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There has been no nationwide survey on the prognosis of pediatric restrictive cardiomyopathy (RCM) in Japan; therefore, this retrospective multicentered study was designed to investigate the long-term survival rate of pediatric patients with RCM in Japan.Methods and Results: A multicentered, retrospective observational study was performed between 1990 and 2014 and included patients diagnosed with RCM who were aged18 years from 18 Japanese institutions. A total of 54 patients were diagnosed with RCM. The median age at diagnosis was 4.4 years, and the median duration of observation was 2.2 years at the time of this study. Of these patients, 54% had symptoms, including heart failure. Twelve patients died without heart transplantation, mostly due to heart failure. The median time to death from diagnosis was 2.5 years. Freedom from death at 1, 5, and 10 years was 91%, 68%, and 62%, respectively. Death occurred within 5 years of diagnosis in most patients. Twenty-two patients underwent heart transplantation. Freedom from heart transplantation at 1, 5, and 10 years was 77%, 58%, and 53%, respectively. Freedom from death or heart transplantation at 1, 5, and 10 years was 72%, 40%, and 34%, respectively. The presence of symptoms was a risk factor for death or transplantation.The prognosis of pediatric RCM is poor, and the heart transplantation rate is low in Japan.

Catheter-based micro-axial ventricular assist device Impella® (Abiomed, Danvers, MA) has been used in Japanese patients with drug-refractory acute heart failure (AHF) since 2017. This is the first interim analysis of the ongoing Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) to investigate the safety and efficacy of Impella support. Between October 2017 and January 2020, 823 Japanese patients, who were treated with the Impella 2.5, CP, or 5.0 pump, were enrolled. The primary endpoints were safety profiles and cumulative 30-day survival. Among them, 44.8% of patients were acute myocardial infarction with cardiogenic shock. The Impella pumps were unable to implant in 4 patients. The Impella 2.5, CP, and 5.0 pumps were used in 72.4%, 6.2%, and 16.6%, respectively, and mean support duration was 8.1 ± 10.2 days. Combination use of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO) was applied for 387 patients (47.3%). Pump stop occurred 22 patients (2.7%). Major adverse events included hemolysis (11.2%), hemorrhage/hematoma (6.1%), peripheral ischemia (1.6%), and stroke (1.6%). The overall 30-day survival was 62.2%. Survival of patients with single Impella support was significantly higher than patients with Impella combined with VA-ECMO support (81.1% vs 49.6%; p 0.01), who had lower blood pressure, lower left ventricular ejection fraction, and higher degree of inotropic support. Results suggest that short-term outcome of Impella support for Japanese patients was favorable with acceptable safety profiles.

Recessive mutations in the Myosin regulatory light chain 2 (MYL2) gene are the cause of an infantile-onset myopathy, associated with fatal myocardial disease of variable macromorphology. We here present the first Japanese family affected with recessive MYL2 myopathy. Affected siblings manifested typical features and the proband's autopsy findings were compatible with the diagnosis of noncompaction cardiomyopathy. The rapidly progressive clinical course of this recessive MYL2 cardiomyopathy highlights the crucial role of c-terminal tails in MYL2 protein in maintaining cardiac morphology and function.

Recessive mutations in the Myosin regulatory light chain 2 (MYL2) gene are the cause of an infantile-onset myopathy, associated with fatal myocardial disease of variable macromorphology. We here present the first Japanese family affected with recessive MYL2 myopathy. Affected siblings manifested typical features and the proband's autopsy findings were compatible with the diagnosis of noncompaction cardiomyopathy. The rapidly progressive clinical course of this recessive MYL2 cardiomyopathy highlights the crucial role of c-terminal tails in MYL2 protein in maintaining cardiac morphology and function.

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.

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.

