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Vol 15, No 1
Vol 15, No 1 February 2019 ISSN 1708-8569
Review articles
Original articles
Clinical summary
Early child development: a challenge in China
  Jie Shao
  [Abstract] [Full Text] [PDF]  
Review articles:
An update on the role of RANKL每RANK/osteoprotegerin and WNT- ß-catenin signaling pathways in pediatric diseases
  Giacomina Brunetti, Gabriele D*Amato, Mariangela Chiarito, Apollonia Tullo, Graziana Colaianni, Silvia Colucci, Maria Grano, Maria Felicia Faienza
Background: Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells. This equilibrium is regulated by numerous cytokines, but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/汕-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis, respectively. The pro-osteoblastogenic activity of the Wnt/-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1). RANKL, sclerostin and DKKs-1 are often up-regulated in bone diseases, and they are the target of new monoclonal antibodies.
Data sources: The authors performed a systematic literature search in PubMed and EMBASE to June 2018, reviewed and selected articles, based on pre-determined selection criteria.
Results: We re-evaluated the role of RANKL, osteoprotegerin, sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases, such as type 1 diabetes mellitus (T1DM), alkaptonuria (AKU), hemophilia A, osteogenesis imperfecta (OI), 21-hydroxylase defi ciency (21OH-D) and Prader-Willi syndrome (PWS). To do so, we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-汕-catenin signaling pathways have been investigated, and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.
Conclusions: The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases. Furthermore, for some of them, bone damage began in childhood but only manifested with age. The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children, although further studies need to be carried out.
  [Abstract] [Full Text] [PDF]  
Complications in children with percutaneous endoscopic gastrostomy (PEG) placement
  Brigitta Balogh, Tam芍s Kov芍cs, Amulya Kumar Saxena
Background: The aim of this study was to analyze the complication rates and mortality in association with different operative techniques of percutaneous endoscopic gastrostomy (PEG), age, underlying diseases and other risk factors. Moreover, analysis of the indications of PEG insertion and the underlying comorbidities was also performed.
Methods: This study performs a literature analysis of PEG-related complications in children. Literature was searched on PubMed® (1994-2017) using terms ※percutaneous endoscopic gastrostomy§, ※complications§, ※mortality§ and ※children§.
Results: Eighteen articles with 4631 patients were analyzed. The mean age was 3 years (0-26 years). Operative techniques were: pull technique in 3507 (75.7%), 1 stage PEG insertion in 449 (9.7%), introducer technique in 435 (9.4%), image-guided technique in 195 (4.2%) and laparoscopic-assisted PEG in 45 (1.6%). Most frequent indications for PEG insertion were dysphagia (n = 859, 32.6%), failure to thrive (n = 723, 27.5%) and feeding difficulties (n = 459, 17.4%). Minor complications developed in n 1518 patients (33%), including granulation (n = 478, 10.3%), local infection (n = 384, 8.3%) and leakage (n = 279, 6%). In 464 (10%) patients, major complications occurred; the most common were systemic infection (n = 163, 3.5%) and cellulitis (n = 47, 1%). Severe complication like perforation occurred in less than 0.3%. Patients with lethal outcomes (n = 7, 0.15%) had severe comorbidities; and the cause of mortality was sepsis in all cases. Prematurity or young age did not affect complication rate. Patients with ventriculoperitoneal (VP) shunt had higher risk of major complications. In high-risk patients, laparoscopic-assisted PEG insertion had less major and severe complication than traditional pull technique.
Conclusions: PEG is a safe operative technique; although minor complications are relatively common and occur in up to 1/3 of patients, there is a fairly low rate of severe complications. Two-thirds of PEG patients have at least one comorbidity. Patients with VP shunt have higher risk of major complications. In high-risk patients, laparoscopic-assisted PEG is recommended.
  [Abstract] [Full Text] [PDF]  
Autism spectrum disorders: autistic phenotypes and complicated mechanisms
  Xi-Cheng Zhang, Li-Qi Shu, Xing-Sen Zhao, Xue-Kun Li
Background: Autism spectrum disorder (ASD), a pervasive developmental neurological disorder, is characterized by impairments in social interaction and communication, and stereotyped, repetitive patterns of interests or behaviors. The mechanism of ASDs is complex, and genetic components and epigenetic modifications play important roles. In this review, we summarized the recent progresses of ASDs focusing on the genetic and epigenetic mechanisms. We also briefly discussed current animal models of ASD and the application of high-throughput sequencing technologies in studying ASD.
