Highly visible-light-active sulfur and carbon co-doped TiO2 (SC-TiO2) heterogeneous photocatalysts prepared by underwater discharge plasma.

To promptly and simply create highly crystalline S/C co-doped TiO2 (SC-TiO2) photocatalysts at room temperature and atmospheric pressure, we suggest a novel plasma-assisted sol-gel synthesis method. This method is a simultaneous synthetic process, in which an underwater plasma undergoes continuous reactions to generate high-energy atomic and molecular species that enable TiO2 to achieve crystallinity, a large surface area, and a heterogeneous structure within a few minutes. In particular, it was demonstrated that the heterogeneously structured TiO2 was formed by doping that sulfur and carbon replace O or Ti atoms in the TiO2 lattice depending on the composition of the synthesis solution during underwater plasma treatment. The resultant SC-TiO2 photocatalysts had narrowed bandgap energies and extended optical absorption scope into the visible range by inducing the intermediate states within bandgap due to generation of oxygen vacancies on the surface of TiO2 through synthesis, crystallization, and doping. Correspondingly, SC-TiO2 showed a significant degradation efficiency ([k] = 6.91 h-1) of tetracycline (TC, antibiotics) under solar light irradiation, up to approximately 4 times higher compared to commercial TiO2 ([k] = 1.68 h-1), resulting in great water purification. Therefore, we anticipate that this underwater discharge plasma system will prove to be an advantageous technique for producing heterostructural TiO2 photocatalysts with superior photocatalytic efficiency for environmental applications.

Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease.

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.

Molecular Aggregation Behavior and Microscopic Heterogeneity in Binary Osmolyte-Water Solutions.

Osmolytes, small organic compounds, play a key role in modulating the protein stability in aqueous solutions, but the operating mechanism of the osmolyte remains inconclusive. Here, we attempt to clarify the mode of osmolyte action by quantitatively estimating the microheterogeneity of osmolyte-water mixtures with the aid of molecular dynamics simulation, graph theoretical analysis, and spatial distribution measurement in the four osmolyte solutions of trimethylamine-N-oxide (TMAO), tetramethylurea (TMU), dimethyl sulfoxide, and urea. TMAO, acting as a protecting osmolyte, tends to remain isolated with no formation of osmolyte aggregates while preferentially interacting with water, but there is a strong aggregation propensity in the denaturant TMU solution, characterized by favored hydrophobic interactions between TMU molecules. Taken together, the mechanism of osmolyte action on protein stability is proposed as a comprehensive one that encompasses the direct interactions between osmolytes and proteins and indirect interactions through the regulation of water properties in the osmolyte-water mixtures.

Nocturnal systolic blood pressure dipping and progression of chronic kidney disease.

The relationship between declining nocturnal blood pressure (BP) and adverse cardiovascular outcomes is well-recognized. However, the relationship between diurnal BP profile and the risk of chronic kidney disease (CKD) progression is unclear. Herein, we examined the association between nocturnal systolic SBP (SBP) dipping and CKD progression in 1061 participants at the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI). The main exposure was diurnal systolic BP (SBP) profile and diurnal SBP difference ([nighttime SBP-daytime SBP] × 100/daytime SBP). The primary outcome was CKD progression, defined as a composite of ≥ a 50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy. During 4749 person-years of follow-up (median, 4.8 years), the composite outcome occurred in 380 (35.8%) participants. Compared to dippers, the hazard ratios (HRs) for the risk of adverse kidney outcomes were 1.02 (95% confidence interval [CI], 0.64-1.62), 1.30 (95% CI, 1.02-1.66), and 1.40 (95% CI, 1.03-1.90) for extreme dipper, non-dipper, and reverse dipper, respectively. In a continuous modeling, a 10% increase in diurnal SBP difference was associated with a 1.21-fold (95% CI, 1.07-1.37) higher risk of CKD progression. Thus, decreased nocturnal SBP decline was associated with adverse kidney outcomes in patients with CKD. Particularly, patients with non-dipping and reverse dipping patterns were at higher risk for CKD progression than those with a dipping pattern.

