血清可溶性髓系细胞触发受体-1在脓毒症中的临床应用价值

发布时间：2018-06-23 23:25

本文选题：脓毒症 + 可溶性髓系细胞表达触发受体-1　；参考：《广州医科大学》2013年硕士论文

【摘要】：目的通过连续、动态测定脓毒症患者血清中可溶性髓系细胞触发受体1（sTREM-1）、降钙素原（PCT）、促炎因子白细胞介素-6（IL-6）及抗炎因子白细胞介素-10（IL-10）的表达水平，进一步深入探讨sTREM-1水平对脓毒症诊断、病情危重程度评估及预后的临床价值。方法选取广州医科大学附属第一医院重症医学科（Intensive Care Unit,ICU）2012年10月至2013年5月收治的58例首次诊断全身炎症反应综合征（SystemicInflammatory Response Syndrome，SIRS)的患者，参照1991年美国胸科医师学会／危重病医学会(American College of Chest Physicians/Society of Critical CareMedicine，ACCP/SCCM)联席会议脓毒症的诊断标准，根据是否存在感染分为脓毒症组(40例）和非脓毒症组（18例）。根据病情严重程度将脓毒症组分为sepsis组11例、严重脓毒症组(severe sepsis组)11例、脓毒性休克组(septic shock组)18例。另选健康成年人作为正常对照组（12例）。动态测定患者第1、3、7、14天的sTREM-1、PCT、IL-6、IL-10的血清表达水平。再按28天转归将脓毒症组40例分为存活组（27例）和死亡组（13例），，结合APACHEII评分及SOFA评分，进行前瞻性研究。结果 1.第1天血清sTREM-1、PCT、IL-6、IL-10在脓毒症组（n=40）的中位数（25%-75%）水平[217.28（136.02-377.01）pg/ml、6.11（1.09-43.90）ng/ml、218.76（123.32-548.58）pg/ml、93.86（54.23-143.10）pg/ml]均显著高于非脓毒症组（n=18）[55.51（39.50-77.33）pg/ml、0.05（0.05-0.25）ng/ml、75.98（34.89-141.03）pg/ml、52.49（45.66-56.72）pg/ml]和正常对照组（n=12）[43.99（36.28-53.81）pg/ml、0.05（0.05-0.05）ng/ml、46.07（40.23-53.72）pg/ml、49.79（43.31-53.14）pg/ml]（P均＜0.01）。 2.单个炎症指标诊断脓毒症ROC曲线下面积最大是PCT[ROC曲线下面积（AUC）0.85，95%置信区间（0.76-0.90）]，sTREM-1[AUC0.82，95%置信区间（0.70-0.94）]次之；sTREM-1（截点浓度75.67pg/ml）诊断脓毒症的敏感性80%低于PCT（截点浓度2.17ng/ml，敏感性94%），sTREM-1诊断脓毒症特异性比PCT高（83%vs70%），sTREM-1的阳性似然比（3.90）要略好于其他指标，即诊断价值更稳定；联合PCT加sTREM-1诊断脓毒症[AUC0.87，95%置信区间（0.77-0.97）]能提高诊断的特异性到86%，敏感性80%，阳性似然比（6.22）远高于单一炎症指标。 3.在不同部位感染的脓毒症患者入组第1天中，肺部和腹腔感染的脓毒症患者sTREM-1和PCT水平分别与非脓毒症组比较均有统计学差异（P0.05）；血流感染患者的PCT中位数（25%-75%）水平[3.60（0.99-9.70）ng/ml]与非脓毒症组[0.05（0.05-0.25）ng/ml]比较差异有统计学意义（P=0.009）；血流感染患者的sTREM-1中位数（25%-75%）水平[80.00（48.00-519.70）pg/ml]与非脓毒症组[55.51（39.50-77.33）pg/ml]比较差异无统计学意义（P=0.161），sTREM-1无法早期识别血流感染的脓毒症。 4.脓毒症患者疾病严重程度评估中，入组第1天血清sTREM-1、PCT、IL-10水平在sepsis（n=11）和severe sepsis+septic shock（n=29）之间比较有统计学差异（P均0.05），IL-6和IL-6/IL-10之间比较无统计学差异（P0.05）。 5.根据Spearman相关分析，脓毒症患者第1天血清sTREM-1水平与APACHEII评分、SOFA评分、IL-6、IL-10及IL-6/IL-10均呈正相关（相关系数r分别为0.624、0.409、0.454、0.407及0.324，P均0.05）。 6.用重复测量分析的方法动态评估各个炎症指标在三个脓毒症亚组（septicshock，severe sepsis，sepsis）中的差异，PCT在第1、3、7、14天的水平随着时间推移差异有统计学意义（F=7.197，P=0.008），sTREM-1水平差异无统计学意义，但sTREM-1在三个亚组中的均数水平随时间推移始终septic shockseveresepsissepsis。 7.用重复测量分析的方法评估各炎症指标在生存组（n=27）和死亡组（n=13）之间的差异，存活组血清sTREM-1在第1、3、7、14天的水平随着时间呈下降趋势，差异有统计学意义（P=0.015）；死亡组血清sTREM-1在第1、3、7、14天的水平则随时间逐步上升，且差异有统计学意义（P=0.019）。 8.单因素logistic回归分析显示，血清sTREM-1水平[RR=1.005，95%CI（1.000-1.009），P=0.040]是脓毒症预后的危险因素。校正年龄、性别、APACHEII评分、SOFA评分、白细胞计数（WBC）及血乳酸后，logistic回归分析显示，sTERM-1并非独立的危险因素[RR=1.007，95%CI(0.999-1.016)，P0.05]。结论 1.高水平的血清sTREM-1有助于早期识别脓毒症，联合监测PCT和sTREM-1两个指标能提高诊断脓毒症的效能。 2.严重脓毒症患者血清sTREM-1水平高表达，与sepsis的严重程度相关，提示sTREM-1可作为评价脓毒症疾病严重程度的客观炎性指标。 3.脓毒症患者血清sTREM-1与IL-10及IL-6/IL-10均呈正相关，且与促炎因子IL-6的正相关性更高，提示sTREM-1在脓毒症炎症反应中可能主要起促炎作用。
[Abstract]:Purpose

