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The relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single-nucleotide polymorphisms (SNPs) and diabetes mellitus (DM) has not been investigated. Therefore, we performed a case-control study to examine this relationship.The study subjects included 2,390 Japanese men and women aged 34 to 88 years. In total, 190 cases were defined as having a fasting plasma glucose level ≥126 mg/dL, having a glycated hemoglobin ≥6.5% or currently using diabetic medication. The 2,200 remaining participants served as control subjects.Compared with study subjects with the CC genotype of AGXT2 SNP rs37369, those with the TT, but not CT, genotype had a significantly increased risk of DM: the adjusted odds ratio (OR) for the TT genotype was 1.83 (95% confidence interval [CI], 1.04 to 3.47). AGXT2 SNPs rs37370 and rs180749 were not significantly associated with the risk of DM. The CTA haplotype of rs37370, rs37369 and rs180749 was significantly positively associated with the risk of DM (crude OR, 1.25; 95% CI, 1.01 to 1.56), whereas the CCA haplotype was significantly inversely related to DM (crude OR, 0.53; 95% CI, 0.27 to 0.95). The multiplicative interaction between AGXT2 SNP rs37369 and smoking status with regard to the risk of DM was not significant (p=0.32 for interaction).This is the first study to show significant associations between AGXT2 SNP rs37369, the CTA haplotype, and the CCA haplotype and DM. No interaction with regard to the risk of DM was observed between rs37369 and smoking.

In pulmonary valve replacement (PVR) after tetralogy of Fallot (TOF) repair, it is recommended that PVR be performed before the right ventricular end-diastolic volume index (RVEDVI) reaches 170 ml/m2 on cardiac magnetic resonance imaging (cMRI) to normalize the RV volume after PVR. We examined the utility of QRS duration, cardiothoracic ratio (CTR), and plasma brain natriuretic peptide (BNP) as markers of an enlarged RV volume to perform PVR at the optimal timing. We assessed the correlation of QRS duration, CTR, and BNP with RVEDVI and RVESVI on cMRI in 26 patients after TOF repair. Fifteen patients underwent PVR (age, 45.2 ± 11.4 years). The RV volume changes from before to after PVR were investigated. Twelve patients underwent post-PVR cMRI. QRS duration, BNP, and CTR were positively correlated with RVEDVI and RVESVI after TOF repair. The post-PVR QRS duration was also positively correlated with post-PVR RVEDVI (p = 0.017) and RVESVI (p = 0.001). From before to after PVR, in cases with QRS duration ≤ 160 ms, the QRS duration decreased from 110.4 ± 28.9 to 101.8 ± 30.5 ms (p = 0.063). Both RVEDVI and RVESVI decreased to the normal range in 4 of 5 cases. In contrast, in cases with QRS duration > 160 ms, the QRS duration decreased from 183.0 ± 17.4 to 160.3 ± 23.8 ms (p = 0.013); however, RVESVI did not normalize in 6 of 7 cases. A prolonged QRS duration is a useful marker of RVEDVI and RVESVI enlargement after TOF repair. A QRS duration of 160 ms is a sensitive cutoff value for predicting RV volume normalization after PVR.

Epidemiological evidence regarding the relationship between fish and fatty acid intake and carotid intima-media thickness (CIMT) has been limited and inconsistent. The current cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study.Study subjects were 2024 Japanese men and women aged 34-88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value ＞1.0 mm.The prevalence of carotid wall thickening was 13.0%. In men, intake of n-3 polyunsaturated fatty acids (PUFA) was independently positively related to the prevalence of carotid wall thickening, while no associations were found between intake of fish and the other fatty acids and carotid wall thickening or maximum CIMT. In women, intake levels of fish, n-3 PUFA, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were independently inversely associated with carotid wall thickening and intake levels of fish, n-3 PUFA, α-linolenic acid, n-6 PUFA, and linoleic acid were independently inversely associated with the maximum CIMT. No significant relationships were found between intake of total fat, saturated fatty acids, or monounsaturated fatty acids and carotid wall thickening or maximum CIMT regardless of sex.In women, higher intake of fish and n-3 and n-6 PUFA may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT.

In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old.This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed.A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase.Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.

