Bedside Genomics in Severe Trauma

严重创伤的床边基因组学

• 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
• 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

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(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岁以下个人死亡的主要原因。创伤后感染、败血症和多器官功能衰竭的发生率仍然很高，这在很大程度上是由于严重创伤的宿主免疫反应的异质性，以及无法准确识别入院后早期免疫异常的患者，因此他们面临着复杂结局的高风险。我们的主要假设是，严重钝性创伤后人类血液白细胞转录组(&lt；12-24小时)的早期变化可以用来识别哪些患者将有不利的临床结果，哪些患者最终可能受益于针对先天性和获得性免疫反应的干预治疗。我们建议开发一个临床床边平台，基于总的和丰富的血液白细胞群体的基因组表达模式，在此平台上开发基于基因组学的床边严重损伤患者的快速诊断，并可整合到临床治疗计划中。其具体目标有三：(1)利用400多名创伤患者的现有RNA样本和来自“炎症”GUE Grant的2,300多名创伤患者的数据库，建立基于白细胞转录组的统计模型，该模型可用于预测严重创伤后复杂的临床转归；(2)开发一种能够在床边分离白细胞和中性粒细胞并在数小时内使用“纳米串”技术测定信使核糖核酸丰度的护理设备；(3)对75名严重创伤患者前瞻性地验证统计模型和护理点设备，以确定具有复杂临床轨迹风险的患者。该计划的成功完成将创建一种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。这一努力的成功将大大有助于实现整合生物技术、基因组学和生物信息学、改变临床实践以及振兴危重患者个性化医疗概念的目标。 公共卫生相关性：这项研究的数据将有助于开发一种临床诊断测试，以预测严重创伤后的患者结果，并发现可以帮助医生为个别患者选择个性化药物治疗的特征。