Aldehyde Dehydrogenase 2 (ALDH2) Deficiency, Obesity, and Atrial Fibrillation Susceptibility: Unraveling the Connection.

Atrial fibrillation (AF), characterized by structural remodeling involving atrial myocardial degradation and fibrosis, is linked with obesity and transforming growth factor beta 1 (TGF-ß1). Aldehyde dehydrogenase 2 (ALDH2) deficiency, highly prevalent in East Asian people, is paradoxically associated with a lower AF risk. This study investigated the impact of ALDH2 deficiency on diet-induced obesity and AF vulnerability in mice, exploring potential compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1). Wild-type (WT) and ALDH2*2 knock-in (KI) mice were administered a high-fat diet (HFD) for 16 weeks. Despite heightened levels of reactive oxygen species (ROS) post HFD, the ALDH2*2 KI mice did not exhibit a greater propensity for AF compared to the WT controls. The ALDH2*2 KI mice showed equivalent myofibril degradation in cardiomyocytes compared to WT after chronic HFD consumption, indicating suppressed ALDH2 production in the WT mice. Atrial fibrosis did not proportionally increase with TGF-ß1 expression in ALDH2*2 KI mice, suggesting compensatory upregulation of the Nrf2 and HO-1 pathway, attenuating fibrosis. In summary, ALDH2 deficiency did not heighten AF susceptibility in obesity, highlighting Nrf2/HO-1 pathway activation as an adaptive mechanism. Despite limitations, these findings reveal a complex molecular interplay, providing insights into the paradoxical AF-ALDH2 relationship in the setting of obesity.

Metabolomics Assessment of Volume Overload-Induced Heart Failure and Oxidative Stress in the Kidney.

The incidence of heart failure (HF) is increasing and is associated with a poor prognosis. Moreover, HF often coexists with renal dysfunction and is associated with a worsened outcome. In many experimental studies on cardiac dysfunction, the function of other organs was either not addressed or did not show any decline. Until now, the exact mechanisms for initiating and sustaining this interaction are still unknown. The objective of this study is to use volume overload to induce cardiac hypertrophy and HF in aortocaval fistula (ACF) rat models, and to elucidate how volume overload affects metabolic changes in the kidney, even with normal renal function, in HF. The results showed the metabolic changes between control and ACF rats, including taurine metabolism; purine metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; and histidine metabolism. Increasing the downstream purine metabolism from inosine to uric acid in the kidneys of ACF rats induced oxidative stress through xanthine oxidase. This result was consistent with HK-2 cells treated with xanthine and xanthine oxidase. Under oxidative stress, taurine accumulation was observed in ACF rats, indicating increased activity of the hypotaurine-taurine pathway as a defense mechanism against oxidative stress in the kidney. Another antioxidant, ascorbic acid 2-sulfate, showed lower levels in ACF rats, indicating that the kidneys experience elevated oxidative stress due to volume overload and HF. In summary, metabolic profiles are more sensitive than clinical parameters in reacting to damage to the kidney in HF.

A Novel KCNH2 S981fs Mutation Identified by Whole-Exome Sequencing Is Associated with Type 2 Long QT Syndrome.

KCNH2 loss-of-function mutations cause long QT syndrome type 2 (LQT2), an inherited cardiac disorder associated with life-threatening ventricular arrhythmia. Through whole-exome sequencing, we discovered a novel AGCGACAC deletion (S981fs) in the hERG gene of an LQT2 patient. Using a heterologous expression system and patch clamping, we found that the mutant K channel had reduced cell surface expression and lower current amplitude compared to the wild type. However, functional expression was restored by lowering temperature and using potassium channel inhibitors or openers (E4031, cisapride, nicorandil). Co-immunoprecipitation experiments confirmed the assembly of mutant proteins with wild-type hERG. Confocal imaging showed decreased hERG distribution on the cell membrane in cells expressing S981fs. Notably, treatment with G418 significantly increased hERG current in wild-type/S981fs heterozygotes. In conclusion, our study identifies a novel hERG mutation leading to impaired Kv11.1 function due to trafficking and nonsense-mediated RNA decay defects. These findings shed light on the mechanisms underlying LQT2 and offer potential therapeutic avenues.

