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Abstract Previous studies have suggested that vitamin D has a protective effect on allergic diseases, while an individual's sex may have a moderating effect on the relationship between vitamin D and allergic‐related immunity. This study aimed to determine the role of vitamin D in children with coexisting allergic diseases in the context of sex differences and to explore the behavioral profiles of these patients. We recruited a total of 103 children with atopic diseases and divided them into four groups: males with one allergic disease (MA1, n = 20), males with two or more allergic diseases (MA2, n = 26), females with one allergic disease (FA1, n = 30), and females with two or more allergic diseases (FA2, n = 27). We measured serum calcium levels using the colorimetric method and serum 25‐OH vitamin D total levels using electrochemiluminescence immunoassay. We found that MA2 had significantly lower vitamin D levels than MA1 and FA2. The levels of IgE were negatively correlated with vitamin D in females, whereas the levels of IgE were not significantly correlated with vitamin D in males. Furthermore, serum IgE was significantly correlated with children's adaptive skills, and different sexes were associated with different aspects of adaptive skills. Our findings suggest a protective role of vitamin D in the development of one allergic disease against the coexistence of allergic diseases in males, as well as extend the evidence for sex differences in immunity by demonstrating a sex‐different correlation between IgE and vitamin D and the relationship between IgE and children's adaptive skills.

BackgroundInfection with SARS-CoV-2 virus has been associated with cardiovascular sequelae including multisystem inflammatory syndrome (MIS-C) in children. Patients with a prior history of Kawasaki disease, may be more susceptible to changes in echocardiographic or laboratory findings after COVID-19. The objective of this study was to investigate the echocardiographic and laboratory findings in children with a prior history of Kawasaki disease after SARS-CoV-2 infection.Materials and methodsIn this study, we performed a retrospective chart review of 41 children younger than 18 years old who were diagnosed with COVID-19 from April to August of 2022 and had a prior history KD. We included echocardiography and blood draw data obtained at the last outpatient follow-up at our hospital for KD, and within 4 months of SARS-CoV-2 infection. Echocardiographic data obtained from 82 age-matched and gender matched controls were also included for comparison.ResultsWe found that COVID-19 resulted in slightly higher RCA Z-scores within the first month after infection (mean ± SE, 1.20 ± 0.18 vs. 0.83 ± 0.18, p = 0.030), although this increase did not result in coronary artery dilatation, defined as a Z-score of at least 2.5. In addition, we found that degree of RCA dilatation after COVID-19 infection was negatively correlated with the change in monocyte percentage (Pearson's correlation coefficient—0.363, p = 0.020). Moreover, RCA Z-score changes were lower in patients who received at least one dose of mRNA COVID-19 vaccine when compared those who did not receive any (mean ± SE, −0.23 ± 0.16 vs. 0.39 ± 0.17, p = 0.031).ConclusionIn this pilot study we found that COVID-19 infection resulted in slightly higher RCA Z-scores in children with a prior history of KD, although not large enough to be classified as coronary aneurysms. While these changes could be the result of measurement imprecision or interobserver variation, further study of the cardiac outcomes of COVID-19 infection in children with a prior history of KD are needed in the future.

BackgroundIn 2016, Lin et al. developed a prediction score of non-responsiveness to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD) (Lin et al., 2016). Various studies have attempted to validate the Formosa score, but inconsistent results have given us new opportunities and challenges. The aim of this meta-analysis is to explore the role of the Formosa score as a risk score in detecting IVIG-resistant KD patients and then compare the pooled sensitivity and specificity of four Asian risk scores, Egami, Formosa, Kobayashi, and Sano risk scores.MethodsA comprehensive search of Cochrane, Embase, and PubMed was conducted through 20 December 2021, using key terms relevant to the research question “What are the sensitivities and specificities of the four Asian predicting scores, Egami, Formosa, Kobayashi, and Sano, in Kawasaki disease patients with IVIG resistance?” The reference lists of the included studies were manually reviewed to identify pertinent references. A random-effects bivariate model was used to estimate the summary of sensitivity and specificity of the tools.ResultsWe found 41 relevant studies of the four Asian risk scores that were eligible to analyze for pooled accuracy. Eleven studies involving 5,169 KD patients reported the diagnostic performance of the Formosa score for the risk of IVIG resistance. The overall performance of the Formosa score was as follows: pooled sensitivity, 0.60 [95% confidence interval (CI), 0.48–0.70]; pooled specificity, 0.59 (95% CI, 0.50–0.68); and area under the hierarchical summary receiver operating characteristic curve, 0.62. The Formosa score exhibited the highest sensitivity 0.76 (95% CI, 0.70–0.82) for detecting IVIG-resistant KD patients among the 21,389 children included in the 41 studies. In terms of specificity estimates, Formosa had the lowest specificity of 0.46 (95% CI, 0.41–0.51).ConclusionPatients at high risk for IVIG resistance may receive adjunctive treatment to reduce coronary lesions and thus also cardiovascular morbidity. Among all of the included studies, we found Formosa score to have the best sensitivity (0.76) but unsatisfactory specificity (0.46) for predicting IVIG resistance in Kawasaki disease. In the future, network meta-analysis should also incorporate the accuracy of the new scores after they have undergone a certain degree of validation around the world.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO CRD42022341410.

IntroductionKawasaki disease (KD) may increase the risk of myocardial infarction or sudden death. In children, delayed KD diagnosis and treatment can increase coronary lesions (CLs) incidence by 25% and mortality by approximately 1%. This study focuses on the use of deep learning algorithm-based KD detection from cardiac ultrasound images.MethodsSpecifically, object detection for the identification of coronary artery dilatation and brightness of left and right coronary artery is proposed and different AI algorithms were compared. In infants and young children, a dilated coronary artery is only 1-2 mm in diameter than a normal one, and its ultrasound images demonstrate a large amount of noise background-this can be a considerable challenge for image recognition. This study proposes a framework, named Scaled-YOLOv4-HarDNet, integrating the recent Scaled-YOLOv4 but with the CSPDarkNet backbone replaced by the CSPHarDNet framework.ResultsThe experimental result demonstrated that the mean average precision (mAP) of Scaled-YOLOv4-HarDNet was 72.63%, higher than that of Scaled YOLOv4 and YOLOv5 (70.05% and 69.79% respectively). In addition, it could detect small objects significantly better than Scaled-YOLOv4 and YOLOv5.ConclusionsScaled-YOLOv4-HarDNet may aid physicians in detecting KD and determining the treatment approach. Because relatively few artificial intelligence solutions about images for KD detection have been reported thus far, this paper is expected to make a substantial academic and clinical contribution.

