Language：English   Publisher：The Japanese Circulation Society  

<p><b><i>Background:</i></b>The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.</p><p><b><i>Methods and Results:</i></b>ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria.</p><p><b><i>Conclusions:</i></b>Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.</p>

DOI： 10.1253/circj.CJ-21-0376

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Type I interferonopathies are a recently established subgroup of autoinflammatory diseases caused by mutations in genes associated with proteasome degradation or cytoplasmic RNA- and DNA-sensing pathways. OBJECTIVE: This study aimed to unveil the molecular pathogenesis of a patient with novel type I interferonopathy, for which no known genetic mutations have been identified. METHODS: We performed the whole-exome sequencing of a 1-month-old boy with novel type I interferonopathy. We also investigated proteasome activities using patient-derived B lymphoblastoid cell lines (LCLs) and normal LCLs transduced with the mutant gene. RESULTS: Whole-exome sequencing identified a de novo proteasome 20S subunit beta 9 (PSMB9) p.G156D mutation in the patient who developed fever, a chilblain-like skin rash, myositis, and severe pulmonary hypertension due to the hyperactivation of IFN-α. Patient-derived LCLs revealed reduced proteasome activities, and exogenous transduction of mutant PSMB9 p.G156D into normal LCLs significantly suppressed proteasome activities, and the endogenous PSMB9 protein was lost along with the reduction of other immunoproteasome subunits, PSMB8 and PSMB10 proteins. He responded to the administration of a Janus kinase inhibitor, tofacitinib, and he was successfully withdrawn from venoarterial extracorporeal membranous oxygenation. At age 7 months, he received an unrelated cord blood transplantation. At 2 years posttransplantation, he no longer required tofacitinib and experienced no disease recurrence. CONCLUSIONS: We present the case of a patient with a novel type I interferonopathy caused by a de novo PSMB9 p.G156D mutation that suppressed the wild-type PSMB9 protein expression. Janus kinase inhibitor and stem cell transplantation could be curative therapies in patients with severe interferonopathies.

DOI： 10.1016/j.jaci.2021.03.010

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: A gain-of-function mutation in germline ABL1 causes a syndrome including congenital heart defects. However, the molecular mechanisms of this syndrome remain unknown. In this study, we found a novel ABL1 mutation in a Japanese family with ventricular septal defect, finger contracture, skin abnormalities and failure to thrive, and the molecular mechanisms of these phenotypes were investigated. METHODS AND RESULTS: Whole-exome sequencing on several family members revealed a novel mutation (c.1522A > C, p.I508L) in the tyrosine kinase domain of ABL1, and complete co-segregation with clinical presentations was confirmed in all members. Wild-type and mutant ABL1 were transfected into human embryonic kidney 293 cells for functional analysis. Western blotting confirmed that tyrosine phosphorylation in STAT5, a substrate of ABL1, was enhanced, and the novel mutation was proved to be a gain-of-function mutation. Since this novel mutation in ABL1 enhances tyrosine kinase activity, phosphorylated proteome analysis was used to elucidate the molecular pathology. The proteome analysis showed that phosphorylation in proteins such as UFD1, AXIN1, ATRX, which may be involved in the phenotypes, was enhanced in the mutant group. CONCLUSIONS: The onset of congenital heart defects associated with this syndrome appears to involve a mechanism caused by UFD1 common to 22q.11.2 deletion syndrome. On the other hand, AXIN1 and ATRX may be important in elucidating the mechanisms of other phenotypes, such as finger contracture and failure to thrive. Verification of these hypotheses would lead to further understanding of the pathophysiology and the development of treatment methods.

DOI： 10.1016/j.ijcard.2020.10.032

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ped.14326

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Language：English   Publishing type：Research paper (scientific journal)  

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.

