外周血和骨髓微量神经母细胞瘤细胞检测的临床意义

目的 探讨CD45/CD56/GD2单克隆抗体(单抗)流式细胞仪分析法检测周围血和骨髓微量神经母细胞瘤(NB)细胞的临床意义。方法 11例腹部神经母细胞瘤(NB组)和23例其他肿瘤(对照组)患儿,年龄6个月至12岁,用单抗CD45/CD56/GD2流式细胞术检测外周血和骨髓穿刺标本微量NB细胞。结果 NB组入院时血和骨髓微量NB细胞阳性率分别为90.9％(10/11)和72.7％(8/11),对照组血和骨髓均为阴性(P<0.001)。NB组骨髓微量NB细胞检测与涂片细胞学检查阳性率有较好的相关性(P<0.05),但前者阳性率更高,不受骨髓稀释影响。骨髓NB细胞阳性率与临床分期有关,Ⅱ～Ⅳ期明显高于Ⅰ期(P<0.01)。化疗后血和骨髓NB细胞数均明显减少(P<0.05)。术后转移者血NB细胞重新出现阳性。结论 CD45/CD56/GD2单抗流式细胞术检测周围血和骨髓微量NB细胞具有高度敏感性和特异性,有助诊断、鉴别诊断、疗效观察和复发转移监测。     

UBE2C在神经母细胞瘤组织表达及临床意义分析

目的 通过检测泛素偶联酶2C（UBE2C）在神经母细胞瘤（NB）患儿中的表达情况,分析其表达与NB患儿的临床特征及预后的相关性。方法 收集上海交通大学医学院附属新华医院2012年1月至2015年1月51例NB患儿术后石蜡包埋的组织样本,通过免疫组织化学方法检测其UBE2C 蛋白的表达水平。回顾性分析NB患儿的临床特征,采用Kaplan-Meier法分析其生存曲线。 结果 51例患儿中,男女比例为1.8∶1,中位诊断年龄为36个月（3.3～156.0个月）,中位随访时间为25.6个月（5.5～42.7个月）。免疫组化结果显示,Ⅲ、Ⅳ期患儿UBE2C蛋白表达的阳性率（90.0%）明显高于Ⅰ、Ⅱ、Ⅳs期患儿（47.6%）（P＜0.001）;复发NB患儿的UBE2C表达阳性率（91.3%）明显高于无复发者（57.1%）（P＝0.001）。生存曲线分析显示, UBE2C蛋白阳性表达组预后较差（P＝0.006）。结论 UBE2C的表达与NB的分期及复发密切相关,UBE2C表达阳性提示NB患儿预后不良。UBE2C可能在NB侵袭、转移和复发过程中发挥重要的作用,有望成为NB潜在的生物标记物和治疗新靶点。     

利妥昔单抗治疗儿童特发性膜性肾病1例报告

目的观察利妥昔单抗治疗儿童特发性膜性肾病的疗效及安全性。方法应用利妥昔单抗前检查血T、B淋巴细胞亚群、血尿常规及肝肾功能。予利妥昔单抗500 mg(375 mg/m2)静脉输注治疗,每周1次,连用4周。同时激素减量至隔日口服。结果应用利妥昔单抗治疗后血总B淋巴细胞由13%降为0%,1个月后患儿的尿蛋白显著下降,2个月后尿蛋白转阴、肾病缓解。同时该患儿对利妥昔单抗治疗耐受性好,未出现相关的不良反应。结论利妥昔单抗治疗儿童特发性膜性肾病有一定疗效,但其治疗肾病的确定性及安全性仍需进一步临床随机试验加以证实。     

用流式细胞仪对小儿神经母细胞瘤的诊断与监测

目的　建立一种快速而特异的流式细胞仪 (flowcytometer,FCM)分析方法用于神经母细胞瘤 (NB)患儿的诊断与监测。方法　采用多色FCM和抗人神经节苷脂D2 (gangliosideD2 ,GD2 )单抗12 6 4、CD56、CD45组合对 13例 36份NB标本和 2 4例非NB标本进行检测、比较和分析。结果　NB患儿的阳性检出率 (12 / 13例或 92 % )明显高于非NB患儿的阳性检出率 (0 / 2 4 ,P =7 0 2× 10 -9)。外周血标本的阳性检出率 (17/ 2 1份或 81% )与骨髓标本的阳性检出率 (7/ 9份或 78% )差异无显著意义(χ2 =1 0 35 ,P >0 7) ,初诊病例与病理检查的诊断结果符合率达 92 %。2例随访结果表明 ,1例GD2阳性细胞随治疗及病情进展而变化 ,另 1例则确诊后 38d内外周血标本中始终含有NB细胞。结论　多色FCM分析GD2 阳性细胞能简便、快速、特异地检测NB细胞 ,对NB患儿的诊断与微小残留病(minimalresidualdisease ,MRD)的监测具有重要意义     

