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Neutrophil Decision Making in Confined Environments in Health and Disease

健康和疾病中受限环境中的中性粒细胞决策

基本信息

批准号：
9897528
负责人：
Daniel Irimia
金额：
$ 36.12万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9897528
关键词：
Acquired Immunodeficiency Syndrome Antibiotic Resistance Antibiotic Therapy Bacteria Biological Assay Blood Blood specimen Budgets Case-Control Studies Cessation of life Chemotaxis Chromatin Clinic Clinical Clinical Research Colon Carcinoma Congestive Heart Failure Containment Decision Making Detection Device Designs Devices Diagnosis Diagnostic Disease Drops Early Diagnosis Early identification Environment Goals Gold Health Hospitalization Hour Human Incidence Individual Infection Inflammation Inflammatory Inflammatory Response Innate Immune System Intensive Care Intervention Laboratories Leukocytes Measurement Measures Mechanics Medical Medicare Microbe Microfluidics Mission Monitor Pathology Patient Care Patient Monitoring Patients Pattern Phagocytosis Phenotype Population Population Study Process Retrospective Studies Risk Role Sepsis Symptoms Technology Testing Time Trauma Trauma patient Work accurate diagnosis antimicrobial base cohort cost design extracellular fungus improved migration neutrophil new technology novel novel strategies patient stratification personalized diagnostics prevent septic patients targeted treatment tool treatment response treatment strategy

项目摘要

Sepsis diagnosis poses significant clinical and scientific challenges. The incidence of sepsis in the US is twice the rate of congestive heart failure, six times the rate of colon cancer, and 20 times the incidence of AIDS, and sepsis is the single most significant expense in Medicare budget. Early and more accurate diagnostic of sepsis could save lives, reduce costs, and improve treatment. However, the precision of early sepsis diagnosis today is ~70% (one in every three patients is misdiagnosed). Blood cultures are the gold standard, but their results are available 3-4 days after clinical decisions have been made. Towards the goal of early and accurate sepsis diagnosis, we will focus on microfluidic tools that measure neutrophil inflammatory and anti-microbial functions. We will pursue three enabling technologies to better understand the functionality of neutrophils in the context of sepsis. We will increase the sensitivity and reduce the duration of a new assay for sepsis based on the spontaneous neutrophil migration, we will make precision measurements of neutrophil cooperation against live microbes using new swarming arrays, and we will design devices to trap neutrophil-derived chromatin from blood (cNETs) and identify bacteria in blood during sepsis.

脓毒症诊断提出了重大的临床和科学挑战。美国败血症的发病率是充血性心力衰竭的发病率是结肠癌的6倍，艾滋病的发病率是20倍，败血症是医疗保险预算中最重要的一项费用。早期和更准确地诊断脓毒症可以挽救生命，降低成本，改善治疗。然而，当今早期脓毒症诊断的精确性约为70%（每三名患者中就有一名被误诊）。血培养是金标准但他们的结果在作出临床决定后3-4天内可用。朝着早期和准确脓毒症的目标迈进诊断，我们将专注于测量中性粒细胞炎症和抗微生物功能的微流体工具。我们将寻求三种使能技术，以更好地了解中性粒细胞在以下背景下的功能：败血症我们将增加灵敏度，并减少持续时间的一个新的测定脓毒症的基础上，中性粒细胞自发迁移，我们将精确测量中性粒细胞与肝脏的合作，微生物使用新的群集阵列，我们将设计设备来捕获嗜中性粒细胞衍生的染色质，血液（cNET），并确定败血症期间血液中的细菌。