Direct Oral Anticoagulants in Chronic Thromboembolic Pulmonary Hypertension: First Meta-Analysis of Prospective Studies.

Direct oral anticoagulants (DOACs) are becoming increasingly popular clinically, but their safety and effectiveness profile in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is not well-established. Literature from the PubMed and EMBASE databases was systematically screened up to February 2024 to identify relevant studies on the use of DOACs in CTEPH patients. The bias risk of RCTs was assessed using the Cochrane Risk of Bias Tool 2.0. The quality of observational prospective cohorts was assessed using the Newcastle-Ottawa Scale tool. Data pooled from different studies were analyzed. Results from 4 studies were gathered, including 2 randomized controlled trials and 2 prospective cohorts, with a total of 2038 patients, of which 751 were on DOACs and 1287 were on vitamin K antagonists (VKAs). Similar rates of all-cause mortality (3.33% vs 3.33%, RD = -0.01%, 95% CI [-0.02%, 0.00%], P = .17), VTE recurrence (1.46% vs 2.12%, RD = -0.00%, 95% CI [-0.01%, 0.01%], P = .92) were observed. DOACs were associated with a nonsignificant reduction in bleeding events including major bleeding (2.22% vs 3.71%, RD = -0.01%, 95% CI [-0.04%, 0.01%], P = .30), any bleeding (5.33% vs 9.94%, RD = -0.03%, 95% CI [-0.07%, 0.01%], P = .10), and minor bleeding (4.17% vs 13.3%, RD = -0.06%, 95% CI [-0.23%, 0.10%], P = .45). Data pooled from existing perspective trials suggests the use of DOACs in CTEPH patients as an effective and safe alternative to VKAs.

Efficacy and Safety of Direct Oral Anticoagulants in Cerebral Venous Thrombosis: Meta-Analysis of Randomized Clinical Trials.

Current guidelines recommend the standard-of-care anticoagulation (vitamin K antagonists or low-molecular-weight heparin) in patients with cerebral venous thrombosis (CVT). Herein, we performed a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy and safety of direct oral anticoagulants (DOACs) compared with the current standard of care in patients with CVT. We systematically searched the PubMed and Embase databases up to December 2023 to identify clinical trials on the effect of DOACs in patients with CVT. A Mantel-Haenszel fixed effects model was applied, and the effect measures were expressed as the absolute risk differences (RDs) and 95% confidence intervals (CIs). A total of 4 RCTs involving 270 participants were included. In the pooled analysis, DOACs and standard of care had low incidence rates of recurrent VTE and all-cause death, and similar rates of any recanalization (78.2% vs 83.2%; RD = -4%, 95%CI:-14% to 5%) and complete recanalization (60.9% vs 69.4%; RD = -7%, 95%CI:-24% to 10%). Compared with the standard of care, DOACs had non-significant reductions in the rates of major bleeding (1.2% vs 2.4%; RD = -1%, 95%CI: -6% to 3%), intracranial hemorrhage (1.9% vs 3.6%; RD = -2%, 95%CI:-7% to 3%), clinically relevant non-major bleeding (3.8% vs 7.4%; RD = -4%, 95%CI:-9% to 2%), and any bleeding (17.3% vs 21.4%; RD = -4%, 95%CI:-16% to 8%) in patients with CVT. DOACs and standard of care showed similar efficacy and safety profiles for the treatment of CVT. DOACs might be safe and a convenient alternative to vitamin K antagonists for thromboprophylaxis in patients with CVT.

Surface Passivation to Enhance the Interfacial Pyro-Phototronic Effect for Self-Powered Photodetection Based on Perovskite Single Crystals.