Impact of Selection Preference on Longer-Term Outcomes between Bioresorbable Vascular Scaffold versus Everolimus-Eluting Stent for True Lumen Tracking-Recanalized Chronic Total Occlusion.

Creation of sizable subintima during intervention for chronic total occlusions (CTO) could lead to the key selection preference of metallic stents rather than bioresorbable vascular scaffolds (BVS) and then possibly deviate the outcome comparisons in real-world studies. By including recanalized CTO with true lumen tracking, we tested if any selection preference remained and compared the outcomes between everolimus-eluting stent (EES) and BVS implantation.Among 211 consecutive CTO interventions with true lumen tracking from August 2014 to April 2018 when BVS was available, we compared the clinical and interventional features between 28 patients with BVS and 77 patients with EES implantation. With propensity score matching and a median follow-up of 50.5 (37.3-60.3) months, we further assessed 25 patients with BVS and 25 with EES for target vessel failure (TVF: cardiac death, target vessel myocardial infarction, and target lesion revascularization).Multivariate analyses showed that BVS was still favored in the presence of LAD CTO (odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.0-11.7) and an average scaffold/stent size ≥ 3 mm (OR = 10.5, 95% CI = 3.0-37.3). EES was preferred for lesions with a J-CTO score ≥ 3 (OR = 19.3, 95% CI = 3.4-110.8) and multivessel intervention necessary at index procedure (OR = 11.3, 95% CI = 1.9-67.3). With matched comparisons, the TVF-free survival of EES was better than that of BVS for CTO recanalization (P = 0.049 by log-rank test) at long-term follow-up.Even with true lumen tracking techniques, selection bias remained substantial when determining either device for CTO implantation. The matched comparison of outcomes suggested the unfavorable longer-term impacts of the first generation of BVS on CTO lesions.

Effects of platelet-rich plasma glue placement at the prostatectomy site on erectile function restoration and cavernous nerve preservation in a nerve-sparing prostatectomy rat model.

BACKGROUND: Despite the widespread use of nerve-sparing prostatectomy techniques, the incidence of post-operative erectile dysfunction (ED) remains high. Early intracavernous (IC) injection of platelet-rich plasma (PRP) after nerve crushing improves erectile function (EF) in rats by promoting cavernous nerve (CN) regeneration and preventing structural changes in the corpus cavernosum. However, the neuroprotective effects of the in situ application of PRP glue in rats after CN-sparing prostatectomy (CNSP) remain unclear. AIM: This study aimed to investigate the effects of PRP glue treatment on EF and CN preservation in rats after CNSP. METHODS: After prostatectomy, male Sprague-Dawley rats were treated with PRP glue, IC PRP injection, or their combination. The intracavernous pressure (ICP), mean arterial pressure (MAP), and CN preservation status in the rats were evaluated after 4 weeks. Results were corroborated using histology, immunofluorescence, and transmission electron microscopy. RESULTS: The PRP glue-treated rats showed 100% CN preservation and significantly higher ICP responses (the ratio of maximum ICP to MAP (0.79 ± 0.09)) than the CNSP rats (the ratio of maximum ICP to MAP (0.33 ± 0.04)). PRP glue also significantly increased neurofilament-1 expression, indicating its positive effect on the CNs. Furthermore, this treatment significantly increased the expression of α-smooth muscle actin. Electron micrographs revealed that PRP glue preserved the myelinated axons and prevented atrophy of the corporal smooth muscle by maintaining the adherens junctions. CONCLUSIONS: These results indicate that PRP glue is a potential solution for EF preservation by neuroprotection in patients with prostate cancer who are likely to undergo nerve-sparing radical prostatectomy.

