Bedside Genomics in Severe Trauma

严重创伤的床边基因组学

基本信息

批准号：
8275159
负责人：
RONALD GARY TOMPKINS
金额：
$ 42.97万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-25 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8275159
关键词：
Address Admission activity Adverse event Age Antigen Presentation Beds Benchmarking Bioinformatics Biological Assay Biological Products Biotechnology Blunt Trauma Cause of Death Cessation of life Clinical Clinical Treatment Coupled Coupling Critical Illness Data Databases Defect Development Devices Diagnostic Diagnostic tests Event FarGo Frequencies Gene Expression Profile Genomics Glues Goals Grant Heterogeneity Hospital Mortality Hospitalization Hour Human Immune response Immunity Immunosuppression Incidence Individual Infection Inflammation Inflammatory Response Leukocytes Measurement Mediating Medicine Messenger RNA Microfluidics Morbidity - disease rate Natural Immunity Nosocomial Infections Organ failure Outcome Patient Admission Patients Pattern Pharmacotherapy Population Population Intervention RNA Recovery Regulatory T-Lymphocyte Reproducibility Research Resuscitation Risk Sampling Scheme Secondary to Sepsis Side Statistical Models System T-Lymphocyte Technology Testing Therapeutic Therapeutic Intervention Time Trauma adaptive immunity adverse outcome base clinical practice cohort digital high risk immunological status indexing injured neutrophil novel patient population point of care programs prospective response response to injury sample collection secondary infection success trauma centers treatment program

项目摘要

DESCRIPTION (provided by applicant): Severe trauma not only remains a major cause of hospitalization and morbidity, but is also the leading cause of death in individuals under the age of 45. The frequency of post-trauma infections, sepsis, and MSOF remain all too frequent due, in large part, to the heterogeneity of the host immune response to severe trauma, and the inability to accurately identify patients who have immunological abnormalities early after admission and who are therefore at high risk of complicated outcomes. Our overarching hypothesis is that early changes in the human blood leukocyte transcriptome (<12-24 hrs) after severe blunt trauma can be used to identify patients who will have an adverse clinical outcome, and who ultimately may benefit from intervention therapies targeting innate and adaptive immune responses. We propose to develop a clinical bed-side platform, based on genomic expression patterns from total and enriched blood leukocyte populations, on which to develop a rapid genomics-based diagnostic at the bedside in severely injured patients, which can be integrated into clinical treatment programs. There are three specific aims: (1) Using existing RNA samples from over 400 trauma patients and a database of over 2,300 trauma patients from the "Inflammation" Glue Grant, develop statistical models based on the leukocyte transcriptome that can be validated for predicting a complicated clinical outcome after severe trauma; (2) develop a point of care device that can isolate blood leukocytes and PMNs at the bedside and determine mRNA abundance in a matter of hours using a NanoString" technology; and (3) validate prospectively in 75 severe trauma patients the statistical model and point of care device to identify patients at risk of having a complicated clinical trajectory. Successful completion of the program will create a genomics-based diagnostic that can provide in the clinical setting, timely genomic data predictive of clinical outcomes in critically ill trauma patients. Success in this endeavor will go far to reach the goals to integrate biotechnology, genomics and bioinformatics, to change clinical practice, and to invigorate the concept of personalized medicine in the critically ill patient. PUBLIC HEALTH RELEVANCE: Data from this study would help develop a clinical diagnostic test to predict patient outcomes after severe trauma, and to discover signatures that could help doctors select a personalized drug therapy for an individual patient.

描述（由申请人提供）：严重创伤不仅仍然是住院和发病的主要原因，而且也是 45 岁以下个体死亡的主要原因。创伤后感染、败血症和 MSOF 的发生率仍然很高过于频繁，在很大程度上是由于宿主对严重创伤的免疫反应的异质性，以及无法准确识别入院后早期出现免疫异常的患者，因此这些患者面临复杂结果的高风险。我们的总体假设是，严重钝性创伤后人类血液白细胞转录组（<12-24小时）的早期变化可用于识别将出现不良临床结果的患者，以及最终可能受益于针对先天性和适应性的干预疗法的患者。免疫反应。我们建议开发一个基于总和富集血液白细胞群的基因组表达模式的临床床边平台，在此基础上为严重受伤的患者开发基于基因组学的快速床边诊断，该诊断可以整合到临床治疗计划中。有三个具体目标：(1) 使用来自 400 多名创伤患者的现有 RNA 样本以及来自“炎症”Glue Grant 的 2,300 多名创伤患者的数据库，开发基于白细胞转录组的统计模型，该模型可以验证用于预测复杂的情况。严重创伤后的临床结果； (2) 开发一种护理设备，可以在床边分离血液白细胞和中性粒细胞，并使用“NanoString”技术在几小时内确定 mRNA 丰度；(3) 在 75 名严重创伤患者中前瞻性验证统计模型和点该项目的成功完成将创建基于基因组学的诊断，可以在临床环境中提供及时的基因组数据，预测危重创伤患者的临床结果。这项努力将进一步实现整合生物技术、基因组学和生物信息学的目标，改变临床实践，并激发危重患者个体化医疗的概念。公共健康相关性：这项研究的数据将有助于开发临床诊断测试来预测严重创伤后患者的结果，并发现可以帮助医生为个体患者选择个性化药物治疗的特征。