【作者】 王丽平；

【导师】 孙锟；

【作者基本信息】 上海交通大学 ， 儿内科， 2014， 硕士

【摘要】 第一部分:Kobayashi评分体系在单中心川崎病患者中的应用目的探讨Kobayashi评分体系预测单中心IVIG(intravenous immunoglobulin)无反应型KD(Kawasaki disease)患者的效能。方法回顾性分析我院(上海交通大学医学院附属新华医院)2001年1月至2014年1月期间诊断明确的624例KD患儿的临床资料,并将其分为IVIG敏感组和IVIG无反应组;应用Kobayashi评分体系对所有患儿进行评分,并验证Kobayashi评分体系中各个危险因素在我院KD患者中有无统计学意义及评分后危险分层有无统计学意义,最后分析其预测中国IVIG无反应型KD患者的效能。结果624例KD患者中,IVIG敏感组547例,IVIG无反应组77例。应用Kobayashi评分体系对所有624例KD患者进行危险分层,高危组(4~11分)113例,低危组(0~3分)511例,高危组IVIG无反应的发生率明显高于低危组;Kobayashi评分体系的灵敏度为39%、特异度为85%、误诊率为15%、漏诊率为61%、Kappa值为0.198。此外,χ2检验结果显示,Kobayashi评分体系中C反应蛋白(C reaction protein,CRP)≥100mg/L、外周血中性粒细胞百分比≥80%、血小板≤300×109/L和血钠≤133mmol/L是IVIG无反应的危险因素。结论Kobayashi评分体系预测IVIG无反应型KD患者的效能不高。此外,该评分体系中CRP≥100mg/L、外周血中性粒细胞百分比≥80%、血小板≤300×109/L和血钠≤133mmol/L被证实是IVIG无反应型KD的危险因素。第二部分:免疫球蛋白无反应型川崎病患者危险因素的研究目的探讨IVIG无反应型KD患者的危险因素。方法回顾性分析我院(上海交通大学医学院附属新华医院)2001年1月至2014年1月期间明确诊断的624例KD患儿的临床资料,并将其分为IVIG敏感组和IVIG无反应组;对IVIG初始治疗前的相关因素进行单因素分析(t检验),从而确定IVIG无反应型KD患者的独立危险因素;进而利用受试者工作特征(receiver operating characteristic,ROC)曲线确定独立危险因素的最佳临界值及曲线下面积(the area under the curve,AUC)。结果624例KD患者中,IVIG敏感组547例,IVIG无反应组77例;单因素分析结果显示:C反应蛋白(C reaction protein,CRP)、中性粒细胞百分比(N%)、红细胞比容(HCT)、血清白蛋白、血小板计数(Platelet count)、血清钠、总胆红素、pro-BNP、IL-2R和IL-10是IVIG无反应型KD患者的独立危险因素;以上危险因素的最佳临界值分别为:58.5(mg/L)、77.75(%)、29.65(%)、33.35(g/L)、322.5(109/L)、132.9(mmol/L)、7.75(μmol/L)、687.9(pg/ml)、3648.5(U/ml)和35.6(pg/ml)。结论我们证实CRP、N%、HCT、血清白蛋白、血小板计数、血清钠、总胆红素、pro-BNP、IL-2R和IL-10是IVIG无反应的独立危险因素。第三部分免疫球蛋白无反应型川崎病危险程度评分体系的探讨目的建立IVIG无反应型KD患者危险程度的简单评分体系。方法将本研究第二部分中的危险因素进行Logistic逐步回归分析,筛选出能够进入回归方程的危险因素,从而建立Logistic回归模型;根据Logistic回归系数对各危险因素分别赋值,建立简单评分体系,进而利用ROC曲线及回顾性验证评价简单评分体系预测IVIG无反应的效能。结果Logistic逐步回归分析结果显示:HCT、血清白蛋白、血小板计数和总胆红素最终进入回归方程;Logistic回归模型为:P=ey/(1+ey),y=∑βx×Xx,y=0.864×HCT+0.729×血小板计数+0.801×血清白蛋白+1.275×总胆红素。最终建立的预测IVIG无反应危险程度的简单评分体系为:①HCT≤29.65%(0.9分);②血小板计数≤322.5×109/L(0.7分);③白蛋白≤33.35g/L(0.8分);④总胆红素≥7.75μmol/L(1.3分)。该简单评分体系的总分为3.7分,0~1.4分为低危组,1.5~3.7分为高危组。该简单评分体系的ROC曲线下面积、灵敏度和特异度分别为0.772、83.1%和57.0%。结论我们建立的简单评分体系在预测我院IVIG无反应型KD患者中有较高的灵敏度(83.1%),但特异度较低(57.0%)。更多还原