The interfacial pyro-phototronic effect (IPPE) presents a novel approach for improving the performance of self-powered photodetectors (PDs) based on metal halide perovskites (MHPs). The interfacial contact conditions within the Schottky junctions are crucial in facilitating the IPPE phenomenon. However, the fabrication of an ideal Schottky junction utilizing MHPs is a challenging endeavor. In this study, we present a surface passivation method aimed at enhancing the performance of self-powered photodetectors based on inverted planar perovskite structures in micro- and nanoscale metal-halide perovskite SCs. Our findings demonstrate that the incorporation of a lead halide salt with a benzene ring moiety for surface passivation leads to a substantial improvement in photoresponses by means of the IPPE. Conversely, the inclusion of an alkane chain in the salt impedes the IPPE. The underlying mechanism can be elucidated through an examination of the band structure, particularly the work function (WF) modulated by surface passivation. Consequently, this alteration affects the band bending and the built-in field (VBi) at the interface. This strategy presents a feasible and effective method for producing interfacial pyroelectricity in MHPs, thus facilitating its potential application in practical contexts such as energy conversion and infrared sensors.

A Self-Powered UV Photodetector With Ultrahigh Responsivity Based on 2D Perovskite Ferroelectric Films With Mixed Spacer Cations.

Self-powered photodetectors (PDs) have the advantages of no external power requirement, wireless operation, and long life. Spontaneous ferroelectric polarizations can significantly increase built-in electric field intensity, showing great potential in self-powered photodetection. Moreover, ferroelectrics possess pyroelectric and piezoelectric properties, beneficial for enhancing self-powered PDs. 2D metal halide perovskites (MHPs), which have ferroelectric properties, are suitable for fabricating high-performance self-powered PDs. However, the research on 2D metal halide perovskites ferroelectrics focuses on growing bulk crystals. Herein, 2D ferroelectric perovskite films with mixed spacer cations for self-powered PDs are demonstrated by mixing Ruddlesden-Popper (RP)-type and Dion-Jacobson (DJ)-type perovskite. The (BDA0.7 (BA2 )0.3 )(EA)2 Pb3 Br10 film possesses, overall, the best film qualities with the best crystalline quality, lowest trap density, good phase purity, and obvious ferroelectricity. Based on the ferro-pyro-phototronic effect, the PD at 360 nm exhibits excellent photoelectric properties, with an ultrahigh peak responsivity greater than 93 A W-1 and a detectivity of 2.5 × 1015 Jones, together with excellent reproducibility and stability. The maximum responsivities can be modulated by piezo-phototronic effect with an effective enhancement ratio of 480%. This work will open up a new route of designing MHP ferroelectric films for high-performance PDs and offers the opportunity to utilize it for various optoelectronics applications.

Worsening Renal Function and Adverse Outcomes in Patients with HFpEF with or without Atrial Fibrillation.

Since worsening renal function (WRF) and atrial fibrillation (AF) often coexist in preserved ejection fraction (HFpEF), we aimed to investigate the effect of WRF on the prognosis of HFpEF patients with and without AF. The study population of this study (n = 1763) was based on the subset of the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). We found that the cumulative probabilities of the primary composite outcome and cardiovascular death were significantly higher in AF patients post-WRF when compared to non-AF patients. In the time-dependent Cox proportional hazard model, WRF was significantly associated with higher risks of adverse outcomes (primary composite outcome: HR = 1.58 (95% CI, 1.19-2.11); all-cause death: HR = 1.50 (95% CI, 1.10-2.06); cardiovascular death: HR, 2.00 (95% CI, 1.34-3.00)) after adjustments for confounding factors at baseline in HFpEF patients with AF, whereas in HFpEF patients without AF, WRF was not significantly associated with any adverse outcome. p for interactions for the primary composite outcome, cardiovascular death, and AF were significant. In conclusion, these findings highlight that WRF was associated with a greater risk of the primary composite outcome, all-cause death, and cardiovascular death in HFpEF patients with AF.

Effect of Oral Anticoagulants in Atrial Fibrillation Patients with Polypharmacy: A Meta-analysis.

BACKGROUND: The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy. METHODS AND RESULTS: Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69-0.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69-0.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74-1.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79-1.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy. CONCLUSION: In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.

Body mass index and clinical outcomes in patients with heart failure with preserved ejection fraction mediated by diastolic blood pressure status?

