中性粒细胞与淋巴细胞比值和中性粒细胞胞外诱捕网与脓毒症肝损伤的临床研究

目的:探讨外周血中性粒细胞与淋巴细胞比值（neutrophil/lymphocyte ratio, NLR）联合中性粒细胞胞外诱捕网(neutrophil extracellular traps, NETs)对预测脓毒症患者发生肝损伤的临床价值。方法:采用前瞻性观察性研究方法，选择2019年03月至2020年06月南京医科大学附属无锡人民医院重症医学科收治的符合脓毒症3.0诊断标准、肝损伤诊断标准的患者作为研究对象，记录患者的基础资料，根据入院时血常规计算NLR，使用PicoGreen荧光定量检测试剂盒检测患者入院时外周血浆游离DNA（cf-DNA/NETs）定量水平，根据是否发生肝损伤，将患者分为脓毒症非肝损伤组和脓毒症肝损伤组，二元logistics回归分析发生脓毒症肝损伤的危险因素，绘制受试者工作特征曲线（ROC），并分析NLR、NETs、NLR联合NETs对预测脓毒症患者发生肝损伤的价值。结果:入选脓毒症患者122例，其中发生脓毒症肝损伤的患者45例，发生率为36.89%。脓毒症肝损伤组NLR为（21.63±4.71），脓毒症非肝损伤组NLR为（15.03±4.71），脓毒症肝损伤组NETs水平为（505.86±250.05）μg/L，脓毒症非肝损伤组NETs水平为（179.27±67.20）μg/L，两组间比较差异均有统计学意义（均 P<0.05）。二元Logistics回归分析发现，入院时NLR（ OR=1.470, 95% CI:1.121~1.926, P<0.05）、NETs（ OR=1.018, 95% CI: 1.005~1.030, P<0.05）是脓毒症患者发生肝损伤的独立危险因素。NLR的最佳截断值为16.68，NETs的最佳截断值为317μg/L，联合应用NLR和NETs预测脓毒症患者发生肝损伤的灵敏度为77.78%，特异度为98.70%，曲线下面积为0.930，约登指数为0.765。 结论:外周血NLR和NETs水平是脓毒症患者发生肝损伤的独立危险因素，联合应用NLR和NETs对脓毒症患者发生肝损伤具有一定的预测价值。以NLR为16.68、NETs为317 μg/L作为界值，可以作为预测脓毒症患者发生肝损伤的早期预警指标。

Clinical study on neutrophil to lymphocyte ratio and neutrophil extracellular traps with liver injury in patients with sepsis

Objective:To explore the clinical value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) combined with neutrophil extracellular traps (NETs) in predicting liver injury in patients with sepsis.Methods:A prospective observational study was conducted. The patients who met the diagnostic criteria for sepsis 3.0 admitted to the Department of Intensive Care Unit in Wuxi People’s Hospital Affiliated to Nanjing Medical University from March 2019 to June 2020 were selected as the research objects. The basic informations of the patients were recorded. NLR based on blood routine at admission was calculated. PicoGreen fluorescence quantitative detection kit was used to detect the quantitative level of free DNA (cf-DNA/NETs) in the peripheral plasma of patients at admission. According to whether liver injury occurred, the patients were divided into the sepsis without liver injury group and sepsis with liver injury group. Binary Logistics regression analysis was used to predict the risk factors of sepsis with liver injury. The receiver operating characteristic (ROC) curve was drawn. The value of NLR, NETs, NLR combined with NETs in predicting liver injury in patients with sepsis was analyzed.Results:A total of 122 patients with sepsis were enrolled, of which 45 patients suffered from septic liver injury, with an incidence rate of 36.89%. The NLR of the sepsis wth liver injury group was (21.63 ± 4.71), the NLR of the sepsis without injury injury group was (15.03 ± 4.71), and the NETs level of the sepsis with liver injury group was (505.86 ± 250.05) μg/L, the level of NETs in the sepsis without liver injury group was (179.27 ± 67.20) μg/L, and the differences between the two groups were statistically significant (all P<0.05). Binary logistic regression analysis found that NLR ( OR=1.470, 95% CI: 1.121-1.926, P<0.05) and NETs ( OR=1.018, 95% CI: 1.005-1.030, P<0.05) at admission were the independent risk factors for liver injury in patients with sepsis. The best cut-off value of NLR was 16.68, and the best cut-off value of NETs was 317 μg/L. The sensitivity of combined application of NLR and NETs to predict liver injury in patients with sepsis was 77.78%, specificity was 98.70%, the area under the curve was 0.930, and the Youden Index was 0.765. Conclusions:The peripheral blood NLR and NETs levels are independent risk factors for liver injury in patients with sepsis. The combined application of NLR and NETs has a certain predictive value for liver injury in patients with sepsis. Taking NLR of 16.68 and NETs of 317 μg/L as the cut-off values, they can be used as early warning indicators to predict liver injury in patients with sepsis.