Maternal and neonatal outcomes in women with congenital heart disease: A nationwide population-based study.

BACKGROUND: We evaluated the outcomes of pregnancy in women with congenital heart disease (CHD) and their offspring in Taiwan. We also investigated how different severity levels may influence the outcomes. METHODS: We used data (2009-2017) from the Birth Certificate Application database in Taiwan, which is linked to the National Health Insurance Research Database and Taiwan Maternal and Child Health Database. We identified 2990 women with CHD who had 4227 births. Based on the CHD subtypes, patients were further divided into "severe CHD" and "simple CHD" groups. RESULTS: Women with CHD have a significant risk of stillbirth. In maternal cardiac events, they had the highest risk of heart failure, followed by arrhythmia. The severity of CHD had a significant effect on the outcomes as well. The neonatal birth event that mothers with CHD have the highest risk of is preterm birth at < 32 weeks of gestation. The prominent difference in neonatal morbidities between mothers with severe and simple CHD is recurrent CHD in the offspring. The offspring of the severe CHD group had a higher risk of severe CHD, whereas those of the simple CHD group had a higher risk of simple CHD. CONCLUSION: During pregnancy, the monitoring of heart function and cardiac rhythm could be more intensive in mothers with CHD. In addition to accurately assessing fetal growth and development during antenatal care, mothers with severe CHD should be provided with careful fetal heart structure assessment and genetic testing along with counseling.

RNA editing of 5-HT2C R impairs insulin secretion of pancreatic beta cells via altered store-operated calcium entry.

Recent studies emphasize the importance of 5-HT2C receptor (5-HT2C R) signaling in the regulation of energy homeostasis. The 5-HT2C R is the only G-protein-coupled receptor known to undergo post-transcriptional adenosine to inosine (A-to-I) editing by adenosine deaminase acting on RNA (ADAR). 5-HT2C R has emerged as an important role in the modulation of pancreatic ß cell functions. This study investigated mechanisms behind the effects of palmitic acid (PA) on insulin secretion in different overexpressed 5-HT2C R edited isoforms in pancreatic MIN6 ß cells. Results showed that the expressions of 5HT2C R and ADAR2 were upregulated in the pancreatic islets of mice fed with high-fat diet (HFD) compared to control mice. PA treatment significantly induced the expressions of 5-HT2C R and ADAR2 in pancreatic MIN6 ß cells. PA treatment significantly induced the editing of 5-HT2C R in pancreatic MIN6 ß cells. There was no significant difference in cell viability between naïve cells and three overexpressed 5-HT2C R edited isoforms in pancreatic MIN6 ß cells. Overexpressed 5-HT2C R edited isoforms showed reduced glucose-stimulated insulin secretion (GSIS) compared with green fluorescent protein (GFP) expressed cells. Moreover, 5-HT2C R edited isoforms displayed reduced endoplasmic reticulum (ER) calcium release and store-operated calcium entry (SOCE) activation, probably through inhibition of stromal interaction molecule 1 trafficking under PA treatment. Altogether, our results show that PA-mediated editing of 5-HT2C R modulates GSIS through alteration of ER calcium release and SOCE activation in pancreatic MIN6 ß cells.

Clinical characteristics and outcomes of mixed virus or bacterial infection in children with laboratory-confirmed influenza infection.

BACKGROUND/PURPOSE: This study investigated the demographic characteristics and influenza complications of paediatric patients and explored the association of different influenza virus types and viral and bacterial coinfections with disease severity. METHODS: This retrospective cohort study used data collected in 2010-2016 from the Chang Gung Research Database (CGRD), the largest collection of multi-institutional electronic medical records in Taiwan. Data were retrieved for children aged 0-18 years with laboratory-confirmed influenza. We extracted and analysed the demographic characteristics and the data on clinical features, complications, microbiological information, and advanced therapies of each case. RESULTS: We identified 6193 children with laboratory-confirmed influenza, of whom 1964 (31.7%) were hospitalised. The age of patients with influenza A infection was lower than that of patients with influenza B (4.48 vs. 6.68, p < 0.001). Patients with influenza B infection had a higher incidence of myositis or rhabdomyolysis (4.4%, p < 0.001) and a higher need for advanced therapies (OR, 1.96; 95% CI, 1.32-2.9, p < 0.001). In addition to bacterial (OR, 9.07; 95% CI, 5.29-15.54, p < 0.001) and viral coinfection (OR, 7.73; 95% CI, 5.4-11.07, p < 0.001), dual influenza A and B infection was also a risk factor for influenza complications (OR, 2.13; 95% CI, 1.47-3.09, p < 0.001). CONCLUSION: Dual influenza A and B infection and bacterial coinfection can contribute to influenza complications. Early recognition of any influenza complication is critical for the timely initiation of organ-specific advanced therapies to improve influenza-associated outcomes.

