Realization of thin-film m-plane InGaN laser diode fabricated by epitaxial lateral overgrowth and mechanical separation from a reusable growth substrate.

A nonpolar edge emitting thin film InGaN laser diode has been separated from its native substrate by mechanical tearing with adhesive tape, combining the benefits of Epitaxial Lateral Overgrowth (ELO) and cleavability of nonpolar GaN crystal. The essence of ELO is mainly to weakening strength between native substrate and the fabricated laser device on top of it. We report a 3 mm long laser bar removed from its native GaN substrate. We confirmed edge emitting lasing operation after cleaving facets on a separated thin bar. Threshold current density of the laser was measured to be as low as 2.15 kA/cm2.

Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin.

AIM: Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non-TT. Among such treatment-refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non-TT. METHODS: Patients were randomly assigned to receive simeprevir (100 mg/day) for 12 weeks plus PEG IFN/ribavirin for 24 weeks (control group, n = 58), or vitamin D (2000 IU/day) for 16 weeks including a lead-in phase plus PEG IFN/ribavirin for 24 weeks (vitamin D group, n = 57). The primary end-point was sustainably undetectable viremia 24 weeks after the end of treatment (SVR). RESULTS: SVR rates were 37.9% in the control group and 70.2% in the vitamin D group. In subgroup analysis, SVR rates of prior null responders were 11.8% and 54.5%, respectively. SVR rates for advanced fibrosis were 28.6% and 65.4%. SVR rates for patients with vitamin D3 deficiency at the baseline were 25.0% in the control group and 66.7% in the vitamin D group. Overall, the SVR rate was significantly higher in patients with high serum 25(OH)D3 levels at the beginning of combination therapy than in those with low serum 25(OH)D3 levels. CONCLUSION: Native vitamin D3 supplementation improved SVR rates in simeprevir with PEG IFN/ribavirin for chronic hepatitis C genotype 1b patients with refractory factors.

Influencing factors on serum 25-hydroxyvitamin D3 levels in Japanese chronic hepatitis C patients.

BACKGROUND: Serum 25-hydroxyvitamin D3 levels are generally lower in chronic hepatitis C patients than in healthy individuals. The purpose of this study is to clarify the factors which affect serum 25-hydroxyvitamin D3 levels using data obtained from Japanese chronic hepatitis C patients. METHODS: The subjects were 619 chronic hepatitis C patients. Serum 25-hydroxyvitamin D3 levels were measured by using double-antibody radioimmunoassay between April 2009 and August 2014. Serum 25-hydroxyvitamin D3 levels of 20 ng/mL or less were classified as vitamin D deficiency, and those with serum 25-hydroxyvitamin D3 levels of 30 ng/mL or more as vitamin D sufficiency. The relationship between patient-related factors and serum 25-hydroxyvitamin D3 levels was analyzed. RESULTS: The cohort consisted of 305 females and 314 males, aged between 18 and 89 years (median, 63 years). The median serum 25-hydroxyvitamin D3 level was 21 ng/mL (range, 6-61 ng/mL). On the other hand, the median serum 25-hydroxyvitamin D3 level in the healthy subjects was 25 ng/mL (range, 7-52), being significantly higher than that those in 80 chronic hepatitis C patients matched for age, gender, and season (p = 1.16 × 10(-8)). In multivariate analysis, independent contributors to serum 25-hydroxyvitamin D3 deficiency were as follows: female gender (p = 2.03 × 10(-4), odds ratio = 2.290, 95 % confidence interval = 1.479-3.545), older age (p = 4.30 × 10(-4), odds ratio = 1.038, 95 % confidence interval = 1.017-1.060), cold season (p = 0.015, odds ratio = 1.586, 95 % confidence interval = 1.095-2.297), and low hemoglobin level (p = 0.037, odds ratio = 1.165, 95 % confidence interval = 1.009-1.345). By contrast, independent contributors to serum 25-hydroxyvitamin D3 sufficiency were male gender (p = 0.001, odds ratio = 3.400, 95 % confidence interval = 1.635-7.069), warm season (p = 0.014, odds ratio = 1.765, 95 % confidence interval = 1.117-2.789) and serum albumin (p = 0.016, OR = 2.247, 95 % CI = 1.163-4.342). CONCLUSIONS: Serum 25-hydroxyvitamin D3 levels in chronic hepatitis C Japanese patients were influenced by gender, age, hemoglobin level, albumin and the season of measurement.

Long-term outcomes after catheter ablation for idiopathic atypical atrial flutter.