Background: The "obesity paradox" has been elucidated in patients with heart failure (HF). Current guidelines introduce a target diastolic blood pressure (DBP) < 80 mmHg but >70 mmHg in HF patients. Due to reduced coronary perfusion, low DBP has a deleterious impact on cardiovascular outcomes. This present study aimed to assess the relationship between BMI and adjudicated clinical outcomes in HFpEF patients according to the status of DBP. Methods: We analyzed the data in 1749 HFpEF patients from the Americas of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) Trial. The population was stratified by DBP (<70 mmHg, and ≥70 mmHg) and BMI strata (normal weight, overweight, and obesity). Cox proportional hazards models and competing-risks regression analysis were performed. Results: At baseline, the median BMI and DBP were 32.9 kg/m2 (interquartile range 28.0-38.5 kg/m2) and 70 mmHg (interquartile range 62-80 mmHg), respectively. In the multivariable analysis, obesity was associated with better survival rates in the total HFpEF population (all-cause death: HR = 0.439, 95% CI 0.256-0.750; and cardiovascular death: HR = 0.378, 95% CI 0.182-0.787). In patients with DBP<70 mmHg, obesity was not significantly associated with reduced risks for all-cause death (HR = 0.531, 95% CI: 0.263-1.704) and cardiovascular death (HR = 0.680, 95% CI: 0.254-1.819). However, multivariate analyses for cardiovascular death (HR = 0.339, 95% CI: 0.117-0.983) and all-cause death (HR = 0.389, 95% CI: 0.156-0.969) were significant in patients with DBP≥70 mmHg. Nevertheless, there were no interactions between DBP and BMI. Conclusions: The obesity paradox was observed in patients with HFpEF, regardless of DBP strata (<70 mmHg, and ≥70 mmHg).

Patterned 2D Ferroelectric Perovskite Single-Crystal Arrays for Self-Powered UV Photodetector Boosted by Combining Ferro-Pyro-Phototronic and Piezo-Phototronic Effects.

Metal halide perovskite ferroelectrics possess various physical characteristics such as piezoelectric and pyroelectric effects, which could broaden the application of perovskite ferroelectrics and enhance the optoelectronic performance. Therefore, it is promising to combine multiple effects to optimize the performance of the self-powered PDs. Herein, patterned 2D ferroelectric perovskite (PMA)2PbCl4 microbelt arrays were demonstrated through a PDMS template-assisted antisolvent crystallization method. The perovskite arrays based flexible photodetectors exhibited fine self-powered photodetection performance under 320 nm illumination and much enhanced reproducibility compared with the randomly distributed single-crystal microbelts-based PDs. Furthermore, by introducing the piezo-phototronic effect, the performance of the flexible PD was greatly enhanced. Under an external tensile strain of 0.71%, the responsivity was enhanced by 185% from 84 to 155.5 mA/W. Our findings offer the advancement of comprehensively utilizing various physical characteristics of the ferroelectrics for novel ferroelectric optoelectronics.

Ferro-Pyro-Phototronic Effect in Monocrystalline 2D Ferroelectric Perovskite for High-Sensitive, Self-Powered, and Stable Ultraviolet Photodetector.

2D hybrid perovskite ferroelectrics have drawn great attention in the field of photodetection, because the spontaneous polarization-induced built-in electric field can separate electron-hole pairs, and makes self-powered photodetection possible. However, most of the 2D hybrid perovskite-based photodetectors focused on the detection of visible light, and only a few reports realized the self-powered and sensitive ultraviolet (UV) detection using wide bandgap hybrid perovskites. Here, 2D ferroelectric PMA2PbCl4 monocrystalline microbelt (MMB)-based PDs are demonstrated. By using the ferro-pyro-phototronic effect, the self-powered Ag/Bi/2D PMA2PbCl4 MMB/Bi/Ag PDs show a high photoresponsivity up to 9 A/W under 320 nm laser illumination, which is much higher than those of previously reported self-powered UV PDs. Compared with responsivity induced by the photovoltaic effect, the responsivity induced by the ferro-pyro-phototronic effect is 128 times larger. The self-powered PD also shows fast response and recovery speed, with the rise time and fall time of 162 and 226 µs, respectively. More importantly, the 2D PMA2PbCl4 MMB-based PDs with Bi/Ag electrode exhibit significant stability when subjected to high humidity, continuous laser illumination, and thermal conditions. Our findings would shed light on the ferro-pyro-phototronic-effect-based devices, and provide a good method for high-performance UV detection.

