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Vol 14, No 6
Vol 14, No 6 November 2018 ISSN 1708-8569
Personal viewpoint
Review articles
Original articles
Clinical image
Letter to the editors
Antimicrobial resistance: a global one-health problem for all ages
  Yong-Hong Yang, Jim Buttery
  [Abstract] [Full Text] [PDF]  
World Society for Pediatric Infectious Diseases declaration on combating antimicrobial resistance in children
  Jim Buttery, Yonghong Yang, Mike Sharland, on behalf of the World Society for Pediatric Infectious Diseases
  [Abstract] [Full Text] [PDF]  
Personal viewpoint:
ADHD-juvenile bipolar disorder: mimics and chameleons!
  Ahmed Naguy
  [Abstract] [Full Text] [PDF]  
Review articles:
Two decades of off-label prescribing in children: a literature review
  Shamala Balan, Mohamed Azmi Ahmad Hassali, Vivienne S. L. Mak
Background: In the past two decades, many legislative and regulatory initiatives were taken globally to improve drug use in children. However, children are still found to be prescribed with off -label drugs. This study was conducted to provide an overview of the worldwide trend in off -label prescribing in children from the year 1996 to 2016.
Data sources: The articles published in PubMed, MEDLINE and Google Scholar were searched using text words: off-label, unlicensed, paediatric and children. Additional articles were identified by reviewing the bibliography of the retrieved articles. Full-text articles published in English which reported on the prevalence of off -label prescribing in children between January 1996 and December 2016 were included.
Results: A total of 101 studies met the inclusion criteria. Off-label prescribing definition included four main categories: age, indication, dose and route of administration. The three most common reference sources used in the studies were summary of product characteristics, national formularies and package inserts. Overall, the off每label prescribing rates in children ranged from 1.2 to 99.7%. The most common category of off -label prescribing in children was dose and age.
Conclusions: This review highlighted that off-label prescribing in children was found to be highly prevalent throughout the past two decades, persistently in the neonatal intensive care units. This suggests that besides legislative and regulatory initiatives, behavioural, knowledge aspects and efforts to integrate evidence into practice related to off-label prescribing also need to be evaluated and consolidated as part of the concerted efforts to narrow the gaps in prescribing for children.
  [Abstract] [Full Text] [PDF]  
Advances in diagnosis of chronic liver diseases in pediatric patients
  Lucija Ruzman, Ivana Mikolasevic, Kristina Baraba Dekanic, Sandra Milic, Goran Palcevski
Background: Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recognition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available.
Methods: A non-systematic literature search was performed to summarize the current knowledge about transient elastography (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population.
Results: Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized.
Conclusions: TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient*s demographics, disease etiology, and essential laboratory parameters.
  [Abstract] [Full Text] [PDF]  
Erythema nodosum
  Alexander K. C. Leung, Kin Fon Leong, Joseph M. Lam
Background: Erythema nodosum can be associated with a number of systemic diseases. There is, however, a paucity of information in the pediatric literature on this condition. The purpose of this article is to familiarize pediatricians with the evaluation, diagnosis, and treatment of erythema nodosum.
Data sources: A PubMed search was completed in Clinical Queries using the key terms ※erythema nodosum§.
Results: Clinically, erythema nodosum presents with a sudden onset of painful, erythematous, subcutaneous nodules mainly localized to the pretibial areas. Lesions are usually bilateral and symmetrical, ranging from 1 to 5 cm in diameter. Erythema nodosum may be associated with a variety of conditions such as infection, medications, sarcoidosis, pregnancy, inflamatory bowel disease, vaccination, autoimmune disease, malignancy, and miscellaneous causes. The condition is idiopathic in approximately 50% of cases. The diagnosis is mainly clinical with biopsy reserved for atypical cases. To evaluate for the underlying cause, some basic laboratory screening studies are worthwhile in most cases and include a complete blood cell count, erythrocyte sedimentation rate and/or C-reactive protein, throat swab culture, antistreptococcal O titers, and a chest radiograph. Other tests should be individualized, guided by the history and physical examination results. Most cases of erythema nodosum are self-limited and require no treatment. Bed rest and leg elevation are generally recommended to reduce the discomfort. Nonsteroidal anti-inflammatory drugs are the first-line treatment for pain management.
