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Vol 17, No 1
Vol 17, No 1 February 2021 ISSN 1708-8569
Review articles
Original articles
Social responsibilities of a pediatric journal: considerations and future directions
  Li-Li Yang, Xian-Jun Wang, Qi Qi, Si-Yun Xu, Yi-Cheng Xie, Zheng-Yan Zhao, Qiang Shu
  [Abstract] [Full Text] [PDF]  
Addressing e-cigarette health claims made on social media amidst the COVID-19 pandemic
  Nilanga Aki Bandara, Jay Herath, Vahid Mehrnoush
  [Abstract] [Full Text] [PDF]  
Winter is coming: care of the febrile children in the time of COVID-19
  Nicole Gerber, Jonathan S. Farkas, Adam J. Ratner
  [Abstract] [Full Text] [PDF]  
Laboratory diagnosis of COVID-19 in secondary care hospitals in India: will standalone serology suffice?
  Sara Chandy, Sundaram Balasubramanian, Anand Manoharan
  [Abstract] [Full Text] [PDF]  
Review articles:
Why COVID-19 is less frequent and severe in children: a narrative review
  Reza Sinaei, Sara Pezeshki, Saeedeh Parvaresh, Roya Sinaei
Background: Despite the streaks of severity, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is, in general, less frequent and severe in children than in adults. We searched for causal evidence of this mystery.
Data sources: An extensive search strategy was designed to identify papers on coronavirus disease 2019 (COVID-19). We searched Ovid MEDLINE, PubMed, EMBASE databases, and Cochrane library and carried out a review on the causes of this dilemma.
Results: Our searches produced 81 relevant articles. The review showed that children accounted for a lower percentage of reported cases, and they also experienced less severe illness courses. Some potential explanations, including the tendency to engage the upper airway, the different expression in both receptors of angiotensin-converting enzyme and renin-angiotensin system, a less vigorous immune response, the lower levels of interleukin (IL)-6, IL-10, myeloperoxidase, and P-selectin and a higher intracellular adhesion molecule-1, a potential protective role of lymphocytes, and also lung infiltrations might have protective roles in the immune system-respiratory tract interactions. Finally, what have shed light on this under representation comes from two studies that revealed high-titer immunoglobulin-G antibodies against respiratory syncytial virus and mycoplasma pneumonia, may carry out cross-protection against SARS-CoV-2 infection, just like what suggested about the vaccines.
Conclusions: These results require an in-depth look. Properties of the immune system including a less vigorous adaptive system beside a preliminary potent innate response and a trained immunity alongside a healthier respiratory system, and their interactions, might protect children against SARS-CoV-2 infection. However, further studies are needed to explore other possible causes of this enigma.
  [Abstract] [Full Text] [PDF]  
Assessment of left-ventricular diastolic function in pediatric intensive-care patients: a review of parameters and indications compared with those for adults
  Morgan Recher, Astrid Botte, Jerome Soquet, Jean-Benoit Baudelet, François Godart, Stephane Leteurtre
Background: The incidence of diastolic heart failure has increased over time. The evaluation of left-ventricular diastolic function is complex, ongoing, and remains poorly performed in pediatric intensive-care patients. This study aimed to review the literature and to provide an update on the evaluation of left-ventricular diastolic function in adults and children in intensive care.
Data sources: We searched data from PubMed/Medline. Thirty-two studies were included. Four pragmatic questions were identified: (1) What is the physiopathology of diastolic dysfunction? (2) Which tools are required to evaluate diastolic function? (3) What are the echocardiographic criteria needed to evaluate diastolic function? (4) When should diastolic function be evaluated in pediatric intensive care?
