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Objectives: The purpose of this study was to evaluate the influence of pulmonary regurgitation inequality on differential perfusion of the lungs in tetralogy of Fallot (TOF) after repair. Background: Asymmetry of lung perfusion is one of the best predictors of outcome in TOF after repair. A recent phase-contrast magnetic resonance imaging (PC-MRI) study found prominent regurgitation inequality between the bilateral pulmonary arteries in TOF after repair. Methods: Forty-three TOF post-repair patients (median age = 51 months, 31 men) received PC-MRI and 99mTc-labeled macroaggregates of albumin perfusion scintigraphy (PS) in the same day. We took PC-MRI measurements of forward flow volume (FFV), backward flow volume (BFV), and net flow volume (NFV) (NFV = FFV - BFV) and regurgitation fraction (RF) (RF = BFV/FFV) at the left and right pulmonary arteries (LPA and RPA). The differential perfusion of the left lung (L%) (L% = left lung/left + right lung) as calculated by NFV ratio, by FFV ratio of PC-MRI, and by PS were compared. Results: The discrepancy between L% by NFV versus L% by PS was affected by the severity of RF of LPA (r = -0.51, p = 0.001); agreement between L% by NFV versus L% by PS was good (intraclass correlation coefficient [Ri] = 0.87) if RF of LPA <0.4 (n = 23) but downgraded (Ri = 0.51) and underestimated the L% (median of error = -14%, range = -25.3% to 5.5%) if RF of LPA > or =0.4 (n = 20). In contrast, agreement between L% by FFV versus L% by PS was high and unaffected by RF of LPA (Ri = 0.94, 0.92, respectively). Conclusions: While integrating PC-MRI of pulmonary artery as a comprehensive MRI evaluation of TOF after repair, conventional NFV ratio method tended to underestimate the left lung perfusion and may lead to unnecessary intervention. The FFV ratio method should be used for precise assessment of differential lung perfusion. [ABSTRACT FROM AUTHOR]

Background: Congenital heart diseases (CHDs), particularly atrial and ventricular septal defects, pose significant health risks and common challenges in detection via echocardiography. Doctors often employ the cardiac structural information during the diagnostic process. However, prior CHD research has not determined the influence of including cardiac structural information during the labeling process and the application of data augmentation techniques., Methods: This study utilizes advanced artificial intelligence (AI)-driven object detection frameworks, specifically You Look Only Once (YOLO)v5, YOLOv7, and YOLOv9, to assess the impact of including cardiac structural information and data augmentation techniques on the identification of septal defects in echocardiographic images., Results: The experimental results reveal that different labeling strategies substantially affect the performance of the detection models. Notably, adjustments in bounding box dimensions and the inclusion of cardiac structural details in the annotations are key factors influencing the accuracy of the model. The application of deep learning techniques in echocardiography enhances the precision of detecting septal heart defects., Conclusions: This study confirms that careful annotation of imaging data is crucial for optimizing the performance of object detection algorithms in medical imaging. These findings suggest potential pathways for refining AI applications in diagnostic cardiology studies., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) affects patients after recovering from acute coronavirus disease 2019 (COVID-19). This study investigates the impact of SARS-CoV-2 vaccination on PASC symptoms in children in Taiwan during the Omicron pandemic., Methods: We enrolled children under 18 years with PASC symptoms persisting for more than 4 weeks. Data collected included demographics, clinical information, vaccination status, and symptom persistence. We used logistic regression models to compare symptoms in the acute and post-COVID-19 phases and to assess the association between vaccination and these symptoms., Results: Among 500 PASC children, 292 (58.4%) were vaccinated, 282 (52.8%) were male, and the mean (SD) age was 7.6 (4.6) years. Vaccinated individuals exhibited higher odds of experiencing symptoms in the previous acute phase, such as cough (adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI]: 1.02-2.42), rhinorrhea/nasal congestion (AOR = 1.74; 95% CI: 1.13-2.67), sneezing (AOR = 1.68; 95% CI: 1.02-2.76), sputum production (AOR = 1.91; 95% CI: 1.15-3.19), headache/dizziness (AOR = 1.73; 95% CI: 1.04-2.87), and muscle soreness (AOR = 2.33; 95% CI: 1.13-4.80). In contrast, there were lower odds of experiencing abdominal pain (AOR = 0.49; 95% CI: 0.25-0.94) and diarrhea (AOR = 0.37; 95% CI: 0.17-0.78) in children who had received vaccination during the post-COVID-19 phase., Conclusions: This study revealed clinical features and vaccination effects in PASC children in Taiwan. Vaccination may reduce some gastrointestinal symptoms in the post-COVID-19 phase.

Multisystem inflammatory syndrome in children (MIS-C) is an imperative pediatric inflammatory condition closely linked to COVID-19, which garners substantial attention since the onset of the pandemic. Like Kawasaki illness, this condition is characterized by an overactive immune response, leading to symptoms including pyrexia, cardiac and renal complications. To elucidate the pathogenesis of MIS-C and identify potential biomarkers, we conducted an extensive examination of specific cytokines (IL-6, IL-1β, IL-6R, IL-10, and TNF-α) and microRNA (miRNA) expression profiles at various intervals (ranging from 3 to 20 days) in the peripheral blood sample of a severely affected MIS-C patient. Our investigation revealed a gradual decline in circulating levels of IL-6, IL-1β, IL-10, and TNF-α following intravenous immune globulin (IVIG) therapy. Notably, IL-6 exhibited a significant reduction from 74.30 to 1.49 pg./mL, while IL-6R levels remained consistently stable throughout the disease course. Furthermore, we observed an inverse correlation between the expression of hsa-miR-596 and hsa-miR-224-5p and the aforementioned cytokines. Our findings underscore a robust association between blood cytokine and miRNA concentrations and the severity of MIS-C. These insights enhance our understanding of the genetic regulatory mechanisms implicated in MIS-C pathogenesis, offering potential avenues for early biomarker detection and therapy monitoring through miRNA analysis., Competing Interests: J-JH and M-HC were employed by the Inti Taiwan, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tsai, Hong, Cheng, Cheng, Chen, Hsieh, Hsieh and Shen.)