DOI： 10.1016/j.jcyt.2020.01.009

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study was to investigate whether a dual endothelin receptor antagonist bosentan modulates the kinetics of bone marrow-derived stem cells in inhibiting the development of pulmonary hypertension. Bone marrow chimeric mice, transplanted with enhanced green fluorescent protein (eGFP)-positive bone marrow mononuclear cells, were exposed to hypobaric hypoxia or kept in the ambient air, and were daily treated with bosentan sodium salt or saline for 21 days. After the treatment period, right ventricular pressure was measured and pulmonary vascular morphometry was conducted. Incorporation of bone marrow-derived cells was analyzed by immunohistochemistry. Gene expression and protein level in the lung tissue were evaluated by quantitative real-time PCR and western blotting, respectively. The results showed that, in hypoxic mice, right ventricular pressure and the percentage of muscularized vessel were increased and pulmonary vascular density was decreased, each of which was reversed by bosentan. Bone marrow-derived endothelial cells and macrophages in lungs were increased by hypoxia. Bosentan promoted bone marrow-derived endothelial cell incorporation but inhibited macrophage infiltration into lungs. Quantitative real-time PCR analysis revealed that interleukin 6, stromal cell-derived factor-1, and monocyte chemoattractant protein-1 were upregulated by hypoxia, in which interleukin 6 and monocyte chemoattractant protein-1 were downregulated and stromal cell-derived factor-1 was upregulated by bosentan. Protein level of endothelial nitric oxide synthase (eNOS) in the whole lung was significantly upregulated by hypoxia, which was further upregulated by bosentan. Bosentan modulated kinetics of bone marrow-derived ECs and macrophages and related gene expression in lungs in ameliorating pulmonary hypertension in mice. Altered kinetics of bone marrow-derived stem cells may be a novel mechanism of the endothelin receptor blockade in vivo and confer a new understanding of the therapeutic basis for pulmonary hypertension.

DOI： 10.1177/2045894020919355

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Association for the Advancement of Science (AAAS)  

Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of <italic>Atoh8</italic> did not cause an arteriovenous malformation–like phenotype, which may arise because of dysregulated Notch signaling. In contrast, <italic>Atoh8-</italic>deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, <italic>ATOH8</italic> expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2α (HIF-2α) and decreased its abundance, leading to reduced induction of HIF-2α target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.

DOI： 10.1126/scisignal.aay4430

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijcard.2019.06.020

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Publisher：Journal of Human Genetics  

ORAI1 encodes a calcium channel essential in the store-operated calcium entry mechanism. A previous genetic association study identified a rare in-frame insertion variant of ORAI1 conferring Kawasaki disease (KD). To deepen our understanding of the involvement of rare variants of ORAI1 in KD pathogenesis, we investigated 3812 patients with KD and 2644 healthy individuals for variations in the protein-coding region of ORAI1. By re-sequencing the study participants’ DNA, 27 variants with minor allele frequencies (MAFs) < 0.01 that had not been examined in the previous study were identified. Although no significant association with KD was observed either in single-variant analyses or in a collapsing method analysis of the 27 variants, stratification by MAFs, variant types, and predicted deleteriousness revealed that six rare, deleterious, missense variants (MAF < 0.001, CADD C-score ≥ 20) were exclusively present in KD patients, including three refractory cases (OR = ∞, P = 0.046). The six missense variants include p.Gly98Asp, which has been demonstrated to result in gain of function leading to constitutive Ca2+ entry. Conversely, five types of frameshift variants, all identified near the N terminus and assumed to disrupt ORAI1 function, showed an opposite trend of association (OR = 0.35, P = 0.24). These findings support our hypothesis that genetic variations causing the upregulation of the Ca2+/NFAT pathway confer susceptibility to KD. Our findings also provide insights into the usefulness of stratifying the variants based on their MAFs and on the direction of the effects on protein function when conducting association studies using the gene-based collapsing method.

DOI： 10.1038/s10038-019-0588-2

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijcard.2018.09.032

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1253/circj.CJ-66-0153

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Medical Association (AMA)  

DOI： 10.1001/jamapediatrics.2018.0030

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi:10.1016/j.echo.2016.03.017.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author,　Corresponding author   Language：English  

DOI： 10.1017/S104795112402585X

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Language：English   Publisher：Journal of Dermatology  

