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There has been no multicenter study on the prognosis of pediatric hypertrophic cardiomyopathy (HCM) in Japan. Therefore, we conducted a retrospective multicenter observational study on the long-term survival rate in patients diagnosed with HCM under the age of 18 between 1990 and 2014. Twenty institutions participated. A total of 180 patients were identified. The median age at diagnosis was 5.8 years old and median duration of observation was 8.3 years. Although six patients (3%) deteriorated into the dilated phase of HCM, no patient received heart transplantation. Freedom from death at 1, 5, 10, and 20 years were 97%, 92%, 84%, and 80%, respectively. There were 26 deaths. Among them, 11 patients died suddenly, presumably due to arrhythmia, and 15 patients died of heart failure. The presence of heart failure symptoms and a greater cardiothoracic ratio were significant risk factors for heart failure-related death. There were no significant risk factors identified for arrhythmia-related death. In conclusion, the prognosis of pediatric HCM in Japan is good and similar to those reported in population-based studies in the United States and Australia. Significant risk factors for heart failure-related death were identified in pediatric patients with HCM in Japan. [ABSTRACT FROM AUTHOR]

Stenting is an important treatment option for pulmonary artery stenosis (PS) associated with congenital heart disease (CHD). However, no stent has been approved for this indication in Japan, despite negotiation between academia and the regulatory bodies for longer than 20 years. To evaluate efficacy and safety of the CP stent, we performed the first investigator-initiated clinical trial for pediatric interventional cardiology in Japan. This trial was designed as a single-arm, prospective, clinical trial. Patients who had postoperative PS associated with CHD were included. Stenting was attempted in 24 cases and succeeded in 22 cases. The median age of the patients was 11 years (3–36 years) and weight was 38 kg (12–69 kg), while follow-up for 12 months was completed. In all 22 cases, stenting was successful, with a 50% increase in the minimum lumen diameter (MLD) in 86.4% of patients (90% confidence interval, 68.4–96.2%). The mean percent change in MLD was 119.3 ± 52.5%. In two-ventricle repair, the mean percent change in systolic right ventricular/aortic pressure was − 8.5 ± 16.1%, while that of pressure gradient was − 55.9 ± 41.7%. In single-ventricle repair, the percent change in the mean pressure gradient was − 100.0 ± 0%, while that of SaO2 was 1.4 ± 1.7%. No serious adverse events or significant restenosis was reported. The CP stent is highly effective and safe for PS associated with CHD. This study has significant importance in not only scientific but also social considerations. [ABSTRACT FROM AUTHOR]

Background As treatment outcomes for congenital heart disease ( CHD) have improved, the social independence of adult CHD patients has become a key goal. The aims of this study were therefore to (i) determine the relationship between social independence and psychological profile, and (ii) identify patient anxieties, difficulties, and demands related to life in society. Methods A total of 143 patients aged ≥15 years with physical disability certificates were selected using a questionnaire distributed by a patients' association. Each participant was asked about employment status, income, and receipt of disability pension as a social independence index, and about financial and psychological distress as a psychological status index. Furthermore, each participant was asked to freely describe his or her difficulties, anxieties, and needs pertaining to life in society. Results The subjects were 15-73 years old. Seventy-one (50%) were female, and 94 (66%) had a grade 1 physical disability certificate. Fifty-nine subjects (41%) were employed, 37 (26%) were unemployed, and 45 (31%) were students. Of those employed, 34 subjects (58%) reported annual individual income ≤2 million yen. Frequent hospital visits, low total household income, low individual annual income, work dissatisfaction, and receipt of a disability pension were associated with poorer psychological profile. In an open description section, subjects expressed desires for better pension systems, support for medical fees, and employment support. Conclusions Because financial issues can adversely affect the psychological profiles of adult CHD patients, enhancement of social welfare and employment support may improve their social independence. [ABSTRACT FROM AUTHOR]

