[Show abstract][Hide abstract]ABSTRACT: Background:
A form of systemic vasculitis, Kawasaki disease (KD) occurs most frequently in children under the age of five years old. Previous studies have found that Prostaglandin E2 (PGE2) correlates with KD, although the related mechanisms are still unknown. CD40L may also be a marker of vasculitis in KD, so this study focuses on PGE2 and CD40L expression in KD.
Materials and methods:
This study consisted of a total of 144 KD patients, whose intravenous immunoglobulin (IVIG)/coronary arterial lesion (CAL) formation resistance was evaluated. PGE2 levels were evaluated in vitro to study the effect of CD40L on CD4+ T lymphocytes.
PGE2 levels significantly increased after IVIG treatment (p<0.05), especially in patients who responded to initial IVIG treatment (p = 0.004) and for patients without CAL formation (p = 0.016). Furthermore, an in vitro study revealed that IVIG acted as a trigger for PGE2 expression in the acute-stage mononuclear cells of KD patients. According to our findings, both IVIG and PGE2 can impede surface CD40L expressions on CD4+ T lymphocytes (p<0.05).
The results of this study are among the first to find that plasma PGE2 is correlated with the prevention of IVIG resistance and CAL formation through CD40L in KD.
[Show abstract][Hide abstract]ABSTRACT: For the past decades, although the rash at the bacillus Calmette-Guérin (BCG) inoculation site has been recognized as a diagnostic clue in Kawasaki disease, the present study is the first known one attempting to characterize BCG inoculation by dermatoscopy in Kawasaki disease and correlate the grade of BCG reaction with systemic involvement. Thirty-four patients diagnosed with Kawasaki disease by pediatric specialists were enrolled. We performed detailed history taking, laboratory examination, physical examination and dermatoscopy examinations. Based on the BCG reaction pattern by dermatoscopy, we were able to characterize three patterns: (A) Bull's eye pattern in 18 patients; (B) faint homogenous erythema in nine; and (C) central white patch in seven. Patients from group A exhibited the highest elevation of blood aspartate aminotransferase levels (P < 0.05). Notably, three patients from group A had a significantly dilated coronary artery despite i.v. immunoglobulin injection. We concluded that the bull's eye dermatoscopy sign is not only a useful diagnostic clue but also a severity biomarker in patients with Kawasaki disease.
[Show abstract][Hide abstract]ABSTRACT: Background
Kawasaki disease (KD) is also known as multiple mucocutaneous lymph node syndrome of systemic vasculitis and is a leading cause of coronary artery lesions (CAL) in childhood. Intravenous immunoglobulin (IVIG) has been proven to effectively reduce the incidence of CAL, but the role and effect dose of aspirin in KD is still unclear. Moreover, overt bleeding and anemia are associated with the use of aspirin, and anemia is common in patients with KD. Thus, the aim of this study was conducted to compare the treatment efficacy, degree of anemia and inflammation, and changes in serum hepcidin in children who received a combination of high-dose aspirin and IVIG in the acute stage of KD, and those who received IVIG alone.
Materials and Methods
KD patients from two medical centers were retrospectively analyzed from 1999–2009. All patients were initially treated with a single dose of IVIG (2 g/kg) as the standard care of treatment. In group 1, high-dose aspirin was prescribed (> 30 mg/kg/day) until the fever subsided, and then low-dose aspirin (3–5 mg/kg/day) was prescribed until all the inflammation signs had resolved. In group 2, low-dose aspirin was prescribed without high-dose aspirin. Laboratory data were collected for analysis in both groups.
