Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and ...clopidogrel monotherapy in this population.
We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6–18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250.
Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 49·8%) or to the aspirin group (2728 50·2%). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 95% CI 0·59–0·90; p=0·0035).
Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events.
ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Extracellular vesicles (EVs) are cell-derived, nanoscale vesicles that carry nucleic acids and proteins from their cells of origin and show great potential as biomarkers for many diseases, including ...cancer. Efficient isolation and detection methods are prerequisites for exploiting their use in clinical settings and understanding their physiological functions. Here, we presented a rapid, label-free, and highly sensitive method for EV isolation and quantification using a lab-on-a-disc integrated with two nanofilters (Exodisc). Starting from raw biological samples, such as cell-culture supernatant (CCS) or cancer-patient urine, fully automated enrichment of EVs in the size range of 20–600 nm was achieved within 30 min using a tabletop-sized centrifugal microfluidic system. Quantitative tests using nanoparticle-tracking analysis confirmed that the Exodisc enabled >95% recovery of EVs from CCS. Additionally, analysis of mRNA retrieved from EVs revealed that the Exodisc provided >100-fold higher concentration of mRNA as compared with the gold-standard ultracentrifugation method. Furthermore, on-disc enzyme-linked immunosorbent assay using urinary EVs isolated from bladder cancer patients showed high levels of CD9 and CD81 expression, suggesting that this method may be potentially useful in clinical settings to test urinary EV-based biomarkers for cancer diagnostics.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Anti-programmed death-ligand 1 (PD-L1) Ab-based therapies have demonstrated potential for treating metastatic urothelial cancer with high PD-L1 expression. Urinary exosomes are promising biomarkers ...for liquid biopsy, but urine's high variability requires normalization for accurate analysis. This study proposes using the PD-L1/Alix ratio to normalize exosomal PD-L1 signal intensity with Alix, an internal exosomal protein less susceptible to heterogeneity concerns than surface protein markers. Extracellular vesicles were isolated using ExoDisc and characterized using various methods, including ExoView to analyze tetraspanins, PD-L1, and Alix on individual exosomes. On-disc ELISA was used to evaluate PD-L1 and Alix-normalized PD-L1 in 15 urothelial cancer patients during the initial treatment cycle with Tecentriq. Results showed that Alix signal range was relatively uniform, whereas tetraspanin marker intensity varied for individual exosome particles. On-disc ELISA was more reliable for detecting exosomal PD-L1 expression than standard plate ELISA-based measurement. Using exosomal Alix expression for normalization is a more reliable approach than conventional methods for monitoring patient status. Overall, the study provides a practical and reliable method for detecting exosomal PD-L1 in urine samples from patients with urothelial cancer.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives This study sought to determine whether computational modeling can be used to predict the functional outcome of coronary stenting by virtual stenting of ischemia-causing stenoses identified ...on the pre-treatment model. Background Computed tomography (CT)-derived fractional flow reserve (FFR) is a novel noninvasive technology that can provide computed (FFR ct ) using standard coronary CT angiography protocols. Methods We prospectively enrolled 44 patients (48 lesions) who had coronary CT angiography before angiography and stenting, and invasively measured FFR before and after stenting. FFR ct was computed in blinded fashion using coronary CT angiography and computational fluid dynamics before and after virtual coronary stenting. Virtual stenting was performed by modification of the computational model to restore the area of the target lesion according to the proximal and distal reference areas. Results Before intervention, invasive FFR was 0.70 ± 0.14 and noninvasive FFR ct was 0.70 ± 0.15. FFR after stenting and FFR ct after virtual stenting were 0.90 ± 0.05 and 0.88 ± 0.05, respectively (R = 0.55, p < 0.001). The mean difference between FFR ct and FFR was 0.006 for pre-intervention (95% limit of agreement: –0.27 to 0.28) and 0.024 for post-intervention (95% limit of agreement: –0.08 to 0.13). Diagnostic accuracy of FFR ct to predict ischemia (FFR ≤0.8) prior to stenting was 77% (sensitivity: 85.3%, specificity: 57.1%, positive predictive value: 83%, and negative predictive value: 62%) and after stenting was 96% (sensitivity: 100%, specificity: 96% positive predictive value: 50%, and negative predictive value: 100%). Conclusions Virtual coronary stenting of CT-derived computational models is feasible, and this novel noninvasive technology may be useful in predicting functional outcome after coronary stenting. (Virtual Coronary Intervention and Noninvasive Fractional Flow Reserve FFR; NCT01478100 )
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this study, a new digital technique for the analysis of the mechanical aperture and contact area of rock fractures under various normal stresses is proposed. The technique requires point cloud ...data of the upper and lower fracture surfaces, pressure film image data of the fracture, and normal deformation data of the fracture as input data. Three steps of algorithms were constructed using these input data: (1) a primary matching algorithm that considers the shape of the fracture surfaces; (2) a secondary matching algorithm that uses pressure film images; and (3) a translation algorithm that considers the normal deformation of a fracture. The applicability of the proposed technique was investigated using natural fracture specimens sampled at an underground research facility in Korea. In this process, the technique was validated through a comparison with the empirical equation suggested in a previous study. The proposed technique has the advantage of being able to analyze changes in the mechanical aperture and contact area under various normal stresses without multiple experiments. In addition, the change in the contact area on the fracture surface according to the normal stress can be analyzed in detail.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The purpose of this article is to compare the diagnostic performances of shearwave and strain elastography for the differentiation of benign and malignant breast lesions.