Montelukast does not increase the risk of attention-deficit/hyperactivity disorder in pediatric asthma patients: A nationwide population-based matched cohort study.

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.

Remote and onsite scoring of OSCEs using generalisability theory: A three-year cohort study.

Introduction: Onsite scoring is common in traditional OSCEs although there is the potential for an audience effect facilitating or inhibiting performance. We aim to (1) analyze the reliability between onsite scoring (OS) and remote scoring (RS); and (2) explore the factors that affect the scoring in different locations. Methods: A total of 154 students and 84 raters were enrolled in a single-site during 2013-2015. We selected six stations randomly from a 12-station national high-stakes OSCE. We applied generalisability theory for the analysis and investigated the perceptions that affected RS scoring. Results: The internal consistency reliability Cronbach's α of the checklists was 0.92. The kappa agreement was 0.623 and the G value was 0.93. The major source of variance comes from the students themselves, but some from locations and raters. The three-component analysis including Technical Feasibility, Facilitates Wellbeing, and Observational and Attention Deficits explained 73.886% of the total variance in RS scoring. Conclusions: Our study has demonstrated moderate agreement and good reliability between OS and RS ratings. We validated the factors of facility operation and quality for RS raters. Remote scoring can provide an alternative forum for the raters to overcome the barriers of distance, space, and avoid the audience effect.

Evaluation of endothelial dysfunction, endothelial plasma markers, and traditional metabolic parameters in children with adiposity.

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.

Left Ventricle Decompression Strategies in Pediatric Peripheral Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used in patients with potentially reversible acute cardiac and/or pulmonary failure who are unresponsive to conventional treatment. Patients with profound left ventricular (LV) dysfunction under venous-arterial (V-A) ECMO may experience LV distention, pulmonary edema, and thrombus formation. It is critical to unload the left ventricle to prevent such complications. The aim of this study was to identify the risks, timing and methods of LV decompression in pediatric peripheral ECMO. METHODS: Between August 2006 and November 2017, 51 patients received peripheral ECMO support in our pediatric intensive care unit. All of them were less than 18 years of age and non-cardiotomy surgery-related. We retrospectively reviewed the patients' clinical presentations, decompression methods and outcomes. RESULTS: The overall success rate of ECMO removal was 76.5% (39/51), and the survival rate after discharge was 62.7% (32/51). The myocarditis group had the most favorable outcomes among the ECMO patients (100% survival). LV decompression was needed in 12 patients who had profound LV dysfunction under V-A ECMO. Five patients received medical treatment successfully, and the other 7 patients underwent intra-aortic balloon pump (IABP) procedures. In the IABP group, 1 patient still needed further pigtail-decompression. All of our decompression patients survived with good neurological outcomes (Glasgow Outcome Scale 5). CONCLUSIONS: The patients with profound LV dysfunction under peripheral VA ECMO were at risk of thromboembolic events and LV decompress was needed. If medical decompression fails, IABP is a feasible approach for LV decompression in pediatric peripheral ECMO.

Regulation of calcification in human aortic smooth muscle cells infected with high-glucose-treated Porphyromonas gingivalis.

Porphyromonas (P.) gingivalis infection leading to the periodontitis has been associated with the development of systemic diseases, including cardiovascular diseases and diabetes. However, the effect of a high concentration of glucose (HG) on the invasion efficiency of P. gingivalis and the consequent modulation of pathogenesis in vascular cells, especially in the vascular smooth muscle cells (VSMCs), remains unclear. Hence, the aim of this study was to investigate whether treating P. gingivalis with HG could change its invasion capability and result in VSMC calcification and the underlying mechanism. Human aortic SMCs (HASMCs) and P. gingivalis strain CCUG25226 were used in this study. We found that HGPg infection of HASMCs could initiate the HASMC calcification by stimulating the autocrine regulation of bone morphogenetic protein (BMP) 4 in HASMCs. The upregulation of BMP4 expression in HASMCs was mediated by toll-like receptor 4 and ERK1/2-p38 signaling after P. gingivalis infection. Moreover, the autocrine action of BMP4 in HGPg infection-initiated HASMC calcification upregulated BMP4-specific downstream smad1/5/8-runx2 signaling to increase the expressions of bone-related matrix proteins, that is, osteopontin, osteocalcin, and alkaline phosphatase. This study elucidates the detailed mechanism of HGPg infection-initiated calcification of HASMCs and indicates a possible therapeutic role of BMP4 in P. gingivalis infection-associated vascular calcification.