A total of 851 KD patients (group 1, N = 305, group 2, N = 546) were enrolled in this study. There were no significant differences between group 1 and group 2 in terms of gender (p = 0.51), IVIG resistance rate (31/305 vs. 38/546, p = 0.07), CAL formation (52/305 vs. 84/546, p = 0.67), and duration of hospitalization (6.3 ± 0.2 vs. 6.7 ± 0.2 days, p = 0.13). There were also initially no significant differences in total white blood cell count, hemoglobin level, platelet count, and CRP before IVIG treatment between groups (all p>0.1). After IVIG treatment, group 1 had significantly lower levels of hemoglobin (p = 0.006) and higher CRP (p<0.001) as well as a smaller decrease in CRP level (p = 0.012). Furthermore, there was also a higher serum level of hepcidin and a delayed decrease in hepcidin level after receiving IVIG in group 1 (p = 0.04 and 0.02, respectively).
These results provide evidence demonstrating that high-dose aspirin in the acute phase of KD does not confer any benefit with regards to inflammation and it does not appear to improve treatment outcomes. Therefore, high-dose aspirin is unnecessary in acute phase KD.
[Show abstract][Hide abstract]ABSTRACT: Arginine (ARG) and citrulline (CIT) are essential for nitric oxide (NO) synthesis. Their metabolites are interrelated, and involved in blood pressure (BP) control, chronic kidney disease (CKD), and cardiovascular disease (CVD). Although CVD is the leading cause of mortality in CKD, little is known about subclinical CVD in early-stage childhood CKD. Twenty-four-hour ambulatory BP monitoring and arterial stiffness assessment allows the earlier possible detection of subclinical CVD. We investigated whether urinary CIT and ARG metabolites and their ratios are correlated with BP load and vascular abnormalities in children and adolescents with early-stage CKD. We enrolled 55 pediatric patients with mild-to-moderate CKD. Seventy percent (30/43) had at least one out of BP load abnormality on ambulatory BP monitoring, mainly increased asleep systolic BP (SBP) load (40%), asleep SBP or diastolic BP load > 95th percentile (40%), and nocturnal SBP nondipping (35%). Low urinary CIT level and CIT/ARG ratio were associated with BP load abnormalities in children with early CKD. Urinary CIT/ARG ratio was correlated with arterial stiffness, represented as pulse-wave velocity and augmentation index. SBP and diastolic BP loads were negatively correlated with urinary CIT, ARG, asymmetric dimethylarginine (an endogenous NO synthase inhibitor), and CIT/ARG ratio, while positively associated with dimethylamine/asymmetric dimethylarginine ratio and pulse-wave velocity. Early assessments of BP load abnormalities, urinary biomarkers in the CIT-ARG-NO pathway, and arterial stiffness parameters should increase early preventive care toward decreasing hypertension and CV remodeling in pediatric CKD.
Full-text Article · Nov 2015 · Journal of the American Society of Hypertension (JASH)
[Show abstract][Hide abstract]ABSTRACT: Kawasaki disease shock syndrome (KDSS) and toxic shock syndrome (TSS)can present as shock and fever with skin rash, but the management of these two groups of patients is different. This report proposes to help clinicians earlier distinguish these two diseases and expedite institution of appropriate therapy.
We retrospectively reviewed the medical records of patients admitted to the pediatric intensive care unit (PICU) with the diagnosis of KDSS or TSS from January 2000 through December 2010. Clinical, laboratory and echocardiographic data were collected for analysis of differences between them.
Seventeen patients met the inclusion criteria of KDSS and 16 had a confirmed diagnosis of TSS. The mean age of the KDSS group was significantly younger than that of the TSS group (36.8 ± 41.1 months vs. 113.3 ± 55.6 months, P < 0.001). Significantly lower hemoglobulin and age-adjusted hemoglobulin concentrations were noted in the KDSS group [Hb, age-adjusted z score -1.88 (range: -3.9 ~ 3.9) vs. 0.89 (range -6.4 ~ 10.8), P = 0.006]. The median platelet count of the KDSS group was nearly twice that of the TSS group [312 × 10/µL (range: 116 ~ 518) vs. 184.5 × 10/µL (range: 31~629), P = 0.021]. Echocardiographic abnormalities, such as valvulitis (mitral or tricuspid regurgitation) and coronary artery lesions weresignificantly more common in the KDSS group (p=0.022).
