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Background: Patent foramen ovale (PFO) is associated with transient ischemia attack (TIA) or stroke, paradoxical embolism, and migraines. PFO closure decreases the recurrent incidence of cerebral ischemic events and reduces the incidence of syncope in adults. However, whether PFO is associated with syncope in pediatric patients has not been investigated. Methods: 1001 pediatric patients (aged 4 to 17 years, mean age 10.31 ± 2.61 years, 519 males) who complained of unexplained syncope, palpitation, headache, dizziness and chest pain and were hospitalized in the Syncope Ward, The Second Xiangya Hospital, Central South University between January 2013 and April 2022 were recruited. Children with definite etiology of syncope, neurological, cardiogenic, psychological and other system diseases were excluded. PFO was measured by transthoracic echocardiography and right-heart contrast echocardiography was performed to identify the presence of right-to-left shunting. The demographic data and medical records were retrospectively reviewed and analyzed. Results: 276 cases were included in the simple syncope group, 379 cases in the headache/dizziness group, 265 cases in the chest pain group, and 81 cases in the palpitation group. The incidence of PFO between the four groups was insignificant (4.71%, 4.74%, 4.15%, 6.17%, respectively, P = 0.903). Multivariate Logistic regression demonstrated that PFO is not associated with the increased risk of syncope (P = 0.081). Conclusion: PFO may not increase the risk of syncope in pediatric patients. Further study may include a large and multicenter sample to investigate the association between PFO and unexplained syncope. [ABSTRACT FROM AUTHOR]

As the most commonly used coagulation factor VIII (FVIII) concentrate in China, the individualized dosing prediction model of Kovaltry (BAY81–8973) is not fully investigated in pediatric patients. The prophylaxis tailored by population pharmacokinetic (PopPK) model can optimize dosing regimens. This study aimed to develop PopPK models of BAY 81–8973 in pediatric patients, identify quantitative relationships of blood type (as a substitution for von Willebrand factor) on FVIII clearance and provide model-informed precision dosing (MIPD) procedures. Pediatric patients with severe hemophilia A were enrolled and PK tests were conducted. The blood samples were collected at six time point. One-stage-based activated partial thromboplastin time was used for FVIII activity. Basic demographics and key covariates (blood type and von Willebrand factor antigen) were collected. A nonlinear mixed-effect modeling (NONMEM) approach was employed to establish PopPK model. Simulations were performed to evaluate current dosing regimens and present MIPD strategies. A total of 30 pediatric patients were included in the analysis. In the final model, Fat-free mass calculated from weight, age, and height was included as a size descriptor which affect FVIII apparent volume of distribution and clearance. Both von Willebrand factor antigen (VWF:Ag) and blood type accounted for the interindividual variability of FVIII clearance, but only one can retain in the final model. Therefore, two PopPK models based on VWF:Ag or blood type were developed. When the VWF:Ag value is doubled, the FVIII clearance is reduced by 35 %. Compared with blood type non-O, the clearance in pediatric patients with blood type O increased by 25.9 %. Weight-based dosing without regard to age and blood type resulted in large differences in FVIII trough activity. Patient demographics, dosing information, sparse blood samples and PopPK model together with Bayesian estimate constituted the MIPD workflow. Using it, the individual parameters and optimized dosing regimen could be achieved. This is the first predictive model designed to predict individualized dosing of BAY 81–8973 in pediatric patients with Hemophilia A. These results are useful in the PK-guided prophylaxis among pediatric patients and hold great potential to improve their long-term clinical outcomes. [Display omitted] • Two population PK models of FVIII concentrate BAY 81-8973 in pediatric patients were developed for the first time. • Both von Willebrand factor antigen (VWF:Ag) and blood type accounted for the interindividual variability of FVIII clearance. • VWF:Ag can explain 5.8% of interindividual variability in clearance more than blood type. • Blood type can act as a substitute for VWF:Ag and the CL with blood type O increased by 25.9% compared with blood type non-O. • The models hold great potential to improve long-term clinical outcomes by predicting individualized dosing of FVIII. [ABSTRACT FROM AUTHOR]

Purpose: The safety and effectiveness of perampanel in clinical settings involving Chinese pediatric patients are limited, as perampanel has only recently been approved for use in China, in September 2019. We aimed to evaluate the efficacy and tolerability of perampanel as an adjunctive therapy for pediatric patients with epilepsy aged ≥ 4 years in Xinjiang, Northwest China. Methods: Efficacy was assessed by measuring changes in seizure frequency at 3-, 6-, and 12-month follow-up compared with baseline. The baseline was 3 months before the addition of perampanel, and the seizure frequency was based on the patients' seizure diary. The safety and tolerability depended on the type and frequency of any adverse event during epilepsy treatment across all pediatric patients. Results: Overall, 67 pediatric patients from 2 different hospitals were enrolled in the study. Among the pediatric patients with seizures during the baseline period, the effective rates for all seizure types at 3, 6, and 12 months were 59.1%, 58.7%, and 57.4%, respectively. During perampanel treatment, 34 patients (50.7%) experienced at least 1 adverse reaction. Conclusion: Overall, this real-world retrospective study of pediatric patients validated that perampanel is an effective treatment option as an adjunctive therapy among pediatric patients with epilepsy aged ≥4 years. [ABSTRACT FROM AUTHOR]

