熊 燚，王 健，魏 笛，馮 亞

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·論著·

血清S-100β水平和小兒危重病例量表評分預(yù)測手足口病并發(fā)腦炎患兒預(yù)后的價(jià)值研究

熊 燚，王 健，魏 笛，馮 亞

目的探討血清S-100β水平與小兒危重病例量表(PCIS)評分對手足口病(HFMD)并發(fā)腦炎患兒預(yù)后評估的價(jià)值。方法選取2012年12月—2014年12月遵義市第二人民醫(yī)院收治的HFMD患兒190例為研究對象，根據(jù)是否并發(fā)腦炎，將患兒分為HFMD并發(fā)腦炎組(60例)和HFMD普通組(130例)。另選取同期本院體檢中心體檢健康的兒童40例為對照組。收集HFMD并發(fā)腦炎患兒入院24 h內(nèi)各項(xiàng)資料，并依據(jù)PCIS對患兒進(jìn)行病情危重程度評分，據(jù)此將患兒分為非危重、危重、極危重?；純河谌朐汉?2 h、對照組體檢時(shí)抽取空腹靜脈血3 ml檢測S-100β水平及白細(xì)胞計(jì)數(shù)(WBC)，記錄HFMD患兒住院期間死亡情況。結(jié)果各組S-100β水平、WBC比較，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)；其中，HFMD并發(fā)腦炎組S-100β水平高于HFMD普通組及對照組，HFMD普通組與HFMD并發(fā)腦炎組WBC高于對照組(P<0.05)。HFMD并發(fā)腦炎組病死率為20%(12/60)，高于HFMD普通組的4.6%(6/130)(χ2=18.32，P<0.05)。不同危重程度的HFMD并發(fā)腦炎患兒S-100β水平及病死率比較，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)；其中危重者S-100β水平及病死率高于非危重者，極危重者S-100β水平及病死率高于非危重和危重者(P<0.01)。HFMD并發(fā)腦炎患兒S-100β水平與PCIS評分呈負(fù)相關(guān)(r=-0.478，P<0.01)。S-100β水平預(yù)測HFMD并發(fā)腦炎患兒死亡的受試者工作特征(ROC)曲線下面積為0.888〔95%CI(0.834,0.947),P<0.01〕,取臨界值為2.91 μg/L時(shí)，靈敏度為84.46%，特異度為82.50%。PCIS評分預(yù)測HFMD并發(fā)腦炎患兒死亡的ROC曲線下面積為0.873〔95%CI(0.808,0.938),P<0.01〕,取臨界值為69分時(shí)，靈敏度為83.10%，特異度為81.24%。結(jié)論血清S-100β水平和PCIS評分可特異反映HFMD并發(fā)腦炎患兒嚴(yán)重程度，對預(yù)測HFMD并發(fā)腦炎患兒預(yù)后具有較高的準(zhǔn)確性。

手足口??；腦炎；S-100β；小兒危重病例量表；預(yù)后

熊燚，王健，魏笛，等.血清S-100β水平和小兒危重病例量表評分預(yù)測手足口病并發(fā)腦炎患兒預(yù)后的價(jià)值研究[J].中國全科醫(yī)學(xué)，2016，19(23)：2780-2784.[www.chinagp.net]

XIONG Y,WANG J,WEI D,et al.Values of serum S-100β level and pediatric critical illness scale in predicting hand-foot-mouth disease children complicated with encephalitis[J].Chinese General Practice，2016，19(23)：2780-2784.

手足口病(hand-foot-mouth disease，HFMD)是兒科常見急性傳染病，主要由多種腸道病毒感染引起[1]，該病好發(fā)于5歲以下兒童，主要臨床表現(xiàn)為發(fā)熱及手、足、口腔等部位出現(xiàn)皰疹，一般預(yù)后良好，但少數(shù)患兒可出現(xiàn)心肌炎、腦炎等嚴(yán)重并發(fā)癥，致使患兒病死率顯著增加。其中，HFMD并發(fā)腦炎病情發(fā)展迅速，是導(dǎo)致患兒死亡的主要原因之一[2]。因此，早期特異評估患兒預(yù)后，對于改善其生存率具有重要臨床意義。S-100β主要由神經(jīng)膠質(zhì)細(xì)胞合成分泌，腦損傷時(shí)腦脊液及血清中S-100β水平明顯升高，其可特異性反映腦損傷的嚴(yán)重程度[3]。小兒危重病例量表(PCIS)是臨床中常用的針對危重患兒病情嚴(yán)重程度評分系統(tǒng)之一,但其在HFMD并發(fā)腦炎患兒病情評估及預(yù)后判斷的臨床意義尚不完全明確。本研究擬通過探討HFMD并發(fā)腦炎患兒血清S-100β水平、PCIS與預(yù)后的關(guān)系，為HFMD并發(fā)腦炎患兒的早期診斷及預(yù)后評估提供更有價(jià)值的指標(biāo)。

