Giant splenic hematoma in a patient with infectious mononucleosis: successful nonoperative management

Infectious mononucleosis is rarely complicated by spontaneous splenic rupture, but the latter is the most common cause of death in this disease. We report a young girl with a giant subcapsular splenic hematoma complicated by a left-sided pleural effusion that was managed nonoperatively. Gradual and complete healing occured.     

Necrotizing enterocolitis after red blood cell transfusion in preterm infants with patent ductus arteriosus: a case series

Aim: Both patent ductus arteriosus (PDA) and packed red blood cell (PRBC) transfusion are risk factors for necrotizing enterocolitis (NEC). The combination of PDA and PRBC transfusion may have a synergistic effect on the intestinal circulation. Methods: We present four cases of NEC in very low birth weight (VLBW) infants within 14 h after PRBC transfusion. Results: All infants were growing on full enteral feeding, and they all had a PDA. Conclusion: We are concerned that the simultaneous presence of a PDA and PRBC transfusion in VLBW infants may place the infant at even greater risk of NEC than each of these factors alone.     

Establishment of immunity against Epstein‐Barr virus infection in a patient with CHARGE/complete DiGeorge syndrome after peripheral blood lymphocyte transfusion

CHARGE syndrome is a rare congenital malformation syndrome which may share symptoms with DiGeorge syndrome. Complete DiGeorge syndrome (cDGS) is a severe form of DiGeorge syndrome, characterized by a CD3+ T‐cell count of <50/mm³ due to athymia, and is fatal without immunologic intervention. We performed peripheral blood lymphocyte transfusion (PBLT) from an HLA‐identical sibling without pretransplant conditioning in a CHARGE/cDGS patient with a novel CHD7 splice site mutation. Cyclosporine and short‐term methotrexate were used for graft versus host disease (GVHD) prophylaxis, and neither acute nor chronic GVHD was observed. After PBLT, T‐cell proliferative response to phytohemagglutinin and concanavalin A recovered, and intractable diarrhea improved. EBV infection, evidenced by a gradual increase in the viral genome copy number to a maximum of 2861 copies/μgDNA on day 42 after PBLT, resolved spontaneously. HLA A2402 restricted, EBV‐specific CTLs were detected from peripheral blood on day 148, and EBV seroconversion was observed on day 181. Thus, EBV‐specific immunity was successfully established by PBLT. Our results indicate that PBLT is a simple and effective therapy to reconstitute immune systems in CHARGE/DiGeorge syndrome.     

Association of increased numbers of peripheral blood double-negative T-lymphocytes with elevated serum lgG levels in severely handicapped children

CD3⁺4^–8^– double negative cells in peripheral blood lymphocytes were examined in 21 severely handicapped children divided into two groups according to serum IgG level. All children were bedridden and were taking multiple anticonvulsants and there were no apparent clinical differences between these two groups. Serum levels of IgG correlated well with percentages of CD3⁺4^–8^– double negative lymphocytes in patients of both groups. In comparisons between the two groups, the high IgG group had higher counts of CD3⁺4^–8^– double negative lymphocytes in peripheral blood than the normal IgG group. Two distinct types of double negative cells were identified in the patients with high IgG: one had T-cell antigen receptors of heterodimers, the other had receptors of chains on their surface. As double negative T-cells are reported to have an important role in defence against bacterial infections, the increased numbers of CD3⁺4^–8^– T-cells of both phenotypes in the high IgG patients may reflect exposure to repetitive bacterial stimuli or persistent subclinical infection which in many cases, may be undetectable clinically. Moreover, the hyperimmune states shown by the high serum IgG of these patients may result from the appearance of these unique lymphocytes because they are reported to have a helper function for IgG synthesis in vitro. Taken together, the increased numbers of double negative cells in patients with high IgG may reflect activated defence mechanisms and the development of hyperimmune status.     

Development of hypogammaglobulinaemia in a patient with common variable immunodeficiency

A 3-year-old boy who developed common variable immunodeficiency was investigated for the development of hypogammaglobulinaemia. During a period of 4 years, the combined deficiency of IgA, IgG2 and IgG4 proceeded to include IgG1 and finally IgG3 and IgM. This order of isotypes of IgG subclass deficiencies corresponded to the gene order for the heavy chain constant region for immunoglobulins on chromosome 14.     