DOI： 10.1111/1346-8138.17382

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Congenital Heart Disease  

Background: There is no gold standard sedation method for pediatric cardiac catheterization. In congenital heart diseases with intracardiac shunts, hemodynamic parameters are prone to change depending on the ventilation conditions and anesthetics, although few studies have examined these effects. The purpose of this study was to investigate the effects of two different sedation methods on the hemodynamic parameters. Methods: This study retrospectively evaluated consecutive patients with ventricular septal defect (VSD) below 1 year of age who underwent cardiac catheterization at Aichi Children’s Health and Medical Center, who were divided into age-and VSD diameter-matched general anesthesia (GA) and monitored anesthesia care (MAC) under the natural airway groups (n = 40 each), for comparison of hemodynamic parameters. Results: In the GA group, arterial blood pH and arterial partial pressure of oxygen were significantly higher (p < 0.01), whereas arterial partial pressure of carbon dioxide was significantly lower than in the MAC group (p < 0.01). Mean pulmonary artery pressure (p < 0.05) and systemic blood pressure (p < 0.01) were lower in the GA group. Pulmonary vascular resistance index (p < 0.01) and systemic vascular resistance index (p < 0.01) were also significantly lower in the GA group than the MAC group. There were no significant differences in pulmonary blood flow index, systemic blood flow index, and pulmonary/systemic blood flow ratio between the two groups. Conclusions: Cardiac catheterization under GA in VSD patients results in different hemodynamic parameters compared to that under MAC. In par-ticular, when using pulmonary artery pressure and pulmonary vascular resistance measured under GA for judg-ment regarding the surgical indications or perioperative management, consideration should be given to the fact that these parameters might be lower compared to those measured under MAC.

DOI： 10.32604/chd.2023.027590

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Pediatrics  

Pulmonary hypertension (PH) with developmental lung disease is a life-threatening disease and accounts for 10%–12% of pediatric PH patients. Administration of specific pulmonary vasodilators to pediatric PH patients has brought about improvement of their long-term prognosis. Intravenous epoprostenol therapy is a gold standard therapy for severe idiopathic pulmonary arterial hypertension (IPAH), but there are few reports demonstrating the efficacy of epoprostenol for pediatric PH patients with developmental lung disease, especially when treating with high doses of epoprostenol. Two cases of pediatric PH patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) and congenital diaphragmatic hernia (CDH) with bronchopulmonary dysplasia (BPD), respectively, treated with epoprostenol above 100 ng/kg/min are presented. In these two cases, severe PH was improved significantly by an aggressive increase of the epoprostenol infusion rate with administration of oral pulmonary vasodilators and appropriate respiratory management, without any significant adverse effects. High-dose epoprostenol therapy may be one of the therapeutic options in pediatric PH patients with developmental lung disease.

DOI： 10.3389/fped.2023.1116434

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Language：English   Publisher：The Japanese Circulation Society  

DOI： 10.1253/circj.CJ-21-0821

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Language：English   Publisher：Pediatrics International  

DOI： 10.1111/ped.14995

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Authorship：Corresponding author   Language：English   Publisher：Pediatrics International  

DOI： 10.1111/ped.15395

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Language：English   Publishing type：Research paper (scientific journal)  

Pulmonary hypertension (PH) is associated with high morbidity in children undergoing hematopoietic stem cell transplantation (HSCT). However, owing to the lack of sequential echocardiography, the nature of the condition is not fully understood. This study was conducted to investigate whether routine echocardiography performed after HSCT could detect patients with PH at an earlier stage and elucidate the role of intervention using tadalafil. The study population comprised 93 consecutive children age <18 years who underwent a total of 109 HSCTs. All patients underwent routine transthoracic echocardiography during HSCT. Four children (4%) with a median age of 4 years (range, 0.7 to 6 years) were found to have PH, and their median tricuspid regurgitation peak velocity (TRV) was 4.1 m/s (range, 3.5 to 4.2 m/s). PH was diagnosed at a median of 52 days (range, 21 to 118 days) after HSCT. Three of them were diagnosed with neuroblastoma, and 1 was diagnosed with infantile leukemia. One patient developed PH after autologous HSCT, and 3 received killer immunoglobulin-like receptor ligand-mismatched cord blood. Busulfan was used for conditioning in all patients, and the proportion of patients receiving this medication was significantly higher in the PH group compared with the non-PH group (100% versus 30%; P = .011). Three of the 4 patients had a durable response (TRV ≤2.8 m/s) at a median of 46 days (range, 14 to 79 days) after starting treatment with tadalafil. No patient experienced exacerbation of PH, and treatment was completed at median of 96 days (range, 46 to 212 days). Our data suggest that routine echocardiography monitoring after HSCT should be considered in children receiving busulfan, although the precise follow-up timing needs further study. In addition, safe and effective administration of tadalafil must be ensured by close monitoring.