Data sources: Original research articles and literature reviews published in PubMed-indexed journals.
Results: Individuals with ASDs exhibit a set of phenotypes including neurological alteration. Genetic components including gene mutation, copy-number variations, and epigenetic modifications play important and diverse roles in ASDs. The establishment of animal models and development of new-generation sequencing technologies have contributed to reveal the complicated mechanisms underlying autistic phenotypes.
Conclusions: Dramatic progress has been made for understanding the roles of genetic and epigenetic components in ASD. Future basic and translational studies should be carried out towards those candidate therapeutic targets.
  [Abstract] [Full Text] [PDF]  
Exclusive enteral nutrition versus corticosteroids for treatment of pediatric Crohn*s disease: a meta-analysis
  Yu Yu, Kang-Chen Chen, Jie Chen
Background: Many studies have examined the effects of exclusive enteral nutrition (EEN) in children with Crohn*s disease (CD), but corticosteroids are considered a superior therapy and are frequently used in China. This meta-analysis aims to compare the efficacy of EEN with corticosteroids in treating pediatric CD.
Methods: A comprehensive retrieval from medical databases, including PubMed, EMBASE, MEDLINE, Web of Science, Wanfang data, VIP and CNKI, was performed using the search terms ※diet therapy§, ※exclusive enteral nutrition§, ※Crohn*s disease§, ※inflammatory bowel diseases§, ※child§ and ※pediatrics§ from January 1990 to April 2017.
Results: We included 18 studies from 1329 identified sources in this meta-analysis. EEN was as effective as corticosteroids in inducing remission rate of children suffering from CD (OR = 1.35; 95% CI 0.90, 2.10; P = 0.14). Nevertheless, patients who received EEN were more likely to achieve both endoscopic mucosal healing (OR = 5.24; 95% CI 2.06, 13.37; P = 0.0005) and histological mucosal healing (OR = 4.78; 95% CI 1.89, 12.08; P = 0.0009) than those who received corticosteroids; the Pediatric Crohn*s Disease Activity Index was lower [mean difference (MD) = − 3.67; 95% CI − 4.91, − 2.43] and weight gain was higher (MD = 1.92; 95% CI 0.02, 3.83; P = 0.05) in those patients who received EEN than in those who received corticosteroids. No difference was found in relapse rate (OR = 0.57; 95% CI 0.25, 1.29; P = 0.18), height for age or body mass index between the patients treated with EEN and corticosteroids at the 1-year end point.
Conclusions: This meta-analysis reveals that there is no significant difference between EEN and corticosteroids in the efficacy of inducing remission rate of CD in a pediatric population, but EEN is superior to corticosteroids in improving short-term mucosal inflammation and reducing the PCDAI index.
  [Abstract] [Full Text] [PDF]  
Original articles:
Comparison of the demographic characteristics of pediatric and adult colorectal cancer patients: a national inpatient sample based analysis
  Thomas M. Attard, Caitlin E. Lawson
Background: Colorectal cancer in children is rare, but characterized by late presentation, unfavorable histology and poor prognosis. Risk factors for colorectal cancer in children overlap with those for adults with greater influence of hereditary syndromes. The epidemiology of colon cancer in children is poorly understood; the aim of this study was to characterize and compare the demographics and relevant clinical characteristics of pediatric and adult colon cancer, using a national inpatient sample.
Methods: The AHRQ online resource HCUPnet/KID database was queried for children, under the age of 18 admitted with ICD 9 CM diagnoses relating to colorectal cancer, at the time of discharge. For comparison, the corresponding diagnoses in adult patients were queried for each successive year. Patient demographics including residential type and median income by zip-code, tumor localization; if recorded, and mean hospital charges were all accrued and analyzed.
Results: Inpatient admissions for pediatric colorectal cancer were more likely male (54%), in the 15-17 years age bracket (57%). They were significantly more likely from Southwestern regions of the Unites States, and were significantly more likely from residential zip-codes identified as at or below the lowest income quartile than adult CRC patients or pediatric patients as a whole. Hospital charges have more than quadrupled over the time period studied (1997-2012).
Conclusions: Pediatric colorectal cancer is the most common primary gastrointestinal malignancy in children. Better understanding associated risk factors including those associated with gender, geographic region and social economic status may contribute to future prevention or early detection strategies.