BACKGROUND: Idiopathic atypical (non-cavotricuspid isthmus-dependent) atrial flutter (IAAFL) may be seen in patients without structural heart disease and without previous cardiac surgery or ablation. OBJECTIVE: This study sought to determine the patient characteristics, electrophysiologic and electroanatomic properties, and clinical outcomes after ablation in patients with IAAFL. METHODS: We retrospectively compared IAAFL patients with cavotricuspid isthmus-dependent AFL (C-AFL) patients undergoing catheter ablation. The primary outcome was a composite of death from cardiovascular causes, ischemic stroke, and hospitalization for worsening of heart failure. RESULTS: Of 180 patients who underwent catheter ablation for AFL, 89 were included in this study (22 IAAFL and 67 C-AFL). Electrophysiologic study showed significantly longer intra-atrial conduction time and lower atrial voltage during sinus rhythm in the IAAFL group compared with the C-AFL group. The atrial scar was observed in all 22 IAAFL patients, with the most common sites being the posterior or lateral wall of the right atrium in 10 (45.5%) and the anterior wall of the left atrium in 8 (36.4%). During 3.5 ± 2.8 years of follow-up, the composite primary end point occurred significantly more frequently in the IAAFL group (hazard ratio [HR], 3.45; 95% confidence interval [CI], 1.20-9.89; P = .015). In multivariable analysis, brain natriuretic peptide levels (HR, 1.01; 95% CI, 1.00-1.01, per 1 pg/mL; P = .01) and IAAFL (HR, 4.14; 95% CI, 1.21-14.07; P = .02) were independently associated with the primary outcome. CONCLUSION: IAAFL in patients had distinct electrophysiologic features suggestive of atrial cardiomyopathy. These patients are at risk for development of cardiovascular adverse events after ablation.

Precordial ST-Segment Elevation: Anterior Myocardial Infarction or Something Else?

The differential diagnosis of ST-segment elevation on electrocardiogram is multifaceted. Particularly, in cases of precordial ST-segment elevation, considering anterior myocardial infarction is crucial. Herein, we present a case of precordial ST-segment elevation with normal left coronary arteries.

Narrow QRS Complex Tachycardia With Variable R-R Intervals and Discrete P Waves.

Irregular narrow QRS complex tachycardia is associated with a wide range of differential diagnoses, including atrial fibrillation and atrial tachyarrhythmia with altered atrioventricular conduction. Here, we present a case of narrow QRS complex tachycardia with variable R-R intervals and discrete P waves. (Level of Difficulty: Intermediate.).

Acute pulmonary vein stenosis during radiofrequency catheter ablation for atrial fibrillation.

We encountered acute pulmonary vein (PV) stenosis during radiofrequency catheter ablation. PV stenosis was not apparent before redo ablation (A). However, acute PV stenosis was observed after repeat ablation, including carina ablation (B, C). Computed tomography performed 6 months post-ablation revealed chronic PV stenosis (D).

Acute hypoxemia caused by Impella in a patient with fulminant myocarditis and patent foramen ovale.

Impella ™ (Abiomed, Danvers, MA, USA) is effective in the acute management of fulminant myocarditis and myocardial infarction with cardiogenic shock. Here, we report a case of a 70-year-old man with fulminant myocarditis in cardiogenic shock who developed right-left shunt via patent foramen ovale during acute management with Impella 5.0, resulting in sudden hypoxemia. With combined support of veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA), his circulation and oxygenation became stable. The same phenomenon is well known in left ventricular assist device. In such situations, ECPELLA is effective to improve the hypoxic condition. It should be kept in mind that hypoxemia can occur in patients with intracardiac shunt disease when using Impella. Learning objective: Impella is effective to maintain circulation in patients with cardiogenic shock; however, several complications have been reported. Intra-cardiac shunt can suddenly cause severe hypoxemia by Impella. We should mention the presence of intra-cardiac shunt, if the patients have sudden hypoxemia when using left ventricular assist.