Results: Early diastole allows characterization of relaxation, whereas compliance assessments and filling pressures are evaluated during late diastole. The evolution of diastolic function differs between adults and children. Unlike in adults, decreased compliance occurs at the same time as delayed relaxation in children. Diastolic function can be evaluated by Doppler echocardiography. The echocardiographic criteria for ventricular relaxation include the E wave, E/A wave ratio, and isovolumic relaxation time. Ventricular compliance can be assessed by the E/e¡¯ wave ratio, atrial volume, and Ap wave duration during pulmonary vein flow. In adult intensive-care patients, the E/e¡¯ ratio can be used as an index of tolerance for volume expansion in septic patients and to adjust the inotropic support.
Conclusions: Clinical studies would allow some of these parameters to be validated for use in children in intensive care.
  [Abstract] [Full Text] [PDF]  
Bartter¡¯s syndrome: clinical findings, genetic causes and therapeutic approach
  Flavia Cristina Carvalho Mrad, S¨ªlvia Bouissou Morais Soares, Luiz Alberto Wanderley de Menezes Silva, Pedro Versiani dos Anjos Menezes, Ana Cristina Simões-e-Silva
Background: Bartter¡¯s syndrome (BS) is a rare group of salt losing tubulopathies due to the impairment of transport mechanisms at the thick ascending limb of the Henle¡¯s loop.
Data sources: Literature reviews and original research articles were collected from database, including PubMed and Scopus.
Results: According to the time of onset and symptoms, BS can be classified into antenatal and classic BS. Molecular studies have identified different subtypes of BS. BS types I, II and III are caused by mutations on genes encoding the luminal Na+¨CK+¨C2Cl- co-transporter, the luminal K+ channel ROMK, and the basolateral chloride channel ClC-Kb (CLCNKB), respectively. Loss-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type IVa. Simultaneous mutations of CLCNKB and CLCNKA cause BS type IVb. BS type V consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member D2. Severe gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of BS. Main clinical and biochemical alterations in BS include polyuria, dehydration, hypokalemia, hypochloremic metabolic alkalosis, hyperreninemia, high levels of prostaglandins, normal or low blood pressure, hypercalciuria and failure to thrive. Treatment focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria, including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 production.
Conclusions: Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure, nephrocalcinosis and end-stage renal disease.
  [Abstract] [Full Text] [PDF]  
Intestinal microbiota and juvenile idiopathic arthritis: current understanding and future prospective
  Le Xin, Feng He, Sen Li, Zhi-Xuan Zhou, Xiao-Lin Ma
Background: Juvenile idiopathic arthritis (JIA) characterized by arthritis of unknown origin is the most common childhood chronic rheumatic disease, caused by both host genetic factors and environmental triggers. Recent evidence has mounted to focus on the intestinal microbiota, a potentially recognized set of environmental triggers affecting JIA development. Here we offer an overview of recently published animal and human studies that support the impact of intestinal microbiota in JIA.
Data sources: We searched PubMed for animal and human studies publications with the search terms ¡°intestinal microbiota or gut microbiota¡± and ¡°juvenile idiopathic arthritis or juvenile chronic arthritis or juvenile rheumatoid arthritis or childhood rheumatoid arthritis or pediatric rheumatoid arthritis¡±.
Results: Several comparative studies have demonstrated that intestinal microbial alterations might be triggers in disease pathogenesis. Alternatively, a slice of studies has suggested environmental triggers in early life might disrupt intestinal microbial colonization, including cesarean section, formula feeding, and antibiotic exposure. Aberrant intestinal microbiota may infl uence the development of JIA by mediating host immune programming and by altering mucosal permeability.
Conclusions: Specific microbial factors may contribute to the pathogenesis of JIA. Intensive studies, however, are warranted to investigate the causality between intestinal dysbiosis and JIA and the mechanisms behind these epidemiologic relationships. Studies are also needed to design the best interventional administrations to restore balanced intestinal microbial communities.