Background: Kawasaki disease (KD) is a form of systemic vasculitis that primarily affects children under the age of 5 years old. Antibiotics are often prescribed for KD patients even before a diagnosis is made due to their prolonged fever and elevated inflammatory markers. Therefore, the purpose of this study was to investigate the impact of antibiotics usage on the disease outcome of KD. Methods: We carried out a retrospective chart review of children between 2005 and 2017 for initial immunoglobulin (IVIG) treatment of KD. KD children with initial IVIG treatment more than 10 days after the onset of symptoms were excluded. Results: In total, 280 children were eligible for this study, among which 209 had been treated with antibiotic(s) and 71 had not been. The IVIG resistance rates were 5.6% (4/71), 8.9% (10/112), and 21.6% (21/97) in non-users, single-drug users, and multiple-drug users, respectively (r = 0.205, p = 0.003). The IVIG resistance rate of the multiple antibiotics drug users in KD patients was significantly higher than the other two groups. Furthermore, the likelihood of IVIG resistance was found to increase with elevated C-reactive protein (CRP) values (1.010/unit, p

Background: Patients with Kawasaki disease (KD) are at a significantly increased risk of allergic diseases. Immunoglobulin E (IgE) is an immunoglobulin that mediates allergic sensitization to various allergens and is related to various allergic diseases. However, few studies have analyzed specific IgE on allergy biomarkers after KD is diagnosed. Objective: This study aimed to investigate the pattern of specific IgE levels against food and inhalant allergens. Methods: This retrospective study was conducted in Taiwan to identify patients admitted with KD. A subset of 453 admitted KD children younger than or equal to five years of age with intravenous immunoglobulin (IVIG) was followed up at our clinic with available specific IgE data. Results: The most common allergens were Dermatophagoides farina or pteronyssinus, house-dust, and cockroach mix. Positive specific IgE for Dermatophagoides farina or pteronyssinus was less common in children diagnosed with KD who were two years old or younger (p = 0.028). KD patients with higher basophils before IVIG (p = 0.010 and 0.018 for two different mites) and higher C-reactive protein (CRP, p = 0.030 and 0.028) after IVIG were at higher risk of mite sensitization. Integrated mite sensitization demonstrated higher basophils before IVIG, age at KD diagnosis, and the male sex to be clinically meaningful after logistic regression models. Conclusions: This study is the first to suggest that specific IgE in KD patients may be correlated with age at KD diagnosis, as well as basophils. Further longitudinal prospective studies are warranted to clarify the unique profile of specific IgE in KD patients.

BackgroundKawasaki disease (KD) is the leading cause of acquired heart disease in children. The major challenge in KD diagnosis is that it shares clinical signs with other childhood febrile control (FC) subjects. We sought to determine if our algorithmic approach applied to a Taiwan cohort.MethodsA single center (Chang Gung Memorial Hospital in Taiwan) cohort of patients suspected with acute KD were prospectively enrolled by local KD specialists for KD analysis. Our previously single-center developed computer-based two-step algorithm was further tested by a five-center validation in US. This first blinded multi-center trial validated our approach, with sufficient sensitivity and positive predictive value, to identify most patients with KD diagnosed at centers across the US. This study involved 418 KDs and 259 FCs from the Chang Gung Memorial Hospital in Taiwan.FindingsOur diagnostic algorithm retained sensitivity (379 of 418; 90.7%), specificity (223 of 259; 86.1%), PPV (379 of 409; 92.7%), and NPV (223 of 247; 90.3%) comparable to previous US 2016 single center and US 2020 fiver center results. Only 4.7% (15 of 418) of KD and 2.3% (6 of 259) of FC patients were identified as indeterminate. The algorithm identified 18 of 50 (36%) KD patients who presented 2 or 3 principal criteria. Of 418 KD patients, 157 were infants younger than one year and 89.2% (140 of 157) were classified correctly. Of the 44 patients with KD who had coronary artery abnormalities, our diagnostic algorithm correctly identified 43 (97.7%) including all patients with dilated coronary artery but one who found to resolve in 8 weeks.InterpretationThis work demonstrates the applicability of our algorithmic approach and diagnostic portability in Taiwan.

Kawasaki disease (KD), a multisystem inflammatory syndrome that occurs in children, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) may share some overlapping mechanisms. The purpose of this study was to analyze the differences in single-cell RNA sequencing between KD and COVID-19. We performed single-cell RNA sequencing in KD patients (within 24 hours before IVIG treatment) and age-matched fever controls. The single-cell RNA sequencing data of COVID-19, influenza, and health controls were downloaded from the Sequence Read Archive (GSE149689/PRJNA629752). In total, 22 single-cell RNA sequencing data with 102,355 nuclei were enrolled in this study. After performing hierarchical and functional clustering analyses, two enriched gene clusters demonstrated similar patterns in severe COVID-19 and KD, heightened neutrophil activation, and decreased MHC class II expression. Furthermore, comparable dysregulation of neutrophilic granulopoiesis representing two pronounced hyperinflammatory states was demonstrated, which play a critical role in the overactivated and defective aging program of granulocytes, in patients with KD as well as those with severe COVID-19. In conclusion, both neutrophil activation and MHC class II reduction play a crucial role and thus may provide potential treatment targets for KD and severe COVID-19.

