A Blood Test for Pre-symptomatic Detection of Sepsis

描述(由申请人提供)：据估计，美国每年有170万患者经历医院感染(CDC)。其中约750,000例感染导致严重败血症，超过200,000名患者死亡[1]。因此，160亿美元(占所有密集型产品的40% 每年用于管理脓毒症患者[1]。脓毒症是一种潜在的致命疾病，感染的存在会导致全身炎症状态，随后是多器官功能障碍。脓毒症的延迟识别，或在脓毒症被识别后延迟开始治疗，仍然是一个严重的问题。已发表的研究表明，适当的治疗每延迟一小时，死亡率就相应增加7%[2]。虽然分子技术缩短了临床观察和脓毒症确认之间的差距，但临床样本中必须存在足够水平的微生物-通常是血液-以进行检测。事实上，这是主要的限制，因为血液样本中并不总是存在细菌水平。一种可能更敏感和更有效的检测感染性病原体及其相关败血症的方法是通过测量患者的免疫状况。我们的工作重点是开发一种快速血液测试，检测出症状前败血症相关转录本(PreSepT)的签名。PreSepT有可能在临床症状(例如发烧、心率加快、血细胞计数增加)出现之前发现急性细菌感染。与现有的诊断方法不同，PreSepT还可以通过测量患者对治疗干预的反应来改善患者的护理。最终，我们的目标是PreSepT将为医生提供更长的机会窗口来治疗患者，个性化患者治疗以获得更好的护理，并降低脓毒症和脓毒症相关死亡率。拟议研究的目标是：(1)优化快速、集中的血液rna图谱分析；(2)构建集成的数据采集和分析软件系统；以及(3)在回溯性试点中验证诊断测试。 使用相关患者样本进行研究。一种非侵入性的血液诊断可以检测细菌感染，并提供败血症的症状前诊断和预后，这将在减少与住院患者相关的脓毒症病例方面提供深刻的医学进步。 与公共卫生相关：目前诊断和确认败血症的诊断方法灵敏度有限。该项目旨在开发一种新的针对无症状患者的血液检测方法。 败血症的检测，它描述了一个人的免疫反应。成功将为医生提供更早的患者治疗机会，从而显著降低美国和全球与脓毒症相关的发病率和死亡率及其相关成本。

DESCRIPTION (provided by applicant): Each year, an estimated 1.7 million patients in the U.S. experience a hospital infection (CDC). Approximately 750,000 of these infections lead to severe sepsis, with over 200,000 patients dying [1]. As a result, $16 billion (40% of all intensive care unit expenditures) is spent each year managing patients with sepsis [1]. Sepsis is a potentially fatal condition in which the presence of an infection results in a whole-body inflammatory state, followed by multiple organ dysfunction. Delayed identification of sepsis, or a delay in initiation therapy after sepsis is recognized, remains a serious problem. Published studies have demonstrated that for every one hour delay in the administration of appropriate therapy there is an associated 7% rise in mortality [2]. While molecular techniques have shortened the gap between clinical observation and confirmation of sepsis, the microorganism must be present in the clinical sample-usually the blood-at a sufficient level for detection. Indeed, this is the major limitation, as bacterial levels are not always present in the blood sample. A potentially more sensitive and efficient method for detecting an infectious agent and its associated sepsis is by measurement of the patient's immune profile. Our work has focused on developing a rapid blood test that detects a Pre-symptomatic Sepsis-related Transcript (PreSepT) signature. PreSepT has the potential to detect acute bacterial infections before the onset of clinical symptoms (e.g., fever, increase heart rate, increased blood count.). Unlike existing diagnostics, PreSepT can also be used to improve patient care by measuring their response to therapeutic intervention. Ultimately, the goal is that PreSepT will provide physicians a longer window of opportunity to treat patients, personalize patient treatment for better care, and decrease sepsis and sepsis-related death rates. The objectives of the proposed studies are to: (1) optimize a rapid, focused blood RNA profiling assay; (2) prototype an integrated data capture and analysis software system; and (3) validate the diagnostic test in a retrospective pilot study using relevant patient samples. A non-invasive, blood diagnostic that detects bacterial infections and provides a pre-symptomatic diagnosis and prognosis for sepsis would provide profound medical advancement in decreasing sepsis cases associated with hospitalized patients. PUBLIC HEALTH RELEVANCE: Current diagnostic assays to diagnose and confirm sepsis are limited in sensitivity. This project aims to develop a novel blood test for the pre-symptomatic detection of sepsis that profiles a person's immune response. Success would provide physicians an earlier opportunity for patient treatment, resulting in a significant reduction in sepsis-related morbidity and mortality and its associated costs in the US, and globally.