Predictive values of serum 8-hydroxydeoxyguanosine on disease progression and prognosis of patients with sepsis
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摘要:
目的 探讨血清8-羟基脱氧鸟苷（8-OHdG）对脓毒症患者病情进展及预后预测的作用。 方法 采用前瞻性观察性研究方法。2015年4月—2016年7月，温州医科大学附属第一医院急诊科收治124例符合入选标准的脓毒症患者，其中男79例、女45例，年龄（62±15）岁。计算所有患者入院第2天及入院时脓毒症相关性器官功能衰竭评价（SOFA）评分及二者的差值ΔSOFA评分，并将患者分为ΔSOFA评分<2分的非进展组（101例）和ΔSOFA评分≥2分的进展组（23例）。根据患者住院期间存活情况将患者分为生存组（85例）和死亡组（39例）。分别比较非进展组与进展组及生存组与死亡组患者性别、年龄、住急诊重症监护病房（ICU）天数、是否吸烟、有无高血压、有无糖尿病，入院时血清白细胞计数、C反应蛋白及降钙素原，入院24 h内血清8-OHdG。采用多因素logistic回归分析筛选124例脓毒症患者病情进展和住院期间死亡的独立危险因素并根据独立危险因素，绘制受试者操作特征（ROC）曲线，计算曲线下面积（AUC）和最佳阈值及最佳阈值下的敏感度、特异度。根据住院期间死亡ROC曲线中的最佳阈值将患者分为高8-OHdG组（35例）和低8-OHdG组（89例），比较2组患者性别、年龄、入院时SOFA评分、入院第2天SOFA评分和ΔSOFA评分，采用Kaplan-Meier法分析2组患者入院90 d内存活率差异。对数据行独立样本t检验、Mann-Whitney U检验、χ2检验、Log-rank检验。 结果 非进展组和进展组患者性别、年龄、住急诊ICU天数、吸烟情况、合并高血压情况、合并糖尿病情况及入院时血清白细胞计数、C反应蛋白、降钙素原均相近（P>0.05）。进展组患者入院24 h内血清8-OHdG水平明显高于非进展组（Z=-2.31，P<0.05）。多因素logistic回归分析显示，入院24 h内血清8-OHdG为124例脓毒症患者病情进展的独立危险因素（比值比=1.06，95%置信区间为1.01~1.11，P<0.05）。入院24 h内血清8-OHdG预测124例脓毒症患者住院期间病情进展的ROC的AUC为0.65（95%置信区间为0.52~0.79，P<0.05），最佳阈值为32.88 ng/mL，最佳阈值下的敏感度、特异度分别为52.2%、79.2%。生存组和死亡组患者性别、年龄、住急诊ICU天数、吸烟情况、合并高血压情况、合并糖尿病情况及入院时血清白细胞计数、C反应蛋白和降钙素原均相近（P>0.05）。死亡组患者入院24 h内血清8-OHdG水平明显高于存活组（Z=-2.37，P<0.05）。多因素logistic回归分析显示，入院24 h内血清8-OHdG为124例脓毒症患者住院期间死亡的独立危险因素（比值比=1.04，95%置信区间为1.00~1.09，P<0.05）。入院24 h内血清8-OHdG水平预测124例脓毒症患者住院期间死亡的ROC的AUC为0.63（95%置信区间为0.52~0.75，P<0.05），最佳阈值为32.43 ng/mL，最佳阈值下的敏感度、特异度分别为51.3%、84.7%。高8-OHdG组与低8-OHdG组患者性别和年龄均相近（P>0.05），高8-OHdG组患者入院时SOFA评分、入院第2天SOFA评分、ΔSOFA评分均明显高于低8-OHdG组（Z值分别为-2.49、-3.01、-2.64，P<0.05或P<0.01）。低8-OHdG组患者入院90 d内存活率明显高于高8-OHdG组（χ2=14.57，P<0.01）。 结论 早期血清8-OHdG水平是脓毒症患者病情进展及预后的独立危险因素，预测患者病情进展及预后的能力有限。患者血清8-OHdG水平越高，入院90 d内死亡风险越大。 -
关键词:
- 脓毒症 /
- 预后 /
- 病情进展 /
- 8-羟基脱氧鸟苷 /
- 脓毒症相关性器官功能衰竭评价评分
Abstract:Objective To investigate the values of serum 8-hydroxydeoxyguanosine (8-OHdG) in predicting disease progression and prognosis of patients with sepsis. Methods The prospective observational research methods were used. A total of 124 patients with sepsis who met the inclusion criteria were admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from April 2015 to July 2016, including 79 males and 45 females, aged (62±15) years. The sepsis-related organ failure assessment (SOFA) scores of all patients on admission and on the second day of admission and their difference (ΔSOFA) were calculated. The patients were divided into non-progression group with ΔSOFA score<2 (n=101) and progression group with ΔSOFA score ≥2 (n=23), and according to the survival during hospitalization, the patients were divided into survival group (n=85) and death group (n=39). Data of patients between non-progression group and progression group, survival