肺炎支原体肺炎患儿气道黏液栓形成的危险因素

目的 探讨肺炎支原体肺炎(MPP)患儿气道黏液栓形成的危险因素.方法 回顾性分析2012年5月至2014年1月收治的行纤维支气管镜治疗的116例MPP患儿的临床资料.根据患儿纤维支气管镜下黏膜损害情况分为黏液栓组(67例)和对照组(49例),对两组患儿的性别、发病年龄、热程、有无胸腔积液、血常规白细胞计数及中性粒细胞比例、C反应蛋白(CRP)、乳酸脱氢酶(LDH)、发病后开始使用大环内酯类药物时间、首次行纤维支气管镜时间等,进行单因素分析及logistic回归分析;绘制受试者工作特征(ROC)曲线,评价logistic回归模型的预测能力.结果 单因素分析结果显示,黏液栓组的年龄、总热程、CRP和LDH水平、合并胸腔积液比例均高于对照组,差异有统计学意义(P均<0.05).logistic回归分析显示,年龄≥3岁(OR=7.45,95%CI:1.52~36.71),热程≥10 d(OR=4.01,95%CI:1.58~10.20), CRP≥40 mg/L(OR=5.41,95%CI:1.87~15.67)和LDH≥350 U/L(OR=3.63,95%CI:1.35~9.75)是MPP患儿气道黏液栓形成的独立危险因素;ROC曲线下面积(AUC)为0.846(95%CI:0.773~0.919,P=0.000).结论 当MPP患儿年龄≥3岁、热程≥10 d、CRP≥40 mg/L、LDH≥350 U/L时,有气道内黏液栓形成的可能.     

传染性单核细胞增多症患儿T细胞免疫功能变化及匹多莫德干预治疗的研究

目的 探讨传染性单核细胞增多症(IM)T细胞亚群的变化及匹多莫德干预治疗的有效性.方法 将60例IM患儿随机分为两组,各30例,IM对照组急性期予以更昔洛韦抗病毒及对症等常规治疗;IM干预组在常规治疗的基础上加用免疫调节剂匹多莫德,疗程2周.另选择30例正常儿童作为健康对照组.检测治疗前后T细胞亚群的变化.结果 与健康对照组比较,IM患儿各种T细胞比例均有明显变化(P＜0.05).IM对照组患儿治疗前后CD3、CD4、CD8 T细胞及CD4/CD8比值差异无显著性(P＞0.05);IM干预组患儿治疗后CD3、CD8 T细胞比例降低,CD4 T细胞比例及CD4/CD8比值明显升高,差异有显著性(P＜0.05).IM干预组临床症状及体征较IM对照组消失快(P＜0.05);IM干预组平均住院日为(9.2±4.3)d,较IM对用组(13.8±5.1)d明显缩短(t=-4.24,P＜0.05).结论 IM患儿在急性期治疗中加用免疫调节剂匹多莫德能缩短IM的病程,能促进T细胞免疫功能的尽快恢复.     

严重脓毒症患儿白蛋白水平与危重度关系研究

目的探讨严重脓毒症患儿的低蛋白血症与其病情危重度及预后的关系。方法回顾性收集湖南省儿童医院重症监护病房(PICU)2015年6月1日至2017年6月1日住院治疗的119例严重脓毒症患儿的资料,依据入住PICU 24 h内的血清白蛋白水平分为重度低蛋白血症组(≤25 g/L),中度低蛋白血症组(~30 g/L),轻度低蛋白血症组(~35 g/L)和正常白蛋白组(35 g/L)。分析不同白蛋白水平与其危重度及预后的变化。结果严重脓毒症患儿低蛋白血症发生率为71.43%。(1)严重脓毒症患儿白蛋白水平越低,器官衰竭数目越多,病死率越高(r=-0.457,P=0.000)。(2)单因素分析发现,随着血清白蛋白水平的降低,儿童死亡危险因素评分(PRISMⅢ)呈显著升高趋势,儿童危重病例评分(PICS)呈下降趋势;机械通气时间、入住PICU时间和住院时间均呈升高趋势。(3)多因素分析显示,白蛋白水平≤25 g/L、器官衰竭数目≥3个为严重脓毒症患儿预后的独立危险因素。结论严重脓毒症患儿血清白蛋白水平与器官衰竭数目及病情危重程度呈负相关,白蛋白水平越低,病情越严重,预后越差。     