常规肺通气功能检测在儿童哮喘评估中的应用

目的探讨哮喘病情与肺功能指标变化特点,为哮喘规范化治疗提供客观依据。方法采用肺功能测定系统对25例哮喘患儿于急性期、缓解期6个月及1年分别行常规肺通气功能测定,比较各期实测值与预计值比值之间的差异。结果哮喘患儿的症状与肺功能指标呈现出一致性,急性期大气道指标用力肺活量(FVC)、1秒钟用力呼气量(FEV1)、最大呼气峰流量(PEF)及75%、50%、25%肺活量时用力呼气流速(FEF25、50、75)、中段呼气流速(MMEF75/25)等实测值与预计值比值均降低,治疗6个月后FVC、FEV1等大气道功能指标基本恢复,1年后小气道功能指标FEF50、75及MMEF75/25等指标恢复。结论肺功能指标在哮喘的病情评估方面具有重要作用,对于哮喘治疗具有重要指导作用。     

Second transplant for a thalassemia patient after graft rejection: with immunosuppression and allogeneic peripheral blood stem cell

A 13-year-old girl suffering from β-thalassaemia major received bone marrow transplantation (BMT) from her HLA identical brother. After initial engraftment, she developed mixed chimerism. Secondary graft rejection occurred at 10 months after BMT and resulted in marrow aplasia. A second transplant with the same bone marrow donor was performed. The patient was conditioned with antithymocyte globulin 90 mg/kg followed by peripheral blood stem cell infusion. There was prompt engraftment and patient reverted to complete chimerism. There were no severe treatment-related complications or acute or chronic graft versus host disease after second transplant. The patient remained transfusion independent at 26 months after second transplant.     

Donor cell-derived acute myeloid leukemia after second allogenic cord blood transplantation in a patient with Fanconi anemia

DCL following hematopoietic stem cell transplantation has been reported in approximately 5% of all leukemic relapses. There have been several reports on DCL, mainly AML after umbilical cord blood transplantation. In this case study, we present a young boy diagnosed with Fanconi anemia who underwent an umbilical cord blood transplantation. Because of the graft failure, he was retransplanted one month later, also with a cord blood transplant. Two years after the second transplant, he developed AML, where 100% of the cells were of female donor origin. The donor, a now 14-yr-old female, was recently reported healthy.     

The role of epigenetics in childhood autoimmune diseases with hematological manifestations

Autoimmune diseases with hematological manifestations are often characterized by chronicity and relapses despite treatment,and the underlying pathogenetic mechanisms remain unknown.Epigenetic alterations play a vital role in the deregulation of immune tolerance and the development of autoimmune diseases.In recent years,study of epigenetic mechanisms in both adult and childhood autoimmune disorders has been seeking to explain the pathophysiology of these heterogeneous diseases and to elucidate the interaction between genetic and environmental factors.Various mechanisms,including DNA methylation,histone modifications(chromatin remodeling),and noncoding RNAs(ncRNAs),have been studied extensively in the context of autoimmune diseases.This paper summarizes the epigenetic patterns in some of the most common childhood autoimmune disorders with hematological manifestations,based on epigenetic studies in children with primary immune thrombocytopenia(ITP),systemic lupus erythematosus(SLE),and juvenile idiopathic arthritis(JIA).Research findings indicate that methylation changes in genes expressed on T cells,modifications at a variety of histone sites,and alterations in the expression of several ncRNAs are involved in the pathogenesis of these diseases.These mechanisms not only determine the development of these diseases but also affect the severity of the clinical presentation and biochemical markers.Further studies will provide new tools for the prevention and diagnosis of childhood autoimmune disorders,and possible novel treatment options.     

Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia

A retrospective cohort study of children with sickle cell anemia (SCA) and strokes was used to test the hypothesis that exchange transfusion at the time of stroke presentation more effectively prevents second strokes than does simple transfusion. Children receiving simple transfusion had a 5-fold greater relative risk (95% confidence interval = 1.3 to 18.6) of second stroke than those receiving exchange transfusion.     

The role of cardiopulmonary exercise testing in evaluating children with exercise induced dyspnoea

Exercise induced dyspnoea (EID) is a common manifestation in children and adolescents. Although EID is commonly attributed to exercise induced bronchoconstriction, several conditions other than asthma can cause EID in otherwise healthy children and adolescents. Cardiopulmonary exercise testing (CPET) offers a non-invasive comprehensive assessment of the cardiovascular, ventilatory and metabolic responses to exercise and is a powerful diagnostic and prognostic tool. CPET is a reproducible, non-invasive form of testing that allows for comparison against age- and gender-specific norms. CPET can assess the child’s exercise capacity, determine the limiting factors associated with this, and be used to prescribe individualised interventions. EID can occur due to asthma, exercise induced laryngeal obstruction, breathing pattern disorders, chest wall restriction and cardiovascular pathology among other causes. Differentiating between these varied causes is important if effective therapy is to be initiated and quality of life improved in subjects with EID.     

