-1, -133a/133b, -206, will accurately identify muscle injury in AUD patients with ARF. To test this hypothesis, subjects will undergo serial EP testing and muscle ultrasound (Aim 1) to identify prevalent alcohol-related muscle disease and incident NMD. Subjects will undergo serial c-miRNA measurement (Aim 3) followed by a percutaneous muscle biopsy at day 7 of mechanical ventilation to determine the concordance between muscle and circulating miRNA expression. Finally, this cohort will be followed longitudinally (Aim 2) with functional testing and detailed alcohol assessment at hospital discharge, 2 weeks and 6 months post-hospitalization to determine the long-term impact of alcohol- related muscle disease on functional impairment. These assessments will provide the applicant with training in 1) the pathophysiology of muscle injury and the regulation of muscle repair, 2) minimally invasive techniques for assessing muscle mass and function, 3) molecular techniques for identifying muscle injury, and 4) integrative approaches to the evaluation of AUD. This will advance the applicant towards her expressed goal of becoming an independent investigator studying the long-term impacts of alcohol-related muscle disease on critical illness.