Background A collaborative network for pediatric research has not been fully established in Japan. To identify the network infrastructure, we conducted a survey on the support and education for clinical research currently available in children's hospitals. Methods In November 2014, a 27-question survey was distributed to 31 hospitals belonging to the Japanese Association of Children's Hospitals and Related Institutions ( JACHRI) to assess clinical research support, research education, research achievements, and their expectations. Results All the hospitals responded to the survey. Overall, 74.2% of hospitals had clinical research support divisions. Although all hospitals had ethics committees, <30% of the hospitals had a data manager, intellectual property management unit, biostatistician, and English-language editor. Seven hospitals had education programs for clinical research. The number of seminars and workshops for clinical research had significant correlations with the number of physicians ( r = 0.927), pediatricians ( r = 0.922), and clinical trial management physicians ( r = 0.962). There was a significant difference in the number of clinical trials initiated by physicians between hospitals with research education programs and those without ( P < 0.01). The number of education programs was significantly correlated with the number of original articles and case reports in English ( r = 0.788), and the number of publications in Japanese ( r = 0.648). All hospitals recognized the need for a leader to establish a collaborative network for clinical research. Conclusions Important factors for creating a collaborative system for pediatric research in Japan were identified. Human resources to support clinical research are a key factor to improve clinical research education and research achievements. [ABSTRACT FROM AUTHOR]

Background Thrombolytic therapy for coronary aneurysm thrombosis of Kawasaki disease ( KD) includes antiplatelet and anticoagulants, i.v. coronary thrombolysis ( IVCT), and i.c. thrombolysis ( ICT). Therapeutic methods, drugs and doses vary among medical facilities. Methods and Results A nationwide survey of thrombolytic therapy was conducted under the auspices of the Ministry of Health, Labour and Welfare Research Program to Intractable Diseases Research Grants. A secondary survey targeted 14 facilities conducting thrombolytic therapy during a 5 year period (2004-2009). The primary survey investigated performance of thrombolytic therapy for 23 KD patients at 14 facilities, and of these, five with acute myocardial infarction had received ICT and combined therapy. The secondary survey investigated the pre-treatment condition of aneurysm and thrombosis and actual treatment methods. ICT was effective for small thrombi (≤10 mm), while IVCT was effective even for giant thrombi (>10 mm). ICT was also effective for thrombi within several hours after formation. Conclusion In the present nationwide survey, thrombolytic therapy was more effective in cases of a shorter duration between thrombus formation and the start of treatment. It was found that many facilities used only IVCT for thrombus alone. Medications given to KD children did not cause serious hemorrhagic complications, unlike in adults. Although doses exceeded recommended levels in many cases, the only complications were nasal bleeding and fever. [ABSTRACT FROM AUTHOR]

In Japan, self-monitoring of blood glucose ( SMBG) devices are widely used both at home and in hospitals, but many analytical errors and safety concerns have been reported about the SMBG devices used in hospitals. Analytical performances of StatStrip ( Nova Biomedical Corporation, MA, USA), a new point-of-care testing device and Glutest ( Sanwa Chemical, Aichi, Japan), a routinely used SMBG device were compared in glucose measurement of pre- and postdialysis blood samples and we evaluated which factors in blood modified by hemodialysis affect accuracy of these devices. Subjects in this study were 44 hemodialysis patients. Blood samples were obtained from patients just before and just after the hemodialysis. Blood glucose concentrations of samples were measured by StatStrip and Glutest. Hematocrit and plasma concentrations of electrolytes, metabolites, etc. of the samples were measured in the central laboratory. StatStrip showed no difference between pre- and postdialysis blood samples and showed very little bias from reference method. On the other hand, Glutest showed difference between pre- and postdialysis samples. Although there is no problem in the data of predialysis blood samples by Glutest, however, these of the postdialysis blood samples by Glutest were >10% less than reference method. Factors in blood modified by hemodialysis such as hematocrit, uric acid, albumin, potassium, and calcium affected glucose readings by Glutest. Glucose readings by Glutest of samples from hemodialysis patients were affected by hematocrit and several factors, which were modified by hemodialysis. StatStrip is considered as a better device in dialysis hospitals. [ABSTRACT FROM AUTHOR]

Several linkage studies have predicted that human chromosome 20q is closely related to type 2 diabetes, but there is no clear evidence that certain variant(s) or gene(s) have strong effects on the disease within this region. To examine disease susceptibility variant in Japanese, verified SNPs from the databases, with a minor allele frequency larger than 0.15, were selected at 10-kb intervals across a 19.31-Mb region (20q11.21-13.13), which contained 291 genes, including hepatocyte nuclear factor 4α (HNF4α). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By searching for HNF4α as a representative disease-susceptible gene, no variants of HNF4α were strongly associated with disease. To identify other genetic variant related with disease, we designed an extensive two-stage association study (725 first and 1,093 second test samples). Although SNP1146 (rs220076) was selected as a landmark within the 19.31 Mb region, the magnitude of the nominal P value ( P = 0.0023) was rather weak. Subsequently, a haplotype-based association study showed that two common haplotypes were weakly associated with disease. All of these tests resulted in non-significance after adjusting for Bonferroni’s correction and the false discovery rate to control for the impact of multiple testing. Contrary to the initial expectations, we could not conclude that certain SNPs had a major effect on this promising locus within the framework presented here. As a way to extend our observations, we emphasize the importance of a subsequent association study including replication and/or meta-analysis in multiple populations. [ABSTRACT FROM AUTHOR]

