Ken-Pen Weng

Treatment of acute Kawasaki disease: aspirin's role in the febrile stage revisited.

Objective. To evaluate the effect of treatment without aspirin in the acute phase of Kawasaki disease (KD) and to determine whether it is necessary to expose children to high- or medium-dose aspirin. Methods. A total of 162 patients who fulfilled the established criteria of acute KD between 1993 and 2003 were included in this retrospective study. All patients were treated with high-dose intravenous immunoglobulin (IVIG; 2 g/kg) as a single infusion without concomitant aspirin treatment. Low-dose aspirin (3–5 mg/kg per day) was subsequently prescribed when fever subsided. Patients who had defervescence within 3 days after the completion of IVIG treatment were classified as the IVIG-responsive group, and those whose fever persisted for >3 days were classified as the IVIG-nonresponsive group. The 162 patients were divided further into 2 groups: those who were treated with IVIG before illness day 5, and those who were treated after illness day 5. We compared the response rate of IVIG therapy, duration of fever, and incidence of coronary artery abnormalities (CAAs) between these groups. Results. A total of 153 patients were classified into the IVIG-responsive group, and 128 (83.66%) of them had defervescence within 24 hours after completion of IVIG therapy. Nine (5.56%) patients were classified into the IVIG nonresponsive group, and all received additional IVIG (2 g/kg) without aspirin. Six (66.67%) had defervescence within 3 days after additional therapy. Patients in the IVIG-nonresponsive group had a significantly higher incidence of CAAs than those in the IVIG-responsive group (25% vs 2.92%). In the group that was treated before illness day 5 (n = 16), all patients had defervescence within 3 days after IVIG therapy and 13 (81.25%) had defervescence within 24 hours. In the group that was treated after illness day 5 (n = 146), 137 (93.84%) patients had defervescence within 3 days and 115 (78.77%) had defervescence within 24 hours. One (6.67%) patient in the group that was treated before illness day 5 got a new onset of CAAs, as did 5 (3.85%) in the group that was treated after illness day 5. There was no statistically significant difference in the response rate of IVIG therapy, duration of fever, and incidence of CAAs between these 2 groups. Conclusion. The results of our study indicate that the treatment without aspirin in acute stage of KD had no effect on the response rate of IVIG therapy, duration of fever, or incidence of CAAs when children were treated with high-dose (2 g/kg) IVIG as a single infusion, despite treatment before or after day 5 of illness. We conclude that it seems unnecessary to expose children to high- or medium-dose aspirin therapy in acute KD when the available data show no appreciable benefit in preventing the failure of IVIG therapy, formation of CAAs, or shortening the duration of fever.

Recent advances in the treatment of Kawasaki disease

Abstract Kawasaki disease (KD) is acute systemic vasculitis that occurs mainly in infants and children under 5 years of age. The etiology of KD remains unknown. KD is liable to be complicated by coronary artery lesions (CALs), which develop in approximately 15–25% of untreated KD children and in approximately 5% of KD children after intravenous immunoglobulin (IVIG) therapy. A single high dose of IVIG (2 g/kg) is the gold standard therapy in the acute stage of KD. However, approximately 8–38% of children are unresponsive to initial IVIG treatment and at increased risk for CAL development. Anti‐inflammatory high doses of aspirin are recommended in conjunction with IVIG, but our study demonstrated that there is no evidence of efficacy in preventing CAL development. The usefulness of steroids in initial therapy for KD or treatment of IVIG‐resistant patients is not well established. Other immunosuppressive therapies, including infliximab, have been used in the treatment of refractory KD, but merit additional investigation. Subclinical atherosclerosis may develop early in KD patients, which makes early initiation of therapy to improve chronic inflammation an important issue. Future multicenter studies may help to define the optimal management of KD patients.