HAS-BLED vs. ORBIT scores in anticoagulated patients with atrial fibrillation: A systematic review and meta-analysis.

Background: The 2021 UK National Institute for Health and Care Excellence guidelines tend to recommend the ORBIT score for predicting bleeding risk in patients with atrial fibrillation (AF) with anticoagulants. Herein, we comprehensively re-assessed the predicted abilities of the HAS-BLED vs. ORBIT score since several newly published data showed different findings. Methods: We comprehensively searched the PubMed electronic database until December 2021 to identify relevant studies reporting the ORBIT vs. HAS-BLED scores in anticoagulated patients with AF. Their predicted abilities were assessed using the C-index, reclassification, and calibration analysis. Results: Finally, 17 studies were included in this review. In the pooled analysis, the ORBIT score had a C-index of 0.63 (0.60-0.66), 0.59 (0.53-0.66), and 0.57 (0.48-0.67) for major bleeding, any clinically relevant bleeding, and intracranial bleeding, respectively, while the HAS-BLED score had a C-index of 0.61 (0.59-0.63), 0.59 (0.56-0.63), and 0.57 (0.51-0.64) for major bleeding, any clinically relevant bleeding, and intracranial bleeding, respectively. There were no statistical differences in the accuracy of predicting these bleeding events between the two scoring systems. For the outcome of major bleeding, the subgroup analyses based on vitamin K antagonists vs. direct oral anticoagulants suggested no differences in the discrimination ability between the HAS-BLED and ORBIT scores. Reclassification and calibration analyses of HAS-BLED vs. ORBIT should be further assessed due to the limited and conflicting data. Conclusion: Our current findings suggested that the HAS-BLED and ORBIT scores at least had similar predictive abilities for major bleeding risk in anticoagulated (vitamin K antagonists or direct oral anticoagulants) patients with AF, supporting the use of the HAS-BLED score in clinical practice.

Increased Blood Retinol Levels Are Associated With a Reduced Risk of TIA or Stroke in an Adult Population: Lifestyle Factors- and CVDs-Stratified Analysis.

Background: Data on the existing evidence for the association between blood retinol and transient ischemic attack (TIA)/stroke risk are limited, and the results are inconclusive. This study aimed to further assess the associations between the blood retinol levels and the risk of TIA/stroke after controlling the lifestyle factors and age-related confounders. Methods: The cross-sectional data from 1,113 individuals (aged 34-84 years old) were obtained from the Midlife in the United States (MIDUS) study. The multivariable analyses were performed to investigate the association of blood retinol levels with ever and currently TIA/stroke. Results: There was an inverse association between the blood retinol levels and the risk of ever TIA or stroke (for per 1 µmol/L adjusted odds ration [OR]: 0.93; 95% CI: 0.89-0.97; for per 1-SD adjusted OR: 0.89; 95% CI: 0.83-0.96) and currently diagnosed TIA or stroke (for per 1 µmol/L adjusted OR: 0.91; 95% CI: 0.87-0.96; for per 1-SD adjusted OR: 0.84; 95% CI: 0.80-0.91) after controlling the lifestyle factors and age-related confounders. The significance of these associations was maintained after a sensitivity analysis and involving "ever chronic respiratory diseases" as a covariate. Moreover, the stratified analyses suggested that the inverse associations could be affected by overweight [body mass index (BMI) ≥ 28, kg/m2], hypertension, and diabetes. Conclusions: A significant inverse association between blood retinol and the risk of TIA or stroke was found. This inverse association did not change even after adjustment for many potential confounders. Moreover, the potential protective effect of retinol on TIA/stroke could be blunted by overweight [BMI ≥ 28, kg/m2], hypertension, and diabetes.

A Self-Powered Photodetector Based on MAPbI3 Single-Crystal Film/n-Si Heterojunction with Broadband Response Enhanced by Pyro-Phototronic and Piezo-Phototronic Effects.