TAZ在神经母细胞瘤组织中表达及临床意义

目的分析转录共激活因子(TAZ)在神经母细胞瘤(NB)患儿肿瘤组织中的表达及与患儿临床特征和预后的相关性。方法收集我院普外科58例NB患儿肿瘤组织标本,免疫组化(IHC法)检测TAZ在NB肿瘤组织中的表达,结合临床资料分析TAZ与临床病理学特征的关系,采用Kaplan-Meier和Cox回归分析分析TAZ表达对NB生存的影响。结果 IHC结果显示TAZ主要在细胞核内表达,且发现TAZ在NB的表达高于节细胞神经母细胞瘤(GNB),进一步分析发现TAZ在肿瘤临床分期(Ⅲ、Ⅳ期)、MYCN扩增、高危状态、Shimada病理(u FH)、肿瘤骨髓浸润、肿瘤复发、NSE升高、LDH≥500 U/L表达升高时,与相对应的上述各因素比较差异有显著性(P 0.01)。Kaplan-Meier生存分析提示NB患儿3年存活率TAZ高表达组低于TAZ低表达组(46.2%vs. 85.4%),差异有显著性(P=0.002);单因素Cox回归分析发现TAZ高表达、临床分期(Ⅲ和Ⅳ期)、高危状态、Shimada病理(u FH)、肿瘤复发是NB患儿预后危险因素,但多因素Cox回归分析发现仅TAZ表达增高是预后危险因素,差异有显著性(P 0.001)。结论 TAZ的表达和已知的患儿预后危险因素、不良病理类型、肿瘤复发及肿瘤标志物升高呈正相关性,TAZ表达阳性提示NB患儿预后不良,因此TAZ可作为NB患儿潜在判断预后的分子标志物和治疗新靶点。     

利妥昔单抗治疗儿童重型及难治性自身免疫性溶血性贫血疗效观察

目的探讨利妥昔单抗治疗儿童重型及难治性自身免疫性溶血性贫血(AIHA)的疗效。方法回顾性分析我院自2012年9月—2020年1月共34例应用利妥昔单抗治疗的重型及难治性AIHA患者的临床资料,分析总结疗效及用药经验。结果 12例重型AIHA患者利妥昔单抗用在一线治疗方案中,其余22例难治及复发性AIHA患者作为二线用药。共有3例无效患者未完成治疗而放弃,另有2例患者分别随访2年及7个月后失访,失访前疗效评估分别为CR及PR。其余29例患者随访至今均有效,其中23例达CR,6例达PR。11例(32%)患者利妥昔单抗治疗后复发。5例患者复发后再次应用利妥昔单抗治疗仍有效。全部患者用药半年内共5例出现感染并发症。结论利妥昔单抗用于初治重型及复发难治性AIHA显示了良好疗效,如有复发,再次应用仍有效。     

利妥昔单抗治疗儿童难治性慢性特发性血小板减少性紫癜9例近期疗效

目的观察利妥昔单抗治疗儿童难治性慢性特发性血小板减少性紫癜(ITP)的近期疗效。方法选择我院2008年6月-2010年6月期间确诊为难治性、慢性ITP患儿9例,给予利妥昔单抗100 mg静脉滴注,每周1次,连用4周。结果治疗起效时间1~6周,有效率为67%,复发率为33%,2例切脾患儿无效。结论利妥昔单抗治疗儿童难治性、慢性ITP起效快、缓解率较高、毒副作用小,但有复发倾向。     