In extracardiac Fontan, an epicardial pacemaker implantation has many limitations, especially given that it is highly invasive and a high-risk procedure due to repeat thoracotomy. Herein we illustrate a case with the possibility of transvenous pacing in extracardiac Fontan being less invasive and lower risk transvenous dual-chamber pacemaker implantation by electrophysiological assessment.

Lack of correlation between subjective and objective measurements of daytime sleepiness is common. Here, the frequency of discrepancy between subjective and objective sleepiness, as well as possible predictors, were examined for an adolescent cohort.This study included pediatric patients (aged 10-18 years, n = 211) with various sleep disorder symptoms were evaluated between August 2011 and February 2021. Subjective and objective sleepiness were assessed based on eleven or more scores of the Japanese version of Epworth Sleepiness Scale and a mean sleep latency of 8.0 min or less on the Multiple Sleep Latency Test, respectively. Patients were then classified as both subjectively and objectively sleepy, objectively sleepy, subjectively sleepy, and non-sleepy. Discrepancy-related factors were identified with multivariable logistic regression analysis.The frequency of discrepancy between subjective and objective sleepiness was 46.4%, with 35.5% (75/211) of the patients exhibiting subjective sleepiness without objective sleepiness and 10.9% (23/211) of the patients exhibiting objective sleepiness without subjective sleepiness. Co-existence of neurodevelopmental disorders was associated more often with subjective sleepiness compared to non-sleepiness (odds ratio (OR), 4.12; 95% confidence interval (CI), 1.30 to 12.99) or concordant sleepiness (OR, 7.54; 95% CI, 2.43 to 23.38).Nearly half of the patients exhibited discrepancy between subjective and objective sleepiness, and it more often involved subjective sleepiness. Furthermore, age, bedtime, and neurodevelopmental disorders were identified as significant factors related to subjective sleepiness without objective sleepiness.

Background The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.Methods and Results: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. Conclusions 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.

Background Epidemiological evidence for the relationship between education and income and carotid intima-media thickness (CIMT) has been limited and inconsistent. The present cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study. Methods Study subjects were 2012 Japanese men and women aged 34−88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value > 1.0 mm. Results The prevalence of carotid wall thickening was 13.0%. In participants under 60 years of age (n = 703) and in those aged 60 to 69 years (n = 837), neither education nor household income was associated with carotid wall thickening or with maximum CIMT. Among those aged 70 years or older (n = 472), however, higher educational level, but not household income, was independently related to a lower prevalence of carotid wall thickening: the multivariate-adjusted odds ratio for high vs. low educational level was 0.43 (95% confidence interval 0.21−0.83, p for trend = 0.01). A significant inverse association was observed between education, but not household income, and maximum CIMT (p for trend = 0.006). Conclusions Higher educational level may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT only in participants aged 70 years or older.

An 11-month-old Japanese girl was diagnosed with food protein-induced enterocolitis syndrome (FPIES) after presenting with vomiting approximately two hours after wheat intake. She showed positive results on the first wheat oral food challenge (OFC) at nine months of age, although serum wheat- and ω-5 gliadin-specific immunoglobulin E (IgE) were not detected. The second wheat OFC, performed at age 13 months, induced wheezing (usually an IgE-mediated symptom) 4.5 hours after ingestion, probably owing to gastroesophageal reflux caused by repetitive vomiting. The third wheat OFC, performed at age 25 months, did not trigger reactions. Therefore, gradual low-dose wheat was reintroduced at home. The fourth wheat OFC performed at age 30 months induced no response either; thus, the patient was deemed to have developed tolerance to wheat. This case report, therefore, demonstrates that careful assessment of natural history and physician-supervised OFCs are necessary for adequate diagnosis and the successful management of reintroduction in wheat-induced FPIES.

The introduction of the arterial switch operation has improved the surgical outcome of transposition of the great arteries. However, coronary anomalies such as intramural coronary arteries, single coronary artery, or coronary arteries originating from a single arterial sinus have been reported as independent risk factors for early mortality and late morbidity after an arterial switch operation. We performed an arterial switch operation using a unique technique for translocation of the coronary arteries originating from a single left-side arterial sinus, to prevent coronary artery distortion and subsequent coronary malperfusion.