Hyperbilirubinemia is a common pathological condition in neonates. Free bilirubin can penetrate the blood–brain barrier (BBB), which can lead to bilirubin neurotoxicity. In the context of predicting the risk of bilirubin neurotoxicity, although the specificity and sensitivity of free bilirubin levels are higher than those of total serum bilirubin (TSB), free bilirubin is not widely monitored in clinical practice. The threshold TSB levels at which phototherapy must be administered have been established previously. However, TSB levels are not well correlated with neurodevelopmental outcomes. Currently, TSB levels are commonly used to guide phototherapy for neonatal hyperbilirubinemia. Some clinical drugs can displace bilirubin from its albumin-binding sites, and consequently upregulate plasma bilirubin. Daily dosages play a vital role in regulating bilirubin levels. A drug with both a high protein binding capacity and high daily dosage significantly increases bilirubin levels in infants. Premature or very low birth weight (VLBW) infants are vulnerable to the upregulation of bilirubin levels as they exhibit the lowest reserve albumin levels and consequently the highest bilirubin toxicity index. Because bilirubin is involved in maintaining the balance between pro-oxidant and antioxidant agents, the downregulation of bilirubin levels is not always desirable. This review provides insights into the impact of protein binding capacity and daily dosage of drugs on the bilirubin levels in susceptible infants.

Food sensitization in early life identifies children at risk of developing allergic diseases. We investigated the sensitization to cow milk (CM), egg whites, and wheat. Newborns and infants under 3 years of age with available specific immunoglobulin E (sIgE) data were identified. A retrospective survey was conducted using data from the Chang Gung Research Database. Perinatal characteristics, such as singleton or multiples in a single pregnancy, parity, meconium staining, maternal age, spontaneous delivery or cesarean section, meconium passage, weeks of gestation, birth length, body weight, head and chest circumferences, and season, were obtained. The data on sIgE were collected, and a logistic regression model was used to determine the odds of sensitization. Positive sIgE for CM and egg whites was more likely to occur in boys than in girls. Early-life egg white and wheat sensitization was associated with increased birth body length and weight. A multivariate analysis indicated an association between egg white sIgE positivity and logarithmic total IgE. Higher total IgE levels and younger age were associated with egg white sensitization, and elevated weight and length at birth were linked to food sensitization, particularly to egg whites and wheat.

Background: Attention-deficit/hyperactivity disorder (ADHD) has been linked to pediatric asthma patients treated with montelukast. This study is the first to use a nationwide health insurance research database (NHIRD) to study whether asthmatic children using montelukast are at an increased risk of ADHD. Methods: We used data from the Taiwan NHIRD, which is a longitudinal database of one million randomly selected subjects. The enrolled patients were followed up until 2013. Patients younger than and equal to 12 years old with new-onset asthma (ICD-9 CM code 493.X) diagnosed between 1997 and 2013 were enrolled. A multivariate Cox regression analysis was conducted to evaluate the association between montelukast treatment and the risk of ADHD (ICD-9-CM code 314.X). Results: We enrolled a total of 54,487 asthmatic children younger than and equal to 12 years old who had at least one claim of inpatient admission or at least three claims of an ambulatory visit. Montelukast users and match controls were identified by matching age, gender, residence, the comorbidities including allergic rhinitis and atopic dermatitis, admission or emergency department visits due to asthma attack, and index date of starting montelukast in a 1:1 ratio, with 12,806 in the montelukast group and 12,806 in the non-montelukast group. The montelukast group had a similar risk of ADHD (n = 632, 4.94%) as the non-montelukast group (n = 610, 4.76%) [adjusted hazard ratio 1.04; 95% confidence interval, 0.93 to 1.17]. In children treated with montelukast, high cumulative days of montelukast use did not increase the risk of ADHD. Conclusion: This nationwide population-based cohort study reveals that asthma children treated with montelukast were not at an increased risk of developing ADHD. Nevertheless, validation of our retrospective survey requires further prospective study.

Summary: Background: Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD. Methods: An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100–400 mg), medium (1 g), and high (at least 2 g). Findings: A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=−1.76 days (95% confidence intervals (95% CIs): −3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18–1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00–0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00–1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07–0.62) in refractory-stage KD. Interpretation: The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results. Funding: None.

Background: Infective endocarditis (IE) is an important cause of morbidity and mortality in pediatric patients with heart disease. Little literature has explored differences in the presentation of endocarditis in children with and without heart disease. This study aimed to compare the clinical outcomes and determine the risk of in-hospital death in the study population. Methods: Data were retrospectively collected from 2001 to 2019 from the Chang Gung Research Database (CGRD), which is the largest collection of multi-institutional electronic medical records in Taiwan. Children aged 0–20 years with IE were enrolled. We extracted and analyzed the demographic and clinical features, complications, microbiological information, and outcomes of each patient. Results: Of the 208 patients with IE, 114 had heart disease and 94 did not. Compared to those without heart disease, more streptococcal infections (19.3% vs. 2.1%, p < 0.001) and cardiac complications (29.8% vs. 6.4%, p < 0.001) were observed in patients with heart disease. Although patients with heart disease underwent valve surgery more frequently (43.9% vs. 8.5%, p < 0.001) and had longer hospital stays (28.5 vs. 12.5, p = 0.021), their mortality was lower than that of those without heart disease (3.5% vs. 10.6%, p = 0.041). Thrombocytopenia was independent risk factor for in-hospital mortality in pediatric patients with IE (OR = 6.56, 95% CI: 1.43–40.37). Conclusion: Among pediatric patients diagnosed with IE, microbiological and clinical features differed between those with and without heart disease. Platelet counts can be used as a risk factor for in-hospital mortality in pediatric patients with IE.