Abstract: Background: There are few articles on mortality and morbidity of adult patients with Eisenmenger's syndrome (ES) in the current era when disease targeting therapy (DTT) has been available. Methods and results: 198 patients (a median age 35years, 64% female) with ES who visited the 16 participating institutes in Japan and Korea from 1998 to 2009 were enrolled. Clinical data during adulthood were collected from each institutional chart and analyzed centrally. During a median follow-up of 8years, 30 patients died including 14 sudden deaths. 89 patients took oral medication of DTT and clinical improvement was observed in 54 of them. However, survival rate in patients taking DTT was not different from those without (87% vs 84%, p=0.55). When the clinical data in between first and last clinic visits were compared in 85 patients, the patients with NYHA ≧ III increased from 24% to 48% (p<0.001), SpO2 decreased from 89% to 85% (p=0.008) and hematocrit increased from 51.4% to 52.9% (p=0.04). Non-survivors had poorer NYHA function class, lower body weight (BW), lower body mass index (BMI), and higher serum level of Cr at the first visits than survivors. Conclusions: Long term survival and clinical status of adult patients with ES remains unsatisfactory even in the current era of DTT. Poor NYHA functional class, low BW, low BMI and high serum level of Cr were related to mortality. DTT therapy improved clinical status in many patients with Eisenmenger's syndrome, but no significant impact on survival could be shown. [Copyright &y& Elsevier]

Introduction: Although stenting for great vessel stenosis associated with congenital heart diseases (CHD) has been established, there is no stent officially approved for pulmonary stenosis (PS). As no stent has been approved for CHD also in Japan, despite negotiation between academia and the regulatory for longer than 20 years, we decided to apply for the fund to do Investigator-Initiated Clinical Trial from Japan Agency for Medical Research and Development (AMED). Hypothesis: The efficacy of stenting for PS is better than historical data of balloon angioplasty (BA). Methods: We prospectively evaluated efficacy and safety of stenting for PS using CP stent (NuMED, Hopkinton, NY). Study was performed in 11 institutions from May 2014 to April 2017. Inclusion criteria are the following: 1) patients who have post-operative PS, 2) age <40 years, 3) weight >10 kg and 4) history of ineffective BA or findings which suggest that efficacy of BA is unlikely. The lesions as following were include: 1) systolic RV/aortic pressure >0.7, 2) systolic pressure gradient (PG) >20 mmHg in two-ventricle repair, 3) SaO2 <85% and mean PG >3 mmHg in single-ventricle repair and 4) stenosis ratio >0.5 in both single/two-ventricle repair. Primary end point is the effective ratio of stenting; effective stenting is defined as 50% increase in minimum lumen diameter (MLD) following stenting. Secondary end point are the following: 1) percent changes in MLD and re-stenosis within 12 months in both single/two-ventricle repair; 2) percent changes in systolic RV/aortic pressure and percent changes of PG in two-ventricle repair; 3) changes in SaO2 in single-ventricle repair. Results: Thirty three cases are included; the median age was 11(3-36) years and weight was 38(12-69) kg. Underling CHDs were two-ventricle in 27 cases and single-ventricle in 5 cases. Stenting was completed in 22 cases and effective in 86.4% of patients; significantly better than historical control of BA. Percent changes of MLD was 119.3±52.5%. Percent changes of systolic RV/aortic pressure was -8.5±16.1%. Percent changes of PG was -100±0%. There was no re-stenosis and serious adverse events related to CP stent. Conclusions: CP Stent implantation for PS complicated by CHD is safe and effective. [ABSTRACT FROM AUTHOR]