The management of systemic artery aneurysms secondary to Kawasaki disease (KD) in adults remains a therapeutic challenge. KD guidelines recommend the use of anticoagulation therapy with warfarin in addition to antiplatelet therapy when a giant coronary aneurysm or a history of thrombosis is documented. However, long-term use of warfarin presents several concerns. This case reports acute thrombotic occlusion due to the giant arterial aneurysm in an adult KD. A surgical resection of the aneurysm was performed because of recurrent thrombotic events, despite anticoagulant therapy with warfarin. Pathological examinations revealed a layered thrombus with inflammation in the aneurysm and Factor Xa expression mainly in newly formed thrombus. This study provides an insight into the anticoagulation therapy for cardiovascular sequelae after KD.

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort. Methods: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing. Results: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia ( P =0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure. Conclusions: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

Our previous report indicated that vascular injury enhances vascular remodeling in fetal growth restriction (FGR) mice. The angiotensin II type 2 receptor (AT2R) is relatively highly expressed in fetal mice. Therefore, we investigated the roles of AT2R in FGR-induced cardiovascular disease using AT2R knockout (AT2KO) mice. Dams (wild-type and AT2KO mice) were fed an isocaloric diet containing 20% protein (NP) or 8% protein (LP) until delivery. Arterial blood pressure, body weight, and histological changes in organs were investigated in offspring. The birth weight of offspring from dams fed an LP diet (LPO) was significantly lower than that of offspring from dams fed an NP diet. The heart/body and kidney/body weight ratios in AT2KO-LPO at 12 weeks of age were significantly higher than those in the other groups. Greater thickness of the left ventricular wall, larger cardiomyocyte size and enhancement of perivascular fibrosis were observed in AT2KO-LPO. Interestingly, mRNA expression of collagen I and inflammatory cytokines was markedly higher in the AT2KO-LPO heart at 6 weeks of age but not at 12 weeks of age. AT2R signaling may be involved in cardiovascular disorders of adult offspring with FGR. Regulation of AT2R could contribute to preventing future cardiovascular disease in FGR offspring.

To assess a two-phase contrast injection protocol for contrast enhancement during cardiac computed tomography (CT) in children with congenital heart disease. Forty-three children (20 boys, 23 girls) of median age 13 months (range 3 days-8.3 years) and weighing ≤ 20 kg who underwent cardiac CT using a two-phase contrast injection protocol at our institution were retrospectively identified. High-pitch spiral third-generation dual-source cardiac CT (tube voltage 70 kV) was performed with a fixed delay of 60 s after contrast injection in the order of 10 mgI/kg/s (30 s), 15 mgI/kg/s (20 s), and a saline chaser (10 s). Attenuation in the inferior vena cava (IVC), superior vena cava (SVC), right atrium (RA), right ventricle (RV), pulmonary artery (PA), left atrium (LA), left ventricle (LV), and descending aorta (AO) was compared using the Steel-Dwass and Fisher's exact tests. The median (interquartile range) attenuation in the IVC, SVC, RA, RV, PA, LA, LV, and AO was 285 (264-347) Hounsfield units (HU), 416 (370-445) HU, 368 (320-388) HU, 373 (322-417) HU, 397 (330-432) HU, 425 (373-469) HU, 435 (385-468) HU, and 437 (392-491) HU, respectively (p 0.05, IVC vs. the other anatomic sites). There was no significant difference in diagnostic success rate for attenuation 250 HU between the IVC (41 children, 95.3%) and the other sites (43 children, 100%). A two-phase contrast injection protocol is useful for effective contrast enhancement in pediatric cardiac CT.

We report the first case of transcatheter perimembranous ventricular septal defect (pmVSD) closure in Japan where none of existing devices for VSD closure has been approved. The pmVSD was successfully closed with first generation Amplatzer® duct occluder (ADO-I; St Jude Medical, St Paul, MN, USA). The procedure was performed under general anesthesia with transesophageal echocardiographic and fluoroscopic guidance. The left ventricular volume overload after the procedure was remarkably improved and no major complications occurred. ADO-I can be a safe and effective option for transcatheter pmVSD closure. The incidence of heart block may be less than reported with the original device.