Freedom From Stent Fracture-Related Complications of Vascular Longitudinal Remodeling in a Patient With Heart Failure and a Degraded Bioresorbable Vascular Scaffold.

Because vascular geometric change during the long-term process of cardiac chamber remodeling in heart failure is usually unpredictable after coronary stenting, the risk of acquired metallic stent fracture can persist. This rare but possible complication could be minimized with the implantation of bioresorbable vascular scaffold because of its unique properties. Here, the authors report on 1 patient with heart failure who received optical coherence tomography evaluation between 3 and 3.5 years after bioresorbable vascular scaffold implantation. Measurement of the discernible struts of bioresorbable vascular scaffold provided evidence of coronary longitudinal remodeling without serious risk of complications related to metallic stent fracture resulting from cardiac remodeling.

Outcomes of Percutaneous Coronary Interventions for Long Diffuse Coronary Artery Disease with Extremely Small Diameter.

BACKGROUND: The optimal percutaneous coronary intervention (PCI) strategy and clinical outcomes of long lesions with an extremely small residual lumen remain unclear. This study aimed to assess the efficacy of a modified stenting strategy for diffuse coronary artery disease (CAD) with an extremely small distal residual lumen. METHODS: 736 Patients who received PCI using second-generation drug-eluting stents (DES) ≥38 mm long were retrospectively included and categorized into an extremely small distal vessel (ESDV) group (≤2.0 mm) and a non-ESDV group (>2.0 mm) according to the maximal luminal diameter of the distal vessel (dsDMax). A modified stenting technique was applied by landing an oversized DES in the distal segment with the largest luminal diameter and maintaining the distal stent edge partially expanded. RESULTS: The mean dsDMax and stent lengths were 1.7 ± 0.3 mm and 62.6 ± 18.1 mm in the ESDV group and 2.7 ± 0.5 mm and 59.1 ± 16.0 mm in non-ESDV groups, respectively. The acute procedural success rate was high in both the ESDV and non-ESDV groups (95.8% and 96.5%, p = 0.70) with rare distal dissection (0.3% and 0.5%, p = 1.00). The target vessel failure (TVF) rate was 16.3% in the ESDV group and 12.1% in the non-ESDV group at a median follow-up of 65 months without significant differences after propensity score matching. CONCLUSIONS: PCI using contemporary DES with this modified stenting technique is effective and safe for diffuse CAD with extremely small distal vessels.

Osteopontin mediation of disturbed flow-induced endothelial mesenchymal transition through CD44 is a novel mechanism of neointimal hyperplasia in arteriovenous fistulae for hemodialysis access.

In dysfunctional arteriovenous fistulae (AVF) for hemodialysis access, neointimal hyperplasia (NH) is prone to occur in the region exposed to disturbed flow. We hypothesized that disturbed flow contributes to NH in AVF by inducing endothelial mesenchymal transition (EndMT) through activation of the osteopontin/CD44 axis. In rats with aortocaval fistula, a rodent model of AVF, we demonstrated development of EndMT and expression of osteopontin and CD44 specifically in the vicinity of the arteriovenous junction using immunostaining. Duplex scan confirmed this region was exposed to a disturbed flow. A mixed ultrastructural phenotype of endothelium and smooth muscle cells was found in luminal endothelial cells of the arteriovenous junction by electron microscopy ascertaining the presence of EndMT. Endothelial lineage tracing using Cdh5-Cre/ERT2;ROSA26-tdTomato transgenic mice showed that EndMT was involved in NH of AVF since the early stage and that the endothelial-derived cells contributed to 24% of neointimal cells. In human umbilical vein endothelial cells (HUVECs) in culture, osteopontin treatment induced EndMT, which was suppressed by CD44 knockdown. Exposure to low oscillatory wall shear stress using a parallel-plate system induced EndMT in HUVECs, also suppressed by osteopontin or CD44 knockdown. In AVF of CD44 knockout mice, EndMT was mitigated and NH decreased by 35% compared to that in wild-type mice. In dysfunctional AVF of patients with uremia, expressions of osteopontin, CD44, and mesenchymal markers in endothelial cells overlying the neointima was also found by immunostaining. Thus, the osteopontin/CD44 axis regulates disturbed flow-induced EndMT, plays an important role in neointimal hyperplasia of AVF, and may act as a potential therapeutic target to prevent AVF dysfunction.