(1) Objective: Atopic dermatitis (AD) is a recurring skin disease that affects children’s daily activities and sleep quality. Due to the limitations of children’s understanding and ability to express themselves, shared decision making (SDM) is often made by guardians, which thus affects the acceptance and effectiveness of children’s treatments. Previous studies have demonstrated that involving both children and parents in decision making may help improve treatment outcomes; thus, we designed a multimedia mixed reality (MR) interactive game of SDM for children with moderate to severe AD. (2) Methods: Research participants included 6–18-year-old patients with moderate to severe AD. This research consisted of the following steps: designing SDM; character setting and visual design; performing games; system modification and optimization; screen editing and dubbing; and user testing and questionnaires by the System Usability Scale (SUS). (3) Results: We completed the SDM design for children with moderate to severe AD. Four different treatments were biologics, oral immune-modulating drugs, phototherapy, and wet wrap. An animated PowerPoint slide showed the AD apple rolling around before treatments and the AD apple sleeping soundly after treatments. Instructions with video teaching for the four different treatments were played, and then, the MR was turned on so that the patients could help the AD apple in the metaverse to undergo these four treatments. A total of 12 moderate to severe AD patients and six control patients used the game, all aged between six and eighteen years old, with an average SUS score of 81.0 and a standard error of 2.1 points. Adjective ratings yielded a rating between good and excellent. The game showed acceptable usability. We found no statistically significant differences in SUS scores between patients with and without moderate to severe AD or between boys and girls nor significant associations between SUS and age or severity. The analysis identified that the two items with the lowest SUS scores were “I think that I would need the support of a technical person to be able to use this product” and “I needed to learn a lot of things before I could get going with this product”. Both of these comments show the limitations of this game. (4) Conclusions: Overall, this study provides the first MR SDM game that has passed the SUS and can be used as an aid in clinical SDM.

Kawasaki disease (KD) is an autoimmune-like vasculitis of childhood involving the coronary arteries. Macrophages require scavenger receptors such as CD36 to effectively clear cellular debris and induce self-tolerance. In this study, we hypothesized that CD36 plays an important role in the immunopathogenesis of KD, by aiding in the clearance of plasma mitochondrial DNA, and by amplifying the immune response by activating the inflammasome pathway via AIM2. Fifty-two healthy controls, 52 febrile controls, and 102 KD patients were recruited for RT-PCR of target mRNA expression and plasma mitochondrial DNA. Blood samples were obtained 24 hours prior and 21 days after the administration of intravenous immunoglobulin (IVIG) therapy. Patients with acute KD had higher plasma levels of cell-free mitochondrial DNA (ND1, ND4, and COX1), and higher mRNA expressions of CD36 and AIM2 when compared to both healthy and febrile controls. A greater decrease in both CD36 and AIM2 mRNA expression after IVIG therapy was associated with the development of coronary artery lesions. Coronary artery lesions were associated with a larger decrease of CD36 expression following IVIG therapy, which may indicate that prolonged expression of the scavenger receptor may have a protective effect against the development of coronary artery lesions in KD.

Abstract Background Kawasaki disease (KD) causes coronary artery lesions (CAL) and is the leading cause of acquired heart disease in children. The aim of this study is to evaluate the risk factors and set-up a scoring system for predicting CAL of KD. Methods We retrospectively reviewed a total of 478 patients diagnosed with KD. We compared age, gender, laboratory data, and treatment response in two groups and developed a scoring system for predicting CAL. Results During the study period, 365 of these patients had complete medical records of coronary surveys by echocardiography. Anemia, hypoalbuminemia, C reactive protein (CRP), alanine aminotransferase, neutrophil count, and neutrophil/lymphocyte ratio (NLR) showed significant differences with CAL formation. We determined the cut-off value using a receiver-operating-characteristic (ROC) curve, and following multivariate logistic regression analysis, four independent risk factors demonstrated a significant difference with CAL formation, including CRP > 103 mg/L, NLR > 3.5, male gender, and intravenous immunoglobulin (IVIG) resistance. We established a score system based on the above evaluation, for which a ROC curve was performed, and a total score of ≥ 2 points showed a sensitivity of 60.8% and a specificity of 70.6%, with an area under the ROC curve of 0.696. Conclusions Identifying children at risk is important in order to prevent CAL from developing. Four independent risk factors that can predict CAL formation were CRP > 103 mg/L, NLR > 3.5, male gender, and IVIG resistance. This first report incorporated NLR into score systems to predict CAL reinforces previously well-known risk factors for the CAL formation among KD patients.

Abstract Background Although the sternoclavicular joint (SCJ) may be involved in ankylosing spondylitis, rheumatic arthritis, and Behçet’s disease and participates in the systemic inflammatory process of arthritis, it is often neglected during routine rheumatologic clinical examinations. To the best of our knowledge, this is the first study to report etanercept treatment in juvenile idiopathic arthritis (JIA) with SCJ involvement. Case presentation In this study, we describe an unusual case of a child with juvenile idiopathic arthritis with an initial presentation of sternoclavicular mass. The patient (age, 14 years 10 months) presented with an insidious onset atraumatic swelling of the left SCJ and complained of right hip and bilateral ankle tenderness without an apparent cause. Initial ultrasonography indicated a heterogeneous mass in the left SCJ, while computed tomography identified mild swelling of the left SCJ with a thickened synovial lining, mild bone erosion, and some turbid fluid. The patient ultimately underwent left SCJ arthrotomy, during which tapping of the SCJ revealed 2 cc of yellowish fluid, inflammation and necrosis of tissues within the SCJ. A clear yellow joint fluid was aspirated, and testing revealed a negative culture result. The patient was diagnosed with JIA. The joint tenderness improved and erythrocyte sedimentation rate decreased after administering anti-tumor necrosis factor etanercept. An additional ultrasonography demonstrated that the initial imaging findings have been resolved. At the end of a 2-year follow-up period, the patient was completely symptom-free. Conclusions JIA with SCJ involvement is an uncommon presentation in adolescents. Etanercept may be a beneficial treatment for SCJ involvement in patients with JIA. The upper limbs showed no signs of limited range of motion during the follow-up period. Further studies are warranted to elucidate the efficacy of etanercept in JIA with sternoclavicular joint involvement.

