本文選題：膿毒癥 + 可溶性髓系細(xì)胞表達(dá)觸發(fā)受體-1　； 參考：《廣州醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的 通過連續(xù)、動態(tài)測定膿毒癥患者血清中可溶性髓系細(xì)胞觸發(fā)受體1（sTREM-1）、降鈣素原（PCT）、促炎因子白細(xì)胞介素-6（IL-6）及抗炎因子白細(xì)胞介素-10（IL-10）的表達(dá)水平，進(jìn)一步深入探討sTREM-1水平對膿毒癥診斷、病情危重程度評估及預(yù)后的臨床價值。 方法 選取廣州醫(yī)科大學(xué)附屬第一醫(yī)院重癥醫(yī)學(xué)科（Intensive Care Unit,ICU）2012年10月至2013年5月收治的58例首次診斷全身炎癥反應(yīng)綜合征（SystemicInflammatory Response Syndrome，SIRS)的患者，參照1991年美國胸科醫(yī)師學(xué)會／危重病醫(yī)學(xué)會(American College of Chest Physicians/Society of Critical CareMedicine，ACCP/SCCM)聯(lián)席會議膿毒癥的診斷標(biāo)準(zhǔn)，根據(jù)是否存在感染分為膿毒癥組(40例）和非膿毒癥組（18例）。根據(jù)病情嚴(yán)重程度將膿毒癥組分為sepsis組11例、嚴(yán)重膿毒癥組(severe sepsis組)11例、膿毒性休克組(septic shock組)18例。另選健康成年人作為正常對照組（12例）。動態(tài)測定患者第1、3、7、14天的sTREM-1、PCT、IL-6、IL-10的血清表達(dá)水平。再按28天轉(zhuǎn)歸將膿毒癥組40例分為存活組（27例）和死亡組（13例），，結(jié)合APACHEII評分及SOFA評分，進(jìn)行前瞻性研究。 結(jié)果 1.第1天血清sTREM-1、PCT、IL-6、IL-10在膿毒癥組（n=40）的中位數(shù)（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]均顯著高于非膿毒癥組（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]和正常對照組（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.單個炎癥指標(biāo)診斷膿毒癥ROC曲線下面積最大是PCT[ROC曲線下面積（AUC）0.85，95%置信區(qū)間（0.76-0.90）]，sTREM-1[AUC0.82，95%置信區(qū)間（0.70-0.94）]次之；sTREM-1（截點濃度75.67pg/ml）診斷膿毒癥的敏感性80%低于PCT（截點濃度2.17ng/ml，敏感性94%），sTREM-1診斷膿毒癥特異性比PCT高（83%vs70%），sTREM-1的陽性似然比（3.90）要略好于其他指標(biāo)，即診斷價值更穩(wěn)定；聯(lián)合PCT加sTREM-1診斷膿毒癥[AUC0.87，95%置信區(qū)間（0.77-0.97）]能提高診斷的特異性到86%，敏感性80%，陽性似然比（6.22）遠(yuǎn)高于單一炎癥指標(biāo)。 3.在不同部位感染的膿毒癥患者入組第1天中，肺部和腹腔感染的膿毒癥患者sTREM-1和PCT水平分別與非膿毒癥組比較均有統(tǒng)計學(xué)差異（P0.05）；血流感染患者的PCT中位數(shù)（25%-75%）水平[3.60（0.99-9.70）ng/ml]與非膿毒癥組[0.05（0.05-0.25）ng/ml]比較差異有統(tǒng)計學(xué)意義（P=0.009）；血流感染患者的sTREM-1中位數(shù)（25%-75%）水平[80.00（48.00-519.70）pg/ml]與非膿毒癥組[55.51（39.50-77.33）pg/ml]比較差異無統(tǒng)計學(xué)意義（P=0.161），sTREM-1無法早期識別血流感染的膿毒癥。 4.膿毒癥患者疾病嚴(yán)重程度評估中，入組第1天血清sTREM-1、PCT、IL-10水平在sepsis（n=11）和severe sepsis+septic shock（n=29）之間比較有統(tǒng)計學(xué)差異（P均0.05），IL-6和IL-6/IL-10之間比較無統(tǒng)計學(xué)差異（P0.05）。 5.根據(jù)Spearman相關(guān)分析，膿毒癥患者第1天血清sTREM-1水平與APACHEII評分、SOFA評分、IL-6、IL-10及IL-6/IL-10均呈正相關(guān)（相關(guān)系數(shù)r分別為0.624、0.409、0.454、0.407及0.324，P均0.05）。 6.用重復(fù)測量分析的方法動態(tài)評估各個炎癥指標(biāo)在三個膿毒癥亞組（septicshock，severe sepsis，sepsis）中的差異，PCT在第1、3、7、14天的水平隨著時間推移差異有統(tǒng)計學(xué)意義（F=7.197，P=0.008），sTREM-1水平差異無統(tǒng)計學(xué)意義，但sTREM-1在三個亞組中的均數(shù)水平隨時間推移始終septic shockseveresepsissepsis。 7.用重復(fù)測量分析的方法評估各炎癥指標(biāo)在生存組（n=27）和死亡組（n=13）之間的差異，存活組血清sTREM-1在第1、3、7、14天的水平隨著時間呈下降趨勢，差異有統(tǒng)計學(xué)意義（P=0.015）；死亡組血清sTREM-1在第1、3、7、14天的水平則隨時間逐步上升，且差異有統(tǒng)計學(xué)意義（P=0.019）。 8.單因素logistic回歸分析顯示，血清sTREM-1水平[RR=1.005，95%CI（1.000-1.009），P=0.040]是膿毒癥預(yù)后的危險因素。校正年齡、性別、APACHEII評分、SOFA評分、白細(xì)胞計數(shù)（WBC）及血乳酸后，logistic回歸分析顯示，sTERM-1并非獨立的危險因素[RR=1.007，95%CI(0.999-1.016)，P0.05]。 結(jié)論 1.高水平的血清sTREM-1有助于早期識別膿毒癥，聯(lián)合監(jiān)測PCT和sTREM-1兩個指標(biāo)能提高診斷膿毒癥的效能。 2.嚴(yán)重膿毒癥患者血清sTREM-1水平高表達(dá)，與sepsis的嚴(yán)重程度相關(guān)，提示sTREM-1可作為評價膿毒癥疾病嚴(yán)重程度的客觀炎性指標(biāo)。 3.膿毒癥患者血清sTREM-1與IL-10及IL-6/IL-10均呈正相關(guān)，且與促炎因子IL-6的正相關(guān)性更高，提示sTREM-1在膿毒癥炎癥反應(yīng)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 .
【學(xué)位授予單位】：廣州醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R459.7

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 俞森洋;;嚴(yán)重膿毒癥和膿毒性休克的治療新進(jìn)展[J];臨床肺科雜志;2009年04期

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