Graft versus graft and graft versus host reactions after HLA-identical bone marrow transplantation in a patient with severe combined immunodeficiency with transplacentally acquired lymphoid chimerism

We describe a patient with severe combined immunodeficiency and transplacental transfer of maternal T cells who received an unfractionated HLA-identical sibling bone marrow transplant without prior conditioning. He presented prior to transplantation with a dermatitis later diagnosed as mild graft versus host disease. He had a normal absolute lymphocyte count, but proliferative responses to mitogens were very low. Antigens of the noninherited maternal HLA haplotype were detected on his blood lymphocytes. After transplantation, he developed a severe reaction including fever, cutaneous erythema and hepatosplenomegaly. Lymphocytes carrying the noninherited maternal HLA haplotype disappeared from his circulation, and his unprimed mononuclear cells became spontaneously cytotoxic to maternal lymphoblasts. He subsequently developed a lymphocytosis of 69,000/mm³, diarrhea, elevated transaminases and a worsening rash, necessitating treatment with immunosuppressive agents. Full T-cell engraftment and evidence of B-cell function later ensued and spontaneously cytotoxic lymphocytes against maternal cells disappeared by 47 days post-transplantation. We postulate that the patient's constellation of signs and symptoms after transplantation represented a combination of severe graft versus graft and mild graft versus host reactions.     

不同血清型视神经脊髓炎谱系疾病双向队列研究

背景：视神经脊髓炎谱系疾病（NMOSD）根据血清学可分为AQP4-IgG阳性、MOG-IgG阳性和血清学阴性（2种抗体均阴性）,目前对于不同血清型NMOSD患儿的临床表型及影像学特征的差异尚不明确。 目的：通过建立NMOSD患儿双向随访队列,比较不同血清型NMOSD临床表型差异,以利于临床识别。 设计：动态双向队列研究。 方法：2012年1月至2021年3月在北京大学第一医院儿科诊断为NMOSD患儿即进入队列,依据事先设计的临床观察量表进行临床特征信息收集,回顾性采集既往的临床资料（首次诊断收集发病以来的临床症状和体征,他院诊断的收集既往的诊疗经过）,对临床特征进行随访观察,队列终点为起病至末次随访时间≥6个月。以AQP4-IgG阳性、MOG-IgG阳性和血清学阴性分为3组。 主要结局指标：不同血清型的临床特征。 结果：46例NMOSD患儿中,MOG-IgG阳性组、AQP4-IgG阳性组和血清学阴性组分别为21、12和13例,3组起病年龄、起病至末次随访中位病程和发作次数差异均无统计学意义,性别构成比差异有统计学意义,AQP4-IgG阳性组以女孩多见。首次发作的临床表型共74个,3组大脑综合征和脑干症状差异有统计学意义,大脑综合征在MOG-IgG阳性组（42.9%）和血清学阴性组（43.8%）常见,脑干症状在AQP4-IgG阳性组（33.3%）和血清学阴性组（23.1%）常见;病程中所有发作临床表型共196个,3组横贯性脊髓炎（TM）、大脑综合征、脑干症状和延髓最后区症状差异均有统计学意义,TM在AQP4-IgG阳性组占比最高（43.9%）,大脑综合征在MOG-IgG阳性组（36.2%）和血清学阴性组（34.4%）常见,脑干症状在AQP4-IgG阳性组（17.1%）和血清学阴性组（18.0%）占比较高、延髓最后区症状在AQP4-IgG阳性组（12.2%）常见。头颅MR共收集到134个,主要受累部位为皮层下白质（59.0%）和脑干 （47.8%）;脊髓MR共采集到42个,3组皮层下白质、脑室旁白质、胼胝体、丘脑、基底节、脑干差异均有统计学意义,皮层下白质在MOG-IgG阳性组和血清学阴性组占比较大,脑室旁白质在AQP4-IgG阳性组和血清学阴性组占比较大,胼胝体在AQP4-IgG阳性组中常见,丘脑在AQP4-IgG阳性组、MOG-IgG阳性组占比较大,基底节在MOG-IgG阳性组占比较大,脑干在AQP4-IgG阳性组占比较大。3组胸髓和长节段脊髓炎差异均有统计学意义,在3组中普遍受累,以AQP4-IgG阳性组更常见（94.1%和100%）。共收集94次急性期脑脊液和46次自身免疫性抗体数据,3组脑脊液有核细胞数、蛋白和不同自身免疫性抗体差异均无统计学意义。46例均得到了末次随访EDSS评分,中位数为1.5（0~4.5）分,3种不同血清型末次随访EDSS评分差异无统计学意义。 结论：AQP4-IgG阳性及血清学阴性NMOSD以女孩多见。大脑综合征常见于MOG-IgG阳性和血清学阴性NMOSD。延髓最后区症状常见于AQP4-IgG阳性患儿。皮质下白质受累在MOG-IgG阳性和血清学阴性患儿更常见,长节段脊髓炎在AQP4-IgG患儿中更常见。     

