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Abstract Background The relationships between frailty and clinical outcomes in elderly Japanese patients with non‐valvular atrial fibrillation (NVAF) after catheter ablation (CA) have not been established. We evaluated the frailty rate of patients undergoing CA for NVAF, examined whether CA for NVAF improves frailty, and analyzed the CA outcomes of patients with and without frailty. Methods Elderly Japanese patients (≥65 years; mean age: 72.8 years) who participated in the real‐world ablation therapy with anti‐coagulants in management of atrial fibrillation registry and who responded to the frailty screening index survey were included (n = 213). Frailty and AF recurrence were assessed preoperatively and at 3 and 6 months after CA. Results Twenty‐six patients (12.8%) were frail, 109 (53.7%) were pre‐frail, and 68 (33.5%) were robust. Cardiovascular (frailty: 0.5%/person‐year; pre‐frailty: 0.1%/person‐year; robust: 0.1%/person‐year) and cardiac (frailty: 0.5%/person‐year; pre‐frailty: 0.1%/person‐year; robust: 0.1%/person‐year) events, as well as major bleeding (frailty: 0.3%/person‐year; pre‐frailty: 0.1%/person‐year; robust: 0.1%/person‐year), were numerically more frequent in the frailty group. No deaths from cardiovascular or stroke/systemic thromboembolic events occurred. A large proportion of patients did not experience 3‐month (frailty: 96.2%; pre‐frailty: 96.3%; robust: 88.2%) or 6‐month (frailty: 88.5%; pre‐frailty: 91.7%; robust: 86.8%) AF recurrence after CA. Weight loss, walking speed, and fatigue improved in the frailty and pre‐frailty groups after CA. Conclusion Japanese patients aged ≥65 years with frailty or pre‐frailty had improved frailty screening index components, such as weight loss, walking speed and fatigue, after CA. Therefore, elderly patients with frailty or pre‐frailty may benefit from CA for NVAF.

The effect of laser peening-induced compressive residual stress on the fatigue strength improvement of A7075 specimens was investigated. Rotary bending fatigue tests and residual stress distribution measurements using the sequential polishing method were conducted on untreated, shot-peened, and laser-peened specimens. The results revealed that laser peening provides a deeper compressive stress and a deeper fracture origin, resulting in higher fatigue strength. Furthermore, controlling the laser parameters could extend the depth of the compressive stress layer by approximately 5 mm, indicating the possibility of applying laser peening to thicker materials to improve the fatigue strength.

Abstract Background Although the development of atrial fibrillation (AF) and the progression of chronic kidney disease are known to be interrelated, it remains unclear when and how renal function changes during the clinical course of AF. Methods This study retrospectively enrolled 131 patients who were able to collect data on estimated glomerular filtration rate (eGFR) at least five times during the 500 days before and 500 days after the first visit (baseline) of new-onset AF, respectively. To investigate the temporal relationship between the development of AF and the beginning of worsening renal function (WRF), a piecewise regression model was applied to the eGFR time series data. The time point at which the slopes of the two regression lines changed (inflection -point), the slope before and after the inflection-point (β1 and β2, respectively), and the difference in slope (Δβ) were estimated. The presence of WRF was defined as having the inflection-point at which both Δβ and β2 were

Abstract Objective Pretreatment systemic inflammation and nutrition‐based prognostic indices (SINBPI) have demonstrated significance. This study investigated the prognostic value of pretreatment SINBPI for patients with oropharyngeal cancer and identified unfavorable prognostic markers. Methods We retrospectively reviewed the data of 124 patients with oropharyngeal squamous cell carcinoma (OPSCC) who received definitive treatment between January 2010 and December 2018. The prognostic utility of the neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio (PLR), lymphocyte‐to‐monocyte ratio (LMR), prognostic nutritional index, and high‐sensitivity modified Glasgow prognostic score (HS‐mGPS) was assessed for disease‐free survival (DFS), disease‐specific survival (DSS), and overall survival (OS) using univariate and multivariate analyses. Results Multivariate analyses revealed that human papillomavirus (HPV) status and HS‐mGPS were significantly associated with DFS, DSS, and OS. Patients with a HS‐mGPS of 2 had a significantly higher rate of treatment‐related deaths than those with a HS‐mGPS of 0 or 1. The combination of the HS‐mGPS and PLR had more accurate predictive ability in DFS and OS compared with the HS‐mGPS alone, and the combination of the HS‐mGPS and LMR had more accurate predictive ability in DSS and OS. Conclusion Our results indicated that the HS‐mGPS was a useful prognostic marker for patients with OPSCC, and combined markers consisting of the HS‐mGPS and PLR or LMR may provide more accurate prognostic predictions. Level of Evidence: 3.