Backgrounds: Few paediatric and perinatal quality indicators (QIs) have been developed in the Japanese setting, and the quality of care is not assured or validated. The aim of this study was to develop QIs in paediatric and perinatal care in Japan using an administrative database and confirm the feasibility and applicability of the indicators using a single-site practice test., Methods: We used a RAND-modified Delphi method that integrates evidence review with expert consensus development. QI candidates were generated from clinical practice guidelines (CPGs) available in English or Japanese and existing QIs in nine selected paediatric or perinatal conditions. Consensus building was based on independent panel ratings. The performance of QIs was retrospectively assessed using data from an administrative database at the National Children's Hospital. Data between April 2018 and March 2019 were used, while data between April 2019 and March 2021 were also used for selected condition, considering the small number of patients. Each QI was calculated as follows: number of times the indicator was met/number of participants×100., Results: From the literature review conducted between 2010 and 2020, 124 CPGs and 193 existing indicators were identified to generate QI candidates. Through the consensus-building process, 133 QI candidates were assessed and 79 QIs were accepted. The practice test revealed wide variations in the process-level performance of QIs in four categories: patient safety: median 43.9% (IQR 16.7%-85.6%), general paediatrics: median 98.8% (IQR 84.2%-100%), advanced paediatrics: median 94.4% (IQR 46.0%-100%) and advanced obstetrics: median 80.3% (IQR 59.6%-100%)., Conclusions: We established 79 QIs for paediatric and perinatal care in Japan using an administrative database that can be applied to hospitals nationwide. The practice test confirmed the measurability of the developed QIs. Benchmarking these QIs will be an attractive approach to improving the quality of care., Competing Interests: Competing interests: None declared, (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There has been no nationwide survey on the prognosis of pediatric dilated cardiomyopathy (DCM) in Japan. Therefore, we designed this retrospective multicenter study to investigate the long-term survival rate in pediatric patients with DCM in Japan., Methods and results: In this multicenter retrospective observational study, data were reviewed for 106 patients aged <18 years who had been diagnosed with DCM at any 1 of 18 Japanese institutions between 1990 and 2014. The median age at diagnosis was 2.0 years and the median duration of observation was 3.3 years. Most DCM patients were diagnosed because of symptoms of heart failure. On echocardiography, the median left ventricular end-diastolic dimension z score was 5.4 and fractional shortening was 0.10. Freedom from death or transplantation rates at 1, 3, 5, 10, and 20 years after diagnosis were 76%, 66%, 64%, 58%, and 43%, respectively. Freedom from death rates at 1, 5, 10, and 20 years after diagnosis were 81%, 75%, 72%, and 53%, respectively. The incidence of heart transplantation at 1, 5, 10, and 20 years after diagnosis was 6%, 15%, 20%, and 20%, respectively, suggesting that only 15% of patients in Japan underwent heart transplantation within 5 years of diagnosis., Conclusions: In Japan, the prognosis of pediatric DCM is poor and the rate of heart transplantation is low.

Background: Although advances in cardiac surgery have led to an increased number of survivors with congenital heart disease (CHD), epidemiological data regarding the pregnancies and deliveries of patients with repaired CHD are scarce., Methods and results: In this study, we retrospectively reviewed the clinical outcomes of pregnancies and deliveries of women with repaired CHD. Overall, 131 women with repaired CHD were enrolled and there were 269 gestations. All patients were classified as New York Heart Association (NYHA) Class I or II. The prevalence of cesarean sections was higher in patients with (CyCHD) than without (AcyCHD) a past history of cyanosis (51% vs. 19%, respectively; P<0.01). There were 228 offspring from 269 gestations and the most prevalent neonatal complication was premature birth (10%), which was more frequent in the CyCHD than AcyCHD group (15.7% vs. 5.6%, respectively; P<0.01). Five maternal cardiac complications during delivery were observed only in the CyCHD group (8%); these were classified as NYHA Class II and none was fatal., Conclusions: Delivery was successful in most women with repaired CHD who were classified as NYHA Class I or II, although some with CyCHD and NYHA Class II required more attention. Cesarean sections were more common in the CyCHD than AcyCHD group, and CyCHD may be a potential risk for preterm deliveries.

