An Observation Study of Exosome Proteomics Released From Cardiopulmonary Organs and Hemodynamic Parameters in Sepsis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change of hemodynamic parameters (heart contractility: CFI)
研究概览
简要总结
This research will be the first study for exosomes purified in blood and urine from septic patients who had multiple organ failures. Proteomics studies in exosomes from blood or urine specimens. Analyze autophage, and apoptosis related biomarkers of exosomes by bioinformatics. To find the correlations between exosomes biomarkers and hemodynamic parameters.
详细描述
Background: Sepsis, defined as an infection with evidence of systemic infection, continues to be a source of considerable morbidity and mortality. Many animal sepsis models had found that sepsis induced multiple organ failure. Autophagy, apoptosis may involve the process of sepsis related multiple organ failure. Mass spectrometry-based proteomics studies in clinical populations and in rodent and mammalian animal models had started with discovered many novel biomarkers of sepsis. Esoxomes had been found in blood or urine presented the signal of autophagy and apoptosis. On the other hand, pulse contour cardiac output (PiCCO) can calculate hemodynamic parameters that had been used for evaluation in cardiopulmonary failure of sepsis.
Aims of the study: This research will be the first study for exosomes purified in blood and urine from septic patients who had multiple organ failures. Proteomics studies in exosomes from blood or urine specimens. Analyze autophage, and apoptosis related biomarkers of exosomes by bioinformatics. To find the correlations between exosomes biomarkers and hemodynamic parameters.
Materials and Methods
A total of 30 patients with sepsis, septic shock, or multiple organ failure will be included, of whom 15 septic patients had cardiopulmonary organ failure, others will be not. All patients included and classified according to the surviving sepsis campaign criteria, also treat according to surviving sepsis campaign guidelines. Data will be collected from January 2016 to December 2016. Exosome will be isolated and purified by sucrose gradient ultracentrifugation. Magnetic beads purification, 2D gel electrphoresis, and MALDI-TOF will be used to analyze proteomics of exosome in urine or blood of septic patients. Western blotting will be done to prove the proteins found by proteomics. Pulse contour cardiac output monitored heart contractility, end-diastolic volume parameters, and lung water parameters. Finally, to find the correlations between exosome specific organ and autophagy-apoptosis biomarkers and hemodynamic parameters.
Possible effect: Systematic establishment of exosome proteomics in blood and urine from septic patients who had multiple organ failure or not will be done. Autophagy-apoptosis biomarkers in exosomes will be detected and correlated to hemodynamic parameters, to judge specific organ failure in sepsis.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with sepsis who admit to ICU
- •Sepsis diagnostic criteria: acute change in total SOFA score ≥ 2 points attributable to infection
- •Pulse indicator continuous cardiac output monitor (PiCCO) is accept by patient for hemodynamic monitoring
排除标准
- •Patients with acute SOFA changes < 2 points are excluded
- •auria, no urine can be collected
- •Previous cardiopulmonary co-morbidity. Chronic respiratory failure with ventilator dependence and chronic heart failure.
结局指标
主要结局
Change of hemodynamic parameters (heart contractility: CFI)
时间窗: Baseline, 6 hours
Change from Baseline Cardiac function index (CFI; L/min) at 6 hours. Cardiac function index (CFI; L/min) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany)
Change of hemodynamic parameters (preload: GEDI)
时间窗: Baseline, 6 hours
Change from Baseline Global end-diastolic index (GEDI; mL/m2) at 6 hours. Global end-diastolic index (GEDI; mL/m2) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany).
Change of hemodynamic parameters (fluid responsiveness: SVV)
时间窗: Baseline, 6 hours, one day, and 3 days
Change from Baseline Stroke volume variation (SVV, %) at 6 hours. Stroke volume variation (SVV, %) will be calculated spontaneously by PiCCO2 device (Pulsion Medical Systems, Munich, Germany).
Change of hemodynamic parameters (afterload: SVRI)
时间窗: Baseline, 6 hours
Change from Baseline Systemic vascular resistance index (SVRI; dynes x sec x cm-5/m2) at 6 hours. Systemic vascular resistance index (SVRI; dynes x sec x cm-5/m2) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany).
Change of hemodynamic parameters (lung permeability: PVPI)
时间窗: Baseline, 6 hours
Change from Baseline pulmonary vascular permeability index (PVPI; ratio) at 6 hours. pulmonary vascular permeability index (PVPI) will be calculated by the PiCCO device (Pulsion Medical Systems, Munich, Germany). EVLWI means total water in lung tissue, it increase in pulmonary edema or ARDS. PVPI means pulmonary vascular permeability and always high in ARDS (acute respiratory distress syndrome)
Change of hemodynamic parameters (lung water: ELWI)
时间窗: Baseline, 6 hours
Change from Baseline Extravascular lung water index (EVLWI; mL/kg) at 6 hours. Extravascular lung water index (EVLWI; mL/kg) will be calculated by the PiCCO device (Pulsion Medical Systems, Munich, Germany). EVLWI means total water in lung tissue, it increase in pulmonary edema or ARDS. PVPI means pulmonary vascular permeability and always high in ARDS (acute respiratory distress syndrome)
次要结局
- Autophagy biomarkers in exosomes: LC3II (NTA)(6 hours)
- Exosomes marker: CD9 (NTA)(6 hours)
- Hospital mortality(Up to 90 days)
- Autophagy modifiers in exosomes: HSP70 (NTA)(6 hours)
- Length of stay in hospital(Up top 90 days)
- Autophagy modifiers in exosomes: mTOR (NTA)(6 hours)
- Autophagy modifiers in exosomes: HSP70 (Western blots)(6 hours)
- Autophagy modifiers in exosomes: sequestosome 1 (Western blots)(6 hours)
- Exosomes marker: CD9 (Western blots)(6 hours)
- 28-day mortality(Up to 28 days)
- Length of stay in ICU(Up to 30 days)
- Autophagy modifiers in exosomes: sequestosome 1 (NTA)(6 hours)
- Autophagy biomarkers in exosomes: LC3II (Western blots)(6 hours)
- Autophagy modifiers in exosomes: mTOR (Western blots)(6 hours)
- ICU mortality(Up to 30 days)