A New Z Score Curve of the Coronary Arterial Internal Diameter Using the Lambda-Mu-Sigma Method in a Pediatric Population.

BACKGROUND: Several coronary artery Z score models have been developed. However, a Z score model derived by the lambda-mu-sigma (LMS) method has not been established. METHODS: Echocardiographic measurements of the proximal right coronary artery, left main coronary artery, proximal left anterior descending coronary artery, and proximal left circumflex artery were prospectively collected in 3,851 healthy children ≤18 years of age and divided into developmental and validation data sets. In the developmental data set, smooth curves were fitted for each coronary artery using linear, logarithmic, square-root, and LMS methods for both sexes. The relative goodness of fit of these models was compared using the Bayesian information criterion. The best-fitting model was tested for reproducibility using the validation data set. The goodness of fit of the selected model was visually compared with that of the previously reported regression models using a Q-Q plot. RESULTS: Because the internal diameter of each coronary artery was not similar between sexes, sex-specific Z score models were developed. The LMS model with body surface area as the independent variable showed the best goodness of fit; therefore, the internal diameter of each coronary artery was transformed into a sex-specific Z score on the basis of body surface area using the LMS method. In the validation data set, a Q-Q plot of each model indicated that the distribution of Z scores in the LMS models was closer to the normal distribution compared with previously reported regression models. Finally, the final models for each coronary artery in both sexes were developed using the developmental and validation data sets. A Microsoft Excel-based Z score calculator was also created, which is freely available online (http://raise.umin.jp/zsp/calculator/). CONCLUSIONS: Novel LMS models with which to estimate the sex-specific Z score of each internal coronary artery diameter were generated and validated using a large pediatric population.

Clinical analysis of the pediatric inpatients with lower respiratory tract infection due to human metapneumovirus.

Human metapneumovirus (hMPV) is known as one of popular agents of acute respiratory infection in children. We reviewed the patients' background, result of initial blood test, bacterial culture, chest X-ray and clinical features of hospitalized children with lower respiratory tract infections caused by hMPV from March 2014 to February 2015 and compared them with the infections due to respiratory syncytial virus (RSV) and other causative agents. Of 419 patients tested by rapid virus antigen tests, 35 were positive for hMPV, 145 were positive for RSV, and 239 were negative for both viruses. Most of hMPV infections occurred between March and June, and 72% of households of hMPV-positive children got sick. hMPV-positive children did not have any specific symptoms such as wheezing in RSV- positive children. However, many of them were admitted due to prolonged high fever and/or ill appearance despite of no respiratory distress. Although it is said that hMPV-positive children admitted to hospitals tend to have pneumonia, the ratio of children'with pneumonia in this study was less than 60%.

Acute scrotum in Kawasaki disease: two case reports and a literature review.

Acute scrotum is a rare complication of acute Kawasaki disease (KD), less well recognized than other disease manifestations. We describe the cases of two patients, aged 59 months and 19 months, with hydrocele testis in the acute phase of KD. Scrotal ultrasound and trans-illumination were used in the diagnosis of hydrocele testis. One patient underwent eventual surgical intervention. We reviewed the literature for a better understanding of the pathogenesis of scrotal symptoms in acute KD and investigated the clinical importance of hydrocele testis. Careful further clinical observation may elucidate the true incidence of this extracardiac symptoms, thereby clarifying the diagnostic value of this possible complication in acute KD.

Myocarditis in a pediatric case of pandemic 2009H1N1 influenza.

We report a 6-year-old boy with no major disease history or allergic conditions initially presented with pneumonia, progressed to acute respiratory distress syndrome and acute myocarditis caused by pandemic 2009H1N1 influenza diagnosed with RT-PCR testing, successfully managed with mechanical ventilation and percutaneous cardiopulmonary support system. Marked transient elevation of IgE in acute phase of the disease and the subsequent diagnosis of atopic asthma in our patient suggested a possible role of an underlying allergic condition in the clinicopathological process. Critically ill 2009H1N1-infected patient with acute respiratory failure should carefully be physiologically monitored together with serial assessment of biomarkers aiming at a favorable cardiac outcome by giving the timely diagnosis and intervention.

Intravenous immune globulin plus corticosteroids in refractory Kawasaki disease.