Abstract Objectives To analyze various aspects of complex tissue, there is increasing demand to study each sample at different length scales in biology. Correlative light and electron microscopy (CLEM) is the latest technique to correlate two different types of information on the exact same histological area of interest: histology (from light microscopy) and ultrastructure (from electron microscopy). The three‐dimensional fine structures of the maculae flavae (MFe) of the human vocal fold were investigated using CLEM. Methods Five normal human adult vocal folds as specimens embedded in paraffin, sectioned, and mounted on glass slides with/without a chemical digestion method (modified sodium hydroxide maceration method) were investigated. Observations using CLEM were performed. Results The fine structures of cells and extracellular matrices in the MFe and their peripheral regions were able to be observed on the exact same histological area of interest with the light microscope and field emission‐scanning electron microscope. Cobblestone‐like polygonal cells, vocal fold stellate cell‐like cells, and fibroblast‐like spindle cells were intermingled in the MFe of the human vocal fold. The extracellular matrices surrounding each three types of cell in the MFe differed, suggesting the cells were different in functional property. Conclusion CLEM is a useful technique to observe the three‐dimensional fine structures of the human vocal fold mucosa. The results of the present study are consistent with the hypothesis that the cells in the MFe of the human vocal fold have heterogeneity and each three types of cell have different properties.

Facioscapulohumeral muscular dystrophy (FSHD), one of the most common muscular dystrophies, is caused by an abnormal expression of the DUX4 gene in skeletal muscles, resulting in muscle weakness. In this study, we investigated MT-DUX4-ASO, a novel gapmer antisense oligonucleotide (ASO). MT-DUX4-ASO decreased the expression of DUX4 and its target genes in FSHD patient-derived myoblasts. For the first time, we demonstrated that a systemically administered ASO, even without a ligand for drug delivery, could significantly improve muscle injury and motor function in the ACTA1-MCM/FLExDUX4 (DUX4-TG) mouse model of FSHD. Tamoxifen (TMX) injection transiently induces skeletal-muscle-specific DUX4 expression in DUX4-TG mice, while the skeletal muscles of TMX-untreated DUX4-TG mice have leaky DUX4 expression in a small subset of myofibers similar to those of FSHD patients. Subcutaneous 10 mg/kg of MT-DUX4-ASO at two-week intervals significantly suppressed muscular DUX4 target gene expression, histological muscle injury, and blood muscle injury marker elevation in TMX-untreated DUX4-TG mice. Notably, MT-DUX4-ASO at 10 mg/kg every other week significantly prevented the TMX-induced declines in treadmill test running speed and muscle force in DUX4-TG mice. Thus, the systemically administered unconjugated MT-DUX4-ASO suppressed disease progression in DUX4-TG mice, extending the potential of unconjugated ASOs as a promising FSHD treatment strategy.

Syphilis is a sexually transmitted disease caused by Treponema pallidum (TP). We report a case of syphilis that was initially suspected as tongue cancer. An 86-year-old man consulted a neighborhood clinic with an approximately one-month history of pain in the right tongue. The result of scraping cytology of the tongue performed at the clinic was classified as class V, squamous cell carcinoma, and the patient was referred to our hospital. Physical examination revealed a mass on the right side of the tongue and a firm cervical mass. Biopsy revealed no evidence of malignancy; however, the imaging findings led to the suspicion of tongue cancer and lymph node metastasis. The results of blood examination revealed that the patient had syphilis, but since the patient showed few other symptoms, we decided to treat the infection after the planned surgery. We performed right partial glossectomy and neck dissection; however, the postoperative histopathology revealed no evidence of malignancy but nonspecific inflammatory changes with TP spirochetes. The incidence of syphilis has increased dramatically around the world, including Japan, during the last 20 years, and it no longer remains a rare disease. Therefore, syphilis should be included in the differential diagnosis of oral or cervical masses.

