Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children

Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Benign liver tumors in pediatric patients-Review with emphasis on imaging features

Benign hepatic tumors are commonly observed in adults,but rarely reported in children.The reasons for this remain speculative and the exact data concerning the incidence of these lesions are lacking.Benign hepatic tumors represent a diverse group of epithelial and mesenchymal tumors.In pediatric patients,most benign focal liver lesions are inborn and may grow like the rest of the body.Knowledge of pediatric liver diseases and their imaging appearances is essential in order to make an appropriate differential diagnosis.Selection of the appropriate imaging test is challenging,since it depends on a number of age-related factors.This paper will discuss the most frequently encountered benign liver tumors in children(infantile hepatic hemangioendothelioma,mesenchymal hamartoma,focal nodular hyperplasia,nodular regenerative hyperplasia,and hepatocellular adenoma),as well as a comparison to the current knowledge regarding such tumors in adult patients.The current emphasis is on imaging features,which are helpful not only for the initial diagnosis,but also for pre- and posttreatment evaluation and follow-up.In addition,future perspectives of contrast-enhanced ultrasound(CEUS) in pediatric patients are highlighted,with descriptions of enhancement patterns for each lesion being discussed.The role of advanced imaging tests such as CEUS and magnetic resonance imaging,which allow for non-invasive assessment of liver tumors,is of utmost importance in pediatric patients,especially when repeated imaging tests are needed and radiation exposure should be avoided.

Determinants for asthma control, quality of life and use of complementary and alternative medicine in asthmatic pediatric patients in four cities

Background Asthma is a significant chronic health problem worldwide. Management aims at disease control by reducing functional impairment and exacerbations and improving quality of life (QoL). We report a multi-center study to survey asthma control and QoL in four cities in the Pearl River Delta. Methods The conjoint survey involved ten Hong Kong pediatric hospitals/units, two Shenzhen hospitals, two Macao hos-pitals, and two Guangzhou hospitals on asthma control (using Asthma Control Test) and QoL (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ). Acceptability of a treatment is graded as very good/good/fair/poor. Results Good asthma control was only reported in 80% subjects in Hong Kong, but higher in sister cities (85–94%, P<0.001). Allergic rhinitis, 'incense burning', and 'smoker in family' were prevalent among the four cities. Logistic regres-sion showed better control of asthma was associated with better PADQLQ (B=?0.029, P < 0.001), better acceptability of bronchodilator (B=?1.488, P = 0.025), negatively with 'smoker in family' (B=?0.83, P = 0.015) and various PADQLQ domains. Conversely, worse PADQLQ was associated with allergic rhinitis severity (B=4.77, P <0.001), poor control of asthma (B=7.56, P <0.001), increased frequency of traditional Chinese medicine use (B=1.7, P < 0.05), increased fre-quency of bronchodilator usage (B=1.05, P < 0.05), 'smoker in family' (B=4.05, P < 0.05), and incense burning at home (B=3.9, P < 0.05). Conclusions There are some clinical and cultural differences among the four southern Chinese cities within the Guangdong province. This study identifies potentially modifiable environmental and treatment factors associated with poor asthma control and QoL for health-care interventions. Having a smoker in the family is independently associated with poor asthma control and QoL.

Serum proteomic profiling for autism using magnetic bead-assisted matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a pilot study

Background The pathogenesis of autism spectrum disorders remains elusive and currently there are no diagnostic or pre-dictive biomarkers in autism available. Proteomic profiling has been used in a wide range of neurodevelopmental disorder studies, which could produce deeper perceptions of the molecular bases behind certain disease and potentially becomes useful in discovering biomarkers in autism spectrum disorders. Methods Serum samples were collected from autistic children about 3 years old in age (n = 32) and healthy controls (n = 20) in similar age and gender. The samples were identified specific proteins that are diff erentially expressed by magnetic bead-based pre-fractionation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS). Results Eight protein peaks were significantly different in autistic children from the healthy controls (P < 0.0001). The two peaks with the most significant diff erences were 6428 and 7758 Da in size. Conclusion According to diff erences in serum protein profiles between the autistic children and healthy controls, this study identified a set of diff erentially expressed proteins those are significant for further evaluation and might function as biomark-ers in autism.

