ABSTRACT:The aim of our study was to evaluate the efficacy of infliximab for the treatment of patients with refractory Kawasaki disease (KD) and investigate the dynamic changes of cytokines during infliximab treatment. We have performed a study of cytokine and proinflammatory molecule levels in 43 KD patients including 18 responders to IVIG, 14 nonresponders, and 11 patients treated with infliximab. We determined serum levels of soluble TNF receptor I (sTNFR I) and IL-6, as well as VEGF, damage associated molecular pattern (DAMP) molecules; myeloid-related protein (MRP)8/MRP14 and S100A12 sequentially. In eight patients, fever subsided immediately upon infliximab treatment. Four patients, who started infliximab after 12 d of illness, developed coronary artery lesions. Each of the cytokines was elevated before infliximab treatment in all patients. Although serum levels of proinflammatory cytokines decreased dramatically after infliximab treatment, DAMP molecules and VEGF and markers of local tissue damage were not suppressed. In contrast, in IVIG responders all cytokines decreased markedly after IVIG treatment. We show that infliximab is one of the adoptive therapies in refractory KD patients. Different behaviors of proinflammatory cytokines and DAMP molecules and VEGF after infliximab treatment suggest that infliximab is effective for suppression of cytokinemediated inflammation, but could not completely block local vasculitis. (Pediatr Res 65: 696-701, 2009) K awasaki disease (KD) is the most common systemic vasculitis syndrome primarily affecting small and medium-sized arteries, particularly the coronary artery. Although timely treatment with high-dose i.v. immune globulin (IVIG) is now accepted as reducing the incidence of coronary artery lesions (CAL), approximately 15% of the patients do not respond to IVIG treatment and have persistent fever as a manifestation of ongoing inflammation. These patients are at highest risk for development of CAL (1). The current practice for patients with KD and persistent or recrudescent fever after IVIG is to institute additional therapies, which may include one or more repeat doses of IVIG, high-dose pulse methylprednisoline, cyclophosphamide, methotrexate, ulinastatin, cyclosporine A (CyA), or plasmapheresis (2,3). Recently, potential new therapeutic approaches with infliximab (Remicade), a chimeric mouse-human MAb against tumor necrosis factor (TNF)-␣, have been reported in refractory KD patients (4).During the acute phase of KD, serum levels of proinflammatory cytokines such as TNF-␣ are elevated (5). In experimental studies of this syndrome, characterized by vasculitis resulting in coronary, as well as extracoronary, aneurysms, and stenosis, the attenuation of cytokine responses, especially IL-6, after infusions of IVIG may play an integral role in the rapid resolution of most of the symptoms in children with KD (6). In addition to these proinflammatory cytokines, VEGF, and markers of local inflammation of the family of damageassociated molecular pattern molecules (DAMP...

ardiac resynchronization therapy (CRT) has become the standard of care for the treatment of heart failure in adults with decreased ventricular function and conduction delay who remain symptomatic despite optimal medical therapy. Although there are no prospective and randomized trial data, a retrospective series show that CRT is similarly effective for managing dyssynchronyassociated heart failure in children. [1][2][3] The heterogeneity of anatomical and functional substrates in which CRT shows efficacy calls for further studies defining the usefulness of CRT in children. 4 Children with systolic dysfunction secondary to cardiomyopathy have mechanical dyssynchrony, unrelated to electrical dyssynchrony, and are potential candidates for CRT. 5 Left ventricular non-compaction (LVNC) is a unique form of cardiomyopathy, characterized by numerous prominent left ventricular (LV) trabeculations and deep intertrabecular recesses. 6,7 In patients with LVNC, mechanical dyssynchrony between non-compacted and compacted myocardium contribute to global LV dysfunction. 8 Tissue Doppler velocities are significantly reduced in patients with LVNC, and help identify children with LVNC who are at risk of adverse clinical outcomes, including death, and need cardiac transplantation. 9 Successful CRT in adults with isolated LVNC has been reported recently, 10 however, the efficacy of CRT for pediatric patients with LVNC has not been reported. The use of CRT in children has gained a great deal of attention, especially in Japan where there is little chance of heart transplantation.Here we report the successful use of CRT in a 3-year-old girl with intractable heart failure caused by isolated LVNC with narrow QRS complex. Case ReportThe patient was diagnosed with heart failure caused by isolated LVNC at 3 months of age. LVNC was diagnosed by echocardiographic criteria including: (1) presence of prominent or numerous LV trabeculations, predominantly in the distal portion (apex) of the left ventricle; (2) a 2-layered structure of the myocardium with an increased non-compacted to compacted ratio (>1.4); and (3) Cardiac resynchronization therapy (CRT) is a new method of treatment for refractory heart failure. However, for children, its indication, efficacy, and long-term prognosis remain unclear. This study describes the use of CRT for a 3-year-old girl with intractable heart failure caused by isolated left ventricular non-compaction (LVNC) with narrow QRS complex. Echocardiography showed diffuse hypokinetic left ventricular (LV) wall motion (ejection fraction =29.3%) with dyssynchrony between the apex, posterior and lateral walls, where numerous prominent trabeculations existed, and severe mitral regurgitation. Biventricular resynchronization using epicardial pacing leads was performed under general anesthesia. Pacing sites for optimal synchronization in the ventricular walls where chosen using tissue Doppler imaging, and AV delay was adjusted to achieve maximal systolic blood pressure and maximal cardiac output. Over a follow-up period of 2...

