Risk Factors of Long-Term Sequelae After Transcatheter Closure of Perimembranous Ventricular Septal Defect in Young Children.

BACKGROUND: Complications arising from transcatheter closure of perimembranous ventricular septal defects (pmVSD) in children, such as residual shunts and aortic regurgitation (AR), have been observed. However, the associated risk factors remain unclear. This study identified risk factors linked with residual shunts and AR following transcatheter closure of pmVSD in children aged 2-12 years.Methods and Results: The medical records of 63 children with pmVSD and a pulmonary-to-systemic blood flow ratio <2.0 who underwent transcatheter closure between 2011 and 2018 were analyzed with a minimum 3-year follow-up. The success rate of transcatheter closure was 98.4%, with no emergency surgery, permanent high-degree atrioventricular block, or mortality. Defects ≥4.5 mm had significantly higher odds of persistent residual shunt (odds ratio [OR] 6.85; P=0.03). The use of an oversize device (≥1.5 mm) showed a trend towards reducing residual shunts (OR 0.23; P=0.06). Age <4 years (OR 27.38; 95% confidence interval [CI] 2.33-321.68) and perimembranous outlet-type VSD (OR 11.94, 95% CI 1.10-129.81) were independent risk factors for AR progression after closure. CONCLUSIONS: Careful attention is crucial for pmVSDs ≥4.5 mm to prevent persistent residual shunts in transcatheter closure. Assessing AR risk, particularly in children aged <4 years, is essential while considering the benefits of pmVSD closure.

Kawasaki disease in children with Bacillus Calmette-Guérin scar reactivity: Focus on coronary outcomes.

BACKGROUND: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes. METHODS: This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019-2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups. RESULTS: BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2-3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2-3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2-3 months in children with incomplete KD. CONCLUSION: BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2-3 months.

Normal ECG standards and percentile charts for infants, children and adolescents.

BACKGROUND: Normal ECG standards in newborns, infants, children and adolescents have been collected and published by many authors. Only those by Davignon et al., Rijinbeek et al. and our two studies covered all ages from birth to adolescence. The standards reflecting the growth and development of the heart in infants, children and adolescents remained to be studied and explored. METHODS: We selected from our ECG database, after discussions and consultation, 15 key ECG parameters and analyzed for their age- and sex-specific mean, standard deviation and 2nd to 98th percentiles and their percentile charts were constructed. RESULTS: The ranges and distributions of the normal ECG standards, means and 2nd to 98th percentiles of 15 key parameters were established. CONCLUSION: A complete set of normal ECG standards of 15 key parameters from birth to adolescents is available for clinicians and researchers.

Cross-protective humoral immunity to coronaviruses from SARS coronavirus 2-naïve sera of children with Kawasaki disease.

OBJECTIVES: SARS coronavirus 2 (SARS-CoV-2)-associated multi-system inflammatory syndrome in children indicates that viruses can trigger a Kawasaki disease (KD)-like hyperinflammation. A plausible hypothesis was that coronavirus-specific 'holes' in humoral immunity could cause both diseases. METHODS: To determine whether SARS-CoV-2-naïve patients with KD have inferior humoral immunity for the novel coronavirus, sera of children with KD and control children from year 2015 to 2021 were subjected to ELISA, microwestern, and neutralization assays to evaluate the capabilities in recognizing the receptor-binding domain of SARS-CoV-2, spotting spike proteins of three respiratory syndromic coronaviruses, and blocking SARS-CoV-2 from binding to angiotensin-converting enzyme 2 receptors in vitro, respectively. RESULTS: 29 patients with KD before 2019, 74 patients with KD in 2019 or 2020, 54 non-febrile controls, and 24 febrile controls were included in the study. SARS-CoV-2 was recognized on ELISA for both patients with KD in 2016 and those with KD in 2020. Microwestern demonstrated cross-reactive IgG in an all-or-none manner towards three spike proteins of syndromic coronaviruses regardless of sample year or KD status. The ratio between the sera that recognized all spike proteins and those that recognized none (51 vs. 47) was significantly higher from patients with KD than from non-febrile controls (17 vs. 32; p 0.047) but not from febrile controls (13 vs. 11; p 0.85). Most positive sera (12 of 17 controls, 5 of 8 patients with KD before 2019, and 28 of 33 patients with KD in 2019 or 2020) offered protection comparable to low-titre sera from the WHO reference panel. DISCUSSION: Humoral immunity of SARS-CoV-2-naïve children with KD was not inferior to that of controls in offering cross-protection against the novel coronavirus.