儿童传染性单核细胞增多症临床特点与发病年龄的关系:附312例分析

目的 探讨儿童传染性单核细胞增多症(IM)的临床特点与发病年龄的关系.方法 312例IM儿童分成0 ～ 3岁、～ 6岁、～ 15岁3组,进行回顾性分析.结果 IM儿童中6岁以下占74.4%,春季和秋季高发.0 ～ 3岁组发热天数平均(7.08 ± 3.31)d,～ 6岁组平均(7.91 ± 3.78)d,～ 15岁组平均(12.38 ± 4.14)d,～ 15岁组与其他组差异有统计学意义(P ＜ 0.01).各年龄组咽峡炎(100%)、淋巴结肿大(82.69%)、肝肿大(66.7%)、脾肿大(62.5%)、鼻塞(42.3%)组之间差异无统计学意义(P ＞ 0.05);眼睑浮肿(36.2%)～ 15岁组明显低于其他组(P ＜ 0.05),皮疹(23.1%)在0 ～ 3岁组多见(P ＜ 0.05).外周血白细胞年幼儿升高明显,异型淋巴细胞年幼儿偏低,血清ALT、AST在年长儿偏高,血清LDH在各年龄组均呈高值,血清嗜异凝集试验年长儿阳性率高.结论儿童IM某些临床特点与发病年龄有关,应予以重视,以提高确诊率.     

中国川崎病患儿并发冠状动脉病变高危因素的Meta分析

目的 探讨中国川崎病患儿并发冠状动脉病变的高危因素.方法 检索包括中国学术文献总库、中文科技期刊数据库、万方期刊及学位论文数据库、中国生物医学文献数据库,并辅以文献追溯、手工检索等方法,收集2000年1月至2009年12月国内公开发表的文章和学位论文中关于川崎病并发冠状动脉病变高危因素的临床资料,对所纳入的研究数据采用Coehrane协作网提供的Review Manager软件(Revman4.2)进行统计分析.根据文献异质性检验结果,进行固定效应模型或随机效应模型的Meta分析.计算各指标的比值比(OR)及其95%的可信区间(CI).结果 共纳入文献20篇,提取资料行统计分析结果示:发病年龄≤1岁[OR=1.58,95%CI(1.23,2.04),P=0.0004],男性[OR=1.48,95%CI(1.29,1.71),P＜0.000 01],WBC＞20×109/L[OR=1.73,95%CI(1.32,2.26),P＜0.0001],CRP＞100 mg/L[OR=2.37,95% CI(1.49,3.77),P=0.0003],发热＞10 d[OR=3.23,95%CI(2.08,5.02),P＜0.000 01],丙种球蛋白使用时发病时间＞10 d[OR=2.50,95%CI(1.98,3.16),P＜0.000 01],差异均有统计学意义.ESR＞100 mm/1 h[OR=1.34,95%CI(1.02,1.75),P=0.03],差异有统计学意义,但结论不稳定.PLT＜300×109/L[OR=0.85,95%CI(0.62,1.15),P=0.29],差异无统计学意义.结论 目前中国川崎病患儿发生冠状动脉病变的主要高危因素为发病年龄≤1岁、性别为男性、WBC＞20×109/L、CRP＞100 mg/L、发热天数＞10 d、丙种球蛋白使用时发病时间＞10 d.

Abstract：

Objective Coronary artery lesion (CAL)is a serious complication of Kawasak disease (KD).Whether there is CAL and the severity arc the most critical factors of the prognosis of KD.The incidence of KD is currently increasing year by year.KD has replaced rheumatic fever as the main entity of acquired heart disease of children.This study aimed to identify risk factors of CAL secondary to KD and take early interventions to prevent CAL or reduce its incidence.MethOd Literature search was performed at Chinese Academic Literature Main Database,Chinese Science and Technology Periodical Database,Wanfang Periodicals and Dissertation Database.and the Chinese Biomedical Literature Database comprehensively,besides,retrospective retrieval and manual retrieval were also performed from the domestic public actions and the dissertations dating from January,2000 to December, 2009.RayMan 4.2 provided by Cochrane was used for meta analysis.Fixed or random model was selected according to the results of heterogeneity test.Sensitivity analysis was done according to the different results.The publication bias was evaluated by funnel plots.Odds ratio(OR)and 95% confidence interval(CI)were estimated in the dissertation.Result Twenty studies were confirmed to be eligible.A11 the 20 studies were retrospective.OR and 95%CI of the risk factors were as follows:age≤1 year,OR=1.58,and 95%CI(1.23,2.04),P=0.0004;male gender, OR=1.48,95%CI(1.29,1.71),P＜0.000 01;WBC＞20×109/L,OR=1.73,95% CI(1.32,2.26),P＜0.000l;C-reactive protein(CRP)＞100 mg/L,OR=2.37,95%CI(1.49,3.77),P=0.0003:fever duration＞10 d,OR=3.23,95%CI(2.08,5.02),P＜0.000 01;use of intravenous gamma globulin(IVIG)＞10 d,OR=2.50,95%CI(1.98,3.16),P＜0.000 01.Conclusion The high risk factors for coronary artery lesion secondary to Kawasaki disease are age≤1 year,male,WBC＞20×109/L,CRP＞100 mg/L,fever duration＞10 d,and use of intravenous gamma globulin(IVIG)＞10 d.     