Objective: This study aims to understand the differences in intestinal flora, expression of helper T cells, allergy-related indicators, and cytokine levels between children with bronchial asthma and healthy children. The study seeks to clarify the effectiveness and safety of probiotic preparations in the treatment of bronchial asthma in children, and to provide new methods for the treatment of bronchial asthma., Methods: A total of 66 pediatric patients aged 3-6 years with bronchial asthma and 35 healthy children undergoing physical examination during the same period were enrolled, designated as the asthma group and the healthy group, respectively. The asthma group was further divided into the probiotic group and the non-probiotic group based on whether probiotics were used. The gut microbiota, serum IgE antibody levels, cytokines (IL-4, IL-5, IL-9, IL-13 levels), proportions of helper T cells (Th1, Th2), and hypersensitive C-reactive protein were measured and compared among the groups., Results: Children with bronchial asthma had decreased abundance and reduced diversity of intestinal flora compared to the healthy group. At the genus level, the asthma group showed increased abundance of Bacteroides and decreased abundance of Faecalibacterium and Veillonella; The probiotic group demonstrated a significantly higher improvement in the abundance of these genera before and after treatment compared to the non-probiotic group (P < 0.05). Compared to the healthy group, children with asthma had elevated levels of serum IgE, IL-4, IL-5, IL-9, and IL-13, as well as a decreased Th1/Th2 ratio, all of which showed statistical differences (P < 0.05). After treatment, all immune indicators improved. Specifically, the probiotic group exhibited a more significant decrease in serum IgE, IL-4, and IL-13 levels compared to the non-probiotic group (P < 0.05)., Conclusion: Children with bronchial asthma exhibit dysbiosis of intestinal flora, characterized by an increased abundance of the Bacteroides and decreased abundance of the Faecalibacterium and Veillonella. This imbalance in intestinal flora increases the risk of allergic diseases. Probiotics can effectively improve dysbiosis of intestinal flora, contributing to the balance of immune function in children, and can be used as an adjunct therapy for the treatment of bronchial asthma., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bihong Feng reports financial support was provided by Zhejiang Provincial Health Commission of China (2021KY1040). Other authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Children have been reported to be less affected and to have milder severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults during the coronavirus disease 2019 (COVID-19) pandemic. However, children, and particularly those with underlying disorders, are still likely to develop critical illnesses. In the case of SARS-CoV-2 infection, most previous studies have focused on adult patients. To aid in the knowledge of in-hospital care of children with COVID-19, this study presents an expert review of the literature, including the management of respiratory distress or failure, extracorporeal membrane oxygenation (ECMO), multisystem inflammatory syndrome in children (MIS-C), hemodynamic and other organ support, pharmaceutical therapies (anti-viral drugs, anti-inflammatory or antithrombotic therapies) and management of cardiopulmonary arrest., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Acute coronary syndrome (ACS) in early adulthood (<40 years old) may be associated with unrevealed diagnoses of Kawasaki disease (KD) in childhood. Daniels et al. showed that 5% of young adults with acute coronary syndrome might have antecedent Kawasaki disease in a cohort with Kawasaki disease incidence rates ranging from about 9 to 20 per 100,000 children under 5 years of age. However, there is no relevant research from the cohort with higher incidence rates (>80-100 per 100,000 children under 5 years of age) of Kawasaki disease., Methods: We conducted a multicenter, retrospective study by reviewing medical records and angiographic data from two institutions (middle and southern Taiwan, respectively) of adults <40 years of age who underwent coronary angiography for clinically suspected acute coronary syndrome (2009-2019). Angiographic images were independently analyzed by three cardiologists who were blinded to the medical records. Demographic and laboratory data and risk factors of coronary artery disease were integrated to assess the likelihood of antecedent KD., Results: All 323 young adults underwent coronary angiography, and 27 had coronary aneurysms. The patients' clinical and angiographic characteristics were evaluated, and 7.4% had aneurysms likely to be associated with KD. Most subjects were male (23/24), and their low-density lipoprotein (LDL) levels were significantly higher ( p  = 0.028) than those of subjects unlikely to have KD., Conclusion: This study proposed that the cohort with higher Kawasaki disease incidence rates may have a higher prevalence of young adult ACS associated with antecedent KD. The importance of determining the clinical therapeutic significance of antecedent Kawasaki disease in young adult ACS warrants advanced research. Higher LDL levels may have a long-term cardiovascular impact in KD patients with persistent coronary aneurysms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shyu, Wu, Fu, Peng, Chuang, Kuo, Hsieh and Tai.)

Introduction: Community-acquired pneumonia (CAP) is lethal in elderly individuals who are more vulnerable to respiratory failure and require more emergency ventilation support than younger individuals. Interleukin-6 (IL-6) plays a crucial role and has predictive value in CAP; high serum IL-6 concentrations in adults are associated with high respiratory failure and mortality rates. Early detection of IL-6 concentrations can facilitate the timely stratification of patients at risk of acute respiratory failure. However, conventional enzyme-linked immunosorbent assay (ELISA) IL-6 measurement is laborious and time-consuming. Methods: The IL-6 rapid diagnostic system combined with a lateral flow immunoassay-based (LFA-based) IL-6 test strip and a spectrum-based optical reader is a novel tool developed for rapid and sequential bedside measurements of serum IL-6 concentrations. Here, we evaluated the correlation between the IL-6 rapid diagnostic system and the ELISA and the efficacy of the system in stratifying high-risk elderly patients with CAP. Thirty-six elderly patients (median age: 86.5 years; range: 65-97 years) with CAP were enrolled. CAP diagnosis was established based on the Infectious Diseases Society of America (IDSA) criteria. The severity of pneumonia was assessed using the CURB-65 score and Pneumonia Severity Index (PSI). IL-6 concentration was measured twice within 24 h of admission. Results: The primary endpoint variable was respiratory failure requiring invasive mechanical or non-invasive ventilation support after admission. IL-6 rapid diagnostic readouts correlated with ELISA results ( p < 0.0001) for 30 samples. Patients were predominantly male and bedridden (69.4%). Ten patients (27.7%) experienced respiratory failure during admission, and five (13.9%) died of pneumonia. Respiratory failure was associated with a higher mortality rate ( p = 0.015). Decreased serum IL-6 concentration within 24 h after admission indicated a lower risk of developing respiratory failure in the later admission course (Receiver Operating Characteristic [ROC] curve = 0.696). Conclusion: Sequential IL-6 measurements with the IL-6 rapid diagnostic system might be useful in early clinical risk assessment and severity stratification of elderly patients with pneumonia. This system is a potential point-of-care diagnostic device for sequential serum IL-6 measurements that can be applied in variable healthcare systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Fu, Lee, Hsieh, Shen and Cheng.)