Background: Acute coronary syndrome (ACS), which is emerging in adults long after confirmed (followed-up or lost-to-follow), or missed Kawasaki disease (KD), is poorly characterized.Methods and Results: A Japanese retrospective nationwide hospital-based questionnaire survey of ACS during 2000–09 was conducted to characterize such patients. Among a total of 67 patients (median age 35, male 76%) recruited, low conventional coronary risks (≤1/6) was noted in 75%, a diagnosis of ST-elevation and myocardial infarction or cardiac arrest in 66%, medication before ACS in 22% (warfarin in 4%), and no prior history of acute myocardial infarction in 94%. One-month mortality was 19%. KD diagnosis was made in 32 during acute illness (Group A), in which 17 were lost to follow, and retrospectively in the other 35 from coronary imaging at ACS (Group B). Group A developed ACS at lower coronary risks (≤2/5 in 87 vs. 65% in group B, p = 0.043) at a younger age (26.5 vs. 40 yo, p < 0.001). In group A, followed-up patients developed ACS under medication before ACS (87 vs. 0% in lost-to-follow patients, p < 0.001) for giant aneurysm in culprit lesions (69 vs. 29%, p = 0.030). One-month mortality was comparable between groups A and B, and between patients followed-up and lost-to-follow in group A. The culprit lesion in group A was characterized by the association of an aneurysm ≥6 mm in acute KD (100%), lack of significant stenosis (61%) or giant aneurysm (50%) in the long-term (median interval 16 y), and the presence of intravascular ultrasound-derived calcification at ACS (86%).Conclusions: The present retrospective nationwide questionnaire survey demonstrated nationwide emergence of initial ACS in young adults at low coronary risks, who are followed-up or lost-to-follow after confirmed KD and initial coronary aneurysms ≥6 mm.

Congenital long QT syndrome (LQTS) caused by compound mutations is usually associated with more severe clinical phenotypes. We identified a LQTS family harboring three compound mutations in different genes (KCNQ1-R174C, hERG-E1039X and SCN5A-E428K). KCNQ1-R174C, hERG-E1039X and SCN5A-E428K mutations and/or relevant wild-type (WT) cDNAs were respectively expressed in mammalian cells. IKs-like, IKr-like, INa-like currents and the functional interaction between KCNQ1-R174C and hERG-E1039X channels were studied using patch-clamp and immunocytochemistry techniques. (1) Expression of KCNQ1-R174C alone showed no IKs. Co-expression of KCNQ1-WT + KCNQ1-R174C caused a loss-of-function in IKs and blunted the activation of IKs in response to isoproterenol. (2) Expression of hERG-E1039X alone and co-expression of hERG-WT + hERG-E1039X negatively shifted inactivation curves and decelerated the recovery time from inactivation. (3) Expression of SCN5A-E428K increased peak INa, but had no effect on late INa. (4) IKs and IKr interact, and hERG-E1039X caused a loss-of-function in IKs. (5) Immunocytochemical studies indicated that KCNQ1-R174C is trafficking defective and hERG-E1039X is defective in biosynthesis/degradation, but the abnormities were rescued by co-expression with WT. Thus, KCNQ1-R174C and hERG-E1039X disrupted IKs and IKr functions, respectively. The synergistic lesion, caused by KCNQ1-R174C and hERG-E1039X in IKs, is very likely why patients showed more severe phenotypes in the compound mutation case.

Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, and sternal malformations' (PHACES) syndrome comprises various defects that require a concrete therapeutic plan. Herein, we report a case of a very low birth weight infant with PHACES syndrome presenting complete sternal cleft, interrupted aortic arch with ventricular septal defect, and absence of communicating cerebral arteries. Due to the infant's very low birth weight, we planned staged surgery for this complex disease. First, bilateral pulmonary artery banding was performed to improve unstable hemodynamics. Then, after sufficient body weight was obtained, aortic arch and intracardiac repair was done. However, when the tracheal tube was removed 2 weeks after surgery, the patient could not breathe well due to paradoxical chest movement related to complete sternal cleft. Consequently, to improve chest wall compliance, the upper sternum was constructed with dislocated ribs. After these treatments, the patient gained adequate weight and was in stable condition. Staged surgical treatment of sternal cleft and congenital heart defects is a potential therapeutic option for PHACES syndrome, particularly in very low birth weight infants with complex cardiovascular disease.