血清学指标对噬血细胞综合征患儿死亡预测价值的临床研究

目的 探讨噬血细胞综合征(hemophagocytic syndrome,HPS)患儿诊断时的血清学指标与死亡的关系及对死亡的早期预测价值.方法 采用回顾性病例对照研究方法,对2005年7月至2012年7月广州市妇女儿童医疗中心收治的108例HPS患儿血清学、病理学改变及预后资料进行系统分析.按随访患儿的生存情况分为存活组和死亡组,应用COX模型对可能与HPS死亡相关的危险因素进行分析;应用决策树探讨各指标对HPS死亡的预测价值.结果 108例HPS患儿中,死亡33例,病死率30.6％,且90.3％在发病后8周内死亡.多因素分析显示白细胞＜5×109/L(HR =9.08,95％ CI3.07 ～26.87)、血红蛋白＜80 g/L(HR =6.15,95％ CI 1.68 ～ 22.49)、白蛋白＜28g/L(HR=4.63,95％CI 1.12 ～7.39)、铁蛋白＞1 100 μg/L(HR =3.05,95％ CI 1.28 ～ 16.75)、甘油三酯≥4 mmol/L(HR=2.88,95％CI 1.51 ～8.60)、凝血酶原时间≥16s(HR=3.60,95％CI 1.28 ～7.24)和发热持续2周以上(HR =5.39,95％CI 1.97～14.66)是造成HPS患儿死亡的独立危险因子.决策树分析显示白细胞＜5×109/L合并血红蛋白＜80 g/L的情况下患儿死亡概率达100％;即使在白细胞≥5×109/L的情况下,若合并发热持续2周以上且总胆固醇≥4 mmol/L,死亡概率亦达66.7％.结论 发病后最初8周是治疗HPS的关键期,HPS患儿死亡与多种因素相关,合并白细胞＜5×109/L且血红蛋白＜80 g/L时,病情极其凶险,及早诊断并采取有针对性的治疗对降低HPS患儿病死率至关重要.     

手足口病的临床特征及中枢神经系统并发症高危因素分析

目的 探讨不同肠道病毒所致手足口病的临床特征及发生中枢神经系统并发症(CNSC)的高危因素.方法 分析272例手足口病患儿,其中肠道病毒71型(EV71)感染92例、柯萨奇病毒组16型(CA16)感染31例、非EV71非CA16感染149例.有CNSC 42例,无CNSC 230例.比较分析不同肠道病毒感染患儿的临床特征,同时对伴有CNSC者进行多因素Logistic分析.结果 3组不同肠道病毒感染患儿的年龄、外周血自细胞计数(WBCC)、C-反应蛋白(CRP)、血糖(BG)水平差异无显著性(P＞0.05);而体温、热程、中性粒细胞百分比(NP)、肢体抖动(MJOL)及CNSC发生率3组间差异有显著性(P＜0.05).多因素Logistic分析发现,MJOL、WBCC＞1.2×109/L、EV71感染是CNSC的高危因素,而且MJOL具有最大相对危险度(OR=242.848,P=0.000).Logistic线性预测因子Z=-12.825+5.492(MJOL)+2.624(WBCC＞1.2×109/L)+1.900(FV71感染).结论 (1)EV71感染者比其他肠道病毒感染者有更高体温、NP、CNSC及MJOL发生率,热程比CA16感染者更长.(2)FV71感染、MJOL、WBCC＞1.2 x109/L是手足口病发生CNSC的高危因素,尤其MJOL对预测CNSC有重要意义.     