Abstract Aims The number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta‐blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio‐selective beta‐blocker use on the long‐term outcomes of patients with HF and COPD. Methods and results Among the 5232 patients with HFrEF (left ventricular ejection fraction of

Abstract Background Anti‐tachycardia pacing (ATP) delivered from an implantable device is a useful tool to terminate ventricular tachycardia (VT). But its real‐world efficacy for those patients having multiple VTs with varying VT rates has not been fully studied. Methods Using the Nippon‐storm study database, efficacy of patient‐by‐patient basis ATP programing for Japanese patients having both non‐fast (120‐187 bpm) and fast VT (≥188 bpm) was assessed. According to the useful criteria of ≥50% success termination by ATP, patients were divided into three subgroups; success ≥50% for both non‐fast and fast VT (both useful), ≥50% only for non‐fast VT (non‐fast VT useful), or ≥50% for neither non‐fast nor fast VT (neither useful). Results During a median follow‐up of 28 months, ATP terminated 184 of the 203 non‐fast VT episodes (91%) and 86 of the 113 fast VT episodes (76%) in all 41 patients. In the patient‐by‐patient analysis, efficacy of ATP was not different between non‐fast and fast VT in most of the patients (36/41 = 88%); 32 patients were in the both useful and four other patients in the neither useful. Neither ischemic nor non‐ischemic structural heart disease was associated with the ATP efficacy, whereas LVEF more than 37.0% and non‐prescribed amiodarone were characteristics of the patients classified into the both useful. Conclusions ATP well terminated both non‐fast and fast VT occurring in individual Japanese patients with various structural heart diseases in the real‐world device treatment and this finding further supports ATP programing for all device tachycardia detection zones in most patients with multiple VTs.

Abstract Background We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT). Methods This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups. Results All patients were diagnosed as having exudative PE by Light’s criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light’s criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4–26.0] vs 17.4 [IQR, 13.7–26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012). Conclusions Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

Abstract Although implantable cardioverter defibrillators (ICDs) are a powerful preventive therapy for cardiac sudden death, there are some populations in whom ICDs cannot be applied because of a lack of a definitive indication (grey‐zone patients), such as in patients during the acute phase of cardiac injury with a susceptible risk for lethal arrhythmias. In such patients, wearable cardioverter defibrillators (WCDs) provide safer bridging period during the acute phase until the final decision‐making for the ICD use and it may eliminate any inappropriate overuse of ICDs in the subacute phase. The JCS/JHRS practical guidelines provide the criteria for WCD use in Japan. Nevertheless, the evidence for that is totally limited in Japan and is dependent on the accumulation of actual real‐world data from other countries in order to be able to discuss the appropriate criteria for WCD use. This study will be conducted retrospectively and/or prospectively, and is an observational and multicenter study among Japanese institutions (J‐WCDR, Japan WCD Registry). This will provide evidence for WCD use in our own country and contribute to upcoming updates for the future guideline revisions.