The dosing of intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD) has been a matter of debate for decades, with recent studies implicating that larger doses lead to better outcomes. Despite this, few have investigated post-IVIG infusion immunoglobulin G (IgG) levels in relation to outcomes of KD such as response to IVIG and development of coronary artery abnormalities (CAAs). The present study investigated how varying levels of post-infusion IgG affected these outcomes.We collected demographic and laboratory data, including post-infusion IgG, from children with KD who were admitted to six hospitals in Japan between 2006 and 2012. We conducted multivariate analyses to examine the relationship between independent variables and non-response to IVIG and development of CAAs. We used random forest, a decision tree-based machine learning tool, to investigate the marginal effect of varying post-infusion IgG levels on non-response to IVIG and development of CAAs.Of 456 patients included in the study, 130 (28.5%) were non-responders and 38 (8.3%) developed CAAs. Sodium, post-infusion IgG, and AST were significantly associated with non-response. Post-infusion IgG and sodium were significantly associated with CAA development. The random forest plots revealed a decrease in non-response and CAA rates with increasing post-infusion IgG until post-infusion IgG was near the median (2821 mg/dL), after which the non-response and CAA rates leveled off.Greater post-infusion IgG is associated with better response to IVIG and decreased CAA development in KD patients, but this effect levels off at post-infusion IgG levels greater than the median. Key points • Though previous studies have shown that post-intravenous immunoglobulin (IVIG) infusion immunoglobulin G (IgG) is associated with non-response to IVIG therapy and coronary artery abnormality (CAA) development in Kawasaki disease (KD) patients, no study has investigated the relationship between varying levels of post-infusion IgG and these clinical outcomes. • Our study showed that non-response to IVIG therapy and CAA development in Kawasaki disease patients follow a decreasing trend with increasing post-infusion IgG at post-infusion IgG levels below the median. • At values of post-infusion IgG greater than the median, non-response and CAA development rates remain relatively constant with increasing post-infusion IgG. • Our study suggests that when post-infusion IgG is greater than the median, IgG may have fully bound to the therapeutic targets of KD, and in these patients, there may be limited benefit in administering additional IVIG.

Aim Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients. Methods We investigated the HV waveforms in 41 Fontan patients and assessed correlations with clinical parameters, liver fibrosis markers, and hemodynamic data. Results Based on our preliminary analysis of 64 adult patients with chronic liver disease who underwent liver biopsy, we classified HV waveforms into five types with reference to the degree of flattening (from type 1, normal triphasic waveform; to type 5, a monophasic waveform indicating cirrhosis), and confirmed a significant correlation between waveform pattern and fibrosis stage. Notably, we detected HV waveforms in all of the Fontan patients and classified them into five types. The HV waveform pattern positively correlated with γ-glutamyl transferase and hyaluronic acid levels, and negatively correlated with albumin level and platelet count, but did not correlate with central venous pressure or brain natriuretic peptide level, suggesting that HV waveform could reflect pathophysiological changes in the liver without being affected by hepatic congestion. The highest area under the receiver operating characteristic curve of the HV waveform for detecting advanced liver fibrosis, as defined by ultrasonic findings and clinical features, was 0.829 (81.8% sensitivity, 73.3% specificity), which was higher than that of other non-invasive fibrosis markers. Conclusions Hepatic vein waveforms change in accordance with liver fibrosis progression in Fontan patients, and can be a useful indicator of liver fibrosis after the Fontan procedure.

A discharge plasma was applied to initiate the combustion of a hydroxylammonium nitrate-based propellant as a substitute for the catalysts that are typically employed. The resulting thrust and thrust-to-power ratio during short interval firing tests as well as the chamber pressure with a single pulse discharge were evaluated. A 1.5-s firing test generated a maximum thrust of 322 mN along with a thrust-to-power ratio of 0.95 mN/W. During the single-pulse discharge trials, pulsed discharge capacitor energies of 5.4, 10.8, and 16.4 J were assessed, and the maximum chamber pressure was found to increase as the energy was raised. The maximum chamber pressures varied widely between experimental trials, and a 16.4-J energy value resulted in the highest chamber pressure of over 1 MPaG. The time spans between the pulsed discharge and the peak chamber pressure were in the range of 1–2 ms, representing a chamber pressure increase rate much higher than those obtained with standard catalysts.

In this paper, we demonstrated parallelized detection of fluorescent microbeads flowing in multiple microfluidic channels coupled with an array of single photon avalanche diodes (SPADs). A complementary metal-oxide-semiconductor (CMOS)-integrated circuit (IC) containing an SPAD array was used for time-domain separation of fluorescence photons from excitation photons using fast gating and active quenching circuits to realize parallelized detection of fluorescence signals without complex microscopy and optical filters. The system can be used for the development of a parallelized flow cytometry system.