Revascularization in Patients With Non-ST Elevation Myocardial Infarction and Advanced Chronic Kidney Disease.

OBJECTIVE: To investigate the impact of revascularization on long-term survival and renal outcome in non-ST-elevation myocardial infarction (NSTEMI) patients with severe chronic kidney disease (CKD). PATIENTS AND METHODS: This study includes NSTEMI patients with an estimated glomerular filtration rate <30 mL/min per 1.73 m2, including those on chronic hemodialysis who were identified from the multicenter Chang Gung Research Database from January 1, 2007, to December 31, 2017. Inverse probability of treatment weighting was used to generate comparable groups. The survival and the risk of progression to chronic hemodialysis between those receiving revascularization, either percutaneous coronary intervention or coronary artery bypass graft, and those receiving medical therapy during index hospitalization were compared. RESULTS: A total of 2821 NSTEMI patients with severe CKD, including 1141 patients on chronic hemodialysis, were identified. Of these, 1149 patients received revascularization and 1672 received medical therapies. The differences in demographics, comorbidities, and presentations between groups were balanced after inverse probability of treatment weighting. After a mean follow-up of 1.82 years, revascularization was associated with a lower risk of all-cause mortality (adjusted HR, 0.61; 95% CI, 0.54-0.70). For non-dialysis-dependent patients who had survival to discharge, revascularization had a higher risk of progression to chronic hemodialysis (adjusted HR, 1.83; 95% CI, 1.49-2.26) after a mean follow-up of 2.3 years. CONCLUSION: Revascularization was associated with a lower risk of all-cause mortality in NSTEMI patients with severe CKD. For non-dialysis-dependent patients who survived to discharge, revascularization was associated with a higher risk of progression to chronic hemodialysis.

Upregulation of Myocardial Neutrophil Gelatinase-Associated Lipocalin during Development of Heart Failure Caused by Volume-Overload and the Effect in Regulating Activity of Matrix Metalloproteinase-9.

Background: In patients with heart failure (HF), circulating neutrophil gelatinase-associated lipocalin (NGAL) level is increased, which is considered to be a predictor of mortality or renal outcomes. The expression of NGAL in the heart and kidney and its role in HF remain unclear. Methods: Aortocaval fistula was created in rats as a model of volume overload (VO)-induced HF. Results: During the development of HF, NGAL expression was upregulated in the heart but not in the kidney at both transcriptional and translational levels in the compensatory and HF phases, with a similar level in both phases. Cardiomyocytes were identified as the cell type responsible for NGAL expression. Consistent with the myocardial NGAL expression pattern, the plasma NGAL level was increased in both phases, and the level was not significantly different between both phases. We demonstrated the presence of a matrix metalloproteinase (MMP)-9/NGAL complex in cultured medium of cardiomyocytes isolated from volume-overloaded hearts by gelatin zymography. Formation of MMP-9/NGAL complex was shown to enhance the enzymatic activity of MMP-9. We found that early growth response (Egr)-1 was upregulated in the heart in both compensatory and HF phases. In neonatal cardiomyocytes, Egr-1 overexpression induced the gene expression of NGAL, which was dose-dependently suppressed by an interleukin-1 receptor antagonist. Conclusions: During the development of HF due to VO, NGAL was upregulated in the heart but not in the kidney in both compensatory and HF phases, with a similar expression level. Myocardial NGAL upregulation enhanced MMP-9 activity through formation of the MMP-9/NGAL complex. The expression of myocardial NGAL was regulated by Egr-1.

Case report: Sudden cardiorespiratory collapse in a healthy male after coronavirus disease 2019 vaccination at a vaccination center.

