Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial.

Background: Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities.

Methods: We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016.

A pediatric case of anaphylactic shock induced by tipepidine hibenzate (Asverin).

Tipepidine hibenzate (Asverin) is commonly used as an antitussive drug for acute and chronic cough in various age groups and is generally safe and well-tolerated. However, we experienced a case of tipepidine hibenzate-induced anaphylactic shock in a 1-year-old boy. After ingesting cold medication including tipepidine hibenzate, the patient presented with generalized erythema and urticaria, swollen face, coughing, wheezing and vomiting, together with hypotension and a decreased level of consciousness.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events.

Importance: Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA).

Objective: To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA.

Design, Setting, And Participants: This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011.

Comprehensive pathogen detection associated with four recurrent episodes of Kawasaki disease in a patient during a single year using next-generation sequencing.

Introduction: Kawasaki disease (KD) is the most common multisystem vasculitis in childhood. Pathogens can be associated with the onset of KD. However, a lack of consistency prevails among reports about this disease.

Study protocol for a phase III multicentre, randomised, open-label, blinded-end point trial to evaluate the efficacy and safety of immunoglobulin plus cyclosporin A in patients with severe Kawasaki disease (KAICA Trial).

Introduction: Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca(2+)/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD.

Disrupted glutamate-glutamine cycle in acute encephalopathy with biphasic seizures and late reduced diffusion.

Introduction: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of AESD; excitotoxicity is postulated to be the pathogenesis based on elevated glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx, or whether MR spectroscopy is useful for an early diagnosis.

[Epidemiological study of respiratory viruses detected in patients under two years old who required admission because of lower respiratory disease].

The etiologic role of recently identified respiratory viruses for lower respiratory tract disease (LRTD) remains unclear in Japan. The purpose of this study was to investigate the prevalence of respiratory viruses in young children with LRTD. We prospectively examined 721 children who were under two years old and admitted to a single medical center in Japan with LRTD between April 2007 and March 2012.

Pneumothorax in patients with severe combined immunodeficiency.

Background: Most infants with pneumothorax have underlying conditions. Pneumocystis jirovecii pneumonia (PCP) frequently occurs in patients with severe combined immunodeficiency (SCID). The aim of this study was to determine clinical features of PCP-associated pneumothorax in SCID patients.

Characteristic systemic cytokine responses in children with human bocavirus-positive lower respiratory tract infection.

To investigate systemic cytokine responses in human bocavirus (HBoV)-associated lower respiratory tract infection, serum cytokine profiles were analyzed in HBoV positive-children (n=14) using multiplex immunoassay. Concentrations of TNF-a, IL-2, IL-5 and IL-8 on admission were significantly different from those of respiratory syncytial virus-positive children (n=28). This unique cytokine response might partly explain some characteristic clinical features of HBoV-associated respiratory infection.

WU polyomavirus detected in respiratory tract specimens from young children in Japan.

Polyomaviruses (PyV) WU and KI are reportedly associated with respiratory tract disease (RTD) worldwide but their incidence is unclear in Japan. In a 2 year prospective study, WU/KIPyV were detected in 48 (13.9%) and in five (1.

Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease.

Background: Kawasaki disease (KD) is an acute systemic vasculitis occurring in medium-sized arteries, especially coronary arteries. Patients with KD who fail to respond to standard therapy with intravenous immunoglobulin (IVIG) face a higher risk of developing coronary artery lesions. Cyclosporin A (CsA) is one treatment option for IVIG-resistant KD.

A genome-wide association study identifies three new risk loci for Kawasaki disease.

We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.

[A case of corpus callosum splenium encephalopathy and 2009 influenza A/H1N1].

Encephalopathy with reversible lesion of the corpus callosum splenium has a favorable prognosis, but that in 2009 influenza A/H1N1 is unknown. We report a case of clinically mild encephalopathy with a reversible lesion of the corpus callosum splenium in which 2009 influenza A/H1N1 virus was confirmed by laboratory tests. A 15-year-old Japanese girl seen at the emergency unit for loss of consciousness 18 hours after fever onset had been diagnosed with influenza A, and administered zanamivir.

Cyclosporin A treatment for Kawasaki disease refractory to initial and additional intravenous immunoglobulin.

Background: There are still no definite treatments for refractory Kawasaki disease (KD). In this pilot study, we evaluated the use of cyclosporin A (CyA) treatment in patients with refractory KD.

Methods: We prospectively collected clinical data of CyA treatment (4-8 mg/kg/d, oral administration) for refractory KD patients using the same protocol among several hospitals.

Increased production of vascular endothelial growth factor-d and lymphangiogenesis in acute Kawasaki disease.

Background: Kawasaki disease (KD) is characterized by systemic vasculitis with tissue edema. During the healing process of inflammation, lymphangiogenesis is essential for reducing tissue edema. One potential responsible candidate for the induction of lymphangiogenesis in the healing process of acute KD is vascular endothelial growth factor-D (VEGF-D).

Early induction of interleukin-5 and peripheral eosinophilia in acute pneumonia in Japanese children infected by pandemic 2009 influenza A in the Tokyo area.

A novel influenza A (2009 H1N1) virus has led to a worldwide pandemic. A significant number of patients with pneumonia have been reported, although its pathogenesis remains to be elucidated. To determine its pathogenesis, we evaluated serum interleukin (IL)-5 and peripheral eosinophil counts in patients with acute pneumonia caused by the 2009 H1N1 virus.

Survey of pediatric ward hospitalization due to respiratory syncytial virus infection after the introduction of palivizumab to high-risk infants in Japan.

Background: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization during the winter among infants and young children. In 2002 palivizumab was introduced to high-risk infants for RSV hospitalization in Japan. It is important to characterize the hospitalized children due to RSV infection after the introduction of palivizumab.

Common variants in CASP3 confer susceptibility to Kawasaki disease.

Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small- and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry.

Distinctive clinical features of human bocavirus in children younger than 2 years.

Background And Objective: Clinical characteristics of human bocavirus (HBoV) infection have been studied worldwide, but their importance of those characteristics remains unknown. We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection (LRTI).

Methods And Results: During April 2007-July 2009, for 402 hospitalized children younger than 2 years with LRTI, we prospectively examined virus genomes in nasopharyngeal swabs for HBoV, respiratory syncytial virus (RSV), rhinovirus, metapneumovirus, parainfluenzavirus, and adenovirus.

Prevalence of adult patients with congenital heart disease in Japan.

Background: Today most patients with congenital heart disease (CHD) can be expected to survive into adulthood. Reports regarding the number of adults with CHD in Japan are scarce. Our study aims to define the number of these adults.

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.

[Treatment for Kawasaki disease--perspective].

In acute management for Kawasaki disease, recent studies are focused on treatment for patients who failed to respond to intravenous gamma globulin (IVGG) and high dose-aspirin. The addition of corticosteroids to IVGG and the use of TNF-alpha blockade are now under discussion. In long-term management, therapeutic angiogenesis is now applied for adult patients with ischemic hind limb or heart.

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms.

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children.

Impairment of angiogenic activity in the serum from patients with coronary aneurysms due to Kawasaki disease.

Background: The inflammatory mediators play an important role in the progression of coronary vasculitis in Kawasaki disease (KD), but effects of KD serum including inflammatory mediators on endothelial cells remain unknown. We hypothesized that serum activity to stimulate in vitro human umbilical vein endothelial cells (HUVEC) tube formation might be impaired in KD.

Methods And Results: Serum from patients with coronary aneurysms was less active in stimulating HUVEC tube formation than serum from patients without coronary aneurysms or febrile controls.