Background: Standardized treatment of fetal tachyarrhythmia has not been established., Objectives: This study sought to evaluate the safety and efficacy of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL)., Methods: In this multicenter, single-arm trial, protocol-defined transplacental treatment using digoxin, sotalol, and flecainide was performed for singleton pregnancies from 22 to <37 weeks of gestation with sustained fetal SVT or AFL ≥180 beats/min. The primary endpoint was resolution of fetal tachyarrhythmia. Secondary endpoints were fetal death, pre-term birth, and neonatal arrhythmia. Adverse events (AEs) were also assessed., Results: A total of 50 patients were enrolled at 15 institutions in Japan from 2010 to 2017; short ventriculoatrial (VA) SVT (n = 17), long VA SVT (n = 4), and AFL (n = 29). One patient with AFL was excluded because of withdrawal of consent. Fetal tachyarrhythmia resolved in 89.8% (44 of 49) of cases overall and in 75.0% (3 of 4) of cases of fetal hydrops. Pre-term births occurred in 20.4% (10 of 49) of patients. Maternal AEs were observed in 78.0% (39 of 50) of patients. Serious AEs occurred in 1 mother and 4 fetuses, thus resulting in discontinuation of protocol treatment in 4 patients. Two fetal deaths occurred, mainly caused by heart failure. Neonatal tachyarrhythmia was observed in 31.9% (15 of 47) of neonates within 2 weeks after birth., Conclusions: Protocol-defined transplacental treatment for fetal SVT and AFL was effective and tolerable in 90% of patients. However, it should be kept in mind that serious AEs may take place in fetuses and that tachyarrhythmias may recur within the first 2 weeks after birth., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to determine preferences regarding transfer of patients with congenital heart disease (CHD) attending a children's hospital in Japan and related factors., Methods and results: We conducted a self-administered questionnaire survey with CHD patients >15 years of age treated at the pediatric cardiology outpatient clinic of a children's hospital. Logistic regression analysis was used to identify factors related to patient preferences regarding the transfer. One hundred and eleven of the 122 patients given a questionnaire provided valid responses (valid response rate, 91.0%). Sixty-six subjects (64.9%) reported "not being told anything specific" by their physicians about the transfer from the children's hospital, and 72 (59.5%) stated that they "wished to continue attending the children's hospital". Visiting outpatient clinic with parents (OR, 11.00; 95% CI: 2.01-60.97), having low uncertainty about continuing to attend the children's hospital (OR, 0.95; 95% CI: 0.92-0.98), and having high uncertainty about leaving the current physician (OR, 1.04; 95% CI: 1.01-1.07) were significantly related to the patient's wish to continue to attend the children's hospital., Conclusions: There is a need to improve patient education regarding the opportunities for transfer, and to develop a systematic transition program for children's hospitals and aligned specialized adult CHD centers.

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.

The standard treatment for Kawasaki disease (KD) is high-dose intravenous immunoglobulin (IVIG). Some patients experienced recurrent fever after IVIG following defervescence. However, little is known about the frequency of such episodes and the clinical outcome for such patients. We classified 195 KD patients into 4 groups based on their fever patterns after initial IVIG treatment: group NR (no response), group EF (early recurrent fever within 72 hours after defervescence), group LF (late recurrent fever >72 hours after defervescence), and group GR (good response). We compared the clinical characteristics and laboratory data among these groups retrospectively. Nearly a third of patients had recurrent fever (group EF, n = 45; group LF, n = 11). In two-thirds of these patients, the fever had subsided spontaneously without retreatment; 2 patients in Group LF with smoldering KD symptoms had developed coronary artery lesions (CALs) even after additional IVIG. Recurrent fever and smoldering symptoms might be risk factors for CAL.

Background: Giant coronary aneurysm is the most severe sequela in Kawasaki disease, occurring in approximately 0.2% of patients in Japan. Regression is rare, while myocardial infarction (MI) and sudden death are relatively common. Herein, we reviewed patients with giant coronary aneurysm in a 10-year period., Methods and results: A nationwide questionnaire survey was conducted based on a national epidemiological database from 1999 to 2010. We identified 355 giant coronary aneurysm patients, of whom 209 were analyzed. The 5- and 10-year total cardiac event-free rates were 0.72 and 0.68, respectively. Twelve patients died, and MI was observed in 32 patients (18.1%). Five and 6 deaths were due to coronary rupture and MI, respectively. All ruptures occurred within 1 month of onset, while most MI occurred within 18 months. There was no death beyond 2 years. Aneurysm size was significantly related to the occurrence of MI in both the right and left coronary arteries. At the time of writing, 55% of patients had no exercise limitations. And including patients who cannot perform strenuous exercises, 81% of patients were leading ordinary lives., Conclusions: Severe cardiac events are likely to occur within 2 years from onset of Kawasaki disease, while no deaths occurred beyond this time. Hence, careful monitoring is needed especially for the first 2 years. Most patients with giant coronary aneurysms can lead ordinary lives with appropriate management.