IL-10 promoter genetic polymorphisms and risk of Kawasaki disease in Taiwan

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (−1082, −819, and −592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci −819 T > C and −592 A > C for KD cases was observed (Ppermutation = 0.029 and Ppermutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090–2.443; Ppermutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. {The haplotype CC (−819, −592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987–1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p = 0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and −592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.

Role of multi-slice and three-dimensional computed tomography in delineating extracardiac vascular abnormalities in neonates.

BACKGROUND Recent advances in multi-slice computed tomography (MSCT) and three-dimensional computed tomography (3D CT) provide good-resolution images and short scan time for complete diagnosis of congenital heart disease (CHD). In the present study, we found that MSCT rapidly provides clinically relevant information for diagnosing extracardiac vascular anatomy in neonates with CHD. It is less invasive, necessitating only minimum or no sedation and a relatively small amount of contrast material. These advantages are crucial, especially for critically ill neonates. METHODS Between January 2007 and December 2008, MSCT scans were conducted on 41 neonates who were admitted to our neonatal intensive care unit. All the neonates were suspected to have complex CHD after an initial echocardiography examination. The scans were focused on detecting extracardiac vascular anatomy and abnormalities. All the image data sets were sent to image processing workstations for multiplanar interactive viewing and 3D reconstruction. RESULTS High-resolution MSCT scan images were obtained from 41 patients. Reported indications and findings of extracardiac abnormalities and related structural anatomy pertaining to congenital heart disease from MSCT and 3D CT findings were confirmed by clinical and surgical findings by a team of multidisciplinary congenital heart disease specialists. CONCLUSION Based on clinical and surgical confirmation of the MSCT scan results from a multidisciplinary congenital heart disease specialist team, we concluded that adequate information on CHD, specifically that regarding extracardiac abnormalities of the anatomy, can be obtained and MSCT can be used to replace cardiac catheterization.

Assessment of Growth From Foot Length in Taiwanese Neonates

BACKGROUND Previous studies have demonstrated a positive correlation between foot length (FL) and birth body weight (BBW), birth body length (BBL), and head circumference (HC). However, there is no data on birth FL in Taiwan. The aim of this study was to evaluate FL measurement in Taiwanese neonates as a method of estimating other anthropometric indices. METHODS In this retrospective study, we enrolled 256 babies born at our hospital and Kaohsiung Veterans General Hospital from 2003-2005. Medical records were reviewed for sex, BBW, BBL, HC, gestational age, and birth FL. Ill newborns, small-for-gestational-age babies, or those with poor birth footprints were excluded. FL at birth was measured from the center of the back of the heel to the tip of the big toe. Linear regression analysis was used to investigate the relation of FL to BBW and BBL. The intraclass correlation coefficient was used to assess inter-rater reliability. RESULTS A total of 256 babies were reviewed. There were 136 male and 120 female neonates. The gestational age was 38.5+/-1.3 (mean+/-standard deviation) weeks, ranging from 35-42 weeks. The BBW was 3137+/-396g. The BBL was 51.1+/-2.1 cm. The HC was 33.5+/-1.7 cm. The FL was 7.4+/-0.46 cm. The regression equation for BBW (y) on FL (x) was as follows: y=486.2+360.4x (p<0.001, r=0.421). The regression equation for BBL (y) on FL (x) was as follows: y=40.1+1.45x (p<0.001, r= 0.305). The regression equation for HC (y) on FL (x) was as follows: y=14.8+2.53x (p<0.001, r=0.423). FL showed excellent reliability, with an intraclass correlation coefficient of 0.965 (p<0.001). CONCLUSION Our study demonstrated a significant degree of correlation between FL and BBW, BBL and HC. However, it did not reliably estimate BBW, BBL, or HC-the three anthropometric indices were weakly correlated (r<0.5) with FL.

