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To enhance the therapeutic effects of exogenous administration of growth factors (GFs) in the treatment of chronic wounds, we constructed GF combinations of highly skin-permeable ...epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and platelet-derived growth factor-A (PDGF-A). We genetically conjugated a low-molecular-weight protamine (LMWP) to the N-termini of these GFs to form LMWP-EGF, LMWP-IGF-I, and LMWP-PDGF-A. Subsequently, these molecules were complexed with hyaluronic acid (HA). Combinations of native or LMWP-fused GFs significantly promoted fibroblast proliferation and the synthesis of procollagen, with a magnification of these results observed after the GFs were complexed with HA. The optimal proportions of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and HA were 1, 1, 0.02, and 200, respectively. After confirming the presence of a synergistic effect, we incorporated the LMWP-fused GFs-HA complex into cationic elastic liposomes (ELs) of 107±0.757nm in diameter and a zeta potential of 56.5±1.13mV. The LMWP-fused GFs had significantly improved skin permeation compared with native GFs. The in vitro wound recovery rate of the LMWP-fused GFs-HA complex was 23% higher than that of cationic ELs composed of LMWP-fused GFs alone. Moreover, the cationic ELs containing the LMWP-fused GFs-HA complex significantly accelerated the wound closure rate in a diabetic mouse model and the wound size was maximally decreased by 65% and 58% compared to cationic ELs loaded with vehicle or native GFs-HA complex, respectively. Thus, topical treatment with cationic ELs loaded with the LMWP-fused GFs-HA complex synergistically enhanced the healing of chronic wounds, exerting both rapid and prolonged effects.
We believe that our study makes a significant contribution to the literature, because it demonstrated the potential application of cationic elastic liposomes as topical delivery systems for growth factors (GFs) that have certain limitations in their therapeutic effects (e.g., low percutaneous absorption of GFs at the lesion site and the requirement for various GFs at different healing stages). Topical treatment with cationic elastic liposomes loaded with highly skin-permeable low-molecular-weight protamine (LMWP)-fused GFs-hyaluronic acid (HA) complex synergistically enhanced the healing of diabetic wounds, exerting both rapid and prolonged effects.
Abstract There is limited data comparing effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in patients with ...non-ST-elevation acute coronary syndromes (NSTE-ACS). We compared the long-term outcomes of the two revascularization strategies in 1,246 patients presented with NSTE-ACS for left main or multivessel coronary artery disease (CAD). Data were pooled from the BEST, PRECOMBAT, and SYNTAX trials. The primary outcome was a composite of death from any causes, myocardial infarction, or stroke. The baseline characteristics were similar between the two study groups. During the median follow-up of 60 months, the rate of the primary outcome was significantly lower with CABG than with PCI (hazard ratio HR: 0.74; 95% confidence interval CI: 0.56−0.98; P=0.036). This difference was mainly attributed to a significant reduction in the rate of myocardial infarction (HR: 0.50; 95% CI: 0.31−0.82, P=0.006). The superiority of CABG over PCI was consistent across the major subgroups. The individual risks of death from any causes or stroke were not different between the two groups. In contrast, the rate of repeat revascularization was significantly lower in the CABG group than in the PCI group (HR: 0.56; 95% CI: 0.41−0.75, P < 0.001). In this study, among patients with NSTE-ACS for left main or multivessel CAD, CABG significantly reduces the risk of death from any causes, myocardial infarction, or stroke compared to PCI with DES.
Left main coronary artery (LMCA) disease is the highest-risk lesion subset of ischemic heart disease, and has traditionally been an indication for coronary artery bypass grafting (CABG). Recent ...evidence suggests comparable clinical outcomes between percutaneous coronary intervention (PCI) and CABG for LMCA disease, with similar rates of mortality and serious composite outcomes, a higher rate of stroke with CABG, and a higher rate of repeat revascularization with PCI. These results have been translated to the current guideline recommendation that PCI is a reasonable alternative to CABG in patients with low to intermediate anatomic complexity. However, how the characteristics, treatment, and clinical outcomes of patients with unprotected LMCA disease have evolved over time has not yet been fully evaluated. We therefore described secular trends in the characteristics and long-term outcomes of unprotected LMCA disease using "real-world" clinical experience from the IRIS-MAIN (Interventional Research Incorporation Society-Left MAIN Revascularization) registry together with a broad review of this topic.
The diamond–graphite hybrid thin film with low‐dimensional nanostructure (e.g., nitrogen‐included ultrananocrystalline diamond (N‐UNCD) or the alike), has been employed in many impactful breakthrough ...applications. However, the detailed picture behind the bottom–up evolution of such intriguing carbon nanostructure is far from clarified yet. Here, the authors clarify it, through the concerted efforts of microscopic, physical, and electrochemical analyses for a series of samples synthesized by hot‐filament chemical vapor deposition using methane–hydrogen precursor gas, based on the hydrogen‐dependent surface reconstruction of nanodiamond and on the substrate‐temperature‐dependent variation of the growth species (atomic hydrogen and methyl radical) concentration near substrate. The clarified picture provides insights for a drastic enhancement in the electrochemical activities of the hybrid thin film, concerning the detection of important biomolecule, that is, ascorbic acid, uric acid, and dopamine: their limits of detections are 490, 35, and 25 nm, respectively, which are among the best of the all‐carbon thin film electrodes in the literature. This work also enables a simple and effective way of strongly enhancing AA detection.