Since 2020, new vaccines were developed to fight the coronavirus disease 2019 (COVID-19). Vaccination is important in preventing mortality and achieving herd immunity. However, due to vast vaccination, fatal adverse events could be seen. We report a case of a previously healthy, young male who had a cardiopulmonary arrest 2 min after receiving the Oxford- AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccination. After targeted temperature management, a coronary angiogram was performed after neurological recovery and showed severe stenosis at the proximal left anterior descending artery. Stenting was done and he was discharge. No similar case of sudden cardiorespiratory collapse immediately after COVID-19 vaccination has been reported. Our patient did not have any effort-related angina or dyspnea on exertion before this event. The sudden cardiorespiratory collapse was probably related to underlying coronary artery disease, complicated with a vasovagal event. We stress the importance of coronary angiography in out of hospital cardiac arrest patients after neurological recovery. In the era of COVID-19 vaccination, even though fatal adverse events following immunization are rare, heightened awareness of severe side effects needing medical attention is very important.

Derangements and Reversibility of Energy Metabolism in Failing Hearts Resulting from Volume Overload: Transcriptomics and Metabolomics Analyses.

Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. Male Sprague-Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF.

Impacts of Lesion Characteristics on Procedures and Outcomes of Chronic Total Occlusion Recanalization With Antegrade Guidewire True Lumen Tracking Techniques: A Substudy of Taiwan True Lumen Tracking Registry.

Background: Lesion characteristics were shown to predict procedural success and outcomes in chronic total occlusion (CTO) recanalization. However, diverse techniques involved in these studies might cause potential heterogeneity. Objective: The study aimed to test the impacts of lesion characteristics on CTO intervention with a pure antegrade wiring-based technique. Methods and Results: We studied consecutive 325 patients (64.5 ± 11.1 years, 285 men) with native CTO lesions intervened by a single operator with an antegrade-based technique between August 2014 and July 2020. Forty-seven patients with antegrade procedural failure (20 with pure antegrade wiring failure and 27 with back-up retrograde techniques) were compared to 278 patients with antegrade-only procedural success. With a median follow-up of 30.8 (16.1-48.6) months, 278 patients with procedural success were further assessed for target vessel failure (TVF: cardiac death, target vessel myocardial infarction [MI], and target lesion revascularization [TLR]). Patients with antegrade procedural success had a lower percentage of history with bypass graft (4 vs. 15%, p = 0.004) and lower Multicenter Chronic Total Occlusion Registry of Japan (J-CTO) score (2.1±1.3 vs. 3.4 ± 1.0, p < 0.001), when compared to those with antegrade failure. The J-CTO score was independently associated with procedural failure (odds ratio = 2.5, 95% CI = 1.8-3.4) in multivariate analysis. However, only clinical features, such as female gender (hazard ratio [HR] = 4.3, 95% CI = 1.4-13.1), estimated glomerular filtration rate <60 ml/min/1.73 m2 (HR = 3.2, 95% CI = 1.0-9.9), and old MI (HR = 4.5, 95% CI = 1.5-12.8), but not J-CTO score, could predict long-term TVF in multivariate Cox regression model. Conclusion: The feasibility of the antegrade guidewire-crossing technique for native CTO intervention was highly determined by lesion characteristics. With such a simpler technique, the prognostic impact of lesion complexity shown in studies with multiple recanalization techniques was negligible. This suggested antegrade true lumen tracking techniques deserved to be tried better even for CTO lesions with higher complexity.

Procedural and One-Year Clinical Outcomes of Long 48 mm Xience Xpedition Everolimus-Eluting Stent in Complex Long Diffuse Coronary Artery Lesions.