Background: Allergic diseases are frequently observed in children with Kawasaki disease (KD). However, the evidence supporting the association between KD and allergies has been conflicting. The objective of the current study is to examine the association between KD and allergic diseases.Methods: We conducted an electronic search using PubMed, Embase, and the Cochrane through 24 July 2021. The inclusion criteria consisted of studies that examined the prevalence of allergic diseases in children with a previous diagnosis of KD and in a comparison group. We pooled studies by using a random effects model. The effects of KD on the subsequent risk of allergic diseases were expressed as odds ratio (OR) with 95% confidence intervals (CI).Results: We included a total of four studies that assessed the effect of KD on asthma, allergic rhinitis, and atopic dermatitis vs. non-KD children (KD individuals for asthma, four studies, n = 8,474; allergic rhinitis, four studies, n = 8,474; atopic dermatitis, three studies, n = 8,330). The overall prevalence of asthma, allergic rhinitis, and atopic dermatitis was 9.12, 27.63, and 6.55% among patients with previous KD. The meta-analysis showed a significantly increased risk of asthma (OR:1.437, CI: 1.067–1.937) and allergic rhinitis (OR: 1.726, CI: 1.291–2.307) in patients with KD, compared with the control groups. However, patients with KD did not have a significantly different level of risk of atopic dermatitis (OR: 1.243, 95% CI: 0.857–1.802).Conclusion: This meta-analysis supports that individuals with KD are more likely to have asthma and allergic rhinitis compared to controls.

Aspirin was once believed to reduce the mortality of Kawasaki disease (KD) due to its effect on the thrombotic occlusion of coronary arteries. However, conflicting evidence has been found regarding aspirin treatment and its benefit in patients with acute KD. We compared the efficacy of different aspirin doses in acute KD. A literature search of PubMed, EMBASE, and Cochrane databases was conducted to identify studies comparing different doses of aspirin for acute KD. The primary outcome of interest was coronary artery lesions (CAL). We used random-effects network meta-analysis. Six retrospective studies, including 1944 patients receiving aspirin in doses of 0, 3–5, 30–50, or 80–100 mg/kg/day, were selected. The risks of CAL were not significantly different for the various doses of aspirin compared to the placebo: odds ratio (OR) was 1.10 [95% confidence interval (CI): 0.70–1.71] for patients with aspirin 3–5 mg/kg/day; OR = 1.23 (95% CI: 0.67–2.26) for aspirin 30–50 mg/kg/day, and OR = 1.59 (95% CI: 0.74, 3.421) for 80–100 mg/kg/day. The P-score ranged from 0.76 for placebo to 0.19 for aspirin 80–100 mg/kg/day. The different doses of aspirin exhibited no significant difference with regard to the efficacy of CAL or with the secondary outcomes of intravenous immunoglobulin resistance or hospital stays for acute KD. Therefore, we found that treatment without any aspirin is not inferior to other doses of aspirin and can also slightly reduce the risk of CAL.

Purpose: Eosinophils may rise to a higher level in the acute phase of Kawasaki disease (KD) both before and after intravenous immunoglobulin (IVIG) therapy. A substantial body of research was carried out on the association between KD and allergic diseases. Eosinophils play an important role in type 2 inflammation. Recent studies have shown that there are two distinct subtypes of eosinophils. In addition to their role in inflammation, lung-resident eosinophils (rEOS) also regulate homeostasis. Inflammatory eosinophils (iEOS) reflect type 2 inflammation in tissues. iEOS were considered the primary eosinophils in non-severe allergic asthma, while rEOS were thought to be the primary eosinophils in severe non-allergic eosinophilic asthma. This case–control study aimed to investigate the marker expression of eosinophilic subtypes in KD patients. Materials and Methods: The marker expressions of eosinophilic subtypes in the leukocytes of patients with KD were evaluated by the recently established KDmarkers online tool, a web server including gene expression data. Finally, the results were validated with a quantitative reverse transcriptase polymerase chain reaction (RT-PCR). We analyzed the mRNA expression levels of SELL and IL10RA in leukocytes from KD patients and febrile children. Results: Included in our screening tools were transcriptome arrays, which provided clues showing the importance of rEOS, whose role was identified by three genes (lower IL10RA, higher SELL, and SERPINB1 than controls). In contrast, the iEOS representative gene CD101 was not elevated in KD. It was found that the gene IL10RA, a marker of inflammatory eosinophilic leukocytes, was more highly expressed in the leukocytes of KD patients (n = 43) than febrile controls (n = 32), especially those without coronary artery lesions (CAL) (n = 26). Before treatment, SELL expression was higher in leukocytes of CAL patients (CAL, 1.33 ± 0.18, n = 39; non-CAL, 0.87 ± 0.12, n = 55; p = 0.012). SELL was significantly higher after half a year compared to febrile controls. Conclusions: To our knowledge, this is the first study to demonstrate that KD patients have increased SELL than febrile controls after 6 months of treatment. We present evidence here that dynamically different eosinophilic involvement exists between KD patients with and without CAL. The role of eosinophilic subtypes in KD patients warrants further investigation.

Backgrounds: Drugs with the ability to displace bilirubin from albumin-binding sites subsequently leading to an increased bilirubin level may cause hyperbilirubinemia in neonates. Ibuprofen is commonly used to treat patent ductus arteriosus (PDA) in neonates, yet the use of ibuprofen has drawn mixed conclusions. We performed a retrospective study to determine how ibuprofen use influences the total serum bilirubin (TSB) level in neonates of differing birth weight (BW). Materials and methods: Neonates (including premature infants) born at Chang Gung Memorial Hospital, Taiwan during January 2004 to July 2020 were entered into this study. We recorded the phototherapy duration, including the initial day and end day, and determined the average influence of one-day phototherapy on TSB level. The highest monitored TSB level post-ibuprofen use minus the one measured prior to ibuprofen use was considered the TSB change following ibuprofen administration in this study, and the above-mentioned influence of daily phototherapy on the TSB level was used to correlate the results. Neonates with any of the following conditions were excluded: those who received ceftriaxone, those with intraventricular hemorrhage, and those infected with TORCH. Results: The average daily influence of phototherapy on the TSB level of neonates was −0.20 (−0.57~0.05) mg/dL, −0.28 (−0.84~0.13) mg/dL, −0.75 (−1.77~0.10) mg/dL, and −1.60 (−2.70~−0.50) mg/dL in neonates with BWs of p = 0.026, one-way analysis of variance (ANOVA)). Conclusions: As ibuprofen use is correlated with an apparent increase in TSB level in neonates with a lower BW, especially in those with a BW < 1 kg, iv acetaminophen can be an appropriate alternative to ibuprofen for ELBW neonates for the treatment of PDA if they are experiencing severe unconjugated hyperbilirubinemia.