Mid- to long-term follow-up of pediatric patients with coronary artery fistula.

BACKGROUND/PURPOSE: To investigate mid- to long-term outcomes in children with coronary artery fistula (CAF). METHODS: We retrospectively reviewed the medical records of patients seen between September 1996 and August 2011. We enrolled those diagnosed with CAF via echocardiography (Philips SONOS 7500 system and Philips IE33) or angiography. The mean follow time was 42.58 ± 3.4 months (range, 1-166 months). For comparative purposes, participants were grouped as acquired versus congenital, and symptomatic versus asymptomatic. We also measured the size of the coronary artery (CA) in patients with CA dilatation (CAD). RESULTS: Out of 122 CAF patients, spontaneous closure was detected in 37 patients at 21.59 ± 3.45 months after diagnosis. This timeframe did not differ between the acquired and congenital groups (21.64 ± 6.26 months vs. 21.57 ± 4.15 months; p = 0.991). Ninety patients were asymptomatic and remained so; their spontaneous closure rate was 28.89%. Moreover, 24 patients had CAD, including 17 with Kawasaki disease and seven with congenital CAF. The CAs of all congenital-CAF-plus-CAD patients were initially > 5 mm; these patients underwent percutaneous transcatheter intervention, and their CA sizes decreased significantly (6.11 ± 0.79 mm vs. 3.76 ± 0.36 mm; p = 0.002). CONCLUSION: With the advanced sensitivity of echocardiography, CAF can be detected more easily than ever before. Most patients with small CAFs are asymptomatic and may experience spontaneous closure. Therefore, management of CAF depends on symptoms; if patients are asymptomatic and have small CAFs, intervention may not be necessary, especially in acquired cases. However, if patients present with symptoms or persistent dilatation of the proximal CA, surgical or percutaneous closure should be performed.

Homocysteine and Arginine-to-Asymmetric Dimethylarginine Ratio Associated With Blood Pressure Abnormalities in Children With Early Chronic Kidney Disease.

BACKGROUND: Less attention has been paid to evaluating subclinical cardiovascular disease (CVD) in the early stage of pediatric chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) and arterial stiffness are the earliest detectable assessments of subclinical CVD. Asymmetric dimethylarginine (ADMA) is an analog of L-arginine (ARG) that inhibits nitric oxide (NO) production; thus the ARG-to-ADMA ratio (AAR) is an index of NO. Homocysteine (HCY) is a risk factor for CVD and it can be metabolized to L-cysteine (CYS). Given that HCY and ADMA/NO are closely linked and related to hypertension, we therefore investigated whether ARG and HCY metabolites, arterial stiffness parameters, ABPM profile, and left ventricular hypertrophy (LVH) are interrelated in children and adolescents with early CKD. METHODS AND RESULTS: This cross-sectional study included 57 pediatric patients with CKD stages 1-3. Two-thirds of the children with CKD stages 1-3 exhibited BP abnormalities accessed by ABPM. Children with CKD stages 2-3 had higher HCY, but lower CYS levels. The plasma HCY level was increased in children with LVH and abnormal ABPM. Systolic BP positively correlated with biomarkers AAR, HCY, and CYS. LV mass positively correlated with AAR, HCY, and CYS. CONCLUSIONS: BP abnormalities were prevalent and associated with AAR, HCY, and CYS in children with early CKD. Our data highlighted the effect of NO and the HCY pathway on CKD-related hypertension.

Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes.

