婴儿血管瘤合并PHACE综合征的发病机制与诊治进展

婴儿血管瘤(IH)是儿童时期最常见的良性肿瘤,以出生后迅速增长和后期缓慢自然消退为其典型的临床特征。部分面部节段型IH患者可合并PHACE综合征。PHACE综合征为累及全身多个系统的血管神经、血管皮肤病变,常常造成机体结构以及功能损害。近期的研究表明,PHACE综合征发病的可能机制主要包括:缺氧假说、中胚层血管内皮细胞异常假说、基因异常假说、胎盘绒毛膜绒毛间质干细胞假说。目前,IH合并PHACE综合征的治疗药物主要包括β受体阻滞剂、糖皮质激素、m TOR受体抑制剂。本文主要针对IH合并PHACE综合征的发病机制、诊断以及治疗进展进行综述,以期为该病的临床诊治提供帮助。     

Japanese familial case of myoclonus–dystonia syndrome with a splicing mutation in SGCE

Myoclonus–dystonia syndrome (MDS) is a rare autosomal‐dominant movement disorder characterized by brief, frequently alcohol‐responsive myoclonic jerks that begin in childhood or early adolescence, caused by mutations in the ε‐sarcoglycan gene (SGCE). The patient was a 6‐year‐old boy. At 2 years 8 months, he had abnormal movement when he ran due to dystonia of his left leg. At 3 years 5 months, he exhibited dystonia and myoclonic movement of his arms when eating. Myoclonus was likely to develop when he felt anxiety or exhaustion. Genomic DNA showed a heterozygous mutation in SGCE (c.109 + 1 G > T). His father and uncle with the same mutation also experienced milder dystonia or myoclonic movements. SGCE mutation can cause a broad range of clinical symptoms between and within families. We should consider MDS as a differential diagnosis for patients with paroxysmal walking abnormalities and/or myoclonic movements.     

Chemotherapy and interferon‐α treatment of Erdheim–chester disease

Erdheim–Chester disease (ECD) is a rare non‐Langerhans cell histiocytosis of an unknown origin. The prognosis of ECD is variable, and it mainly depends on the involved anatomic sites. The treatment modalities have not been standardized. Interferon‐α (IFN) has been reported to be effective in the management of ECD. We report here on an uncommon case with ECD in a 17‐year‐old female who had multiple lesions in the whole body and she was treated with chemotherapy and IFN. She has remained disease‐free for 2 years after the completion of treatment. Pediatr Blood Cancer. 2010;55:745–747. © 2010 Wiley‐Liss, Inc.     

Trends in the off‐label use of β‐blockers in pediatric patients

The use of US Food and Drug Administration (FDA)‐approved drugs for the treatment of an unapproved indication or in an unapproved age group, or at doses or route of administration not indicated on the label is known as off‐label use. Off‐label use may be beneficial in circumstances when the standard‐of‐care treatment has failed, and/or no other FDA‐approved medications are available for a particular condition. In pediatric patients, off‐label use may increase the risk of adverse events as pharmacokinetic and pharmacodynamic data are limited in children. Approximately 73% of off‐label drugs currently prescribed for various conditions do not have sufficient scientific evidence for safety and efficacy. For example, β‐blockers are a class of drugs with FDA‐approval for very few indications in pediatrics but are commonly used for various off‐label indications. Interestingly, the proportion of off‐label use of β‐blockers in adults is at about 52% (66.2 million) of the total number of β‐blockers prescribed. The frequency of off‐label use of β‐blockers in children is also high with limited data on the indications as well as safety and efficacy. We present trends in off‐label use of β‐blockers in children to discuss drug safety and efficacy and include recommendations for pediatric providers.     

β–HCG Elevation in Wilms Tumor: An Uncommon Presentation

Wilms tumor (nephroblastoma) is a readily diagnosed common abdominal tumor in children. Rarely, it may present with factors that may confound the diagnosis. We report a 6‐year‐old female child who presented with a rapidly growing and invasive abdominal mass with the histopathologic features of Wilms tumor associated with an elevated serum beta human chorionic gonadotropin, which has not been previously reported in this condition.     