Echocardiography, anemia and thrombocytosis are useful early differentiating features between KDSS and TSS patients.
Article · Jul 2015 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract]ABSTRACT: 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.
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.
Full-text Article · Jun 2015 · Circulation Journal
[Show abstract][Hide abstract]ABSTRACT: Background
Kawasaki disease (KD) is known to be associated with T help (Th) 2 reaction and subsequently allergic diseases. Interleukin-31 (IL-31) has also been reported to be involved in Th2 mediated diseases such as allergic diseases. However, the role of IL-31 in KD has not been previously reported. The aim of this study is to investigate whether IL-31 is associated with KD and its clinical outcome.
A total of 78 KD patients who met the criteria of KD were enrolled in this study as well as 20 age-matched controls. Plasma samples were conducted to measure IL-31 before intravenous immunoglobulin (IVIG) treatment (KD1), within 3 days after IVIG treatment (KD2) and at least 3 weeks after IVIG treatment (KD3) by utilizing enzyme-linked immunosorbent assay (ELISA).
Our findings showed that IL-31 expression was higher in KD patients after IVIG treatment significantly (KD2>KD1: 1265.0±199.3 vs. 840.2±152.5 pg/ml, p<0.0001). Further analysis revealed that IL-31 level was significantly higher in KD patients with coronary artery lesion (CAL) (656.6±139.5 vs. 1373.0±422.0 pg/ml, p = 0.04) before IVIG treatment (KD1). There were no significant differences between the IVIG resistance and IVIG responsiveness groups.
IL-31 was increased after IVIG treatment in patients with KD and was significantly associated with CAL formation. The results from this study may help to identify a novel risk factor for predicting KD and CAL formation.
[Show abstract][Hide abstract]ABSTRACT: Kawasaki disease (KD) is a multi-systemic vasculitis that preferentially affects children. A single nucleotide polymorphism (SNP) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) has been identified to be an important polymorphism in the risk of KD. This study was conducted to comprehensively investigate the associations between all tagging SNPs of ITPKC in the risk of KD in a Taiwanese population. A total of 950 subjects (381 KD patients and 569 controls) were recruited. Seven tagging SNPs (rs11673492, rs7257602, rs7251246, rs890934, rs10420685, rs2607420, rs2290692) were selected for TaqMan allelic discrimination assay. Clinical data of coronary artery lesions (CAL) and aneurysms were collected for analysis. A significant association was found between rs7251246 in ITPKC and CAL formation. Haplotype analysis for ITPKC polymorphisms also confirmed this association in the patients with CAL and aneurysm formation. This is the first study to identify that SNP rs7251246 in ITPKC is associated with the severity of KD.
[Show abstract][Hide abstract]ABSTRACT: 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.
Plasma CIT-to-ARG ratio may serve as a useful marker of cardiovascular outcome in children with early CKD.
Full-text Article · Jan 2013 · Circulation Journal
[Show abstract][Hide abstract]ABSTRACT: Arginine (ARG) metabolites are interrelated and are involved in chronic kidney disease (CKD) and cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) appears to correlate with cardiovascular outcomes. We investigated the relationship between ARG metabolites, and their combined ratios in urine, and the ABPM profiles of children and adolescents with CKD. This cross-sectional study included 45 children and adolescents (age, 5-18 years) with stage 1 to 4 CKD. Each child underwent office blood pressure (BP) measurements, 24-hour ABPM, and urinary ARG metabolite determinations. Seventy percent of children with CKD had abnormal 24-hour ABPM profiles, including nocturnal hypertension, increased BP load, and nondipping nocturnal BP. The urinary ARG-to-asymmetric dimethylarginine (ADMA) ratio was lower, and the ADMA-to-symmetric dimethylarginine (SDMA) ratio was higher in children with advanced CKD (stages 2-4) than those with stage 1 CKD. CKD patients with BP abnormalities also had reduced urinary ARG and dimethylamine (DMA) levels. The higher urinary (ADMA+SDMA)-to-ARG ratios were correlated to ABPM abnormalities, including increased systolic BP load and non-dipping nocturnal BP. ABPM abnormalities were significantly associated with a high urinary (ADMA+SDMA)-to-ARG ratio, suggesting the possible involvement of methylated ARG in the development of hypertension among children with CKD.