1　對象與方法

1.1研究對象選取2012年12月—2014年12月遵義市第二人民醫(yī)院收治的HFMD患兒190例為研究對象，其中男105例，女85例；平均月齡(20.8±12.2)月?；純壕显l(wèi)生部制定的《手足口病診療指南(2010年版)》[4]診斷標(biāo)準(zhǔn)。排除非HFMD腸道病毒感染者，近3個(gè)月內(nèi)有呼吸道感染、神經(jīng)系統(tǒng)疾病及腦腫瘤、腦創(chuàng)傷史者。根據(jù)是否有神經(jīng)系統(tǒng)受累如嗜睡、嘔吐、腦膜刺激征、腱反射減弱等表現(xiàn)，以及實(shí)驗(yàn)室檢查和影像學(xué)特征[4]，確診HFMD并發(fā)腦炎患兒60例(HFMD并發(fā)腦炎組)，余130例為HFMD普通組。另選取同期本院體檢中心體檢健康的兒童40例為對照組。受試者監(jiān)護(hù)人均簽署知情同意書，本研究方案由本院倫理委員會(huì)批準(zhǔn)。

1.2方法

1.2.1PCIS評分收集HFMD并發(fā)腦炎患兒入院24 h內(nèi)臨床資料，包括心率、血壓、呼吸頻率、氧分壓、pH值、Na+、K+、肌酐、血紅蛋白、胃腸系統(tǒng)(如應(yīng)激性潰瘍、應(yīng)激性潰瘍出血等)情況，每項(xiàng)計(jì)為4、6或10分，計(jì)算總分。危重程度評價(jià)標(biāo)準(zhǔn)：PCIS評分>80分為非危重，71～80分為危重，<71分為極危重。

1.2.2觀察指標(biāo)患兒于入院后12 h及對照組體檢時(shí)抽取空腹靜脈血3 ml檢測S-100β水平及血常規(guī)。血清S-100β水平采用酶聯(lián)免疫試劑盒進(jìn)行測定，試劑盒購自瑞士羅氏公司，操作過程嚴(yán)格按說明書進(jìn)行，血常規(guī)采用全自動(dòng)生化分析儀測定。記錄HFMD患兒住院期間死亡情況。

2　結(jié)果

2.1各組一般資料及血清S-100β水平、WBC比較各組性別、月齡比較，差異均無統(tǒng)計(jì)學(xué)意義(P>0.05)。各組S-100β水平、WBC比較，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)；其中，HFMD并發(fā)腦炎組S-100β水平高于HFMD普通組及對照組，HFMD普通組及HFMD并發(fā)腦炎組WBC高于對照組，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05，見表1)。

表1各組一般資料及血清S-100β水平、WBC比較

Table 1Comparison of the general data and serum levels of S-100β,WBC among each group

組別例數(shù)性別(男/女)月齡(月)S-100β(μg/L)WBC(×109/L)對照組4024/1620.6±5.60.45±0.156.28±0.93HFMD普通組13071/5921.0±6.20.51±0.1811.32±0.92aHFMD并發(fā)腦炎組6034/2620.8±5.93.54±0.57ab11.72±0.73aF(χ2)值0.88c0.9721.4524.74P值>0.05>0.05<0.01<0.01

注：HFMD=手足口病，WBC=白細(xì)胞計(jì)數(shù)；與對照組比較，aP<0.01；與HFMD普通組比較，bP<0.01；c為χ2值

2.2各組病死率比較HFMD普通組治愈124例，治愈率為95.4%，6例患兒因病情加重死亡，病死率為4.6%。HFMD并發(fā)腦炎組治愈48例，治愈率為80.0%，死亡12例，病死率為20.0%。HFMD并發(fā)腦炎組患兒病死率高于HFMD普通組，差異有統(tǒng)計(jì)學(xué)意義(χ2=18.32，P<0.05)。