Pyro-phototronic and piezo-phototronic effect have shown their important roles for high performance heterojunction-based photodetectors (PDs). Here, a coupling effect of pyro-phototronic and piezo-phototronic effect is utilized to fabricate a self-powered and broadband PD based on the MAPbI3 single-crystal film/n-Si heterojunction. First, by using the pyro-phototronic effect derived from MAPbI3 , the maximum photoresponsivity of the self-powered PD is 1.5 mA W-1 for 780 nm illumination, which is enhanced by more than 20 times in consideration of the relative peak-to-peak output current. Light-induced temperature change in MAPbI3 film will create pyro-charges distributed at heterojunction interface, resulting in a downward bending of the energy band, facilitating the transport of photon-generated electrons and holes, and generating spike-like output currents. Second, piezo-phototronic effect is further introduced by applying vertical pressures onto the PD. With a vertical pressure of 155 kPa, the responsivity can be improved by more than 120% compared to the condition with no pressure. The overall enhancement is due to the piezo-phototronic and pyro-phototronic coupling effects which utilize the polarization charges to modulate the band structure of heterojunction. These results provide a promising approach to develop high-performance self-powered and broadband perovskite-based PDs by coupling pyro-phototronic and piezo-phototronic effect.

FAT10 protects against ischemia-induced ventricular arrhythmia by decreasing Nedd4-2/Nav1.5 complex formation.

The human leukocyte antigen F-associated transcript 10 (FAT10) is a member of the small ubiquitin-like protein family that binds to its target proteins and subjects them to degradation by the ubiquitin-proteasome system (UPS). In the heart, FAT10 plays a cardioprotective role and affects predisposition to cardiac arrhythmias after myocardial ischemia (MI). However, whether and how FAT10 influences cardiac arrhythmias is unknown. We investigated the role of FAT10 in regulating the sodium channel Nav1.5, a major regulator of cardiac arrhythmias. Fat10 was conditionally deleted in cardiac myocytes using Myh6-Cre and Fat10F/F mice (cFat10-/-). Compared with their wild-type littermates, cFat10-/- mice showed prolonged RR, PR, and corrected QT (QTc) intervals, were more likely to develop ventricular arrhythmia, and had increased mortality after MI. Patch-clamp studies showed that the peak Na+ current was reduced, and the late Na+ current was significantly augmented, resulting in a decreased action potential amplitude and delayed depolarization. Immunoblot and immunofluorescence analyses showed that the expression of the membrane protein Nav1.5 was decreased. Coimmunoprecipitation experiments demonstrated that FAT10 stabilized Nav1.5 expression by antagonizing Nav1.5 ubiquitination and degradation. Specifically, FAT10 bound to the lysine residues in the C-terminal fragments of Nav1.5 and decreased the binding of Nav1.5 to the Nedd4-2 protein, a ubiquitin E3 ligase, preventing degradation of the Nav1.5 protein. Collectively, our findings showed that deletion of the Fat10 in cardiac myocytes led to increased cardiac arrhythmias and increased mortality after MI. Thus, FAT10 protects against ischemia-induced ventricular arrhythmia by binding to Nav1.5 and preventing its Neddylation and degradation by the UPS after MI.

The "Obesity Paradox" in Patients With HFpEF With or Without Comorbid Atrial Fibrillation.

Background: Overweight and mildly obese individuals have a lower risk of death than their normal-weight counterparts; this phenomenon is termed "obesity paradox." Whether this "obesity paradox" exists in patients with heart failure (HF) or can be modified by comorbidities is still controversial. Our current study aimed to determine the association of body mass index (BMI) with outcomes with patients with HF with preserved ejection fraction (HFpEF) with or without coexisting atrial fibrillation (AF). Methods: Patients with HFpEF from the Americas in the TOPCAT trial were categorized into the 3 groups: normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥30 kg/m2). The Cox proportional-hazards models were used to calculate the adjusted hazard ratios (HRs) and CIs. Results: We identified 1,749 patients with HFpEF, 42.1% of which had baseline AF. In the total population of HFpEF, both overweight (HR = 0.59, 95% CI: 0.42-0.83) and obesity (HR = 0.49, 95% CI: 0.35-0.69) were associated with a reduced risk of all-cause death. Among patients with HFpEF without AF, overweight (HR = 0.51, 95% CI: 0.27-0.95) and obesity (HR = 0.64, 95% CI: 0.43-0.98) were associated with a lower risk of all-cause death. In those with AF, obesity (HR = 0.62, 95% CI: 0.40-0.95) but not overweight (HR = 0.81, 95% CI: 0.54-1.21) was associated with a decreased risk of all-cause death. Conclusions: The "obesity paradox" assessed by BMI exists in patients with HFpEF regardless of comorbid AF. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT00094302.