Ulmus macrocarpa Hance trunk bark extracts inhibit RANKL-induced osteoclast differentiation and prevent ovariectomy-induced osteoporosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus macrocarpa Hance (UmH) bark has been traditionally utilized for medicinal purposes. The bark extract of this plant has diverse health benefits, and its potential role in enhancing bone health is of distinct interest, particularly when considering the substantial health and economic implications of bone-related pathologies, such as osteoporosis. Despite the compelling theoretical implications of UmH bark in fortifying bone health, no definitive evidence at the in vivo level is currently available, thus highlighting the innovative and as-yet-unexplored potential of this field of study. AIM OF THE STUDY: Primarily, our study aims to conduct a meticulous analysis of the disparity in the concentration of active compounds in the UmH root bark (Umrb) and trunk bark (Umtb) extracts and confirm UmH bark's efficacy in enhancing bone health in vivo, illuminating the cellular mechanisms involved. MATERIALS AND METHODS: The Umrb and Umtb extracts were subjected to component analysis using high-performance liquid chromatography and then assessed for their inhibitory effects on osteoclast differentiation through the TRAP assay. An ovariectomized (OVX) mouse model replicates postmenopausal conditions commonly associated with osteoporosis. Micro-CT was used to analyze bone structure parameters, and enzyme-linked immunosorbent assay and staining were used to assess bone formation markers and osteoclast activity. Furthermore, this study investigated the impact of the extract on the expression of pivotal proteins and genes involved in bone formation and resorption using mouse bone marrow-derived macrophages (BMMs). RESULTS: The findings of our study reveal a significant discrepancy in the concentration of active constituents between Umrb and Umtb, establishing Umtb as a superior source for promoting bone health. I addition, a standardized pilot-scale procedure was conducted for credibility. The bone health benefits of Umtb were verified using an OVX model. This validation involved the assessment of various parameters, including BMD, BV/TV, and BS/TV, using micro-CT imaging. Additionally, the activation of osteoblasts was evaluated by Umtb by measuring specific factors such as ALP, OCN, OPG in blood samples and through IHC staining. In the same investigations, diminished levels of osteoclast differentiation factors, such as TRAP, NFATc1, were also observed. The observed patterns exhibited consistency in vitro BMM investigations. CONCLUSIONS: Through verification at both in vitro levels using BMMs and in vivo levels using the OVX-induced mouse model, our research demonstrates that Umtb is a more effective means of improving bone health in comparison to Umrb. These findings pave the way for developing health-functional foods or botanical drugs targeting osteoporosis and other bone-related disorders and enhance the prospects for future research extensions, including clinical studies, in extract applications.

Time-resolved photoluminescence analysis of ceramic Ce:GAGG scintillators.

This paper introduces the characteristics and efficiency of post-treatment methods for enhancing the timing resolution of ceramic Ce:GAGG scintillators. The thermal annealing and surface treatments were included to analyze their impact on time-resolved photoluminescence (TRPL) and thermoluminescence (TL) characteristics. Optical properties were improved by suppressing nonradiative recombination due to the reduced surface defects, while heat-treatment removes traps as confirmed by TL measurements. TRPL decay characteristics revealed that samples treated with mechanical polishing followed by heat treatment exhibited the best scintillation performance, with a slow component of 272.3 ns. These findings will aid in developing techniques for improving the luminescence of other inorganic scintillators.

PRID: Prediction Model Using RWR for Interactions between Drugs.