Objective Kawasaki disease (KD) is an acute form of febrile vasculitis that occurs in early childhood. The multisystemic vasculitis common in patients with KD may influence blood perfusion in the brain, and thus caregivers of children with KD may feel stress with regard to caring for them. Intravenous immunoglobulin (IVIG) infusion is the standard treatment for acute KD, and the most serious complication of KD is coronary artery aneurysms (coronary artery lesion (CAL)). This study aimed to investigate the relationships between KD heterogeneity and the risk of patients’ cognitive impairment or caregivers’ parenting stress.Design A case–control study with consecutive sampling.Setting A medical centre (Kaohsiung Chang Gung Memorial Hospital, Taiwan).Participants This study consisted of 176 patients with KD (mean age: 5.5 years, 60.8% boys) and 85 healthy children (mean age: 6.4 years, 54.1% boys).Primary and secondary outcome measures Based on the children’s age, each patient with KD and control subject was administered an assessment using the Mullen Scales of Early Learning or the Wechsler Intelligence Scale, and parenting function of their caregivers was assessed using the Parenting Stress Index (PSI)-Short Form.Results We observed no significant differences in any developmental index, cognitive function or parenting stress between patients with KD and controls. Among the children with KD, IVIG administration nor CAL was associated with children’s cognitive scores. However, the caregivers of patients who had CAL suffered from greater PSI total scores than those of patients without CAL. Furthermore, the caregivers who had education levels of a master’s degree or above showed less parenting stress than those who had an education level of college or lower.Conclusion Caregivers’ education is associated to parenting stress, and caregivers of patients with KD who developed CAL may feel stress about the unpredictable sequela caused by CAL for their children. Such caregivers may require support to fulfil their parenting roles.

Abstract Background The etiology of Kawasaki disease (KD) is still unknown; perinatal factors may have role with few studies. This study was aim to survey the perinatal factors and clinical outcome of KD, including coronary artery lesion (CAL) formation and intravenous immunoglobulin (IVIG) treatment response. Methods We enrolled a total of 185 KD patient–caregiver dyads in this study using questionnaires. The questionnaire included two categories: children’s characteristics, which consisted of age at disease onset, gender, gestational age at delivery, birth body weight, delivery methods, and breastfeeding status, and caregivers’ characteristics, which consisted of parents or not, education levels, maternal age at giving birth, total number of offspring, and family income. We analyzed the association of these factors with CAL formation and IVIG treatment response of KD. Results KD patients with CAL formation had a higher maternal age than non-CAL patients (32.49 ± 3.42 vs. 31.01 ± 3.92 years, p = 0.016). We also found that maternal age ≥ 32 years group had a higher rate of having KD patients with CAL (39/81 vs. 24/74, odds ratio 1.935, 95% confidence interval [1.007, 3.718], p = 0.047). The maternal age ≥ 35 years group had a higher rate of having KD patients with IVIG resistance (6/31 vs. 6/116, odds ratio 4.400, 95% confidence interval [1.309, 14.786], p = 0.01). There was no significant difference in either CAL formation or IVIG resistance in KD with regard to patient’s age at disease onset, gestational age, birth body weight, delivery methods, breastfeeding, caregiver type, caregivers’ education level, total number of offspring, or family income (p > 0.05). Conclusions This study is the first to report that maternal age is significantly associated with CAL formation and IVIG resistance in KD. We hypothesize that a maternal age less than 32 years would benefit KD offspring.

Kawasaki disease (KD) is a febrile coronary vasculitis that affects younger children and includes complications such as coronary artery aneurysm. KD diagnoses are diagnosed based on clinical presentations, a process that still poses a challenge for front-line physicians. In the current study, we developed a novel predictor using the hemoglobin-for-age z-score (HbZ) and plasma hepcidin to differentiate Kawasaki disease (KD) from febrile children (FC). There were 104 FC and 115 KD subjects (89 typical KD; 26 incomplete KD) for this study, and data were collected on the biological parameters of hemoglobin and plasma hepcidin levels. A receiver operating characteristic curve (auROC), multiple logistics regression, and support vector machine analysis were all adopted to develop our prediction condition. We obtained both predictors, HbZ and plasma hepcidin, for distinguishing KD and FC. The auROC of the multivariate logistic regression of both parameters for FC and KD was 0.959 (95% confidence interval = 0.937–0.981), and the sensitivity and specificity were 85.2% and 95.9%, respectively. Furthermore, the auROC for FC and incomplete KD was 0.981, and the sensitivity and specificity were 92.3% and 95.2%, respectively. We further developed a model of support vector machine (SVM) classification with 83.3% sensitivity and 88.0% specificity in the training set, and the blind cohort performed well (78.4% sensitivity and 100% specificity). All data showed that sensitivity and specificity were 81.7% and 91.3%, respectively, by SVM. Overall, our findings demonstrate a novel predictor using a combination of HbZ and plasma hepcidin with a better discriminatory ability for differentiating from WBC and CRP between children with KD and other FC. Using this predictor can assist front-line physicians to recognize and then provide early treatment for KD.

Background: The atopy rate in children has increased significantly. Atopy and growth are connected in a multifactorial manner and are important health issues for children around the world. The principal research question in this cross-sectional investigation concerned the association between serum total, specific immunoglobulin E (IgE) levels, and body height (BH)/weight (BW)/body mass index (BMI). Methods: A total of 993 subjects were enrolled for analysis retrospectively with allergic diseases and aged from 6 months to 18 years during the years 2015–2016. A complete panel of 36 allergen-specific IgE was taken from each participant using the MAST allergen test as well as their BH, BW, BMI, and total IgE levels. Results: There was a statistically significant positive association between the total IgE levels with BH (N = 348) and BW (N = 623) in the preschool age group (p-values of 0.009 and 0.034, respectively). In the preschool group, the total IgE levels showed a positive association with house dust (p < 0.001), cockroach mix (p < 0.001), Dermatophagoides farina (p < 0.001), and Dermatophagoides pteronyssinus (p < 0.001). After performing a general linear model followed by a backward selection of variables with age, sex, specific IgE, and total IgE, egg white sensitization demonstrated a significant negative association with BH (p = 0.009), and Dermatophagoides farina sensitization showed a significant positive association with BH (p = 0.006). The analysis showed that, in this model, the level of total IgE was not associated with BH. Conclusions: The results of this study indicate that the level of total IgE was not associated with BH in the preschool age group. Future studies are needed to replicate the results in outcome with follow-up allergic cohorts.

