Association of an IGHV3-66 gene variant with Kawasaki disease.

In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10-9). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10-10 in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.

Impact of time to treatment of oseltamivir on influenza hospitalization cost among Korean children.

BACKGROUND: Although oseltamivir is a common influenza treatment, there is a lack of data on the economic benefits of timely oseltamivir treatment. METHODS: From February 2004 through June 2007, 116 hospitalized children ≤ 15 years of age with laboratory-confirmed influenza who received oseltamivir were identified via retrospective medical chart review. Demographic, clinical, and cost data were abstracted and multivariate linear regression was used to assess the association between oseltamivir time to treatment and treatment-related costs among hospitalized children with laboratory-confirmed influenza. RESULTS: Overall, 28% (n = 33) of patients were treated with oseltamivir ≥ day 3 of admission. Rapid influenza diagnostic test was used in a significantly lower proportion of patients treated with oseltamivir ≥ day 3 of admission compared with those who received oseltamivir earlier. On multivariate linear regression, initiation of oseltamivir ≥ day 3 of admission was associated with a 60.84% increase (95%CI: 32.59-95.11) in treatment-related hospital costs, compared with initiation on admission. CONCLUSION: Delayed initiation of oseltamivir was found to be associated with increased treatment-related hospital costs among children hospitalized with laboratory-confirmed influenza.

Clinical manifestations of respiratory adenoviral infection among hospitalized children in Korea.

BACKGROUND: The objective of our study was to understand the epidemiological and clinical features of respiratory adenoviral infections among children at a single institution over the course of several years. METHODS: From January 2005 to April 2009, 1836 children (≤15 years old) who had been admitted to Korea University Ansan Hospital were tested for acute respiratory infection. The patients who were positive for an adenovirus infection were enrolled in this study, and their medical records were retrospectively reviewed. RESULTS: Adenoviruses were isolated from 310 patients. The male to female ratio was 1.6:1 and mean age was 32 ± 24 months. Children under 5 years of age had the highest prevalence. In 2007, adenovirus infections occurred endemically throughout the year. The clinical diagnoses were primarily upper respiratory tract infections (45.4%), lower respiratory tract infections (48.1%), and neurologic disease (5.2%). Associated symptoms, signs and laboratory findings included fever (91.9%), cough (83.9%), pharyngeal injection (62.3%), rale (32.6%) and elevated C-reactive protein (93.9%). The most common radiologic findings were perihilar and peribronchial infiltrates (42.6%). Co-infections were observed in 29 cases. The mean durations of hospitalization and fever were 6.2 ± 6.5 and 4.8 ± 3.1 days, respectively. The lengths of hospitalization were similar for patients admitted for upper respiratory tract infections with severe morbidity and those admitted for lower respiratory tract infections. No children in the study died. CONCLUSION: Our study demonstrates that respiratory adenovirus infections are an important cause of hospitalization in young children, and contribute to a significant morbidity.

Incomplete clinical manifestation as a risk factor for coronary artery abnormalities in Kawasaki disease: a meta-analysis.

Incomplete Kawasaki disease (KD) comprises a large proportion of the total number of cases. Although it has the potential of delaying diagnosis, it is not conclusive whether an incomplete presentation is a risk factor for coronary artery abnormalities (CAAs). We performed a meta-analysis to establish the risk of CAA in 20 studies including 4,504 cases and 32,519 controls, and the risk of giant aneurysm in two studies including 5,390 cases and 37,648 controls. The pooled results indicated that incomplete KD was associated with an increased risk of CAA [odds ratio (OR) = 1.447, 95 % confidence interval (CI) = 1.158-1.808, p = 0.001]. Subgroup analyses demonstrated higher associations in patients younger than 12 months (OR = 2.023, 95 % CI = 1.252-3.271, p = 0.004), Asians and Indians (OR = 1.57, 95 % CI = 1.234-1.999, p < 0.001 and OR = 7.088, 95 % CI = 1.640-30.631, p = 0.009, respectively). Subgroup analysis according to the period of patient enrollment before and after 2004 showed increased association of incomplete KD with CAA only among studies with patients enrolled after 2004 (OR = 1.969, 95 % CI = 1.240-3.127, p = 0.004). In conclusion, incomplete KD seems to be associated with an increased risk of CAA, and this is more prominent in patients younger than 12 months, Asians and Indians.

Risk factors for Kawasaki disease-associated coronary abnormalities differ depending on age.