Drug-drug interactions (DDI) occur because of the unexpected pharmacological effects of drug pairs. Although drug efficacy can be improved by taking two or more drugs in the short term, this may cause inevitable side effects. Currently, multiple drugs are prescribed based on the experience or knowledge of the clinician, and there is no standard database that can be referred to as safe co-prescriptions. Thus, accurately identifying DDI is critical for patient safety and treatment modalities. Many computational methods have been developed to predict DDIs based on chemical structures or biological features, such as target genes or functional mechanisms. However, some features are only available for certain drugs, and their pathological mechanisms cannot be fully employed to predict DDIs by considering the direct overlap of target genes. In this study, we propose a novel deep learning model to predict DDIs by utilizing chemical structure similarity and protein-protein interaction (PPI) information among drug-binding proteins, such as carriers, transporters, enzymes, and targets (CTET) proteins. We applied the random walk with restart (RWR) algorithm to propagate drug CTET proteins across a PPI network derived from the STRING database, which will lead to the successful incorporation of the hidden biological mechanisms between CTET proteins and disease-associated genes. We confirmed that the RWR propagation of CTET proteins helps predict DDIs by utilizing indirectly co-regulated biological mechanisms. Our method identified the known DDIs between clinically proven epilepsy drugs. Our results demonstrated the effectiveness of PRID in predicting DDIs in known drug combinations as well as unknown drug pairs. PRID could be helpful in identifying novel DDIs and associated pharmacological mechanisms to cause the DDIs.

Controlling the Chameleonic Behavior and Membrane Permeability of Cyclosporine Derivatives via Backbone and Side Chain Modifications.

Some macrocycles exhibit enhanced membrane permeability through conformational switching in different environmental polarities, a trait known as chameleonic behavior. In this study, we demonstrate specific backbone and side chain modifications that can control chameleonic behavior and passive membrane permeability using a cyclosporin O (CsO) scaffold. To quantify chameleonic behavior, we used a ratio of the population of the closed conformation obtained in polar solvent and nonpolar solvent for each CsO derivative. We found that ß-hydroxylation at position 1 (1 and 3) can encode chameleonicity and improve permeability. However, the conformational stabilization induced by adding an additional transannular H-bond (2 and 5) leads to a much slower rate of membrane permeation. Our CsO scaffold provides a platform for the systematic study of the relationship among conformation, membrane permeability, solubility, and protein binding. This knowledge contributes to the discovery of potent beyond the rule of five (bRo5) macrocycles capable of targeting undruggable targets.

Risk Factors and Outcomes With Progressive Mitral Annular Calcification.

Background Mitral annular calcification (MAC) is a chronic degenerative process that may progress. This study aimed to investigate associating factors and clinical implications of MAC progression. Methods and Results Among 560 patients with MAC identified by transthoracic echocardiography between January 2012 and June 2016, 138 patients (mean±SD age 72.7±10.2 years, 73 women) with mild or moderate MAC who received follow-up examination within 18 to 36 months were retrospectively analyzed. Progressive MAC was defined as hemodynamic or structural profiles that had worsened by more than 1 grade. Hemodynamic features were assessed by the transmitral mean diastolic pressure gradient (MDPG), and structural features were assessed by the MAC angle in the parasternal short-axis view. The clinical outcome was defined as a composite of all-cause mortality, hospitalization for heart failure, and occurrence of ischemic stroke. Forty-three patients (31.2%) showed progressive MAC. Patients with progressive MAC had higher systolic blood pressure, pulse pressure, MAC angle, and MDPG than those with stable MAC. Patients with progressive MAC had smaller left ventricular (LV) end-systolic dimensions and higher LV ejection fractions compared with those with stable MAC. In multivariate analysis, pulse pressure, LV ejection fraction, MAC angle, and MDPG at baseline were significantly associated with MAC progression. During a median of 39.2 months' follow-up, patients with progressive MAC showed poorer clinical outcomes than those with stable MAC (log-rank P=0.015). Conclusions MAC progression is not rare and is associated with structural substrate and hemodynamic loads that result in mechanical stress. Patients with progressive MAC have poor outcomes.

Phantom study of layered sensor module for photon-counting BMD detector.

In this study, we perform bone mineral density (BMD) calculation by designing a layered sensor module (LSM) that divides high- and low-energy spectra from a single shot of X-rays. Gamma-ray evaluation supports this mechanism; low-energy gamma rays are absorbed in the front detector, whereas high-energy gamma rays are absorbed in the rear detector. In this phantom study, LSM divides a single shot of X-ray into two spectra with different distributions of energy, thereby affording X-ray images with different properties, such as contrast and gray scale. The region of interest (ROI) is classified by the Prewitt operator to sort the pixels for BMD calculation or Rs value. The calculated final value is 1.2051 g/cm2 with a standard deviation (SD) of 0.3690 g/cm2, as obtained from our previous study. An improved SD results from the layered structure with two channels for signal processing, the introduction of Rs value, and the use of Prewitt filter to sort reliable data. Overall, this study displays the feasibility of LSM for BMD calculation with a small error, thereby enabling the diagnosis of osteoporosis with novel mechanism.