  [Abstract] [Full Text] [PDF]  
Dent disease: classification, heterogeneity and diagnosis
  Yan-Yan Jin, Li-Min Huang, Xiao-Fang Quan, Jian-Hua Mao
Background: Dent disease is a rare tubulopathy characterized by manifestations of proximal tubular dysfunction, which occurs almost exclusively in males. It mainly presents symptoms in early childhood and may progress to end-stage renal failure between the 3rd and 5th decades of human life. According to its various genetic basis and to clinical signs and symptoms, researchers define two forms of Dent disease (Dent diseases 1 and 2) and suggest that these forms are produced by mutations in the CLCN5 and OCRL genes, respectively. Dent diseases 1 and 2 account for 60% and 15% of all Dent disease cases, and their genetic cause is generally understood. However, the genetic cause of the remaining 25% of Dent disease cases remains unidentified.
Data sources: All relevant peer-reviewed original articles published thus far have been screened out from PubMed and have been referenced.
Results: Genetic testing has been used greatly to identify mutation types of CLCN5 and OCRL gene, and next-generation sequencing also has been used to identify an increasing number of unknown genotypes. Gene therapy may bring new hope to the treatment of Dent disease. The abuse of hormones and immunosuppressive agents for the treatment of Dent disease should be avoided to prevent unnecessary harm to children.
Conclusions: The current research progress in classification, genetic heterogeneity, diagnosis, and treatment of Dent disease reviewed in this paper enables doctors and researchers to better understand Dent disease and provides a basis for improved prevention and treatment.
  [Abstract] [Full Text] [PDF]  
Advance in the understanding of vasovagal syncope in children and adolescents
  Hong-Xia Li, Lu Gao, Yue Yuan
Background: Vasovagal syncope (VVS) accounts for 60-80% of cases of neurally mediated syncope. VVS results from acute orthostatic intolerance and recurrent syncopal attacks, which can seriously affect an individual¡¯s quality of life. In addition, some children even experience trauma during attacks. Therefore, it is particularly important to clarify the pathogenesis of VVS. The aim of our study is to reveal the latest research progress of VVS.
Data sources: Literature that involved the pathogenesis of VVS were selected from Cochrane Library (1990-2019), EMBASE (1991-2019) and PubMed (1968-2019) databases.
Results: Hypovolemia, autonomic dysfunction, vasomotor dysfunction, baroreceptor reflex abnormalities, endothelial dysfunction, serotonin surges, and gut microbiota were involved in the underlying mechanism of VVS.
Conclusions: VVS is not always a benign prognosis. Various aspects were involved in its pathogenesis. Bezold-Jarish reflex, dysfunction of the autonomic nervous system, genetic factors and so on played important roles in VVS; however, the mechanism remains unclear.
  [Abstract] [Full Text] [PDF]  
Current status of fecal calprotectin as a diagnostic or monitoring biomarker for cow¡¯s milk protein allergy in children: a scoping review
  Li-Jing Xiong, Xiao-Li Xie, Yang Li, Xiao-Zhi Deng
Background: There are few approved biomarkers for diagnosis and monitoring of cow¡¯s milk protein allergy (CMPA), thus the oral food challenge remains to be the golden diagnostic standard. A potential biomarker is fecal calprotectin, a cytosolic protein, elevating in the presence of intestinal mucosal inflammation. We aimed to undertake a scoping review of the evidence pertaining to the current status of fecal calprotectin used for diagnosis and monitoring CMPA in children, and tried to indicate the aspects needed to be concerned in the future investigations and researches.
Methods: A scoping review was performed using the literature searched from PUBMED, EMBASE, and Web of Science Databases until July 2019 on the studies about the application of fecal calprotectin as a biomarker of CMPA in children. Studies were examined according to the inclusion and exclusion criteria. Data were extracted, and a narrative synthesis was conducted to summarize and analyze.
Results: Thirteen studies with different study design embracing 1238 children were included. The age range was from infants to adolescents. Most children with CMPA presented gastrointestinal symptoms, among which hematochezia was most common. Amount of data suggested that infants with CMPA represented elevated levels of fecal calprotectin, particularly with distinct significance in non-IgE-mediated CMPA groups. Decreases of fecal calprotectin after elimination diet were demonstrated in enrolled studies. However, no matter in the CMPA positive or negative groups, the changes of fecal calprotectin before or after challenge showed no significance. Contradictory results were generated from studies on the role of fecal calprotectin in predicting allergic disease.
