Adrenal insufficiency (AI) is a well-known cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear.

We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI.

Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis.

Conclusion: Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

 

Intracranial germ cell tumors (IGCTs) are a group of rare pediatric brain tumors which include various subtypes. The current understanding of the etiology of the tumors and their optimal management strategies remain controversial.

The data on IGCTs were collected from articles published in the past 20 years, and the origin and etiology of IGCTs at molecular level as well as the relative roles of varied treatment strategies in different prognosis groups according to Matsutani's classifi cation were reviewed.

Recent cellular and molecular evidence suggests that IGCTs may arise from the transformation of endogenous brain cells; and findings in the molecular characterization of IGCTs suggest roles of CCND2, RB1, and PRDM14 in the pathogenesis of IGCTs and identify the KIT/RAS and AKT1/mTOR pathways as potential therapeutic targets in future. According to Matsutani's classifi cation of IGCTs, the good prognosis group includes both germinomas and mature teratomas. For germinomas, both radiation alone and reduced-dose radiotherapy in combination with adjuvant chemotherapy are effective, while complete surgical excision is recommended for mature teratomas. In the intermediate prognosis group, immature teratoma has been successfully treated with gamma knife surgery. However, for intermediate prognosis IGCTs other than immature teratomas, gross total resection with adjuvant chemotherapy and radiotherapy or gamma knife surgery may be necessary to achieve cure. In the poor prognosis group, survival outcomes are unsatisfactory, and complete surgical resection combined with more intensive chemotherapy and radiotherapy remains the best available treatment option at this time.

IGCTs should be strictly classified according to their pathological categories before administering pathology-specific treatments. Although open microsurgical excision is the traditional surgical strategy for IGCTs, recent publications also support the role of endoscopic surgical options for pineal region IGCTs.

 

Key words: etiology; germ cell tumor; prognosis; treatment

The incidence of asthma and allergic rhinitis (AR) is significantly increased, especially in younger children. Current treatment for children with asthma and allergic rhinitis include allergen avoidance, standard pharmacotherapy, and immunotherapy. Since standard pharmacotherapy is prescribed for symptoms, immunotherapy at present plays an important role in the treatment of allergic diseases. This article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and asthma.

PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms "asthma", "allergic rhinitis", "children", and "immune therapy". Additional articles were identified by hand searching of the references in the initial search.

Numerous studies have shown that sublingual application of allergen specific immunotherapy (SLIT) is an adequate, safe and efficient substitution to subcutaneous route of allergens administration (SCIT) in the treatment of IgE-mediated respiratory tract allergies in children. According to the literature, better clinical efficacy is connected with the duration of treatment and mono sensitized patients.

Conclusions: At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT. SLIT reduces the symptoms of allergic diseases and the use of medicaments, and improves the quality of life of children with the diseases.

 

Key words: allergic asthma; allergic rhinitis; allergic sensitization; immunotherapy

Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases.

Original research articles and literature reviews published in PubMed-indexed journals.

DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development.

Conclusions: DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

 

Key words: congenital heart disease; development; DNA modifi cation; 5-hydroxymethylcytosine; neurological disorders; RNA modifi cation

There is no consensus on the effectiveness of prenatal diagnosis except for hospitalized outcomes. Hence, a meta-analysis of published literature was conducted to assess the effect of prenatal diagnosis.

Literature review has identified relevant studies up to December 2013. A meta-analysis was performed according to the guidelines from the Cochrane review group and the PRISMA statement. Studies were identified by searching PubMed, Embase, the Cochrane Central Register of Controlled Trials and World Health Orgnization clinical trials registry center. Meta-analysis was performed in a fixed/random-effect model using Revman 5.1.1 according to the guidelines from the Cochrane review group and the PRISMA guidelines.

The results from 13 cohort studies in 12 articles were analyzed to determine the optimal treatment with the lower rate of perioperative mortality in prenatal diagnosis. The superiority of a prenatal diagnosis has been proven because the surgical procedure could be done in the early neonatal period (95% CI, -0.76, -0.40). The prenatal diagnosis has also remarkably reduced the preoperative and postoperative mortality rates in cases of transposition of the great arteries (95% CI=0.06, 0.80; 95% CI=0.01, 0.82, respectively), as well as the overall results with all subtypes (95% CI=0.18, 0.94; 95% CI=0.46, 0.94, respectively).