可溶性白细胞介素-2受体检测在儿童EB病毒感染相关疾病中的应用价值

目的探讨可溶性白细胞介素(白介素)-2受体检测在儿童EB病毒(EBV)感染相关疾病鉴别诊断中的应用价值。方法将72例患儿分为IM组、IM转化EBV相关的噬血细胞淋巴组织细胞增生症(EBV-HLH)组和EBV-HLH组;采用酶联免疫吸附试验(ELISA)分别检测患儿血清可溶性白介素-2受体和EBV抗体四项(EBV壳抗原VCA-IgM、VCA-IgG和EBV早期抗原EA-IgG、EBV核抗原-1 EBNA-1-IgG),荧光实时定量PCR检测患儿血浆EBV-DNA的表达,流式细胞术分析淋巴细胞亚群(CD3,CD4,CD8,CD19,CD56)。结果 72例患儿急性期可溶性白介素-2受体水平均超过2 400 U/ml;IM转化组在急性期可溶性白介素-2受体水平仅轻度增高(4 320 U/ml),与IM组(3 310 U/ml)无明显差异,治疗后却明显增高(8 970 U/ml),并接近EBV-HLH组水平(11 230U/ml);EBV抗体四项显示IM转化组和EBV-HLH组在治疗后VCA-IgG和EA-IgG仍然持续高滴度,同时EBV核抗原-1-IgG仍持续阴性;三组急性期都有EBV-DNA拷贝数从低拷贝至高拷贝的病例,治疗后IM转化组和EBV-HLH组仍可检测到EBV-DNA(3×103~4×105copies/ml);IM转化组和EBV-HLH组CD8+细胞在治疗后仍持续较高水平[(61.32±4.63)%,(68.36±4.32)%],并同时出现NK细胞(CD56+)比例下降[(9.23±3.28)%,(10.52.±3.34)%]。结论结合EBV抗体、EBV-DNA和淋巴细胞亚群检测,可溶性白介素-2受体检查有可能成为追踪观察EBV感染相关疾病的指标之一。     

EB病毒相关性噬血细胞综合征的临床特征及外周血淋巴细胞亚群的变化

目的 分析EB病毒相关性噬血细胞综合征(EBV-AHS)患儿的临床特点,了解其外周血淋巴细胞亚群的变化.方法 20例EBV-AHS患儿,均符合噬血细胞综合征的诊断标准,并有EBV感染的证据,对其临床特点进行总结分析,并采用流式细胞术检测外周血淋巴细胞亚群CD4+、CD8+、CD19+、CD16+CD56+、CD4+/CD8+的水平.选择20例健康儿童作为对照组.结果 在EBV-AHS的诊断标准中,以发热、血常规2系以上降低、乳酸脱氢酶升高(＞1 000 U/L)、高密度脂蛋白降低及铁蛋白增高(＞1 500 g/L)5项指标异常发生率最高,均为100%.与对照组相比,EBV-AHS患儿外周血CD8+T及CD19+B细胞比例增高(分别为53.70% ±10.6% vs 27.05% ±8.22%,24.95% ±5.34% vs11.85% ±4.53%),而CD4+T及CD16+CD56+NK细胞比例下降(分别为23.60% ±6.42% vs 45.20% ±5.74%,5.55% ±2.87% vs 14.70% ±4.16%),CD4+/CD8+比值降低(0.46±0.16 vs 1.84±0.68),差异均有显著性(P＜0.01).结论 EBV-AHS患儿细胞及体液免疫功能发生紊乱,导致了疾病的发生发展.     

PICU儿童脓毒症相关性肝损伤的临床特征与预后分析

目的 探讨儿童脓毒症相关性肝损伤的发病率、临床特征以及影响预后的危险因素.方法 对上海市儿童医院PICU 2011年1月至2015年12月收治的脓毒症合并肝损伤患儿的资料进行总结,Logistic回归分析筛选出影响患儿预后的危险因素.结果 PICU脓毒症相关性肝损伤的发生率为9.7%(120/1242),病死率35.8%(43/120).原发感染部位主要为呼吸道感染(50.0%)、腹腔感染(33.3%)和中枢神经系统感染(6.7%).病原检测结果依次为革兰阴性菌58例(51.3%)、病毒30例(26.5%)、革兰阳性菌20例(17.7%).肝功能障碍特征依次为谷丙转氨酶升高117例(97.5%)、凝血酶原时间(PT)延长93例(77.5%)、白蛋白下降83例(69.2%)和总胆红素(total bilirubin,TBIL)升高(>17.1μmol/L)70例(58.3%).单因素分析显示,死亡组患儿的TBIL、PT、活化部分凝血活酶时间、总胆汁酸明显高于存活组.Logistic回归分析示TBIL升高是影响预后的独立危险因素(OR=2.937,95%CI 1.179-7.315,P=0.021),受试者工作特征曲线下面积为0.736;TBIL=64.5μmol/L是判断脓毒症相关性肝损伤患者预后的最佳截点,敏感度57.7%,特异度84.8%.结论 儿童脓毒症相关性肝损伤发病率高,革兰阴性杆菌感染是其主要病原菌;肝功能损害主要表现为谷丙转氨酶升高、PT延长、白蛋白下降及高胆红素血症,高胆红素血症是影响预后的独立危险因素.     