Background: Wilson's disease (WD) is an autosomal recessive disease that is caused by mutations in the ATP7B (a copper-transporting P-type ATPase) gene. The disease has a low prevalence and is characterized by a copper metabolism disorder. However, various characteristics of the disease are determined by race and geographic region. We aimed to discover novel ATP7B mutations in pediatric patients with WD from Yunnan province, where there is a high proportion of ethnic minorities. We also performed a comprehensive analysis of ATP7B mutations in the different ethnic groups found in Southwest China. Methods: We recruited 45 patients who had been clinically diagnosed with WD, from 44 unrelated families. Routine clinical examinations and laboratory evaluations were performed and details of age, gender, ethnic group and symptoms at onset were collected. Direct sequencing of the ATP7B gene was performed in 39 of the 45 patients and their families. Results: In this study, participants came from seven different ethnic groups in China: Han, Bai, Dai, Zhuang, Yi, Hui and Jingpo. Three out of ten patients from ethnic minorities presented with elevated transaminases, when compared to the majority of the Han patients. Forty distinct mutations (28 missense, six splicing, three non-sense, two frameshift and one mutation of uncertain significance) were identified in the 39 patients with WD. Four of the mutations were novel and the most frequent mutation was c.2333G > T (p.R778L, allelic frequency: 15.38%). Using the phenotype-genotype correlation analysis, patients from ethnic minorities were shown to be more likely to have homozygous mutations (p = 0.035) than Han patients. The patients who carried the c.2310C > G mutation had lower serum ceruloplasmin levels (p = 0.012). In patients with heterozygous mutations, c.3809A > G was significantly associated with ethnic minorities (p = 0.042). The frequency of a protein-truncating variant (PTV) in Han patients was 34.38% (11/32), while we did not find PTV in patients from ethnic minorities. Conclusion: This study revealed genetic defects in 39 pediatric patients with WD from Yunnan province. Four novel mutations were identified and have enriched the WD database. We characterized the genotypes and phenotypes in different minorities, which will enhance the current knowledge on the population genetics of WD in China. [ABSTRACT FROM AUTHOR]

Context: Since the outbreak of COVID-19 in late 2019, the transmission dynamics and clinical presentation patterns of influenza A (Flu A) virus have undergone changes., Objectives: This article conducted a comparative analysis in clinical characteristics and laboratory results of pediatric patients with Flu A before, during, and after the COVID-19 pandemic., Methods: The medical records of 885 children hospitalized with Flu A virus infection at a tertiary hospital in Guangdong Province, China, were retrospectively analyzed. Flu A was confirmed in these cases using a direct immunofluorescence antigen assay. The clinical data for this study span from January 1, 2018, to May 31, 2023., Results: In our study, we observed a total of 340 cases before the COVID-19 pandemic, 196 cases during the pandemic, and 349 cases after the pandemic. Patients after the pandemic had a higher median age on admission (5.66 years, range 3.41-7.70) and exhibited more respiratory symptoms such as cough, sore throat, and nasal stuffiness. The length of hospital stay was longer, and there was a higher percentage of patients with fever duration ≥ 5 days among Flu A patients during the pandemic. Compared to before and during the COVID-19 pandemic, Flu A patients after the pandemic showed significantly reduced white blood cell (WBC) and platelet (PLT) counts (P < 0.001), along with elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in laboratory indexes (P < 0.001). Furthermore, more hospitalized children after the pandemic were diagnosed with benign acute childhood myositis (BACM)., Conclusion: Our research results indicates a significant decrease in Flu A cases during the COVID-19 pandemic, and hospitalized children with Flu A have more severe clinical symptoms after the COVID-19 pandemic. These findings have implications for public health policy and clinical management of Flu A cases., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving humans were approved by the Institute Ethics Committee of Chaozhou Central Hospital (No. 2023009) and People’s Hospital of Yangjiang (No. 20230003). The studies were conducted in accordance with the local legislation and institutional requirements. The Ethics Committee/Institutional Review Board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A major hurdle in pediatric formulation development is the lack of safety and toxicity data on some of the commonly used excipients. While the maximum oral safe dose for several kinds of excipients is known in the adult population, the doses in pediatric patients, including preterm neonates, are not established yet due to the lack of evidence-based data. This paper consists of four parts: (1) country-specific perspectives in different parts of the world (current state, challenges in excipients, and ongoing efforts) for ensuring the use of safe excipients, (2) comparing and contrasting the country-specific perspectives, (3) past and ongoing collaborative efforts, and (4) future perspectives on excipients for pediatric formulation. The regulatory process for pharmaceutical excipients has been developed. However, there are gaps between each region where a lack of information and an insufficient regulation process was found. Ongoing efforts include raising issues on excipient exposure, building a region-specific database, and improving excipient regulation; however, there is a lack of evidence-based information on safety for the pediatric population. More progress on clear safety limits, quantitative information on excipients of concern in the pediatric population, and international harmonization of excipients' regulatory processes for the pediatric population are required. [ABSTRACT FROM AUTHOR]