Association of Exclusive Breastfeeding with Asthma Risk among Preschool Children: An Analysis of National Health and Nutrition Examination Survey Data, 1999 to 2014.

Breastmilk contains many important nutrients, anti-inflammatory agents, and immunomodulators. It is the preferred nutrition source for infants. However, the association of the duration of exclusive breastmilk feeding (BMF) with asthma development is unclear. Data on children from the United States who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 were obtained. We examined the association between the duration of exclusive BMF and asthma in 6000 children (3 to 6 years old). After calculating the duration of exclusive breastfeeding according to answers to NHANES questionnaires, the estimated duration of exclusive BMF was divided into five categories: never breastfed or BMF for 0 to 2 months after birth; BMF for 2 to 4 months after birth; BMF for 4 to 6 months after birth; and BMF for ≥6 months after birth. The overall prevalence of asthma in children aged 3 to 6 years was approximately 13.9%. The risk of asthma was lower in children with an exclusive BMF duration of 4 to 6 months (aOR, 0.69; 95% CI, 0.48-0.98), after adjustment for potentially confounding factors. Subgroup analysis revealed that children of younger ages (3 to 4 years old) benefited most from the protective effects of exclusive BMF for 4 to 6 months (aOR, 0.47; 95% CI, 0.27, 0.8). We found that exclusive BMF, especially BMF for 4 to 6 months, is associated with a decreased risk of asthma in preschool-age children. The protective effect appeared to be diminished in older children. The potential mechanism needs further investigation.

Concurrence of imatinib-induced massive pleural/pericardial effusion and Campylobacter bacteremia in an adolescent with chronic myeloid leukemia.

Imatinib is a crucial therapeutic strategy against chronic myeloid leukemia. Though superficial edema is a common adverse effect of imatinib, massive fluid retention is rarely reported. Here, we report the case of an adolescent who had tolerated imatinib for a long time, and then presented with massive pleural/pericardial effusion during an episode of Campylobacter jejuni bacteremia. A stepwise and comprehensive survey excluded all other plausible causes of disease. The Naranjo scale was used to assess the probability of an adverse effect of medication, and the score turned out to be 9, indicating severe fluid retention to be a definite reaction to imatinib. Drug discontinuation, antibiotic administration, and invasive procedures improved this condition. After this episode, the patient could tolerate imatinib again, illustrating the transient and reversible nature of this reaction. Since prolonged imatinib usage is crucial for chronic myeloid leukemia control, alertness to drug-related adverse effects is recommended, even if the subject has previously shown a good tolerance to the drug due to various physical conditions, especially physiological stressors, like infection or inflammation.

Long-Term Outcomes and Prognosticators of Pediatric Primary Dilated Cardiomyopathy in an Asian Cohort.

Background: Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy. The epidemiological profiles and prognosticators of clinical outcomes in Asian populations are not well elucidated. Methods: Data of 104 children aged <18 years with a diagnosis of primary DCM from January 1990 to December 2019 in our institutional database were retrospectively investigated. Relevant demographic, echocardiographic, and clinical variables were recorded for analysis. A P <0.05 was considered statistically significant. Results: The median age at diagnosis was 1.4 years (interquartile range = 0.3-9.1 years), and 52.9% were males. During a median follow-up duration of 4.8 years, 48 patients (46.2%) were placed on the transplantation waitlist, and 52.1% of them eventually received heart transplants. An exceptionally high overall waitlist mortality rate was noted (27.1%), which was even higher (43.5%) if the diagnostic age was <3 years. The 1-, 5-, and 10-year transplant-free were 61.1, 48.0, and 42.8%. Age at diagnosis >3 years and severe mitral regurgitation at initial diagnosis were independent risk factors for death or transplantation (hazard ratios = 2.93 and 3.31, respectively; for both, P <0.001). In total, 11 patients (10.6%) experienced ventricular function recovery after a median follow-up of 2.5 (interquartile range = 1.65-5) years. Younger age at diagnosis was associated a higher probability of ventricular function recovery. Conclusions: Despite donor shortage for heart transplantation and subsequently high waitlist mortality, our data from an Asian cohort indicated that transplant-free long-term survival was comparable with that noted in reports from Western populations. Although younger patients had exceptionally higher waitlist mortality, lower diagnostic age was associated with better long-term survival and higher likelihood of ventricular function recovery.