Deep-learning model for predicting physical fitness in possible sarcopenia: analysis of the Korean physical fitness award from 2010 to 2023.

Introduction: Physical fitness is regarded as a significant indicator of sarcopenia. This study aimed to develop and evaluate a deep-learning model for predicting the decline in physical fitness due to sarcopenia in individuals with potential sarcopenia. Methods: This study used the 2010-2023 Korean National Physical Fitness Award data. The data comprised exercise- and health-related measurements in Koreans aged >65 years and included body composition and physical fitness variables. Appendicular muscle mass (ASM) was calculated as ASM/height2 to define normal and possible sarcopenia. The deep-learning model was created with EarlyStopping and ModelCheckpoint to prevent overfitting and was evaluated using stratified k-fold cross-validation (k = 5). The model was trained and tested using training data and validation data from each fold. The model's performance was assessed using a confusion matrix, receiver operating characteristic curve, and area under the curve. The average performance metrics obtained from each cross-validation were determined. For the analysis of feature importance, SHAP, permutation feature importance, and LIME were employed as model-agnostic explanation methods. Results: The deep-learning model proved effective in distinguishing from sarcopenia, with an accuracy of 87.55%, precision of 85.57%, recall of 90.34%, and F1 score of 87.89%. Waist circumference (WC, cm), absolute grip strength (kg), and body fat (BF, %) had an influence on the model output. SHAP, LIME, and permutation feature importance analyses revealed that WC and absolute grip strength were the most important variables. WC, figure-of-8 walk, BF, timed up-and-go, and sit-and-reach emerged as key factors for predicting possible sarcopenia. Conclusion: The deep-learning model showed high accuracy and recall with respect to possible sarcopenia prediction. Considering the need for the development of a more detailed and accurate sarcopenia prediction model, the study findings hold promise for enhancing sarcopenia prediction using deep learning.

Unlocking Cu(I)-Mediated Catalytic Pathways for Efficient ROS Generation by Incorporating an Oxazole-Based Histidine Surrogate into Cu(II)-ATCUN Complexes.

The catalytic redox activity of Cu(II) bound to the amino-terminal copper and nickel (ATCUN) binding motif (Xxx-Zzz-His, XZH) is stimulating the development of catalytic metallodrugs based on reactive oxygen species (ROS)-mediated biomolecule oxidation. However, low Cu(I) availability resulting from the strong Cu(II) binding affinity of the ATCUN motif is regarded as a limitation to efficient ROS generation. To address this, we replaced the imidazole moiety (pKa 7.0) of Gly-Gly-His-NH2 (GGHa, a canonical ATCUN peptide) with thiazole (pKa 2.7) and oxazole (pKa 0.8), yielding GGThia and GGOxa, respectively. A newly synthesized amino acid, Fmoc-3-(4-oxazolyl)-l-alanine, served as a histidine surrogate featuring an azole ring with the lowest pKa among known analogues. Despite similar square-planar Cu(II)-N4 geometries being observed for the three Cu(II)-ATCUN complexes by electron paramagnetic resonance spectroscopy and X-ray crystallography, the azole modification enabled the Cu(II)-ATCUN complexes to exhibit significant rate enhancement for ROS-mediated DNA cleavage. Further analyses based on Cu(I)/Cu(II) binding affinities, electrochemical measurements, density functional theory calculations, and X-ray absorption spectroscopy indicated that the azole modification enhanced the accessibility of the Cu(I) oxidation state during ROS generation. Our oxazole/thiazole-containing ATCUN motifs provide a new design strategy for peptide ligands with modulated N donor ability, with potential applications in the development of ROS-mediated metallodrugs.