BACKGROUND: Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA), a class of compounds of humic substances, possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. METHODS: Peripheral blood monocytes and U937 cells were used for all experiments. Real-time PCR and ELISA assay were used to analyze the COX-2 mRNA expression and PGE2 secretion, respectively. Specific inhibitors were used to investigate the mechanism of homocysteine-mediating COX-2 mRNA expression and PGE2 secretion. Luciferase assay, transcription factor ELISA, and chromatin immunoprecipitation were used to determine the role of nuclear factor-κB in FA-mediated inhibition of homocysteine effect on monocytes. RESULTS: The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. Stimulation of U937 monocytes with homocysteine induced rapid increases in the phosphorylation of ERK and JNK; the inhibitor for ERK and JNK attenuated the homocysteine-induced nuclear factor-κB activation and COX-2 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that FA blocked the homocysteine-induced increases in the binding activity and in vivo promoter binding of nuclear factor-κB in monocytes. CONCLUSIONS: Our findings provide a molecular mechanism by which FA inhibits homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

Common carotid artery intima-media thickness is useful for diagnosis of the acute stage of Kawasaki disease.

BACKGROUND: This study aimed to investigate intima-media thickness (IMT) of the common carotid arteries in children with acute Kawasaki disease (KD). METHODS: Between 2009 and 2011, patients fulfilling the criteria for KD, including a fever lasting >5 days, were prospectively enrolled in this study. Laboratory data, echocardiography, and IMT were measured and compared with matched controls. RESULTS: A total of 70 common carotid IMTs were measured in 35 children. We studied 21 patients aged 3-60 months old with acute KD and 14 febrile patients aged 3-194 months old with acute infection and similar characteristics to those of KD patients. Children with KD had a significantly higher IMT compared with the controls (0.550 ± 0.081 mm vs. 0.483 ± 0.046 mm, P = 0.01). CONCLUSIONS: IMT during the acute stage of KD is increased, suggesting that IMT could be a useful diagnostic tool in the early diagnosis of KD.

Real-time Automatic M-mode Echocardiography Measurement with Panel Attention.

Motion mode (M-mode) echocardiography is essential for measuring cardiac dimension and ejection fraction. However, the current diagnosis is time-consuming and suffers from diagnosis accuracy variance. This work resorts to building an automatic scheme through well-designed and well-trained deep learning to conquer the situation. That is, we proposed RAMEM, an automatic scheme of real-time M-mode echocardiography, which contributes three aspects to address the challenges: 1) provide MEIS, the first dataset of M-mode echocardiograms, to enable consistent results and support developing an automatic scheme; For detecting objects accurately in echocardiograms, it requires big receptive field for covering long-range diastole to systole cycle. However, the limited receptive field in the typical backbone of convolutional neural networks (CNN) and the losing information risk in non-local block (NL) equipped CNN risk the accuracy requirement. Therefore, we 2) propose panel attention embedding with updated UPANets V2, a convolutional backbone network, in a real-time instance segmentation (RIS) scheme for boosting big object detection performance; 3) introduce AMEM, an efficient algorithm of automatic M-mode echocardiography measurement, for automatic diagnosis; The experimental results show that RAMEM surpasses existing RIS schemes (CNNs with NL & Transformers as the backbone) in PASCAL 2012 SBD and human performances in MEIS. The implemented code and dataset are available at https://github.com/hanktseng131415go/RAMEM.

High citrulline-to-arginine ratio associated with blood pressure abnormalities in children with early chronic kidney disease.

BACKGROUND: Nitric oxide (NO) is involved in hypertension and chronic kidney disease (CKD). NO synthase can metabolize L-arginine (ARG) to generate NO and L-citrulline (CIT). Two methylated ARG derivatives, asymmetric and symmetric dimethylarginine, are also involved in NO deficiency. Thus it was hypothesized that their combined ratios relate to blood pressure (BP) abnormalities in children with early CKD. METHODS AND RESULTS: The relationship between these ARG metabolites in plasma was examined using 24-h ambulatory BP monitoring (ABPM) profile in children and adolescents with CKD stages 1-3 (n=44). Approximately 20.4% (9/44) of children with CKD stages 1-3 were diagnosed with hypertension on clinical BP measurement, and 77.3% (33/44) had BP abnormalities on ABPM, including increased BP load, nocturnal BP non-dipping, and nocturnal hypertension. Children with CKD stages 2-3 were more prevalent with abnormal BP on ABPM, and had a higher level of CIT and CIT-to-ARG ratio than those with stage 1. Furthermore, high CIT-to-ARG ratio was significantly correlated with abnormal ABPM profile, including nocturnal hypertension, increased diastolic BP load, and nocturnal BP non-dipping. Higher CIT level was significantly correlated with increased diastolic BP load and overall ABPM profile. CONCLUSIONS: Plasma CIT-to-ARG ratio may serve as a useful marker of cardiovascular outcome in children with early CKD.