B-mode ultrasound and ...shear-wave and strain elastography were performed in 150 breast lesions; 71 were malignant. BI-RADS final assessment, elasticity values in kilopascals, and elasticity scores on a 5-point scale were assessed before biopsy. The results were compared using the area under the receiver operating characteristic curve (AUC).
The AUC for shear-wave elastography was similar to that of strain elastography (0.928 vs 0.943). The combined use of B-mode ultrasound and either elastography technique improved diagnostic performance in the differentiation of benign and malignant breast lesions compared with the use of B-mode ultrasound alone (B-mode alone, AUC = 0.851; B-mode plus shear-wave elastography, AUC = 0.964; B-mode plus strain elastography, AUC = 0.965; p < 0.001). With the best cutoff points of 80 kPa on shear-wave elastography and a score between 3 and 4 on strain elastography, the sensitivity was higher in shear-wave elastography, and specificity was higher in strain elastography (95.8% vs 81.7%, p = 0.002; 93.7% vs 84.8%, p = 0.016). In cases of infiltrating ductal carcinoma, mean elasticity scores were lower in grade 3 than in grade 1 and 2 cancers (p = 0.017) with strain elastography causing false-negative findings.
The diagnostic performance of shear-wave and strain elastography was similar. Either elastography technique can improve overall diagnostic performance in the differentiation of benign and malignant lesions when combined with B-mode ultrasound. However, the sensitivity and specificity of shear-wave and strain elastography were different according to lesion histologic profile, tumor grade, and breast thickness.
The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to ...12-month DAPT after implantation of drug-eluting stents.
We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60-2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; P=0.005) among diabetic patients.
Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.
The Korea Atomic Energy Research Institute Underground Research Tunnel (KURT) is an underground research laboratory in South Korea, built for investigations into the geological disposal of high-level ...radioactive waste. We characterize in situ stress states at KURT using data from a series of hydraulic fracturing (HF) tests and borehole image logs to depths of ~700 m in two boreholes. The tensile fractures induced by HF tests, plus several borehole stress indicators (e.g., drilling-induced tensile fractures and borehole breakouts) measured from image logs, consistently indicate an ESE–WNW oriented maximum horizontal principal compressive stress (SHmax). This site-scale SHmax orientation varies slightly from the regional-scale SHmax orientation, likely reflecting a local stress perturbation resulting from a fault network that traverses the site. Estimated magnitudes of the minimum horizontal principal compressive stress (Shmin), determined either from the shut-in pressures recorded during HF tests or from stress indicators on image logs, are comparable to the vertical stress, indicating that the stress regime at the KURT site straddles the boundary between strike-slip and reverse faulting. The depth-dependent trend in estimated SHmax magnitudes deviates at ~500 m depth, which we attribute to variations in the distribution of natural fractures in the granitic rock mass. This depth-dependent variation in SHmax magnitudes has implications for the slip stability of pre-existing fractures at the site. That is, at shallow depths, SHmax lies within the Coulomb stress limit for optimally oriented fractures and faults with a frictional coefficient of 0.6, whereas at greater depths, SHmax exceeds this limit, meaning that pre-existing fractures at shallow depth are more susceptible to slip reactivation. Our stress estimation results suggest that the site-scale stress state is strongly coupled with characteristics of natural fractures, emphasizing the importance of detailed geologic and stress data for subsurface utilization and its stability evaluation.
•The stress at KURT is estimated from hydrofrac tests and borehole stress indicators.•Site-scale stress orientations deviate from regional stress due to local faults.•Horizontal stress magnitudes vary with the distribution of natural fractures.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Electrochemical biosensors have shown great potential for simple, fast, and cost‐effective point‐of‐care diagnostic tools. However, direct analysis of complex biological fluids such as plasma has ...been limited by the loss of sensitivity caused by biofouling. By increasing the surface area, the nanostructured electrode can improve detection sensitivity. However, like a double‐edged sword, a large surface area increases the nonspecific adsorption of contaminating proteins. The use of nanoporous structures may prevent fouling proteins. However, there is no straightforward approach for creating nanostructured and nanoporous surfaces compatible with microfabricated thin‐film electrodes. Herein, the preferential etching of chloride and surfactant‐assisted anisotropic gold reduction to create homogeneous, nanostructured, and nanoporous gold electrodes is demonstrated, yielding a 190 ± 20 times larger surface area within a minute without using templates. This process, “surfactant‐based electrochemical etch‐deposit interplay for nanostructure/nanopore growth” (SEEDING), on electrodes enhances the sensitivity and antibiofouling capabilities of amperometric biosensors, enabling direct analysis of tumor‐derived extracellular vesicles (tEVs) in complex biofluids with a limit of detection of 300 tEVs µL−1 from undiluted plasma and good discrimination between patients with prostate cancer from healthy ones with an area under the curve of 0.91 in urine and 0.90 in plasma samples.
A nanostructured surface with nanoporous substrate provides high sensitivity and a low detection limit with antifouling capabilities. This material enables the fabrication of electrochemical biosensors for the detection of biomarkers in undiluted complex biological samples without suffering passivation. Direct analysis of clinical plasma samples reveal that it is sensitive enough to discriminate between a prostate cancer cohort and healthy donors.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