Evaluation of lactate dehydrogenase, creatine kinase and hepatic enzymes for the retrospective diagnosis of perinatal asphyxia among sick neonates

It is difficult to make a retrospective diagnosis of perinatal asphyxia in symptomatic neonates delivered non-institutionally. We studied serum creatine kinase muscle-brain fraction (CK-MB), lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvate transaminase (SGPT) for differentiating asphyxiated (n=25) from non-asphyxiated (n=20) neonates who present with non-specific signs of sickness. CK-MB was assayed at 8 and 24 h; and LDH, SGOT and SGPT at 72 h of life. On comparing cases and controls, median 8-hr CK-MB [80 U/L vs. 26 U/L respectively, P< 0.001], median 24-hr CK-MB [33.5 U/L vs. 21.5 U/L respectively, P=0.009] and median LDH [965 U/L vs. 168 U/L respectively, P< 0.001] were higher in asphyxiated neonates. Raised LDH had 100% sensitivity, while CK-MB had 100% specificity for asphyxia. LDH had the highest area under ROC curve (0.998). We conclude that LDH at 72 hr of life is most accurate at differentiating asphyxiated from non-asphyxiated symptomatic neonates.     

儿童肠息肉术后电凝综合征的临床特征及危险因素分析

目的:探讨儿童肠息肉经结肠镜电切除术后电凝综合征(PPECS)的临床特征及相关危险因素,为儿科内镜医师提供防治依据。方法:回顾性分析郑州大学附属儿童医院内镜中心2015年1月至2019年12月收治的23例行内镜下肠息肉电切术后发生PPECS患儿的临床资料。并采用简单随机数字法选取同期由同一位内镜医师完成的手术115例作为非PPECS组。总结PPECS的发病率、临床特征及处理方案,发生PPECS的高危因素采用Logistic回归分析。结果:23例患儿术后出现PPECS,发病率为1.1%(23/2083),患儿术后均出现腹痛、发热;年龄(3.5±1.5)岁,年龄≤3岁19例(82.6%);肠息肉直径≥25 mm的18例(78.3%)。PPECS组的内镜操作时间[(56±15)比(24±8)min,t=18.086,P<0.01]、分块切除比例[78.3%(18/23)比17.4%(20/115),χ²=17.358,P<0.01]、病变直径大小[(38.4±3.7))比(15.8±4.3)mm,t=15.127,P<0.01]、息肉分布右半结肠[47.8%(11/23)比23.5%(27/115),χ²=7.035,P<0.05]、广基息肉比例[78.3%(18/23)比25.2%(29/115),χ²=29.259,P<0.01]均明显高于非PPECS组;PPECS组白细胞计数[(17.4±4.5)×10⁹/L比(8.5±1.2)×10⁹/L,t=6.085,P<0.05]、C反应蛋白[(25.8±3.6)比(1.1±0.6)mg/L,t=5.531,P<0.05]明显高于非PPECS组。多因素Logistic回归分析显示,病变直径≥25 mm(OR=7.554,95%CI 3.135~20.158,P=0.001)、广基息肉类型(OR=5.676,95%CI 1.153~9.596,P=0.002)及病变位置位于右半结肠(OR=5.845,95%CI 1.737~9.297,P=0.008)均是影响PPECS发生的独立危险因素。结论:PPECS以息肉术后发热、腹痛及白细胞升高为特征。病变直径大小≥25 mm、广基息肉类型及病变位置位于右半结肠是PPECS发生的独立危险因素。     

Comparative analysis of malaria parasite density using actual and assumed white blood cell counts