Background: Because there is limited information on fetal bradyarrhythmia associated with congenital heart defects (CHD), we investigated its prognosis and risk factors., Methods and Results: In our previous nationwide survey of fetal bradyarrhythmia from 2002 to 2008, 38 fetuses had associated CHD. Detailed clinical data were collected from secondary questionnaires on 29 fetuses from 18 institutions, and were analyzed. The 29 fetuses included 22 with isomerism, 4 with corrected transposition of the great arteries (TGA) and 3 with critical pulmonary stenosis; 14 had complete atrioventricular block (AVB), 8 had second-degree AVB, and 16 had sick sinus syndrome; 5 died before birth, and 10 died after birth (5 in the neonatal period). Neonatal and overall survival rates for fetal bradyarrhythmia with CHD were 66% and 48%, respectively. Pacemaker implantation was needed in 17 cases (89%). Beta-sympathomimetics were administered in utero in 13 cases and were effective in 6, but were not associated with prognosis. All cases of corrected TGA or ventricular rate ≥70 beats/min survived. A ventricular rate <55 beats/min had significant effects on fetal myocardial dysfunction (P=0.02) and fetal hydrops (P=0.04), resulting in high mortality., Conclusions: The prognosis of fetal bradyarrhythmia with CHD is still poor. The type of CHD, fetal myocardial dysfunction, and fetal hydrops were associated with a poor prognosis, depending on the ventricular rate.

Background: Recently, infant cases of acute heart failure attributable to rupture of the mitral chordae tendineae have been reported. However, little is known about the pathogenesis and clinical course of this condition., Methods and Results: Ninety-five children with rupture of mitral chordae tendineae were identified in nationwide surveys of Japan diagnosed from 1995 to 2013. The clinical manifestations, management strategies, and prognosis were investigated. Eighty-one (85%) patients were between 4 and 6 months (median, 5 months) of age. In 63 (66%) patients, rupture occurred during the spring or summer. The underlying conditions before rupture included Kawasaki disease (10 cases), maternally derived anti-SSA antibodies (2 cases), and infective endocarditis (1 case). Surgery was performed in 80 patients (94 operations), and the final operations included plasty of mitral chordae in 52 cases and mechanical valve replacement in 26 cases. The histopathologic examinations of the mitral valves and chordae (n=28) revealed inflammatory reactions with predominant mononuclear cell infiltration in 18 cases (64%) and increased fibrous and myxoid tissue in 11 cases (39%), suggesting that nonbacterial infectious or autoimmune endocarditis and myxoid changes are involved in the pathogenesis. Eight patients (8.4%) died before (n=6) and shortly after (n=2) the operation, and significant neurological complications persisted in 10 cases (11%)., Conclusions: Acute heart failure attributable to rupture of the mitral chordae tendineae in infants is a unique disease resulting from diverse causes. This condition should be recognized as a significant cardiovascular disorder that may cause sudden onset of cardiogenic shock and death in infants., (© 2014 American Heart Association, Inc.)

Background: There are few large studies of fetal congenital bradyarrhythmia. The aim of the present study was to investigate the effects and risks of transplacental treatment for this condition., Methods and Results: Using questionnaires, 128 cases of fetal bradyarrhythmia were identified at 52 Japanese institutions from 2002 to 2008. Of the 128 fetuses, 90 had structurally normal hearts. Among these 90 fetuses, 61 had complete atrioventricular block (CAVB), 16 had second-degree AVB, 8 had sinus bradycardia, and 5 had other conditions. The 61 CAVB fetuses were divided into those who did (n = 38) and those who did not (n = 23) receive transplacental medication. Monotherapy with β-sympathomimetics, steroid monotherapy, and combination therapy with these agents was given in 11, 5 and 22 cases, respectively. Beta-sympathomimetics improved bradycardia (P<0.001), but no medication could significantly improve the survival rate. Fetal hydrops was associated with a 14-fold increased risk of perinatal death (P = 0.001), and myocardial dysfunction was a significant risk factor for poor prognosis (P = 0.034). Many adverse effects were observed with steroid treatment, with fetal growth restriction increasing significantly after >10 weeks on steroids (P = 0.043)., Conclusions: Treatment with β-sympathomimetics improved bradycardia, but survival rate did not differ significantly in fetuses with and without transplacental medication. It is recommended that steroid use should be limited to <10 weeks to avoid maternal and fetal adverse effects, especially fetal growth restriction and oligohydramnios.

This report describes six previously healthy infants with acute mitral valve chordal rupture. Although their initial symptoms were mild respiratory distress and fever, all the infants presented with acute progressive left heart failure and required urgent surgical repair. Mitral valve annuloplasty and mitral valve replacement were performed (for three patients each). Two patients died, both of whom had cardiac arrest and required resuscitation before surgery. Histologic examination of excised mitral valve leaflets showed infiltration of gram-positive bacteria in these two patients. All the patients were 4-6 months old, which may suggest underlying congenital factors. The authors believe early diagnosis and surgery are crucial as a life-saving measure for infants with acute mitral valve chordal rupture.