Background: The myocardial kinetic energy (KE) and its association with pulmonary regurgitation (PR) have yet to be investigated in repaired tetralogy of Fallot (rTOF) patients., Purpose: To evaluate the adaptation of myocardial KE in rTOF patients by tissue phase mapping (TPM)., Study Type: Prospective., Population: A total of 49 rTOF patients (23 ± 5 years old; male = 32), 47 normal controls (22 ± 1 year old; male = 29)., Field Strength/sequence: 3-T/2D dark-blood three-directional velocity-encoded gradient-echo sequence., Assessment: Left and right ventricle (LV, RV) myocardial KE in radial (KE r ), circumferential (KE ø ), longitudinal (KE z ) directions. The proportions of KE in each direction to the sum of all KE (KE røz ): %KE r , %KE ø , %KE z . PR fraction., Statistical Test: Student's t test, multivariable regression. Statistical significance: P < 0.05., Results: In rTOF group, LV KE z remained normal in systole (P = 0.565) and diastole (P = 0.210), whereas diastolic LV %KE z (62% ± 14% vs. 72% ± 7%) and systolic LV %KE ø (9% ± 6% vs. 20% ± 7%) were significantly decreased. The KE r and %KE r of both ventricles significantly increased in the rTOF group (RV in diastole: 6 ± 3 vs. 3 ± 1 μJ and 54% ± 13% vs. 27% ± 7%). The rTOF group exhibited significantly higher RV/LV ratios of %KE r (systole: 1.3 ± 0.3 vs. 1.0 ± 0.3) and %KE ø (systole: 1.6 ± 0.8 vs. 1.0 ± 0.3) and significantly lower ratios of %KE z in systole (0.7 ± 0.2 vs. 1.0 ± 0.1) and diastole (0.5 ± 0.2 vs. 0.9 ± 0.1). In multivariable regression analysis, the RV peak systolic KE røz , RV systolic KE z , and LV diastolic %KE ø were independently associated with PR fraction in the rTOF group (adjusted R 2  = 0.479)., Data Conclusion: In rTOF patients, the adaptation of the KE proportion occurred earlier than that of the KE amplitude, and the biventricular balance of %KE was disrupted. PR may cause differential KE adaptation in RV and LV. TPM-derived KE may be useful in investigation of myocardial adaptation in rTOF patients., Evidence Level: 2 TECHNICAL EFFICACY: Stage 3., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction: Kawasaki 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., Methods: Specifically, 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., Results: The 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., Conclusions: Scaled-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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kuo, Chen, Chen, Lin, Chang, Wu, Wang, Chang, Tai and Hsieh.)

Background: Catecholamine-storm is considered the major cause of enterovirus 71-associated cardiopulmonary death. To elucidate the effect of milrinone on cardiac mitochondria and death, a rat model of catecholamine-induced heart failure was investigated., Methods: Young male Spray-Dawley rats received a continuous intravenous infusion of norepinephrine then followed by co-treatment with and without milrinone or esmolol. Vital signs were monitored and echocardiography was performed at indicated time points. At the end of experiments, hearts were extracted to study mitochondrial function, biogenesis, and DNA copy numbers., Results: Hypernorepinephrinemia induced persistent tachycardia, hypertension, and high mortality and significantly impaired the activities of the electron transport chain and suppressed mitochondrial DNA copy number, mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-α. Norepinephrine-induced hypertension could be significantly suppressed by milrinone and esmolol. Milrinone improved but esmolol deteriorated the survival rate. The left ventricle was significantly enlarged shortly after norepinephrine infusion but later gradually reduced in size by milrinone. The impairment and suppression of mitochondrial function could be significantly reversed by milrinone but not by esmolol., Conclusions: Milrinone may protect the heart via maintaining mitochondrial function from hypernorepinephrinemia. This study warrants the importance of milrinone and the preservation of mitochondrial function in the treatment of catecholamine-induced death., Impact: Milrinone may protect the heart from hypernorepinephrinemia-induced death via maintaining myocardial mitochondrial activity, function, and copy number. Maintenance of cardiac mitochondrial function may be a potential therapeutic strategy in such catecholamine-induced heart failure., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Di(2-ethylhexyl) phthalate (DEHP) may produce toxicity, posing a risk to human health. Medical devices composed of DEHP are frequently used in catheterization, but few studies have investigated DEHP exposure during catheterization. The aim of this prospective series was to characterize the exposure pattern of DEHP during catheterization., Methods: We enrolled 16 patients with congenital heart disease undergoing catheterization. Collection of urine was done to measure DEHP metabolites on hospitalization, before catheterization, after catheterization, and at discharge. The following DEHP metabolites were measured: mono-(2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and the ratio of MEHP to overall metabolites (MEHP%) was determined. DEHP exposure from polyvinyl chloride (PVC)-containing catheter and infusion systems were recorded in detail. Differences in DEHP levels before and after catheterization were analyzed., Results: Urinary levels of MEHP, MEHHP, and MEOHP significantly decreased from before catheterization to after catheterization (all p < 0.01), but did not change significantly from initial hospitalization to before catheterization. Urinary MEHP% significantly decreased from initial hospitalization to before catheterization (p < 0.001), then increased after catheterization (p < 0.001), and decreased gradually at discharge (p = 0.03). Urinary MEHP% after catheterization and at discharge was significantly positively related to the duration of using PVC-containing catheter systems. There was a significant positive correlation between urinary MEHP% and the duration of using PVC-containing infusion system before catheterization, and a borderline significant correlation at both post-catheterization time slots., Conclusions: Our results demonstrated that urinary MEHP% may be a potential biomarker of DEHP contamination from the use of PVC-containing catheters or infusion systems.

Acinetobacter baumannii is a well-known nosocomial pathogen that can survive in different environments through the use of intricate networks to regulate gene expression. Two-component systems (TCS) form an important part of such regulatory networks, and in this study, we describe the identification and characterization of a novel EmaSR TCS in A. baumannii . We constructed a Tn 5 -tagged mutagenesis library, from which an emaS sensor kinase gene and emaR response regulator gene were identified. We found that emaS / emaR single-mutants and double-mutants were unable to replicate in M9 medium with 1% ethanol as the single carbon source. Motility and biofilm formation were negatively affected in double-mutants, and transcriptomic analysis showed that mutation of emaSR dysregulated genes required for carbon metabolism. In addition, emaS / emaR single-mutants and double-mutants were unable to survive in acetic acid- and sodium acetate-containing medium, indicating that the EmaSR TCS is also important for acetate metabolism. Furthermore, virulence against Galleria mellonella was diminished in emaS / emaR single- and double-mutants. Taken together, these results show that this novel EmaSR TCS is involved in the regulation of A. baumannii ethanol metabolism and acetate metabolism, with important implications on motility, biofilm formation, and virulence if mutated. Further research on the underlying mechanisms is warranted.