【Abstract】 Part I: The application of Kobayashi scoring system inpatients with Kawasaki disease in a single centerObjective To investigate the efficiency of Kobayashi scoring system in prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease.Method We retrospectively reviewed the clinical records of 624 KD patients in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2001 to January 2014, and divided them into IVIG-sensitive group and IVIG-irresponsive group.Kobayashi scoring system was applied to score for all the patients, and we would verify that all risk factors of Kobayashi scoring system in 624 KD patients and the risk stratification whether there is statistical significance. At last, the efficiency of Kobayashi scoring system in prediction of intravenous immunoglobulin unresponsiveness in Chinese patients with Kawasaki disease was analyzed.Results There were 547 cases in IVIG-sensitive group and 77 cases in IVIG-irresponsive group. According to Kobayashi Scoring system, 113 cases were divided into high-risk group(4~11 scores), and 511 cases into low-risk group(0~3 scores), and the incidence of intravenous immunoglobulin unresponsiveness in high-risk group was significantly higher than that in low-risk group. The sensitivity, specificity, misdiagnosis rate,rate of missed diagnosis and Kappa value of Kobayashi scoring system were 39%, 85%, 15%,61% and 0.198 respectively. In addition, χ2tests showed that CRP≥100mg/L, N%≥80%,Platelet ≤300×109/L and serum sodium ≤ 133mmol/L were the risk factors for intravenous immunoglobulin unresponsiveness.Conclusion The efficiency of Kobayashi scoring system in prediction of intravenous immunoglobulin unresponsiveness in our patients with Kawasaki disease was not high. In Kobayashi scoring system, CRP ≥ 100mg/L, N% ≥ 80%, Platelet ≤ 300×109/L and serum sodium≤133mmol/L were the risk factors for intravenous immunoglobulin unresponsiveness.Part II: Study on risk factors of patients with Kawasakidisease unresponsiveness to intravenous immunoglobulinObjective To investigate the risk factors of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease.Method We retrospectively reviewed the clinical records of 624 KD patients in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2001 to January 2014, and divided them into IVIG-sensitive group and IVIG-irresponsive group.Single factor analysis was performed in related factors before IVIG treatment to identify independent predictors of IVIG unresponsiveness. Receiver operating characteristic(ROC)curves were drawn to determine the optimal cut-off value and the area under the curve(AUC)of the independent predictors.Results There were 547 cases in IVIG-sensitive group and 77 cases in IVIG-irresponsive group. Single factor analysis showed that CRP, N%, HCT, serum albumin,platelet count, serum sodium, total bilirubin, pro-BNP, IL-2R and IL-10 were independent predictors of IVIG unresponsiveness, and the optimal cut-off value was 58.5(mg/L), 77.75(%),29.65(%), 33.35(g/L), 322.5(109/L), 132.9(mmol/L), 7.75(μmol/L),687.9(pg/ml), 3648.5(U/ml)and 35.6(pg/ml)respectively.Conclusion Our study confirmed that CRP, N%, HCT, serum albumin, platelet count,serum sodium, total bilirubin, pro-BNP, IL-2R and IL-10 were independent predictors of IVIG unresponsiveness.Part III: The investigation on risk scoring system in patientswith Kawasaki disease unresponsiveness to intravenousimmunoglobulinObjective To investigate and establish a new risk scoring system of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease.Method Logistic stepwise regression analysis was conducted among risk factors according to the part II to screen out high risk factors and build a logistic regression model. A simple scoring system was constructed according to the regression coefficient. The efficiency of the simple scoring system was evaluated by ROC curve and retrospective validation.Results Among the seven risk factors, HCT, serum albumin, platelet count and total bilirubin were eventually included into logistic regression model. The logistic regression model was constructed:P=ey /(1+ey),y=0.864×HCT+0.729×platelet count+0.801×serum albumin+1.275×total bilirubin. A simple scoring system was constructed on the basis of the logistic regression model:①HCT≤29.65%(0.9 points); ②platelet count≤322.5×109/L(0.7points); ③serum albumin≤33.35g/L(0.8 points); ④total bilirubin≥7.75μmol/L(1.3 points).Total scores were 3.7points, two risk strata were identified:low-risk group, with scores of 0 to1.4 points; high-risk group, with scores of 1.4 to 3.7 points. The area under the curve(AUC),the sensitivity and specificity of the simple scoring system were 0.772, 83.1% and 57.0%respectively.Conclusion Our simple scoring system showed better sensitivity but low specificity.Our study needs multicenter, large sample and prospective studies to further validate and perfect.更多还原