For uremic patients, Kidney Disease: Improving Global Outcomes suggest that parathyroid hormone (PTH) levels should be maintained within approximately 2-9 times the upper normal limit for the assay. One of reasons for the lack of definite approximate PTH values is the inability to use the Allegro Intact PTH assay from Nicols. We aimed to evaluate whether other parathyroid hormone assays were suitable for these assessments. We compared the parathyroid hormone concentrations measured with five commercial immunoassays by using three serum pools and seven artificially spiked samples of parathyroid hormone; the Total Intact parathyroid hormone assay was used as the reference assay. Although the results of parathyroid hormone assays showed high correlation, the concentrations differed from Yamasa's assay to another. And the third/second-generation assay ratio was approximately 60%. Further, the Immulite assay overestimated the levels of 1-84 PTH. We showed important inter-method variations in the parathyroid hormone assays used in Japan., (© 2011 The Authors. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.)

The standard measurement of parathyroid hormone (PTH) is the intact PTH (iPTH) assay, which is used for approximately 90% of Japanese dialysis patients. The iPTH assay reacts not only with 1-84 PTH, but also with large truncated fragments of non-1-84 PTH, including 7-84 PTH. On the other hand, the whole PTH assay is specific for 1-84 PTH. The aim of the current study was to define the validity of both whole and intact PTH assays. A total of 738 hemodialysis patients were enrolled from twelve dialysis services. The serum PTH level was evaluated by both intact and whole PTH assays simultaneously. Non-1-84 PTH was determined by subtracting the whole PTH value from that of the intact PTH assay. The median level of whole PTH was 121 pg/mL, and that of iPTH was 210 pg/mL. The whole PTH assay had a very high correlation with the iPTH assay (r = 0.870, P < 0.001). For 43 out of 738 patients (5.8%) the value for intact PTH-whole PTH was <0. Both assays significantly correlated with non-1-84 PTH (P < 0.001), while the iPTH assay, particularly, had a very high correlation with non-1-84 PTH (r = 0.791). As a whole, 18% of the total population was misclassified into a different Japanese guideline category. Stratified by Japanese guideline classifications, 28% of patients within an iPTH target range were misclassified. Using Bland-Altman plot analysis, as the serum PTH level increased, there was a large difference between two assays. Both PTH assays correlate strongly, although the whole PTH assay may be more useful for precise evaluation of PTH function than the iPTH assay., (© 2011 The Authors. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.)

Although varicella is a benign and self-limited disease in children, serious complications can occur. We herein report a case of a 15-month-old boy who required a permanent pacemaker because of complete atrioventricular block as a complication of varicella. Universal vaccination is warranted to prevent such a potentially fatal complication in Japan where varicella is still endemic.

Several previous linkage scans in type 2 diabetes (T2D) families indicated a putative susceptibility locus on chromosome 12q15-q22, while the underlying gene for T2D has not yet been identified. We performed a region-wide association analysis on 12q15-q22, using a dense set of >500 single-nucleotide polymorphisms (SNPs), in 1492 unrelated Japanese individuals enrolled in this study. We identified an association between T2D and a haplotype block spanning 13.6 kb of genomic DNA that includes the entire SOCS2 gene. Evolutionary-based haplotype analysis of haplotype-tagging SNPs followed by a "sliding window" haplotypic analysis indicated SNPs that mapped to the 5' region of the SOCS2gene to be associated with T2D with high statistical significance. The SOCS2 gene was expressed ubiquitously in human and murine tissues, including pancreatic beta-cell lines. Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion. Our data indicate that SOCS2 may play a role in susceptibility to T2D in the Japanese.