Changing Spectrum of Cardiac Diseases in Children: An Extended Longitudinal Observation Study of a Pediatric Cardiac Screening Program.

BACKGROUND: The spectrum of cardiac diseases in children is distinct from that in adults, and changes with advances in medical care and socioeconomic conditions. Such data are important for the allocation of medical resources, but are unclear. Based on a longitudinal pediatric cardiac screening program, we sought to delineate the spectrum and the trends. METHODS: From 2002 to 2018, citywide screening programs of cardiac diseases for children were performed in Taipei, Taiwan. Participants, mainly students entering the first grade of elementary school, were evaluated using questionnaires, simplified 4-lead electrocardiography (EKG), phonocardiography, and physical examinations. Those suspected of having abnormal cardiac lesions received detailed evaluations by pediatric cardiologists for a final diagnosis. RESULTS: The median prevalence of cardiac lesions in the children was 19.60/1000 (range from 14.9 to 24.65/1000), including congenital heart disease (32.02%), EKG abnormalities (33.34%), mitral valve prolapse (15.17%), Kawasaki disease (6.89%), rheumatic heart disease (0.17%) and others (12.41%). A significant time trend was only observed in a trend of decline in rheumatic heart disease. The median prevalence rates of congenital heart disease, Kawasaki disease, rheumatic heart disease, mitral valve prolapse, and EKG abnormalities were 6.20, 1.37, 0, 3.12, and 6.46 per 1000 children, respectively. CONCLUSIONS: This study, based on a citywide cardiac screening program, indicates that the spectrum of cardiac diseases in children has not changed in recent decades, except for a decline or disappearance of rheumatic heart disease in the Taipei metropolitan area. While congenital heart disease and EKG abnormalities were the most common, Kawasaki disease was the most commonly acquired heart disease in children.

Child Growth Curves in High-Altitude Ladakh: Results from a Cohort Study.

High prevalence of child underweight and stunting in high-altitude areas has often been reported. However, most previous studies on this topic were cross-sectional. Another critical concern is that using the World Health Organization (WHO) Child Growth Standards to evaluate child growth in high-altitude areas may lead to overestimations of underweight and stunting. Our study aimed to evaluate the long-term growth pattern of children (3 to 18 years) above the altitude of 3500 m in Ladakh, India. The participants' body weight (BW), body height (BH), and body mass index (BMI) were measured annually according to the WHO Child Growth Standards for children under 5 years old and the WHO reference data for children aged 5 to 19 years. The generalized estimating equation (GEE) was used to estimate the means and z-scores of BW, BH, and BMI at different ages. A total of 401 children were enrolled from 2012 to 2018. Their mean z-scores of BW, BH, and BMI were -1.47, -1.44, and -0.85 in 2012 and increased to -0.74, -0.92, and -0.63 in 2018. This population's specific growth curve was also depicted, which generally fell below the 85th percentile of the WHO standards. This is the first cohort study about long-term child growth patterns in a high-altitude area. The detailed underlying mechanisms of our findings need future research on more representative data of high-altitude populations.

Reference levels for glucose-6-phosphate dehydrogenase enzyme activity in infants 7-90 days old in Taiwan.