Small-bore pigtail catheters for the treatment of primary spontaneous pneumothorax in young adolescents.

OBJECTIVE: Small-bore pigtail catheters have been found to be effective in the treatment of primary spontaneous pneumothorax (PSP) in adults. The aim of this study was to compare the effectiveness of small-bore pigtail and large-bore catheters in the treatment of PSP in young adolescents. MATERIALS AND METHODS: Young adolescents (<18 years) with initial PSP were treated with aspiration (control group), small-bore pigtail catheters or large-bore catheters. Treatment was determined on a case-by-case basis with parental consultation. Success rate, recurrence rate (within 12 months), duration of hospital stay, duration of catheter insertion, and complications were analysed. MAIN RESULTS: There were 41 patients treated: aspiration, n=8; small-bore pigtail catheters, n=10; large-bore catheters, n=23. Demographic and baseline clinical characteristics were similar between groups. The success rates were 50.0% and 65.2% in the small-bore pigtail and large-bore catheter groups, respectively. Corresponding recurrence rates were 20.0% and 56.5%. There was no difference between the small-bore pigtail and large-bore catheter groups in the duration of hospital stay in patients for whom treatment was successful; however, the duration of catheter insertion was significantly shorter in the small-bore pigtail catheter group compared with the large-bore catheter group in patients for whom treatment was successful (p<0.05). There were no major complications in either catheter treatment group and few minor complications (small-bore pigtail catheter, n=2; large-bore catheter, n=4). CONCLUSIONS: The findings suggest that small-bore pigtail catheters may be as effective as large-bore catheters for the initial treatment of PSP in young adolescents.

Predictors for Regression of Large Secundum Atrial Septal Defects Diagnosed in Infancy.

PUPOSE: To determine predictive factors of spontaneous closure or size reduction in large secundum-type atrial septal defects (ASD) diagnosed in infancy prior to catheterization or surgical intervention. METHODS: From June 2003 to October 2009, 59 infants diagnosed with secundum-type ASDs measuring ≥ 8 mm in the first year of life were retrospectively enrolled. We reviewed medical records, as well as electrocardiography and echocardiography findings. Patients were divided into 2 groups according to the last ASD size: group A (n = 23), ASD reduction in size to < 5 mm or spontaneous closure; group B (n = 36), size of ASD remained ≥ 5 mm. RESULTS: The ASDs spontaneously closed in 10 (17%) patients at a median age of 26.0 ± 5.1 months (range, 15-58 months), or decreased to < 5 mm in 13 (22%) (range, 6-27 months) patients. There was a significant difference in age at diagnosis between the 2 groups (p = 0.014). Patients in group A were younger than those in group B at the time of diagnosis. Changes in ASD size (p < 0.001) and body weight percentile (p = 0.01) were also significantly different fromthe 6-month follow-up. ASD diameter of ≥ 10 mm was a negative predictive factor for size reduction (p = 0.017). CONCLUSIONS: Spontaneous closure or size reduction of large ASDs was not uncommon in patients diagnosed during infancy. Patients with initial ASD sizes between 8 and 10 mm who were younger at the time of diagnosis and showed better weight gain were more likely to have favorable outcomes. KEY WORDS: Infancy; Large secundum atrial septal defect; Natural course; Spontaneous closure.

Guideline-Adherent Hypertension in Children and Adolescents: A Multi-Institutional Database Analysis from Taiwan.