Summary Background Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities. Methods We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174. Findings We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25–0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78). Interpretation Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG. Funding Japan Agency for Medical Research and Development (grant CCT-B-2503).

Background Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history. Case presentation A 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8. Conclusions This case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals.

Infantile hemangioma (IH) is the most common tumor of infancy, and it sometimes associated with Kasabach-Meritt syndrome (KMS) characterized by anemia, intraperitoneal hemorrhage secondary to rupture, coagulopathy, jaundice, and vascular malformations involving the brain, skin, gut, and other organs. Here, we report two newborn patients having IH with KMS at birth. The first patient had a giant hemangioma in the liver, which was successfully treated with i.v. corticosteroid and coil embolization. The second patient had a large hemangioma of the right axillary region, which was also successfully treated with i.v. corticosteroid, beta-blocker, coil embolization and local irradiation. All symptoms were controlled without any side-effects in both patients. According to these findings, combination therapy including coil embolization and corticosteroid is effective for IH patients with KMS. The indications for and timing of coil embolization should be determined further cases have been accumulated.

Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O2−) rapidly inactivates NO and forms peroxynitrite (ONOO−). It is known that ONOO− accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE.

Background Serum procalcitonin (PCT) increases in various respiratory disorders such as acute respiratory distress syndrome. Elevated PCT is also observed in healthy neonates. In this study, we investigated whether PCT is a good marker of respiratory disorder in neonates. Methods A total of 155 neonates with or without respiratory disorder, were eligible for the study. PCT was measured on electrochemiluminescence immunoassay. Each neonate was allocated to the non-respiratory disorder (control) group (n = 95), or a respiratory disorder group (n = 60). PCT was compared between the groups, and association with other markers, including C-reactive protein (CRP) and white blood cell (WBC) count, was analyzed. Results Of the 60 neonates in the respiratory disorder group, 39, 10, five, one, two, two, and one neonates had transient tachypnea of the newborn, respiratory distress syndrome, air leak syndrome, meconium aspiration syndrome, 18-trisomy, neonatal asphyxia, and congenital diaphragmatic hernia, respectively. Mean PCT, CRP and WBC count in the respiratory disorder group were 9.01 ng/mL, 0.26 mg/dL, and 16 100 cells/μL, respectively. The area under the curve obtained for PCT in distinguishing between the respiratory disorder and control groups was 0.85 (sensitivity, 66.7%; specificity, 93.0%; optimum cut-off, 3.73 ng/mL), that for CRP was 0.72 (sensitivity, 75.0%; specificity, 64.6%; optimum cut-off, 0.14 mg/dL), and for WBC it was 0.44 (sensitivity, 60.0%; specificity, 29.6%; optimum cut-off, 15 000 cells/μL). Conclusions PCT is more susceptible, as a diagnostic parameter of infection, to the effect of respiratory disturbance than CRP and WBC.

Aortic coarctation rarely occurs after an arterial switch operation for D-transposition of the great arteries with intact ventricular septum. We report the case of a neonate patient in whom aortic coarctation developed 28 days after an uncomplicated arterial switch operation. Preoperatively, the aorta was noted to have an irregular shape, but there was no pressure gradient across the lesion. The patient underwent successful reoperation to correct the coarctation. We hope that our report raises awareness of a rare early complication after arterial switch operation with intact ventricular septum, and the need to carefully monitor the aortic isthmus in patients who have aortic irregularities, even in the absence of a pressure gradient.

22q11.2 deletion syndrome is one of the most common human microdeletion syndromes. The clinical phenotype of 22q11.2 deletion syndrome is variable, ranging from mild to life-threatening symptoms, depending mainly on the extent of the deleted region. Brain malformations described in association with 22q11.2 deletion syndrome include polymicrogyria, cerebellar hypoplasia, megacisterna magna, and agenesis of the corpus callosum (ACC), although these are rare. We report here for the first time a patient who manifested combined D-2- and L-2-hydroxyglutaric aciduria as a result of a hemizygous mutation in SLC25A1 in combination with 22q11.2 deletion. The girl was diagnosed to have ACC shortly after birth and a deletion of 22q11.2 was identified by genetic analysis. Although the patient showed cardiac anomalies, which is one of the typical symptoms of 22q11.2 deletion syndrome, her rather severe phenotype and atypical face prompted us to search for additional pathogenic mutations. Three genes present in the deleted 22q11.2 region, SLC25A1, TUBA8, and SNAP29, which have been reported to be associated with brain malformation, were analyzed for the presence of pathogenic mutations. A frameshift mutation, c.18_24dup (p.Ala9Profs*82), was identified in the first exon of the remaining SLC25A1 allele, resulting in the complete loss of normal SLC25A1 function in the patient's cells. Our results support the notion that the existence of another genetic abnormality involving the retained allele on 22q11.2 should be considered when atypical or rare phenotypes are observed.