BACKGROUND: The aim of the present study was to investigate the efficacy of i.v. immune globulin (IVIG) therapy combined with corticosteroids for additional treatment of acute Kawasaki disease (KD) unresponsive to initial IVIG treatment. METHODS: In 50 prospective KD patients, six IVIG non-responders without clinical improvement within 24-48 h after completion of initial IVIG, received 2 g/kg IVIG concurrently with 2 mg/kg i.v. prednisolone sodium succinate (PSL) until normalization of C-reactive protein level. Treatment was then changed to oral PSL, which was tapered over time. Clinical and coronary artery lesion (CAL) outcomes were compared with those of 13 IVIG non-responders who received additional heterogeneous therapies in 125 retrospective KD patients. In addition, the scoring system of Kobayashi et al. for prediction of non-responsiveness to initial IVIG treatment was retrospectively verified in 175 KD subjects, consisting of 50 prospective and 125 retrospective patients in order to evaluate the efficacy of the re-treatment regimen. RESULTS: Incidence of CAL in the study patients was lower than in the control patients, although differences were not significant both in the acute stage (within 1 month: 1/6, 16.7% vs 7/13, 53.8%; P= 0.177) and in the convalescent stage (after 1 month: 0/6, 0.0% vs 4/13, 30.8%; P= 0.255). According to the non-responder prediction system, the scores of six study and 13 control patients before initial IVIG treatment were similar (7.2 ± 1.9 vs 5.3 ± 3.1; P= 0.200). No serious adverse effects related to each treatment were noted in patients of either group. CONCLUSIONS: Additional IVIG combined with concurrent PSL appears to be safe and worth evaluation for the treatment of acute KD unresponsive to initial IVIG treatment.

Elevated granulocyte colony-stimulating factor levels predict treatment failure in patients with Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis in young children, frequently associated with coronary artery aneurysms. The intravenous infusion of high-dose IgG (IVIG) effectively reduces the systemic inflammation and the incidence of coronary artery lesions, although the precise underlying mechanisms are unknown. OBJECTIVE: We performed expression profiling of whole blood cells to investigate the mechanisms underlying the effect of IVIG and to identify biomarkers associated with unresponsiveness to IVIG. METHODS: We compared the transcript abundance among pre-IVIG and post-IVIG patients and febrile control patients. Then we analyzed the mRNA levels and the protein levels among the different cohort of patients with KD who were either responsive or nonresponsive to the initial IVIG. RESULTS: A total of 298 transcripts were overrepresented or underrepresented in the pre-IVIG patients compared with post-IVIG patients and febrile controls, of which 15 transcripts were differentially expressed in nonresponsive patients with KD compared with responsive patients before IVIG. The protein levels of polycythemia rubra vera 1, which was one of the most variably expressed transcripts in pre-IVIG patients, and the serum granulocyte colony-stimulating factor levels were significantly higher in nonresponsive patients than in responsive patients before the initial IVIG administration. CONCLUSION: These findings suggest that the variable gene expression profiles were correlated to the responses of patients with KD to IVIG administration. Polycythemia rubra vera 1 and granulocyte colony-stimulating factor levels may be good biomarkers for predicting response to IVIG in patients with KD.

Gene expression profiling of the effect of high-dose intravenous Ig in patients with Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis of infants and young children, preferentially affecting the coronary arteries. Intravenous infusion of high dose Ig (IVIG) effectively reduces systemic inflammation and prevents coronary artery lesions in KD. To investigate the mechanisms underlying the therapeutic effects of IVIG, we examined gene expression profiles of PBMC and purified monocytes obtained from acute patients before and after IVIG therapy. The results suggest that IVIG suppresses activated monocytes and macrophages by altering various functional aspects of the genes of KD patients. Among the 18 commonly decreased transcripts in both PBMC and purified monocytes, we selected six genes, FCGR1A, FCGR3A, CCR2, ADM, S100A9, and S100A12, and confirmed the microarray results by real-time RT-PCR. Moreover, the expressions of FcgammaRI and FcgammaRIII on monocytes were reduced after IVIG. Plasma S100A8/A9 heterocomplex, but not S100A9, levels were elevated in patients with acute KD compared with those in febrile controls. Furthermore, S100A8/A9 was rapidly down-regulated in response to IVIG therapy. Persistent elevation of S100A8/A9 after IVIG was found in patients who later developed coronary aneurysms. These results indicate that the effects of IVIG in KD may be mediated by suppression of an array of immune activation genes in monocytes, including those activating FcgammaRs and the S100A8/A9 heterocomplex.

Efficacy of intravenous immune globulin therapy combined with dexamethasone for the initial treatment of acute Kawasaki disease.