2.3不同危重程度的HFMD并發(fā)腦炎患兒S-100β水平及病死率比較不同危重程度的HFMD并發(fā)腦炎患兒S-100β水平及病死率比較，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)；其中危重者S-100β水平及病死率高于非危重者，極危重者S-100β水平及病死率高于非危重和危重者，差異均有統(tǒng)計(jì)學(xué)意義(P<0.01，見表2)。

表2不同危重程度的HFMD并發(fā)腦炎患兒S-100β水平及病死率比較

Table 2Comparison of the S-100β level and fatality rate among different critical illness degrees in the HFMD children complicated with encephalitis

危重程度例數(shù)S-100β(μg/L)病死率〔n(%)〕非危重262.74±0.341(3.8)危重243.92±0.32a4(16.7)a極危重105.46±0.25ab7(7/10)abF(χ2)值8.467.84cP值<0.05<0.05

注：與非危重者比較，aP<0.01；與危重者比較，bP<0.01；c為χ2值

2.4HFMD并發(fā)腦炎不同預(yù)后患兒S-100β水平及PCIS評分比較HFMD并發(fā)腦炎死亡患兒S-100β水平高于存活者，PCIS評分低于存活者，差異有統(tǒng)計(jì)學(xué)意義(P<0.05，見表3)。

Table 3Comparison of the S-100β level and PCIS score between different clinical prognosis in the HFMD children complicated with encephalitis

預(yù)后例數(shù)S-100β(μg/L)PCIS評分(分)存活483.12±0.8377±6死亡125.82±1.1261±4t值4.538.73P值<0.01<0.01

注：PCIS=小兒危重病例量表

2.5血清S-100β水平與PCIS評分的相關(guān)性分析HFMD并發(fā)腦炎患兒S-100β水平與PCIS評分呈負(fù)相關(guān)(r=-0.478，P<0.01,見圖1)。

注：PCIS=小兒危重病例量表

圖1HFMD并發(fā)腦炎患兒S-100β水平與PCIS評分相關(guān)性的散點(diǎn)圖

Figure 1Scatter diagram of the correlation between S-100β level and PCIS score of HFMD children complicated with encephatilis

2.6ROC曲線分析S-100β水平預(yù)測HFMD并發(fā)腦炎患兒死亡的ROC曲線下面積為0.888〔95%CI(0.834,0.947),P<0.01〕,取臨界值為2.91 μg/L時(shí)，靈敏度為84.46%，特異度為82.50%，陽性似然比為4.83，陰性似然比為0.19，Youden′s指數(shù)為66.96%(見圖2)。PCIS評分預(yù)測HFMD并發(fā)腦炎患兒死亡的ROC曲線下面積為0.873〔95%CI(0.808,0.938),P<0.01〕,取臨界值為69分時(shí)，靈敏度為83.10%，特異度為81.24%，陽性似然比為4.43，陰性似然比為0.21，Youden′s指數(shù)為64.34%(見圖3)。

圖2　S-100β水平預(yù)測HFMD并發(fā)腦炎患兒死亡的ROC曲線

Figure 2The ROC curve of the S-100β level for predicting death on the HFMD children complicated with encephalitis

圖3　PCIS評分預(yù)測HFMD并發(fā)腦炎患兒死亡的ROC曲線

Figure 3The ROC curve of the PCIS score for predicting death on the HFMD children complicated with encephalitis

3　討論

HFMD是由腸道病毒引起的兒童急性傳染病，大部分患兒病情較輕，預(yù)后良好，但少數(shù)HFMD重癥患兒可并發(fā)中樞神經(jīng)系統(tǒng)損害，即腦炎的發(fā)生，從而導(dǎo)致其病死率顯著升高[5]。有研究報(bào)道，HFMD并發(fā)腦炎患兒較普通患兒病死率增加4.8%，且神經(jīng)系統(tǒng)損害后遺癥發(fā)生率升高14.3%[6]。因此，就HFMD并發(fā)中樞神經(jīng)系統(tǒng)損害的患兒，及早做出診斷，準(zhǔn)確判斷其預(yù)后，對于降低其病死率及致殘率具有重要的臨床意義。