Coronavirus disease 2019 (COVID-19) patients have distinct clinical features in the pediatric groups. However, there is a paucity of research focused on clinical manifestation within pediatric group in Taiwan. This study is to conduct a retrospective study of the clinical features of COVID-19 in Taiwan pediatric patients. A retrospective study was conducted on pediatric patients (Aged ≤ 18 years) in a Northern Taiwan hospital from May 1st, 2021 to June 30th, 2021. Thirty-eight patients were included from emergency room. They were laboratory confirmed COVID-19 through specimens from nasopharyngeal swab by real-time reverse-transcription polymerase chain reaction (RT-PCR). Data including RT-PCR cycle threshold (Ct) values, clinical and epidemiological features were collected and analyzed. Thirty-eight patients aged from 7-month to 18-year-old were included. The median age of patients was 15-year-old. The patients had sex ratio of 23 males to 15 females. More than half patients were infected from family members. Asymptomatic patients were 47.37%. In the symptomatic patients, fever (34.21%) was the most predominant symptom. Cough, nasal obstruction and sore throat were also common. Asymptomatic children had significantly higher Ct-values than symptomatic children, and diagnosed patients with Ct-values more than 19 were associated with asymptomatic infection (P = .0084). Ct-values higher than 19 were associated with asymptomatic infection, which may be a predictor of pediatric disease severity. Our results highlight the distinct clinical manifestations and outcomes in pediatric COVID-19 patients. Compared to the adults, pediatric patients aged ≤ 18 years with COVID-19 in Taiwan mainly had mild disease., Competing Interests: No funding, grants, or equipment were provided for the project from any source. There are no financial benefits to the authors associated with this work. This work has not been presented previously. The authors declare no conflicts of interest in relation to this work., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aims to compare lactate and central venous blood gas in the prediction of outcome in pediatric venoarterial mode extracorporeal membrane oxygenation (V-A ECMO)., Method: This was a retrospective observational study conducted on patients undergoing V-A ECMO care in the pediatric intensive care unit of a tertiary medical center in Taiwan. Patients under 18 years of age undergoing V-A ECMO from January 2009 to April 2019 were included in this study., Results: This study consisted of 47 children who received V-A ECMO with an overall weaning rate of 66.0%. The mean age was 5.5 years and mean ECMO duration was 11.6 days. Successful weaning group had significantly lower lactate levels at initial (58.7 ± 47.0 mg/dL vs. 108.0 ± 55.3 mg/dL, p = 0.003), 0-12 h (37.8 ± 29.0 mg/dL vs. 83.5 ± 60.0 mg/dL, p Z 0.001), and 12-24 h (29.4 ± 26.9 mg/dL vs. 69.1 ± 59.1 mg/dL, p = 0.003) after ECMO initiation; however, the central venous blood gas including pH, HCO 3 , CO 2 , base excess (BE), and O 2 saturation showed no significant difference. The favorable outcome group had significantly lower lactate levels at 0-12 h (32.8 ± 26.3 mg/dL vs. 71.3 ± 53.3 mg/dL, p = 0.005), and 12-24 h (20.7 ± 10.2 mg/dL vs. 61.9 ± 53.5 mg/dL, p = 0.002); however, the HCO 3 levels (26.2 ± 4.5 mmol/L vs. 22.9 ± 6.8 mmol/L, p = 0.042) and BE (2.2 ± 5.4 vs. 2.2 ± 8.5, p = 0.047) were significantly higher at 12-24 h. In multivariate logistic regression, 12-24 h lactate value was an independent factor for unfavorable outcomes (p = 0.015, odds ratio [OR] = 1.1) with the best cut-off value of 48.6 mg/dL (sensitivity 48%, specificity 100%)., Conclusion: Lactate has better outcome prediction than central venous blood gas in pediatric V-A ECMO. The lactate value 12-24 h after ECMO initiation was an independent factor for unfavorable outcomes., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Vascular endothelial growth factor (VEGF) is an important factor in mediating the inflammation of Kawasaki disease (KD). The literature regarding the relationship between VEGF and KD is sparse. The purpose of this study was to investigate the correlation of VEGF and KD. In a prospective study of 42 Taiwanese KD patients (18.9 ± 12.2 months, M/F 22/20) treated with intravenous immunoglobulin (IVIG), a series of VEGF levels was measured from the acute to convalescent phases. KD patients were classified into two subgroups with (n =20) and without (n = 22) acute coronary artery lesions (CALs). Control samples were obtained from 30 febrile controls (19.1 ± 13.7 months, M/F 13/17). In KD patients, VEGF levels in the pre-IVIG acute phase were significantly higher than those in the subacute and convalescent phases (both p < 0.001). In KD patients with CALs, VEGF levels significantly increased immediately in the post-IVIG phase (p = 0.039), and then significantly decreased in the subacute phase (p = 0.002). KD patients with acute CALs had higher median VEGF levels than those without acute CALs from acute to convalescent phases. In the subacute phase, KD patients with acute CALs had significantly higher VEGF levels (p = 0.022) than those without acute CALs. Our data show that VEGF did not decrease after IVIG treatment, and increased significantly after IVIG treatment in KD patients with acute CALs in acute phase. VEGF might be related to the complications of CALs in KD patients.

Lung ultrasound (LUS) is now widely used in the diagnosis and monitor of neonatal lung diseases. Nevertheless, in the published literatures, the LUS images may display a significant variation in technical execution, while scanning parameters may influence diagnostic accuracy. The inter- and intra-observer reliabilities of ultrasound exam have been extensively studied in general and in LUS. As expected, the reliability declines in the hands of novices when they perform the point-of-care ultrasound (POC US). Consequently, having appropriate guidelines regarding to technical aspects of neonatal LUS exam is very important especially because diagnosis is mainly based on interpretation of artifacts produced by the pleural line and the lungs. The present work aimed to create an instrument operation specification and parameter setting guidelines for neonatal LUS. Technical aspects and scanning parameter settings that allow for standardization in obtaining LUS images include (1) select a high-end equipment with high-frequency linear array transducer (12-14 MHz). (2) Choose preset suitable for lung examination or small organs. (3) Keep the probe perpendicular to the ribs or parallel to the intercostal space. (4) Set the scanning depth at 4-5 cm. (5) Set 1-2 focal zones and adjust them close to the pleural line. (6) Use fundamental frequency with speckle reduction 2-3 or similar techniques. (7) Turn off spatial compounding imaging. (8) Adjust the time-gain compensation to get uniform image from the near-to far-field.

