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Vol 16, No 5
Vol 16, No 5 October 2020 ISSN 1708-8569
Review articles
Original articles
Brief reports
Letters to the editor
Global Pediatric Pulmonology Alliance recommendation to strengthen prevention of pediatric seasonal influenza under COVID-19 pandemic
  Kun-Ling Shen, Leyla Namazova-Baranova, Yong-Hong Yang, Gary Wing Kin Wong, Lanny J. Rosenwasser, Lance E. Rodewald, Anne Eng Neo Goh, Eitan Kerem, Chris O*Callaghan, T. Bernard Kinane, Basil Elnazir, Rina Triasih, Rosemary Horne, Anne B. Chang, Jim Buttery, Ruth A. Etzel, Kazunobu Ouchi, Hilary Hoey, Varinder Singh, Genesis C. Rivera, Spencer S. Li, Yu Guan, on behalf of the Global Pediatric Pulmonology Alliance (GPPA) Council, Ling Cao, Yue-Jie Zheng, Lu-Zhao Feng, Wu Zhong, Zheng-De Xie, Bao-Ping Xu, Rong-Jun Lin, Gen Lu, Qiang Qin, Chun-Mei Zhu, Su-Yun Qian, Gang Liu, Cheng-Song Zhao, Zhuang Wei, Yu-Hong Zhao, on behalf of the Global Pediatric Pulmonology Alliance (GPPA) Expert Panel on Infectious Diseases & COVID-19
  [Abstract] [Full Text] [PDF]  
Review articles:
Childhood obesity, cardiovascular and liver health: a growing epidemic with age
  Maria Felicia Faienza, Mariangela Chiarito, Emilio Molina-Molina, Harshitha Shanmugam, Frank Lammert, Marcin Krawczyk, Gabriele D*Amato, Piero Portincasa
Background: The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic worldwide. With the raising obesity risk, key aspects to consider are accurate body mass index classification, as well as metabolic and cardiovascular, and hepatic consequences.
Data sources: The authors performed a systematic literature search in PubMed and EMBASE, using selected key words (obesity, childhood, cardiovascular, liver health). In particular, they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health.
Results: We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood, as a predisposing factor to cardiovascular and hepatic alterations. We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences.
Conclusions: The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence. Two key abnormalities in this context include cardiovascular diseases, and nonalcoholic fatty liver disease. Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents. Nevertheless, improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity, cardiovascular diseases, and diabetes risk during adulthood.
  [Abstract] [Full Text] [PDF]  
Acute infectious osteomyelitis in children: new treatment strategies for an old enemy
  Sabrina Congedi, Chiara Minotti, Carlo Giaquinto, Liviana Da Dalt, Daniele Don角
Background: Acute osteomyelitis still represents a significant clinical challenge, with an increasing incidence in paediatric population. A careful assessment and a rapid diagnosis with proper timing and choice of empirical antimicrobial therapy are necessary to avoid sequelae. The initial treatment should consist of empirical antibiotic therapy, to cover the major responsible pathogens in each age group.
Data sources: We made a literature search with PubMed and Cochrane database from 2000 to 2019 in English, French, and Spanish languages using the key words ※osteomyelitis, children, clinical, diagnosis, and treatment§.
Results: The child*s clinical features, age, and the microbiological profile of the geographic area should be evaluated for diagnosis and in the choice of antibiotic treatment. Latest data suggest the administration of intravenous antibiotics for a short period, with subsequent oral therapy, according to the improvement of clinical status and inflammatory markers. For children older than 3 months, the shift to oral medications is already possible after a short course of intravenous therapy, until recovery. The timing for the shift from cefazolin to cephalexin or cefuroxime, intravenous clindamycin to oral clindamycin, and intravenous ceftriaxone + oxacillin to oral equivalents will be decided according to the improvement of clinical status and inflammatory markers. We also present the approach to osteomyelitis due to difficult pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin (PVL)-positive S. aureus infections.