有研究證實(shí)，中樞神經(jīng)系統(tǒng)損傷時(shí)血清及腦脊液中S-100β水平顯著升高，其可特異性判斷中樞神經(jīng)系統(tǒng)損傷的嚴(yán)重程度及預(yù)后，從而受到廣泛關(guān)注[7]。S-100β是主要由神經(jīng)膠質(zhì)細(xì)胞合成及分泌的鈣結(jié)合蛋白，具有調(diào)節(jié)能量代謝、維持細(xì)胞膜完整性及參與細(xì)胞內(nèi)信號傳導(dǎo)的作用。生理情況下，腦脊液及血液中S-100β水平較低，但中樞神經(jīng)系統(tǒng)受到損傷時(shí)，神經(jīng)膠質(zhì)細(xì)胞膜結(jié)構(gòu)完整性被破壞，S-100β從細(xì)胞質(zhì)釋放入腦脊液，再通過已破壞的血-腦脊液屏障進(jìn)入外周血[8]。因此，血清S-100β水平可作為評判中樞神經(jīng)系統(tǒng)損傷的特異性標(biāo)志物，同時(shí)其水平的變化可反映中樞神經(jīng)系統(tǒng)損傷的程度及預(yù)后情況。本研究結(jié)果顯示，入院24 h內(nèi)，HFMD并發(fā)腦炎患兒血清S-100β水平明顯高于普通HFMD患兒及健康兒童，而普通HFDM患兒與健康兒童間無差異，說明HFMD并發(fā)腦炎患兒中樞神經(jīng)系統(tǒng)受到損害。同時(shí)，HFMD患兒WBC明顯高于健康兒童，說明其體內(nèi)存在明顯的炎性反應(yīng)，但WBC在HFMD并發(fā)腦炎組與HFMD普通組間無明顯區(qū)別，提示W(wǎng)BC缺乏特異性，不能完全反映病情嚴(yán)重程度。已有相關(guān)研究顯示，WBC對于評估炎癥感染嚴(yán)重程度特異性較低，并且無法準(zhǔn)確反映其預(yù)后情況，這可能與外周血中WBC個(gè)體差異大，不穩(wěn)定即易受各種因素影響有關(guān)[9]。血清S-100β水平在非危重、危重和極危重患兒間呈升高趨勢，其與PCIS評分呈明顯的負(fù)相關(guān)，提示HFMD并發(fā)腦炎患兒病情越危重，其血清S-100β水平越高，死亡風(fēng)險(xiǎn)越高，預(yù)后也越差。已有研究證實(shí)，PCIS評分與患者病死率呈負(fù)相關(guān)[10]。本研究發(fā)現(xiàn)，HFMD并發(fā)腦炎死亡患兒血清S-100β水平高于存活患兒，并且PCIS評分低于存活患兒。S-100β水平及PCIS評分預(yù)測HFMD并發(fā)腦炎患兒死亡的ROC曲線下面積>0.850，可作為判斷預(yù)后的有效指標(biāo)，其中，S-100β取臨界值為2.91 μg/L和PCIS評分取臨界值為69分時(shí)對HFMD并發(fā)腦炎患兒預(yù)后不良的診斷準(zhǔn)確性較高。

綜上所述，血清S-100β水平及PCIS評分可特異反映HFMD并發(fā)腦炎患兒病情嚴(yán)重程度及預(yù)后，其對于指導(dǎo)患兒治療，降低病死率具有重要臨床意義。目前，HFMD并發(fā)腦炎患兒的早期診斷及預(yù)后判斷尚缺乏有效的標(biāo)準(zhǔn)。通過檢測HFMD并發(fā)腦炎患兒血清S-100β水平，同時(shí)結(jié)合PCIS評分可有效判斷其病情的嚴(yán)重程度及預(yù)后。本研究沒有進(jìn)一步對HFMD并發(fā)腦炎患兒腦脊液、腦電圖等方面做同步檢測及觀察，且樣本量有限，研究結(jié)論可能存在一定的局限性，故需進(jìn)一步加大樣本量、多中心綜合分析。

作者貢獻(xiàn)：熊燚進(jìn)行課題設(shè)計(jì)與實(shí)施、資料收集整理、成文并對文章負(fù)責(zé)；王健、魏笛進(jìn)行課題設(shè)計(jì)與實(shí)施、評估、資料收集整理；馮亞進(jìn)行質(zhì)量控制及審校。

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(本文編輯：吳立波)

Values of Serum S-100β Level and Pediatric Critical Illness Scale in Predicting Hand-foot-mouth Disease Children Complicated With Encephalitis

XIONGYi,WANGJian,WEIDi,FENGYa.

