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%的美国人符合以下诊断标准： 酒精使用障碍（AUD）AUD是不良健康结局的重要风险因素， AUD患者每年都需要重症监护。然而，对澳元的整体影响知之甚少 重症监护室（ICU）的生存率。肌肉萎缩是最常见的器官表现， 酒精滥用，并导致呼吸系统受损。然而，迄今为止还没有研究调查过 肌肉疾病对AUD患者呼吸衰竭结局的影响目前，诊断 神经肌肉功能障碍（NMD）依赖于电生理（EP）测试和肌肉功能测试的组合。 活检，这两者在常规ICU护理中通常是不切实际的。最近的数据表明， 肌肉特异性microRNA（myomiRs）可以准确地反映正在进行的肌生成。我们将详细说明 myomiRs可能为酒精相关的肌肉损伤提供一种易于测量的特异性生物标志物， 在急性呼吸衰竭（ARF）患者中区分酒精相关性肌肉疾病和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，将准确识别AUD中的肌肉损伤 ARF患者为了验证这一假设，受试者将接受系列EP测试和肌肉超声检查。 (Aim 1）确定流行的酒精相关肌肉疾病和事件NMD。受试者将接受一系列 c-miRNA测量（目标3），随后在机械刺激第7天进行经皮肌肉活检。 通气，以确定肌肉和循环miRNA表达之间的一致性。最后 队列将纵向随访（目标2），进行功能测试和详细的酒精评估， 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。这些评估将为申请人提供培训 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）鉴定肌肉损伤的分子技术， （4）AUD的综合评价方法。这将推动申请人向她 表达了成为一名独立调查员的目标，研究酒精相关的长期影响。 肌肉疾病的严重疾病。

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.