Reappraisal of the Prostaglandin E1 Dose for Early Newborns with Patent Ductus Arteriosus-Dependent Pulmonary Circulation

OBJECTIVES The usual initial dose of prostaglandin E1 (PGE1) for ductal-dependent congenital heart disease (CHD) is 50-100 ng/kg/minute. The aim of this study was to review our experience of a low initial dose of PGE1 treatment in early newborns with congenital heart disease and patent ductus arteriosus (PDA)-dependent pulmonary flow. METHODS We reviewed the clinical data of 33 newborns with CHD and PDA-dependent pulmonary circulation who were admitted from January 2005 to December 2010. Clinical parameters were collected, including, PGE1 dosage, oxygenation condition, vital signs, and other related clinical parameters during admission. Echocardiography was employed to assess the status of the PDA as clinically indicated. RESULTS Thirty-three newborns, including 17 males and 16 females, with CHD and PDA-dependent pulmonary circulation were enrolled in the study. Their mean age was 2.9 ± 5.1 (within the range of 1-26) days with a median of 1.0 day. Among the 33 cases, 25 were diagnosed with pulmonary atresia and eight with critical pulmonary stenosis. Twenty-five of our patients were treated with the initial low-dosage regimen of 20.0 ± 7.4 ng/kg/minute in our neonatal intensive care unit. None of these 25 patients with had significant apnea necessitating intubation and none had hypotension, fever, convulsion or cortical hyperostosis. Three of the eight patients who were treated with high-dose PGE1 (39 ± 13.2 ng/kg/minute) before referral to our unit had apnea and intubation after PGE1 use. All patients had adequate PDA patency with a low maintenance dose of 10.5 ± 5.3 ng/kg/minute before operation under our protocol. CONCLUSION In our experience, adequate PDA flows in early newborns with CHD and PDA-dependent pulmonary circulation could be achieved at a much lower dose than recommended in the literature. The lower dose of PGE1 also causes much fewer complications, such as apnea, fever, and hypotension. For early newborns with CHD and PDA-dependent pulmonary circulation, treatment with a lower initial dose of PGE1 of 20 ng/kg/minute and a maintenance dose of 10 ng/kg/minute is recommended.

Idiopathic Dilated Cardiomyopathy in Children: A Single Medical Center's Experience

Background: The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) is poor. Most patients die while waiting for cardiac transplantation because of the small number of donors in Taiwan. The purpose of this study was to review our experience with pediatric patients diagnosed with idiopathic DCM and attempt to discover prognostic factors. Methods: Eighteen patients with idiopathic DCM presenting between 1990 and 2004 were identified. They were classified into 2 groups according to outcome: group 1 comprised 13 patients who died; group 2 comprised 5 who survived. Clinical findings and laboratory investigations were compared between the 2 groups. Results: The age at initial diagnosis for the 18 patients (11 males, 7 females) ranged from fetus to 13 years (median, 3 months). The follow‐up period ranged from 12 days to 44 months (median, 7 months) in group 1, and from 1 to 48 months (median, 39 months) in group 2. Of the 18 patients, 13 (72%) died: 11 died from severe heart failure while waiting for cardiac transplantation. The cumulative survival rate was 50% at 1 year and 28% at 4 years. The presence of arrhythmia and low left ventricular ejection fraction were predictive of a poor outcome. Conclusion: The diagnosis of idiopathic DCM in children is associated with a generally poor prognosis. The lack of available donors results in significant mortality for pediatric patients awaiting transplantation. Advocating organ donation to increase the size of the organ donor pool is needed to significantly reduce the mortality rate in such patients.