Background: The emergence of ESBLs producing cephalosporin-resistant Escherichia coli isolates poses a threat to public health. This study aims to decipher the genetic landscape and gain insights into ESBL-producing E. coli strains belonging to the high-risk clone ST410 from pediatric patients., Methods: 29 E. coli ST410 isolates were collected from young children and subjected to antimicrobial susceptibility testing, Whole-genome sequencing (WGS), serotype analysis, MLST, ESBL genes, virulence genes, and plasmid profiling., Results: Antimicrobial susceptibility testing demonstrated a high level of resistance to cephalosporins followed by aminoglycoside, sulfonamide, carbapenem and penicillin group of antibiotics. However, n=20/29 shows MDR phenotype. Phylogenetic group B2 (n=15) dominated, followed by group D (n=7), group A (n=4), and group B1 (n=3). Serotyping analysis identified O1:H7 (n=8), O2:H1 (n=6), O8:H4 (n=5), O16:H5 (n=4), and O25:H4 (n=3). Other serotypes identified included O6:H1, O15:H5, and O18:H7 (n=1 each). The most commonly detected ESBL genes were bla CTX-M , (n=26), followed by bla TEM (n=23), and bla SHV (n=18). Additionally, bla OXA-1 (n=10), bla OXA-48 (n=5), bla KPC-2 (n=3), bla KPC-3 (n=2), bla NDM-1 (n=4), bla NDM-5 (n=1), bla GES-1 (n=2), bla GES-5 (n=1), and bla CYM-1 (n=3). Notable virulence genes identified within the ST410 isolates included fimH (n=29), papC (n=24), hlyA (n=22), and cnf1 (n=18), among others. Diverse plasmids were observed including IncFIS, IncX4, IncFIA, IncCol, IncI2 and IncFIC with transmission frequency ranges from 1.3X10 -2 to 2.7X10 -3 ., Conclusion: The ST410 clone exhibited a complex resistance profile, diverse serotypes, the presence of specific resistance genes (ESBL genes), virulence gene repertoire, and diverse plasmids. The bla CTX-M was the most prevalent ESBL gene detected., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Patil, Pai, Chen, Chen, Xinye, Dong, Kaushik, Lopes, Chen, Liu and Wen.)

High-dose methotrexate (HD-MTX) is widely used in pediatric acute lymphoblastic leukemia (ALL) treatment regimens. In this study, we aimed to develop a population pharmacokinetic (PK) model of HD-MTX in Chinese pediatric patients with ALL for designing personalized dosage regimens. In total, 4,517 MTX serum concentration data for 311 pediatric patients with ALL, aged 0.75–15.2 years and under HD-MTX treatment, were retrospectively collected at a tertiary Children's Hospital in China. The non-linear mixed-effect model was used to establish the population PK model, using NONMEM software. The potential covariate effects of age, body weight, and biochemical measurements (renal and liver function) on MTX PK disposition were investigated. The model was then evaluated using goodness-of-fit, visual predictive check. MTX PK disposition was described using a three-compartment model reasonable well. Body weight, implemented as a fixed allometric function on all clearance and volume of distribution parameters, showed a substantial improvement in model fit. The final population model demonstrated that the MTX clearance estimate in a typical child with body weight of 19 kg was 6.9 L/h and the central distribution of volume estimate was 20.7 L. The serum creatinine significantly affected the MTX clearance, with a 0.97% decrease in clearance per 1 μmol/L of serum creatinine. Other covariates (e.g., age, sex, bilirubin, albumin, aspartate transaminase, concomitant medication) did not significantly affect PK properties of MTX. The proposed population PK model could describe the MTX concentration data in Chinese pediatric patients with ALL. This population PK model combined with a maximum a posteriori Bayesian approach could be used to estimate individual PK parameters, and optimize personalized MTX therapy in target patients, thus aiming to reduce toxicity and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Introduction: the coronavirus disease 2019 in children does not present a high casuistry globally and it is characterized by presenting a wide clinical spectrum. The evolution of the disease is less severe in kids than in adults according to the data which was provided by some studies in China and other countries. Objective: to describe the clinical aspects, the laboratory one and the treatment of COVID-19 in the pediatric population that was treated. Methods: a descriptive cross-sectional study from Villa Clara Province was carried out in 43 patients that were diagnosed with COVID-19 from March to October 2020, the group of people was selected by non-probabilistic sampling. Results: a total of 43 children were affected, the older than 15 years had more predomination, 20 children had the disease asymptomatically and the rest presented mild symptoms. Cutaneous manifestations and mild respiratory symptoms were highlighted. 17 patients presented mild leukopenia in the laboratory tests at 72 hours, the pulmonary radiological pattern was normal except in 2 children. The treatment was applied to everybody according to the actual protocol (kaletra, chloroquine and interferon) and it showed excellent results. Conclusions: the clinical diagnosis favored to register a higher incidence of the disease in the patients older than 15 years, the asymptomatic cases predominated and the patients developed mild symptoms of the disease, the majority presented normal laboratory values and chest X-rays, the treatment was based on triple therapy according to the Cuban action protocol at that time. [ABSTRACT FROM AUTHOR]