As the COVID-19 (Coronavirus disease 19) pandemic spreads worldwide, the massive numbers of COVID-19 patients have created a considerable healthcare burden for every country. The clinical spectrum of SARS-CoV-2 infection is broad, ranging from asymptomatic to mild, moderate, severe, and critical. Most COVID-19 patients present with no or mild symptoms, but nearly one-fifth of all patients develop severe or life-threatening complications. In addition to localized respiratory manifestations, severe COVID-19 cases also show extra-pulmonary complications or induce multiorgan failure. Identifying, triaging, and treating patients at risk early is essential and urgent. This article reviews the potential prognostic value of various biomarkers at different clinical spectrum stages of COVID-19 infection and includes information on fundamental prognostic mechanisms as well as potential clinical implications. Biomarkers are measurable biochemical substances used to recognize and indicate disease severity or response to therapeutic interventions. The information they provide is objective and suitable for delivering healthcare providers with a means of stratifying disease state in COVID-19 patients. This, in turn, can be used to help select and guide intervention efforts as well as gauge the efficacy of therapeutic approaches. Here, we review a number of potential biomarkers that may be used to guide treatment, monitor treatment efficacy, and form individualized therapeutic guidance based on patient response. Implementation of the COVID-19 biomarkers discussed here may lead to significantly improved quality of care and patient outcomes for those infected with SARS-CoV-2 worldwide.

Helicobacter pylori infection is associated with the development of several gastric diseases including gastric cancer. To reach a long-term colonization in the host stomach, H. pylori employs multiple outer membrane adhesins for binding to the gastric mucosa. However, due to the redundancy of adhesins that complement the adhesive function of bacteria, targeting each individual adhesin alone usually achieves nonideal outcomes for preventing bacterial adhesion. Here, we report that key adhesins AlpA/B and BabA/B in H. pylori are modified by glycans and display a two-step molecular weight upshift pattern from the cytoplasm to the inner membrane and from the inner membrane to the outer membrane. Nevertheless, this upshift pattern is missing when the expression of some enzymes related to lipopolysaccharide (LPS) biosynthesis, including the LPS O-antigen assembly and ligation enzymes WecA, Wzk, and WaaL, is disrupted, indicating that the underlying mechanisms and the involved enzymes for the adhesin glycosylation are partially shared with the LPS biosynthesis. Loss of the adhesin glycosylation not only reduces the protease resistance and the stability of the tested adhesins but also changes the adhesin-binding ability. In addition, mutations in the LPS biosynthesis cause a significant reduction in bacterial adhesion in the in vitro cell-line model. The current findings reveal that H. pylori employs a general protein glycosylation system related to LPS biosynthesis for adhesin modification and its biological significance. The enzymes required for adhesin glycosylation rather than the adhesins themselves are potentially better drug targets for preventing or treating H. pylori infection.

Magnetic foreign body misingestion (MFBM) is now occurring more frequently. It may cause remarkable mortality and morbidity in children. A retrospective analysis of the clinical data of children admitted to Xiamen Children's Hospital between March 2017 and July 2020 due to accidental MFBM. A total of 14 children who had MFBM were collected, the proportion between urban and rural areas was 8:6, and the ratio of male to female was 6:1. The age ranged from 1.2 to 8.9 years (median 4.6 years). The number of magnetic foreign bodies ingested by mistake is 1 to 17 (average 6.5). Magnetic foreign objects are divided into magnets (3 cases) + magnetic beads (11 cases). About 40% (5/14) of this patient series showed no available misingestion history. Management includes: 4 cases of open surgery (including 1 case of laparoscopic transfer to operation), 3 cases of laparoscopic surgery, 2 cases of gastroscopy, 5 cases of conservative treatment of foreign bodies discharged through the anus. Of the 7 surgical cases, 6 cases presented with intestinal obstruction and intestinal perforation (at least 1 intestinal perforation and at most 5). Abdominal sonography has limitations in the detection of magnetic foreign bodies in the digestive tract. The proportion of laparoscopic surgery in the 7 surgical cases is nearly half. All surgical cases recovered smoothly after treatment. Our experience shows that MFBM is a big issue for the small children! The early symptoms of MFBM are often atypical especially among young children and MFBM may lead to severe adverse events. We proposed a management strategy for MFBM in children. We advise pediatricians/emergency physicians, parents/children's guardians and society should raise the collaborated alertness of MFBM. Global awareness of risk prevention of magnetic material accidental ingestion cannot be overemphasized., (© 2021. The Author(s).)

A quick prediction method may help confirm the diagnosis of Kawasaki disease (KD), and reduce the risk of coronary artery lesions. The purpose of this study was to evaluate potential candidate diagnostic serum proteins in KD using isobaric tagging for relative and absolute quantification (iTRAQ) gel-free proteomics. Ninety two subjects, including 68 KD patients (1.6 ± 1.2 years, M/F 36/32) and 24 fever controls with evident respiratory tract infection (2.1 ± 1.2 years, M/F 13/11) were enrolled. Medical records were reviewed for demographic and laboratory data. The iTRAQ gel-free proteomics was used to screen serum proteins completely and compare the difference between two groups followed by specific validation with ELISA. The candidate proteins and conventional laboratory items were selected for the prediction model of KD diagnosis by support vector machine. Five selected candidate proteins, including protein S100-A8, protein S100-A9, protein S100-A12, neutrophil defensin 1, and alpha-1-acid glycoprotein 1 were identified for developing the prediction model of KD diagnosis. They were used to develop an efficient KD prediction model with an area under receiver operating characteristic (auROC) value of 0.92 (95% confidence interval: 0.84, 0.98). These protein biomarkers were significantly correlated with the conventional laboratory items as follows: C-reactive protein, glutamic pyruvic transaminase, white blood count, platelet, segment and hemoglobin. These conventional laboratory items were used to develop a prediction model of KD diagnosis with an auROC value of 0.88 (95% confidence interval: 0.80, 0.96). Our result demonstrated that the prediction model with combined five selected candidate protein levels may be a good diagnostic tool of KD. Further prediction model with combined six conventional laboratory data is also an acceptable alternative method for KD diagnosis.

Hypertension in childhood and adolescence is associated with adult cardiovascular morbidity and mortality. However, the reported prevalence of pediatric hypertension varies considerably. We conducted a pioneer nationwide population-based study to investigate the prevalence of hypertension among children and adolescents. Pediatric patients who had been diagnosed with hypertension between 2000 and 2013 were selected from the National Health Insurance Research Database in Taiwan. Other metabolic syndrome-related diseases that would increase cardiovascular risk, including diabetes mellitus (DM), hyperlipidemia, and obesity, were also retrieved for further evaluation. In total, 10,364 children and adolescents diagnosed with hypertension were identified. The prevalence of pediatric hypertension in Taiwan ranged from 0.19 to 0.38 per 1000 children and adolescents between 2000 and 2013. Essential hypertension was most commonly coded (90.6%), which was much more than secondary hypertension (14.3%). Children and adolescents with hypertension were often associated with DM, hyperlipidemia, and obesity, with the odds ratios as 14.05 (95% confidence interval (CI) 11.74-16.81, p < 0.001), 10.65 (95% CI 9.48-11.97, p < 0.001), and 19.08 (95% CI 15.65-23.26, p < 0.001), respectively. To improve lifelong cardiovascular health, our results emphasize the importance of early proper recognition and suitable management of hypertension, as well as metabolic syndrome-related diseases, among children and adolescents.