A prospective, randomized open-label trial of sevelamer hydrochloride with or without calcium carbonate (CC) involved 86 hemodialysis patients in Japan. The dosage of CC was fixed at 3.0 g/day for the 12-week study. After the first 4 weeks all subjects were changed from CC to sevelamer 3.0 g/day for another 4 weeks, then allocated randomly to three groups for the final 4 weeks: group A, sevelamer 6.0 g/day; group B, sevelamer 3.0 g/day and CC 3.0 g/day; group C, CC 3.0 g/day. The target serum phosphorous concentration (P)=5.5 mg/dL and the corrected calcium concentration (Ca) was 9.0-10.0 mg/dL. Of the 86 patients, 62 finished the study without a change of dosage and their data were analyzed (group A, N=16; group B, N=26; group C, N=20). At week 8 compared with week 4, the concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A, and decreased significantly in groups B and C, and in group B compared with groups A and C; groups A and C had similar concentrations at week 8. The Ca concentration decreased significantly from 9.7+/-1.0 to 9.1+/-0.7 mg/dL after the change to sevelamer. At week 8 Ca was not significantly changed in group A, whereas a significant increase occurred in groups B and C. Side-effects with sevelamer administration occurred in 34 of the 86 patients and 24 dropped out of the study, with a high frequency in group A (13/29; 44.8%). In conclusion, there was an additive effect of sevelamer for the treatment of hyperphosphatemia with CC. The combination therapy was better tolerated and showed higher patient compliance than CC or sevelamer monotherapy.

Study of child-raising issues published in newspapers is lacking. The purpose of this article is to determine the spectrum of issues associated with child raising based on a newspaper. We conducted a cross-sectional study of items related to children (aged <19 years) reported in a Japanese newspaper from July 1, 2001, to June 30, 2002. A total of 1287 child-related items were published. The percentages of reports regarding individual health, health-related issues, topics on two or more issues, and global child issues were 5.9%, 28.8%, 62.9%, and 2.4%, respectively. The most common singly reported issues from 446 items were on child play and recreation, welfare activities, security, child abuse, child death, sports, and parenting. These reports assist parents, families, nurses, pediatricians, and child care workers in providing information on healthy child raising.

Objective: Kawasaki disease (KD) was first reported by Tomisaku Kawasaki in 1967 in Japan. Large-scale nationwide epidemiologic surveys have been conducted continuously by the Japan Kawasaki Disease Research Committee; however, there were very few reports of KD before 1967. This study was performed to clarify when KD appeared in Japan., Design: We investigated the medical charts of patients who had been hospitalized at Tokyo University Hospital between 1940 and 1965., Results: We identified 10 patients whose clinical signs fulfilled the criteria for KD. The ages of the patients ranged from 8 months to 5 years, and their final diagnoses were Stevens-Johnson syndrome, allergic toxic erythema, Izumi fever, scarlet fever, and cervical lymphadenitis. These 10 patients presented between 1950 and 1964, and no confirmed cases were seen between 1940 and 1949., Conclusions: Our findings suggested that KD patients were rare before 1950 in Japan.

Objective: Human low-affinity Fcgamma receptors (FcgammaR) constitute a clustered gene family located on chromosome 1q23, that consists of FcgammaRIIA, IIB, IIC, IIIA, and IIIB genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals, and recent animal studies demonstrated a role for FcgammaRIIB deficiency in the development of autoimmunity. Genetic variants of FcgammaRIIA, IIIA, and IIIB and their association with systemic lupus erythematosus (SLE) have been extensively studied in various populations, but the results were inconsistent. To examine the possibility that another susceptibility gene of primary significance exists within the FcgammaR region, we screened for polymorphisms of the human FCGR2B gene, and examined whether these polymorphisms are associated with SLE., Methods: Variation screening of FCGR2B was performed by direct sequencing and polymerase chain reaction (PCR)-single-strand conformation polymorphism methods using complementary DNA samples. Genotyping of the detected polymorphism was done using genomic DNA, with a specific genotyping system based on nested PCR and hybridization probing. Association with SLE was analyzed in 193 Japanese patients with SLE and 303 healthy individuals. In addition, the same groups of patients and controls were genotyped for the previously known polymorphisms of FCGR2A, FCGR3A, and FCGR3B., Results: We detected a single-nucleotide polymorphism in FCGR2B, (c.695T>C), coding for a nonsynonymous substitution, Ile232Thr (I232T), within the transmembrane domain. The frequency of the 232T/T genotype was significantly increased in SLE patients compared with healthy individuals. When the same patients and controls were also genotyped for FCGR2A-131R/H, FCGR3A-176V/F, and FCGR3B-NA1/2 polymorphisms, FCGR3A-176F/F showed significant association. Two-locus analyses suggested that both FCGR2B and FCGR3A may contribute to SLE susceptibility, while the previously reported association of FCGR3B was considered to be secondary and derived from strong linkage disequilibrium with FCGR2B., Conclusion: These results demonstrate the association of a new polymorphism of FCGR2B (I232T) with susceptibility to SLE in the Japanese.