The availability of probiotics and donor human milk is associated with improved survival in very preterm infants

Background To determine whether the introduction of pasteurized donor human milk and probiotics for infants born<32 weeks gestational age or<1500 g birthweight is associated with a reduction in mortality and the incidence of necrotising enterocolitis (NEC) and sepsis. Methods We performed a retrospective analysis of two cohorts: before and after the introduction of probiotics and pasteurised donor human milk. Univariate analysis of primary and secondary outcomes was performed;variables impacting outcomes were assessed using multivariate logistic regression. Results There were 1791 infants: 1334 in the pre-donor milk/probiotic cohort and 457 in the post-donor milk/probiotic cohort. On univariate analysis, mortality (7.6 vs. 2.4%, P<0.001) and incidence of sepsis (6.2 vs. 3.5%, P=0.028) were statistically significantly lower in the post-donor milk/probiotic group. NEC (2.8 vs. 1.5%, P=0.14) and non-NEC associ-ated gastrointestinal perforation (1.6 vs. 0.4%, P=0.052) were lower in the post-donor milk/probiotics cohort, but these were not statistically significant. The difference in mortality remained statistically significant on multivariate analysis in the post-donor milk/probiotic cohort compared to those in the pre-donor milk/probiotic cohort (odds ratio 0.31, 95% confidence interval 0.16–0.61). The decrease in the incidence of NEC was consistent with previous observational studies but the differ-ence was not statistically significant. Conclusion The availability of probiotics and pasteurised donor human milk is associated with a reduction in mortality in very preterm infants.

Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq

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 war-torn 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 blastemal-predominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confirmed dead from disease. Median clinical follow-up was 40.5 months (range 6–78 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.

Socioeconomic inequality in screen time frequency in children and adolescents: the weight disorders survey of the CASPIAN IV study

Background This study aimed to assess the socioeconomic inequality and determinants of screen time (ST) frequency in Iranian children and adolescents. Methods This nationwide study was conducted as part of a national school-based surveillance program among 36,486 students consisting of 50.79% boys and 74.23% urban inhabitants, aged 6–18 years, living in urban and rural areas of 30 provinces of Iran. Socioeconomic inequality in ST, including the time spent for ST, watching TV and leisure-time work-ing with computer, was assessed across quintiles of SES using concentration index (C) and slope index of inequality (SII). Results Overall, 36,486 students completed the study (response rate 91.25%). Their mean (SD) age was 12.14 (3.36) years. The national estimation of frequency of ST was 31.66% (95% CI 31.16–32.17) with ascending change from 20.80% (95% CI 19.81–21.82) to 36.66% (95% CI 35.47–37.87) from the first to the last quintal of SES. EstimatedC value at national level was positive (0.08), which indicate inequality was in favor of low SES groups. Considering the SII values, at national level [? 0.16 (? 0.39, 0.06)], the absolute difference in ST frequency between the bottom and top of the socioeconomic groups had descending trends. In multivariate logistic regression model, family history of obesity, generalized obesity and age were the main significant determinants of prolonged ST, watching TV, and computer working (P < 0.001). Conclusions Socioeconomic inequality in ST frequency was in favor of low SES groups. These findings are useful for health policies, better programming and future complementary analyses.

儿童接受心脏移植术后的淋巴增生性疾病:一项多中心研究

Background: Post-transplant lymphoproliferative disorders (PTLD) are an impor tant cause of morbidity and mortality after organ transplantation. We sought to better define the prevalence, pathology, current therapeutic approaches, and out comes of PTLD in a large group of children who had received heart transplants. M ethods: We assessed data on patients followed up at 19 centres in the Pediatric Heart Transplant Study (PHTS) from 1993 to 2002. Probability of freedom from PTL D was assessed along with details of presentation, pathology, treatment, and out comes. Risk factors for survival and event-free survival were investigated. Findings: Of 1184 primary transplant recipients, 56 (5%) developed PTLD. Probabili ty of freedom from PTLD was 98%at 1 year, 94%at 3 years, and 92%at 5 years. M ean time to PTLD was 23.8 months. Most common sites of disease were gastrointest inal tract (n=22, 39%) and respiratory system (n=14, 25%). Histology was polym orphic in 35 (65%) and monomorphic in 19 (35%). 47 of 48 cases were of B-cell origin, 39 of 45 (87%) were Epstein-Barr virus positive. Probability of survi val was 75%at 1 year, 68%at 3 years, and 67%at 5 years after diagnosis. Death from graft loss was as frequent as death from PTLD. Interpretation: About 5%of paediatric heart-transplant recipients develop PTLD, almost always of B-cell lineage and driven by Epstein-Barr virus. Although many achieve satisfactory ou tcomes, mortality remains substantial with death due to progressive disease and allograft loss. Advances in management should focus on strategies to protect the allograft as well as improved therapies for PTLD.

