Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary ...syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population.
We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453.
Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 2·6% patients vs 39 2·9%; hazard ratio HR 0·90 95% CI 0·57–1·42; p=0·90) and neither did stroke (11 0·8% patients vs 12 0·9%; 0·92 0·41–2·08; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 1·8% patients vs ten 0·8%; 2·41 1·15–5·05; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 95% CI 0·68–3·35; p=0·32). The rate of BARC type 2–5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 95% CI 0·45–1·05; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis.
The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care.
Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.
Slim-panel holographic video display An, Jungkwuen; Won, Kanghee; Kim, Young ...
Nature communications,
11/2020, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Since its discovery almost 70 years ago, the hologram has been considered to reproduce the most realistic three dimensional images without visual side effects. Holographic video has been extensively ...researched for commercialization, since Benton et al. at MIT Media Lab developed the first holographic video systems in 1990. However, commercially available holographic video displays have not been introduced yet for several reasons: narrow viewing angle, bulky optics and heavy computing power. Here we present an interactive slim-panel holographic video display using a steering-backlight unit and a holographic video processor to solve the above issues. The steering-backlight unit enables to expand the viewing angle by 30 times and its diffractive waveguide architecture makes a slim display form-factor. The holographic video processor computes high quality holograms in real-time on a single-chip. We suggest that the slim-panel holographic display can provide realistic three-dimensional video in office and household environments.
Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided ...PCI, are limited.
In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed.
A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events.
Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).
A predictive biomarker of immune checkpoint inhibitor (ICI)-based treatments in hepatocellular carcinoma (HCC) has not been clearly demonstrated. In this study, we focused on the infiltration and ...programmed death ligand 1 (PD-L1) expression of tumor-associated macrophages (TAMs) in the tumor microenvironment of HCC. Immunohistochemistry demonstrated that PD-L1 was preferentially expressed on CD68
macrophages in the tumor microenvironment of HCC, suggestive of its expression in TAMs rather than in T cells or tumor cells (
< 0.05). A co-culture experiment using activated T cells and M2 macrophages confirmed a significant increase in T cell functionality after the pretreatment of M2 macrophages with anti-PD-L1. Syngeneic mouse model experiments demonstrated that TAMs expressed PD-L1 and tumors treated with anti-PD-L1 showed smaller diameters than those treated with IgG. In these mice, anti-PD-L1 treatment increased activation markers in intratumoral CD8
T cells and reduced the size of the TAM population. Regarding nivolumab-treated patients, three of eight patients responded to the anti-PD-1 treatment. The percentage of Ki-67-positive CD4
and CD8
T cells was higher in responders than non-responders after nivolumab. Overall, PD-L1 expression on TAMs may be targeted by immune-based HCC treatment, and ICI treatment results in the reinvigoration of exhausted CD8
T cells in HCC.
The unique properties of graphene oxides (GO) such as water dispersibility, versatile surface modification, and photoluminescence make them suitable for biological applications. In this study, we ...explored the use of GO sheets as a novel DNA biosensor by applying the GO in an array format to recognize specific DNA–DNA hybridization interaction. When the probe DNA linked to the surface of GO by using carbodiimide chemistry is hybridized with a gold nanoparticle (Au NP) labeled complementary DNA strand, the fluorescence emission intensity of the GO array is drastically reduced. TEM data reveal that the Au NPs are dispersed on the GO surface, particularly at edges and folded structures upon hybridization with a density of ∼80 Au NPs per μm
2. This leads to
ca. 87% fluorescence quenching as a consequence of fluorescence energy transfer between Au NPs and the GO sheets. These results suggest that the GO nanomaterials, which are readily synthesized on a large scale from a cheap graphite source, could have a wide range of bioapplications in the fields of biosensors, molecular imaging and nanobiotechnology.
The most common symptom of bladder cancer (BC) is hematuria. However, not all patients with hematuria are diagnosed with BC. Here, we explored a novel method to discriminate BC from hematuria under ...nonmalignant conditions by measuring differences in urinary cell‐free microRNA (miRNA) expression between patients with BC and those with hematuria. A multicenter study was performed using 543 urine samples obtained from the National Biobank of Korea, including 326 BC, 174 hematuria and 43 pyuria without cancer. The urinary miR‐6124 to miR‐4511 ratio was considerably higher in BC than in hematuria or pyuria, and enabled the discrimination of BC from patients with hematuria at a sensitivity of >90% (p < 0.001). Conclusively, the proposed noninvasive diagnostic tool based on the expression ratio of urinary cell‐free miR‐6124 to miR‐4511 can reduce unnecessary cystoscopies in patients with hematuria undergoing evaluation for BC, with a minimal loss in sensitivity for detecting cancer.
What's new?
Noninvasive urinary biomarkers are promising tools for distinguishing nonmalignant hematuria from hematuria associated with bladder cancer during primary patient evaluation. MicroRNAs (miRNAs), which function as oncogenes or tumor suppressors in cancer and are highly stable in body fluids, are emerging markers for this purpose. In the present study, the expression ratio between two urinary cell‐free miRNAs, miR‐6124 and miR‐4511, was found to be significantly higher in patients with bladder cancer than in those with hematuria or pyuria. The findings suggest that noninvasive assessment of miR‐6124/miR‐4511 expression ratio could help prevent unnecessary cystoscopy procedures when discriminating benign from malignant hematuria.