  [Abstract] [Full Text] [PDF]  
Characteristics and outcome of newborn admitted with acute bilirubin encephalopathy to a tertiary neonatal intensive care unit
  Nahed Fahmy Helal, Eman Abdel Ghany Abdel Ghany, Walaa Alsharany Abuelhamd, Amna Yehea Ahmed Alradem
Background: Acute bilirubin encephalopathy (ABE) still represents a significant cause of morbidity and mortality throughout the world, especially in developing countries. We aimed to determine the prevalence of ABE based on the Johnson bilirubin-induced neurologic dysfunction (BIND) score and to describe the discharge outcomes.
Methods: We prospectively studied all newborns ≡ 35 weeks with ABE by evaluating signs of mental sensorium, muscle tone, and cry patterns over 1 year.
Results: 12% (81 out of 674) of the newborns admitted for neonatal hyperbilirubinemia had a BIND score > 1. Their admission age was 6 ㊣ 4.1 days; total serum bilirubin (TSB) was 31.2 ㊣ 10 mg/dL (range 17.5-75.2). Of these newborns, 40.7% and 21% had evidence of haemolysis and sepsis, respectively. Overall mortality was 9.9%; 58% of the newborns showed signs of mild-to-moderate BIND at discharge, while 32.1% survived with an apparently normal outcome. Admission BIND score was significantly correlated with admission TSB (r = 0.476, P < 0.001). Similarly, BIND score at discharge was correlated with admission TSB (r = 0.442, P < 0.001) and admission BIND score (r = 0.888, P < 0.001). The regression model showed that admission TSB (P < 0.001) and maternal illiteracy (P = 0.034) were predictors of the BIND score at admission, while admission BIND score was the best indicator of the discharge score (P < 0.001).
Conclusions: ABE is still a major problem in our community. Admission TSB and maternal illiteracy are good predictors of bilirubin encephalopathy at admission and discharge.
  [Abstract] [Full Text] [PDF]  
Reliability and validity of the translated Chinese version of Autism Spectrum Rating Scale (2每5 years)
  Hao Zhou, Chun-Pei Li, Yi Huang, Xiao-Bing Zou, Xue-Rong Luo, Li-Jie Wu, Lan Zhang, Xiu Xu, Wei-Li Yan, Yi Wang
Background: Early autism screening is of great value, but there is lack of a screening tool of early age (2-5 years) in China. The Autism Spectrum Rating Scale (ASRS, 2-5 years) is a newly developed autism screening tool in the USA. This study aimed to evaluate the reliability and validity of the translated Chinese version of ASRS (C_ASRS) in Chinese children population before its application in China for early autism screening.
Methods: Caregivers of general children aged 2-5 years from 17 kindergartens and autism spectrum disorder (ASD) cases from five special education schools in five cities were recruited to complete the C_ASRS. 1910 valid questionnaires from kindergarteners and 192 from ASD cases were included for analyses.
Results: The item reliability (Cronbach*s alpha) was more than 0.80 in the screening scale and DSM-5 scale, and 0.51-0.81 in the treatment scale. ASD cases scored higher on total score and most subscales compared to the kindergarteners (Cohen*s d ranging from 1.34 to 3.37). C_ASRS showed good discriminatory validity with an area under the receiver operating characteristic curve of 0.850 (95% confidence interval: 0.819-0.881). The cutoff ≡ 60 achieved sensitivity of 65.63% and specificity of 85.63% in discriminating autism children from the general population.
Conclusion: The results indicate that C_ASRS (2-5 years) could be used as an early level-2 screening tool for autism screening in China and should be further revised for level-1 screening.
  [Abstract] [Full Text] [PDF]  
How online ADHD-related information affects Chinese parents* decisions?
  Xiao-He Yu, Le Zhong, Jia Huang
Background: Attention deficit hyperactivity disorder (ADHD) is a major public health problem in China. Parents of children with confirmed, or suspected ADHD often face a difficult process in making decisions concerning diagnosis and treatment. The internet is a major source of information for parents. The purpose of this study is to survey Chinese parental motivation and experience in using the internet to retrieve ADHD-related information, and how well online information is associated with making decisions.
Methods: Parents were recruited to fill out an online questionnaire in the health portal. A total of 404 valid questionnaires were collected.
Results: A total of 47.8% of parents agree that the internet helps them to understand the potential treatment options, but 77.7% of all parents still have conflict during decision-making.
Conclusions: Parents search for ADHD-related information online, but their acquisition skills need to be improved. Internet information affects their health decisions. Parents still have highly conflicting decision-making. Improving the ability of parents to obtain information on the Internet may reduce the conflict in decision-making.