BACKGROUND/AIMS: Childhood-onset hypertension is associated with cardiovascular morbidity and adult mortality. This study aimed to assess guideline-adherent hypertension among Taiwanese youth and the agreement on hypertension between the 2017 American Academy of Pediatrics guidelines and the 2004 Fourth Report. METHODS: In this cross-sectional study, we collected outpatient blood pressure (OBP) measurements obtained during routine care visits from a large healthcare delivery system between 2009 and 2018 to evaluate the rate of guideline-adherent hypertension and assess patient-related factors of pediatric hypertension. RESULTS: In total, 12,469 children and adolescents who underwent three separate ≥3 OBP measurements over 33,369 person-years with a total of 95,608 BP measurements in an outpatient setting were analyzed. According to the 2017 American Academy of Pediatrics (AAP) guidelines, the rate of pediatric hypertension in the study setting, which included participants aged 1 to 17 years, ranged from 0.78 to 5.95 per 1000 persons. Although there was perfect agreement between the thresholds of the two guidelines for defining hypertension in the age groups of 1-7, 8-12, and 13-17 years (all κ statistic ≥ 0.85), the use of the AAP threshold classified more adolescents as having hypertension. Children and adolescents with hypertension often had complex chronic diseases and required substantial healthcare services in outpatient, emergency, and inpatient settings. CONCLUSIONS: The present study provides evidence of guideline-adherent pediatric hypertension and highlights the importance of regularly monitoring blood pressure to identify and manage hypertension in children and adolescents. Further research is required to determine the impact of new thresholds on the detection of target organ damage at a pediatric age.

Evaluation of Infective Endocarditis in Children: A 19-Year Retrospective Study in Taiwan.

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.

Perception and Mental Health Status Regarding COVID-19 Vaccination Among Taiwanese Adolescents and Their Caregivers.

Background: Vaccinating adolescents is a vital strategy to enhance population protection without imposing overly restrictive measures on our daily lives during the COVID-19 pandemic. As teenagers gain more independence, their willingness to get vaccinated may depend on their own understanding of the pandemic, vaccines, and mental well-being, as well as that of their caregivers. Our study aimed to examine how Taiwanese adolescents and their caregivers perceive COVID-19 vaccination and assess their mental health status. Methods: We invited a total of 138 vaccinated adolescents and their caregivers to complete several questionnaires, including the Drivers of COVID-19 Vaccination Acceptance Scale (DrVac-COVID19S), Impact of Event Scale (IES), and Chinese Health Questionnaire (CHQ). Results: Among the adolescents, 76.8% considered the BNT162b2 vaccine (Pfizer-BioNTech) as the ideal option for COVID-19 vaccination, while 27.5% of caregivers expressed acceptance of any available vaccine. Adolescents scored higher than caregivers in terms of vaccine value (p<0.001) and autonomy (p<0.001), but lower in knowledge (p<0.001), as assessed by the DrVac-COVID19S subscales. The adolescents' intention to get vaccinated against COVID-19 (DrVac-COVID19S total score) showed a positive correlation with their perception of the pandemic's impact (IES scores, r=0.214, p=0.012) and their caregivers' vaccination intention (r=0.371, p<0.001). Furthermore, adolescents' mental health demonstrated a positive association with the mental health of their caregiver (CHQ total scores, r=0.481, p<0.001). Conclusion: During the COVID-19 outbreak, caregivers have encountered heightened levels of mental stress, and this stress has been found to be positively correlated with the mental stress experienced by adolescents and their intentions regarding vaccination. These findings can serve as crucial references for healthcare providers and governments when formulating vaccination policies for adolescents in the future.

High glucose-treated macrophages augment E-selectin expression in endothelial cells.

E-selectin expression by endothelial cells (ECs) is crucial for leukocyte recruitment during the inflammatory response. Macrophage accumulation and serum E-selectin elevation are features of type 2 diabetes mellitus. However, the interactions between macrophages and ECs in regulating vascular endothelial function are not clearly understood. We investigated the mechanisms underlying the modulation of EC E-selectin expression by high glucose (HG)-treated macrophages. Macrophage-conditioned media (MCM) were prepared from HG-treated macrophages. EC stimulation with HG-MCM induced increases the expression and secretion of E-selectin. By using specific inhibitors and small interfering RNAs, we demonstrate that the activation of the JNK and p38 MAPK pathways are critical for HG-MCM-induced E-selectin expression. Transcription factor ELISA and chromatin immunoprecipitation assays further showed that HG-MCM increases the NF-κB- and AP-1 DNA-binding activities in ECs. The inhibition of NF-κB and AP-1 activation by specific siRNAs blocks the HG-MCM-induced E-selectin promoter activity and expression. Protein arrays and blocking assays using neutralizing antibodies demonstrated that macrophage inflammatory protein 1α and 1ß in HG-MCM are major mediators for the induction of EC E-selectin expression. These data support the hypothesis that E-selectin up-regulation stimulated by macrophages may play an active role in atherogenesis in the HG condition and suggest a new mechanism by which arterial disease is accelerated in diabetes.