AIM: To compare malaria parasite densities, calculated using the white cell counts (WBC) of individual children with a standard WBC count of 8.0 x 10(9)/L. METHODS: In a cross-sectional study, the prevalence of malaria WBCs and malaria parasite densities were estimated in 240 healthy Nigerian children aged 1-8 years. RESULTS: Of 240 children, 75 (31.25%) were infected with malaria, 69 (28.75%) with P. falciparum and 9 (3.75%) with other species. The mean (SD) WBC count was 5.1 (2.0) x 10(9)/L. There was an age-related significant difference in the mean WBC counts (t=2.000, p<0.05), with values higher in the under-5s [5.6 (2.0) x 10(9)/L] than in the > or =5-years group [5.0 (1.8) x 10(9)/L]. No significant difference was observed with regard to gender and malaria infection. The mean (SD) parasite densities of P. falciparum obtained using the assumed value of 8.0 x 10(9)/L [1936 (1119.5)] was significantly higher than the parasite densities estimated using the individual WBC counts [1140 (862.8) for P. falciparum] (p<0.0001). CONCLUSION: Parasite density estimation using the assumed count of 8.0 x 10(9)/L might result in over-estimation of the parasite burden. The WBCs of individual patients should always be estimated when parasite density is required.     

Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis

BACKGROUND: The optimal management of childhood acute lymphoblastic leukemia (ALL) with hyperleukocytosis is unclear, largely because the risk of leukostasis-related complications is poorly characterized. PROCEDURE: We reviewed the presenting characteristics, initial management, and frequency and type of complications in all children seen at St. Jude Children's Research Hospital with previously untreated ALL and an initial leukocyte count >200 x 10(9)/L. RESULTS: A total of 178 children, representing 8% of all children with ALL, had an initial leukocyte count >200 x 10(9)/L; 67 patients had a leukocyte count >400 x 10(9)/L. Sixteen patients (9%) had neurological complications with 12 of these patients experiencing symptoms at presentation. Four patients (2%), all with initial leukocyte counts >400 x 10(9)/L, suffered a CNS hemorrhage. Pulmonary leukostasis occurred in 11 patients (6%). The degree of hyperleukocytosis was significantly predictive of neurological (P = 0.006) and respiratory (P = 0.014) complications. The majority of complications occurred at presentation. Cytoreduction (94 patients) decreased the leukocyte count but delayed initiation of chemotherapy (P = 0.013). CONCLUSIONS: Serious leukostasis-related complications are relatively uncommon in childhood ALL and most occur at presentation. Their incidence increases in proportion to the leukocyte count. A large subset of cases can be managed successfully without cytoreduction. Cytoreduction may be considered for patients with leukocyte counts >400 x 10(9)/L or patients who have complications at presentation.     

Granulocyte colony-stimulating factor ameliorates toxicity of intensification chemotherapy for acute lymphoblastic leukemia

BACKGROUND: Intensification chemotherapy improves the prognosis for children with acute lymphoblastic leukemia (ALL), but results in considerable morbidity, primarily due to myelosuppression with resultant neutropenia. Recombinant granulocyte colony-stimulating factor (G-CSF) shortens neutropenia following intensive chemotherapy, but potential benefits in the therapy of ALL remain inadequately explored. Accordingly, a randomized, crossover study was undertaken to clarify this issue. PROCEDURE: Seventeen children with acute lymphoblastic leukemia or T-cell non-Hodgkin lymphoma and treated on standard protocols were randomized to receive G-CSF following either the first or second intensification blocks of chemotherapy. G-CSF was administered as a single daily subcutaneous injection of 5 mcg/kg from day 9 following the start of intensification therapy, and continued until the neutrophil count exceeded 0.5 x 10(9)/l for 3 days. Study endpoints were days of neutropenia (neutrophils < 1 x 10(9)/l) and severe neutropenia (neutrophils < 0.5 x 10(9)/l), days in hospital, days of fever, and days on antibiotics. RESULTS: There were significant reductions in the duration of neutropenia (95% confidence interval 3.8-8 days, P = 0.0001), severe neutropenia (95% confidence interval 1.8-7.4 days, P = 0.002), and days in hospital (95% confidence interval 0.9-6.3 days, P = 0.01) for children receiving G-CSF. Overall, the duration of neutropenia was longer following the second block (95% confidence interval 2.2-6.4 days, P = 0.0003), but this difference was abolished by G-CSF, and children, receiving G-CSF after the second intensification were more likely to restart maintenance chemotherapy on schedule (P = 0.05). CONCLUSIONS: G-CSF reduces the hematological toxicity of intensification chemotherapy and may allow improved compliance with treatment scheduling.     

Thrombopoietin has a primary role in the regulation of platelet production in preterm babies.