The expression level of soluble myeloid cell trigger receptor 1 ( sTREM - 1 ) , calcitonin ( PCT ) , pro - inflammatory factor interleukin - 6 ( IL - 6 ) and anti - inflammatory factor interleukin - 10 ( IL - 10 ) in serum of patients with sepsis were measured continuously and dynamically .

method

The serum levels of sTREM - 1 , PCT , IL - 6 , IL - 10 in sepsis group ( n = 11 ) , severe sepsis group ( n = 11 ) and septic shock group ( 18 cases ) were divided into sepsis group ( n = 11 ) , severe sepsis group ( n = 11 ) and septic shock group ( n = 18 ) .

Results

1 . Serum sTREM - 1 , PCT , IL - 6 , IL - 10 in sepsis group ( n = 40 ) were significantly higher than those in non - sepsis group ( n = 18 ) pg / ml , 6.11 ( 1.09 - 43.90 ) ng / ml , 75.98 ( 34.89 - 145.58 ) pg / ml , 52.49 ( 45.66 - 56.72 ) pg / ml , 46.07 ( 40.23 - 53.72 ) pg / ml , 49.79 ( 43.31 - 53.14 ) pg / ml respectively ( P < 0.01 ) .

2 . The area under ROC curve of single inflammatory index was the largest under the ROC curve of PCT curve ( AUC ) 0.85 , 95 % confidence interval ( 0.76 - 0.90 ) , sTREM - 1 estimator AUC0 . 82 , 95 % confidence interval ( 0.70 - 0.94 ) .
The sensitivity of sTREM - 1 ( intercept concentration 75.67pg / ml ) was 80 % lower than that in PCT ( 2.17ng / ml , sensitivity 94 % ) . The specificity of sTREM - 1 was higher than that in PCT ( 83 % vs 70 % ) . The positive likelihood ratio ( 3.90 ) of sTREM - 1 was better than that of other indexes , that is , the diagnostic value is more stable ;
Combined PCT plus sTREM - 1 diagnostic sepsis AUC0 . 87 , 95 % confidence interval ( 0.77 - 0.97 ) could improve the specificity of diagnosis to 86 % , sensitivity was 80 % , positive likelihood ratio ( 6.22 ) was much higher than that of single inflammatory index .

3 . The sTREM - 1 and PCT levels in patients with sepsis infected with different sites were significantly different from those of non - sepsis group ( P0.05 ) .
The PCT median ( 25 % -75 % ) of patients with bloodstream infection was 3.60 ( 0.99 - 9.70 ) ng / ml , and that of non - sepsis group was 0.05 ( 0.05 - 0.25 ) ng / ml ) .
The sTREM - 1 median ( 25 % -75 % ) of patients with bloodstream infection was 80.00 ( 48.00 - 519.70 ) pg / ml , but there was no statistical significance ( P = 0.161 ) . sTREM - 1 was unable to identify the sepsis of bloodstream infection in early stage .

4 . The levels of sTREM - 1 , PCT and IL - 10 in serum sTREM - 1 , PCT and IL - 10 were significantly different between sepsis ( n = 11 ) and severe sepsis + septic shock ( n = 29 ) . There was no statistical difference between IL - 6 and IL - 6 / IL - 10 ( P0.05 ) .

5.The levels of serum sTREM - 1 were positively correlated with APACHEII score , SOFA score , IL - 6 , IL - 10 and IL - 6 / IL - 10 ( r = 0.624 , 0.409 , 0.454 , 0.407 and 0.324 , P < 0.05 ) .

6 . Using the method of repeated measurement and analysis , the difference of each inflammatory index in three sepsis subgroups ( sepsis shock , severe sepsis , sepsis ) was dynamically assessed . PCT levels were statistically significant over time ( F = 7.197 , P = 0.008 ) and sTREM - 1 levels were not statistically significant at the 1st , 3rd , 7th , 14th day , but the mean level of sTREM - 1 in the three subgroups was always septic against severesepsissepsis over time .

7 . The difference of each inflammatory index between survival group ( n = 27 ) and death group ( n = 13 ) was assessed by repeated measurement and analysis . The level of serum sTREM - 1 in survival group decreased with time at 1,3,7,14 days ( P = 0.015 ) .
The serum sTREM - 1 of the death group increased gradually with time at the 1st , 3rd , 7th and 14th days , and the difference was statistically significant ( P = 0.019 ) .

Logistic regression analysis showed that sTERM - 1 was not an independent risk factor , RR = 1.007 , 95 % CI ( 0.999 - 1.016 ) , P < 0.05 ) .

Conclusion

1 . High levels of serum sTREM - 1 contribute to early identification of sepsis , and combined monitoring of PCT and sTREM - 1 can improve the efficacy of diagnosis sepsis .

2 . The level of sTREM - 1 in patients with severe sepsis was highly correlated with the severity of sepsis , suggesting that sTREM - 1 could be used as an objective inflammatory index to evaluate the severity of sepsis .

3 . Serum sTREM - 1 was positively correlated with IL - 10 and IL - 6 / IL - 10 in septic patients , and the positive correlation of serum sTREM - 1 with pro - inflammatory factor IL - 6 was higher , suggesting that sTREM - 1 might play an important role in the inflammatory response of sepsis .
【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R459.7

【参考文献】