Prognostic Value of Left Atrial Calcification After Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Left atrial calcification (LAC) has occasionally been observed in patients who underwent catheter ablation for atrial fibrillation (AF) by chest computed tomography (CT). However, the evidence regarding the clinical impact of LAC in patients with AF is lacking. OBJECTIVES: This study aims to investigate the prevalence of LAC in AF patients and evaluate its clinical significance after AF ablation. METHODS: This observational registry included AF patients who received computed tomography and serial transthoracic echocardiography between January 2010 and November 2017. The primary composite outcome included cardiovascular death, hospitalization for worsening heart failure, and ischemic stroke. RESULTS: Among 534 patients (age 72 ± 13 years, 62.5% men) who met the inclusion criteria, 31 (5.8%) had LAC. In multivariable analysis, AF ablation was associated with an 11.8-fold (OR: 11.8; 95% CI: 2.03-227.65) increased risk of the development of LAC in AF patients. Among 218 patients with AF ablation, LAC was detected in 30 (13.8%) patients. Prior stroke (HR: 2.73; 95% CI: 1.08-6.93) and multiple ablation procedures (HR: 4.21; 95% CI: 1.63-10.87) were independently associated with the development of LAC in AF-ablation patients. During a median follow-up of 5.8 years, the primary composite outcome occurred in 11 patients in the LAC group (39.8 per 1,000 person-years) and 10 patients in the non-LAC group (8.9 per 1,000 person-years). The adjusted HR for the primary composite outcome in the LAC group, as compared with the non-LAC group, was 2.81 (95% CI: 1.16-6.84; P = 0.02). CONCLUSIONS: The presence of LAC was a significant and independent prognostic factor for identifying major adverse cardiovascular events after AF ablation.

Greater effectiveness of ε-viniferin in red wine than its monomer resveratrol for inhibiting vascular smooth muscle cell proliferation and migration.

Resveratrol is a strong candidate for explaining an irreversible correlation between red wine consumption and coronary heart disease. The present study examined the effect of ε-viniferin, a dehydrodimer of resveratrol, on vascular smooth muscle cells (VSMCs), because ε-viniferin functions are poorly understood in spite of its comparable content to resveratrol in red wines and grapes. Both ε-viniferin and resveratrol inhibited platelet-derived growth factor-induced cell proliferation, migration, and reactive oxygen species (ROS) production, in addition to inducing nitric oxide generation. ε-Viniferin was more effective than resveratrol in these effects, except for inhibiting ROS production. The compounds also increased the expression of the antioxidant enzyme, hemeoxygenase-1, via transcription factor Nrf2. The phosphatidylinositol 3-kinase-Akt pathway was implicated in resveratrol-dependent nuclear Nrf2 accumulation, whereas extracellular signal-regulated kinase and p38 were involved in ε-viniferin-induced Nrf2 accumulation. These data suggest that ε-viniferin may function more effectively than resveratrol in different mechanisms and cooperatively with resveratrol in preventing atherosclerosis.

Hydroxytyrosol induces vascular smooth muscle cells apoptosis through NO production and PP2A activation with subsequent inactivation of Akt.

Olive oil has been shown to exhibit beneficial effects in the prevention of cardiovascular diseases although its molecular mechanism still remains unclear. In the present study, we investigated the effect of hydroxytyrosol (HT), a major phenolic component in olive oil and leaves from OLEA EUROPAEA L. (Oleaceae family), on vascular smooth muscle cells (VSMCs) survival, migration, and apoptosis. HT treatment resulted in a dose-dependent decrease of cell survival and migration in the presence or absence of platelet-derived growth factor (PDGF) by inducing apoptosis of VSMCs. HT enhanced nitric oxide (NO) production in a dose-dependent manner, and the NO synthase inhibitor L-NMMA blocked HT-mediated effects on VSMCs survival. HT as well as the NO donor SNAP reduced the phosphorylation levels of Akt, suggesting that HT inactivates Akt via NO production with subsequent apoptosis of VSMCs. Moreover, HT-dependent apoptosis and reduction in the phosphorylation level of Akt were suppressed by okadaic acid, an inhibitor of protein phosphatase 2A (PP2A) that dephosphorylates Akt. In contrast, the phosphorylation of phosphoinositide-dependent protein kinase 1 (PDK1), an upstream activator of Akt, was not affected by HT. Together, these findings indicate that HT could induce VSMCs apoptosis through NO production and PP2A activation followed by inactivation of Akt signaling pathway.

Prolonged survival in patients with hand-foot skin reaction secondary to cooperative sorafenib treatment.