Thrombocytopenia in the first days of life, in association with evidence of reduced megakaryocytopoiesis and platelet production at birth, is common in sick preterm babies. Thrombopoietin (Tpo) is the major regulator of platelet production in adults. However, these babies have low Tpo levels at birth, suggesting that the Tpo response to thrombocytopenia may be impaired. To test this hypothesis we 1) measured Tpo levels, 2) measured circulating megakaryocyte progenitors serially over the first 12 d of life in 13 preterm babies with early onset thrombocytopenia and in 14 control babies with evidence of normal megakaryocytopoiesis, and 3) measured Tpo levels in thrombocytopenic children (n = 13). In control babies, platelet counts and progenitor numbers remained normal and Tpo levels were consistently low-d 1:160+/-23 pg/mL (mean+/-SEM), d 4/5: 154+/-18 pg/mL and d 12: 150+/-58 pg/mL. In thrombocytopenic babies, platelet counts and megakaryocyte progenitor numbers were significantly lower than controls at d 1: platelets 130+/-14 x 10(9)/L versus 255+/-20 x 10(9)/L (p < 0.001) and megakaryocyte progenitors 552 versus 3907 colonies/mL (mean, p < 0.001), and fell further to nadir on d 4/5: platelets 76+/-6 X 10(9)/L versus 259+/-21 x 10(9)/L (p < 0.001) and MK progenitors 479 versus 2742 colonies/mL (p < 0.05). Tpo levels were only slightly raised on d 1:247+/-52 pg/mL (p = 0.24), but then rose sharply by d 4/5: 425+/-75 pg/mL (p < 0.001). By d 12, platelet count, megakaryocyte progenitors and Tpo level (145+/-29 pg/mL) had returned to control levels. Tpo levels at platelet nadir in thrombocytopenic babies were significantly lower than in thrombocytopenic children: mean 425 versus 1383 pg/mL (p < 0.001). These data show that Tpo is important in platelet homeostasis in preterm babies, with a close reciprocal relationship with platelet count and progenitor numbers during thrombocytopenia. However, the increase in Tpo levels seen in these babies was modest, despite significantly impaired megakaryocytopoiesis, and when compared with that seen in children with thrombocytopenia. This offers further evidence that preterm babies have an impaired Tpo response to thrombocytopenia and suggests that recombinant human Tpo may have a role in the prevention/treatment of preterm thrombocytopenia.     

Clinical characteristics of chronic idiopathic thrombocytopenia in Chinese children

PURPOSES: Clinical course and treatment outcome of childhood chronic ITP are quite variable in the literature. We report in the current paper our observation on the clinical behavior of chronic ITP in Chinese children. PATIENTS AND METHODS: We performed a retrospective review (Jan. 1990 to Dec. 2000) of children having low platelet count (plt <150 x 10(9)/L) for more than 6 months without identifiable cause. The indication for treatment was plt < or =20 x 10(9)/L. Remission is defined as plt > or =150 x 10(9)/L. RESULTS: Thirty-four children were identified within these 11 years. Their median age at diagnosis was 6.7 years (range from 0.4 to 16.8 years). The M:F ratio was 16:18. Bone marrow aspiration was performed in 30/34 cases. The median plt count at presentation was 24 x 10(9)/L (range 2 to 135 x 10(9)/L). Fourteen of 34 (41%) children eventually achieved durable remission. The chance of remission at 5 years was 66.62% with a median follow-up time of 5.86 years (range 0.72 to 10.41 years). Concerning therapy, 17/34 (50%) required no treatment while for the remaining 17, treatment included steroid (n = 16), IVIG (n = 7) or splenectomy (n = 3). In spite of temporary improvement in most, treatment induced prolonged complete remission (plt >150 x 10(9)/L) in only 2 patients. Twenty of 31 tested had abnormal immune marker(s) at presentation but none evolved into specific autoimmune disease later on. There was no correlation between the remission status, response to treatment, and the presence of autoimmune markers. CONCLUSION: About half of our chronic ITP patients achieved remission within 5 years. Medical treatment does not seem to alter the natural course of the disease but induced a transient response in most cases. Positive autoimmune markers are common among chronic ITP patients and have no significance in predicting outcome.     

