儿童急性B淋巴细胞白血病患者诱导化疗后免疫表型的改变及其临床意义

目的探讨儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)诱导结束时白血病细胞抗原表达的变化情况及其对预后的影响。 方法回顾性研究于2010年至2015年期间被诊断为B-ALL的691例儿童患者。患儿骨髓标本在初诊时进行白血病免疫分型检测,并在治疗第33天时进行微小残留病(minimal residual disease,MRD)检测。其中,155例MRD≥0.01%的患者被纳入本次研究。用四色单克隆荧光抗体组合通过多参数流式细胞术进行白血病细胞免疫表型变化的研究。 结果86例(55.5%)患者至少有一个抗原标志出现了表型转换,CD19是最稳定的标记。然而,将近1/3患儿的CD20在初诊和化疗第33天时表达有显著性差异。抗原表达的变化与无事件生存率(event-free survival,EFS)、无复发生存率(relapse-free survival,RFS)或总生存率(overall survival,OS)无显着相关(P>0.05)。多因素分析显示白细胞计数(white blood cell,WBC)和BCR-ABL在儿童ALL中具有独立的预后价值。 结论虽然抗原表达的改变在诱导缓解治疗结束时很普遍,但是在化疗第33天MRD阳性的患者中,抗原表达的改变与预后价值无关。     

Synophrys

IntroductionMeeting of the medial eyebrows in the midline (synophrys) may serve as a cutaneous marker lesion for syndromal disorders (e.g. Cornelia de Lange syndrome).Case presentationA 31-year-old man showed supercilia forming a single band of terminal hairs between left and right lateral orbital rim. Medical examination of the patient revealed coldness-inducable urticaria, xanthelasma formation and long eyelashes without any signs of a syndromal disorder.ConclusionSynophrys can be found in some syndromal disorders, but are not pathognomonic for any illness per se.     

早产儿支气管肺发育不良的研究进展

随着新生儿重症监护技术的迅速发展,早产儿,尤其是极低出生体重儿的存活率得到较大提高。早产是导致支气管肺发育不良(BPD)的重要因素之一,加之早产儿可能合并低出生体重、围生期感染和动脉导管未闭等,以及进行机械通气与给氧治疗所致并发症,而使早产儿BPD的发生率呈逐年上升趋势。BPD早产儿的初次住院时间及BPD导致的病死率,均明显高于非BPD早产儿,因此早产儿BPD已成为临床最棘手的问题之一。笔者拟就目前早产儿BPD的研究进展,包括相关危险因素、早期预测生物学标志物及防治等进行综述。     

枸橼酸钠抗凝在脓毒症伴急性肾损伤患儿连续性静脉-静脉血液滤过治疗中的应用

目的探讨枸橼酸钠抗凝在脓毒症伴急性肾损伤患儿连续性静脉-静脉血液滤过(CVVH)中的应用。 方法选择2008年5月至2016年4月,在四川大学华西第二医院住院并拟行CVVH治疗的51例脓毒症伴急性肾损伤患儿为研究对象。对其在CVVH治疗中采用枸橼酸钠抗凝。检测不同观察时间点及滤器前、后活化部分凝血活酶时间(APTT)及血清Ca^2＋浓度。观察本组患儿治疗前、后血肌酐、尿素氮、急性生理与慢性健康(APACHE)Ⅱ评分、滤器凝血情况及治疗不良反应。本研究遵循的程序符合四川大学华西第二医院人体试验委员会所制定的伦理学标准,得到该委员会批准,征得受试对象监护人的知情同意,并与之签署临床研究知情同意书。 结果①本组患儿治疗前与治疗结束后0.5 h APTT水平比较,差异无统计学意义(t＝－1.06,P>0.05);治疗2、4、8 h时,患儿滤器后APTT水平均显著高于滤器前,并且差异有统计学意义(t＝－28.30、－7.14、－26.11,P<0.001)。②本组患儿治疗结束后0.5 h血清Ca^2＋浓度较治疗前显著降低,并且差异有统计学意义(t＝4.63,P<0.05);治疗2、4、8 h时,患儿滤器后血清Ca^2＋浓度显著低于滤器前,差异也有统计学意义(t＝6.00、7.47、13.90,P<0.05)。③治疗后患儿血清肌酐、尿素氮及APACHEⅡ评分均较治疗前明显下降,差异有统计学意义(t＝3.03、4.10、3.16,P<0.05)。④本研究无1例患儿发生3级滤器凝血和治疗不良反应。 结论枸橼酸抗凝技术在儿童CVVH治疗中能有效发挥抗凝作用,治疗不良反应小,临床使用较安全。     