Background: The Nippon Storm Study was a prospective observational study designed to gather clinical data on implantable cardioverter-defibrillator (ICD) therapy in Japanese patients. Objective: The purpose of this subanalysis was to compare the incidence of ICD therapy in patients with left ventricular dysfunction owing to coronary artery disease (CAD) for primary and secondary prophylaxis of sudden cardiac death. Methods: We analyzed data of 493 patients with CAD and ICDs (men, 87%; age, 68 ± 10 years; left ventricular ejection fraction, 36% ± 13%; primary prophylaxis, 36%). All patients were followed up for at least 2 years. Propensity score matching was used to select patient subgroups for comparison: 133 patients with ICD for primary prophylaxis and 133 with ICD for secondary indications. Results: There were no significant differences between primary and secondary prophylaxis groups with respect to the incidence of appropriate ICD therapy within 2 years (0.153 vs 0.239; hazard ratio, 1.565 [95% confidence interval (CI), 0.898–2.727]; P = .114). Two-year electrical storm risks were 3.3% and 9.6% with HR = 3.236 (95% CI, 1.058–9.896; P = .039) in patients with primary and secondary prophylaxis, respectively. Conclusion: The incidence of ICD therapy received by patients with CAD for primary and secondary prophylaxis was not significantly different based on our propensity score–matched analysis. However, secondary-prophylaxis ICD therapy seems to be associated with a significantly higher risk for electrical storm than primary-prophylaxis ICD therapy.

Aim Understanding how medical students perceive emergency medical care is important in promoting education and recruitment in the field of emergency medicine. This study aimed to clarify the perceptions of undergraduate medical students on emergency medical care with a focus on comparing their perceptions before and during the coronavirus disease 2019 (COVID‐19) pandemic. Methods Fourth‐year undergraduate medical students were invited to complete a self‐administered questionnaire in 2017 and 2020. Free comments on emergency medical care were analyzed via text mining. The relationships among categorical words were evaluated via correlation matrix and correspondence analysis. Results The number of written words per student were not significantly different between 2017 (4.9 ± 3.4) and 2020 (5.3 ± 4.1). In 2017, the most frequently used word was “busy,” and the words “patients,” “life,” and “care” were not related to each other significantly. In 2020, the frequency of the word “busy” decreased and the word “patients” was related to “life” (P

Aims: The clinical impact of the type of atrial fibrillation (AF) has not been completely elucidated in non-ischemic cardiomyopathy (NICM). Although the structure and function of the left atrium (LA) provide prognostic information in patients with heart failure, the relationship of the AF type with LA structure and function in NICM is unclear.Methods: Consecutive patients with NICM who underwent cardiac magnetic resonance were evaluated and followed. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for major adverse cardiovascular events (MACE) related to the AF type, such as paroxysmal AF, chronic AF, and new-onset AF (NOAF).Results: Among 625 patients with NICM (mean age, 64.4 ± 14.2 years; women, 39.7%), 133 had a history of AF at baseline; of these, 60 had paroxysmal AF. Each baseline AF type was associated with higher LA volume and lower LA emptying fraction but not with an increased incidence of MACE (p = 0.245). New-onset AF developed in 5.9% of patients with sinus rhythm over a median follow-up period of 609 days, and maximum LA volume was a strong and independent predictor [p < 0.001, area under the ROC curve (AUC): 0.795]. Maximum LA volume was superior to LA emptying fraction and B-type natriuretic peptide (AUC: 0.683 and 0.680, respectively). The use of β-blocker and the age of the patient were associated with the incidence of NOAF (HR: 0.37, 95% CI: 0.16–0.84 and HR: 1.05, 95% CI: 1.01–1.09, respectively). Kaplan–Meier analysis showed that patients with NOAF had a higher incidence of MACE than those with sinus rhythm or baseline AF (p = 0.002). NOAF and LA emptying fraction were independent predictors of MACE (HR: 2.28, 95% CI: 1.20–3.97 and HR: 0.98, 95% CI: 0.96–0.99, respectively) after adjusting for age, sex, body mass index, and diagnosis.Conclusions: Paroxysmal and chronic AF in patients with NICM were not associated with an increased incidence of MACE despite their association with LA volume and function. NOAF was independently associated with poor prognosis. Higher maximum LA volume predicted the onset and lower LA emptying fraction was independently associated with poor prognosis.