  [Abstract] [Full Text] [PDF]  
Application of isoxanthopterin as a new pterin marker in the differential diagnosis of hyperphenylalaninemia
  Pei-Zhong Bao, Jun Ye, Lian-Shu Han, Wen-Juan Qiu, Hui-Wen Zhang, Yong-Guo Yu, Jian-Guo Wang, Xue-Fan Gu
Background: This study aimed to explore the value of applying a new pterin marker (isoxanthopterin) to the traditional urine pterin analysis to reduce the rate of mis-diagnosis of 6-pyruvoyltetrahydropterin synthase deficiency (PTPSD) and improve the accuracy of diagnosis.
Methods: We compared the urine neopterin (N), biopterin (B), isoxanthopterin (Iso), B% and Iso% levels between patients with phenylalanine hydroxylase deficiency and those with PTPSD, and found the most specific pterin biomarkers by ROC analysis. A positive cut-off value of urine pterins was determined. The effect of combined Iso% + B + B% in reducing PTPSD mis-diagnosis was evaluated, and the different urine pterin levels in PTPSD and false PTPSD (FPTPSD) were compared. The concordance of PTPSD diagnosis by the new pterin scheme and gene mutation analysis was determined.
Results: (1) Urinary B, B%, Iso and Iso% were significantly lower in PTPSD than those in phenylalanine hydroxylase-deficiency group (P < 0.01); (2) Iso%, B%, and B were the most specific markers; (3) The positive cut-off values of B, B%, Iso% for PTPSD were < 0.17 mmoL/moLCr, < 5.0%, and < 9.5%, respectively; (4) urinary B + B% + Iso% scheme significantly reduced the false-positive rate of PTPSD compared to traditional ones. The Iso% levels in FPTPSD group were higher than the ones in PTPSD group; (5) an accuracy of diagnosis for PTPSD was increased by 9-19% when Iso% was introduced to urinary pterin scheme.
Conclusions: Iso% is helpful to reduce the rate of misdiagnosis of PTPSD in the diagnosis by urinary pterin analysis for hyperphenylalaninemias and improve the accuracy of diagnosis. This approach is worthy of further development and increased utilization.
  [Abstract] [Full Text] [PDF]  
Transcutaneous bilirubin nomogram for evaluating the risk of hyperbilirubinemia in Iranian healthy newborns
  Robabe Seyedi, Mojgan Mirghafourvand, Abdollah Jannat Dost, Sakineh Mohammad-Alizadeh-Charandabi, Mohammad Asghari Jafarabadi, Shirin Osouli Tabrizi
Background: Hyperbilirubinemia, which is mostly benign, is one of the most common problems in neonates. This study was conducted to draw a skin bilirubin nomogram for evaluating the risk of hyperbilirubinemia requiring treatment.
Methods: This cross-sectional study recruited 1066 healthy infants. The first transcutaneous bilirubin (TcB) measurement was performed before hospital discharge and within 12-48 h of birth. The neonates were followed up for 6 days after discharge based on their age at the time of discharge. The neonates were divided into four groups based on the TcB values before discharge and age in hours, including the low-risk, medium每low-risk, medium每high-risk and high-risk groups. The percentage of neonates who progressed toward severe hyperbilirubinemia was then calculated in each percentile based on the follow-up TcB measurement. Stata software was used to draw the nomogram. Based on the TcB values at discharge and the neonate*s age in hours, the skin bilirubin nomogram was drawn in 40, 75 and 95 percentiles.
Results: A total of 4.9% of the neonates were in the high-risk group, 18.9% in the medium每high-risk group, 34.8% in the medium每low-risk group and 41.2% in the low-risk group. The risk of severe jaundice in the follow-up of the neonates in the highest-risk to the lowest-risk groups was 48.9, 14.5, 9.7 and 3.3%, respectively.
Conclusion: The skin bilirubin nomogram can be used to predict severe hyperbilirubinemia in Iranian infants.
  [Abstract] [Full Text] [PDF]  
Effect of vitamin D treatment in children with attention-deficit hyperactivity disorder
  Nadia Dehbokri, Gholamreza Noorazar, Aida Ghaffari, Gita Mehdizadeh, Parvin Sarbakhsh, Saba Ghaffary
Background: In this research the symptom improvement of attention-deficit hyperactivity disorder (ADHD) of children was assessed by oral vitamin D administration in Tabriz, Iran.