Peripheral expansion of Vδ1-Jδ1/Jδ2+γδT cells and large granular lymphocytes in a patient with Wiskott-Aldrich syndrome

A 7 month old Japanese boy was diagnosed to have Wiskott-Aldrich syndrome (WAS) because of eczema, thrombocytopenia, progressive immune defect and CD43 (sialophorin) abnormality. He had developed repeated infections since 16 months of age. γδT cell-receptor positive T cells in the peripheral blood were gradually increased from 3.1% (7 months of age) to 5.6% (12 months), 19.6% (18 months) and 56.7% (25 months). The phenotypes of expanded γδT cells were δTCS1-positive (Vδ1-Jδ1/Jδ2) and CD8 dim-positive. The proportion of increased granular lymphocytes correlated well with that of γδT cells. The significance of peripheral expansion of γδT cells and granular lymphocytes in WAS is discussed.     

Hemophagocytic lymphohistiocytosis: Pathogenesis,diagnosis, and management

Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that is classified into primary and secondary HLH. Primary HLH consists of monogenic disorders that mainly affect the perforin‐mediated cytotoxicity of cytotoxic T lymphocytes and natural killer cells. Secondary HLH occurs as a complication in various settings such as infection, malignancy, autoimmune disease, and post‐allogeneic hematopoietic stem cell transplantation. Both primary and secondary HLH are characterized by uncontrolled hypercytokinemia that results in myelosuppression and vascular endothelium damage. More than 10% of patients with HLH die within 2 months of diagnosis due to bleeding in the visceral organs, opportunistic infection due to neutropenia, or multiple organ failure. The most obvious presentations of HLH are persistent fever refractory to antimicrobial agents and hyperferritinemia due to hypersecretion of various cytokines. The first rule is not to overlook signs of hypercytokinemia and to settle the hyperactivated immunological state as soon as possible. In addition, to improve outcome, it is essential to identify the disorders underlying HLH and provide disorder‐appropriate treatment.     

WASP–WIP complex in the molecular pathogenesis of Wiskott–Aldrich syndrome

Wiskott–Aldrich syndrome (WAS) is an X‐linked primary immunodeficiency disease characterized by recurrent infection, thrombocytopenia, and eczema. The gene responsible for X‐linked WAS encodes the Wiskott–Aldrich syndrome protein (WASP), which is expressed in hematopoietic cells and which regulates T‐cell activation and cytoskeletal reorganization in T‐cell receptor (TCR) signaling. Here, I review my recent research on WASP and the WASP‐interacting protein (WIP) complex in T cells. I and my colleagues first established a diagnostic screening method using flow cytometry and genetic analysis, and elucidated the molecular pathogenesis in WAS patients with unique clinical manifestations. We investigated the mechanisms by which WASP is recruited to lipid rafts following TCR stimulation and to immunological synapses between antigen‐presenting cells and T cells. Subsequently, we elucidated the molecular mechanisms by which WASP is degraded by calpain and ubiquitinated by Cbl‐family proteins, which terminate WASP activation. More importantly, we found that WIP plays a critical role in WASP stability in T cells. These results provide new insights into the molecular pathogenesis of X‐linked WAS and have facilitated the identification of WIP deficiency as an autosomal recessive form of WAS.     

TCR α+β+/CD19+ cell–depleted hematopoietic stem cell transplantation for pediatric patients

TCR α⁺β⁺/CD19⁺ cell depletion is an emerging technique for ex vivo graft manipulation in HSCT. We report 20 pediatric patients who underwent TCR α⁺β⁺/CD19⁺ cell–depleted HSCT in four Australian centers. Conditioning regimen was dependent on HSCT indication, which included immunodeficiency (n = 14), Fanconi anemia (n = 3), and acute leukemia (n = 3). Donor sources were haploidentical parent (n = 17), haploidentical sibling (n = 2), or matched unrelated donor (n = 1). Mean cell dose was 8.2 × 10⁸/kg TNC, 12.1 × 10⁶/kg CD34⁺ cells, and 0.4 × 10⁵/kg TCR α⁺β⁺ cells. All patients achieved primary neutrophil and platelet engraftment, with average time to neutrophil engraftment 11 days (range 8‐22) and platelet engraftment 24 days (range 12‐69). TRM at 1 year was 15%. Rate of grade II‐IV aGVHD at 1 year was 20% with no grade III‐IV aGVHD seen. CMV reactivation occurred in 81% of CMV‐positive recipients, with one patient developing CMV disease. Average time to CD4 recovery (>400 × 10⁶/L) was 258 days. Overall survival for the cohort at 5 years was 80%. This report highlights the initial experience of TCR α⁺β⁺/CD19⁺ cell–depleted HSCT in Australian centers, with high rates of engraftment, low rates of aGVHD, and acceptable TRM.     