Background: Whether low-risk Kawasaki disease (KD) patients are at increased risk of cardiovascular disease later in life remains controversial. The purpose of this study is to examine the arterial stiffness and exercise performance of KD patients in chronic stage., Methods: This study included 158 subjects. They were divided into three groups: 37 KD patients with regressed coronary artery lesions (CALs) (M/F 23/14, 13.6 ± 6.5 years) (group I), 43 KD patients without CALs (M/F 26/17, 13.9 ± 6.2 years) (group II), and 78 age- and gender-matched normal controls (M/F 44/34, 13.2 ± 6.9 years) (group III). They all underwent brachial-ankle pulse wave velocity (baPWV), an exercise test, and blood sampling to measure the levels of high-sensitivity C-reactive protein (hs-CRP), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol (TC). The differences among the groups were compared., Results: There were significant differences among the three groups in terms of right and left baPWV (p < 0.01 respectively), HDL level (p < 0.05), TC/HDL ratio (p < 0.05), and oxygen consumption (VO2) peak (p < 0.05). Moreover, group I subjects had significantly higher right and left baPWV (p < 0.05 respectively), lower HDL level (p < 0.05), and lower VO2 peak (p < 0.05) than group II subjects. Furthermore, baPWV was significantly correlated with TG level (r = 0.326, p < 0.05), TC/HDL ratio (r = 0.483, p < 0.01), LDL level (r = 0.386, p < 0.01), and VO2 peak (r = -0.385, p < 0.05) in group I subjects. Only the TC/HDL ratio was found to be a significant correlating factor for an increase of baPWV (beta = 0.68, p < 0.05) in KD patients after multiple linear regression., Conclusion: Our results suggest that arterial stiffness is present late after KD and may adversely affect exercise performance, especially in patients with regressed CALs. Regular measurement of baPWV may be indicated in the long-term follow-up of KD patients.

Background: Kawasaki Disease (KD) is considered a major acquired heart disease in children under the age of 5. Coronary artery aneurysm (CAA) can occur in serious cases despite extreme therapy efforts. Previous studies have reported low serum albumin level was associated with disease outcome, but no further investigation was addressed yet., Method: This retrospective (case-control) study randomly included children with KD who were admitted and underwent laboratory tests before undergoing IVIG treatment in this institution, the largest tertiary medical center in southern Taiwan from 2012 to 2016. Prognostic nutrition index (PNI), an albumin-based formula product, was evaluated as a predictor of CAA the first time. The progression of CAA was monitored using serial echocardiography for six months. We performed multivariable logistic regression analysis on the laboratory test and PNI with the disease outcome of the KD patients., Result: Of the 275 children, 149 had CAA, including transient dilatation, while the other 126 did not develop CAA during the 6-month follow-up period. A multivariate logistic regression model revealed that PNI, gender, IVIG non-responder, and platelet count are significant predictors of CAA with a 95% confidence interval estimator of 1.999, 3.058, 3.864 and 1.004, respectively. Using PNI to predict CAA presence gave an area under the receiver-operating-characteristics (ROC) curve of 0.596. For a cutoff of 0.5 in the logistic regression model and the PNI cut-off point is taken as 55 together with IVIG non-responder, boy gender, and platelet count take into account, sensitivity and specificity were 65.7 and 70.4%., Conclusion: PNI could be a candidate of adjunctive predictor of coronary artery aneurysm in addition to IVIG non-responder. Together with low PNI, IVIG non-responder, male gender and platelet count will give high odds to predict coronary artery aneurysm within 6 months of illness.

Background: The relationship between adenovirus infection and Kawasaki disease (KD) is unclear. The purpose of this study was to determine the relationship between adenovirus infection and KD using a cohort study in Taiwan., Methods: We used Taiwan National Health Insurance data (from 2000 to 2008) to conduct a population-based cohort study, analyzing children that was under 18 years of age. In total, 5280 children had adenovirus infection, and 5280 children without adenovirus infection were matched and followed up. Subsequent KD was the major outcome event. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence intervals (CIs) of developing KD associated with adenovirus infection., Results: There was a significantly higher cumulative incidence of KD in the adenovirus-infected cohort than that in the control cohort (log-rank test, p < 0.001). In the adenovirus-infected cohort, overall incidence of KD was 5.29 times higher than that of the control cohort (adjusted HR 5.29, 95% CI: 2.48-11.3). Increased KD risk was associated with previous adenovirus infection in children aged 3-5 years, in female patients, in those with a low urbanization level, and in those with allergies., Conclusion: An association between previous adenovirus infection and KD was identified in Taiwanese children, but other potential risk factors were not fully analyzed. The relationship between infection and KD requires further study.

Background: Hepatic dysfunction is an important long-term complication in Fontan patients. The purpose of this study was to evaluate the hepatic computed tomography (CT) findings after Fontan surgery and identify their association with clinical parameters., Methods: This study recruited 43 patients (23 male and 20 female patients aged 15.3 ± 6.8 years), who underwent Fontan surgery. Medical records were reviewed to collect their age, sex, congenital heart disease type, date of Fontan surgery, laboratory data, and hepatic CT findings. The relationship between hepatic findings and clinical parameters was analyzed., Results: The follow-up duration was 6.8 ± 4.1 years. Abnormal hepatic parenchymal enhancement was observed in 77% of the patients, with mild degree in 18, moderate degree in 10, and severe degree in 5 patients. According to the univariate analysis, risk factors for hepatic parenchymal enhancement were follow-up duration (odds ratio [OR]: 1.354 [95% confidence interval (CI): 1.024-2.078]; p = 0.042), hypoplastic left heart syndrome (HLHS) (OR: 3.262 [95% CI: 1.145-5.628]; p = 0.002), mean pulmonary artery pressure (OR: 1.598 [95% CI: 1.089-2.132]; p = 0.026), pulmonary vascular resistance index (OR: 1.263 [95% CI: 1.068-1.245]; p = 0.032), and brain natriuretic peptide (OR: 1.956 [95% CI: 1.085-2.673]; p = 0.045). According to the multivariate analysis, only HLHS (OR: 3.856 [95% CI: 1.389-5.863]; p = 0.001), mean pulmonary artery pressure (OR: 1.846 [95% CI: 1.362-2.549]; p = 0.015), and pulmonary vascular resistance index (OR: 1.185 [95% CI: 1.042-1.736]; p = 0.047) were significant risk factors for abnormal parenchymal enhancement., Conclusion: Abnormal hepatic parenchymal enhancement detected through CT is common in Fontan patients. Regular liver function test in conjunction with imaging studies may be considered when following up Fontan patients.