BACKGROUND AND OBJECTIVES: Long 48 mm drug-eluting stents (DES) used to treat long coronary lesions decreases the number of stents needed and avoids stent overlapping. Disadvantages include difficulty in delivery and size discrepancy between proximal and distal stent landing zones. The present study analyzed the rate of procedural, immediate angiographic, and 1-year clinical outcomes of long diffuse coronary artery lesions treated with 48 mm everolimus-eluting stents (EES) and compared the clinical outcomes with multiple overlapping DES. METHODS: This retrospective analysis included 213 patients with 228 lesions treated with at least one 48 mm EES at 2 hospitals in Taiwan. RESULTS: About 40.4% of the lesions had moderate-severe calcification and 20.2% had acute angulation. The mean lesion length was 49.2 ± 18.1 mm. In 161 lesions requiring a single 48 mm EES, 67.1% had a discrepancy between proximal and distal reference diameter of ≥0.5 mm and 36% had a discrepancy of ≥1.0 mm. The procedural success rate was 98.6%. Target-vessel failure (TVF) rate at 1 year was 4.2%. Cardiac death occurred in 3 patients. The rates of target-vessel myocardial infarction (TV-MI), target-vessel revascularization (TVR) and definite/ probable stent thrombosis were 1.4%, 3.3%, and 0.9%, respectively. After adjusting patient variables by propensity score matching, no significant difference was found for cardiac death, TVF, TV-MI, and clinically driven TVR. CONCLUSION: Use of 48 mm EES to treat long coronary lesions in clinically and anatomically complex patients is safe and effective. In the propensity score-matched analysis, the 48 mm EES and multiple stents have comparable clinical outcomes.

Weather Impact on Acute Myocardial Infarction Hospital Admissions With a New Model for Prediction: A Nationwide Study.

Introduction: Cardiovascular disease is one of the leading causes of mortality worldwide. Acute myocardial infarction (AMI) is associated with weather change. The study aimed to investigate if weather change was among the risk factors of coronary artery disease to influence AMI occurrence in Taiwan and to generate a model to predict the probabilities of AMI in specific weather and clinical conditions. Method: This observational study utilized the National Health Insurance Research Database and daily weather reports from Taiwan Central Weather Bureau to evaluate the discharge records of patients diagnosed with AMI from various hospitals in Taiwan between January 1, 2008 and December 31, 2011. Generalized additive models (GAMs) were used to estimate the effective parameters on the trend of the AMI incidence rate with respect to the weather and health factors in the time-series data and to build a model for predicting AMI probabilities. Results: A total of 40,328 discharges were listed. The minimum temperature, maximum wind speed, and antiplatelet therapy were negatively related to the daily AMI incidence; however, a drop of 1° when the air temperature was below 15°C was associated with an increase of 1.6% of AMI incidence. By using the meaningful parameters including medical and weather factors, an estimated GAM was built. The model showed an adequate correlation in both internal and external validation. Conclusion: An increase in AMI occurrence in colder weather has been evidenced in the study, but the influence of wind speed remains uncertain. Our analysis demonstrated that the novel GAM model can predict daily onset rates of AMI in specific weather conditions.

Antithrombotic Treatment of Stable Coronary Artery Disease.

Coronary artery disease (CAD) is one of the leading causes of death in Taiwan. Despite the use of current guideline-recommended therapies for secondary prevention, the residual risk of recurrent cardiovascular events remains high in CAD, warranting the need for new treatment options. Antithrombotic drugs are one of the most important medical therapies for CAD. In this article, we review the unmet needs of the current antithrombotic agents and summarize the results of clinical trials with dual antiplatelet therapy in stable CAD. We also review data from a recent study demonstrating the benefits of a dual pathway inhibition strategy with antiplatelet and anticoagulant therapy, a new option for CAD treatment. Finally, we propose a treatment algorithm for choosing different antithrombotic regimens for CAD based on current scientific evidence and expert opinions.

Outcomes after ticagrelor versus clopidogrel treatment in end-stage renal disease patients with acute myocardial infarction: a nationwide cohort study.