Prenatal diagnosis is effective in perinatal management with an earlier intervention for major congenital heart disease, but only results in a reduced perioperative mortality in cases of transposition of the great arteries. Further investigations are required to evaluate the effect of prenatal diagnosis on life quality during a long-term follow-up.

 

Key words: congenital heart disease; delivery; echocardiography; fetal diagnosis; meta-analysis

 

Kawasaki disease (KD) has now become the leading cause of acquired heart disease among children in developed countries. This study investigated whether patients with KD have an increased risk of atherosclerosis.

Electronic databases, including PubMed, Embase and Springer link, were searched through June 1, 2015, for eligible studies. Studies were included when they met the following criteria: 1) an observational study focusing on evaluating the risk factors for atherosclerosis in patients with KD; 2) KD was diagnosed clinically according to the Japan Kawasaki Disease Research Committee or American Heart Association's diagnostic criteria; 3) the study subjects were KD patients without coronary heart disease or related cardiovascular disease (KD group) and non-KD patients as control (control group), and 4) investigation of important atherosclerosis risk factors, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglycerides (TG), systolic blood pressure (SBP), and flow mediated dilatation (FMD). The methodological quality of the included studies was evaluated using the Newcastle- Ottawa Scale. Mean difference (MD) and relative risk (RR) and corresponding 95% confidence intervals (CI) were used to calculate the pooled results.

Sixteen studies were included with a total of 870 patients, including 421 KD patients and 449 non-KD controls. Differences in TG and SBP between KD patients and controls were not significant; in contrast, TC and LDL levels were significantly higher in KD patients than the controls, whereas FMD in the KD patients was significantly lower.

KD patients may have an increased risk of developing atherosclerosis.

 

Key words: atherosclerosis; flow-mediated dilatation; Kawasaki disease; meta-analysis; total cholesterol

To investigate strategies used for the management of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants.

A survey of neonatal specialists working in US academic institutions with fellowship training programs.

Eighty percent (72/89) of the identifi ed academic institutions had at least one physician who responded to the survey. Among respondents, 85% (171/201) agreed or strongly agreed to use continuous positive airway pressure (CPAP) initially for the management of RDS, and the majority agreed or strongly agreed to use a fraction of inspired oxygen (FiO2) ≥0.4 and a mean airway pressure (MAP) ≥10 cm H2O as a criteria for surfactant therapy; and 73% (146/200) sometimes or always used caffeine to prevent BPD. Only 25% (50/202) sometimes or almost always used steroids to prevent or treat BPD. Identified indications to use steroids were 3 or more extubation failures or inability to extubate beyond 8 weeks of age.

Variability in treatment strategies of ELBW is common among neonatal specialists. However, the majority of the respondents agreed or strongly agreed to use early CPAP for the management of RDS, consider a FiO2 ≥0.4 and a MAP ≥10 cm H2O as criteria for surfactant therapy, and sometimes or almost always used caffeine to prevent BPD. Steroids continue to have a role in the management of BPD in infants who are diffi cult to extubate.

 

Varicella-zoster virus infection is associated with significant morbidity and mortality in immune-compromised children, despite treatment with antiviral agents. Universal varicella vaccine programs have significantly decreased this risk in many high income countries, but in most low-income and middle income countries, the burden of varicella in children treated for malignancy is poorly defined.

We retrospectively reviewed records of children at the National Unit of Pediatric Oncology (UNOP) in Guatemala diagnosed with varicella between January 2009 and March 2013 in order to calculate incidence of varicella and evaluate morbidity, mortality, treatment interruption, and cost.

Fifty-nine cases of varicella were identified. Incidence was 23.4 cases per 1000 person-years (p-y). 66.1% of cases occurred in children with leukemia (median age 5.2 years; interquartile range 3.4-7 years) and 41.0% of these occurred during maintenance therapy. Source of exposure was identified for 14/59 (23.7%) children. Most were hospitalized (71.2%) and given intravenous acyclovir (64.4%). Eight (13.6%) children required critical care, and two (3.4%) died from disseminated varicella with multiorgan failure. Chemotherapy was delayed or omitted due to varicella in 50%. No significant differences in outcomes based on nutritional and immunologic status were detected. The minimum average cost of treatment per episode was 598.75 USD.