Conclusions: Available evidence is not sufficient to confirm the utilization of fecal calprotectin both in diagnosis and monitoring of CMPA and predicting for allergic disease. More clinical and bench researches with elaborate design should be conducted and the exact cut-off values of fecal calprotectin in different groups remain to be determined.
  [Abstract] [Full Text] [PDF]  
Original articles:
COVID-19 and congenital heart disease: a case series of nine children
  Elmira Haji Esmaeil Memar, Babak Pourakbari, Mojtaba Gorgi, Meisam Sharifzadeh Ekbatani, Amene Navaeian, Mahmoud Khodabandeh, Shima Mahmoudi, Setareh Mamishi
Background: Coronavirus disease 2019 (COVID-19) is the current pandemic disease without any vaccine or efficient treatment to rescue the patients. Underlying diseases predispose the patients to a more severe disease and to a higher mortality rate. However, little evidence exists about COVID-19 outcomes in the pediatric population with congenital heart disease (CHD). Here, we report nine children with COVID-19 and concomitant CHD.
Methods: Our study included nine children with COVID-19 and concomitant CHD who were admitted to Children Medical Center Hospital during March and April 2020. The patients were classified based on the final outcome (death), and their clinical sign and symptoms, type of CHD, and drugs administered were compared.
Results: Among the nine patients, two died and we compared different characteristics, laboratory results and clinical findings of these cases based on the mortality. The deceased patients had severe types of CHD, worse arterial blood gases, severe clinical symptoms, higher mean level of partial thromboplastin time and C-reactive protein, and required more medications.
Conclusions: The present study showed that the general consideration of mild COVID-19 in children does not include patients with CHD and that it is necessary to pay greater attention to children with CHD to determine guidelines for treatment of COVID-19 in these children. Owing to the scarcity of CHD and COVID-19, we reported only nine cases. However, further studies are highly required in this regard.
  [Abstract] [Full Text] [PDF]  
Differences between radiological findings of COVID-19 and non-COVID-19 infections in pediatric patients
  Beyza Nur Kuzan, B¨¹lent Aslan, Taha Yusuf Kuzan, Ayşeg¨¹l Karahasan Yağcı, Nuri Çagatay Çimşit
Background: This study aimed to reveal the differences between coronavirus disease 2019 (COVID-19) infections and non-COVID-19 respiratory tract infections in pediatric patients.
Methods: Sixty pediatric patients admitted to the hospital between March 11, 2020 and April 15, 2020 with respiratory tract infections were evaluated retrospectively. Among them, 20 patients with reverse transcription-polymerase chain reaction (RT-PCR) tests and chest computed tomography (CT) examinations were included in the study. According to the RT-PCR test results, the patients were divided into the COVID-19 and non-COVID-19 groups. The clinical observations, laboratory results, and radiological features from the two groups were then compared.
Results: According to the RT-PCR test results, 12 patients were assigned to the COVID-19 group and 8 to the non-COVID-19 group. There were no significant differences between the two groups in terms of clinical or laboratory features. In terms of radiological features, the presence of bronchiectasis and peribronchial thickening was statistically significantly higher in the non-COVID-19 group (P = 0.010 and P = 0.010, respectively).
Conclusion: In pediatric cases, diagnosing COVID-19 using radiological imaging methods plays an important role in determining the correct treatment approach by eliminating the possibility of other infections.
  [Abstract] [Full Text] [PDF]  
ECIEN-2020 study: the effect of COVID-19 on admissions for non-COVID-19 diseasesECIEN-2020 study: the effect of COVID-19 on admissions for non-COVID-19 diseases
  Beatriz Ramos-Lacuey, Mercedes Herranz Aguirre, Clara Calder¨®n Gallego, Andrea Ilundain L¨®pez de Munain, Eva Gembero Esarte, Laura Moreno-Galarraga
Background: The pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has had great effects on health systems worldwide, not only in relation to coronavirus disease 2019 (COVID-19) cases but also affecting patients with other pathologies.
