記述言語：英語   掲載種別：研究論文（学術雑誌）  

Coronary artery bypass grafting (CABG) for severe cardiac sequelae of Kawasaki disease (KD) complicated by myocardial ischemia is feasible even in childhood. However, no report has summarized the prognosis of CABG in preschool-aged children. Therefore, we evaluated the outcomes of seven preschool-aged children who underwent CABG for the cardiac sequelae of KD in our hospital. The median age at KD onset and CABG was 36 and 59 months, respectively. The median period from KD onset to CABG was 12 months. The median post-operative observation period was 108 months. CABG between the left internal thoracic artery and left anterior descending artery was performed in all patients. In all patients, postoperative cardiac catheter examination revealed good graft patency and no anastomotic stenosis. Further, pre-operative abnormality of coronary flow reserve returned to normal after CABG. Currently, only one patient is taking warfarin. Regarding school-life management, no patient has exercise limitations, except for one patient who had acute myocardial infarction before CABG. Further, the risk of graft stenosis or occlusion was evaluated in the included patients. However, no accidents have been reported to date, and myocardial ischemia and school-life management have improved. Thus, CABG is an effective treatment in preschool-aged children.

DOI： 10.3390/jcm11051421

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Coronary peripheral circulatory disturbances in the remote stage of Kawasaki disease have been reported. In this study, of the 50 patients in the remote stage of Kawasaki disease who underwent coronary perfusion evaluation using adenosine-loaded 13N-ammonia positron emission tomography, 28 patients who did not have stenosis of ≥75% in the left coronary artery underwent an evaluation for myocardial flow reserve (MFR) of the left anterior descending artery (LAD) and left circumflex artery (LCx). Clinical findings were compared between patients with normal (≥2.0) and abnormal (<2.0) MFRs. In the group with an abnormal MFR in the LAD, the responsiveness of the coronary vascular resistance to adenosine stress decreased even in the LCx (3.50 ± 1.23 vs. 2.39 ± 0.25, p = 0.0100). In the group with an abnormal MFR in the LCx, the responsiveness of the coronary vascular resistance in the LAD also decreased (3.27 ± 1.39 vs. 2.03 ± 0.25, p = 0.0105), and the age of onset of Kawasaki disease tended to be younger in the group with abnormal MFR in the LAD and LCx. We found that the peripheral coronary circulation was extensively impaired in the remote stage of Kawasaki disease, suggesting that an early onset of Kawasaki disease may affect the peripheral coronary circulation in later years.

DOI： 10.3390/jcm11041134

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Residual shunt after the closure of an inferior sinus venosus defect (ISVD) is a rare complication with a high rate of reintervention. CASE PRESENTATION: Here, we report a rare case of a patient with a recurrent defect identified 22 years after the closure of ISVD. The 25 × 10-mm defect was situated at the inferior vena cava-right atrial junction and was closed directly at 5 years of age. No residual shunt was detected, and when the patient reached 12 years of age, follow-up was discontinued. However, the residual atrial septal defect shunt was detected incidentally at 27 years of age. During the second surgery, the lower end of the original defect was opened and then closed using an expanded polytetrafluoroethylene patch. CONCLUSIONS: In light of the high rate of reintervention for residual shunt after ISVD closure, patch closure appeared to be a better option to reduce the tension in the inferior-posterior border. Moreover patients with this profile should be followed up closely at least in their childhood, including assessment by echocardiography.

DOI： 10.1272/jnms.JNMS.2023_90-301

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: There has been significant progress in reducing perinatal mortality in Japan. However, due to changes in social conditions, the total fertility rate and the number of births are decreasing, whereas the number of low birth weight infants is increasing along with the number of newborn babies that require intensive care. Further, although the number of high-level perinatal medical centers has increased, so has that of infants who need long-term hospitalization. Conversely, the number of regular obstetric facilities has decreased, thus resulting in insufficient beds for neonatal care. To fill this gap, we established a neonatal intensive care unit (NICU) at our hospital. This study aimed to evaluate our new type by comparing the data from ours with that from other facilities. METHODS: The other facilities assessed were two high-level NICU facilities and two regular obstetric facilities. Data, including sex, gestational age, birth weight, Apgar scores at 1 and 5 min, delivery method, and presence of breathing disorders, were extracted from medical records. RESULTS: The birth weight and gestational age distributions were significantly different in the institutions, except in one facility without a NICU. The new NICU saw more infants with low birth weight and respiratory disorders than the regular obstetric facilities. CONCLUSION: The comparison of birth weight and gestational age distributions, cases of respiratory disorders, and delivery methods indicate that our new NICU is positioned as an intermediate facility between a high-level NICU and a regular obstetrics facility.