UNLABELLED: We studied the effects of a new regimen consisting of intravenous immune globulin (IVIG) combined with dexamethasone (DEX) on clinical outcome and serum levels of vascular endothelial growth factor (VEGF) in the initial treatment of Kawasaki disease (KD). A total of 46 KD patients received 0.3 mg/kg per day DEX plus heparin i.v. for 3 consecutive days, together with 2 g/kg IVIG over 4 to 5 days (DEX group). Low-dose acetylsalicylic acid was started after completion of DEX therapy. The control group consisted of 46 KD patients retrospectively treated earlier with 2 g/kg IVIG over 4 to 5 days plus higher dose acetylsalicylic acid (CONTROL group). No serious adverse effect was noted in either group. There were no differences in baseline and post-treatment laboratory data except for C-reactive protein between the groups. Post-treatment C-reactive protein in the DEX group (median 0.9 mg/dl, range 0.0 to 24.7 mg/dl) was lower than that (1.2 mg/dl, range 0.2 to 19.5 mg/dl) in the CONTROL group ( P=0.033 by Mann-Whitney U test). In addition, the mean duration of fever after the first IVIG infusion was 2.2 days (median 1 day, range 1 to 12 days) in the DEX group and 2.8 days (2 days, 1 to 16 days) in the CONTROL group ( P=0.015 by Mann-Whitney U test). The new regimen did not reduce VEGF levels. Two patients in each group developed small- or medium-sized coronary artery aneurysms. CONCLUSION: Although this regimen did not affect coronary outcome, intravenous immune globulin therapy combined with dexamethasone for the initial treatment of Kawasaki disease was safe and may accelerate the resolution of systemic inflammation.

Influence of early repair of tetralogy of fallot without an outflow patch on late arrhythmias and sudden death: a 27-year follow-up study following a uniform surgical approach.

Pulmonary regurgitation and older age at the time of repair may have a large impact late after repair on subsequent mortality of patients with tetralogy of Fallot. We aimed to identify whether age at repair, and preservation of the pulmonary valve, had a favorable influence on morbidity and mortality. We also analyzed risk factors for late death subsequent to surgical repair. We identified 167 patients who, between 1965 and 1975, and at a mean age of 6 years, underwent total repair of tetralogy of Fallot by a single surgical team without use of an outflow patch. All patients were known to have survived for at least 30 days after repair, and late mortality was identified though the use of hospital records, interviews, and death certificates. The 29-year actuarial survival rate was 86%, with 24 late deaths. Of these deaths, seven occurred suddenly (4.2%). Morbidity was analyzed in 99 of the patients by means of a written questionnaire and telephone interview. It proved possible to analyze ventricular and valvar function in 50 of the patients. Survivors experienced no re-intervention, and 89% of them were in class I of the grading system of the New York Heart Association. We found evidence of 3 episodes of sustained ventricular tachycardia (3.0%), and two episodes of atrial tachycardia (2.0%). Of the 50 patients in whom serial examinations were available, 18 had pulmonary regurgitation of moderate degree or greater, and none had more than moderate tricuspid regurgitation, with a mean QRS duration of 148 ms and an ejection fraction for the left ventricle of 50%. Older age at repair (p = 0.03), and longer periods of cardiac arrest during repair (p = 0.02), were associated with late mortality. Although the mortality was similar to that observed in previous reports, our operative method might have a better effect in terms of late morbidity.

Peripheral blood eosinophilia and eosinophil accumulation in coronary microvessels in acute Kawasaki disease.

BACKGROUND: Early stage Kawasaki disease (KD) histopathology includes perivasculitis and vasculitis of the microvessels. The lesions then extend to larger vessels. Therefore the analysis of microvessel lesions is important to better understand the initial pathogenesis of KD vasculitis. METHODS AND RESULTS: We studied epicardial microvessel lesions (<50 microm) and aneurysm lesions of paraffin-embedded cardiac tissues from 4 Japanese patients who died 7 to 22 days after KD onset. The cellular composition in the microvessel lesions was different from that in coronary aneurysm lesions; eosinophils were preferentially accumulated in the microvessel lesions. The average population of eosinophils was 16% of total infiltrated cells in the microvessel lesions, whereas it was 3% in the intima of aneurysm walls. We examined peripheral blood eosinophil cell counts in 95 KD patients and 95 febrile age-matched controls. Baseline eosinophil cell counts in KD patients were higher than those in febrile control patients (361 +/- 441 65 +/- 133; < 0.0001). Eosinophilia (>350 cells/microl) before therapy was documented in 36% of KD patients, but in only 4% of febrile controls ( < 0.0001). Sixty-six KD patients (69%) developed eosinophilia within 2 weeks of illness. CONCLUSIONS: Because the numbers of circulating eosinophils in the body are tightly regulated, eosinophil accumulation in blood or tissues may reflect the host's immune response against KD related antigen(s).