Myelotoxicity, pharmacokinetics, and relapse rate with methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia

White blood cell and absolute neutrophil counts (WBC, ANC), aminotransferase (AT) levels, methotrexate (MTX) and 6-mercaptopurine (6MP) doses, metabolites in erythrocytes (E-MTX and E-6TGN), and the prognostic significance of these parameters were studied in 58 children receiving MTX/6MP maintenance therapy for acute lymphoblastic leukemia diagnosed from July 1986 to December 1991. At the end of follow-up July 1995, 13 patients had relapsed (pEFS = 0.77). Weighted means of AT, WBC, and ANC during and after maintenance therapy (mAT, mWBCON, mWBCOFF, mANCON, mANCOFF), E-MTX (mE-MTX), and E-6TGN (mE-6TGN) were calculated, as well as the product of mE-MTX and mE-6TGN (mE-MTX*6TGN), as MTX and 6MP probably act synergistically. Beyond higher MTX and 6MP doses to patients with high mWBCON, neither mWBCON, (median 3.5 x 10(9)/L), mANCON, nor mAT was correlated with the dose of MTX and 6MP, mE-MTX, mE-6TGN, or risk of relapse. Patients with mE-MTX*6TGN above or below 828 (nmol/mmol Hb)2 (median value) had pEFS values of 0.84 and 0.70, respectively (P = .16). All 5 patients who relapsed during therapy had mE-MTX*6TGN < 828 (nmol/mmol Hb)2 (P = .03). mWBCOFF and the degree of myelosuppression (= mWBCSHIFT = mWBCOFF - mWBCON; median: 2.5 x 10(9)/L) were related to age (rs = -0.50, P = .001 and rs = -0.40, P = .006, respectively). All eight relapses off therapy occurred in patients with mWBCSHIFT < 2.5 x 10(9)/L (P = .02). WBC levels during MTX/6MP therapy may underestimate the degree of MTX/6MP treatment intensity, especially in order children. Pharmacokinetic monitoring could be useful for optimizing MTX/6MP maintenance therapy.     

儿童重症腺病毒肺炎的临床特征及高危因素分析

目的分析儿童重症腺病毒肺炎的临床特征、危重症及其死亡高危因素,为早期诊断及合理治疗提供临床依据。方法回顾性分析华中科技大学同济医学院附属同济医院儿童重症医学科(PICU)2019年1至10月收治的75例重症腺病毒肺炎患儿的临床资料和实验室检查资料,按照病情分析分为重症组和危重症组,采用χ²检验或Mann-Whitney秩和检验对比分析进行组间比较,危重症及其死亡的高危因素分析采用单因素和多因素Logistic回归分析。结果75例重症腺病毒肺炎患儿中男52例、女23例,年龄为3月龄至8岁,重症组30例、危重症组45例。鼻咽拭子腺病毒抗原阳性率为21%(15/72),血清腺病毒IgM抗体阳性率为13%(10/75),鼻咽拭子腺病毒核酸阳性率为75%(21/28)。血浆和肺泡灌洗液的病原微生物宏基因组二代测序(mNGS)阳性率分别为92%(33/36)和96%(54/56),95%(63/66)确定为腺病毒7型。采用较大剂量利巴韦林和综合治疗措施(呼吸支持、糖皮质激素、免疫球蛋白及器官功能维护等),治愈率为77%(58/75),好转率8%(6/75),病死率为15%(11/75)。危重症组的利巴韦林治疗后发热>3 d比率明显高于重症组[51%(18/35)比8%(2/26),χ²=12.949,P<0.05]。重症病例发生危重症的高危因素包括年龄<4岁、入PICU前发热时间、入PICU后发热时间、氧合指数(P/F)<300 mmHg(1 mmHg=0.133 kPa)、铁蛋白>1000μg/L、乳酸脱氢酶(LDH)>1500 U/L、5个肺叶受累、并发胸腔积液和(或)气漏(均P<0.05)。其中,5个肺叶受累为独立高危因素(校正OR=49.641,95%CI 4.186~588.618,P=0.002)。危重症病例的死亡高危因素包括入PICU后发热时间、P/F<100 mmHg、铁蛋白>2000μg/L、白细胞介素(IL)-6>100 ng/L、LDH>1500 U/L、并发胸腔积液和(或)气漏(均P<0.05)。其中,IL-6>100 ng/L为独立高危因素(校正OR=16.094,95%CI 2.059~25.787,P=0.008)。结论腺病毒7型所致儿童重症腺病毒肺炎的病死率较高;鼻咽拭子腺病毒核酸和血浆或肺泡灌洗液mNGS检出率高,有助于早期诊断,后者可用于分型;对于4岁以下儿童,持续发热、肺部广泛病变和IL-6水平明显增高者应高度警惕危重症和不良预后;早期较大剂量利巴韦林联合综合疗法有助于改善其预后。