Background/purpose: To investigate the correlations among endothelial function assessment parameters, asymmetric dimethylarginine (ADMA)-related biomarkers, and traditional risk factors in adipose children., Methods: We enrolled adipose children aged 7-18 years between July 2014 and August 2016 as well as normal-weight controls from the outpatient clinic. Vascular measurements including echocardiography, carotid intima media thickness, pulse wave velocity (PWV), and flow-mediated dilation (FMD) were measured. Venous blood samples including traditional metabolic and endothelial dysfunction parameters were analyzed. Participants were grouped as adipose vs. normal-weight and as adipose with hypertension vs. adipose without hypertension. Clinical presentations, laboratory data, and cardiovascular measurement were compared., Results: Of the 105 enrolled children, 85 were adipose. Adipose children had higher systolic blood pressure, larger left ventricular (LV) mass, and adverse traditional metabolic biomarkers. FMD was significantly reduced (8.25 (5.32-12.06) % vs. 12.49 (7.18-16.58) %, p = 0.018) in the adipose group. PWV was markedly increased (4.65 (4.2-5.5) m/sec vs. 3.95 (3.38-4.35) m/sec, p < 0.001) in the hypertensive adipose children. Endothelial dysfunction parameters were not significantly changed in this study., Conclusion: Adipose children were at higher risk of hypertension and LV hypertrophy. FMD, PWV and traditional cardiovascular biomarkers can detect subtle vascular changes. Hypertension is an important sign of arterial involvement in adipose children. Although ADMA-related biomarkers were not statistically significant, future studies are needed to confirm its correlation with adiposity and hypertension in children. The early detection and prevention of endothelial dysfunction may decrease the rate of progression to cardiovascular consequences in later life., (Copyright © 2018. Published by Elsevier B.V.)

Although usually self-limiting, Mycoplasma pneumoniae pneumonia (MPP) may lead to clinical or radiological deterioration despite macrolide antibiotic therapy, resulting in the development of refractory MPP (RMPP). Corticosteroids have been used to treat RMPP with beneficial effects. Serum lactate dehydrogenase (LDH) is a suggested biomarker for the use of steroid therapy. Since serum LDH is a non-specific marker and elevated in many inflammatory processes, this study investigates the predicting level of LDH isoenzymes for RMPP. Fifty-four children with non-refractory M. pneumoniae pneumonia (NRMPP) and 16 children with RMPP were enrolled in this study. In comparison to the NRMPP group, the RMPP group showed significantly higher levels of serum LDH. Concerning LDH isoenzymes, the RMPP group showed significantly lower proportions of LDH1 and LDH2, while higher LDH4 and LDH5 percentage. Receiver operating characteristic curve analysis showed that the area under the curve for the total LDH data was 0.812 with a cut-off of 408 IU/L (sensitivity of 75.0%, specificity of 72.2%). The areas under the curve for LDH4, LDH5, and [LDH4 + LDH5] were estimated to be 0.813, 0.818, and 0.829, respectively. The threshold for [LDH4 + LDH5] was estimated to be 109.4 IU/L (sensitivity, 75.0%; specificity, 87.0%). These results indicate that for the initiation of corticosteroid therapy, serum [LDH4 + LDH5] level is a more sensitive biomarker than total LDH., (Copyright © 2018. Published by Elsevier B.V.)

Background: Kawasaki disease (KD) is an acute febrile systemic vasculitis most commonly seen in children under 5 years old. High-dose aspirin is often administered, but the duration of such treatment varies. Many centers reduce the aspirin dose once the patient is afebrile, even before treating said patient with intravenous immunoglobulin (IVIG). However, a randomized controlled trial regarding high-dose aspirin in the acute stage of KD has not previously been carried out., Methods/design: This trial has been designed as a multi-center, prospective, randomized controlled, evaluator-blinded trial with two parallel groups to determine whether IVIG alone as the primary therapy in acute-stage KD is as effective as IVIG combined with high-dose aspirin therapy. The primary endpoint is defined as coronary artery lesion (CAL) formation at 6-8 weeks. Patients meeting the eligibility criteria are randomly assigned (1:1) to a test group (that receives only IVIG) or a standard group (that receives IVIG plus high-dose aspirin). This clinical trial is conducted at three medical centers in Taiwan., Discussion: Since high-dose aspirin has significant anti-inflammatory and anti-platelet functions, it does not appear to affect disease outcomes. Furthermore, it can decrease hemoglobin levels. Therefore, we have initiated this randomized controlled trial to evaluate the necessity of high-dose aspirin in the acute stage of KD., Trial Registration: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan. ClinicalTrials.gov Identifier: NCT02951234. Release Date: November 3, 2016.

Background: Hypertension may result from high-fat (HF) diet induced-obesity and overexposure to glucocorticoids in utero. Recent studies demonstrated the potent contribution of adipose tissue's renin-angiotensin system (RAS) to systemic RAS, which plays a key role in regulating blood pressure (BP). In this study, we investigated the effects of prenatal dexamethasone (DEX) exposure and postnatal HF diet on RAS of adipose tissue., Methods: RAS and BP of 6-month old rats exposed to prenatal DEX and/or postnatal HF diet were examined., Results: Prenatal DEX plus postnatal HF exerted a synergistic effect on systolic BP. Prenatal DEX exposure suppressed plasma angiotensin (ANG) I and ANG II, whereas postnatal HF suppressed plasma ANG-(1-7) level. Prenatal DEX increased prorenin receptor and renin levels, but suppressed angiotensinogen (AGT) and angiotensin-converting-enzyme 1 (ACE1) mRNA expressions in adipose tissue. Postnatal HF increased AGT mRNA expression, but suppressed prorenin receptor, renin, ACE2, ANG II type 2 receptor (AT2R), and Mas receptor (MasR) mRNA expression levels., Conclusions: Prenatal GC exposure altered the ACE1/ANG II/ANG II type 1 receptor (AT1R) axis, whereas postnatal HF negatively impacted the ACE2/ANG-(1-7)/MasR axis. Prenatal DEX exposure and postnatal HF synergistically elevated BP through a distinct programming mechanism of systemic and adipose RAS. Adipose RAS might be a target for precise hypertension treatment.