Methods: ECIEN-2020 is an observational study conducted in a tertiary referral hospital in Navarra, Spain. It describes the effects of COVID-19 pandemic and the preventive measures adopted, in pediatric admissions for non-COVID-19 diseases. Admissions during March-June 2020 (first wave of the COVID-19 pandemic in Spain) are described and compared with the same quarter in 2019. A sub-analysis was performed delving into epidemiology. Patient characteristics (age, sex, past medical history), disease characteristics (symptoms, duration of symptoms, previous consultation in Primary Care Health Center), and admission characteristics (place and average stay) were analyzed.
Results: A 33% reduction in the number of pediatric hospital admissions was observed, decreasing from 529 hospitalizations in 2019 to 353 in 2020 (P < 0.001). This highlights a 48% reduction in patients admitted for pulmonary diseases. There were no significant changes in average hospital-stay, percentage of intensive care unit admissions, or in admissions for other reasons. Percentage of patients admitted among those seen in the emergency department rose from 5.1% in 2019 to 10.9% in 2020, whereas the total number of consultations in the emergency department decreased by 68%.
Conclusion: The pandemic and the measures adopted due to SARS-CoV-2 have significantly decreased pediatric admissions for non-COVID-19 diseases, especially due to a reduction in the hospitalization for respiratory diseases.
  [Abstract] [Full Text] [PDF]  
Efficacy of oral magnesium therapy in the treatment of chronic constipation in spastic cerebral palsy children: a randomized controlled trial
  Sahar M. A. Hassanein, Shaymaa M. Deifallah, Hend A. Bastawy
Background: Constipation is a common problem in children with spastic cerebral palsy (sCP) with a prevalence that reaches 75%. We hypothesized that treating constipation in those children will improve their health and shorten time spent in daily care. Our aim was to evaluate the efficacy and safety of oral magnesium sulfate for treating chronic constipation in children with sCP.
Methods: A prospective, double-blinded randomized control trial was carried out involving 100 children aged 2-12 years with sCP (level III-V of the Gross Motor Functional Classification system) and chronic constipation. They were followed up in the Pediatric neurology clinic, Children¡¯s hospital, Ain Shams University, May 2017- January 2019. The intervention group (O-Mg) received oral magnesium sulfate 1 mL/kg/day daily for 1 month compared to the placebo. Outcome measures were constipation improvement and decrease in bowel evacuation time after 1 month.
Results: Initially, weekly bowel movements, constipation scores and stool consistency were comparable in both groups. After 1 month of regular administration of oral magnesium sulfate, the constipation score, stool frequency and consistency improved compared to the placebo group (P < 0.001). Effective safe treatment was achieved in 31 (68%) and 4 (9.5%) patients in the O-Mg and placebo groups, respectively (RR, 2.95; 95% CI 2.0-4.5) (P < 0.001). Painful bowel evacuation attempts spent by mothers decreased from 25 (55.6%) of the cases initially to 10 (22%) cases after one month in the O-Mg group (P = 0.001). In contrast, in the placebo group, the decrease went from 21 (50%) cases initially to 18 (42.9%) after 1 month and was not significant (P = 0.5).
Conclusions: Oral magnesium sulfate seems effective in alleviating chronic constipation and pain experience in children with sCP. Consequently, saving maternal time spent in daily bowel evacuation attempts.
  [Abstract] [Full Text] [PDF]  
Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes
  Jin-Na Yuan, Jian-Wei Zhang, Wayne S. Cutfield, Guan-Ping Dong, You-Jun Jiang, Wei Wu, Ke Huang, Xiao-Chun Chen, Yan Zheng, Bi-Hong Liu, Jos¨¦ G. B. Derraik, Jun-Fen Fu
Background: No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population.
Methods: Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes.
Results: Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5 years had SID compared to none among patients aged ¡Ý 11 years.
Conclusions: Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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