Ubiquitin-like protein FAT10 suppresses SIRT1-mediated autophagy to protect against ischemic myocardial injury.

Autophagy plays a deleterious role in ischemic myocardial injury. The deacetylase SIRT1 is a well-established regulator of autophagy that can be modified by the ubiquitin-like protein SUMO1. Our previous work demonstrated that another ubiquitin-like protein, FAT10, exerts cardioprotective effects against myocardial ischemia by stabilizing the caveolin-3 protein; however, the effects of FAT10 on autophagy through SIRT1 are unclear. Here, we constructed a Fat10-knockout rat model to evaluate the role of FAT10 in autophagy. In vivo and in vitro assays confirmed that FAT10 suppressed autophagy to protect the heart from ischemic myocardial injury. Mechanistically, FAT10 was mainly involved in the regulation of the autophagosome formation process. FAT10 affected autophagy through modulating SIRT1 degradation, which resulted in reduced SIRT1 nuclear translocation and inhibited SIRT1 activity via its C-terminal glycine residues. Notably, FAT10 competed with SUMO1 at the K734 modification site of SIRT1, which further reduced LC3 deacetylation and suppressed autophagy. Our findings suggest that FAT10 inhibits autophagy by antagonizing SIRT1 SUMOylation to protect the heart from ischemic myocardial injury. This is a novel mechanism through which FAT10 regulates autophagy as a cardiac protector.

Human Respiratory Monitoring Based on Schottky Resistance Humidity Sensors.

Two types of Schottky structure sensors (silicon nanowire (SiNW)/ZnO/reduced graphene oxide (rGO) and SiNW/TiO2/rGO) were designed, their humidity resistance characteristics were studied, and the sensors were applied to detect sleep apnea through breath humidity monitoring. The results show that the resistance of the sensors exhibited significant changes with increasing humidity, the response times of the two sensors within the relative humidity range of 23-97% were 49 s and 67 s, and the recovery times were 24 s and 43 s, respectively. Meanwhile, continuous breathing monitoring results indicate that the sensitivity of the sensors remained basically unchanged during 10 min of normal breathing and simulated apnea. The response of the sensor is still good after 30 days of use. We believe that the Schottky structure composite sensor is a very promising technology for human breathing monitoring.

The obesity paradox for outcomes in atrial fibrillation: Evidence from an exposure-effect analysis of prospective studies.

The impact of obesity on the prognosis of atrial fibrillation (AF) remains controversial. We conducted an exposure-effect meta-analysis of prospective studies to clarify the relationship between body mass index (BMI) and outcomes in patients with AF. The Cochrane Library, PubMed, and Embase databases were searched through May 1, 2019. Summary relative risks (RRs) were calculated using random-effects models. Nonlinear associations were explored using restricted cubic spline models. Twenty publications involving 161,922 individuals were included. Categorical variable analysis showed that underweight was associated with an increased risk of all-cause mortality (RR: 2.6), cardiovascular death (RR: 2.91), major bleeding (RR: 1.57), stroke or systemic embolism (RR: 1.62), and a composite endpoint (RR: 2.23). In exposure-effect analysis, the risk per 5 BMI increase was reduced for adverse outcomes (RR=0.86, 95% CI: 0.80-0.92 for all-cause death; RR=0.82, 95% CI: 0.71-0.95 for cardiovascular death; RR=0.89, 95% CI: 0.84-0.95 for stroke or systemic embolism; and RR=0.78, 95% CI: 0.67-0.92 for a composite endpoint). There was a significant "U"-shaped exposure-effect relationship with all-cause death, and the nadir of the curve was observed at a BMI of approximately 28. Our results showed that underweight is associated with a worse prognosis, but that overweight and obesity are associated with improved adverse outcomes in patients with AF.