BACKGROUND: Sorafenib is an oral drug that prolongs overall survival (OS) in patients with hepatocellular carcinoma. Adverse events, including hand-foot skin reaction (HFSR), lead to permanent sorafenib discontinuation. AIM: To clarify the association between interventions for adverse events and patient prognosis. METHODS: We performed a retrospective, multicenter study of patients treated with sorafenib monotherapy between May 2009 and March 2018. We developed a mutual cooperation system that was initiated at the start of sorafenib treatment to effectively manage adverse events. The mutual cooperation system entailed patients receiving consultations during which pharmacists provided accurate information about sorafenib to alleviate the fear and anxiety related to adverse events. We stratified the patients into three groups: Group A, patients without HFSR but with pharmacist intervention; Group B, patients with HFSR and pharmacist interventions unreported to oncologists (nonmutual cooperation system); and Group C, patients with HFSR and pharmacist interventions known to oncologists (mutual cooperation system). OS and time to treatment failure (TTF) were evaluated using the Kaplan-Meier method. RESULTS: We enrolled 134 patients (Group A, n = 41; Group B, n = 30; Group C, n = 63). The median OS was significantly different between Groups A and C (6.2 vs 13.9 mo, p < 0.01) but not between Groups A and B (6.2 vs 7.7 mo, P = 0.62). Group A vs Group C was an independent OS predictor (HR, 0.41; 95%CI: 0.25-0.66; P < 0.01). In Group B alone, TTF was significantly lower and the nonadherence rate was higher (P < 0.01). In addition, the Spearman's rank correlation coefficients between OS and TTF in each group were 0.41 (Group A; P < 0.01), 0.13 (Group B; P = 0.51), and 0.58 (Group C; P < 0.01). There was a highly significant correlation between OS and TTF in Group C. However, there was no correlation between OS and TTF in Group B. CONCLUSION: The mutual cooperation system increased treatment duration and improved prognosis in patients with HFSR. Future prospective studies (e.g., randomized controlled trials) and improved adherence could help prevent OS underestimation.

Anatomical evaluation of the esophagus using computed tomography to predict acute gastroparesis following atrial fibrillation ablation.

BACKGROUND: Catheter ablation for atrial fibrillation is an effective treatment; however, periesophageal vagal nerve injury is not rare and sometimes results in acute gastroparesis (AGP) after atrial fibrillation ablation (AFA). We sought to investigate the incidence and risk factors of AGP via preprocedural computed tomography (CT) analysis. METHODS: We retrospectively reviewed 422 patients who underwent index AFA at our center. Using contrast-enhanced CT performed before ablation, the anatomical characteristics of the esophagus were compared between patients with and without post-ablation AGP. AGP was diagnosed by the presence of symptoms, fasting abdominal X-ray radiography as a screening test, and additional abdominal imaging. RESULTS: Of the 422 patients (age, 67 ± 11 years; male, 68.5%; cryoballoon, 63.7%), AGP developed in 14 (3.3%) patients, and six of 14 patients were asymptomatic. AGP resolved in all patients within 4 weeks without invasive treatment. In the AGP group, the esophagus was frequently located on the vertebra (middle-positioned esophagus) (AGP vs non-AGP, 42.9% vs 11.5%; P = .01), and additional posterior wall ablation was frequently performed (50.0% vs 14.5%; P = .02). In the multivariate analysis, middle-positioned esophagus (P = .02; odds ratio, 9.0; 95% confidence interval [CI], 1.5-53.3) and additional posterior wall ablation (P = .01; odds ratio, 7.6; 95% CI, 1.5-42.1) were independent predictors of AGP. CONCLUSIONS: Anatomical evaluation of the esophagus using CT may be simple and useful for predicting AGP after AFA. High-risk patients who have middle-positioned esophagus or who underwent excessive posterior wall ablation should be followed up closely.

Responsiveness to bepridil predicts atrial substrate in patients with persistent atrial fibrillation.

BACKGROUND: The low voltage zone (LVZ) detected with three-dimensional electroanatomical mapping is a surrogate marker of atrial scar in patients with persistent atrial fibrillation (PeAF) and is associated with poor clinical outcomes after catheter ablation. However, fewer studies have reported the relationship between responsiveness to antiarrhythmic drugs and the LVZ. METHODS: We retrospectively analyzed 76 patients who underwent catheter ablation for PeAF at our center. Rhythm control with bepridil was initiated before ablation in all patients, and electrical cardioversion was performed in cases of failure to restore sinus rhythm with bepridil alone. Patients with successful sinus restoration with bepridil alone (≤200 mg/d) were defined as "responders", while those who required electrical cardioversion as well were defined as "non-responders". We compared the LVZ ratio (ratio of the LVZ surface area to the left atrium surface area on three-dimensional electroanatomical mapping) and the recurrence-free rate after ablation between the two groups. RESULTS: Of the 76 patients, 48 (63.2%) were responders to bepridil. The median LVZ ratio was significantly lower in the responder group than in the nonresponder group (7.5% vs 14.0%, P = .009). Multivariate analysis revealed that response to bepridil was an independent predictor of normal voltage (P = .02, odds ratio = 0.20, 95% confidence interval = 0.04-0.76). The recurrence-free rate at 1 year after catheter ablation was significantly higher in the responder group than in the nonresponder group (87.1% vs 62.3%, P = .03). CONCLUSIONS: Response to bepridil is a marker of normal voltage in electroanatomical mapping and is significantly associated with better clinical outcomes after catheter ablation.