DOI： 10.1016/j.jtct.2021.05.017

PubMed

Language：English   Publisher：Pediatric Rheumatology  

Background: Tenascin-C (TN-C) is an extracellular matrix glycoprotein related to tissue inflammation. Our previous retrospective study conducted in 2016 revealed that the serum tenascin-C level was higher in patients with Kawasaki disease (KD) who were resistant to intravenous immunoglobulin (IVIG) and developed coronary artery lesions (CALs). The present study is a prospective cohort study to assess if the serum level of tenascin-C could be used as a novel biomarker to predict the risk of resistance to initial treatment for high-risk patients. Methods: A total of 380 KD patients were registered and provided serum samples for tenascin-C measurement before commencing their initial treatment. Patients who did not meet the inclusion criteria were excluded from analysis; of the 181 remaining subjects, there were 144 low-risk patients (Kobayashi score: ≤4 points) and 37 high-risk patients (Kobayashi score: ≥5 points). The initial treatments for low-risk patients and high-risk patients were conventional therapy (IVIG with aspirin) and prednisolone combination therapy, respectively. The patient clinical and laboratory data, including the serum tenascin-C level, were compared between initial treatment responders and non-responders. Results: In the low-risk patients, there was no significant difference in the median levels of serum tenascin-C between the initial therapy responders and non-responders. However, in the high-risk patients, the median serum tenascin-C level in initial therapy non-responders was significantly higher than that in initial therapy responders (175.8 ng/ml vs 117.6 ng/ml). Conclusions: Serum tenascin-C could be a biomarker for predicting the risk of high-risk patients being non-responsive to steroid combination therapy. Trial registration: This study was a prospective cohort study. It was approved by the ethics committee of each institute and performed in accordance with the Declaration of Helsinki.

DOI： 10.1186/s12969-021-00562-w

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagnosis of KD, the pathogen of the trigger may already be diminished. The aim of this study was to explore comprehensive pathogens in the sera at the acute stage of KD using high-throughput sequencing (HTS). METHODS: Sera of 12 patients at an extremely early stage of KD and 12 controls were investigated. DNA and RNA sequences were read separately using HTS. Sequence data were imported into the home-brew meta-genomic analysis pipeline, PATHDET, to identify the pathogen sequences. RESULTS: No RNA virus reads were detected in any KD case except for that of equine infectious anemia, which is known as a contaminant of commercial reverse transcriptase. Concerning DNA viruses, human herpesvirus 6B (HHV-6B, two cases) and Anelloviridae (eight cases) were detected among KD cases as well as controls. Multiple bacterial reads were obtained from KD and controls. Bacteria of the genera Acinetobacter, Pseudomonas, Delfita, Roseomonas, and Rhodocyclaceae appeared to be more common in KD sera than in the controls. CONCLUSION: No single pathogen was identified in serum samples of patients at the acute phase of KD. With multiple bacteria detected in the serum samples, it is difficult to exclude the possibility of contamination; however, it is possible that these bacteria might stimulate the immune system and induce KD.

DOI： 10.1186/s12887-020-02380-7

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ped.14252

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Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Circulation Society  

DOI： 10.1253/circj.CJ-20-0139

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Heart Journal Association  

<p>Percutaneous occlusion of atrial septal defect (ASD) has recently become a standard therapeutic strategy, but little is known about left atrial (LA) function thereafter. The present study aimed to determine LA function in 43 children with ASD and 13 controls based on LA strain measured by two-dimensional echocardiographic speckle tracking (2DE-ST). Among these children, 12 underwent surgery (ASD-S), 31 had device closure (ASD-D), and 13 were included as controls. LA strain was significantly decreased after ASD-D but was not significantly altered after ASD-S, indicating that percutaneous occlusion of an ASD might decrease LA function. Furthermore, the size of the ASD device negatively correlated with LA strain. These results imply that ASD occlusion devices negatively influence LA function and might be important when decided therapeutic strategies for ASD. LA strain measured by 2DE-ST should become a good indicator of LA function after ASD treatment in children.</p>

DOI： 10.1536/ihj.19-173

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1017/S1047951119002567

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ped.14029

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1017/S1047951119001744

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：Japanese Society of Pediatric Cardiology and Cardiac Surgery  

DOI： 10.9794/jspccs.35.132

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Language：English   Publishing type：Research paper (scientific journal)  