Ankyrin-B Q1283H Variant Linked to Arrhythmias Via Loss of Local Protein Phosphatase 2A Activity Causes Ryanodine Receptor Hyperphosphorylation.

BACKGROUND: Human loss-of-function variants of ANK2 (ankyrin-B) are linked to arrhythmias and sudden cardiac death. However, their in vivo effects and specific arrhythmogenic pathways have not been fully elucidated. METHODS: We identified new ANK2 variants in 25 unrelated Han Chinese probands with ventricular tachycardia by whole-exome sequencing. The potential pathogenic variants were validated by Sanger sequencing. We performed functional and mechanistic experiments in ankyrin-B knockin (KI) mouse models and in single myocytes isolated from KI hearts. RESULTS: We detected a rare, heterozygous ANK2 variant (p.Q1283H) in a proband with recurrent ventricular tachycardia. This variant was localized to the ZU5C region of ANK2, where no variants have been previously reported. KI mice harboring the p.Q1283H variant exhibited an increased predisposition to ventricular arrhythmias after catecholaminergic stress in the absence of cardiac structural abnormalities. Functional studies illustrated an increased frequency of delayed afterdepolarizations and Ca2+ waves and sparks accompanied by decreased sarcoplasmic reticulum Ca2+ content in KI cardiomyocytes on isoproterenol stimulation. The immunoblotting results showed increased levels of phosphorylated ryanodine receptor Ser2814 in the KI hearts, which was further amplified on isoproterenol stimulation. Coimmunoprecipitation experiments demonstrated dissociation of protein phosphatase 2A from ryanodine receptor in the KI hearts, which was accompanied by a decreased binding of ankyrin-B to protein phosphatase 2A regulatory subunit B56α. Finally, the administration of metoprolol or flecainide decreased the incidence of stress-induced ventricular arrhythmias in the KI mice. CONCLUSIONS: ANK2 p.Q1283H is a disease-associated variant that confers susceptibility to stress-induced arrhythmias, which may be prevented by the administration of metoprolol or flecainide. This variant is associated with the loss of protein phosphatase 2A activity, increased phosphorylation of ryanodine receptor, exaggerated delayed afterdepolarization-mediated trigger activity, and arrhythmogenesis.

Efficacy and safety of triple versus dual antithrombotic therapy in atrial fibrillation and ischemic heart disease: a systematic review and meta-analysis.

The optimal antithrombotic regimen for patients with atrial fibrillation and ischemic heart disease remains unclear. Therefore, we aimed to compare the efficacy and safety of triple therapy (TT [an anticoagulant and 2 antiplatelet drugs]) with dual therapy (DAPT [2 antiplatelet drugs] or DT [an anticoagulant and a single antiplatelet drug]) in patients with atrial fibrillation and ischemic heart disease. We systematically searched the Cochrane Library, PubMed and Embase databases for all relevant studies up to August 2017. The overall risk estimates were calculated using the random-effects model. A total of 17 observational studies were included. Regarding the efficacy outcomes, no differences were observed between the triple therapy and the dual therapy for all-cause death, cardiovascular death, or thrombotic complications (i.e., acute coronary syndrome, stent thrombosis, thromboembolism/stroke, and major adverse cardiac and cerebrovascular events). Regarding the safety outcomes, compared with DAPT, TT was associated with increased risks of major bleeding (a relative risk of 1.96 [1.40-2.74]), minor bleeding (1.69 [1.06-2.71]) and overall bleeding (1.80 [1.23-2.64]). Compared wtih DT, TT was associated with a greater risk of major bleeding (1.65 [1.23-2.21]), but rates of minor bleeding (0.99 [0.56-1.77]) and overall bleeding (1.14 [0.76-1.71]) were similar. Overall, TT confers an increased hazard of major bleeding with no thromboembolic protection compared with dual therapy in patients with atrial fibrillation and ischemic heart disease.

Artificial Olfactory System for Trace Identification of Explosive Vapors Realized by Optoelectronic Schottky Sensing.

A rapid, ultrasensitive artificial olfactory system based on an individual optoelectronic Schottky junction is demonstrated for the discriminative detection of explosive vapors, including military explosives and improvised explosives.