Conclusions: In this review, we present the current approach to the clinical diagnosis and management of osteomyelitis in childhood, with an update on recent recommendations, as a useful instrument to understand the rationale of antibiotic therapy.
  [Abstract] [Full Text] [PDF]  
Psychological interventions for adherence, metabolic control, and coping with stress in adolescents with type 1 diabetes: a systematic review
  Yousef M. Aljawarneh, Nesreen M. Al-Qaissi, Hana Y. Ghunaim
Background: The aim of this review was to summarize and identify the variations in the effectiveness of psychological interventions on adherence, metabolic control, and coping with stress in adolescents with type 1 diabetes (T1D).
Methods: An electronic search of literature was performed using PubMed (NLM), Embase (Ovid), CINAHL Plus (EBSCOhost), PsycINFO (Ovid), and Google Scholar. The search was limited to include articles reported the effect of one of the psychological interventions: cognitive behavioral therapy (CBT), coping skills training (CST), stress management, or psychotherapy intervention. The report included peer-reviewed articles published in English from January 1990 until May 2019 in adolescents with T1D, and summarizes the results of 24 studies that met the inclusion criteria.
Results: Psychological interventions showed differential effects on adherence, metabolic control, and coping with stress in adolescents with T1D. Behavioral interventions using principles of CBT appear to have a superior positive effect on regimen adherence compared with other types of psychological protocols. In contrast, metabolic control was significantly improved with the implementation of CST and some forms of CBT. Stress management and psychotherapy interventions showed significant promises for adolescents to cope with their diabetes-related daily stressors.
Conclusions: However, the findings may add some promises to diabetes management in adolescents, additional research to understand the effect of these interventions is needed.
  [Abstract] [Full Text] [PDF]  
Cesarean section and risk of childhood leukemia: a systematic review and meta-analysis
  Li-Li Jiang, Yin-Yan Gao, Wen-Bo He, Ting Gan, Hou-Qian Shan, Xue-Mei Han
Background: A large number of studies pointed that being delivered by cesarean section (CS) would affect the health outcomes of off spring, however, whether CS would affect the risk of childhood leukemia remained uncertain. This study conducted a meta-analysis to quantitatively evaluate whether being delivered by CS would influence the onset of childhood leukemia.
Methods: PubMed, Embase and Web of Science databases were searched from 3rd June, 1950 to 13th October, 2019 to identify the literature, which examined the relationship between CS and childhood leukemia. This study used Newcastle每Ottawa Scale to assess the quality of literature. Subgroup analyses were conducted on region, mode of delivery, design of the study and number of confounders adjusted. Egger*s test and Begg*s test were performed to evaluate possible publication bias.
Results: The pooled odds ratio (OR) estimates illustrated that children delivered by CS had a higher risk of developing leukemia [OR 1.10, 95% confidence interval (CI) 1.04每1.17, P = 0.002] and lymphoblastic leukemia (OR 1.12, 95% CI 1.03每1.23, P = 0.009), while a significant association for myeloid leukemia was not observed (OR 1.05, 95% CI 0.92每1.20, P = 0.451). Results of subgroup analyses indicated that elective CS would increase the risk of childhood lymphoblastic leukemia (OR 1.16, 95% CI 1.06每1.27, P = 0.002). However, a statistical relationship between emergency CS and lymphoblastic leukemia was not observed (OR 1.07, 95% CI 0.93每1.23, P = 0.364).
Conclusions: CS would increase the risk of childhood lymphoblastic leukemia. It is worth noting that subgroup analyses shows that elective CS rather than emergency CS increases the risk of lymphoblastic leukemia in off spring.
  [Abstract] [Full Text] [PDF]  
Etiology and therapeutic management of neonatal jaundice in Iran: a systematic review and meta-analysis
  Yadollah Zahed Pasha, Shaghayegh Alizadeh-Tabari, Ermia Zahed Pasha, Mohammad Zamani
Background: Jaundice is a life-threatening disorder in the neonates. In the present study, we aimed to assess systematically available evidence on causes and management of jaundice in Iranian newborn patients.