Full-text Article · Oct 2012 · Journal of the American Society of Hypertension (JASH)
[Show abstract][Hide abstract]ABSTRACT: 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.
[Show abstract][Hide abstract]ABSTRACT: Purpose: To investigate the outcome of outlet-type ventricular septal defect (VSD) after surgery in pediatric patients. Methods: A total of 152 children who underwent surgical repairs for outlet-type VSD were enrolled. Clinical features associated with development of congestive heart failure (CHF), aortic valve prolapse (AVP), and aortic regurgitation (AR) were analyzed. Results: CHF was noted in 34 (22.4%) of 152 patients. Patients with CHF had a larger VSD size (p < 0.0001), a higher Qp/Qs ratio (p < 0.0001), and a higher mean pulmonary pressure (p < 0.0001) compared with patients without CHF. AVP was noted in 106 (69.7%) of 152 patients. Patients with AVP had an older operation age (p < 0.0001), a smaller Qp/Qs ratio (p < 0.0001), a higher systolic pressure gradient between the left and right ventricles (p < 0.0001), and a higher diastolic pressure gradient between the aorta and the right ventricle (p = 0.022) compared with the patients without AVP. Among 43 (28.3%) patients with AVP and AR, 17 had mild and 4 had moderate-severe AR after surgery. Severe AVP (p = 0.0231) and pre-operative AR (p < 0.001) are two risk factors for the presence of postoperative residual AR. Conclusion: Long-term outcome of surgical repairs for outlet-type VSD is excellent in most pediatric patients without severe CHF or moderate-severe AR. AVP and AR are more frequent and severe in patients with delayed surgery, highlighting the importance of early surgical treatment of outlet-type VSD.
[Show abstract][Hide abstract]ABSTRACT: Pediatric patients with atrial septal defect (ASD) may have failure to thrive. This study aimed to investigate body weight changes in pediatric patients after transcatheter closure of ASD.
From June 2003 to September 2008, we enrolled 60 pediatric patients who underwent transcatheter closure of ASD. Changes in body weight percentile, heart rate, and resolution of right ventricular hypertrophy were compared before and after ASD closure. Patients were divided into two groups according to initial weight percentile: group A, <50(th) percentile (n = 39) and group B, ≥50(th) percentile (n = 21). Echocardiography and routine weight measurements were performed before the procedure and at 3, 6, and 12 months during follow-up. Clinical presentations, laboratory data, and outcomes were measured.
Increased body weight percentile (41±4 vs. 48±4, p<0.01), lower heart rate (100±2 beats/min vs. 89±2beats/min, p<0.01), and resolution of right ventricular hypertrophy (59/60 vs. 1/60, p<0.01) were achieved after ASD closure at the 12-month follow-up. Patients in group A were significantly younger (4.6±0.5 years vs. 7.0±0.9 years, p = 0.016), had a higher pulmonary/systemic blood flow ratio (2.2±0.1 vs. 1.8±0.l, p = 0.044), a largerratio of ASD diameter/body surface area (25.0±1.4 vs. 16.4±1.9, p<0.01), and higher percentage of weight gain increase ≥ 5 percentile compared with patients in group B (22/39 vs. 6/21, p = 0.039).
Transcatheter closure of ASD positively affects weight gain. An increase of 7 percentile weight was observed at 1 year of follow-up. Patients with a younger age, higher pulmonary/systemic blood flow ratio, and a larger ratio of ASD diameter/body surface area may have better weight gain after ASD closure.
Article · Jul 2011 · Journal of the Formosan Medical Association