Maternal and umbilical cord blood levels of mercury, manganese, iron, and copper in southern Taiwan: A cross-sectional study

Background The effect of maternal exposure to essential minerals and heavy metals on fetus is an important issue, which affects women around the world. Few data are available on the concentration of both essential minerals and heavy metals in maternal/fetal medicine. The aims of this study were to (1) assess the correlation of mercury (Hg), manganese (Mn), iron (Fe), and copper (Cu) in paired maternal/fetal blood samples, and (2) study potential confounding factors during pregnancy. Methods Our study recruited 145 healthy pregnant women with a mean age of 28.06 years, gathering information by collecting interviewer‐administered questionnaires. Paired maternal/fetal blood samples were collected by delivery. Results There was a positive correlation of Hg (r = 0.78, p < 0.001), Mn (r = 0.31, p < 0.001), Fe (r = 0.17, p = 0.038), and Cu (r = 0.21, p = 0.010) in paired maternal/fetal samples. Prenatal vitamin use (>3 times/wk) was significantly associated with lower maternal Hg (adjusted odds ratio 0.272, p = 0.005) and lower maternal Cu (adjusted odds ratio 0.267, p = 0.004) levels. Median fetal Hg, Mn, and Fe levels were higher than corresponding maternal levels, while median fetal Cu level was lower than maternal Cu level. Conclusion There was a positive correlation of Hg, Fe, Cu, and Mn in paired maternal/fetal samples in this series. Our findings have raised the possibility of reducing maternal Hg and Cu by way of prenatal vitamin supplementation.

Interleukin-18 and coronary artery lesions in patients with Kawasaki disease

Background: Interleukin‐18 (IL‐18) plays an important role in mediating cytokine cascade leading to coronary artery lesions (CALs) in Kawasaki disease (KD). However, our research suggested that the literature regarding IL‐18 and KD is limited. Consequently, this study aimed to evaluate the correlation between IL‐18 and CALs in patients with KD. Methods: In this prospective study of 14 children with KD (seven without and seven with CALs in the acute phase), we obtained patient measurements of a series of serum IL‐18 levels in the acute, subacute, and convalescent phases. Serum IL‐18 levels were measured with a Bio‐Plex cytokine assay. Control samples were obtained from 18 febrile children with viral infection. Results: Compared with febrile controls, patients with acute‐stage CALs [postintravenous immunoglobulin (post‐IVIG) period] had a significantly higher IL‐18 level (88.4 ± 20.7 vs 56.0 ± 35.0 pg/mL, p = 0.006). However, those without acute‐stage CALs (post‐IVIG period) lacked similarly elevated IL‐18 level readings (62.0 ± 40.6 vs 56.0 ± 35.0 pg/mL, p = 0.762). The IL‐18 level of patients with acute‐stage CALs did not decrease significantly until the convalescent phase (97.4 ± 55.8 vs 38.7 ± 22.6 pg/mL, p = 0.018), but for those without CALs, it decreased significantly in the subacute phase (60.2 ± 37.4 vs 23.6 ± 13.8 pg/mL, p = 0.018). In the subacute stage, there was a significant difference of IL‐18 level between patients with and without acute‐stage CALs (p = 0.048). Conclusion: Our data show that IL‐18 levels were elevated in the acute phase of KD and might be related to the formation of CALs.

Effects of Flow Rate on Delivery of Bubble Continuous Positive Airway Pressure in an In Vitro Model

BACKGROUND There has been concern over the effect of vigorous bubbling on the delivery pressure during the operation of the bubble nasal continuous positive airway pressure (CPAP) system. We investigated the relationship between intra-tubing pressure changes and flow rates in a closed bubble CPAP system in vitro. METHODS Using an experimental (in vitro) model, the distal connecting tube of the CPAP system was immersed under the water seal to a depth of 5 cm. Sixteen different flow rates, ranging from 2 L/min to 20 L/min, were tested. The procedure was repeated 10 times at each flow rate, and the intra-tubing pressure was recorded. RESULTS The intra-tubing pressure within the model increased as the air flow rates were adjusted from 2 L/min to 20 L/min. The relationship was represented by the following equation, pressure (cmH(2)O) = 5.37 + 0.15 x flow rate (L/min) (R(2) = 0.826, p < 0.001). CONCLUSION These results demonstrated that the intra-tubing pressure in a bubble CPAP system was highly correlated with flow rate in vitro.