Methods: We searched the databases of PubMed, Web of Sciences, Scopus and Google Scholar for English articles published since inception until May 2019. A search was also done for Persian articles in Magiran and Scientific Information Database. Studies were evaluated based on predefined criteria by two reviewers. Data analysis was performed by STATA software.
Results: A total of 33 articles were finally included. The overall pooled prevalence of causes of jaundice among Iranian neonates was as follows: ABO blood groups incompatibility, 16.9% [95% confidence interval (CI) 10.9每22.8]; Rh blood group incompatibility, 4% (95% CI 2.5每5.5); ABO and Rh blood groups incompatibility, 3.6% (95% CI 0每7.7); glucose-6-phosphate dehydrogenase (G6PD) deficiency, 6.3% (95% CI 5.1每7.5); infection, 6.6% (95% CI 5.2每8.1); hypothyroidism, 4.2% (95% CI 0.1每8.3); infant of diabetic mother: 2.3% (95% CI 0.1每4.5); unknown, 50.7% (95% CI 33.4每68); cephalohematoma, 0.6% (95% CI 0.3每0.9). Regarding treatment of icterus, seven and eight articles were found on phototherapy and exchange transfusion, respectively. In five studies, all patients underwent phototherapy, but rate of exchange transfusion use was between 6.6% and 50.9%.
Conclusions: According to the results, unknown factors were the most common causes of icterus in Iranian neonates, followed by ABO blood groups incompatibility, infections and G6PD deficiency. By the way, phototherapy and exchange transfusion were found as therapeutic choices of neonatal jaundice.
  [Abstract] [Full Text] [PDF]  
Original articles:
Neonatal surgical outcomes after prenatal diagnosis of complex congenital heart disease: experiences of a perinatal integrated diagnosis and treatment program
  Xu Liu, Hai-Fa Hong, Hai-Bo Zhang, Zhuo-Ming Xu, Jin-Fen Liu, Hao Zhang
Background: This study aimed to evaluate neonatal surgical outcomes of patients diagnosed with complex congenital heart disease (CHD) during pregnancy and treated by the newly initiated ※perinatal integrated diagnosis and treatment program (PIDTP)§.
Methods: We reviewed clinical data of 207 neonates (surgical age ≒ 28 days) who underwent cardiac surgeries in a single center from January 2017 to December 2018, including 31 patients with referrals from the ※PIDTP§ (integration group) and 176 patients with routine referral treatment (non-integrated group).
Results: In the integration group, median admission age was 0 days and median age at surgery was 4 days. In the nonintegrated group, median admission age was 8 days (P = 0.001) and median age at surgery was 13 days (P = 0.001). The emergency surgery rate in patients with duct-dependent defects was 36% in the integration group and 59% (P = 0.042) in the non-integrated group, respectively. The in-hospital mortality was 16% in the integration group and 14% (P = 0.78) in the non-integrated group. The 2-year cumulative survival rate after surgery was 83.9% ㊣ 6.6% in the integration group and 80.3% ㊣ 3.1% (P = 0.744) in the non-integrated group. According to multivariable regression analysis, independent risk factors for early mortality of overall neonatal cardiac surgery were low body weight, high serum lactate level, postoperative extracorporeal membrane oxygenation (ECMO) support and prolonged cardiopulmonary bypass (CPB) time.
Conclusions: PIDTP shortens the postnatal transit interval, reduces the emergency operation rate of neonatal critical CHD, and provides better preoperative status for surgery. Patients treated by the PIDTP tend to have more complicated anatomical deformity and a greater requirement for the operation and postoperative management, but early outcome and follow-up prognosis are satisfactory.