Real-Time Monitoring of Multitarget Antimicrobial Mechanisms of Peptoids Using Label-Free Imaging with Optical Diffraction Tomography.

Antimicrobial peptides (AMPs) are promising therapeutics in the fight against multidrug-resistant bacteria. As a mimic of AMPs, peptoids with N-substituted glycine backbone have been utilized for antimicrobials with resistance against proteolytic degradation. Antimicrobial peptoids are known to kill bacteria by membrane disruption; however, the nonspecific aggregation of intracellular contents is also suggested as an important bactericidal mechanism. Here,structure-activity relationship (SAR) of a library of indole side chain-containing peptoids resulting in peptoid 29 as a hit compound is investigated. Then, quantitative morphological analyses of live bacteria treated with AMPs and peptoid 29 in a label-free manner using optical diffraction tomography (ODT) are performed. It is unambiguously demonstrated that both membrane disruption and intracellular biomass flocculation are primary mechanisms of bacterial killing by monitoring real-time morphological changes of bacteria. These multitarget mechanisms and rapid action can be a merit for the discovery of a resistance-breaking novel antibiotic drug.

Reclassification of moderate aortic stenosis based on data-driven phenotyping of hemodynamic progression.

The management and follow-up of moderate aortic stenosis (AS) lacks consensus as the progression patterns are not well understood. This study aimed to identify the hemodynamic progression of AS, and associated risk factors and outcomes. We included patients with moderate AS with at least three transthoracic echocardiography (TTE) studies performed between 2010 and 2021. Latent class trajectory modeling was used to classify AS groups with distinctive hemodynamic trajectories, which were determined by serial systolic mean pressure gradient (MPG) measurements. Outcomes were defined as all-cause mortality and aortic valve replacement (AVR). A total of 686 patients with 3093 TTE studies were included in the analysis. Latent class model identified two distinct AS trajectory groups based on their MPG: a slow progression group (44.6%) and a rapid progression group (55.4%). Initial MPG was significantly higher in the rapid progression group (28.2 ± 5.6 mmHg vs. 22.9 ± 2.8 mmHg, P < 0.001). The prevalence of atrial fibrillation was higher in the slow progression group; there was no significant between-group difference in the prevalence of other comorbidities. The rapid progression group had a significantly higher AVR rate (HR 3.4 [2.4-4.8], P < 0.001); there was no between-group difference in mortality (HR 0.7 [0.5-1.0]; P = 0.079). Leveraging longitudinal echocardiographic data, we identified two distinct groups of patients with moderate AS: slow and rapid progression. A higher initial MPG (≥ 24 mmHg) was associated with more rapid progression of AS and higher rates of AVR, thus indicating the predictive value of MPG in management of the disease.

Effects of continuous positive airway pressure therapy on left ventricular performance in patients with severe obstructive sleep apnea.

We investigated myocardial performance concerning obstructive sleep apnea (OSA) severity and the benefits of continuous positive airway pressure (CPAP) therapy. In this randomized sham-controlled trial, 52 patients (mean age, 49 years; 92%, males; mean AHI, 59) with severe OSA were randomly assigned to receive either CPAP or sham treatment for 3 months. The severity of OSA was determined using the apnea/hypopnea index (AHI), oxygen desaturation index (ODI), percentage of sleep time below 90% oxygen saturation (T90), and average O2 saturation during sleep (mean SpO2). We compared the changes in myocardial work after 3 months of CPAP (n = 26) versus the sham group (n = 26) at rest and during an exercise stress test. Unlike AHI or ODI, indices of hypoxemia including T90 and mean SpO2 were significantly correlated with global constructive work, as defined by work of left ventricle (LV) that contributes to LV ejection during systole (T90, ß = 0.393, p = 0.012; mean SpO2, ß = 0.331, p = 0.048), and global wasted work (GWW), as defined by work of LV that does not contribute to LV ejection (T90, ß = 0.363, p = 0.015; mean SpO2, ß = - 0.370, p = 0.019). After 3 months, GWW decreased (80.0 ± 49.2 to 60.8 ± 26.3, p = 0.009) and global work efficiency increased (94.0 ± 4.5 to 95.7 ± 2.0, p = 0.008) in the CPAP group compared to those in the sham group. At the 3-month follow-up exercise stress echocardiography, worsening of GWW during exercise was significantly decreased in the CPAP group compared to that in the sham group (p = 0.045 at 50 W). Hypoxemia indices were closely associated with myocardial performance in patients with severe OSA. CPAP treatment for 3 months improved left ventricular myocardial performance by decreasing wasted work and increasing work efficacy compared to the sham treatment.