(1) Background: Kawasaki disease (KD) mainly affects children under the age of 5 years and eosinophilia in KD patients might be associated with the development of allergic diseases. We compared the age-adjusted Z-score (Z) of eosinophils and aimed to evaluate the impact of onset age on eosinophils in KD patients. (2) Methods: We divided 398 KD patients into seven age subgroups. Laboratory data and the age-adjusted Z-score of eosinophils during the phases of Kawasaki disease were analyzed. (3) Results: The absolute eosinophil count among all age groups showed significant differences in the post-intravenous immunoglobulin (IVIG) phase and throughout the course of KD with Z-score adjusted for age. Further analysis showed persistent elevation of the age-adjusted Z-score of eosinophils (Z-eosinophil) especially in the under six-month-old age subgroup. In addition, we divided the Z-eosinophil into two groups to find the relationship with coronary artery lesions (CALs). Patients with a higher eosinophil count than average age values had a higher risk of developing CALs, while those with a lower eosinophil count than average age values had a lower risk of having CALs. (4) Conclusions: These findings may provide information to clinicians to pay attention to allergic diseases during the follow-up of KD, especially for children who are younger than 6 months old at the onset of KD, and eosinophil count could be a crucial focus in KD.

Background: Kawasaki disease (KD) is an inflammatory disorder with an unknown etiology. It is the leading cause of acquired heart disease, which leads to coronary vasculitis among children. Studies of frequent manifestation of allergic diseases in children with KD have been the subject of mounting clinical interest. However, evidence supporting the association between KD and allergies has yet to be systematically reviewed.Methods: In this article, we reviewed current literature regarding the association between KD and allergic diseases. References for this review were identified through searches of PubMed, Cochrane, and Embase through the end of August 2020.Results: The results of the analyses of immune repertoire, clinical, and epidemiological studies have indicated some of the characteristics of infectious disease for KD. Although some allergic disorders, such as asthma, may be exacerbated by viral infections, allergies are typically caused by an allergen that triggers an immune response, with the potential involvement of type 2 inflammation and immune disturbances leading to tissue remodeling in genetically susceptible hosts. The effect of intravenous immunoglobulin is multi-faceted and results in a decrease in activating Fc gamma receptor IIA and an increase in anti-inflammatory eosinophils. The findings from this review demonstrate that children who have suffered from KD are more likely to have allergic rhinitis than the general population and their siblings, a condition that lasts until the age of 17. When followed up as teenagers and adults, children with KD are more likely to develop urticaria.Conclusions: This review supports that allergic diseases, such as allergic rhinitis, have been demonstrated to increase following KD. Therefore, the importance of allergic diseases in patients with KD should be emphasized in long-term care. Interventions that include strategies for managing allergies in children with KD would be beneficial.

Fruit is a kind of plant food which is rich in nutrients and immune-regulating ingredients. A meta-analysis has demonstrated that fruits have a protective effects against asthma. On the other hand, clinical syndromes of allergic reactions to fruits manifest as an oral allergy syndrome. We aimed to investigate the patterns and associated factors of fruit allergen-specific IgE (sIgE) sensitization among patients with suspected clinical symptoms. Data were extracted from the Chang Gung Research Database. Fruit sensitization in Taiwan was evaluated using the presence of IgE antibodies against specific fruits. The overall prevalence of positive sIgE responses to fruit allergens in Taiwan, in order of decreasing importance, was pineapple, kiwi, banana, and papaya. Children aged 0–18 had a higher positive rate of allergic responses to pineapple, kiwi, banana, and papaya than adults over the age of 18. Positive specific IgE for kiwi, banana, or papaya was more frequent in younger than in older children and children with a higher total IgE of both logarithmic (log) and arithmetic values. The analysis of log IgE for pineapple positive vs. negative children determined an optimal cutoff value, log IgE 2.2, with both sensitivity (0.9) and specificity (0.5). Dermatitis was significantly more prevalent in children with positive IgE for pineapple, kiwi, banana, and papaya than negative specific IgE. The highest positive rate of sIgE against fruits was pineapple among children. Even in older children, the positive rate of pineapple allergens was high. IgE discriminates with and without sIgE for pineapple, with an optimal cutoff of 158.5 U/mL.

Kawasaki disease (KD) is a febrile childhood vasculitis that involves the coronary arteries. Most previous studies have focused on the genes activated in the acute phase of KD. However, in this study, we focused on suppressed genes in the acute stage of KD and identified novel targets with clinical significance and potential prognostic value for KD patients. We enrolled 18 patients with KD, 18 healthy controls (HC), and 18 febrile controls (FC) for human transcriptome array analysis. Another 19 healthy controls, 20 febrile controls, and 31 patients with KD were recruited for RT-PCR validation of target mRNA expressions. The results of Human Transcriptome Array (HTA) 2.0 showed 461 genes that were significantly higher in KD and then normalized after IVIG, as well as 99 suppressed genes in KD. Furthermore, we identified the four genes in KD with the most downregulation, including BCL11B, DUSP2, DDX24, and CDR2, as well as the upregulation of their expression following IVIG administration. The mRNA expression of CDR2 by qRT-PCR was the most compatible with the pattern of the HTA2.0 results. Furthermore, we found higher DDX24 mRNA expression in KD patients with CAL when compared to those without CAL 3 weeks after IVIG administration. In summary, activated gene expression represented a majority in the immune response of KD. In this study, we identified CDR2 as a novel suppressed gene for Kawasaki disease via human transcriptome array analysis and DDX24 associated with CAL formation, which may contribute to further understanding of CAL pathogenesis in KD.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed or diagnosis delayed when initial clinical symptoms do not fulfill the traditional criteria or a normal echocardiography was found. In this study, we aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD.Method: We retrospectively enrolled in this study a total of 50 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data (initial data in the first visit).Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A higher neutrophil-to-lymphocyte ratio (NLR, p = 0.037) and higher C-reactive protein levels (CRP, p = 0.02) were found in group 1 when compared to group 2. A patient with a NLR >1.33 combined with a CRP more than 33 mg/L was more likely to have KD (Sensitivity 90%, specificity 69.2%, p = 0.001; Odds ratio 20.25, 95% confident interval 2.3–178.25).Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