Varicella is a significant problem in children treated for cancer in Guatemala, where effective post-exposure prophylaxis is limited. In the absence of universal varicella vaccination, strategies to improve recognition of exposure and the future use of novel inactivated vaccines currently under investigation in clinical trials could mitigate this burden.

 

Key words: cancer; developing countries; immunocompromised host; oncology; varicella

This study aimed to determine for the first time the age- and gender-specific reference intervals for biomarkers of bone, metabolism, nutrition, and obesity in a nationally representative sample of the Iranian children and adolescents.

We assessed the data of blood samples obtained from healthy Iranian children and adolescents, aged 7 to 19 years. The reference intervals of glucose, lipid profile, liver enzymes, zinc, copper, chromium, magnesium, and 25-hydroxy vitamin D [25(OH)D] were determined according to the Clinical & Laboratory Standards Institute C28-A3 guidelines. The reference intervals were partitioned using the Harris–Boyd method according to age and gender.

The study population consisted of 4800 school students (50% boys, mean age of 13.8 years). Twelve chemistry analyses were partitioned by age and gender, displaying the range of results between the 2.5th to 97.5th percentiles. Significant differences existed only between boys and girls at 18 to 19 years of age for low density lipoprotein-cholesterol. 25(OH)D had the only reference interval that was similar to all age groups and both sexes.

This study presented the first national database of reference intervals for a number of biochemical markers in Iranian children and adolescents. It is the first report of its kind from the Middle East and North Africa. The findings underscore the importance of providing reference intervals in different ethnicities and in various regions.

 

Key words: adolescents; biomarkers; chemistry; pediatrics; reference intervals

Exposure to household domestic animals such as cats and dogs in early life may have some role in pathogenesis of asthma. Racial differences exist in the prevalence of asthma. We hypothesized that there may also be racial differences in pet ownership in families with asthma.

A cross sectional study was conducted from June 2011 to December 2014 on 823 of 850 (97%) families of children with asthma for pet ownership. Comparisons among racial groups were done using chi square analysis and one-way analysis of variance.

The mean age of the cohort was 6.9±4.4 years. A total of 540 (65.62%) patients were Caucasian, 195 (23.7%) African American, 42 (5.1%) hispanics, and 26 (3.2%) biracial with one Caucasian parent. Pets in the home were reported by 470 (58.5%) households. Signifi cantly fewer African American and hispanic families had pets in the home (26.9% and 44.7%) than biracial and Caucasian families (72% and 69.9%, P<0.001). Likewise, significantly more biracial and Caucasian families were noted to have dogs (52% and 54.4%) or cats (25.4% and 40%) or both cats and dogs (28% and 18%) than African Americans families (20.3%, P<0.001; 7.1%, P<0.001) and (4.6%, P<0.001), respectively.

Among families with asthmatic children, pet ownership is significantly more likely in Caucasian families compared with African-American and Hispanic families, thus there is a racial diversity in pet ownership among families of children with asthma.

 

Key words: asthma; cat; children; dog; ethnicity; pets

Hepatitis B virus-associated glomerulonephritis (HBV-GN) is one of the extrahepatic manifestations after HBV infection, which would cause great clinical harm to people. The present study was undertaken to investigate the HBV-GN genotypes and its clinical relevance in Chinese children.

A total of 41 HBV-infected children diagnosed with HBV-GN were enrolled in the study. All patients underwent liver and kidney biopsy. The genotypes and cccDNA were detected in their serum samples to analyze the relationship between HBV genotypes and clinical characteristics, cccDNA, and pathology.

Among the 41 children with HBV-GN, 29 (70.7%) had genotype C, 10 (24.4%) had genotype B, 2 (4.9%) had genotype B/C, and none of them had genotype non-B/C. Most children had genotypes B or C; moreover, the genotype C was the most frequent one. The incidence of hematuria and albuminuria, reduction in complement C3, increase in serum alanine aminotransferase levels and renal insufficiency in the children with genotype C were signifi cantly higher than those in the children with genotype B (P<0.05); however, there was no statistically significant difference in hypertension and hepatomegaly (P>0.05). The frequency of HBV cccDNA positive in the genotype C group was significantly higher than that in the genotype B group (72.4% vs. 30.0%, P<0.05). No difference was observed in hepatic inflammation grades and stages of fibrosis between the two groups (P>0.05).