We evaluated the long-term effect of stereotactic body radiation therapy (SBRT) for primary small hepatocellular carcinoma (HCC) ineligible for local therapy or surgery.
Forty-two HCC patients with ...tumors ≤ 100 cc and ineligible for local ablation therapy or surgical resection were treated with SBRT: 30-39 Gy with a prescription isodose range of 70-85% (median 80%) was delivered daily in three fractions. Median tumor volume was 15.4 cc (3.0-81.8) and median follow-up duration 28.7 months (8.4-49.1).
Complete response (CR) for the in-field lesion was initially achieved in 59.6% and partial response (PR) in 26.2% of patients. Hepatic out-of-field progression occurred in 18 patients (42.9%) and distant metastasis developed in 12 (28.6%) patients. Overall in-field CR and overall CR were achieved in 59.6% and 33.3%, respectively. Overall 1-year and 3-year survival rates were 92.9% and 58.6%, respectively. In-field progression-free survival at 1 and 3 years was 72.0% and 67.5%, respectively. Patients with smaller tumor had better in-field progression-free survival and overall survival rates (<32 cc vs. ≥32 cc, P < 0.05). No major toxicity was encountered but one patient died with extrahepatic metastasis and radiation-induced hepatic failure.
SBRT is a promising noninvasive-treatment for small HCC that is ineligible for local treatment or surgical resection.
Background:Data regarding complex relationships between age, sex, obesity and N-terminal pro B-type natriuretic peptide (NT-proBNP) remain scarce. Thus, we investigated sex-specific associations of ...obesity and NT-proBNP levels among adults in the general healthy population in Korea.Methods and Results:The associations of age, sex and obesity-associated parameters (waist circumference WC, body mass index BMI and body weight) with NT-proBNP were analyzed in 39,937 healthy adult participants. Multivariable regression models adjusted for factors known to affect NT-proBNP were used to identify associations between NT-proBNP and obesity-related parameters. NT-proBNP levels were higher in females than males. Older age was also associated with higher NT-proBNP levels in the overall population (P<0.001). When accounting for age in multivariable linear regression models, there was a strong inverse association between WC, BMI, and NT-proBNP in females and a weaker inverse association in males, with a significant difference between the sexes (P interaction <0.001). After adjusting for the effects of WC and BMI on each other, abdominal obesity was associated with lower NT-proBNP levels in females but not males (P interaction <0.001).Conclusions:In this large sample of young and healthy Asians, younger age, male sex, and increases in obesity-related parameters were related to lower levels of NT-proBNP. Further comprehensive studies are needed to understand the factors affecting NT-proBNP levels in different populations.
The use of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. However, ...whether there is a difference between the two agents in the extent of improving such outcomes has not been clarified thus far. Therefore, we aimed to compare TDF and ETV on the risk of HCC and mortality.
A total of 7015 consecutive patients with CHB who were treated with TDF or ETV between February 2007 and January 2018 at the liver units of the Catholic University of Korea were screened for study eligibility and 3022 patients were finally analysed. Study end points were HCC and all-cause mortality or liver transplantation (LT) within 5 years after the initiation of antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting methods were used.
No difference was observed between TDF and ETV in the incidence rates of HCC in the entire cohort (HR 1.030; 95% CI 0.703 to 1.509, PSM model, p=0.880) and subgroups of patients with chronic hepatitis and cirrhosis. Also, no difference was observed between TDF and ETV in the incidence rates of all-cause mortality or LT in the entire cohort (HR 1.090; 95% CI 0.622 to 1.911, PSM model, p=0.763), and patients with chronic hepatitis and cirrhosis.
This study has demonstrated the clinical outcomes in patients with CHB who received TDF or ETV treatment. There was no difference in the intermediate-term risk of HCC and mortality or LT between the two drugs.
4-O-methylascochlorin (MAC) is a 4-fourth carbon-substituted derivative of ascochlorin, a compound extracted from a phytopathogenic fungus
. MAC induces apoptosis and autophagy in various cancer ...cells, but the effects of MAC on apoptosis and autophagy in cervical cancer cells, as well as how the interaction between apoptosis and autophagy mediates the cellular anticancer effects are not known. Here, we investigated that MAC induced apoptotic cell death of cervical cancer cells without regulating the cell cycle and promoted autophagy by inhibiting the phosphorylation of serine-threonine kinase B (Akt), mammalian target of rapamycin (mTOR), and 70-kDa ribosomal protein S6 kinase (p70S6K). Additional investigations suggested that Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP-3), but not Hypoxia-inducible factor 1 alpha (HIF-1α), is a key regulator of MAC-induced apoptosis and autophagy. BNIP-3 siRNA suppressed MAC-induced increases in cleaved- poly (ADP-ribose) polymerase (PARP) and LC3II expression. The pan-caspase inhibitor Z-VAD-FMK suppressed MAC-induced cell death and enhanced MAC-induced autophagy. The autophagy inhibitor chloroquine (CQ) enhanced MAC-mediated cell death by increasing BNIP-3 expression. These results indicate that MAC induces apoptosis to promote cell death and stimulates autophagy to promote cell survival by increasing BNIP-3 expression. This study also showed that co-treatment of cells with MAC and CQ further enhanced the death of cervical cancer cells.
PDF