Background: Transesophageal echocardiography (TEE) is currently the gold standard technique for diagnosing left atrial appendage (LAA) thrombi. Cardiac computed tomography (CT) has been expected to become an alternative method to TEE; however, a reliable quantitative evaluation method has not been established. Methods and results: We enrolled 177 patients with persistent atrial fibrillation who underwent both cardiac CT and TEE before catheter ablation. The patients were classified into two groups according to the TEE results: the thrombus group (13 patients) and non-thrombus group (164 patients). The Hounsfield unit (HU) density at the proximal LAA (LAAp) and distal LAA (LAAd) was measured on cardiac CT images. The LAAd/LAAp HU ratio and standard deviation of HU density (HU-SD) at the LAAd were evaluated. We created an algorithm by decision tree analysis to predict LAA thrombus formation using the HU ratio and HU-SD. Definite absence of LAA thrombus (Category-I) was diagnosed for 139 patients by combining the first and second branching of the decision tree (Category-Ia: HU ratio of ≥0.26, Category-Ib: HU ratio of

Introduction: Various risk factors for the first inappropriate implantable cardioverter-defibrillator (ICD) therapy event have been reported, including a history of atrial fibrillation/atrial flutter (AF/AFL), younger age, and multiple zones. Nonetheless, which factors are concordant with real-world data has not been clarified, and risk factors for the second inappropriate ICD therapy event have not been well examined. This study aimed to clarify the risk factors for the first and second inappropriate ICD therapy events. Methods: We conducted a post-hoc secondary analysis of data from a multicenter, prospective observational study (the Nippon Storm Study) designed to clarify the risk factors for electrical storm. Results: The analysis included data from 1549 patients who received ICD or cardiac resynchronization therapy with defibrillator (CRT-D). Over a median follow-up of 28 months, 293 inappropriate ICD therapy events occurred in 153 (10.0%) patients. On multivariate Cox regression analysis, the risk factors for the first inappropriate ICD therapy event were younger age (hazard ratio [HR], 0.986; p = 0.028), AF/AFL (HR, 2.324; p = 0.002), ICD without CRT implantation (HR, 2.377; p = 0.004), and multiple zones (HR, 1.852; p = 0.010). “No-intervention” after the first inappropriate ICD therapy event was the sole risk factor for the second inappropriate ICD therapy event. Conclusions: Risk factors for the first inappropriate ICD therapy event were similar to those previously reported. Immediate intervention after the first inappropriate ICD therapy event could reduce the risk of the second inappropriate event.

Objectives There is growing evidence to suggest that the cells in the maculae flavae of the vocal fold mucosa are tissue stem cells of the human vocal fold. This study investigated the metabolic activity of the cells in the maculae flavae of the human vocal fold from the aspect of mitochondrial microstructure. Study Design Histologic analysis of the human vocal folds. Methods Five normal human adult vocal folds obtained from autopsy cases were investigated under transmission electron microscopy. Results Mitochondria were randomly distributed in the cytoplasm of the cells. The morphological features of the mitochondria consisted of a double‐membrane‐bounded body containing matrices and a system of cristae. In each mitochondria, the lamellar cristae were sparse. The intercristal space was occupied by a mitochondrial matrix which contained electron‐dense matrix granules, mitochondrial DNA, and ribonucleoprotein granules. Some mitochondria spread out over or fused to the surface of a lipid droplet in the cytoplasm. In addition, both the mitochondrial outer and inner membranes and the membranes of the lipid droplets had disappeared. Some close association between mitochondria and rough endoplasmic reticulum was present. Conclusions The features of the mitochondria of the cells in the maculae flavae of the human vocal fold suggested that their metabolic activity and oxidative phosphorylation were low and that they may have shifted to the utilization of lipids to some extent for their metabolic needs. Level of Evidence NA