免疫毒素去除脐血T细胞的效率及对免疫功能重建的影响

目的：比较不同亚型抗体免疫毒素（IT）体外去除挤血T细胞的效率及其对髓系和淋巴系造血祖细胞增殖反应的影响。方法：（1）间拉免疫荧光法测定脐血、外周血及富集干细胞的正常供者外周血中CD2^ 、CD3^ 、CD4^ 、CD5^ 、CD7^ 、CD8^ T亚群细胞的含量;（2）直接免疫荧光法测定脐血CD3^－CD5^ T亚群细胞含量;（3）噻唑蓝（MTT）比色法分别观察三组抗入白细胞分化抗原的单克隆抗体（CD2^ 、CD4^ 、CD7^ ）与完整蓖麻毒素（ricin)耦联制备的三组免疫毒素（CD2ricin、CD4ricin、CD7ricin）对挤血T淋巴细胞转化功能的影响;（4）用造血祖细胞培养的方法分别观察三组免疫毒素对脐血粒单系造血祖细胞（CFU－GM）和T淋系祖细胞（CFU－TL）增殖反应的影响。结果：（1）脐血中含有一定比例的CD2^ 、CD3^ 、CD4^ 、CD5^ 、CD7^ 、CD8^ T亚群细胞,同时可检测到低比例的CD^－CD5^ 早期T细胞;（2）CD2ricin在10^10-10^-8mol/L,CD4ricin在10^-8-10^-7mol/L,CD7ricin在10^-9-10^-8mol/L均能有效抑制脐血T淋巴细胞的转化功能;（3）CD2ricin和CD7ricin在10^-10-10^-9mol/L,CD4ricin在10^-9-10^-7mol/L范围内对CFU－GM的增殖反应无显著影响,CD2ricin在10^-10-10^-9mol/L,CD4ricin在10^-8-10^-7mol/L浓度范围内对CFU－TL的增殖有轻度的抑制作用;CD7ricin在10^-10-10^-8mol/L范围对CFU－TL的增殖有显著范围内对CFU－TL的增殖有轻度的抑制作用;CD7ricin在10^-10-10^-8mol/L范围对CFU－TL的增殖有显著的抑制作用,不能作为去除T细胞的免疫毒素;（4）三组免疫毒素对CFU－TL的抑制作用均高于对CFU－GM的抑制作用。结论：CD2ricin、CD4ricin两种免疫毒素在一定浓度范围内可去除不同亚型的T细胞,并且不影响其造血的恢复。但对免疫功能重建可能会产生一定的影响。     

Three relapses after a haploidentical transplantation in a pediatric patient: Cure with no further transplantation

Isolated extramedullary relapse (EMR) after hematopoietic stem cell transplantation (HSCT) is a highly fatal condition that creates uncertainty regarding treatment options. Although certain approaches such as repeat HSCT and donor lymphocyte infusion are recommended, we report a patient with acute lymphoblastic leukemia who had three isolated EMRs after HSCT at different locations and at different times that were responsive to local and systemic therapies, without the need for a second transplantation.     

Nondisclosure of human immunodeficiency virus and hepatitis C virus coinfection in a patient with hemophilia: medical and ethical considerations

This article discusses a medical and ethical dilemma: whether to disclose a positive HIV (human immunodeficiency virus)/HCV (hepatitis C virus) coinfection to an adolescent boy without symptoms with hemophilia despite the objections of his parents. An actual case history is presented and the dilemma faced by the medical team is discussed. Numerous family conferences, all excluding the patient, held during the last 5 years discussed the medical team's obligation for full disclosure, the emerging autonomy of the patient, and the potential for medical disaster (e.g., HIV transmission) if full disclosure were not permitted. Despite this, the family did not agree to allow disclosure. The patient and parents assured us of his sexual inactivity. Legal opinion was sought from the university counsel. The dilemmas are multiple. Is there a convincing argument to insist on disclosure of these facts to this patient, particularly when there is ambiguity regarding the appropriateness of HIV and HCV treatment? Does the ethical argument that he is at potential risk for transmitting HIV/HCV outweigh the rights of the family? What are the rights of the rest of the family? What are the rights of the minor? Is it our ethical responsibility to disclose a probably fatal diagnosis?