儿童伯基特淋巴瘤62例临床特征及预后分析北大核心CSCD

目的分析儿童伯基特淋巴瘤(Burkitt’s lymphoma,BL)的临床特点、化疗疗效,以及利妥昔单抗治疗对BL患儿预后的影响。方法回顾性收集62例BL患儿的临床资料,对BL患儿的临床特点、疗效及预后相关因素进行分析,采用Cox回归分析BL患儿预后不良的相关因素。根据是否应用利妥昔单抗治疗将晚期(Ⅲ/Ⅳ期)BL患儿分为化疗联合利妥昔单抗组和单纯化疗组,比较两组预后情况。结果62例患儿发病时中位年龄5(范围1~14)岁,男58例(94%),女4例(6%)。原发部位为腹腔者41例(66%),头颈部者16例(26%)。Ⅰ、Ⅱ、Ⅲ、Ⅳ期患儿分别为1例(2%)、8例(13%)、33例(53%)、20例(32%)。中位随访时间29个月,进展/复发患儿15例(24%),3年总生存率、无事件生存率分别为82.8%±5.2%、77.3%±5.8%。Ⅲ/Ⅳ期患儿中,化疗联合利妥昔单抗组(n=16)与单纯化疗组(n=30)3年总生存率分别为93.3%±6.4%、65.6%±9.9%,差异有统计学意义(P=0.042);3年无事件生存率分别为86.2%±9.1%、61.8%±10.1%,差异无统计学意义(P>0.05)。Cox回归分析结果显示:中枢神经系统侵犯、乳酸脱氢酶水平>1000 U/L、早期未完全缓解为BL患儿预后不良的相关因素(P<0.05)。结论化疗联合利妥昔单抗治疗能改善Ⅲ、Ⅳ期BL患儿预后;中枢神经系统侵犯、乳酸脱氢酶水平升高、早期未完全缓解可能提示BL患儿预后不良。     

神经母细胞瘤中BCL11A的表达及对临床预后评估的意义

目的探讨BCL11A在神经母细胞瘤(NB)患儿中的表达水平与临床特征及预后之间的相关性。方法收集2012年9月—2019年7月在我院收治的60例NB患儿的肿瘤组织石蜡切片及相关的临床信息,通过免疫组织化学染色法检测肿瘤组织中BCL11A蛋白的表达情况,采用Kaplan-Meier和COX回归分析BCL11A表达水平与NB患儿预后之间的关系。结果免疫组化结果显示BCL11A在86.7%(52/60)的NB患儿阳性表达。高危NB患儿BCL11A表达水平明显高于低、中危患儿(χ~2=6.877,P=0.009),伴有远处转移的NB患儿BCL11A表达水平显著高于无远处转移的患儿(χ~2=4.207,P=0.040)。生存分析结果显示BCL11A高表达的NB患儿5年总体生存率(54.6±12.0)%明显低于低表达的患儿(96.4±3.5)%(P=0.002),且更有可能出现复发或进展(P=0.020)。多因素分析发现危险度为高危组和BCL11A高表达水平是影响NB患儿预后的独立危险因素(P=0.036和P=0.049)。结论 BCL11A高表达和NB患儿的高危状态与远处转移相关,是影响NB患儿预后的独立危险因素。     

儿童异基因造血干细胞移植后淋巴细胞增殖性疾病的临床研究

目的探讨儿童异基因造血干细胞移植（allo-HSCT）后淋巴细胞增殖性疾病（PTLD）的诊治及预后。方法回顾性分析4例allo-HSCT后EBV相关性PTLD（EBV．PTLD）患儿的临床资料。其中,急性淋巴细胞白血病（高危）（ALL—HR）2例,重型再生障碍性贫血（SAA）2例。异基因外周血造血干细胞移植（allo-PBSCT）3例,异基因脐血造血干细胞移植（allo-UCBSCT）1例。结果4例患儿分别于allo．HSCT后第53、101、22、42d发生PTLD。临床表现为发热、鼻塞、扁桃体肿大、淋巴结肿大和肝脾肿大,移植前均EBNA-1-IgG（＋）、VCA．IgG（＋）;移植后EBV．DNA1．69×10^4～8．62×10^8 copies／mL。经淋巴结病理活检确诊为EBV-PTLD,其中1例为T细胞来源,3例为B细胞来源。例1予减停免疫抑制剂、使用利妥昔单抗、联合COP方案化疗及供者淋巴细胞输注（DU）治疗,PTLD反复且发生严重皮肤GVHD、肺部感染,移植后第193d死亡。余3例予减停免疫抑制剂及利妥昔单抗治疗,临床表现消失且EBV．DNA转阴,分别随访17、12、7个月均无病存活。结论动态监测EBV—DNA对PTLD早期发现具有重要意义。减停免疫抑制剂联合利妥昔单抗治疗EBV-PTLD疗效明显。化疗可导致严重感染,DLI治疗存在严重GVHD危险,不宜作为一线治疗。     

2 X 2 tables

Fourfold (2 X 2) tables are used to describe enumeration data; they are concise and useful for summarizing many kinds of biomedical information. A familiar form is with two samples, each of which provides a two-valued outcome or observation, such as lived-died, normal-abnormal. These tables may be from research designs of several types: cross-sectional surveys, prospective models, retrospective models, and randomized clinical trials. Several methods of analysis of 2 X 2 tables are discussed, without the mathematical detail: chi 2 test, critical ratio test, Fisher's exact test, and other less commonly used tests. The use of the relative risk ratio and the odds ratio to describe 2 X 2 tables is discussed. Some pitfalls in the use and interpretation of 2 X 2 tables are reviewed.     

