The Sepsis ClinicAl Resource And Biorepository (SCARAB) Project

败血症临床资源和生物储存库 (SCARAB) 项目

基本信息

批准号：
10543451
负责人：
Julie Anne Bastarache
金额：
$ 22.81万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2024-02-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10543451
关键词：
Academic Medical Centers Acute Respiratory Distress Syndrome Adult Affect Age Antibiotics Bioinformatics Biological Biological Factors Blood Blood specimen Caring Censuses Cessation of life Child Childhood Clinical Clinical Data Collection Communities Complement Coupled Critical Illness DNA Data Data Collection Data Security Data Set Delirium Development Distal Electronic Health Record Elements Enrollment 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 Trachea Urine Validation Whole Blood antimicrobial aspirate 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 ventilation web portal

项目摘要

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.

脓毒症是世界各地儿童和成人器官衰竭和死亡的主要原因。除了抗生素和支持治疗外，没有其他具体疗法。缺乏针对性的一个重要原因治疗是我们对遗传、环境、微生物、社会经济和生物学的不完全理解人类脓毒症风险和结果的潜在因素以及导致该临床中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存储库（SCARAB），一项针对成人和儿童脓毒症以及重症对照的两个中心前瞻性研究旨在全面且可扩展至大型多中心实施。要创建此资源，我们将利用我们在 ICU 进行大规模前瞻性观察研究的经验，我们的小说对机械通气患者远端空气进行无创采样的方法，我们的世界一流生物信息学专业知识、最先进的表型分析方法和独特的机构资源。 SCARAB 将前瞻性地从 VUMC 和 Meharry Medical 的儿科和成人 ICU 招募受试者学院，一个主要照顾少数族裔的机构。受试者将尽早注册疾病和血液、DNA、呼吸道微滴的系列生物样本（来自热湿交换（HME）过滤器）、气管抽吸物和尿液将被收集。研究最常受伤的终末器官脓毒症，我们将建立收集、处理和储存从 HME 收集的肺液的最佳实践过滤器，一种对通气患者远端空气进行采样的新方法。与我们的合作者一起工作生物医学信息学，我们将开发自动表型分析算法来识别脓毒症患者和器官衰竭，包括 ARDS、AKI 和谵妄。我们将使用最先进的自然语言处理概念图等方法对临床重要变量进行详细的亚表型分析大规模的表型具有挑战性，例如过度活跃和低活跃形式的谵妄。圣甲虫将还可以链接到独特的 VUMC 资源，例如 MicroVU，它保留了所有微生物的临床分离株 VUMC 的标本允许使用当代多组学对宿主-病原体相互作用进行大规模研究接近。 SCARAB 临床数据和生物样本将可供更广泛的研究界使用通过我们基于网络的学习门户上的应用程序。提案将由资源利用部门审核委员会由研究研究者和脓毒症和器官功能障碍方面的国家专家组成。数据将是使用最严格的安全标准进行去识别化。 SCARAB 的设计还考虑到了易于访问通过提供统计支持、定制表型分析和进入工作室的方式，为早期职业研究人员提供帮助专家参与研究设计。将所有这些创新元素结合在一起将允许机制研究、预测生物标志物的开发、对院前因素和临床的了解对脓毒症患者进行结果研究并进行适当的对照，其规模以前是不可能的。