  [Abstract] [Full Text] [PDF]  
Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis
  Hong-Wei Li, Hua-Song Zeng
Background: Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis (sJIA). The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA.
Methods: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) in active JIA patients. The relative expressions of miR-21, STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay. Rheumatoid arthritis fibroblast-like synovial cell (RASF) was stimulated to become to osteoclasts using macrophage colony-stimulating factor (M-CSF) and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21. The expression of STAT3/p-STAT3 was measured by western blot, and the levels of interleukin (IL)-17A, p65, matrix metalloproteinases (MMP)-3, MMP-4 and receptor activator of nuclear factor-百B after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay. Finally, the miR-21 targeted STAT3 gene was detected by the dual-luciferase reported assay.
Results: The expression of miR-21 was significantly lower in JIA patients than in healthy control (P < 0.05). The level of STAT3 was increased in PBMCs of JIA group compared with control group (P < 0.05). Furthermore, the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3 (r = − 0.5854/r = − 0.6134, P < 0.05). The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21. The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21 (P < 0.05). RASFs were induced into osteoclasts using M-CSF. The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group (P < 0.05).
Conclusions: We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control. MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3. MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.
  [Abstract] [Full Text] [PDF]  
The clinical phenotype and genotype of NLRP12-autoinflammatory disease: a Chinese case series with literature review
  Wei Wang, Yu Zhou, Lin-Qing Zhong, Zhuo Li, Shan Jian, Xiao-Yan Tang, Hong-Mei Song
Background: The nucleotide-binding oligomerization domain-like receptor protein 12 (NLRP12)-autoinflammatory disorder (NLRP12-AD) is a rare autoinflammatory disease characterized by recurrent fever, rash as well as musculoskeletal symptoms, which is rarely reported in Asian populations.
Methods: Three cases of NLRP12-AD presented to our hospital were studied after parental consents were obtained. Clinical presentations were recorded on a standardized case report form. Mutations of NLRP12 were detected by primary immunodeficiency disease panels and further examined by Sanger sequencing. PubMed literature search for relevant studies of systemic autoinflammatory disorders, especially NLRP12-AD between January, 2000 and January, 2019 was carried and the clinical data were summarized. Comparisons were made between groups in terms of onset age and of ethnicity.
Results: All our patients presented with fever, rash and arthritis/arthralgia, and sensorineural as well as sensorineural deafness (1/3), uveitis (1/3), abdominal pain (1/3), and myalgia (1/3). Two novel mutation variations, p.W581X and p.L558R, are reported here. In addition, we also found that two patients inherited the mutated alleles from their healthy parents, and this may be evidence of haploinsufficiency.
Conclusions: Although the genotypes are similar, the clinical manifestations between Chinese patients and Western patients vary thus highlighting the possible influence of ethnic and environmental factors. On the other hand, some genetic mutations may lead to specific phenotype, as we have found a high prevalence of sensorineural hearing loss among p.R284X patients.
  [Abstract] [Full Text] [PDF]  
Brief reports:
Hypercalcaemia after treatment with denosumab in children: bisphosphonates as an option for therapy and prevention?
  Carmen Sydlik, Hans Roland D邦rr, Susanne Bechtold-Dalla Pozza, Claudia Weißenbacher, Julia Roeb, Heinrich Schmidt
Background: Pharmacologic options for treatment of osteolytic diseases especially in children are limited. Although not licensed for use, denosumab, a fully humanized antibody to RANKL, is used in children with good effects. Among others, one possible indication are giant cell tumors and aneurysmatic bone cysts. However, there are reports of severe hypercalcemia during weeks to months after termination of denosumab, that are rarely seen in adults.
Methods: We collected data of four patients, aged 6每17 years, who experienced severe hypercalcemia after completion of treatment with denosumab for unresectable giant cell tumors of bone or aneurysmal bone cysts and methods of their treatment. The detailed case information were described.
