The Sepsis ClinicAl Resource And Biorepository (SCARAB) Project

败血症临床资源和生物储存库 (SCARAB) 项目

• 批准号: 10353314
• 负责人: Julie Anne Bastarache
• 金额: $ 24.64万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10353314
• 关键词: Academic Medical Centers; Acute Respiratory Distress Syndrome; Adult; Affect; Age; Antibiotics; Aspirate substance; Bioinformatics; Biological; Biological Factors; Blood; Blood specimen; Caring; Censuses; Cessation of life; Child; Childhood; Clinical; Clinical Data; Collection; Communities; Complement; Coupled; Critical Illness; Custom; DNA; Data; Data Collection; Data Security; Data Set; Delirium; Development; Distal; Electronic Health Record; Elements; Enrollment; Epidemiology; Functional disorder; Gene Expression; Genetic; Heterogeneity; Hospitals; Human; Image; Immune response; Institution; Link; Liquid substance; Lung; Manuals; Mechanical ventilation; Medical Records; Methodology; Methods; Microbiology; Minority Groups; Molecular; Natural Language Processing; Observational Study; Online Systems; Organ; Organ failure; Outcome; Outcome Study; Pathologic; Patients; Persons; Phase; Phenotype; Plasma; Process; Prospective Studies; Protocols documentation; Registries; Reproducibility; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Sampling; Security; Sepsis; Sepsis Syndrome; Socioeconomic Factors; Specimen; Supportive care; Syndrome; Testing; Urine; Validation; Whole Blood; antimicrobial; base; biobank; biological heterogeneity; biomedical informatics; career; clinical phenotype; concept mapping; data de-identification; data modeling; data sharing; design; epidemiology study; ethnic diversity; experience; indexing; injured; innovation; interest; lung microbiome; medical schools; microbial; multidisciplinary; multiple omics; novel; organ injury; participant enrollment; pathogen; patient population; phenotyping algorithm; predictive marker; prospective; racial diversity; respiratory; sample collection; scale up; screening; septic patients; sociodemographics; socioeconomics; targeted treatment; web portal

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.

败血症是世界各地儿童和成人的器官衰竭和死亡的主要原因 除了抗生素和支持性护理外，没有其他特定疗法。缺乏目标的主要原因 疗法是我们对遗传，环境，微生物，社会经济和生物学的不完全理解 人类败血症的风险和结果的风险以及在本临床内推动异质性的因素 综合征。我们建议创建一个独特的资源，败血症临床资源和生物库 （圣acab），对成人和患有败血症和严重控制的儿童进行的两个中心前瞻性研究， 设计为大型多中心实施既全面又可扩展。为了创建此资源， 我们将利用ICU的大规模前瞻性观察研究来利用我们的经验 在机械通风患者中非侵入性采样远端空域的方法，我们的世界一流 生物信息学专业知识，最先进的表型方法和独特的机构资源。 Scarab将在VUMC和Meharry Medical的儿科和成人ICU的前瞻性招募受试者 大学，一个主要关心少数民族人口的机构。受试者将在早期入学 疾病和血液，DNA，呼吸微滴滴的序列生物学标本（来自热水交换 （HME）过滤器），气管抽吸物和尿液将被收集。研究最终器官最常见受伤 败血症，我们将建立从HME收集，加工和存储肺液的最佳实践 过滤器，一种新的方法，用于对通风患者进行远端空域采样。与我们的合作者合作 生物医学信息学，我们将开发自动表型算法，以鉴定患有败血症的患者 器官故障，包括Ards，Aki和Delirum。我们将使用尖端的自然语言处理 诸如概念映射之类的方法，以对临床上重要的变量进行详细的子表型进行 大规模的表型具有挑战性，例如del妄的超触觉和低连接形式。圣甲虫会 还与独特的VUMC资源（例如Microvu）链接，该资源保留了所有微生物的临床分离株 VUMC的标本允许使用现代多摩尼 方法。大大的研究社区将可以访问圣甲虫临床数据和生物测量 通过我们基于Web的学习门户上的应用程序。建议将通过资源利用来审查 委员会由败血症和器官功能障碍的研究人员和国家专家组成。数据将是 使用最严格的安全标准被取消识别。圣甲虫也被设计为容易访问 通过提供统计支持，定制表型和访问工作室的早期职业调查人员 研究设计专家参与。将所有这些创新元素汇总在一起将允许 机械研究，预测生物标志物的发展，对院前因素的理解和临床 以前无法进行败血症患者和适当对照的患者的结果研究。