Kawasaki disease (KD) is a form of systemic vasculitis that generally occurs in children under 5 years old. Currently, KD is still diagnosed according to its clinical symptoms, including prolonged fever, skin rash, conjunctivitis, neck lymphadenopathy, palm erythema, and oral mucosa changes. Because KD is a type of inflammation without specific marker for diagnosis, we plan to profile the plasma antibodies by using E. coli proteome microarray and analyze the differences between KD and healthy subjects. Plasmas were collected from KD patient before intravenous immunoglobulin treatment (KD1), at least 3 weeks after treatment (KD3), nonfever control (NC), and fever control (FC) children. The initial screening, which consisted of 20 KD1, 20 KD3, 20 NC, and 20 FC, were explored using E. coli proteome microarrays (∼4200 unique proteins). About ∼70 proteins were shown to have high accuracy, e.g. 0.78∼0.92, with regard to separating KD1, KD3, NC, and FC. Those proteins were then purified to fabricate KD focus arrays for training ( n = 20 each) and blind-testing ( n = 20 each). It only took 125 pl of plasma, less than a drop of blood, in the focus array assays. The AUC scores for blind tests of KD1 versus NC (17 protein markers), KD1 versus FC (20 protein markers), KD3 versus NC (9 protein markers), and KD1 versus KD3 (6 protein markers) were 0.84, 0.75, 0.99 and 0.98, respectively. This study is the first to profile plasma antibodies in KD and demonstrate that an E. coli proteome microarray can screen differences among patients with KD, nonfever controls, and fever controls., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background/purpose: To investigate whether a palm-held ultrasonocardiographic scanner would be useful for screening and follow-up in congenital heart disease (CHD)., Methods: We retrospectively reviewed the echocardiographic images from June 1, 2014 to November 1, 2014. All patients underwent two ultrasonographic examinations including palm-held scanner examination and standard echocardiography. To compare the quality of the two instruments, we developed a diagnostic scoring system ranging from 1 point to 10 points, with 10 points indicating the best quality. Two experienced echocardiographers retrospectively reviewed all recorded images blindedly and gave each examination a score. Comparisons of diagnostic score between two equipments were performed., Results: A total of 262 patients' images were reviewed. All cardiac lesions could be detected with both instruments. The mean diagnostic score of palm-held scanner and standard echocardiography were 8.20±0.53 versus 9.64±0.37 (p<0.05) in color image and 7.00±1.05 versus 8.56±1.14 (p<0.05) in gray-scale two-dimensional image, respectively. When we compared the score between the two instruments in individual CHDs, we found standard echocardiography had better quality except for detecting muscular ventricular septal defect and pulmonary regurgitation., Conclusion: The diagnostic sensitivity of palm-held scanner in detecting CHD was very good. Despite both instruments having a high diagnostic score in detecting CHD, standard echocardiography had better quality. Traditional echocardiography is still the standard tool for CHD evaluation. However, the palm-held scanner can support physical examination for initial screening and follow-up, and offer cardiologists an opportunity to visualize and listen to the heart at any time., (Copyright © 2017. Published by Elsevier B.V.)

Background: Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD., Methods: We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression., Results: The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types., Conclusion: This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.

Background: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in hospitalized children. In CAP, causative agents are seldom identified using noninvasive diagnostic procedures. For those children not responding to empiric antibiotic therapy, it is vital to identify the causative pathogens for further management., Methods: We aimed to determine the usefulness of identifying the causative agents by bronchoalveolar lavage (BAL) in hospitalized children with nonresponding CAP. Ninety children hospitalized for CAP and treated with empiric antibiotics but having persistent fever ≥48 hours were enrolled, and their BAL data were retrospectively reviewed., Results: Aerobic bacteria were isolated from 38 (42%) of 90 cultures, and anaerobic bacteria were isolated from eight (24%) of 33 cultures. The bacteria isolated most frequently were Streptococcus viridians (26.3%), Pseudomonas aeruginosa (23.7%), and Staphylococcus aureus (15.8%). Streptococcus pneumoniae was isolated from the BALs of only two children, and Haemophilus influenzae from none. For positive aerobic culture results, BAL results guided modifications of antibiotic regimens in 21 episodes (21 of 38, 55.3%)., Conclusion: BAL results guided a change of antimicrobials in 55% of children with positive aerobic cultures (29% of all children in the study) and contributed to a high rate of successful therapy., (Copyright © 2017. Published by Elsevier B.V.)

Background: Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant., Methods and Results: To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10 - 03 and 8.224×10 - 10 , respectively)., Conclusions: This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG., (© 2017 The Authors.)

Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected. Furthermore, we measured plasma hepcidin levels with an enzyme-linked immunosorbent assay. We found that HAMP gene polymorphism (rs7251432, and rs2293689) was significantly correlated with KD risk and that plasma hepcidin levels both before and after IVIG treatment had a significantly positive correlation with length of hospital stays (R = 0.217, p = 0.046 and R = 0.381, p < 0.0001, respectively). In contrast, plasma hepcidin levels has a negative correlation with KD patients' albumin levels (R = -0.27, p < 0.001) prior to IVIG treatment. This study's findings indicate that HAMP might have a role in the disease susceptibility, as well as its expressions correlated length of hospital stays, and albumin levels in Taiwanese children with KD., Competing Interests: CONFLICTS OF INTEREST The authors hereby state that they have no financial interests to disclose in relation to this article.

Background: Kawasaki disease is the most common cause of pediatric acquired heart disease. The role of platelet endothelial cell adhesion molecule-1 in the inflammatory process has been documented. To date, no report has investigated the relationship between coronary artery lesions of Kawasaki disease and platelet endothelial cell adhesion molecule-1 polymorphisms., Methods: A total of 114 Kawasaki disease children with coronary artery lesions and 185 Kawasaki disease children without coronary artery lesions were recruited in this study. The TaqMan assay was conducted to identify the genotype in this case-control study., Results: In three single nucleotide polymorphisms (Leu125Val, Ser563Asn, and Arg670Gly) of platelet endothelial cell adhesion molecule-1, we found that the Leu-Ser-Arg haplotype was associated with a significantly increased risk for coronary artery lesions in the chronic stage (odds ratio 3.05, 95% confidence interval 1.06-8.80, p = 0.039), but not for coronary artery lesions in the acute stage. Analysis based on the diplotypes of platelet endothelial cell adhesion molecule-1 also showed that Kawasaki disease with one or two alleles of Leu-Ser-Arg had a significantly increased risk of chronic coronary artery lesions (odds ratio 3.38, 95% confidence interval 1.11-10.28, p = 0.032) and had increased platelet counts after Kawasaki disease was diagnosed, as compared to those with other diplotypes., Conclusions: The haplotype of platelet endothelial cell adhesion molecule-1 Leu-Ser-Arg might be associated with the increased platelet counts and the following risk of chronic coronary artery lesions in a dominant manner in Kawasaki disease.

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.