Bidirectional atrioventricular reentrant tachycardia using bilateral accessory pathways.

Patients with Wolff-Parkinson-White (WPW) syndrome rarely have multiple accessory pathways (APs). Here, we present a case of a 21-year-old man with the manifest type B WPW syndrome who was experiencing multiple attacks of palpitations. The electrophysiological study revealed two APs located bilaterally: the anterolateral tricuspid annulus and lateral mitral annulus. Atrial/ventricular extrastimulations induced two types of wide QRS tachycardia conducting via two APs in the clockwise and counterclockwise direction. These two APs were eliminated with careful mapping and catheter ablation. .

Atrial pacing and administration of nifekalant hydrochloride for unstable atrial fibrillation: a case report.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with hypertrophic cardiomyopathy (HCM) and can deteriorate haemodynamic status. CASE SUMMARY: We report a case of a 77-year-old woman with cardiogenic shock due to paroxysmal AF, complicated with HCM and aortic stenosis. Atrial fibrillation was successfully managed with temporary atrial pacing and administration of nifekalant hydrochloride without invasive mechanical circulatory support until surgery. Septal myectomy, aortic valve replacement, and pulmonary vein isolation were performed. DISCUSSION: This case suggests that atrial pacing and nifekalant may be safe and effective for rhythm control.

Mahaim fiber connecting the right atrium to the left ventricle: a case report.

In the majority of cases presenting with the Mahaim fiber (MF), the MF connects the lateral right atrium (RA) to the right bundle branch or the right ventricle. We present the case of a 33-year-old man with antidromic atrioventricular reentrant tachycardia using MF connected to the septal RA and left ventricle (LV). Although the Mahaim potential was recorded at the septal RA, ablation at this site could not eliminate the MF and had a potential risk of injury to the atrioventricular node. Additional application at the posterior septal LV achieved successful MF ablation.

Efficacy of hybrid therapy using prior administration of bepridil hydrochloride and cryoballoon ablation in patients with persistent atrial fibrillation.

BACKGROUND: Rhythm control before catheter ablation for persistent atrial fibrillation (PeAF) can improve clinical outcomes. We sought to investigate the efficacy of pretreatment with bepridil prior to cryoballoon ablation (CBA) with respect to clinical outcomes in patients with PeAF. METHODS: We retrospectively analyzed 65 consecutive patients with PeAF who underwent CBA following pretreatment with bepridil hydrochloride (bepridil). Electrical cardioversion was additionally performed in cases involving failure of pharmacological sinus restoration before CBA. The primary endpoint was survival free from atrial tachyarrhythmia at the one-year follow-up, and the secondary endpoints were changes in P-wave morphology and left atrium diameter (LAD) before CBA. RESULTS: At the one-year follow-up, 51 patients (78.5%) achieved the primary endpoint (non-recurrence group). Compared to the P-wave duration (Pdur) and dispersion at the time of sinus restoration, they significantly shortened at the time of CBA in the non-recurrence group, while they did not change in the recurrence group. There were no changes in LAD in both groups. Multivariate analysis revealed that refractoriness of bepridil (p = 0.03, odds ratio = 4.72, 95% confidence interval = 1.18-18.92), and longer Pdur at admission for CBA (p = 0.003, odds ratio = 1.08, 95% confidence interval = 1.01-1.14) were independent predictors of recurrence. CONCLUSIONS: Rhythm control with bepridil induced electrical reverse remodeling; bepridil may improve clinical outcomes after CBA.

A case of small bowel adenocarcinoma wherein nivolumab conferred temporary benefit in disease control.

Small bowel adenocarcinomas are rare. There is no definite consensus as to whether they should be treated in a manner similar to gastric or to colon cancer. We report the case of a young woman with a primary jejunal adenocarcinoma, bilateral ovary metastases, and peritoneal dissemination. First- and second-line chemotherapy for the gastric cancer failed. She was then treated with the immune checkpoint inhibitor nivolumab and had temporary improvement in her condition. To the best of our knowledge, this is the first case wherein nivolumab has been used to treat small bowel adenocarcinoma.