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血浆外泌体计数对脓毒症患者预后的预测价值

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目的 探讨血浆外泌体计数对脓毒症患者预后的预测价值。方法 采用前瞻性观察性研究方法,选择 2020 年 11 月至 2021 年 12 月浙江医院重症医学科收治的脓毒症患者作为研究对象。于患者入重症监护病房(ICU)当天记录性别、年龄、基础疾病、感染部位、平均动脉压(MAP)、病情严重程度评分等,取静脉血检测血常规、血生化、降钙素原(PCT),并取动脉血进行血气分析,同时记录患者去甲肾上腺素(NA)剂量。于入ICU 1、3、5、7 d提取患者血浆外泌体,应用纳米颗粒跟踪分析仪检测外泌体数量。观察终点为患者入ICU 28 d死亡。分析比较不同 28d预后患者基线资料及血浆外泌体计数的差异;采用Spearman相关法分析血浆外泌体计数与其他临床指标的相关性;采用二元多因素Logistic回归分析筛选脓毒症患者 28d死亡的独立危险因素;绘制受试者工作特征曲线(ROC曲线),分析各项指标对脓毒症患者 28d死亡的预测价值。采用Kaplan-Meier法进行28d生存曲线分析。结果 最终共纳入 26 例脓毒症患者,其中 28d存活 21 例,死亡 5 例。与存活组比较,死亡组患者MAP更低,序贯器官衰竭评分(SOFA)、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、白细胞计数(WBC)、心肌肌钙蛋白I(cTnI)更高,氧合更差;死亡组入ICU1d血浆外泌体计数明显高于存活组(×1015/L:16。96±9。11 比 5。20±2。42,P<0。05);随后两组血浆外泌体计数均持续下降,且两组间差异无统计学意义。Spearman相关性分析显示,脓毒症患者入ICU1d血浆外泌体计数与SOFA评分、APACHEⅡ评分、血乳酸(Lac)、丙氨酸转氨酶(ALT)、NA剂量均呈显著正相关(r值分别为0。572、0。585、0。463、0。411、0。696,均P<0。05),与MAP、氧合指数(PaO2/FiO2)均呈显著负相关(r值分别为-0。392、-0。496,均P<0。05)。多因素Logistic回归分析显示,入ICU1d血浆外泌体计数是脓毒症患者 28d死亡的独立危险因素[优势比(OR)=1。385,95%可信区间(95%CI)为 1。075~1。785,P=0。012]。ROC曲线分析显示,入ICU1d血浆外泌体计数预测脓毒症患者 28d死亡的ROC曲线下面积(AUC)为 0。800(95%CI为 0。449~1。000);当最佳截断值取 14。50×1015/L时,敏感度为80。0%,特异度为100%。根据1d血浆外泌体计数最佳截断值将患者分为两组进行28 d Kaplan-Meier生存曲线分析,结果显示,血浆外泌体计数<14。50×1015/L患者28d累积存活率显著高于≥14。50×1015/L患者(Log-Rank检验:χ2=19。100,P<0。001)。结论 脓毒症患者入ICU当天血浆外泌体计数显著升高,且与病情严重程度相关,能够预测 28d死亡风险。
Predictive value of plasma exosome count for the prognosis in septic patients
Objective To investigate the predictive value of plasma exosome count for the prognosis of patients with sepsis.Methods A prospective observational study was conducted.The patients with sepsis admitted to intensive care unit(ICU)of Zhejiang Hospital from November 2020 to December 2021 were enrolled as the study subjects.On the 1st day of admission to the ICU,the patient's gender,age,underlying disease,infection site,mean arterial pressure(MAP)and severity scores were recorded,and venous blood was taken for detecting the blood routine,blood biochemistry,and procalcitonin(PCT),and arterial blood was taken for blood gas analysis,simultaneously,the patient's noradrenaline(NA)dosage was recorded.On the 1st,3rd,5th,and 7th day of ICU admission,plasma exosomes were extracted,and the number of exosomes was detected by nanoparticle tracking analyzer.The endpoint of observation was the death of the patient 28 days after admission to the ICU.The differences in baseline data and plasma exosome counts of patients with different 28-day prognosis were analyzed and compared.The Spearman correlation method was used to analyze the correlation between plasma exosome counts and other clinical indicators.Binary multivariate Logistic regression analysis was used to screen the 28-day death risk factors of septic patients.The receiver operator characteristic curve(ROC curve)was plotted to analyze the predictive value of each index on the 28-day death of septic patients.The Kaplan-Meier method was used to analyze the 28-day survival curve.Results A total of 26 patients with sepsis were enrolled,of whom 21 survived and 5 died on the 28th day.Compared with the survival group,the patients in the death group had lower MAP,higher sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluationⅡ(APACHEⅡ)score,white blood cell count(WBC),cardiac troponin I(cTnI),and worse oxygenation.The plasma exosome count on the 1st day of ICU admission in the death group was significantly higher than that in the survival group(×1015/L:16.96±9.11 vs.5.20±2.42,P<0.05).Subsequently,the plasma exosome counts in both groups continued to decrease,and there was no statistically significant difference between the two groups.Spearman correlation analysis showed that the plasma exosome count on the 1st day of ICU admission in septic patients was significantly positively correlated with SOFA score,APACHEⅡscore,blood lactic acid(Lac),alanine aminotransferase(ALT)and NA dosage(r values were 0.572,0.585,0.463,0.411,0.696,all P<0.05),and it significantly negatively correlated with MAP and oxygenation index(PaO2/FiO2;r values were-0.392 and-0.496,both P<0.05).Multivariate Logistic regression analysis showed that plasma exosome count on the 1st day of ICU admission was an independent risk factor for 28-day death in septic patients[odds ratio(OR)=1.385,95%confidence interval(95%CI)was 1.075-1.785,P=0.012].ROC curve analysis showed that the area under the ROC curve(AUC)of plasma exosome count on the 1st day of ICU admission for predicting 28-day death in septic patients was 0.800(95%CI was 0.449-1.000);when the optimal cut-off value was 14.50×1015/L,the sensitivity was 80.0%and the specificity was 100%.According to the optimal cut-off value of 1-day plasma exosome count,the patients were divided into two groups for Kaplan-Meier survival curve analysis,and the results showed that the cumulative survival rate of patients with plasma exosome count<14.50×1015/L was significantly higher than that of patients with plasma exosome count≥14.50×1015/L(Log-Rank test:χ2=19.100,P<0.001).Conclusion The plasma exosome count of septic patients is significantly increased on the 1st day of admission to the ICU,which is related to the severity,and can predict the risk of death at 28 days.

Plasma exosomeSepsisBiomarkerPrognosis prediction

李雯、潘宇杰、严静、李莉

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浙江中医药大学第二临床医学院,杭州 310053

温州市中心医院重症医学科,浙江温州 325000

浙江医院重症医学科,杭州 310007

血浆外泌体 脓毒症 生物标志物 预测预后

浙江省医药卫生重大科技计划

WKJ-ZJ-2016

2024

中华危重病急救医学
中华医学会

中华危重病急救医学

CSTPCD北大核心
影响因子:3.049
ISSN:2095-4352
年,卷(期):2024.36(7)