group and death group were compared, including the gender, age, days in emergency intensive care unit (ICU), smoking, hypertension, diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission, and serum 8-OHdG within 24 h of admission. The multivariate logistic regression analysis was used to screen the independent risk factors of disease progression and death during hospitalization in 124 patients with sepsis, the receiver's operating characteristic (ROC) curves were drawn according to the independent risk factors, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. The patients were divided into high 8-OHdG group (n=35) and low 8-OHdG group (n=89) according to the best threshold in ROC curve of death during hospitalization. The data including the gender, age, SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in the two groups were compared. The survival rates of patients within 90 d of admission in the two groups were compared by the Kaplan-Meier method. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Log-rank test. Results The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in non-progression group and progression group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in progression group was significantly higher than that in non-progression group (Z=-2.31, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for disease progression of 124 patients with sepsis (odds ratio=1.06, with 95% confidence interval of 1.01-1.11, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict disease progression of 124 patients with sepsis was 0.65 (with 95% confidence interval of 0.52-0.79, P<0.05), the optimal threshold was 32.88 ng/mL, and the sensitivity and specificity under the optimal threshold was 52.2% and 79.2%, respectively. The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, and serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in survival group and death group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in death group was significantly higher than that in survival group (Z=-2.37, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for death of 124 patients with sepsis (odd ratio=1.04, with 95% confidence interval of 1.00-1.09, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict death of patients during hospitalization was 0.63 (with 95% confidence interval of 0.52-0.75, P<0.05), the optimal threshold was 32.43 ng/mL, the sensitivity and specificity under the optimal threshold was 51.3% and 84.7%, respectively. The gender and age of patients in high 8-OHdG group and low 8-OHdG group were similar (P>0.05). The SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in high 8-OHdG group were significantly higher than those in low 8-OHdG group (with Z values of -2.49, -3.01, and -2.64, respectively, P<0.05 or P<0.01). The survival rate within 90 d of admission of patients in low 8-OHdG group was significantly higher than that in high 8-OHdG group (χ2=14.57, P<0.01). Conclusions Serum 8-OHdG level is an independent risk factor for disease progression and death in sepsis patients with limited ability for predicting disease progression and prognosis of sepsis of patients. The patients with higher serum 8-OHdG level have higher death risk within 90 d of admission. -
陈潇荣：研究相关人员的工作分配及文章撰写；蒋丹蔚、唐亚慧：数据整理和分析；徐畅、支绍册、洪广亮：病例收集和汇总；卢中秋、赵光举：提供研究思路、数据处理方法等的指导所有作者均声明不存在利益冲突本刊编辑委员会
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参考文献
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1 入院24 h内血清8-OHdG水平预测124例脓毒症患者病情进展的受试者操作特征曲线
注：图中直线为参考线，曲线为入院24 h内血清8-羟基脱氧鸟苷（8-OHdG）水平
2 入院24 h内血清8-OHdG水平预测124例脓毒症患者住院期间死亡的受试者操作特征曲线
注：图中直线为参考线，曲线为入院24 h内血清8-羟基脱氧鸟苷(8-OHdG)水平
3 Kaplan-Meier分析显示，低8-OHdG组患者入院90 d内存活率明显高于高8-OHdG组（P<0.01）
注：低8-羟基脱氧鸟苷（8-OHdG）组和高8-OHdG组患者例数分别为89、35例
表1 进展与非进展脓毒症患者临床资料比较
组别 例数 性别［例（%）］ 年龄 （岁， 住急诊ICU天数［d，M（Q1，Q3）］ 吸烟［例（%）］ 高血压［例（%）］ 男 女 非进展组 101 61（60.4） 40（39.6） 64±13 5（3，9） 25（24.8） 47（46.5） 进展组 23 18（78.3） 5（21.7） 61±18 7（2，16） 7（30.4） 15（65.2） 统计量值 χ2=2.59 t=-0.45 Z=-0.96 χ2=0.32 χ2=2.62 P值 0.108 0.655 0.340 0.574 0.106 注：将入院第2天与入院时脓毒症相关性器官功能衰竭评价评分的差值<2、≥2分的患者分别纳入非进展组、进展组；ICU为重症监护病房，CRP为C反应蛋白，8-OHdG为8-羟基脱氧鸟苷 
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表2 生存与死亡脓毒症患者临床资料比较
组别 例数 性别［例（%）］ 年龄（岁， 住急诊ICU天数［d，M（Q1，Q3）］ 吸烟［例（%）］ 高血压［例（%）］ 男 女 生存组 85 54（63.5） 31（36.5） 61±14 5（3，9） 23（27.1） 38（44.7） 死亡组 39 25（64.1） 14（35.9） 65±15 5（2，12） 9（23.1） 24（61.5） 统计量值 χ2<0.01 t=-1.93 Z=-0.26 χ2=0.22 χ2=3.03 P值 0.951 0.055 0.798 0.683 0.082 注：ICU为重症监护病房，CRP为C反应蛋白，8-OHdG为8-羟基脱氧鸟苷
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表3 高8-OHdG与低8-OHdG脓毒症患者临床资料比较
组别 例数 性别［例（%）］ 年龄（岁， 入院时SOFA评分［分，M（Q1，Q3）］ 入院第2天SOFA评分［分，M（Q1，Q3）］ ΔSOFA 评分［分，M（Q1，Q3）］ 男 女 高8-OHdG组 35 26（74.3） 9（25.7） 65±15 9（6，12） 9（6，14） 0（-1，2） 低8-OHdG组 89 53（59.6） 36（40.4） 61±14 7（5，10） 7（5，9） -1（-1，0） 统计量值 χ2=2.36 t=1.19 Z=-2.49 Z=-3.01 Z=-2.64 P值 0.125 0.237 0.013 0.003 0.008 注：8-OHdG为8-羟基脱氧鸟苷，SOFA为脓毒症相关性器官功能衰竭评价，ΔSOFA评分为入院第2天SOFA评分与入院时SOFA评分的差值
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脱细胞真皮基质（ADM） 重症监护病房（ICU） 动脉血氧分压（PaO2） 丙氨酸转氨酶（ALT） 白细胞介素（IL） 磷酸盐缓冲液（PBS） 急性呼吸窘迫综合征（ARDS） 角质形成细胞（KC） 反转录-聚合酶链反应（RT-PCR） 天冬氨酸转氨酶（AST） 半数致死烧伤面积（LA50） 全身炎症反应综合征（SIRS） 集落形成单位（CFU） 内毒素/脂多糖（LPS） 超氧化物歧化酶（SOD） 细胞外基质（ECM） 丝裂原活化蛋白激酶（MAPK） 动脉血氧饱和度（SaO2） 表皮生长因子（EGF） 最低抑菌浓度（MIC） 体表总面积（TBSA） 酶联免疫吸附测定（ELISA） 多器官功能障碍综合征（MODS） 转化生长因子（TGF） 成纤维细胞（Fb） 多器官功能衰竭（MOF） 辅助性T淋巴细胞（Th） 成纤维细胞生长因子（FGF） 一氧化氮合酶（NOS） 肿瘤坏死因子（TNF） 3-磷酸甘油醛脱氢酶（GAPDH） 负压伤口疗法（NPWT） 血管内皮生长因子（VEGF） 苏木精-伊红（HE） 动脉血二氧化碳分压（PaCO2） 负压封闭引流（VSD）
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