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias. Methods: We conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test. Results: A total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups. Conclusion: Majority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia. [ABSTRACT FROM AUTHOR]

This study analyzed the pathogen distribution in bloodstream-infected (BSI) children hospitalized in Shandong Province from 2015 to 2018, to identify prevention strategies and select empiric antimicrobial therapy for BSI in children. Blood sample data from 14 107 children from 162 hospitals of Shandong Province were obtained from the China Antimicrobial Resistance Surveillance System and analyzed with WHONET 5.6 software. The results of the blood culture test showed the growth of 70.6% Gram-positive and 29.4% Gram-negative bacteria. Of the 14 107 blood isolates, 59.3% were collected from males and 40.7% were from females. Coagulase-negative staphylococci (47.1%) were the most commonly distributed pathogens. The distribution of pathogens varied according to age group and season. All Staphylococcus isolates were susceptible to vancomycin, teicoplanin and linezolid. Clinically, significant declines in penicillin-resistant Streptococcus pneumonia and carbapenem-resistant Escherichia coli were observed during the study period; however, detection rates of carbapenem-resistant Klebsiella pneumoniae increased over time (p < 0.05). Empiric antimicrobial therapy should be prescribed according to corresponding regional pediatric antimicrobial-resistant data. [ABSTRACT FROM AUTHOR]

Background: Postoperative respiratory adverse events are the most common perioperative complications in pediatric anesthesia, particularly prevalent in children undergoing tonsillectomy and adenoidectomy, with an incidence rate as high as 50%. The choice of anesthetic induction regimen directly influences the incidence of respiratory adverse events during the induction period. However, this effect seems to have minimal impact on postoperative outcomes. The occurrence rate of postoperative respiratory adverse events is likely more closely associated with the anesthetic maintenance phase, yet this relationship remains uncertain at present., Methods: The objective of this study was to assess the impact of different anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients undergoing tonsillectomy and adenoidectomy. The AmPRAEC study is a multicenter, randomized, double-blind controlled trial. A total of 717 pediatric patients were recruited from 12 medical centers and randomly assigned to three groups: group A (intravenous maintenance group, receiving propofol infusion); group B (intravenous-inhalational combination group, maintained with 1% sevoflurane combined with propofol); and group C (inhalational maintenance group, maintained with 2-3% sevoflurane inhalation). The primary outcome measure was the incidence rate of postoperative respiratory adverse events., Discussion: This clinical trial aims to elucidate the impact of various anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients. The outcomes of this study are anticipated to facilitate anesthesiologists in devising more comprehensive perioperative management strategies, enhancing comfort, and improving the clinical outcomes for this patient population., Trial Registration: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074803. Registered on August 16, 2023., (© 2024. The Author(s).)

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections., (© 2024 Wiley Periodicals LLC.)

