Ahmed Asmaa I, Soliman Randa A, Samir Shereif
Clin Lab. 2016 Dec 1;62(12):2395-2404. doi: 10.7754/Clin.Lab.2016.160615.
Cell free DNA (cfDNA) was recently suggested as a new marker of sepsis and poor outcome in ICU patients. Procalcitonin has also been the focus of attention as an early marker for systemic inflammation and sepsis.
cfDNA, procalcitonin (PCT), C-reactive protein (CRP), and lactate levels were measured in 30 ICU patients with multiple trauma or after major surgery on the first day of admission and on 5th and 7th days for PCT, CRP, and lactate. cfDNA was measured by real-time PCR, PCT by ELISA, CRP immunoturbidimetrically, and lactate spectrophotometrically. SOFA score and Injury Severity Score (ISS) for trauma patients were calculated.
Significantly higher levels of cfDNA were observed in non-survivor patients in comparison to survivors and in patients with sepsis in comparison to those without sepsis (p = 0.002 and p = 0.02, respectively). The ROC curve was calculated for cfDNA as a predictor of outcome, the area under the curve (AUC) was 0.847 (95% CI: 0.669 - 0.952), at a cutoff value of 15500 ng/µL, sensitivity = 83.3%, specificity = 77.8% (p < 0.0001). As a prognostic marker of sepsis, the AUC for cfDNA was 0.788 (95% CI: 0.601 - 0.915), sensitivity = 56.25%, specificity = 100% (p = 0.0007). Day 5 PCT levels significantly correlated with SOFA scores on day 5, ISS on admission (p < 0.001 and p = 0.028, respectively), and a significant elevation of its levels was observed in non-survivor patients compared to survivors (p = 0.001). As a predictor of sepsis, PCT showed a sensitivity of 81.3%, specificity of 100% on day 5, (AUC: 0.987, 95% CI: 0.955 - 1.00); at a cutoff value of 202.90 pg/mL (p = 0.001). As a predictor of outcome, PCT on day 5 showed a sensitivity of 94.0% and a specificity of 78.0% at a cutoff value of 194.40 pg/mL (p = 0.001). Day 1 CRP correlated with ISS on admission, and on day 5 it correlated with SOFA score 5, while lactate correlated with length of stay on days 1, 5, and 7, and its levels were significantly higher in non-survivors on days 5 and 7.
cfDNA is a good predictor of patient outcome in ICU and to a lesser extent as a marker of sepsis. PCT is another promising marker that can complement cfDNA to reach better patient management. Other markers can help in less severe cases.
游离DNA(cfDNA)最近被认为是重症监护病房(ICU)患者脓毒症及不良预后的一种新标志物。降钙素原作为全身炎症和脓毒症的早期标志物也一直是关注焦点。
对30例多发伤或大手术后入住ICU的患者在入院第一天以及在第5天和第7天(仅针对降钙素原、C反应蛋白和乳酸)检测cfDNA、降钙素原(PCT)、C反应蛋白(CRP)和乳酸水平。cfDNA采用实时聚合酶链反应测定,PCT采用酶联免疫吸附测定法,CRP采用免疫比浊法,乳酸采用分光光度法测定。计算创伤患者的序贯器官衰竭评估(SOFA)评分和损伤严重度评分(ISS)。
与存活患者相比,非存活患者的cfDNA水平显著更高;与无脓毒症患者相比,脓毒症患者的cfDNA水平显著更高(分别为p = 0.002和p = 0.02)。计算cfDNA作为预后指标的ROC曲线,曲线下面积(AUC)为0.847(95%可信区间:0.669 - 0.952),临界值为15500 ng/µL时,灵敏度 = 83.3%,特异性 = 77.8%(p < 0.0001)。作为脓毒症的预后标志物,cfDNA的AUC为0.788(95%可信区间:0.601 - 0.915),灵敏度 = 56.25%,特异性 = 100%(p = 0.0007)。第5天的PCT水平与第5天的SOFA评分、入院时的ISS显著相关(分别为p < 0.001和p = 0.028),与存活患者相比,非存活患者的PCT水平显著升高(p = 0.001)。作为脓毒症的预测指标,第5天PCT的灵敏度为81.3%,特异性为100%(AUC:0.987,95%可信区间:0.955 - 1.00);临界值为202.90 pg/mL(p = 0.001)。作为预后指标,第5天PCT在临界值为194.40 pg/mL时灵敏度为94.0%,特异性为78.0%(p = 0.001)。第1天CRP与入院时的ISS相关,第5天与第5天的SOFA评分相关,而乳酸与第1天、第5天和第7天的住院时间相关,在第5天和第7天,非存活患者的乳酸水平显著更高。
cfDNA是ICU患者预后的良好预测指标,在一定程度上也可作为脓毒症的标志物。PCT是另一个有前景的标志物,可补充cfDNA以实现更好的患者管理。其他标志物在病情较轻的情况下可能有帮助。