Pathophysiology and Japanese clinical characteristics in Marfan syndrome

Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin‐1, a major component of the microfibrils of the extracellular matrix. Fibrillin‐1 interacts with transforming growth factor‐β (TGF‐β), and dysregulated TGF‐β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF‐β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time‐consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome.     

围产新生儿新型冠状病毒感染防控管理预案（第三版）

自2020年新型冠状病毒（severe acute respiratory syndrome coronavirus 2）全球大流行以来，病毒株几经变异，传染性增强，致病性减弱，人群疫苗接种率提高，国内疫情防控进入新的阶段。中国当代儿科杂志编辑委员会围产新生儿新型冠状病毒感染防控管理预案工作组于2020年1月和2020年3月，先后制定了第一版和第二版围产新生儿新型冠状病毒感染防控管理预案。为适应新的防控需求，有必要对管理预案进行更新，以更好地指导临床实践。因此，该工作组制定了第三版预案。     

Urinary β2‐microglobulin and bronchopulmonary dysplasia: Trends in preterm infants

Background

The developmental process of bronchopulmonary dysplasia (BPD) is not identical between very preterm infants born small for gestational age (SGA) and those born appropriate for gestational age (AGA). In this study, we compared the pattern of the inflammatory response in infants of each group, by measuring urinary β2‐microglobulin (Uβ2M) as an alternative, concise, and less‐invasive biomarker.

Methods

Uβ2M and clinical details were examined at birth and at 4 weeks of age in 146 very preterm infants.

Results

Of the 57 infants diagnosed with BPD, 18 were SGA, and 39 were AGA. Uβ2M at birth was significantly lower in SGA BPD infants than in AGA BPD infants, but it increased with time. The prevalence of chorioamnionitis (CAM) was significantly lower in SGA BPD infants than in AGA BPD infants, while that of pregnancy‐induced hypertension was the opposite.

Conclusions

Exposure to prenatal factors other than CAM may sensitize fetal lungs to become vulnerable to postnatal inflammation in very preterm SGA infants with BPD.     

人类免疫缺陷病毒暴露未感染婴幼儿的神经心理发育状况

目的研究人类免疫缺陷病毒（human immunodeficiency virus，HIV）暴露未感染（HIV-exposed uninfected，HEU）婴幼儿神经心理发育水平，探讨母亲HIV感染对HEU婴幼儿神经心理发育的影响。方法选取2019年6月至2020年12月在云南省4家妇幼保健院专案管理且符合纳入标准的141名0~18月龄HIV感染母亲所生未感染HIV，即HEU婴幼儿作为HEU组，以性别、年龄、出生方式、出生体重、胎龄为配对条件，按1∶1配对141名健康母亲所生婴幼儿，即无HIV暴露、无HIV感染（HIV-unexposed uninfected，HUU）婴幼儿为对照，应用Griffiths发育评估量表中文版（Griffiths Development Scales-Chinese Edition，GDS-C）评估运动、个人-社会、听力语言、手眼协调、表现（视感知空间整合能力）5个领域发育情况，同时采用问卷调查方式收集有关信息。采用多因素logistic回归分析探讨母亲HIV感染对HEU婴幼儿神经心理发育的影响。结果HEU组听力语言和表现2个领域迟缓检出率显著高于HUU组（P<0.05）。多因素logistic回归分析显示，HIV暴露增加了婴幼儿听力语言（OR=2.661，95%CI：1.171~6.047）和表现（OR=2.321，95%CI：1.156~4.658）2个领域迟缓发生的风险（P<0.05）。结论母亲感染HIV可对其分娩的未感染HIV婴幼儿听力语言和表现领域的发育产生负面影响，其机制有待进一步研究。