输卵管妊娠患者发生持续性异位妊娠危险因素及早期诊断的倾向性评分匹配分析

目的探讨输卵管妊娠(FTP)患者发生持续性异位妊娠(PEP)的高危因素，以及对早期诊断PEP的倾向性评分匹配(PSM)分析。 方法选择2011年1月至2018年12月，于四川大学华西第二医院接受腹腔镜保守性手术治疗(COT)后，发生PEP的17例FTP患者为研究对象，纳入PEP组。同时，随机选取同期于本院接受相同术式，并且术后恢复良好的148例FTP患者作为对照，纳入对照组。采用回顾性分析方法，采集2组患者临床病例资料。采用Mann-Whitney U检验，PSM后，2组患者术后血清β-人绒毛膜促性腺激素(hCG)水平下降至<20 mIU/mL与<10 mIU/mL的时间，以及术后24～48 h血清β-hCG水平较术前下降率进行比较。采用χ²检验，比较2组患者的盆腔黏连、输卵管间质部及壶腹部妊娠发生率。绘制2组患者术后24～48 h血清β-hCG水平较术前下降率对于诊断FTP患者接受COT后发生PEP的受试者工作特征(ROC)曲线，并计算ROC曲线下面积(ROC-AUC)。根据约登指数最大原则，确定2组患者术后24～48 h血清β-hCG水平较术前下降率，对诊断FTP患者接受COT后，发生PEP的最佳临界值。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。 结果①PSM后，与研究组成功匹配的对照组患者为65例。PSM后，2组患者年龄、孕次、人体质量指数(BMI)、停经时间等一般临床资料比较，差异亦均无统计学意义(P>0.05)。②PSM后，PEP组患者盆腔黏连、输卵管间质部妊娠发生率分别为88.2%(15/17)、29.4%(5/17)，均显著高于对照组的61.5%(40/65)、3.1%(2/65)，2组分别比较，差异均有统计学意义(χ²＝4.349、P＝0.037，χ²＝8.834、P＝0.003)。③PSM后，PEP组患者术后血清β-hCG水平下降至<20 mIU/mL与<10 mIU/mL的时间分别为45.0 d(32.7～61.2 d)与59.5 d(41.0～68.7 d)，显著长于对照组的15.0 d(10.0～19.0 d)与17.5 d(10.7～27.2 d)，并且差异均有统计学意义(Z＝4.703、4.418，P<0.001)。④PSM后，PEP组患者术后24～48 h血清β-hCG水平较术前下降率为47.0%(－8.0%～70.1%)，显著低于对照组的69.0%(61.2%～79.2%)，2组比较，差异有统计学意义(Z＝3.506、P<0.001)。2组患者术后24～48 h血清β-hCG水平较术前下降率，诊断FTP患者接受COT后，发生PEP的ROC-AUC为0.777(95%CI：0.626～0.929，P<0.001)。根据约登指数最大原则，2组患者术后24～48 h血清β-hCG水平较术前下降率，诊断FTP患者接受COT后，发生PEP的最佳临界值为52.9%，此时其诊断PEP的敏感度为64.7%，特异度为95.4%，阳性预测值为78.6%，阴性预测值为91.2%，准确度为89.0%，漏诊率为35.3%，误诊率为4.6%。 结论输卵管间质部妊娠与盆腔黏连，可能是FTP患者接受COT后发生PEP的高危因素。术后24～48 h血清β-hCG水平较术前下降率，可能可以作为FTP患者接受COT后发生PEP的早期诊断指标之一。     

Is antenatal corticosteroids exposure associated with hearing loss in preterm infants? A systematic review and meta-analysis