Background: Leukemia can create a significant economic burden on the patients and their families. The objective of this study is to assess the medical expenditure and compensation of pediatric leukemia, and to explore the incidence and determinants of catastrophic health expenditure (CHE) among households with pediatric leukemia patients in China. Methods: A cross‐sectional interview was conducted among households living with pediatric leukemia using a questionnaire in two tertiary hospitals. CHE was defined as out‐of‐pocket (OOP) payments that were greater than or equal to 40% of a household's capacity to pay (CTP). Chi‐square tests and logistic regression analysis were performed to identify the determinants of CHE. Results: Among 242 households living with pediatric leukemia, the mean OOP payment for pediatric leukemia healthcare was $9860, which accounted for approximately 35.7% of the mean household's CTP. The overall incidence of CHE was 43.4% and showed a downward trend with the lowest income group at 69.0% to the highest income group at 16.1%. The logistic regression model found that medical insurance, frequency of hospital admissions, charity assistance, and income level were significant predictors of CHE. Conclusion: The results revealed that pediatric leukemia had a significant catastrophic effect on families, especially those with lower economic status. The occurrence of CHE in households living with pediatric leukemia could be reduced by addressing income disparity. In addition, extending coverage and improving compensation from medical insurance could also alleviate CHE. Some other measures that can be implemented are to address the barriers of charity assistance for vulnerable groups. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is no evidence on the most effective nutritional screening tool for hospitalized children. The objective of this study was to develop and validate a pediatric nutritional screening tool to assess undernutrition risk upon hospital admission.Methods and Study Design: The study had a two-phase prospective observational design. A novel pediatric nutritional screening score (PNSS) was developed and sensitivity, specificity, and reliability were evaluated by comparing with a complete dietetic assessment. Length of hospital stay, weight loss, disease complications, and nutritional support were recorded.Results: PNSS consisted of three elements: disease with malnutrition risks, changes in food intake, and anthropometric measurements, with a score of 0-2 for each element. The optimal cut-off score to identify patients (n=96) at risk of undernutrition was two. The agreement between PNSS and the complete dietetic assessment was moderate (κ=0.435, 95% CI=0.373-0.498). Sensitivity and specificity values of PNSS were 82% (95% CI=76%-87%) and 71% (95% CI=67%-74%), respectively. Inter-rater agreement had a κ value of 0.596 (95% CI=0.529-0.664, p<0.001). The percentage of children with undernutrition risk was 44.9%. Children with oncologic, gastrointestinal, and cardiac diseases were most likely to be at risk of undernutrition. The at-risk group was associated significantly with longer length of hospital stay and higher percentage of weight loss compared with the not-at-risk group.Conclusion: PNSS is the first nutritional screening tool developed for hospitalized children and validated in a large population of patients in China. [ABSTRACT FROM AUTHOR]

• Perampanel therapy in pediatric patients remains understudied in China. • Perampanel showed good effectiveness and tolerability in pediatric patients. • Effectiveness of perampanel was not influenced by the etiology or type of epilepsy. • The superior efficacy of PER as early add-on therapy in pediatric patients was demonstrated for the first time. The main aim of this study was to assess the efficacy, safety, and tolerability of adjunctive perampanel (PER) in the treatment of children and adolescents with epilepsy. Pediatric patients who visited the pediatric epilepsy clinic of Henan Provincial People's Hospital between May 2020 and December 2021 were recruited. All participants were treated with PER as adjunctive therapy and were seen routinely (minimum: a baseline and 12-week visit). The efficacy and tolerability of adjunctive PER for the treatment of epilepsy were investigated. One hundred and fourteen patients were enrolled, among whom 7 (6.1%) were lost to follow-up. At 12 weeks, the responder rate and the seizure-free rate were 56.1% (60/107) and 32.7% (35/107), respectively. The responder rate increased with the duration of PER administration and was significantly higher when PER was used as an early add-on (after ≤2 prior antiseizure medications (ASMs)) than a late add-on (after >2 prior ASMs). However, there was no significant difference in the treatment efficacy of adjunctive PER in patients with different epilepsy etiologies or types. Adverse events, including irritability, dizziness, somnolence, ataxic gait, weight gain, and tinnitus, were reported in thirty-two patients (29.9%). In a routine clinical setting of pediatric patients with epilepsy, good effectiveness and tolerability of adjunctive PER were demonstrated. Notably, patients initiating PER as an early add-on showed a better seizure outcome than those initiating PER as a late add-on. [ABSTRACT FROM AUTHOR]

Background: Systemic small blood vessel vasculitis (SSV) is uncommon among pediatric patients, and the predictive value of the new histopathological classification for SSV in terms of renal outcomes in these patients is unknown. Methods: The study cohort comprised 38 pediatric patients and 285 adult patients with SSV who were treated in a medical center between 1993 and 2012. Results: Children accounted for 11.8 % of all patients with SSV diagnosed during the study period. In contrast to the adult patients, the pediatric patients were predominantly female (73.7 vs. 51.9 %; P < 0.05). The prevalence of skin purpura was higher and pulmonary symptoms were less common among pediatric patients than among adult ones (36.8 vs. 13.7 %, P < 0.01 and 26.3 vs. 46.0 %, P < 0.05, respectively). Subtype was correlated with the baseline levels of serum creatinine and treatment response among patients with SSV and was found to have a tendency to predict end-stage renal disease (ESRD) among pediatric patients (hazard ratio 2.273, P < 0.01). The probability of progressing to ESRD was highest in pediatric patients with the sclerotic glomerulonephritis subtype, followed by the mixed, crescentic and focal glomerulonephritis subtypes (in descending order of probability) ( P < 0.01). Conclusions: Estimated histopathological classification has a prognostic value for renal outcome and response to therapy in children with SSV. [ABSTRACT FROM AUTHOR]

COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain "Omicron", with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARS-CoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive (RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Background: Research and development of pediatric drug faces many difficulties and pediatric clinical trials remain a challenge. Since 2011, a series of measures have been taken to encourage research, development of drugs for pediatric patients in China. In this study, we analyzed pediatric clinical trials conducted in China to provide reference for research and development of pediatric drugs and formulation of relevant policies., Methods: We conducted a cross-sectional observational study of pediatric trials registered in the Drug Trial Registration and Information Publication Platform before Oct. 31, 2021. All trials that recruited children (under 18 years old as defined in China) were retrieved and general characteristics of the trials and the research drugs were extracted and analyzed. The data were extracted and statistically analyzed by excel 2010 and SPSS 22.0, respectively., Results: There were 588 registered pediatric clinical trials, which accounted for 3.94% of the total registered trials. The overall average annual growth rate of the number of trials from 2013 to 2020 was 14.47% (P < 0.01). Of the 588 trials included, there were 312 trials (53.06%) with only children as subjects, 127 trials (21.60%) with research drugs only for children use, and the median of target subject number was 320 with the range of 8 to 600,000. The sponsors and the principal investigators were mainly located in the eastern and northern China. 325 trials were vaccine trials, and the dosage form was mainly injection. There were 98 non-vaccine biological product trials (mainly injections), 135 chemical compound drug trials (mainly tablets), 30 traditional Chinese medicine/natural drugs (mainly granules). Indications of the non-vaccine drugs were mainly diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism., Conclusion: The number of pediatric clinical trials in China has increased these years. To further promote pediatric clinical trials and motivate pediatric appropriate drug marketing application and administrative approval, conducting large pediatric clinical trials, further development of dosage forms suitable for children with special attention to neonates and prematurity, and improving uneven geographical distribution of sponsors and researchers are the current challenges., (© 2022. The Author(s).)

Objective: Complicated vascular anomalies (VAs) can be intractable and uncontrollable using conventional treatment and can result in lethal outcomes. We undertook a prospective, multicenter phase II trial to evaluate the efficacy and safety of sirolimus in pediatric patients with complicated VAs., Methods: Eligible patients were required to be aged 0 to 14 years and to have a complicated VA. The patients were treated with daily oral sirolimus for 12 months. The primary endpoint was the response, which was measured using sequential volumetric magnetic resonance imaging. The secondary endpoints were the disease severity score and quality of life., Results: Of 126 patients enrolled on an intention-to-treat basis, 98 (77.8%) had had an objective response to sirolimus, with a ≥20% decrease in lesion volume. Compared with those with arteriovenous malformations, the response rates were higher (>80%) for patients with common lymphatic malformations, venous malformations, kaposiform hemangioendothelioma, and combined malformations with a prominent venous and/or lymphatic component (P < .05). Improvements in the disease severity score and quality of life were obtained in 83.3% and 79.4% of patients, respectively. The most common adverse event was mucositis in 47 patients. More serious adverse events included reversible grade 4 pneumonitis in 3 patients and grade 4 upper respiratory infection in 1 patient. All these adverse events were considered at least possibly related to the treatment., Conclusions: Sirolimus is an apparently effective option for pediatric patients with various types of complicated VAs. Close monitoring of possible adverse events is required. The results from the present trial are the basis for future prospective studies using new therapeutic approaches., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Mycoplasma is one of the most common pathogens causing community-acquired pneumonia in pediatric patients. In recent years, the number of refractory or severe cases with drug resistance has been gradually increasing and cases that developed embolism after Mycoplasma pneumoniae (M. pneumoniae) infection have been reported. The present study retrospectively analyzed the clinical features, diagnosis and treatment of M. pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) in a series of 7 cases encountered between January 1st, 2016 to August 1st, 2019 at the Department of Pediatric Intensive Care Unit of The First Hospital of Jilin University (Changchun, China). Combined with relevant Chinese and international studies published during the last two decades, a comprehensive analysis was performed. All of the pediatric patients of the present study had fever, cough and dyspnea respiratory symptoms at onset and the disease progressed rapidly. Thereafter, PE was confirmed by a series of examinations. Pulmonary CT indicated patchy inflammations and significantly elevated D-dimer levels, accompanied by positive anticardiolipin antibodies. Furthermore, a filling defect in the pulmonary artery branch was observed on CT pulmonary angiography (CTPA) examination. In 2 cases, the condition was improved with anti-infection and anticoagulation treatment with low-molecular-weight heparin and warfarin, respectively, and the pulmonary embolism disappeared after 3-4 months. A total of 5 cases, who were not responsive to the drug treatment, underwent surgical resection. During the operation, the local tissues were determined to be infarcted and the pathological diagnosis was consistent with pulmonary infarction. Among the 5 cases, 2 died of Acute Respiratory Distress Syndrome at 3-8 days after the operation. The remaining patients underwent 6-12 months of follow-up and respiratory rehabilitation and their quality of life is now good. In conclusion, compared with healthy individuals, pediatric patients with critical MPP have an elevated risk of embolism. It is necessary to be vigilant regarding whether MMP is combined with PE and perform timely CTPA examination. Early detection, early treatment and surgical intervention (if necessary) may significantly reduce the risk of mortality and disability. [ABSTRACT FROM AUTHOR]