Background: Patients with implantable cardioverter defibrillator (ICD) use for primary prevention (primary prevention patients) of sudden cardiac death have lower incidence of appropriate ICD therapy (app-Tx) compared with those with ICD use for secondary prevention (secondary prevention patients). However, detail analysis of a second app-Tx after a first app-Tx is still lacking. Objective: This study aimed to compare the incidence of a second app-Tx in primary vs secondary prevention patients. Methods: We conducted sub-analysis of the Nippon Storm Study, which was a prospective, observational study involving 985 patients with structural heart disease (left ventricular ejection fraction ≤ 50%). Of these, we selected 251 patients (62 ± 14 years old, 82% men) who experienced at least one appropriate ICD therapy, and compared occurrence of a second app-Tx between primary (n = 116) and secondary (n = 135) prevention patients. Results: There was no significant difference in the incidence of a second app-Tx between primary and secondary prevention patients (the cumulative incidence for a second app-Tx was 59% at 1 year and 79% at 3 years in primary prevention patients vs the cumulative incidence for the second app-Tx was 59% at 1 year and 75% at 3 years in secondary prevention patients).Additionally, we evaluated the incidence of a second app-Tx according to basal structural disease (ischemic and non-ischemic cardiomyopathy) and found no significant difference between primary and secondary prevention patients. Conclusion: Once app-Tx occurs, primary prevention patients acquire the high risk of subsequent ventricular arrhythmias because there is a comparable incidence of a second app-Tx in secondary prevention patients.

In patients with Brugada syndrome (BS), VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients showed weekly and seasonal patterns. The patients with ESs had peak episodes of VF on Saturday and in the winter and spring, while episodes of VF in patients with single VF events occurred most often on Monday with smaller seasonal variation. Except for age, there was no difference in the clinical or ECG characteristics between the patients with ESs and those with single VF episodes.

Background: There is little information regarding appropriate therapies for coronary artery disease (CAD) patients with implantable devices – such as implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy devices (CRT-Ds) and cardiac resynchronization therapy pacemaker (CRT-P) devices – in Japan. To address this lack of information, we have launched the Japan Implantable Devices in Coronary Artery Disease (JID-CAD) study. Methods: This study has been designed as a prospective, multicenter, non-randomized and observational investigation. All patients will be followed up every six months over a two-year period. The primary endpoint will be the administration of appropriate device therapy. Secondary endpoints include administration of inappropriate therapy, death, hospitalization, or cardiovascular events. Conclusion: In this report, we discuss the current clinical situation of appropriate therapy, and how it is influenced by catheter ablation and revascularization therapy in patients with CAD.

OBJECTIVES:Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells. STUDY DESIGN:Animal experiment using eight beagles (including three controls). METHODS:A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed. RESULTS:A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site. CONCLUSION:The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds.

Purpose: The aim of this study was to describe the recent conditions associated with implantable defibrillation therapy for individual underlying heart diseases. Methods: Ten thousand six hundred and five patients with implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds) that were implanted from 2006 to 2010 were selected from the Japan Cardiac Device Therapy Registry database. They were divided into 12 disease categories and further divided into either primary or secondary prevention of sudden cardiac death. Results: The major underlying diseases of the patients in this cohort were ischemic heart disease (IHD, 35%), dilated cardiomyopathy (DCM, 25%), hypertrophic cardiomyopathy (HCM, 8%), and Brugada syndrome (Brugada, 8%). There were no structural heart diseases in this cohort; the incidence of IHD was relatively lower than that of western countries, while the incidence of cardiomyopathy was higher. The percentage of primary prevention (% primary) among the individual diseases varied. IHD was the most prevalent underlying condition in the patient cohort; however, the % primary was 33%, which was relatively lower than that of the other structural heart diseases. The % primary was relatively higher in patients with DCM (57%) and Brugada (47%). Over 5 years, the % primary gradually increased in patients with DCM, IHD, and HCM, with a particularly dramatic increase in those with DCM. A decrease in the % primary among patients with Brugada began in 2008. Conclusions: In patients that underwent implantable defibrillation therapy, there was a relatively lower % primary in the IHD group, and a substantial increase in the % primary in patients with DCM.

