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美国的两倍充血性心力衰竭的发病率是结肠癌发病率的 6 倍，艾滋病发病率的 20 倍，脓毒症是医疗保险预算中最重要的一项支出。脓毒症的早期和更准确的诊断可以挽救生命、降低成本并改善治疗。然而，当今脓毒症早期诊断的精确度约为 70%（每三个患者中就有一个被误诊）。血培养是金标准，但其结果做出临床决定后 3-4 天即可获得。实现早期准确诊断脓毒症的目标诊断时，我们将重点关注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情况下的功能：败血症。我们将根据以下结果提高脓毒症新检测的灵敏度并缩短持续时间自发性中性粒细胞迁移，我们将精确测量中性粒细胞对抗活体的合作微生物使用新的集群阵列，我们将设计设备来捕获中性粒细胞衍生的染色质血液（cNET）并识别败血症期间血液中的细菌。