Ecthyma gangrenosum (EG) is a serious bacterial infection in immunocompromised patients. EG in transplant recipients is rarely reported and may go unrecognized, which may delay initiation of appropriate treatment. We report a case of EG in a pediatric heart transplant recipient who was treated successfully with antibiotics and surgical debridement.

A novel synthetic method for hyperbranched polymers is reported. A cobalt catalyst previously developed in our group promotes the catalytic alkyne [2 + 2 + 2] cycloaddition polymerization of aromatic diynes with internal alkynes, which proceeds without gelation or production of insoluble materials to give the corresponding soluble polymer in good yields. The method is reproducible, and the polymerization behavior can readily be predicted by the results of model reactions. Thus, the molecular weight and a degree of branching (DB) of the resulting polymer can be controlled by selecting the internal alkyne monomer and its loading amount. The occurrence of effective endcapping reaction was confirmed by degradation of the polymer derived from a diyne bearing a silyl ether linker, and a high DB of more than 0.5 was obtained.

Background Evidence to guide rescue therapy in refractory Kawasaki disease (KD) is lacking. The aim of this study was to determine the most important variables in predicting non-response to rescue therapy in refractory KD. Methods We retrospectively analyzed 171 patients diagnosed with refractory KD resistant to initial i.v. immunoglobulin (IVIG). Participants received rescue therapy consisting of IVIG monotherapy or IVIG plus prednisolone. Characteristics and laboratory variables were compared between rescue therapy non-responders and responders. Multivariate logistic regression analysis was performed to determine the independent predictors of non-response to rescue therapy. Results Among the 171 participants, 54 (31.6%) were non-responders to rescue therapy. On univariate analysis, fever pattern after initial IVIG, day of illness at rescue therapy, rescue therapy regimen and six laboratory variables (pre-IVIG sodium, C-reactive protein [CRP]; post-IVIG white blood cell count, platelet count, sodium, CRP) were useful in discriminating between non-responders and responders. These nine variables were included in multivariate logistic regression analysis. Persistent fever after initial IVIG (aOR, 2.39; 95%CI: 1.07–5.37) and post-IVIG CRP (aOR, 1.09; 95%CI: 1.02–1.17, per 1 mg/dL increase) were identified as independent predictors of non-response to rescue therapy. IVIG rescue monotherapy (aOR, 3.05; 95%CI: 1.05–8.84) also predicted non-response after adjusting for fever pattern and post-IVIG CRP. Conclusions Persistent fever and elevated CRP after initial IVIG are predictive of non-response to rescue therapy for refractory KD. For patients at high risk of non-response, IVIG plus prednisolone, or even further intensified rescue therapy regimens may be preferable.

Heterotaxy syndrome is associated with complex cardiac malformations and cardiac conduction system abnormalities. Those with right atrial isomerism (RAI) have dual sinus nodes and dual atrioventricular nodes predisposing them to supraventricular tachycardia (SVT). Those with left atrial isomerism (LAI) lack a normal sinus node and are at risk of sinus node dysfunction (SND) and atrioventricular block (AV block). We report the occurrence and risk factors associated with arrhythmias in heterotaxy syndrome. A retrospective review of all heterotaxy syndrome patients born and treated at our institution between 2000 and 2014 was performed. A total of 40 patients were identified; 16/40 (40%) with LAI and 24/40 (60%) with RAI. There were 12 deaths during follow-up [LAI 3/16 (19%), RAI 9/24 (38%); p = 0.30]. Twenty-one patients had arrhythmias during a mean follow-up period of 5.4 years; 14/16 (87%) in LAI and 7/24 (29%) in RAI (p

LEOPARD syndrome (LS) is a form of RASopathy caused by mutations in the PTPN11 gene an upstream regulator of RAS/MAPK signaling. Although hypertrophic cardiomyopathy (HCM) is a shared cardiac phenotype among RASopathies, HCM complicating patients with LS is characteristic for its unique early-onset and progressive features. We herein report a neonate with LS who presented with an extremely severe form of HCM. Autopsy revealed remarkable evidence of active cardiomyocyte proliferation contributing to the overt cardiomegaly. The case suggests an intriguing association between the observed dramatic increase in cardiomyocyte mitotic activity and the fatal clinical course of LS-associated HCM. The patient was the second daughter born to nonconsanguineous parents with no significant family history. Marked biventricular hypertrophy was noted on fetal echocardiography at the 28th week of gestation. After an uneventful delivery, the patient was immediately admitted to the neonatal intensive care unit. Physical examination at birth revealed multiple dysmorphic features, including a wide forehead, low set ears, hypertelorism, and wide set nipples. No skin lesions, such as cafe-au-lait spots or lentigines, were noticed, whereas mild hearing loss was detected by newborn screening. The findings were suggestive of LS. Imaging studies were remarkable for cardiomegaly (Figure …