Aspergillus is a rare cause of endocarditis. [1][2][3] The prognosis for AE is poor, with only a third of reported patients surviving the acute episode, in part because of immunocompromise, delay in diagnosis, systemic dissemination, and multiple embolic episodes. 1 Only 5 cases of infective endocarditis caused by the species A terreus have been reported. 1 To the best of our knowledge, this is the first reported case of prosthetic valve endocarditis caused by A terreus.Early and accurate diagnosis is the most critical step in the treatment of AE and requires a high index of suspicion. The occurrence of peripheral emboli is the most common presenting feature and in a culture-negative infective endocarditis setting should raise the suspicion of AE. 1,3,4 Echocardiography reveals large vegetations on the valve(s), but blood cultures are almost always negative. [1][2][3] Ultimately, the diagnosis of Aspergillus requires histology and tissue culture confirmation from vegetations or emboli. Determining species is critical, because A terreus species is almost always resistant to amphotericin B, and voriconazole is the antifungal drug of choice, often in combination with an echinocandin. 1 Mortality is extremely high among those who receive antifungal therapy alone. [1][2][3] Successful treatment of AE requires combination of appropriate antifungal therapy and radical surgical debridement. Despite adequate combined antifungal and radical surgical treatment, recurrence after AE as high as 40% has been reported, adding to the dismal prognosis. [1][2][3] As a consequence, we now recommend antifungal suppression for life.

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Background: The function of the right ventricle (RV) is difficult to evaluate by 2-dimensional echocardiography because it has more complex geometry and function than the left ventricle. The aim of our study was to evaluate right ventricular (RV) systolic function in the neonate using newly developed single beat 3-dimensional echocardiography (sb3DE). Method and Results: We enrolled 15 healthy or premature neonates (0 to 53 days after birth). We scanned one beat full volume using Siemens ACUSON SC2000 (Siemens AG) echocardiography with 4Z1c Full Volume transducer without ECG-gating. RV end-diastolic (RVEDV) and systolic volume (RVESV) were computed with special software dedicated to analysis for RV volume. RV ejection fraction (RVEF) and RV stroke volume (3D-RVSV) were also calculated. While RV stroke volume was also determined from the recordings of ejection blood flow velocity and diameter at the level of the pulmonary orifice in the RV outflow tract (Doppler-RVSV). Tricuspid annular plane systolic excursion (TAPSE) was also measured by 2D echocardiography. Results: It took 15 minutes for total acquisition of echo data including one beat full volume and 4 - 5 minutes to compute for RVEDV and RVESV. Full volume data were obtained successfully in all cases with average volume rate of 60 volumes / sec. RVEDV ranged from 5.1 to 10.7 ml (average 7.5 ml), RVESV ranged from 2.3 to 5.8 ml (average 3.9 ml). There was a good correlation between 3D-RVSV and Doppler-RVSV (r = 0.77). Bland-Altman plots revealed that 3D-RVSV was underestimated by an average of 1.78 ml compared to Doppler-RVSV. TAPSE positively correlated with 3D-RVEF (r = 0.58, P = 0.038). Conclusions: Newly developed sb3DE enables us to perform 3-dimensional acquisition of RV volume without ECG-gating even in neonate. However, 3D-RVSV currently tends to be underestimated in the neonatal measurement.