PurposeTo perform a systematic review and meta-analysis of clinical studies exploring the association between antenatal corticosteroids exposure and hearing loss in preterm infants.MethodPubMed, Cochrane library, and EMBASE databases from the inception dates to December 22, 2020 without language restriction. Key search terms included hearing loss, cortisol steroid, and antenatal. Included studies were case control or cohort studies examining preterm (<37 weeks' gestation) or very low-birth-weight (<1500 g) infants and reporting primary data that could be used to explore the association between antenatal corticosteroids exposure and the development of hearing outcomes. This meta-analysis follows the reporting guidelines (MOOSE) for observational studies. Data were independently extracted by 2 researchers. A fixed effects model was used to calculate odds ratios (OR) and 95 % CI. Subgroup analysis was conducted according to different types of antenatal steroids exposure (dexamethasone vs betamethasone) and subgroup analyses based on betamethasone and betamethasone combined with magnesium sulfate (betamethasone vs betamethasone combined with magnesium sulfate).ResultsA total of 110 potentially relevant studies were found, of which 7 met the inclusion criteria (A total of 8130 preterm infants were included. 5337 preterm infants were exposed to antenatal corticosteroids, and 2793 preterm infants were not exposed to antenatal corticosteroids.). Meta-analysis showed that antenatal corticosteroids exposure was significantly associated with hearing loss in preterm infants. (OR, 0.64; 95 % CI, 0.48–0.87; P = 0.004) In addition, significant differences were found between antenatal betamethasone exposure and antenatal dexamethasone exposure. (OR, 0.27; 95 % CI, 0.10–0.77; P = 0.01) Betamethasone and betamethasone combined with magnesium sulfate showed that the difference was no statistically significant. (OR, 1.34; 95 % CI, 0.74–2.43; P = 0.33).ConclusionThe results of this study confirm that among preterm infants, exposure to antenatal corticosteroids exposure is associated with a lower risk of developing hearing impairment.Systematic review registration numberPROSPERO 2021 CRD42021255665.     

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study

Background

Contemporary risk-directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome.

Methods

The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation.

Results

The overall 5-year event-free survival was 84.4% (95% confidence interval [CI], 80.6–88.3) and 5-year overall survival 88.9% (95% CI, 85.5–92.4). Independent factors associated with lower 5-year event-free survival were male sex (80.4%, [95% CI, 74.8–86.4] vs. 88.9%, [95% CI, 84.1–93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2–87.4] vs. 87.1%, [95% CI, 83.4–90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5-year event-free survival (33.3% [95% CI, 11.6–96.1] vs. 83.0% [95% CI, 77.5–88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2–14.5], p < .001).

Conclusions

These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL.     

我国部分地区留守儿童体质健康现状的系统评价

目的系统评价我国部分地区留守儿童体质健康现状,为留守儿童健康保健服务提供循证医学证据。 方法计算机检索中国知网(CNKI)、中国生物医学文献数据库(CBM)、维普及万方数据库中,关于我国留守儿童体质健康现状相关的横断面研究文献。文献检索时间设定为数据库建库至2019年8月。由2位研究人员按照本研究设定的纳入和排除标准,独立筛选文献,并评价文献质量、提取数据,进行交叉核对后,采用RevMan 5.3统计软件,对符合纳入与排除标准文献的儿童体质健康现状指标进行Meta分析。采用美国卫生保健质量和研究机构(AHRQ)推荐的横断面研究评价标准,对纳入文献的方法学质量进行评价。对各研究间的异质性采用I²检验,若P≥0.10和(或)I²≤50%,则采用固定效应模型进行Meta分析;若P<0.10和(或)I²>50%,则采用随机效应模型进行Meta分析。留守儿童体质健康现状评价指标,包括儿童营养性疾病(营养性贫血、营养不良、锌缺乏)检出率,以及生长发育迟缓检出率与体重不达标率。 结果①通过文献检索,共计9篇横断面研究文献符合本研究纳入与排除标准,研究对象为14 588例来自安徽省、广东省、河南省、湖北省、湖南省、山东省、陕西省的儿童。按照本研究对留守儿童的定义,将其分别纳入留守儿童组(n＝8 010)与非留守儿童组(n＝6 578)。②对纳入文献的方法学质量评价结果显示,低质量文献为1篇,中等质量文献为5篇,高质量文献为3篇。③对本研究纳入的儿童健康现状的Meta分析结果显示,营养不良检出率与儿童生长发育迟缓检出率比较,差异均无统计学意义(P>0.05)。留守儿童组儿童的营养性贫血及锌缺乏检出率、体重不达标率,均显著高于非留守儿童组,并且差异均有统计学意义(OR＝1.93、1.64、1.22,95%CI：1.20～3.11、1.19～2.27、1.03～1.44,P＝0.006、0.003、0.020)。 结论我国部分地区留守儿童,较非留守儿童存在更多健康问题,营养性贫血与锌缺乏检出率及体重不达标率更高。本研究受到纳入文献数量和质量的限制,并且各研究间存在异质性,因此尚需开展大样本、多中心、高质量研究,才能全面了解我国留守儿童体质健康现状,更好地为其提供健康保健服务。