Plasma Protein Biomarker-Based Diagnostics of Outcome in Sepsis and CAP

基于血浆蛋白生物标志物的脓毒症和 CAP 结果诊断

• 批准号: 8053158
• 负责人: Stephen Francis Kingsmore
• 金额: $ 40.23万
• 依托单位: NATIONAL CENTER FOR GENOME RESOURCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-12 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8053158
• 关键词: APACHE II; Accident and Emergency department; Acute Kidney Failure; Acute Physiology and Chronic Health Evaluation; Adult Respiratory Distress Syndrome; Algorithms; American; Antibiotic Resistance; Antigens; Bacteremia; Biological Assay; Biological Markers; Blood; Blood Coagulation Disorders; Blood specimen; Candida; Cessation of life; Chest; Clinical; Clinical Research; Communities; Consensus; Critical Care; Data Set; Detection; Development; Diagnostic; Diagnostic tests; Early Diagnosis; Early identification; Effectiveness; Enrollment; Enterobacter; Escherichia coli; Etiology; Event; Failure; Functional disorder; Genus staphylococcus; Goals; Gold; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospitalization; Hospitals; Human; Immunoassay; In Vitro; Infection; Intensive Care Units; Klebsiella; Legionella pneumophila; Lobar; Mass Spectrum Analysis; Measures; Medical; Medicine; Metabolic; Methods; Monitor; Morbidity - disease rate; Mycoplasma; Organ; Outcome; Outcomes Research; Patient Selection; Patients; Physicians; Plasma Proteins; Pneumonia; Principal Investigator; Proteins; Proteomics; Recombinants; Research Personnel; Resource Allocation; Respiratory Failure; Sepsis; Sepsis Syndrome; Septic Shock; Severities; Societies; Sputum; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae; Technology; Testing; Time; Triage; Urine; Validation; Virus; activated Protein C; antimicrobial; atypical pneumonia; base; body system; candidemia; cohort; college; cost; fungus; indexing; mortality; multidisciplinary; novel; outcome forecast; pathogen; point of care; predictive modeling; prognostic; programs; prospective; symposium; tertiary care

DESCRIPTION (provided by applicant): A multidisciplinary, collaborative effort involving investigators at 6 organizations is proposed to develop novel, in vitro diagnostic tests (IVD) for severe sepsis (SS) and community acquired pneumonia (CAP). Specific Aim 1: Early, accurate identification of sepsis patients who will develop organ dysfunction (SS) is critical for effective management and positive outcome. We propose to develop a rapid, point-of-care (POC) IVD for early diagnosis of SS. Our preliminary studies have identified candidate biomarkers of SS that we propose to validate in a prospective clinical study of sepsis at 3 tertiary care hospitals and emergency departments employing proteomic technologies (mass spectrometry and multiplexed immunoassays). Bivariable analyses will be performed to identify and validate biomarker differences between groups. Multivariable analyses will be performed on validated biomarkers to derive a biomarker panel for early diagnosis of SS. The biomarker panel will be compared with prognostic indices, such as metabolic endpoints and APACHE II score. The biomarker panel will be developed into an oligoplex IVD immunoassay performed on a single blood sample on the Biosite Triage platform, with a time-to-result of less than 30 minutes. Specific Aim 2: Complications of CAP are major determinants of morbidity and mortality. Early, accurate identification of patients with CAP who will have a complicated course or poor outcome (severe CAP) is critical for effective management and positive outcome. We propose to identify biomarkers for early diagnosis of severe CAP by separate analysis of CAP patients in the Aim 1 clinical study. Bi- and multivariable analyses will be performed to identify biomarker differences and derive a biomarker panel for early diagnosis of severe CAP. This panel will be compared with prognostic indices, such as PORT score. Specific Aim 3: Currently, initial antimicrobial treatment of sepsis and CAP is empiric. We propose to identify host biomarkers for early differentiation of common etiologic agents in sepsis and CAP, in order to allow more targeted initial therapy, thereby decreasing cost associated with ineffective therapy and lessening likelihood of antibiotic resistance. Bi- and multi-variable analyses will be performed on groups of patients from the Aim 1 study with confirmed sepsis and CAP pathogens (such as pneumococcus) in order to identify biomarkers and a biomarker panel for early differentiation of specific class agent in sepsis and CAP.

描述（由申请人提供）：一项涉及6个组织研究人员的多学科合作项目，拟开发用于严重脓毒症（SS）和社区获得性肺炎（CAP）的新型体外诊断测试（IVD）。具体目标1：早期，准确识别败血症患者将发展为器官功能障碍（SS）是有效管理和积极结果的关键。我们建议开发一种快速的，即时护理（POC）

项目成果

Deep sequencing of patient genomes for disease diagnosis: when will it become routine?

• DOI: 10.1126/scitranslmed.3002695
• 发表时间: 2011-06-15
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Kingsmore SF;Saunders CJ
• 通讯作者: Saunders CJ

Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans.

• DOI: 10.1016/j.chom.2009.07.006
• 发表时间: 2009-09-17
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Zaas AK;Chen M;Varkey J;Veldman T;Hero AO 3rd;Lucas J;Huang Y;Turner R;Gilbert A;Lambkin-Williams R;Øien NC;Nicholson B;Kingsmore S;Carin L;Woods CW;Ginsburg GS
• 通讯作者: Ginsburg GS

A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

• DOI: 10.1371/journal.pone.0052198
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Woods CW;McClain MT;Chen M;Zaas AK;Nicholson BP;Varkey J;Veldman T;Kingsmore SF;Huang Y;Lambkin-Williams R;Gilbert AG;Hero AO 3rd;Ramsburg E;Glickman S;Lucas JE;Carin L;Ginsburg GS
• 通讯作者: Ginsburg GS

Controlled clinical comparison of BacT/ALERT standard aerobic and standard anaerobic blood culture bottles inoculated directly or after transport in sodium polyanethol sulfonate tubes.

对直接接种或在聚茴香醇磺酸钠管中运输后接种的 BacT/ALERT 标准需氧和标准厌氧血培养瓶进行对照临床比较。

• DOI: 10.1128/jcm.02091-06
• 发表时间: 2007
• 期刊: Journal of clinical microbiology
• 影响因子: 9.4
• 作者: Pien,BrianC;Mirrett,Stanley;Crews,BettyR;Reller,LBarth;Woods,ChristopherW
• 通讯作者: Woods,ChristopherW

A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.

• DOI: 10.1126/scitranslmed.3006280
• 发表时间: 2013-09-18
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Zaas AK;Burke T;Chen M;McClain M;Nicholson B;Veldman T;Tsalik EL;Fowler V;Rivers EP;Otero R;Kingsmore SF;Voora D;Lucas J;Hero AO;Carin L;Woods CW;Ginsburg GS
• 通讯作者: Ginsburg GS