Bedside Genomics in Severe Trauma

严重创伤的床边基因组学

基本信息

批准号：
8550810
负责人：
RONALD GARY TOMPKINS
金额：
$ 39.62万
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/8550810
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 nano-string 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.

描述（由申请人提供）：严重的创伤不仅是住院和发病率的主要原因，而且是45岁以下个体的主要死亡原因。事后感染，败血症和MSOF的频率在很大程度上仍然过于频繁，这在很大程度上都过于频繁，这在很大程度上是由于对宿主的不受欢迎的人的适应性，并且能够识别出对宿主的良好性的准确性，并且能够识别出适应性的良好性，并且能够准确地识别特征，并且能够准确地识别出来，并且能够准确地识别出来，并且能够准确地识别出来的人，并且能够识别出对宿主的良好性，并且能够准确地识别出来，并且能够准确地识别出来。因此，有复杂结果的高风险。我们的总体假设是，在严重钝性创伤后，人类血清白细胞转录组（<12-24小时）的早期变化可用于识别患者，这些患者将有不良的临床结果，他们最终可能会从靶向先天和适应免疫反应的干预疗法中受益。我们建议开发一个临床床边平台，该平台基于总和富集的血清细胞种群的基因组表达模式，在该模式下，在严重受伤的患者的床边开发基于基因组学的快速诊断，这些诊断可以整合到临床治疗方案中。有三个特定的目的：（1）使用来自400多名创伤患者的现有RNA样品，以及一个来自“炎症”胶水的2300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，可以验证，以预测严重创伤后的复杂临床结果；（2）开发一种护理点，可以使用纳米弦乐“技术；（3）在75名严重创伤患者中证明统计模型和统计模型，并确定基于临床临床的临床置换术的风险。在这项工作中成功的基因组数据可以预测这项努力的临床结果。