受到肉体虐待的学龄前儿童的认知和神经影像学改变

Aims: To characterise the cognitive, motor, and language skills of toddlers an d preschoolers who had been physically abused and to obtain concurrent MRIs of t he brain. Methods: A between groups design was used to compare a sample of 19 ch ildren, aged 14-77 months, who had been hospitalised for physical abuse with no evidence of neurological injury to a comparison group of 19 children matched for age and socioeconomic status. Children underwent cognitive, language, and motor testing within three months of their discharge from the hospital. Caregive rs of the injured children were interviewed and were asked to complete questionn aires to characterise the child’s developmental level and behaviour just prior to the hospitalisation. Results: Children who had been physically abused scored significantly lower than the comparison group on measures of cognitive functioni ng, motor skills, and language skills. The groups did not differ in child behavi our ratings completed by the caregivers. MRI of the brain was performed for 15 c hildren in the physical abuse group; two were found to have significant cerebral atrophy. Conclusions: Children who have been physically abused are at high risk for delays in cognitive, motor, and language development. Standard of care for these children should include developmental testing as well as neuroimaging of t he brain to detect occult brain injury.

Chinese clinical practice guidelines for acute infectious diarrhea in children

Background The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. Data sources The experts group of evidence development put forward clinical problems, collects evidence, forms prelimi-nary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic 'acute diarrhea' or 'enteritis' and 'adolescent' or 'child' or'Pediatric patient' or 'Baby' or 'Infant'. Results For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recom-mended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Sac-charomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racec-adotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease;otherwise, antibiotics are not recommended. Conclusion The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Kaposiform hemangioendothelioma in children: a benign vascular tumor with multiple treatment options

Background Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor affecting infants and young children. Although benign, it can be associated with an aggressive locally growing tumor and/or a life-threatening Kasabach–Merritt phenomenon (KMP). To date, only reviews of limited cases have been performed. We, therefore, conducted a comprehensive literature search to collect relevant data and make recommendations for future treatment trials. Methods Review of the available literature between 1993 and 2017 revealed a total of 105 publications involving 215 patients of less than 21 years of age. To this, we added 12 from our department and 4 from the Cooperative Weichteilsarkomstudie database. Results We found that KMP was present in 79% of the infants, in 47% of the 1–5-year olds, in 43% of the 6–12-year olds, and in 10% of the 13–21-year-old patients. KMP was present in nearly all (94%) patients with retroperitoneal tumors and in all patients with extra-regional tumors. The median size of a KHE without KMP was 12 cm2 as compared to 49 cm2 when associated with a KMP. With complete (not further classifiable if R0 or R1) resection, all patients were cured. If inoperable, response regarding KMP/regression of tumor size was seen in 29/28% with steroid-, 47/39% with vincristine-, 44/43% with interferon alpha-, 65/61% with anti-platelet agents-, and in 97/100% with sirolimus-containing therapies. Conclusions Patients with progressive KHE should undergo resection whenever it is considered a safe option. If inoperable, sirolimus should be the first choice for treating KMP and reducing tumor size.

Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition)

Background Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treat-ments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. Methods National Health Commission of China assembled an expert committee for a revision of the guidelines. The com-mittee included 33 members who are specialized in diagnosis and treatment of HFMD. Results Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia;(2) involvement of nervous system;(3) worsening respiratory rate and rhythm;(4) circulatory dysfunction;(5) elevated peripheral WBC count;(6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. Conclusion The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

Oxcarbazepine oral suspension in young pediatric patients with partial seizures and/or generalized tonic-clonic seizures in routine clinical practice in China: a prospective observational study

Background This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China. Methods This 26-week, prospective, single-arm, multicenter, observational study recruited pediatric patients aged 2-5 years with PS or GTCS suitable for OXC oral suspension treatment based on physicians' judgments from 11 medical centers in China. Enrolled subjects started OXC oral suspension treatment as monotherapy or in combination with other antiepileptic drugs. Primary efficacy outcome was the percentage of pediatric subjects achieving ≥ 50% seizure frequency reduction at the end of the 26-week treatment. Secondary efficacy-related parameters and safety parameters such as adverse events (AEs) and serious AEs (SAEs) were also monitored during the 26-week treatment period. Results Six hundred and six pediatric patients were enrolled and 531 (87.6%) completed the study. After 26 weeks of treat-ment, 93.3% subjects achieved ≥ 50% seizure frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared to baseline. Among diff erent seizure types, OXC was eff ective in all subjects with simple PS and in > 90% of subject with other type of seizure present in the study. AEs were observed in 49 (8.1%) subjects. Only three subjects expe-rienced SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued due to AEs. Conclusion This study, reporting the real-world data, further confi rms the efficacy and good safety profi le of OXC oral suspension in Chinese pediatric patients aged 2-5 years with PS and/or GTCS.