INTRODUCTION: The clinical manifestations and risk factors for developing coronary artery abnormalities (CAA) in Kawasaki disease (KD) might differ depending on age. MATERIALS AND METHODS: From January 2001 to July 2007, 161 patients with an age younger than 1 year (younger group) and 60 patients with an age older than 5 years (older group) were diagnosed with KD at the Korea University Medical Center. Their medical records were reviewed retrospectively and the two groups were compared in terms of a number of variables commonly associated with the development of CAA, including clinical manifestations and laboratory findings. RESULTS: While the overall incidence of KD-associated CAA in our hospital was 6.7%, CAA developed in 20 (12.4%) of the younger group and ten (16.7%) of the older group, respectively. The CAA (+) cases of the younger group had a longer duration of total fever (9.1 +/- 3.3 vs 6.3 +/- 1.9 days, p = 0.002) and showed fewer diagnostic symptoms (3.0 +/- 1.2 vs 4.3 +/- 1.1, p < 0.001) than the CAA (-) cases. The CAA (+) cases of the older group had a longer duration of total fever (14.1 +/- 10.4 vs 6.5 +/- 1.9 days, p = 0.045), especially with respect to post-intravenous gamma globulin (IVGG) fever (7.9 +/- 9.6 vs 1.1 +/- 0.8 days, p = 0.052), and had higher total white blood cell counts, erythrocyte sedimentation rates, C-reactive protein levels, total bilirubin levels, and Harada scores and lower serum albumin and sodium levels than the CAA (-) cases. Multivariable logistic regression analysis revealed that the factors that were associated significantly with the development of CAA were the number of total symptoms (OR = 0.494, 95% confidence interval (CI) = 0.281-0.871, p = 0.015) in the younger group and the duration of post-IVGG fever (OR = 1.958, 95% CI = 1.098-3.492, p = 0.023) and the Harada score (OR = 3.455, 95% CI = 1.012-11.796, p = 0.048) in the older group. CONCLUSION: Incomplete clinical manifestations in the younger group and IVGG nonresponsiveness in the older group are associated with the development of KD-associated CAA. These age-specific characteristics could aid the customization of the diagnostic and therapeutic strategies of KD, thereby helping to improve the outcome of this disease.

Incomplete Kawasaki disease in patients younger than 1 year of age: a possible inherent risk factor.

Kawasaki disease (KD) patients younger than 1 year of age are at especially high risk of developing coronary artery abnormalities (CAA). To define the clinical characteristics of this group, as well as the risk factors predisposing them to CAA, we reviewed the medical records of 136 KD patients younger than 1 year of age who were treated at the Korea University Medical Center from January 2001 to July 2006. Of these patients, 16 developed CAA (11.8%). The CAA(+) group had a longer duration of total fever than the CAA(-) group (9.1+/-3.7 days vs. 6.3+/-2.0 days, p=0.011), but did not differ in the duration of pre- and post-intravenous gamma-globulin (IVGG) fever. The CAA(+) group had fewer diagnostic symptoms than the CAA(-) group (2.7+/-1.1 vs. 4.3+/-1.2, p<0.001). Of the hematological findings, the CAA(+) group only differed from the CAA(-) group in having significantly higher total white blood cell (19.2+/-6.0 vs. 14.7+/-4.7 K/mm(3), p=0.007) and platelet (462.9+/-101.0 vs. 383.6+/-121.1 K/mm(3), p=0.014) levels. Multivariable logistic regression analysis showed that the only factors which were significantly associated with the development of CAA were the total number of symptoms (OR=0.493, 95% CI=0.293-0.829, p=0.007) and the duration of total fever (OR=1.405, 95% CI=1.092-1.808, p=0.008). Conclusively, incomplete clinical manifestations and a longer duration of total fever are significantly associated with the development of CAA in KD patients younger than 1 year of age. Therefore, these patients should be monitored for incomplete KD, especially if unexplained fever continues, and treatment to shorten the duration of total fever should be initiated.

Aorta to right atrial fistula following transcatheter closure of an atrial septal defect.

The percutaneous transcatheter closure of atrial septal defects (ASDs) has become an acceptable alternative to surgical repair. The investigators present a case of aorta-to-right atrial fistula after the closure of an ASD using the Amplatzer septal occluder (ASO). After the surgical removal of the ASO, the ASD patch closure, and the repair of the fistula, the patient eventually recovered.