Conclusions: As erythema nodosum is often a cutaneous manifestation of a systemic disease, a thorough search should be performed to reveal the underlying cause.
  [Abstract] [Full Text] [PDF]  
Pregnancy and child developmental outcomes after preimplantation genetic screening: a meta-analytic and systematic review
  Misaki N. Natsuaki, Laura M. Dimler
Background: In in vitro fertilization (IVF) treatment, preimplantation genetic diagnosis/screening (PGD/S) attempts to detect chromosomal abnormalities in embryos before implantation. Using the meta-analytic and qualitative review approaches, this study aims to evaluate the effect of PGD/S on clinical pregnancy, live births, and childhood outcomes.
Methods: We conducted a literature search using 1) PubMed and other search engines, and 2) an ancestry search by tracking references cited in prior work. After screening the studies, we extracted information pertinent to the meta-analysis. We calculated the effect sizes for clinical pregnancy and live birth rates, and performed a moderation analysis by maternal age, type of genetic screening, and timing of the biopsy. For childhood outcomes, we conducted a systematic review of studies reporting the anthropometric, psychomotor, cognitive, behavioral, and family functioning of PGD/S children.
Results: We included 26 studies for clinical pregnancy and live births, and 18 studies for childhood outcomes. Results indicated that women who underwent comprehensive chromosome screening-based PGD/S had significantly higher clinical pregnancy rates (rr 1.207, 95% CI 1.017每1.431) and live birth rates (rr 1.362, 95% CI 1.057每1.755) than those whose IVF treatment did not include PGD/S. Early childhood outcomes of PGD/S children did not differ from those of non-PGD/S children.
Conclusions: Comprehensive chromosome screening-based PGD/S can improve clinical pregnancy and live birth rates without adversely affecting functioning in childhood at least up to age 9. Results are discussed in the context of bioethical, financial, legal, and psychological issues surrounding PGD/S.
  [Abstract] [Full Text] [PDF]  
Original articles:
Characteristics and outcome of impacted button batteries among young children less than 7 years of age in China: a retrospective analysis of 116 cases
  Tao Huang, Wen-Qing Li, Zhong-Fang Xia, Jun Li, Kai-Cheng Rao, En-Ming Xu
Background: Ingestion of button batteries occurs in about ten persons per one million persons each year, with most of them children, and one in every 1000 battery ingestions leads to serious injuries. This study aimed to describe the clinical features and outcome of ingestion or inhalation of button batteries in children spanning a decade from January, 2006 to December, 2016 at a tertiary care hospital.
Methods: We reviewed the clinical records of children who sought treatment for inhaled or ingested button batteries at our hospital during the study period. Data on gender, age, time from ingestion to treatment, site of impaction, imaging findings, and outcomes were retrieved and analyzed.
Results: We identified 116 pediatric cases of ingestion or inhalation of button batteries. Their mean age was 26 months. The time from ingestion or inhalation of button batteries to treatment was 0.5 hours to 2 weeks. Ninety-seven (83.6%) button batteries were located in the nasal cavity, 13 (11.2%) in the gastrointestinal (GI) tract including 6 in the esophagus, and 7 in the stomach and lower GI tract, and 6 (5.2%) in the auditory tract. Twenty-one (21.6%) children with nasal button batteries had preoperative septal perforations and one (1.0%) had postoperative septal perforation. One child with esophageal button battery developed esophageal stricture and one died of sudden cardiac arrest perioperatively. One child had auditory damages in the right tympanic membrane and ossicles.
Conclusions: Inhalation or ingestion may occur in the nasal cavities, the esophagus and GI tract and the auditory tract. Prompt diagnosis and treatment are required for a satisfactory outcome and ingested or inhaled button batteries require different treatment protocols.
  [Abstract] [Full Text] [PDF]  
Calcium-handling abnormalities underlying atrial arrhythmogenesis in a Fontan operation canine model
  Wan-Ping Zhou, Fen Li, Jin-Jin Wu, Ya-Nan Lu, Yi-Jiao Qian
Background: Atrial tachyarrhythmia (AT) is a common complication in patients who have undergone a Fontan operation. In this study, we investigated whether abnormal Ca2+ handling contributes to the Fontan operation-related atrial arrhythmogenic substrate.