BACKGROUND: Nationwide newborn screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency has been implemented in Taiwan since 1987 and the G6PD enzyme activity levels were applied for diagnosis confirmation. As the reference value of G6PD enzyme activity was not available for infants aged 7-90 days, this study was performed to determine the enzyme level in different genotypes. METHODS: Between January 1, 2016 and June 30, 2017, 410 term infants aged 7-90 days old visiting National Taiwan University Hospital Hsinchu branch were enrolled. The comparisons of G6PD enzyme activities among genotype groups were performed. RESULTS: G6PD enzyme activity was negatively correlated with age (R = -0.212, p = 0.01). For infants under 30 days of age, the G6PD enzyme activity levels were 1.4 ± 0.9 U/g Hb in hemizygotes (n = 76), 6.5 ± 2.0 U/g Hb in heterozygotes (n = 47), and 13.6 ± 3.7 U/g Hb in those without G6PD mutations (n = 70). Among infants more than 30 days old, G6PD enzyme activity levels were 0.9 ± 0.5 U/g Hb in hemizygotes (n = 46), 6.0 ± 2.7 U/g Hb in heterozygotes (n = 23), and 11.7 ± 3.4 U/g Hb in those without G6PD mutations (n = 148). G6PD levels differed significantly among the groups defined by genotypes. CONCLUSION: We determined G6PD enzyme activity levels in infants aged between 7 and 90 days in Taiwan. Completing the reference data and determining the cutoff values for different G6PD deficiency disease statuses will help pediatricians to make accurate diagnoses.

Study on ECG in the Adolescent.

Normal ECG values in newborns, infants, and children have been collected and published. ECG in the adolescent, however, remains, to be collected and studied. The present study was designed and carried out to establish the normal ECG standards in male and female adolescents. A total of 898 school children and adolescents screened and examined as healthy were divided by age and sex into 6-9, 9-13, and 13-18 years age-groups. A 12 lead conventional ECG was recorded in 10 mm/mV and 25 mm/s, utilizing an automated Fukuda Denshi FCP-4301, MS-DOS/IBM-AT ECG machine. Lead V3R was not taken. Analog-to-digital conversion was performed by Fukuda signal acquisition module at a sampling rate of 500 Hz. The data on 69 ECG parameters were analyzed for the mean, standard deviation, 2nd to 98th percentiles, 95% confidence intervals, and sex difference. Normal values on 69 ECG parameters, sex-specific heart rate, P-QRS-T interval, duration, axis, wave amplitude, and calculated R/S amplitude ratio and ventricular activation time by age-group and sex were established. Male and female difference was noted in 49 (71.0%) parameters, of which 3 (6.1%) began in 6-9 years age-group, 30 (61.2%) began in 9-13 years age-group, and 16 (32.7%) in 13-18 years age-group. No sex difference occurred in 20 (29.0%) parameters. Normal male and female ECG standards on 69 ECG parameters in the adolescent were established. ECG sex difference began to appear the earliest at ages 6-9 years, and it occurred mostly at ages 9-13 years and 13-18 years, reflecting the anatomical and physiological consequences of puberty.

The prevalence of obesity and metabolic syndrome in Tibetan immigrants living in high altitude areas in Ladakh, India.

OBJECTIVE: To examine the prevalence of obesity and related cardiovascular disease risk factors among Tibetan immigrants living in high altitude areas. RESEARCH METHODS & PROCEDURES: A total of 149 Tibetan immigrants aged 20 years and over were recruited in 2016 in Ladakh, India. Anthropometric indices and biochemical factors were measured. Using the provided Asia-Pacific criteria from the World Health Organization, overweight and obese status were determined. Metabolic syndrome (MetS) was defined according to the American Heart Association. RESULTS: In general, men were older, taller, and had a greater amount of fasting glucose, and uric acid when compared to women. The prevalence of overweight, general obesity, and central obesity was 23.4, 42.6, and 42.6% in men and 7.8, 64.7, and 69.6% in women, respectively. The prevalence of MetS was 10.6% in men and 33.3% in women, respectively. In older subjects, the prevalence of obesity and MetS was found to be greater. In both genders, the prevalence of hypertension, central obesity, and MetS was significantly different among these body mass index (BMI) groups. Compared to the non-central obesity group, the central obesity group has higher weight, BMI, body fat, hip circumference, systolic and diastolic BP, and prevalence of hypertension. No relationship was found between the prevalence of diabetes and fasting glucose and BMI groups or central obesity groups in both genders. CONCLUSIONS: Among this group of Tibetan immigrants living in high altitude areas, women have a higher prevalence of obesity and MetS than men. No relationship was found between diabetes and obesity.

Infectious complications in children with acute lymphoblastic leukemia treated with the Taiwan Pediatric Oncology Group protocol: A 16-year tertiary single-institution experience.

