The Sepsis ClinicAl Resource And Biorepository (SCARAB) Project

脓毒症是导致世界各地儿童和成人器官衰竭和死亡的主要原因 除了抗生素和支持性护理外，没有其他特定的治疗方法。缺乏针对性的一个主要原因 治疗是我们对遗传、环境、微生物、社会经济和生物的不完全理解 低于人类脓毒症风险和结果的因素，以及推动临床异质性的因素 综合症。我们建议创建一个独特的资源，脓毒症临床资源和生物库 (圣甲虫)，一项针对患有脓毒症和重症对照的成人和儿童的双中心前瞻性研究 旨在全面且可扩展到大型多中心实施。要创建此资源， 我们将利用我们在ICU进行的大规模前瞻性观察研究的经验，我们的小说 我们世界一流的机械通气患者远端空隙的无创取样方法 生物信息学专业知识、最先进的表型鉴定方法和独特的机构资源。 圣甲虫有望从VUMC和Meharry Medical的儿科和成人ICU招募受试者 大学，一所主要照顾少数族裔人口的机构。受试者将在他们的 疾病和血液、DNA、呼吸微滴的系列生物标本(来自热湿交换 (HME过滤器)、气管抽吸物和尿液将被收集。研究人类最常损伤的末梢器官 脓毒症，我们将建立收集、处理和储存从HME收集的肺液的最佳做法 滤器，一种新的呼吸机患者远端空气采样方法。与我们的合作者在 生物医学信息学，我们将开发自动表型算法来识别脓毒症患者和 器官衰竭包括急性呼吸窘迫综合征、急性心肌梗死和精神错乱。我们将使用尖端的自然语言处理 概念图等方法对临床上重要的变量进行详细的亚表型分析， 对大规模的表型构成挑战，例如高活动型和低活动型的神志不清。圣甲虫会 还可以链接到独特的VUMC资源，例如保留所有微生物临床分离株的MicroVU VUMC的标本允许使用当代多重组学对宿主-病原体相互作用进行大规模研究 接近了。圣甲虫临床数据和生物标本将可供更广泛的研究社区使用 通过我们基于网络的学习门户上的一个应用程序。建议书将按资源利用率进行审查 由研究人员和脓毒症和器官功能障碍方面的国家专家组成的委员会。数据将是 使用最严格的安全标准取消身份识别。圣甲虫也被设计成很容易接触到 职业生涯早期调查人员，通过提供统计支持、定制的表型分析和访问Studios 研究设计方面的专家参与。将所有这些创新元素结合在一起将允许 机制研究、预测生物标志物的发展、对院前因素和临床的了解 败血症患者的结果研究和适当的对照，这是以前不可能的。

Sepsis is a major cause of organ failure and death in both children and adults around the world for which there are no specific therapies other than antibiotics and supportive care. A major reason for the lack of targeted therapies is our incomplete understanding of the genetic, environmental, microbial, socioeconomic and biologic factors that underly risk of and outcomes from human sepsis and that drive heterogeneity within this clinical syndrome. We propose to create a unique resource, the Sepsis ClinicAl Resource And Biorepository (SCARAB), a two center prospective study in adults and children with sepsis and critically ill controls that is designed to be both comprehensive and scalable to large multicenter implementation. To create this resource, we will leverage our experience with large scale prospective observational studies in the ICU, our novel method of non-invasively sampling the distal airspace in mechanically ventilated patients, our world class bioinformatics expertise, state-of-the-art phenotyping methodologies, and unique institutional resources. SCARAB will prospectively enroll subjects from pediatric and adult ICUs at VUMC and Meharry Medical College, an institution that cares for a primarily minority population. Subjects will be enrolled early in their illness and serial biologic specimens of blood, DNA, respiratory micro-droplets (from Heat Moisture Exchange (HME) filters), tracheal aspirates and urine will be collected. To study the end organ most commonly injured in sepsis, we will establish best practices for collection, processing and storage of lung fluid collected from HME filters, a novel method for sampling the distal airspace in ventilated patients. Working with our collaborators in Biomedical Informatics, we will develop automated phenotyping algorithms to identify patients with sepsis and organ failures including ARDS, AKI and delirium. We will use cutting edge natural language processing methods such as concept mapping to conduct detailed sub-phenotyping for clinically important variables that are challenging to phenotype on a large scale, such as hyper- and hypoactive forms of delirium. SCARAB will also be linked to unique VUMC resources such as MicroVU which retains clinical isolates of all microbial specimens at VUMC allowing large studies of host-pathogen interactions using contemporary multi-omics approaches. SCARAB clinical data and biospecimens will be accessible to the broader research community through an application on our web based study portal. Proposals will be reviewed by a Resource Utilization Committee comprising study investigators and national experts in sepsis and organ dysfunction. Data will be de-identified using the most rigorous security standards. SCARAB is also designed to be readily accessible to early career investigators by providing statistical support, customized phenotyping and access to Studios for expert engagement for study design. Bringing together all of these innovative elements will allow for mechanistic studies, development of predictive biomarkers, understanding of pre-hospital factors and clinical outcome studies in patients with sepsis and appropriate controls at a scale not previously possible.