Methods: Mongrel dogs were randomly assigned to sham and Fontan groups. The Fontan operation model was developed by performing an atriopulmonary anastomosis. After 14 days, an electrophysiological study was performed to evaluate the AT vulnerability. Ca2+ handling properties were measured by loading atrial cardiomyocytes (CMs) with fura-2 AM. The L每type Ca2+ (ICaL) and Na+每Ca2+ exchanger (INCX) currents of the CMs were recorded by the whole-cell patch-clamp technique. The key Ca2+ handling proteins expression was assessed by Western blotting.
Results: The AT inducibility was higher in the Fontan group than in the sham group (85.71 vs. 14.29%, P < 0.05). The Fontan operation resulted in decreased Ca2+ transient (CaT) amplitude and sarcoplasmic reticulum (SR) Ca2+ content, but in enhanced diastolic intracellular Ca2+ concentration and SR Ca2+ leak in the atrial CMs. The spontaneous CaT events, triggered ectopic activity and INCX density were increased, but ICaL density was reduced in CMs from the Fontan atria (all P < 0.05). Additionally, the Fontan operation resulted in decreased SR Ca2+ ATPase expression and Cav1.2 expression, but in increased NCX1 and Ser2814-phosphorylated ryanodine receptor 2. The calmodulin-dependent protein kinase II expression and function were markedly enhanced in the Fontan atria.
Conclusion: The Fontan operation caused atrial CM Ca2+ handling abnormalities that produced arrhythmogenic-triggered activity and increased vulnerability to AT in experimental Fontan dogs.
  [Abstract] [Full Text] [PDF]  
Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq
  Hannah M. Phelps, Mazin F. Al-Jadiry, Natasha M. Corbitt, Janene M. Pierce, Bingshan Li, Qiang Wei, Raina R. Flores, Hernan Correa, Stefania Uccini, Haydar Frangoul, Adel R. Alsaadawi, Safaa A. F. Al-Badri, Amir F. Al-Darraji, Raghad M. Al-Saeed, Salma A. Al-Hadad, Harold N. Lovvorn III
Background: Wilms tumor (WT) is the most common childhood kidney cancer worldwide, yet its incidence and clinical behavior vary according to race and access to adequate healthcare resources. To guide and streamline therapy in the wartorn and resource-constrained city of Baghdad, Iraq, we conducted a first-ever molecular analysis of 20 WT specimens to characterize the biological features of this lethal disease within this challenged population.
Methods: Next-generation sequencing of ten target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, N-MYC, CRABP2, and TOP2A) was completed. Immunohistochemistry was performed for 6 marker proteins of WT (WT1, CTNNB1, NCAM, CITED1, SIX2, and p53). Patient outcomes were compiled.
Results: Mutations were detected in previously described WT ※hot spots§ (e.g., WT1 and CTNNB1) as well as novel loci that may be unique to the Iraqi population. Immunohistochemistry showed expression domains most typical of blastemalpredominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confi rmed dead from disease. Median clinical follow-up was 40.5 months (range 6每78 months).
Conclusions: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets.
  [Abstract] [Full Text] [PDF]  
Polymorphisms in the promoter region of IL10 gene are associated with virus etiology of infant bronchiolitis
  Annukka Holster, Johanna Teräsjärvi, Juho Vuononvirta, Petri Koponen, Ville Peltola, Merja Helminen, Qiushui He, Matti Korppi, Kirsi Nuolivirta
Background: Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (− 1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (− 3575A/T), rs1800871 (− 819C/T) or rs1800872 (− 592C/A) either alone or combined with the SNP at rs1800896 (− 1082G/A), and the etiology and severity of infant bronchiolitis.
Methods: Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization.
Results: Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P = 0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than controls (65.5%, P = 0.009). Twenty-eight infants with bronchiolitis had the variant每variant Grs1800896 Trs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures.
Conclusion: IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and controls, but not between infants with respiratory syncytial virus bronchiolitis and controls.