DOI： 10.1272/jnms.JNMS.2021_88-403

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Coronary artery evaluation by virtual histological intravascular ultrasonography (VH-IVUS) late in Kawasaki disease (KD) shows intimal thickening, calcification, fatty components, and necrosis of regressed coronary artery lesions (CALs). However, it is not clear when these VH-IVUS findings start to occur. Therefore, we evaluated coronary arteries using VH-IVUS in patients with early-stage KD and tried to determine whether these atherosclerotic findings on VH-IVUS were different from that in patients with late-stage KD. METHODS: Eighteen patients with KD aged between 1 and 32 years who had CALs and underwent cardiac catheterization between January 1, 2008 and December 31, 2014 were included. They were divided into 2 groups-those with the disease for <1 year (group A) and those with it for >10 years (group B). VH-IVUS findings were compared between the groups. The coronary arteries were divided based on coronary angiography findings into normal, regressed (dilated CALs regressed to a normal size), and aneurysmal lesions. The Wilcoxon signed-rank test was used in the statistical analysis. RESULTS: In both regressed and aneurysmal lesions, marked intimal proliferation and atherosclerotic findings (fibro-fatty and necrotic core lesions) were observed. In addition, there was no difference in the area percentage of atherosclerosis between the groups. CONCLUSIONS: VH-IVUS revealed that atherosclerotic-like findings exist in CALs in patients with KD, even within a year of onset. The findings were almost the same in those with the disease for >10 years. Because there is no histological evidence of atherosclerosis in KD, these VH-IVUS findings may indicate complex histological findings of KD. Nevertheless, early interventions to help reduce the risk factors of atherosclerosis may be required in these patients.

DOI： 10.1016/j.jjcc.2019.06.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Kawasaki disease (KD), a systemic vasculitis, is suspected to be related to abnormalities in innate immunity. Based on the important role of IL-1 signaling in innate immunity, we investigated the effects of an anti-IL-1β antibody using a Candida albicans water-soluble fraction (CAWS)-induced mouse model of KD. METHODS: CAWS (0.5 mg/mouse) was injected intraperitoneally into 5-week-old DBA/2 mice on five consecutive days. An anti-Murine IL-1β antibody (01BSUR) was administered at various doses (2.5, 5.0, and 10.0 mg/kg) and time points (2 days before, same day, and 2, 5, 7, and 14 days after CAWS administration). After 4 weeks, vasculitis in the aortic root was investigated histologically. Cytokines including IL-1β, -6, -10, and TNF-α were also measured. RESULTS: Groups administered 01BSUR at all doses showed a significant reduction in the area of vasculitis. In addition, 01BSUR inhibited vasculitis until 7 days after CAWS administration. In the analysis of various time points, the level of IL-6 was lower in all groups compared to the CAWS only group, but the levels of IL-1β, TNFα, and IL-10 were lower when 01BSUR was administered before CAWS. On the other hand, TNFα and IL-10 levels were restored when 01BSUR was administered after CAWS, suggesting that 01BSUR may have additional effects beyond blocking IL-1β signaling. CONCLUSIONS: The anti-IL-1β antibody significantly attenuated CAWS-induced vasculitis. The mechanism of inhibiting vasculitis is thought to include inhibition of the IL-1β pathway and additional effects beyond blocking IL-1β signaling.

DOI： 10.1272/jnms.JNMS.2019_86-206

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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. MAIN OUTCOMES AND MEASURES: The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. RESULTS: Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. CONCLUSIONS AND RELEVANCE: Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

DOI： 10.1001/jamapediatrics.2018.0030

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Kawasaki disease (KD) occurs via activation of the innate immune system. Nucleotide oligomerization domain-1 (NOD1) is a pattern recognition receptor regulating the innate immunity. We characterized histopathology of arteritis induced by FK565, a ligand for NOD1, in mice, compared with Candida albicans water-soluble fraction (CAWS)-induced model. METHODS: Vasculitis was induced by injection of FK565 or CAWS into C57BL6/J mice (n = 9 and n = 11, respectively). At 4 weeks, they were sacrificed, and plasma cytokines and chemokines were measured. RESULTS: FK565 injection induced vasculitis mainly involving bilateral coronary arteries whereas the aortic root was diffusely affected in CAWS mice. In FK565 animals, the abdominal aorta and its branching arteries also exhibited inflammation with atherosclerosis. IL-1α, IL-1β, IL-5 and RANTES were increased in FK565 group whereas IL-6, IL-13, G-CSF, IFN-γ, and TNF-α were higher in CAWS animals (p < .05 for all variables). The total area of inflammation in FK565 mice appeared to correlate with IL-1β levels (r = 0.71, p = .05). CONCLUSIONS: Histopathology of FK565-induced model demonstrated 'site-specific' coronary arteritis mimicking KD. This histopathological difference from CAWS model may be due to different cytokine expression profiles.

DOI： 10.1080/14397595.2017.1287150

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