Background: The current status of the efficacy of implantable cardioverter-defibrillator (ICD. and cardiac-resynchronization therapy with implantable defibrillator (CRT-D. in patients with left ventricular dysfunction needs to be clarified. Methods and Results: From the Japanese Cardiac Device Treatment Registry database, a total of 1,584 patients who had an LVEF ≦ 40% and had an ICD or CRT-D were selected as subjects in this study. The difference in the clinical characteristics between the primary and secondary prevention groups and the transition of the indications for device implantation over time were examined. Primary prevention gradually increased up to about 50% in all patients. The implantations of ICD/CRT-D for primary prevention in ischemic hear disease was significantly lower than that in dilated cardiomyopathy (33% vs 51%; p < 0.0001). The number of implantations for CRT-D for primary prevention increased dramatically over a one-year period. Conclusions: In Japan, the implantable defibrillator devices for primary prevention was significantly lower in ischemic heart disease compared with dilated cardiomyopathy. Further, an extension of the indications for ICD/CRT-D implantations has recently been occurring, especially with CRT-D devices for primary prevention.

Recently several randomized trials have demonstrated the excellent role of the implantable cardioverter-defibrillator (ICD) in improving the mortality rate in patients with a high risk of sudden cardiac death regardless of its purpose or the underlying heart disease. However, because such large clinical trials have only been carried out in Western countries, those results may not be fully applicable to Japanese or other Asian patient populations. According to a Japanese study, the total mortality in the patients was approximately 20% during 5 years of follow up, which was comparable to, or slightly better than that in the MADIT-II patients with ICDs. In such a patient population with an excellent prognosis, the MADIT-II criteria can not easily be applied. Therefore, we should strengthen the criteria, i.e. from an EF ≤ 35% to 25% or adopt the usage of additional examinations (e.g. signal averaging ECG, micro-volt T wave alternance or EPS).

Involvement of the dopamine D1 and D2 receptors in the ventral tegmental area (VTA) in the micturition reflex was investigated using female Sprague Dawley rats under urethane anesthesia. Cystometrograms during continuous infusion of warmed saline into the bladder were recorded. When intervals of bladder contraction became constant, the excitatory amino acid DL-homocysteic acid (DLH) was microinjected into the VTA and changes in the cystometric parameters were observed. The selective D1 antagonist SCH23390 (0.3 mg/kg) or D2 antagonist eticlopride (0.1 mg/kg) was subcutaneously injected (s.c.) 15 min prior to the DLH treatment. A low dose of DLH (3 μg) facilitated the micturition reflex, whereas a high dose of DLH (30 μg) inhibited the micturition reflex. However, a middle dose of DLH (10 μg) did not show any effect. The facilitated micturition reflex induced by a low dose of DLH was inhibited by the selective dopamine D2 antagonist eticlopride, but unaltered by SCH23390, a selective dopamine D1 antagonist. In contrast, the inhibitory effect induced by a high dose of DLH on the micturition reflex was suppressed by SCH23390 but not eticlopride. These results suggested that the facilitated micturition reflex might be mediated via the dopamine D2 receptors, while the inhibitory effects on the micturition reflex was mediated via the dopamine D1 receptors.

An understanding of the clinical aspects of electrical storm (E-storms) in patients with implantable cardiac shock devices (ICSDs: ICDs or cardiac resynchronization therapy with defibrillator [CRT-D]) may provide important information for clinical management of patients with ICSDs. The Nippon Storm Study was organized by the Japanese Heart Rhythm Society (JHRS) and Japanese Society of Electrocardiology and was designed to prospectively collect a variety of data from patients with ICSDs, with a focus on the incidence of E-storms and clinical conditions for the occurrence of an E-storm. Forty main ICSD centers in Japan are participating in the present study. From 2002, the JHRS began to collect ICSD patient data using website registration (termed Japanese cardiac defibrillator therapy registration, or JCDTR). This investigation aims to collect data on and investigate the general parameters of patients with ICSDs, such as clinical backgrounds of the patients, purposes of implantation, complications during the implantation procedure, and incidence of appropriate and inappropriate therapies from the ICSD. The Nippon Storm Study was planned as a sub-study of the JCDTR with focus on E-storms. We aim to achieve registration of more than 1000 ICSD patients and complete follow-up data collection, with the assumption of a 5–10% incidence of E-storms during the 2-year follow-up.

We investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells.The effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0-4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined.PEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 μg/kg, 0.06 μg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control.Although in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.