BACKGROUND: Infection is a major complication in pediatric patients with acute lymphoblastic leukemia during chemotherapy. In this study, the infection characteristics were determined and risk factors analyzed based on the Taiwan Pediatric Oncology Group (TPOG) acute lymphoblastic leukemia (ALL) protocol. PROCEDURE: We retrospectively reviewed fever events during chemotherapy in 252 patients treated during two consecutive clinical trials at a single institution between 1997 and 2012. Patients were classified as standard, high, and very high risk by treatment regimen according to the TPOG definitions. We analyzed the characteristics and risk factors for infection. RESULTS: Fever occurred in 219 patients (86.9%) with a mean of 2.74 episodes per person. The fever events comprised 64% febrile neutropenia, 39% clinically documented infections, and 44% microbiologically documented infections. The microbiologically documented infections were mostly noted during the induction phase and increased in very high risk patients (89 vs. 24% and 46% in standard-risk and high-risk patients, respectively). Younger age and higher risk (high-risk and very high risk groups) were risk factors for fever and microbiologic and bloodstream infections. Female gender and obesity were additive risk factors for urinary tract infection (odds ratios = 3.52 and 3.24, P < 0.001 and P = 0.004, respectively). CONCLUSIONS: Infections developed primarily during the induction phase, for which younger age and higher risk by treatment regimen were risk factors. Female gender and obesity were additive risk factors for urinary tract infection.

Population-based study of Kawasaki disease shock syndrome in Taiwan.

By using a National Health Insurance database, we investigated the occurrence of Kawasaki disease (KD) shock syndrome in Taiwan. KD shock syndrome occurred most frequently in winter, and the incidence was 1.45 per 100 patients with KD. Compared with KD patients without shock, KD shock syndrome patients were older, more likely to develop coronary lesions (15.9% vs. 7.0%) and had longer hospitalization duration.

Total anomalous pulmonary venous connection: 15 years' experience of a tertiary care center in Taiwan.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease in which the connection between the pulmonary vein (PV) and left atrium needs to be surgically created. This study investigated the spectrum and outcome of a Taiwanese cohort. METHODS: Isolated TAPVC cases were identified from our institutional database between 1995 and 2009. We reviewed the medical chart and conducted telephone interviews with those lost to follow-up. RESULTS: There were 78 patients (52% male). The anomalous drainage sites were mainly supracardiac type (42.3%) and cardiac type (39.8%). Before operation, PV stenosis was found in 100% of infracardiac type, and in 69.7% of supracardiac type. Among the 75 patients undergoing operation, the surgical mortality was 9% (7/75). Perioperative arrhythmias (mainly of atrial origin) occurred in 35% of the patients. Of the 68 patients who survived the first operation, 28 (41%) developed pulmonary vein restenosis. Half of them progressed to severe PV stenosis, which required reintervention or resulted in mortality. Preoperative PV stenosis was the most significant predictor for postoperative PV restenosis and PV re-intervention. For the cohort, the 1-year and 5-year survivals were 78.9% and 74.2%, respectively, and the predictor for survival was again preoperative PV stenosis. CONCLUSION: The surgical mortality of isolated TAPVC is now low. Preoperative PV stenosis not only increased the risk of late PV restenosis and its reintervention, but also the overall mortality. The spectrum of PV drainage, per se, was not associated with worse outcome. PV restenosis remained the most important issue after correction of TAPVC.

Recurrent bacterial meningitis associated with Mondini dysplasia.

We reported two cases of recurrent meningitis and both of them had Mondini dysplasia, which provides a link between the brain and inner ear and is associated with cerebrospinal fluid, otorrhea/rhinorrhea, hearing impairment, and recurrent meningitis. Patients who have hearing impairment and recurrent meningitis should be evaluated for the possibility of this congenital dysplasia, and early diagnosis and prompt surgical intervention may prevent further episodes.

Left pulmonary artery coarctoplasty by using the right pulmonary artery flap near the arterial duct.

Coarctation of the left pulmonary artery may coexist with tetralogy of Fallot or pulmonary atresia with ventricular septal defect. Various surgical methods, such as autologous pericardial patching and intraoperative pulmonary artery stenting, have been used for solving this condition. We proposed a simple and effective technique for treating patients with left pulmonary artery coarctation and pulmonary atresia with ventricular septal defect by using the right pulmonary artery flap for left pulmonary artery coarctoplasty, plus central shunt creation by V-Y plasty.