Clinical outcomes are unknown after ticagrelor treatment in patients with end-stage renal disease (ESRD) who are diagnosed with acute myocardial infarction (AMI). ESRD patients who were on hemodialysis and received dual antiplatelet therapy (DAPT) for AMI between July 2013 and December 2016 were identified in Taiwan's National Health Insurance Research Database. Using stabilized inverse probability of treatment weighting, patients receiving aspirin plus ticagrelor (n = 530) were compared with those receiving aspirin plus clopidogrel (n = 2462) for the primary efficacy endpoint, a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke, and bleeding, defined according to the Bleeding Academic Research Consortium. Study outcomes were compared between the two groups using Cox proportional hazards model or competing risk model for the hazard ratio or subdistribution hazard ratio (SHR). During 9 months of follow-up, ticagrelor was comparable to clopidogrel with respect to the risks of primary efficacy endpoint [11.69 vs. 9.28/100 patient-months; SHR, 1.16; 95% confidence interval (CI) 0.97-1.4] and bleeding (5.55 vs. 4.36/100 patient-months; SHR 1.14; 95% CI 0.88-1.47). In conclusion, among hemodialysis patients receiving DAPT for AMI, ticagrelor was comparable to clopidogrel with regard to the composite efficacy endpoint and bleeding.

Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells.

Melanoma represents less than 5% of skin cancers, but is the most lethal, mainly because of its high-metastatic potential and resistance to various therapies. Therefore, it is important to develop effective treatments, especially chemotherapeutic drugs with cytotoxicity, anti-metastaticity, and few side effects. One such natural product is hispidulin, a flavone distributed in plants of the Asteraceae. Previous studies have demonstrated that hispidulin has various pharmacological benefits, such as anti-tumor, anti-inflammation, and anti-allergic effects. This study aims to explore the effects of hispidulin against melanoma in vitro and in vivo. Results revealed that hispidulin selectively decreased the cell viability of A2058 cells in a dose- and time-dependent manner. Hispidulin induced cells accumulated in the sub-G1 phase via activating caspase 8 and 9, increased cleaved caspase 3, and cleaved PARP expression. Hispidulin was able to decrease AKT and ERK phosphorylation, which facilitated cell growth and survival. Moreover, hispidulin promoted reactive oxygen species generation in cells and suppressed cell migration through downregulated matrix metalloproteinase-2 expression. Hispidulin significantly inhibited tumor growth in a xenograft model. Based on these results, hispidulin produces its anti-melanoma effects by inducing cancer cell apoptosis and reducing its migration. Therefore, we suggest hispidulin as a potent therapeutic candidate for melanoma treatment.

Role of an e-Health Intervention in Holistic Healthcare: A Quasiexperiment in Patients Undergoing Cardiac Catheterization in Taiwan.

Background: The use of electronic health (e-health) resources is emerging as an alternative method to improve the secondary prevention of coronary artery disease (CAD). The aim of this study was to describe the influence of an e-health application in holistic healthcare for patients with CAD. Methods: A quasiexperiment with nonequivalent groups design recruited outpatients with a high risk of CAD admitted for cardiac catheterization. They were divided into two groups. Before the procedure, the control group received traditional patient education, and the intervention group watched videos on Internet-based social media. EQ-5D and FACIT-Sp-12 questionnaires were used as outcome measures of interest, and they were administered before and after the procedure and at the first return visit to the outpatient clinic after discharge. The effect of each intervention was tested using a linear mixed effects model. In addition, the 90-day readmission rate was also studied. Results: A total of 300 patients were divided into intervention and control groups (150 patients in each group). The interaction effect of EQ-5D was not statistically significant; however, improvements in FACIT-Sp-12 were greater in the intervention group from baseline to before discharge (regression coefficient (B) = 1.70, p < 0.001) and from baseline to postdischarge first outpatient visit (B = 1.81, p < 0.001). Moreover, the 90-day readmission rate was significantly lower in the intervention group (14% vs. 18.7%; p=0.016, log-rank test). Conclusions: e-health intervention with easily accessible Internet-based social media is a promising model to meet the holistic needs of patients with CAD in the modern era.