The authors clarify the nucleation/growth mechanism of diamond–graphite hybrid thin film with 2D nanostructure (the only successful diamond probe material for neural recording/stimulation), based on nanodiamond surface reconstruction controlled by growth species variation in growth environment. It provides insights for the drastic enhancement of the structure‐optimized thin film performance in simultaneous electrochemical detection of dopamine, ascorbic acid, and uric acid.
The adoption of contactless patient monitoring has surged in response to the COVID-19 pandemic. After implementing remote electrocardiogram monitors, systematic management techniques are necessary to ...analyze extensive data and identify measurement errors. During the electrocardiogram measurement process, motion artifacts that may occur are often challenging to distinguish from the electrocardiogram itself because they share similar characteristics in terms of amplitude and frequency. To address these challenges, six deep neural networks capable of recognizing the features of normal electrocardiograms were developed. An algorithm that determines parameters representing the characteristics of electrocardiograms and identifies abnormal waveforms was created by combining the results of six deep neural networks. Waveforms from 10 patients were analyzed, and the differences between leads and individuals were quantified. Additionally, a recognition score was introduced to distinguish highly reliable electrocardiogram parameters while filtering out unreliable values caused by motion artifacts and measurement errors.
Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian ...populations remain uncertain.
In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months.
At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% 45/400 vs 5.3% 21/400; hazard ratio HR, 2.26; 95% confidence interval CI, 1.34 to 3.79;
=0.002). The incidences of major bleeding (7.5% 29/400 vs 4.1% 16/400,
=0.04) and fatal bleeding (1% 4/400 vs 0%,
=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% 36/400 vs 5.8% 23/400; HR, 1.62; 95% CI, 0.96 to 2.74;
=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups.
In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.
We present a silicon nitride (Si x N y ) arrayed waveguide grating (AWG). Crosstalk in this AWG was reduced by decreasing the phase error in a multimode arrayed waveguide (WG) at center wavelength of ...838 nm. 8-channel Si x N y AWGs using arrayed WGs with double-etched inverse-tapered WG structure and cross-sectional area of 1.5 × 1.5 μm 2 were fabricated. The AWG exhibited less than -29.6-dB crosstalk with 0.43-dB insertion loss for transverse electric (TE) polarization.
Introduction
Distal left main (LM) bifurcation disease is one of the most challenging lesion subsets for percutaneous coronary intervention (PCI) and optimal stenting strategy for such complex ...lesions is still debated. This study aimed to compare clinical outcomes following single versus dual stenting for true distal LM bifurcation lesions.
Methods
Patients with true distal LM bifurcation lesions (type 1,1,1 or 0,1,1: both left anterior descending and circumflex artery >2.5 mm diameter) receiving PCI with drug‐eluting stents (DES) from two large clinical registries were evaluated. The primary outcome was target‐lesion failure (TLF), defined as a composite of cardiac death, target‐vessel myocardial infarction (MI), or target‐lesion revascularization (TLR). Outcomes were compared with the use of propensity scores and inverse probability‐weighting adjustment to reduce treatment selection bias.
Results
Among 1,002 patients undergoing true distal LM PCI, 440 (43.9%) and 562 (56.1%) were treated with single and dual stents, respectively. The TLF rates at 3 year was 20.3% in the single‐stent group and 24.1% in the dual‐stenting group (log‐rank p = 0.18). The adjusted risk for TLF did not differ significantly between two groups (hazard ratio HR with dual‐stent vs. single‐stent: 1.27, 95% confidence interval CI: 0.95–1.71). The adjusted risks for death, MI, repeat revascularization, or stent thrombosis were also similar between the single‐ and dual‐stenting groups.
Conclusions
In patients undergoing PCI for true distal LM disease, single‐ and dual‐stent strategies showed a similar adjusted risk of TLF at 3 years. Our findings should be confirmed or refuted through large, randomized clinical trials.
The fourth vaccination dose confers additional protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in individuals with no prior coronavirus disease‐19 ...(COVID‐19). However, its immunological benefit against currently circulating BA.4/5 is unclear in individuals who have received a booster shot and been infected with Omicron variant BA.1/2. We analyzed immune responses in whom had been boosted once and did not have COVID‐19 (n = 16), boosted once and had COVID‐19 when BA.1/2 was dominant in Korea (Hybrid‐6M group, n = 27), and boosted twice and did not have COVID‐19 (Vx4 group, n = 15). Antibody binding activities against RBDo BA.1 and RBDo BA.4/5, antigen‐specific memory CD4+ and CD8+ T‐cell responses against BA.4/5, and B‐cell responses against SARS‐CoV‐2 wild‐type did not differ statistically between the Hybrid‐6M and Vx4 groups. The humoral and cellular immune responses of the Hybrid‐6M group against BA.4/5 were comparable to those of the Vx4 group. Individuals who had been boosted and had an Omicron infection in early 2022 may not have high priority for an additional vaccination.
In a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary ...artery stenosis at 1 year.
This study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis.
We randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis.
At 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio HR: 1.27; 95% confidence interval CI: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012).
During 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease PRECOMBAT; NCT00422968).
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