BackgroundVector flow mapping (VFM) is a novel echocardiographic technology which enables visualization of the intraventricular flow velocity vector. Dissipative energy loss (EL) derived from the velocity vector field of intraventricular blood flow is considered to reflect the efficiency of blood flow, and could be an indicator of left ventricular function. We aimed to determine the reference values of the EL derived from VFM within the left ventricle.MethodsVFM analysis was performed using echocardiography in 64 healthy children. The velocity vector fields of the intra-left ventricular blood flow were obtained from the apical 5-chamber view, and the EL values during systole and diastole were calculated. The measurements were averaged over three cardiac cycles, and indexed to body surface area (BSA).ResultsThe mean subject age was 6.8±4.3 years. The mean EL was 4.10±2.35mW/m/m2 BSA during systole and 16.24±11.63mW/m/m2 BSA during diastole. On multivariate analysis, age and heart rate (HR) were independent predictors of systolic EL, whereas age, HR, and E wave peak velocity were independent predictors of diastolic EL. The regression equations used to predict the BSA-indexed systolic and diastolic EL were as follows: log10 (systolic EL)=−0.0332−0.00213×age (months)+0.00789×HR (beats/min) (adjusted R2, 0.833; p

A colloidal fluid is found to rotate spontaneously during electrolysis when gravity acts perpendicular to the direction of an applied electric field. An aqueous dispersion containing charged colloidal particles is placed inside an O-ring sandwiched between two parallel ITO electrodes. A clip is used to hold the assembly together to prevent the liquid from leaking out. The assembly is positioned such that the electrodes stand vertically, i.e., the electric field during electrolysis points perpendicular to gravity. When a direct-current voltage is applied to initiate the electrolysis of water, a nonlinear colloidal pattern is formed by electroconvective flow. Moreover, the entire fluid rotates spontaneously about the O-ring center with a constant angular velocity. The rotational dynamics are governed by how strong and where the assembly is clipped relative to the gravitational direction. A new phenomenological relationship between the angular velocity, compression vector, and gravity is derived. Coupling of an electrochemical reduction reaction of the ITO film with electroconvection during electrolysis is proposed as a mechanism for the rotational motion.

Background Resistance to intravenous immunoglobulin (IVIG) therapy is a risk factor for coronary lesions in patients with Kawasaki disease (KD). Risk-adjusted initial therapy may improve coronary outcome in KD, but identification of high risk patients remains a challenge. This study aimed to develop a new risk assessment tool for IVIG resistance using advanced statistical techniques. Methods Data were retrospectively collected from KD patients receiving IVIG therapy, including demographic characteristics, signs and symptoms of KD and laboratory results. A random forest (RF) classifier, a tree-based machine learning technique, was applied to these data. The correlation between each variable and risk of IVIG resistance was estimated. Results Data were obtained from 767 patients with KD, including 170 (22.1%) who were refractory to initial IVIG therapy. The predictive tool based on the RF algorithm had an area under the receiver operating characteristic curve of 0.916, a sensitivity of 79.7% and a specificity of 87.3%. Its misclassification rate in the general patient population was estimated to be 15.5%. RF also identified markers related to IVIG resistance such as abnormal liver markers and percentage neutrophils, displaying relationships between these markers and predicted risk. Conclusions The RF classifier reliably identified KD patients at high risk for IVIG resistance, presenting clinical markers relevant to treatment failure. Evaluation in other patient populations is required to determine whether this risk assessment tool relying on RF has clinical value.