Kawasaki disease (KD) is a common systemic vasculitides in children younger than 5 years of age. Activated macrophages are key drivers of vascular inflammation in KD. The aim of this study was to examine differences in M1 and M2 macrophage marker expression in patients with KD. Blood samples were obtained from 18 healthy controls and 18 patients with KD at 24 h prior and 21 days after to intravenous immunoglobulin therapy. GeneChip Human Transcriptome Array 2.0 and Illumina HumanMethylation450 BeadChip were used to examined the mRNA expression and corresponding CpG site methylation ratios of 10 M1 surface markers and 15 M2 surface markers. Of the markers examined 2 M1 markers (TLR2, IL2RA) and 8 M2 markers (ARG1, CCR2, TLR1, TLR8, TLR5, MS4A6A, CD36, and MS4A4A) showed increased mRNA expression in the acute phase of KD which decreased after IVIG therapy (P < 0.05). Corresponding CpG sites in the promoter regions these markers were hypomethylated in the acute phase of KD and significantly increased after IVIG therapy. In conclusion, both M1 and M2 markers showed increased mRNA expression in the acute phase of KD. CpG site methylation may be one of the mechanisms governing macrophage polarization in KD.

The Fc gamma receptor family contains several activating receptors and the only inhibitory receptor, FcγR2B. In this study, we investigated the dynamic methylation change of FcγR2B in different stages of Kawasaki disease (KD). We enrolled a total of 116 participants, which included patients with febrile diseases as controls and KD patients. Whole blood cells of KD patients were collected prior to intravenous immunoglobulin (IVIG) treatment (KD1), three to seven days after IVIG (KD2), three weeks after IVIG treatment (KD3), six months after IVIG (KD4), and one year after IVIG treatment (KD5). In total, 76 KD patients provided samples in every stage. Leukocytes of controls were also recruited. We performed DNA extraction and pyrosequencing. FcγR2B methylation levels were higher in KD3 compared to both the controls and KD1. A significantly higher methylation of FcγR2B was found in KD5 when compared with KD1. FcγR2B methylation levels in the IVIG-resistant group were lower than those in the IVIG-responsive group at KD1-3 (p = 0.004, 0.004, 0.005 respectively). This study is the first to report the dynamic change of FcγR2B methylation and to demonstrate long-term hypermethylation one year after disease onset. Hypomethylation of FcγR2B is associated with IVIG resistance.

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.

A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

In this study, we investigated the risk factors for in-hospital mortality of children beyond infancy with and without underlying diseases. Methods: We performed a retrospective review of all deceased patients aged 1–18 years at Chang-Gung Memorial Hospital-Kaohsiung from 2000 to 2009. The patients were divided into two groups; those with and without underlying diseases. Demographic data, clinical characteristics, and initial laboratory data were analyzed to correlate the risk factors for mortality of pediatric patients with and without underlying diseases. Results: A total of 131 deceased children were found from 2000 to 2009. Forty children were previously healthy (without underlying diseases), whereas 91 had previous underlying diseases. Children with cardiovascular or central nervous system (CNS) infections had a significantly greater risk of mortality than did those without underlying diseases (p=0.004 and p=0.0004, respectively). More cardiovascular and fewer hematologic abnormalities at admission were found in patients without underlying diseases. In multiple logistic regression, it was found that cardiovascular (p=0.006) or CNS infections (p=0.012), consciousness change at admission (p=0.013), and higher liver enzyme levels were most significantly associated with deceased children without underlying diseases. Conclusion: Results from this study suggest that mortality in pediatric patients without underlying diseases is most frequently found in younger children with CNS and cardiovascular infections, consciousness change, and high liver enzyme levels at admission. Results from this analysis will provide information for the awareness of fatal outcomes in previously healthy children.

Pandemic (H1N1) 2009 virus causes severe illness, including pneumonia, which leads to hospitalization and even death. To characterize the kinetic changes in viral load and identify factors of influence, we analyzed variables that could potentially influence the viral shedding time in a hospital-based cohort of 1,052 patients. Viral load was inversely correlated with number of days after the onset of fever and was maintained at a high level over the first 3 days. Patients with pneumonia had higher viral loads than those with bronchitis or upper respiratory tract infection. Median viral shedding time after the onset of symptoms was 9 days. Patients 13 years of age (11 days vs. 7 days). These results suggest that younger children may require a longer isolation period and that patients with pneumonia may require treatment that is more aggressive than standard therapy for pandemic (H1N1) 2009 virus.

BACKGROUND: Concerns have been raised about how the transmission of emerging infectious diseases from patients to healthcare workers (HCWs) and vice versa could be recognized and prevented in a timely manner. An effective strategy to block transmission of pandemic H1N1 (2009) influenza in HCWs is important. METHODOLOGY/PRINCIPAL FINDINGS: An infection control program was implemented to survey and prevent nosocomial outbreaks of H1N1 (2009) influenza at a 2,600-bed, tertiary-care academic hospital. In total, 4,963 employees at Kaohsiung Chang Gung Memorial Hospital recorded their temperature and received online education on control practices for influenza infections. Administration records provided vaccination records and occupational characteristics of all HCWs. Early recognition of a pandemic H1N1 (2009) influenza case was followed by a semi-structured questionnaire to analyze possible routes of patient contact, household contact, or unspecified contact. Surveillance spanned August 1, 2009 to January 31, 2010; 51 HCWs were confirmed to have novel H1N1 (2009) influenza by quantitative real-time reverse transcription polymerase chain reaction. Prevalence of patient contact, household contact, or unspecified contact infection was 13.7% (7/51), 13.7% (7/51), and 72.5% (37/51), respectively. The prevalence of the novel H1N1 infection was significantly lower among vaccinated HCWs than among unvaccinated HCWs (p