Structure-activity relationship analysis of activity-based probes targeting HTRA family of serine proteases.

High temperature requirement A serine proteases (HTRA) are ubiquitously expressed and participate in protein quality control and cellular stress responses. They are linked to several clinical illnesses, including bacterial infection, cancer, age-related macular degeneration, and neurodegenerative diseases. In addition, several recent studies have revealed HTRAs as important biomarkers and potential therapeutic targets, necessitating the development of an effective detection method to evaluate their functional states in various disease models. We developed a new series of HTRA-targeting activity-based probes with enhanced subtype selectivity and reactivity. In conjunction with our previously developed tetrapeptide probes, we established the structure-activity relationship of the new probes for different HTRA subtypes. Our probes are cell-permeable and have potent inhibitory effects against HTRA1 and HTRA2, making them valuable for identifying and validating HTRAs as an important biomarker.

Torilis japonica Extract Suppresses the Induction of Atopic Inflammation.

As one of the major intractable allergic disorders, atopic inflammation is commonly accompanied by itching, dry skin, and inflammation. Atopic inflammation deteriorates the quality of life and has no fundamental cure, so it is crucial to urgently explore and develop natural resources for long-term treatment without any side effects. This study aimed to verify Torilis japonica extract (TJE)'s relieving effect and mechanism against atopic inflammation using skin cells and skin equivalent models, as well as to investigate torilin's effect (obtained from TJE) and other unknown components as marker compounds. Torilin concentration was verified in TJE using high-performance liquid chromatography and analyzed the unknown components using nuclear magnetic resonance spectroscopy. Furthermore, TJE's cytotoxicity, regenerative effect, and cell cycle regulation effects were confirmed using skin cells with atopic inflammation (human dermal fibroblasts and HaCaT keratinocytes) by using TNF-α and IFN-γ treatments. Consequently, TJE was demonstrated to regulate TARC and CTACK expressions as chemokines and those of interleukin-4, -5, and -13 as cytokines related to atopic inflammation. TJE was further confirmed to affect the matrix metalloproteinase-1, -2, and -9 expressions, which are essential in skin damage. Lastly, this study confirmed TJE's relieving effect against atopic inflammation through a 3D skin model and RhCE model using human dermal fibroblasts and HaCaT keratinocytes. These findings on atopic inflammation verified torilin's relieving effects and TJE's other components.

Prognostic Implication of Mitral Valve Disease and Its Progression in East Asian Patients With Hypertrophic Cardiomyopathy.

Background Hypertrophic cardiomyopathy (HCM) is a genetic disorder affecting not only the myocardium but also the mitral valve (MV) and its apparatus. This study aimed to investigate the prognostic implication of MV disease and its progression in East Asian patients with HCM. Methods and Results We assessed MV structure and function on the indexed echocardiogram of 1185 patients with HCM (mean±SD age, 60±14 years; men, 67%) in a longitudinal HCM registry, and 667 patients who performed follow-up echocardiogram after 3 to 5 years were also analyzed. Progression of mitral regurgitation (MR) was defined as the increase of at least 1 grade. Clinical outcomes were defined as a composite of cardiovascular death, heart failure hospitalization, MV surgery or septal myectomy, and heart transplantation. Most of the entire cohort was nonobstructive type (n=1081 [91.2%]). A total of 278 patients (23.5%) showed at least mild MR on indexed echocardiogram. MR, systolic anterior motion, and mitral annular calcification were more prevalent in patients with obstructive HCM. During 7.0±4.0 years of follow-up, presence of MR was independently associated with poor clinical outcomes (hazard ratio [HR], 1.60 [95% CI, 1.07-2.40]; P=0.023). On follow-up echocardiogram, 67 (10.0%) patients showed MR progression, and it was independently associated with poor prognosis (HR, 2.46 [95% CI, 1.29-4.71]; P=0.007). Conclusions In East Asian patients with HCM whose major type is nonobstructive, MV disease is common. MR, systolic anterior motion, and mitral annular calcification are more prevalent in patients with obstructive HCM. The presence and progression of MR are associated with a poor prognosis in patients with HCM.