Results: One patient was treated with long-term, high-dose steroid therapy, leading to typical Cushing*s syndrome. Another patient was restarted on denosumab repeatedly due to relapses of hypercalcemia after every stop. Finally, in two patients, hypercalcemia ceased definitely after treatment with bisphosphonates. However, several applications were necessary to stabilize calcium levels.
Conclusions: There is a considerable risk of hypercalcemia as an adverse effect after denosumab treatment in children. Therapeutic and, preferably, preventive strategies are needed. Bisphosphonates seem to be an option for both, but effective proceedings still remain to be established.
  [Abstract] [Full Text] [PDF]  
Polymyxin for the treatment of intracranial infections of extensively drug-resistant bacteria in children after neurosurgical operation
  Jing Ye, Lin-Hua Tan, Zhi-Peng Shen, Yun-Song Yu, Deng-Ming Lai, Jie Fan, Qiang Shu
Background: Increased meningitis caused by extensively drug-resistant bacillary presents a significant challenge in antibiotic selection. The aim of our study was to evaluate the efficacy and safety of polymyxin in the treatment of post-neurosurgical meningitis due to the extensively drug-resistant bacillary in children.
Methods: We performed a retrospective study on post-neurosurgical meningitis caused by the extensively drug-resistant bacillary in children, who were treated with polymyxin for ≡ 3 days.
Results: Among five post-neurosurgical meningitis cases that were included, the children were infected by Acinetobacter baumannii (n = 3), Klebsiella pneumonia (n = 1), and Pseudomonas aeruginosa (n = 1). The drug susceptibility test showed that they were extensively drug-resistant bacillary. Two patients received intravenous polymyxin E. Three children received intravenous combined with intraventricular injection of polymyxin B. One patient infected by Klebsiella pneumonia eventually died of septic shock. No serious adverse effects of polymyxin were observed.
Conclusion: Polymyxin is a safe and effective therapy for post-neurosurgical, multidrug-resistant bacillary meningitis in children.
  [Abstract] [Full Text] [PDF]  
Joy of gardening: a hospital-based cooking and gardening program
  Grace Kim, Kirsten Thompson
Background: Nutrition interventions aid in implementing healthy eating. Garden-enhanced nutrition intervention programs have been conducted in schools. We sought to assess feasibility of a hospital-based cooking and gardening program.
Methods: The cohort study implemented a 3-week integrated cooking and gardening program in the United States (Seattle, WA). We recruited participants with ages 8每15 years from ambulatory clinics. We conducted three 3-week series hospital-based cooking and gardening program. Children and parents were given pre- and post-program (1 year) surveys. The surveys assessed child participation in food preparation and gardening, strengths and weaknesses of the program, and identified parents* opinions towards sustaining healthy behaviors.
Results: Eighteen children participated in the hospital-based cooking and gardening program. At 1-year follow-up, 78% of participants were gardening at home and 100% of participants were cooking at home.
Conclusions: Novel approaches to combat obesity are needed. A hospital-based cooking and gardening program is a novel intervention to consider for nutrition education.
  [Abstract] [Full Text] [PDF]  
Sleep disturbances as an adverse effect of propranolol use in children with infantile hemangioma
  Ellen M. S. Xerfan, Monica L. Andersen, Anamaria S. Facina, Sergio Tufik, Jane Tomimori
  [Abstract] [Full Text] [PDF]  
Letters to the editor:
Myocardial dysfunction in SARS-CoV-2 infection in infants under 1 year of age
  Amar Taksande
  [Abstract] [Full Text] [PDF]  
Response to ※Myocardial dysfunction in SARS-CoV-2 infection in infants under 1 year of age§
  Dan Sun, Zhi-Sheng Liu
  [Abstract] [Full Text] [PDF]  
Muckle每Wells syndrome: manifestations and diagnosis in four generations of a Portuguese family
  Soraia Raquel Loureiro Azevedo, Daniela Filipa Marinho Peixoto
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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