  [Abstract] [Full Text] [PDF]  
Leptin gene polymorphism affects leptin level in childhood asthma
  Dawid Szczepankiewicz, Paulina Sobkowiak, Beata Narożna, Irena Wojsyk-Banaszak, Anna Bręborowicz, Aleksandra Szczepankiewicz
Background: Leptin may induce inflammation in asthma by activation of Th2 cells. It has also been demonstrated that leptin expression increases upon inflammation and that asthmatic patients show increased serum leptin levels. We hypothesized that the polymorphism in leptin (LEP) and leptin receptor (LEPR) genes is associated with childhood asthma and may affect their serum level. To our knowledge, there are no reports analyzing LEP and LEPR polymorphisms in association with their serum levels in childhood asthma.
Methods: We analyzed 35 subjects: 25 asthmatic pediatric patients and 10 healthy children aged from 6 to 18. The diagnosis of allergic asthma was based on clinical manifestation, lung function, positive skin prick tests and increased immunoglobulin E levels. The polymorphisms were genotyped with use of polymerase chain reaction-restriction fragment length polymorphism method. Serum levels of leptin and leptin receptor were determined using BioVendor enzyme-linked immunosorbent assay kits. Statistical analysis was done with Statistica v.12.
Results: We observed that leptin levels were increased in asthmatic subjects as compared to healthy controls and were significantly higher during exacerbation than in the asymptomatic period (P = 0.025). We observed that LEP polymorphism (rs13228377) was associated with higher serum leptin levels in asthma and these two variables had high predictive value for asthma risk (P = 0.007, odds ratio 17.5, predictive accuracy 83.9%). LEPR polymorphisms did not show association with its serum level and asthma risk.
Conclusion: LEP polymorphism may increase asthma risk via infl uence on its serum level.
  [Abstract] [Full Text] [PDF]  
Citation classics in pediatrics: a bibliometric analysis
  Viswas Chhapola, Soumya Tiwari, Bobbity Deepthi, Sandeep Kumar Kanwal
Background: Citation analysis provides insights into the history and developmental trajectory of scientific fields. Our objective was to perform an analysis of citation classics in the journals of pediatric specialty and to examine their characteristics.
Methods: Initially, all the journals listed under the category of pediatrics (n = 120) were identified using Journal Citation Reports. Web of science database was then searched (1950每2016) to select the top-100 cited articles in the above identified pediatric journals. The top-100 cited article were categorized according the study design, sub-specialty, country, institutional affiliation, and language.
Results: The top-100 articles were published in 18 different journals, with Pediatrics having the highest numbers (n = 40), followed by The Journal of Pediatrics (n = 17). The majority (n = 62) of classics were published after 1990. The most cited article had citation count of 3516 and the least cited had a citation count of 593. The USA (n = 71) was the most commonly represented country, and 60 institutions contributed to 100 articles. Fifteen authors contributed to more than one classic as first or second author. Observational study (n = 55) was the commonest study design across all decades, followed by reviews (n = 12), scale development studies (n = 11), and guidelines (n = 11). Among the pediatric sub-specialties, growth and development articles were highly cited (n = 24), followed by pediatric psychiatry and behavior (n = 21), endocrinology (n = 15), and neonatology (n = 12).
Conclusions: The top-100 cited articles in pediatrics identify the impactful authors, journals, institutes, and countries. Observational study design was predominant〞implying that inclusion among citation classics is not related to soundness of study design.
  [Abstract] [Full Text] [PDF]  
Clinical image:
Atypical, severe presentation of chickenpox
  Nataliya Banadyha, Igor Rogalskyy, Roman Komorovsky
  [Abstract] [Full Text] [PDF]  
Early prediction of acute kidney injury in children: known biomarkers but novel combination
  Qian Lin, Jian-Hua Mao
  [Abstract] [Full Text] [PDF]  
Letter to the editors:
Antibiotic use in children with Kawasaki disease
  Seung Beom Han, Soo-Young Lee
  [Abstract] [Full Text] [PDF]  
Octreotide treatment for neonatal chylothorax
  Carlo Bellini, Laura Costanza De Angelis, Tommaso Bellini
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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