Efficacy and safety of edoxaban in patients early after surgical bioprosthetic valve implantation or valve repair: A randomized clinical trial.

OBJECTIVE: Early warfarin anticoagulation is recommended in patients undergoing surgical bioprosthetic valve implantation or valve repair. It is unclear whether non-vitamin K antagonist oral anticoagulants can be a full alternative to warfarin. This study aimed to compare efficacy and safety of edoxaban with warfarin in patients early after surgical bioprosthetic valve implantation or valve repair. METHODS: The Explore the Efficacy and Safety of Edoxaban in Patients after Heart Valve Repair or Bioprosthetic Valve Replacement study was a prospective, randomized (1:1), open-label, clinical trial conducted from December 2017 to September 2019. Patients were randomly assigned to receive edoxaban (60 mg or 30 mg once daily) or warfarin for the first 3 months after surgical bioprosthetic valve implantation or valve repair. The primary efficacy outcome was a composite of death, clinical thromboembolic events, or asymptomatic intracardiac thrombosis. The primary safety outcome was the occurrence of major bleeding. RESULTS: Of 220 participants, 218 (109 per group) were included in the modified intention-to-treat analysis. The primary efficacy outcome occurred in 4 patients (3.7%) taking warfarin and none taking edoxaban (risk difference, -0.0367; 95% confidence interval, -0.0720 to -0.0014; P < .001 for noninferiority). The primary safety outcome occurred in 1 patient (0.9%) taking warfarin and 3 patients (2.8%) taking edoxaban (risk difference, 0.0183; 95% confidence interval, -0.0172 to 0.0539; P = .013 for noninferiority). CONCLUSIONS: Edoxaban is noninferior to warfarin for preventing thromboembolism and is potentially comparable for risk of major bleeding during the first 3 months after surgical bioprosthetic valve implantation or valve repair.

The ratio of measured and reference effective orifice areas for discriminating prosthetic aortic valve obstruction.

AIMS: We aimed to evaluate the efficacy of the measured effective orifice area (EOA)/reference EOA ratio in discriminating mechanical prosthetic aortic valve (PAV) obstruction. METHODS AND RESULTS: This is a retrospective study of 193 mechanical PAV patients with an elevated mean transprosthetic pressure gradient (PG) over 20 mmHg or peak velocity over 3 m/s. Of those, 143 patients were objectively proven PAV obstruction with cardiac computed tomography or surgical inspection. The EOA was measured using the continuity equation, and the reference EOA values were obtained from previous guidelines. The measured/reference EOA ratio was significantly lower in the obstruction group (0.63 ± 0.18 vs. 0.86 ± 0.17; P < 0.001). The EOA ratio added incremental value for discriminating obstruction from the conventional parameters recommended in the guidelines. Receiver operating characteristic curve analysis revealed that the measured/reference EOA ratio discriminated PAV obstruction from those without obstruction [area under the curve (AUC), 0.840; 95% confidence interval, 0.783-0.898; P < 0.001]. A cutoff of 0.71 had 73.4% sensitivity and 82.0% specificity. The novel diagnostic algorithm adding the EOA ratio had similar accuracy to previous guideline algorithms, including reference EOA, and conventional Doppler parameters (AUC, 0.763 vs. 0.731; P = 0.309). In patients with a large PAV (≥23 mm), the novel algorithm had higher accuracy than the previous algorithm (AUC, 0.788 vs. 0.642; P = 0.019). CONCLUSION: The ratio of measured/reference EOA adds incremental value over conventional Doppler parameters and might be helpful for distinguishing PAV obstruction.