Major aortopulmonary collateral arteries (MAPCAs) are unique vessels associated with hypoxia induced by congenital heart disease (CHD). Although MAPCAs are essential to supply blood to the lungs, their development and proliferation can induce life-threatening complications, such as rupture into the lung. Here, we describe a rare case of esophageal bleeding from MAPCAs in a CHD patient, which was successfully treated by transcatheter arterial embolization (TAE). A 16-year-old male with CHD experienced a hematemesis and melena after the Bentall procedure to treat valvular heart disease. Emergent esophagogastroduodenoscopy revealed spurting bleeding from the middle esophageal vessels; accordingly, endoscopic variceal ligation (EVL) was performed. However, he had a hematemesis again after 2 weeks of EVL. The arterial phase of dynamic computed tomography indicated that a MAPCA associated with CHD was the origin of bleeding. Hence, TAE of this MAPCA with a mixture of n-butyl-2-cyanoacrylate and ethiodized oil was performed to prevent re-bleeding. Color Doppler mode in endoscopic ultrasonography via the esophagus revealed mosaic-like signals in MAPCAs located in the esophageal wall. This finding was consistent with tortuous MAPCAs accompanied by turbulent blood flow. When clinicians encounter CHD patients with unexpected massive esophageal bleeding, bleeding related to MAPCAs should be considered.

DOI： 10.1007/s12328-018-0895-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/jmv.25263

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Language：Japanese   Publisher：(NPO)日本小児循環器学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Publishing Group  

We compared the efficacy and safety of infliximab with intravenous immunoglobulin (IVIG), a standard therapy, in a phase 3 trial (NCT01596335) for Japanese patients with Kawasaki disease (KD) showing persistent fever after initial IVIG. Patients with initial IVIG-refractory KD, aged 1-10 years, received a single dose of IV infliximab 5 mg/kg or IV polyethylene glycol-treated human immunoglobulin (VGIH) 2 g/kg on day 0. Primary outcome was defervescence rate within 48 h after the start of treatment. Safety was evaluated through day 56. Overall, 31 patients were randomized (infliximab, n = 16
VGIH, n = 15)
31.3% and 60.0% patients discontinued due to worsening KD. Defervescence rate within 48 h was greater with infliximab (76.7%) than VGIH (37.0%) (p = 0.023), and defervescence was achieved earlier with infliximab (p = 0.0072). Coronary artery lesions occurred in 1 (6.3%) and 3 (20.0%) patients receiving infliximab and VGIH, respectively, up to day 21. Adverse events occurred in 15 (93.8%) and 15 (100.0%) patients in the infliximab and VGIH groups, respectively. No serious adverse events in the infliximab group and one in the VGIH group were observed. Infliximab improved the defervescence rate within 48 h and time to defervescence versus standard therapy, and was well tolerated in patients with IVIG-refractory KD.

DOI： 10.1038/s41598-017-18387-7

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Language：English   Publisher：International Heart Journal Association  

The use of unilateral pulmonary artery occlusion (UPAO) test for the preoperative evaluation of pneumonectomy was reported in adult patients. On the contrary, in infants, no strategies have yet been recommended to predict hemodynamics after pneumonectomy, nor has use of the UPAO test been reported. We describe the first case of infant with abnormal pulmonary circulation in whom successful pneumonectomy was performed after preoperative evaluation using UPAO test. Right pneumonectomy was planned for an 8-month-old girl, because of decreased right pulmonary function, high risk of pneumothorax, and impaired left lung expansion due to overexpansion caused by severe left bronchial stenosis and bronchomalacia. However, she had also prolonged pulmonary hypertension and there was difficulty in accurate echocardiographic evaluation of its severity due to concomitant left pulmonary artery stenosis. Furthermore, contrast-enhanced computer tomography suggested a certain degree of right pulmonary venous flow, discordant with the result showing scarce right pulmonary flow in perfusion scintigraphy. Predicting postoperative hemodynamic changes was therefore considered difficult. To evaluate these concerns, we performed cardiac catheterization and UPAO test to simulate postoperative hemodynamics. Pulmonary arteriography showed decreased but significant right pulmonary arterial and venous flows. Measurements including pulmonary artery pressure and cardiac index showed no marked changes after occlusion. Based on UPAO test results, the operation was successfully performed and hemodynamics remained stable postoperatively. The UPAO test may be useful for infants with cardiopulmonary impairment to evaluate the tolerability of pneumonectomy.