Methods: In this double-blind, randomized clinical trials, 96 children (2-18 years) were enrolled to placebo and vitamin D groups. Children took vitamin D pearl (50,000 IU/week) or placebo for 6 weeks. Children, who had the change in methylphenidate dosage and received any anticonvulsants and corticosteroids were excluded from the research. ADHD symptoms were diagnosed by Conners parent rating scale (CPRS) test at baseline and after intervention. ADHD Conners divided into inattention (IA), hyperactivity/impulsivity (H/I) and combination type (C) subscales. Vitamin D serum level was assessed at baseline and after 8 weeks in both groups.
Results: The differences between CPRS and its subscales were not significant at baseline (P > 0.05). The Conners IA score was decreased in vitamin D group (P < 0.05; adjusted with age and baseline values). ADHD Conners and all subscale scores reduced remarkably after intervention in patients with insufficient level of vitamin D compared to placebo (P < 0.05).
Conclusions: Oral vitamin D improved ADHD symptoms with a particular effect on inattention symptoms. In addition, symptoms related to all subscales were improved remarkably in patients with insufficient level of vitamin D. Vitamin D treatment in children with ADHD could be considered due to the expand benefit of vitamin D in body.
  [Abstract] [Full Text] [PDF]  
Comparison of decision-making in neonatal care between China and Japan
  Hidehiko Maruyama, Yuka Shibata, Xing-Ge Xia, Yun-Xia Sun, Shao-Ru He, Yushi Ito
Background: Various differences between China and Japan in approaches to medical treatment have been noted, but a few studies have examined differences in medical decision-making, especially in neonatal care. The aim of this study was to clarify these differences by means of a questionnaire.
Methods: The subjects were physicians on the staff of NICUs in China and Japan. The study questionnaire consisted of three parts dealing with the general characteristics of the participants, questions about treatment strategies for hypothetical, critically ill infants, and general questions about the treatment of foreign patients. The Likert scale was used to assess the treatment strategies and the results were analyzed statistically. Subgroup analysis by age, sex, and medical and NICU experience was also performed.
Results: The proportion of respondents in the Chinese and Japanese groups was 26/26 (100%) and 26/31 (84%), respectively. There was a significant difference between the Chinese and Japanese groups for 8 of 75 questions; Chinese physicians chose the positive treatment or examination options for these eight questions unlike their Japanese counterparts. The responses of the younger, less experienced physicians in both countries were more similar to each other, and more positive than those of their older, more experienced colleagues.
Conclusion: Chinese physicians showed a more positive attitude toward examination and treatment, whereas Japanese physicians showed a more cautious attitude.
  [Abstract] [Full Text] [PDF]  
Pediatric off-label use of psychotropic drugs approved for adult use in Japan in the light of approval information regarding pediatric patients in the United States: a study of a pharmacy prescription database
  Nanae Tanemura, Maika Asawa, Mayuko Kuroda, Tsuyoshi Sasaki, Yoshiaki Iwane, Hisashi Urushihara
Background: Off-label use of psychotropic prescriptions for pediatric patients has been increasing in Japan. This study sought to clarify pediatric patients* off-label use of psychotropics approved only for adults in Japan.
Methods: This retrospective study on psychotropic utilization employed a pharmaceutical health insurance claims database supplied by a pharmacy for the fiscal year 2016. Seven psychotropic drugs were examined. For each drug, we calculated the proportion of patients aged < 16 years or who were under the approved age limit set in the United States out of all patients. The maximum daily dose of each drug within the study period was plotted by age.
Results: Data of 45,715 patients (female: 26,799, male: 18,916) with 331,920 prescriptions were examined in this study. For each drug, the proportion of pediatric patients aged < 16 years ranged from 0.15 to 1.1%, while the proportion of those under the approved age limit in the United States ranged from 0 to 0.27%. Olanzapine had the highest reported proportion. No drugs other than olanzapine were taken under the approved age limit in the United States.
Conclusions: We identified the pediatric off -label use of psychotropics that were limited to adult use in Japan. The results indicated the possibility of referring to international guidelines or evidence in clinical practice, but these factors do not discount the existing problems with off -label use. More clinical trials within the pediatric population in Japan are needed to address the issue of off -label use and obtain useful and reliable information in the package inserts for rational use in future pediatric patients.
  [Abstract] [Full Text] [PDF]  
Clinical summary:
Management of persistent pulmonary hypertension in newborns with ECMO support: a single center*s experience
  Li-Fen Ye, Yong Fan, Qiang Shu, Ru Lin
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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