MECP2基因及MECP2相关疾病

<正>Andrea Rett首次于1966年报道一例青年女性在1~1.5岁之前正常发育,以后出现认知、运动倒退以及手的刻板动作,提出一类疾病"认知倒退、脑萎缩伴有高氨血症"~([1])。伴有高氨血症的类似病例因此受到关注,不幸的是血氨升高是实验室误差所致。直到1983年,Hagberg等~([2])在Annals of Neurology报道了类似发育倒退但没有高氨血症     

Multiple endocrine neoplasia type 2b (MEN 2b). Report of 2 pediatric cases

Two new sporadic cases of multiple endocrine neoplasia type 2b (MEN 2b) are described. Both patients were diagnosed in pediatric age and presented the characteristic features of the syndrome (facies "sui generis", Marfanoid habitus, mucosal neuromas, history of chronic gastrointestinal disturbances) and developed medullary thyroid carcinoma (MTC). In the former case, metastatic neck adenopathies were the first sign by which the disease was recognized. Antitumor treatment consisted of total thyroidectomy, cervical node dissection, administration of I131 and neck irradiation. This patient is alive and well 20 months from diagnosis, still having high serum levels of thyrocalcitonin (TC). In the latter case, the syndrome was diagnosed on clinical grounds before the development of a MTC. The patient was then strictly followed-up and thyroidectomy performed only when serum TC levels rose to abnormally high values: no tumor spread was documented at that time. She is alive and well 4 years from diagnosis.--Early recognition of MEN 2b syndrome is necessary in order to detect and properly treat MTC.     

Relationship between PAO2/FIO2 and SATO2/FIO2 with mortality and duration of admission in critically ill children

ObjectivesThe aim of this study is to analyse the relationships and the association between PaO₂/FiO₂ and SatO₂/FiO_2with the duration of admission in Paediatric Intensive Care Units (PICU) and mortality, and to study the relationships between both ratios.Material and methodsA retrospective study was conducted on PICU patients in whom a gas analysis was performed in the first twenty-four hours of admission. Demographic, clinical and ventilation variables were collected, and the relationship between PaO₂/FiO₂ and SatO₂/FiO₂ with days of admission and mortality was determined. Finally, the best cut-off points of SatO₂/FiO₂ were determined for PaO₂/FiO₂ values greater and less than 200.ResultsOf 512 patients admitted during one year, a gas analysis was performed on 358, 65% of those in arterial blood. The median duration of hospitalization was two days and there were 11 patient deaths. There was a low negative correlation between the values of PaO₂/FiO₂ and SatO_2/FiO₂ on admission to PICU and with duration of admission, and an inverse association with mortality (P < .01). This association was stronger for the PaO₂/FiO₂ ratio in patients with heart disease, those undergoing invasive mechanical ventilation, and for arterial blood samples. PaO₂/FiO₂ and SatO₂/FiO₂ ratios were significantly correlated with each other. A cut-off of 200 for SatO₂/FiO₂ had a sensitivity of 97.5% for classifying patients with PaO₂/FiO₂ values lower or higher than 200.ConclusionsPaO₂/FiO₂ and SatO₂/FiO₂ index are markers of severity in critically ill patients. In patients who do not have an arterial line, SatO₂/FiO₂ index can be used for assessment of oxygenation as an indicator of severity in children in critical condition.     

Fanconi-Bickel Syndrome - Mutation in SLC2A2 Gene

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism. The defect in the GLUT 2 receptors in the hepatocytes, pancreas and renal tubules leads to symptoms secondary to glycogen storage, glucose metabolism and renal tubular dysfunction. Derangement in glucose metabolism is classical with fasting hypoglycemia and post-prandial hyperglycemia. The authors report a 4-year-old boy who presented with failure to thrive, motor delay, protuberant abdomen and was noted to have huge hepatomegaly with glycogen deposition in liver, and renal tubular acidosis. Gene sequencing revealed homozygous mutation, c.1330T > C in SLC2A2 gene, thus confirming the diagnosis of FBS. Only three mutations have been reported from India so far. The primary reason for referral to authors’ hospital was for liver transplantation, but an accurate diagnosis led to avoidance of the major surgery and streamlining of treatment with clinical benefit to the child and family.