Background: Circumstances and outcomes of out-of-hospital cardiac arrest (OHCA) in elementary and middle school students while at school in the era of public-access defibrillation are unknown. Methods and Results: We conducted a nationwide hospital-based survey of elementary and middle school students who had had OHCA of cardiac origin and received prehospital resuscitation in 2005–2009. Among 58 cases recruited, 90% were witnessed by bystanders; 86% had ventricular fibrillation as the initial rhythm; 74% were resuscitated by bystanders; 24% were defibrillated by bystanders; 55% occurred at school; 66% were exercise-related; 48% were followed up before the event; 67% had structural heart disease. In total, 53% of overall patients and 79% of those initially defibrillated by bystanders had a favorable neurological outcome. Patients were more likely to be defibrillated by bystanders (38% vs. 8%, P=0.012) and had a more favorable neurological outcome in schools (69% vs. 35%, P=0.017) than in other locations. The majority of arrests in schools were exercise-related (84% vs. 42%, P=0.001), occurred at sports venues, and students were resuscitated by teachers; half of the cases at school occurred in patients with a pre-event follow-up. Conclusions: After OHCA, children were more likely to be defibrillated by bystanders and had a better outcome in schools than in other locations, which may be relevant to the circumstances of events. (Circ J 2014; 78: 701–707)

Background: Electrocardiographic and molecular studies have clarified an association between sudden infant death syndrome (SIDS) and long QT syndrome (LQTS), and few data are available for the QT interval in infancy from birth to 1 year of age. Appropriate time of electrocardiographic screening is not clarified. Medical examinations during infancy are mandatory in Japan. Methods and Results: The study population included 1,058 infants. Electrocardiograms were collected with information of infants at birth and at examination. The QT intervals of three consecutive beats were measured in lead V5. Statistical analysis revealed that the following formula was appropriate to minimize the effect of heart rate for infants: corrected QT interval; QTc = QT interval/RR interval 0.43. Subjects were divided into four groups as follows: 0–2, 3–6, 6–11, and 12–52 weeks of age. Tukey's multiple comparison showed that the QTc intervals were longest (p < 0:0001) in subjects who were 6–11 weeks of age. Conclusions: The QTc interval showed the highest peak at 6-11 weeks of age in infancy. The peak period of occurrence of SIDS is at approximately 2 months of age. An appropriate time of electrocardiographic screening for QT prolongation will be one month of age, and follow-up studies are needed.

Open heart surgery for infants with low body weight (BW) remains still a challenge. Pulmonary artery banding (PAB) is a useful surgical palliation for small neonates and early infants with excessive pulmonary blood flow who are unable to withstand a heart surgery. This study retrospectively reviewed neonates and infants who underwent PAB to assess the surgical results and the validity of our PAB. We selected 38 acyanotic infants and neonates and divided them into 2 groups: low BW (2.5 kg, n = 15, group L) and normal or high BW (≥ 2.5 kg, n = 23, group NH). The average BW at the time of PAB was 2.8 ± 1.1 kg (range, 1.2-5.8 kg), and the average age at the time of PAB was 41.8 ± 44.8 days (range, 2-151 days). Using a 3-mm-wide polyester tape, we tightened the main pulmonary artery to obtain the circumference of (19 mm + 1 mm for each kg of BW). There was no early death but one late death in each group. Postoperative BW continuously increased 1 month after PAB in both groups, although BW was significantly lower in group L than in group NH. Intracardiac repair (ICR) was accomplished in 31 patients (13 in group L and 18 in group NH) at average ages of 1.5 years, while the remaining 5 patients are awaiting ICR. In conclusion, PAB using our formula for the infants even weighing2.5 kg has low mortality and is effective as a bridge to ICR.