• WES is rapid and efficient to diagnose non-selective children with dyslipidemia. • LPL mutation is relatively common in non-selective children with dyslipidemia. • The mutation and phenotype spectra of familial hyperlipidemia were expanded. • In vitro experiments were performed for novel variants. Hyperlipidemia is a group of conditions with abnormally elevated levels of any or all lipids or lipoproteins in the blood. It is highly heterogeneous both genetically and clinically, which contributes to diagnostic challenges and results in many patients to be underdiagnosed and undertreated in China. Precise diagnosis and early management are critical to reduce the incidence of potential coronary artery disease and cardiovascular disease. We performed a single center study to demonstrate the clinical utility of the genome-first approach by whole exome sequencing (WES) for 12 pediatric patients with abnormal lipids or lipoproteins levels. In vitro experiments were performed in COS-7 cells to further evaluate the biological function of the novel variants. We identified ten pathogenic and likely pathogenic variants and three of them were novel. Molecular cause was uncovered in five (41.7%) patients including three lipoprotein lipase deficiency patients, one hypercholesterolemia patient and one sitosterolemia patient. We also found three patients with rare variants of uncertain significance. Copy number variant (CNV) analysis with WES data did not reveal any potential hyperlipidemia related CNVs in all patients. We expanded the mutation and phenotype spectra of familial hyperlipidemia. Our study demonstrated the effectiveness of genome-first approach for evaluation pediatric hyperlipidemia patients and showed that WES can be used as the first-tier test for patients with suspected Mendelian hyperlipidemia disorder. [ABSTRACT FROM AUTHOR]

Background and Objectives: We investigated the clinical significance of indeterminate pulmonary nodules (IPNs) in patients diagnosed with nonmetastatic, high-grade localized osteosarcoma., Methods: We retrospectively analyzed the clinical data of 364 patients with nonmetastatic, high-grade localized osteosarcoma. Based on pulmonary computed tomography findings at presentation, the patients were categorized into the no-nodules and the IPNs group and were further categorized into subgroups based on age (<18 and ≥18 years). We performed an intergroup comparison of event-free survival (EFS) and overall survival (OS)., Results: At presentation, 276 (75.8%) patients showed no nodules, and 88 (24.2%) patients showed IPNs. The EFS and OS were similar between adults with IPNs (n = 54 [30.5%]) and without nodules (n = 123 [69.5%]) (p = .200 and p = .609, respectively). No significant intergroup difference in OS was observed in pediatric patients (p = .093). However, pediatric patients with IPNs (n = 34 [18.2%]) had poorer EFS than those without nodules (n = 153 [81.8%]) (p = .016). Multivariate analyses confirmed that IPNs were independently associated with poorer EFS in pediatric patients (hazard ratio 1.788, 95% confidence interval 1.092-2.926, p = .021)., Conclusions: This study showed that IPNs at presentation did not affect the survival of adults with nonmetastatic, high-grade localized osteosarcoma but were associated with poorer EFS in pediatric patients., (© 2020 Wiley Periodicals LLC.)