Background Although early treatment of Kawasaki disease (KD) with i.v. immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities, the effectiveness of IVIG by day 4 of illness remains to be determined. Methods This was a multi-institutional, retrospective cohort study. Patients diagnosed with KD at ≤4 days of illness were divided into two groups: those who received initial IVIG before and on day 5 of illness. Baseline characteristics were adjusted using propensity scores. The primary endpoint was the need for additional treatment. Results Of 339 patients diagnosed with KD by day 4, 181 and 158 received IVIG before and on day 5 of illness, respectively. Patients in the early treatment group had more adverse prognostic factors: infancy, early onset of the principal symptoms, and abnormal laboratory data. We thus adjusted baseline characteristics before treatment decisions using propensity scores. Propensity score matching of the two groups yielded 100 observations. More patients required additional treatment in the matched early treatment group: 37% vs 24% (adjusted OR, 1.7; 95%CI: 1.06-2.8; P = 0.047). The difference was more pronounced for risk of relapse after initial resolution of fever: 14% vs 5.0% (adjusted OR, 3.2; 95%CI: 1.3-7.7; P = 0.02). The risk of coronary artery lesion did not differ significantly. Conclusions IVIG treatment by day 4 of illness is associated with the requirement for additional treatment even after adjustment of baseline characteristics. Increased resistance to IVIG when given by day 4 should be considered in order to improve the treatment regimen for early-diagnosed KD.

Purpose Congenital heart disease (CHD) is the most common birth anomaly in Japan, occurring in approximately 10.6 of every 1,000 live births. Advancements in medical and surgical care have increased births by women diagnosed with CHD. The study's purpose was to examine the perceptions of pregnancy and childbirth among adolescent girls with CHD. Design and Methods Twelve semi-structured interviews were conducted, and the data were analyzed using a modified grounded-theory approach. Results Three categories and 16 subcategories were extracted. Adolescent girls with CHD reported feelings of distress and anxiety while struggling with their disease, and feared how their disease might negatively influence their future pregnancy. These concerns were related to a desire to become familiar with CHD. The girls also explored how their disease would be managed during pregnancy and childbirth. Overall, these perceptions were influenced by the girls' acceptance of their disease, and support from family, friends, and healthcare professionals. Conclusions Healthcare professionals might assess adolescent girls' awareness of their disease before discussing pregnancy and childbirth risks. To encourage them to understand and cope with their disease, healthcare professionals might provide interventions tailored to the timing, stage, and degree of pregnancy and childbirth awareness. This could allow safer life planning, especially concerning pregnancy and childbirth decisions. Practice Implications To address adolescent girls' needs, healthcare professionals should continuously assess their awareness of pregnancy and childbirth as well as their psychological status, alongside CHD issues.

Although liver fibrosis causes significant morbidity in the late postoperative period of the Fontan procedure, the diagnostic value of hyaluronic acid (HA), a serum marker of liver fibrosis, has not been established in Fontan patients. The purpose of this study was to determine whether increased serum HA concentration in Fontan patients is associated with an increase in inspiratory-to-expiratory flow rate ratio (Qin/Qex) of the portal vein (PV), which is indicative of liver fibrosis. We retrospectively studied 28 consecutive patients with Fontan circulation who underwent cardiac catheterisation for various indications. The median age at examination was 5.5 years (range 2.2-5.6). The median HA concentration was 17.7 ng mL(-1) (range 10.0-82.1), which was used to divide our 28 patients into two groups. Patients in the high-HA group had significantly greater Qin/Qex of the PV than those in the low-HA group (1.25 ± 0.12 vs. 1.12 ± 0.11, p0.05). Platelet counts were significantly lower in the high-HA group (216 ± 74 vs. 294 ± 104 × 10(9) L(-1), p0.05). No significant difference was found in inferior vena caval pressure. In conclusion, increase of HA concentration in Fontan patients accompanies the change in PV hemodynamics peculiar to liver cirrhosis and might be an early indicator of liver fibrosis.