DepartmentofEmergency,theSecondPeople′sHospitalofZunyi,Zunyi563000,China

WANGJian，DepartmentofEmergency,theSecondPeople′sHospitalofZunyi,Zunyi563000,China；E-mail：wjzy02@163.com

ObjectiveTo investigate the value of serum S-100β level and pediatric critical illness scale(PCIS) in prognostic evaluating the hand-foot-mouth disease(HFMD) children complicated with encephalitis.Methods190 children with HFMD,whoP<0.05);the S-100β level of HFMD complicated with encephalitis group was higher than that of the HFMD general group and the control group,and the WBC of the HFMD general group and the HFMD complicated with encephalitis group was higher than that of the control group,which showed significant differences(P<0.05).The fatality rate of the HFMD complicated with encephalitis group was 20%(12/60),which was higher than 4.6%(6/130) in the HFMD general group,which showed significant differences(χ2=18.32，P<0.05).There was significant difference in the S-100β level and the fatality rate of the HFMD children complicated with encephalitis among different critical illness degrees(P<0.05);the S-100β level and the fatality rate of the critical illness cases were higher than those of the non-critical illness cases,and the S-100β level and the fatality rate of extremely critical illness cases were higher than those of the non-critical illness cases and critical illness cases,which showed significant differences(P<0.01).The S-100β level of the HFMD children complicated with encephalitis was negatively correlated with the score of PCIS(r=-0.478,P<0.01).The area under ROC curve of the HFMD children complicated with encephalitis,predicted as death through S-100β level,was 0.888〔95%CI(0.834,0.947),P<0.01〕,when the taken critical value was 2.91 μg/L,the sensitivity and the specificity were 84.46% and 82.50% respectively.The area under ROC curve of the HFMD children complicated with encephalitis,predicted as death through PCIS,was 0.873〔95%CI(0.808,0.938),P<0.01〕,and when the critical value was 69,the sensitivity and the specificity were 83.10% and 81.24% respectively.ConclusionThe serum S-100β level and PCIS score can reflect the severity degree of the HFMD children complicated with encephalitis,and have high accuracy in predicting the prognosis of the HFMD children complicated with encephalitis.

treatment in the Second People′s Hospital of Zunyi from December 2012 to December 2014,were enrolled as the research objects in this study.Based on whether children were complicated with encephalitis,we divided the children into HFMD complicated with encephalitis group(60 cases) and HFMD general group(130 cases).Other 40 children,who were regarded as healthy after physical examination in the physical examination center of this hospital at the same period,were included as the control group.We collected necessary information of the HFMD children complicated with encephalitis within the 24-hour after their being admitted into the hospital,and scored their critical illness condition based on PCIS，then divided the children as non-critical illness cases,critical illness cases and extremely critical illness cases.S-100β and WBC were detected by the extracted 3 ml fasting blood,which were got from HFMD children 12 h after their being admitted into the hospital and from the physical examination of control group.Also HFMD children′s death duration of hospital stay was recorded.ResultsThere were significant difference in S-100β level and WBC among the different groups(

Hand-foot-mouth disease;Encephalitis;S-100β;Pediatric critical illness scale;Prognosis

貴州省衛(wèi)生廳科學(xué)技術(shù)基金項(xiàng)目(gzwkj2013-1-060)；遵義市科學(xué)技術(shù)基金項(xiàng)目[遵義市科合社字(2013)37號]

563000貴州省遵義市第二人民醫(yī)院急診科(熊燚，王健，魏笛)；貴州省遵義市紅花崗區(qū)疾病預(yù)防控制中心(馮亞)

王健，563000貴州省遵義市第二人民醫(yī)院急診科；E-mail：wjzy02@163.com

R 512.5

A

10.3969/j.issn.1007-9572.2016.23.008

2015-06-02；

2016-04-27)