Purpose: This study aimed to analyze the topological characteristics of brain structural network in pediatric epilepsy patients with vagus nerve stimulation (VNS) by applying graph theoretical approaches., Methods: Nine patients with generalized seizures and eight normal controls (NC) were enrolled. Based on diffusion tensor imaging, graph theory analysis was used to characterize the topological properties in preoperative patients (EP-pre), postoperative patients (EP-post) and NC. The global properties included clustering coefficient (Cp), shortest path length (Lp), small-worldness (γ, λ, δ), global network efficiency (Eg) and local network efficiency (Eloc). The regional properties included degree centrality (DC), nodal efficiency (NE), nodal local efficiency (NLE) and nodal shortest path length (Np). Two sample t-test and paired sample t-test were utilized to compare properties difference., Results: All three groups followed small-world characteristics. There was no significant difference in small-worldness, Cp, Lp, Eg or Eloc between EP-pre and EP-post. Compared with EP-pre: DC in EP-post decreased in the right cuneus and right temporal gyri, while increased in the right paracentral lobule; NE in EP-post decreased in the left dorsolateral superior frontal gyrus, right cuneus, right supramarginal gyrus, and right rolandic operculum, while increased in the right paracentral lobule; NLE in EP-post decreased in the left posterior cingulate gyrus and right supramarginal gyrus, while increased in the left parahippocampal gyrus; NP in EP-post decreased in the right paracentral lobule, while increased in the right cuneus., Conclusion: VNS causes topological characteristics changes in pediatric patients with generalized seizures through regulating regional properties in some brain structures., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19., Methods: A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People's Hospital from January 11 th to February 10 th , 2020 were included. The data were obtained from electronic medical records. The epidemiological data, clinical characteristics, length of hospital stays, and outcomes of pediatric and adult patients were compared., Results: Compared with adult patients, pediatric patients had a shorter time of symptom onset to hospitalization than adults [median time, 1 ( IQR , 1.0-1.0) d vs. 3 ( IQR , 2.0-6.0) d, P < 0.001], milder or fewer symptoms, less severe chest CT findings. The clinical severity classification of children was less severe than adults. Up to 15 th March, the end of the follow-up, 33 (100%) children and 292 (97.3%) adult patients had been discharged from hospital. Only 2 (0.7%) adult patients died, with an overall case mortality of 0.6%. The median length of hospital stay of pediatric patients was shorter than that of adult patients [19 (95% CI : 16.6-21.4) d vs. 21 (95% CI : 19.9-22.1) d, P = 0.024]., Conclusion: Pediatric patients with COVID-19 had milder or less clinical symptoms, less evident pulmonary imaging changes, better prognosis, and shorter length of hospital stay., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The specific description, risk factors, and outcomes of aGVHD in pediatric haplo-HSCT using TCR protocols without PT-Cy have not been well described previously. We evaluated the incidence, risk factors, and outcomes of aGVHD in 350 consecutive pediatric patients receiving TCR haplo-HSCT without PT-Cy according to the Glucksberg and NIH aGVHD classifications between January 2015 and December 2017 at Peking University Institute of Hematology. The cumulative incidences of grade I, II, III, and IV aGVHD were 28%, 29.7%, 8.3%, and 5.1%, respectively. The type of aGVHD onset was classic in 243 patients (97.2%), and persistent/recurrent/late-onset aGVHD was in seven patients (2.8%). None of the considered variables significantly influenced the incidence of grade III-IV aGVHD. The 3-year OS, DFS, cumulative incidence of NRM, and relapse in malignant disease between severe aGVHD (III-IV) group and grade 0-II aGVHD group were 61.5% vs 77.2% (P = .027), 58.6% vs 75.1% (P = .014), 19.8% vs 5.3% (P = .002), and 21.6% vs 19.6% (P = .59), respectively; in non-malignant diseases, the 3-year OS, DFS, and NRM were 81.8% vs 97.4% (P = .05), 81.8% vs 97.4% (P = .05), and 18.2% vs 2.6% (P = .05), respectively. Under the protocol of pediatric TCR haplo-HSCT without PT-Cy, the persistent/recurrent/late-onset aGVHD was rare, and the incidence of severe aGVHD was acceptable and significantly contributed to NRM and lower survival in both malignant disease and non-malignant diseases., (© 2020 Wiley Periodicals LLC.)

Introduction: COVID-19 has become a global health security issue, it has caused more than half a million deaths worldwide so far, the treatment strategies are the most concerned issues for clinicians. In this study, the treatments and outcomes in 40 pediatric patients diagnosed with COVID-19 and treated with different drugs were evaluated., Methodology: All cases were diagnosed with COVID-19 nucleic acid positive by using RT-PCR or clinical manifestations, imaging specific characteristics and epidemiological clinical diagnosis. The biological information and first symptom of all cases were collect. A variety of treatments were employed and the outcomes were evaluated by Cox regression analysis. Multivariable analysis was performed to evaluate cure rate at 14 days with different drug treatment., Results: The average length of hospital stay was 10.4 days. The cure rate was increased with the treatment time extended and 90% of pediatric patients were cured and discharged after 14 days' treatment. And multivariable analysis results proved that none of the covariates were related to the cure rate at 14 days with different drug treatment since p values were over 0.05., Conclusions: Multivariable analysis suggested that the present drug treatments cannot significantly shorten the clinical cure time and improve the cure rate of children with COVID-19., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Mengting Li, Yang Wang, Hua Xu, Changlin Liu, Liang Shi, Qi Ye, Jun Wang, Sichan Li, Yan Mei, Liuliu Gao.)

Object: The goal of this study was to evaluate the feasibility of the C-1 posterior arch crossing screw fixation technique in the pediatric age group., Methods: One hundred twenty-three pediatric patients were divided into 6 age groups. Computed tomography morphometric analysis of the C-1 posterior arch was performed. Measurements included height, width, and length. Statistical analysis was performed using the Student t-test and linear regression analysis., Results: The mean measurement of the posterior arch was height (6.35 ± 1.80 mm), width (Width 1: 4.48 ± 1.25 mm; Width 2: 4.42 ± 0.68 mm; Width 3: 4.42 ± 0.50 mm), and length (14.48 ± 1.67 mm). Seven (6.93%) of the 101 children in Groups 1-4 and 13 (59.1%) of the 22 children in Groups 5 and 6 could safely accommodate placement of C-1 posterior arch crossing screws., Conclusions: This investigation found that a C-1 posterior arch crossing screw was feasible in this group of Chinese pediatric patients, particularly in those 13 years and older. Preoperative thin-cut CT is essential for identifying children in whom this technique is applicable and for planning screw placement.