A review examined six consecutive cases of patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) who underwent cardiac surgery at the authors' institution between 2001 and 2011 for associated complex congenital heart diseases. All the patients had a normal karyotype and showed EA with distal TEF. In all cases, gastrostomy was the initial surgical intervention. Cardiac surgery was performed concurrently with gastrostomy for one patient who had a total anomalous pulmonary venous connection with pulmonary venous obstruction. For two patients with duct-dependent pulmonary circulation, EA/TEF was corrected in the neonatal period, and an aortopulmonary shunt operation was electively performed after the first month of life. For two patients with duct-dependent systemic circulation, repair of EA/TEF was performed concurrently with gastrostomy, followed by palliative cardiac surgery during the neonatal period. For another patient without duct-dependent circulation, repair of EA/TEF was performed in the neonatal period. No mortality occurred during a median follow-up period of 6.2 years. However, respiratory complications including severe tracheomalacia for two patients, recurrent episodes of respiratory infection for three patients, and severe gastroesophageal reflux for five patients caused considerable long-term morbidity.

We aimed to elucidate the relationship between severity of secondary mitral regurgitation and mitral valve geometry in children with dilated cardiomyopathy. The medical records of 16 children with dilated cardiomyopathy (median age, 1.2 years; range, 0.4–12.3 years) were reviewed. Mitral valve geometry was evaluated by measuring coaptation depth using echocardiographic apical four-chamber views at the initial presentation. Patients were dichotomised according to the mitral regurgitation severity: patients with moderate or severe secondary mitral regurgitation (n=6) and those with mild secondary mitral regurgitation (n=10). A total of 58 healthy children were considered as normal controls, and a regression equation to predict coaptation depth by body surface area was derived: coaptation depth [mm]=4.37+1.34×ln (body surface area [m2]) (residual standard error, 0.49; adjusted R2, 0.68; p

Because of the rare co-occurrence, it remains a question whether cardiomyopathy is a true association of neurofibromatosis type 1. A boy with café-au-lait spots manifested restrictive cardiomyopathy. Whole exome sequencing confirmed the genetic diagnosis of neurofibromatosis and further identified a novel titin (TTN) missense variant. The significance of the variant is supported by its de novo origin, in silico predictions, and evolutionary conservation. Modern genetics raises an intriguing explanation for the unexpected phenotype and adds to the evolving role of TTN variants in cardiomyopathy.

The effectiveness of transplacental drug therapy for prenatally diagnosed isolated congenital complete atrioventricular block (CCAVB) is controversial. Nine cases of prenatal isolated CCAVB were treated from 2002 to 2007. Ritodrine was administered transplacentally to all fetuses and betamethasone to those whose mothers tested positive for maternal anti-SSA/Ro antibodies. Six of the nine patients had an anti-SSA/Ro-positive mother and received transplacental betamethasone 4 mg/day at a median gestational age of 28 weeks (range, 24-31 weeks). No patients exhibited an improvement in the degrees of complete heart block, and one patient died in utero. No serious adverse events occurred. After the mean follow-up period of 1.7 +/- 1.3 years, all five patients treated with transplacental betamethasone experienced a good cardiac function, whereas one of the three patients not treated with transplacental betamethasone experienced cardiomyopathy and died at the age of 4 months. Pacemaker implantation was required for seven of the eight live-born infants. Transplacental betamethasone therapy for the patients with isolated CCAVB neither improved the degree of atrioventricular block nor decreased the rate of patients requiring pacemaker implantation, but it probably reduced the risk for the development of myocardial disease.

ウンシュウミカン栽培における水管理の指標としての枝体積含水率の可能性を評価するため，TDR法により誘電率を測定して枝体積含水率を推定し，枝体積含水率と土壌水分，気象環境，葉の水ポテンシャル，果実品質との関連性を調査した．主枝基部の枝体積含水率は，4月から上昇して7月に最大値となった．その後は，緩やかに減少して10月中旬の収穫期に最小値を示した後，やや増加して冬季はその水分量を保持した．枝体積含水率の夏季から収穫期にかけての低下と収穫後の増加は，土壌水分の変化との対応関係がみられ，葉の水ポテンシャルを−1 MPa程に維持する水管理を行った場合の枝体積含水率の年間変動パターンは，蒸発散位の変化と対応する傾向にあった．夏秋季に異なる水管理を行い，葉の水ポテンシャルの低下程度が異なった乾燥区と湿潤区では，乾燥区で果実糖度が高く，主枝基部の枝体積含水率は低い値を示した．よって，夏秋季の枝体積含水率と葉の水ポテンシャルとの間に明確な関係はみられなかったものの，枝体積含水率により夏秋季の水分ストレス程度の違いを判別できる可能性が示唆された．