Genotype C was the most frequent genotype in the described group of patients with HBV-GN, and the liver and kidney damage indicators were more likely to occur in patients with genotype C.

 

The role of idiopathic nephrotic syndrome (INS) in the pathogenesis of atherosclerosis in childhood has not been clearly elucidated. However, antioxidative defense in INS is thought to be imbalanced. This study aimed to assess the changes of plasma concentration of selected aminothiols in the blood of children with INS at various stages of the disease.

This cross-sectional study was conducted in 125 children aged 2-18 years. The children were divided into 4 groups: group A, early relapse (n=37); group B, early remission for 4-6 weeks from the onset (n=37); group C, late steroid-free remission (n=31); and group D, long-term remission for 2-5 years (n=20). Control group (E) consisted of 30 age- and gender-matched healthy children. The study protocol comprised an analysis of plasma concentrations of glutathione, homocysteine, cysteine and cysteinylglycine by high-performance liquid chromatography. Fractions of protein-bound and free aminothiols were measured. Endothelial injury was assessed by thrombomodulin, PAI-1 concentration, and von Willebrand factor activity.

The children with INS had unbalanced aminothiol metabolism only in relapse and early remission that shifted towards increased oxidative processes. Administration of cyclosporine A caused a significant increase in homocysteine and cysteine concentration. Changes in aminothiol metabolism were significantly related to endothelial injury.

The findings of this study may be helpful in elucidating the pathogenesis of premature atherosclerosis in patients with INS refractory to the treatment or in the case of frequent relapse.

 

Key words: aminothiols; children; cyclosporine A; homocysteine; nephrotic syndrome

This study was designed to determine whether the occurrence of clubfoot follows a seasonal pattern in neonates from eastern and south-eastern China and to speculate the potential etiology of clubfoot.

We reviewed 239 neonates with clubfeet during a period of 4 years as well as the monthly neonatal population of the Sixth National Population Census. Seasonal variations in terms of month of birth and severity were analyzed.

The incidence of clubfoot in neonates from eastern and south-eastern China showed seasonal variations, and the incidence was higher in autumn with a reference to the average birth rate in this corresponding area. No significant difference was found in severity of clubfoot.

This seasonal pattern is of significant value to further understanding the etiology and pathogenesis of clubfoot in the corresponding area of China.

 

Key words: clubfoot; etiology; seasonality

This study aimed to discribe the experience in supporting children with refractory cardiopulmonary failure with extracorporeal membrane oxygenation (ECMO).

We retrospectively reviewed 12 children with refractory cardiopulmonary failure supported with ECMO from February 2009 to August 2015 in the Pediatric Intensive Care Unit (PICU), Children's Hospital, Zhejiang University School of Medicine.

Seven of the 12 patients were weaned successfully from ECMO and dischaged from the hospital, with a survival rate of 58.3% (7/12). Among them, fi ve patients had acute fulminant myocarditis (AFM). Complications during ECMO included hemorrhage, hemolysis, thrombosis, acute kidney injury, and secondary hematogenous infection. During 1-24 month follow-up, the seven surviving patients recovered with normal cardiopulmonary function.

ECMO is useful for supporting children with refractory cardiopulmonary failure, especially for treatment of AFM.

 

Key words: acute fulminant myocarditis; acute respiratory distress syndrome; extracorporeal membrane oxygenation

Glutaric acidemia type I (GA-I) is a rare metabolic disorder caused by mutation of the glutaryl- CoA dehydrogenase (GCDH) gene. The occurrence of rhabdomyolysis with GA-I is extremely rare.

We reported a child with recurrent rhabdomyolysis and undiagnosed glutaric acidemia type I (GA-I). And a literature review was performed.

A 4.5-year-old girl was admitted to our hospital due to recurrent rhabdomyolysis for 3 times within three years. At the third admission, she was diagnosed with GA-I by biochemical testing and mutation analysis. The girl was found to have a serine to leucine replacement mutation of the GCDH gene in exon 8 at position 764. Other three patients with rhabdomyolysis and GA-I were discovered by literature searching.

This report highlights that patients with GA-I may have an increased risk of rhabdomyolysis.

 

Key words: GCDH mutation; glutaric acidemia type I; rhabdomyolysis