DOI： 10.1536/ihj.16-606

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：Japanese Society of Pediatric Cardiology and Cardiac Surgery  

DOI： 10.9794/jspccs.33.247

CiNii Research

Language：Japanese   Publisher：Japanese Society of Pediatric Cardiology and Cardiac Surgery  

<p><b>Background</b>: The number of patients with trisomy 18 undergoing cardiac surgery has recently been increasing. In our institute, the primary purpose of treatment in patients with trisomy 18 is to facilitate discharge and cardiac surgery has not yet been performed in such cases. In the present report, we reviewed patients treated at our institute to demonstrate the prognosis of patients with trisomy 18 without cardiac surgery.</p><p><b>Methods</b>: We collected detailed clinical information from the medical records of 17 patients with trisomy 18 from April 2005 to December 2015. We retrospectively studied the neonatal condition, survival rate, and cause of death. We also reviewed patients with a high pulmonary flow, the large left-to-right shunt (LS) group, who were at a potential risk of heart failure.</p><p><b>Results</b>: All patients had congenital heart disease (CHD). The 1-year survival rate was 64.7%, with 70.6% of patients discharged at a median age of 129 days (range, 16–285 days). The median survival time of patients who died during the present study was 104.5 days (range, 0–1,054 days). In the LS group, 62.5% of patients survived for one year with no evidence of heart failure. Two patients in the LS group died in hospital from heart failure.</p><p><b>Conclusions</b>: Favorable survival was achieved through standard neonatal intensive treatment without cardiac surgery. Patients with trisomy 18 complicated by CHD with a high pulmonary flow should be maintained in a stable condition without cardiac surgery due to persistent pulmonary hypertension resulting from vascular abnormalities. Further studies are required to evaluate the long-term effectiveness of cardiac surgery for patients with trisomy 18.</p>

DOI： 10.9794/jspccs.33.312

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2016.06.011.

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DOI： doi: 10.1016/j.echo.2016.03.017. Epub 2016 Jun 7.

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DOI： doi:10.1371/journal.pone.0118655.

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese Book type：Scholarly book

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Language：Japanese

Language：English

Missense mutations in the PTPN11 as a cause of cardiac defects associated with Noonan syndrome.

Total pages：5   Responsible for pages：99－103   Language：Japanese Book type：Scholarly book

Language：Japanese

Event date： 2023.6

Language：English   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2021.10

Language：English   Presentation type：Symposium, workshop panel (public)  

Event date： 2021.9 - 2021.10

Language：English   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Country：Indonesia  

Event date： 2021.7

Language：English   Presentation type：Oral presentation (invited, special)  

Venue：奈良  

Event date： 2021.2

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Venue：オンライン  

Event date： 2020.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：京都  

Event date： 2020.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Event date： 2019.11

Language：English   Presentation type：Poster presentation  

Event date： 2018.11

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2018.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Event date： 2018.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Event date： 2018.6

Language：English   Presentation type：Oral presentation (general)  

Event date： 2024.10

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2023.11

Language：English   Presentation type：Poster presentation  

Venue：Philadelphia   Country：United States  

Event date： 2023.11

Language：English   Presentation type：Poster presentation  

Venue：Dublin   Country：Ireland  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Event date： 2023.7

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2023.2

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Event date： 2023.2

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Event date： 2022.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜  

Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：オンライン  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：東京  

Event date： 2022.7

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Venue：札幌  

Event date： 2022.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：郡山  

Event date： 2021.11

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Venue：オンライン  

Event date： 2021.7

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2021.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン  

Event date： 2020.10

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2020.9

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2019.11

Language：English   Presentation type：Poster presentation  

Event date： 2019.10

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2019.6

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2019.6

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2018.7

Language：Japanese   Presentation type：Poster presentation  

Event date： 2018.6

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2018.4

Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2018.2

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2012.7

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2012.2

Language：English   Presentation type：Poster presentation  

Country：Japan  

Event date： 2011.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2010.7

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2009.11

Language：English   Presentation type：Poster presentation  

Event date： 2009.6

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2009.3

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2008.11

Language：English   Presentation type：Poster presentation  

Event date： 2007.7

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2006.7

Language：Japanese   Presentation type：Poster presentation  

Country：Japan  

Event date： 2005.7

Language：Japanese   Presentation type：Poster presentation  

Country：Japan  

Event date： 2004.6

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2002.7

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2001.9

Language：English   Presentation type：Oral presentation (general)  

Event date： 2001.3

Language：Japanese   Presentation type：Poster presentation  

Country：Japan  

Event date： 1997.11

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 1997.9

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 1996.12

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

先天性心疾患の血行動態シミュレーションを通じた病態考察

先天性心疾患の血行動態シミュレーションを通じた病態考察

臨床実習

小児循環器病学一般の総説

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器病学を担当

小児循環器病学を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器病学を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器病学を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当

小児循環器疾患分野を担当

小児循環器病学を担当

小児循環器疾患分野を担当

救急・治療および循環器疾患を担当

小児循環器疾患分野を担当