IMPORTANCE: Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical ...usefulness of IVUS are limited for lesions treated with drug-eluting stents. OBJECTIVE: To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. DESIGN, SETTING, AND PARTICIPANTS: The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. INTERVENTIONS: Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. RESULTS: One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, −2.97% 95% CI, −5.14% to −0.79%) (hazard ratio HR, 0.48 95% CI, 0.28 to 0.83, P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 2.5%) compared with angiography-guided (33 5.0%) stent implantation (HR, 0.51 95% CI, 0.28 to 0.91, P = .02). Cardiac death and target lesion–related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 95% CI, 0.14 to 2.52, P = .48). Target lesion–related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group (P = .32). CONCLUSIONS AND RELEVANCE: Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308281
We compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus ...semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging-quantitative computed tomography (AI-QCT) for patients being referred for nonemergent invasive coronary angiography (ICA).
CCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud-based software (Cleerly, Inc.) that performs AI-QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI-QCT guided findings were related to MACE at 1-year follow-up.
Seven hundred forty-seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI-QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI-QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI-QCT-identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI-QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively.
In stable patients referred for ACC/AHA guideline-indicated nonemergent ICA, application of artificial intelligence and machine learning for AI-QCT can significantly reduce ICA rates and costs with no change in 1-year MACE.
We previously reported the inhibitory effect of chrysin, a natural flavonoid plentifully contained in propolis, vegetables and fruits, on the mast cell-mediated allergic reaction. In this study, we ...evaluated the effect of chrysin on atopic dermatitis (AD) and defined underlying mechanisms of action. We used an AD model in BALB/c mice by the repeated local exposure of 2,4-dinitrochlorobenzene (DNCB) and house dust mite (Dermatophagoides farinae extract, DFE) to the ears. Repeated alternative treatment of DNCB/DFE caused AD-like skin lesions. Oral administration of chrysin diminished AD symptoms such as ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. Chrysin decreased infiltration of mast cells, and reduced serum histamine level. Chrysin also suppressed AD by inhibiting the inflammatory responses of Th1, Th2, and Th17 cells in mouse lymph node and ear. Interestingly, chrysin significantly inhibited the production of cytokines, Th2 chemokines, CCL17 and CCL22 by the down-regulation of p38 MAPK, NF-κB, and STAT1 in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT). Chrysin also inhibited TNF-α/IFN-γ-stimulated IL-33 expression in HaCaT cells and mouse primary keratinocytes. Taken together, the results indicate that chrysin suppressed AD symptoms, suggesting that chrysin might be a candidate for the treatment of AD and skin allergic diseases.
•Chrysin suppresses AD symptoms by inhibiting T helper cell immune reaction.•Chrysin downregulates CCL17 and CCL22 expression via p38 MAPK, STAT1, and NF-κB in human keratinocytes.•Chrysin and tacrolimus have overlapping effects in inhibiting AD immune responses.•Chrysin might be a candidate for the treatment of skin allergic diseases.
Carbohydrates consist of a large proportion of calories in the Asian diet. Therefore, we aimed to investigate the association between carbohydrate intake and metabolic syndrome in Korean women. A ...cross-sectional analysis was conducted with a total of 4294 Korean women aged 40–69 years from the Korean Genomic and Epidemiology Study (KoGES). Carbohydrate intake was calculated based on a validated food frequency questionnaire. Metabolic syndrome was defined by using the National Cholesterol Education Program, Adult Treatment Panel III (NCEPIII). Logistic regression was used to estimate the association of carbohydrate intake with metabolic syndrome and its components. In this study, high carbohydrate intake seemed to be associated with low socioeconomic status and an imbalanced diet. After adjusting for confounding factors, subjects with higher carbohydrate intake showed an increased risk of metabolic syndrome (odds ratio (OR) 1.34, 95% confidence interval (CI) 1.08–1.66, p-trend = 0.004, highest vs. lowest quartile ≥75.2 vs. <67.0% of energy), particularly elevated waist circumference. This association was stronger among those with low levels of C-reactive protein (CRP) and those with low dairy intake. In conclusion, higher carbohydrate intake is associated with a higher risk of metabolic syndrome, particularly abdominal obesity, in Korean women. This association may differ according to individuals’ CRP level and dairy intake.
This study compared the safety and diagnostic yield of a selective referral strategy using coronary computed tomographic angiography (CCTA) compared with a direct referral strategy using invasive ...coronary angiography (ICA) as the index procedure.
Among patients presenting with signs and symptoms suggestive of coronary artery disease (CAD), a sizeable proportion who are referred to ICA do not have a significant, obstructive stenosis.
In a multinational, randomized clinical trial of patients referred to ICA for nonemergent indications, a selective referral strategy was compared with a direct referral strategy. The primary endpoint was noninferiority with a multiplicative margin of 1.33 of composite major adverse cardiovascular events (blindly adjudicated death, myocardial infarction, unstable angina, stroke, urgent and/or emergent coronary revascularization or cardiac hospitalization) at a median follow-up of 1-year.
At 22 sites, 823 subjects were randomized to a selective referral and 808 to a direct referral strategy. At 1 year, selective referral met the noninferiority margin of 1.33 (p = 0.026) with a similar event rate between the randomized arms of the trial (4.6% vs. 4.6%; hazard ratio: 0.99; 95% confidence interval: 0.66 to 1.47). Following CCTA, only 23% of the selective referral arm went on to ICA, which was a rate lower than that of the direct referral strategy. Coronary revascularization occurred less often in the selective referral group compared with the direct referral to ICA (13% vs. 18%; p < 0.001). Rates of normal ICA were 24.6% in the selective referral arm compared with 61.1% in the direct referral arm of the trial (p < 0.001).
In stable patients with suspected CAD who are eligible for ICA, the comparable 1-year major adverse cardiovascular events rates following a selective referral and direct referral strategy suggests that both diagnostic approaches are similarly effective. In the selective referral strategy, the reduced use of ICA was associated with a greater diagnostic yield, which supported the usefulness of CCTA as an efficient and accurate method to guide decisions of ICA performance. (Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization CONSERVE; NCT01810198).
Incorporating bioactive molecules into synthetic ceramic scaffolds is challenging. In this study, to enhance bone regeneration, a magnesium phosphate (MgP) ceramic scaffold was incorporated with a ...novel indene compound, KR-34893. KR-34893 induced the deposition of minerals and expression of osteoblast marker genes in primary human bone marrow mesenchymal stem cells (BMSCs) and a mouse osteoblastic MC3T3-E1 cell line. Analysis of the mode of action showed that KR-34893 induced the phosphorylation of MAPK/extracellular signal-regulated kinase and extracellular signal-regulated kinase, and subsequently the expression of bone morphogenetic protein 7, accompanied by SMAD1/5/8 phosphorylation. Accordingly, KR-34893 was incorporated into an MgP scaffold prepared by 3D printing at room temperature, followed by cement reaction. KR-34893-incorporated MgP (KR-MgP) induced the expression of osteoblast differentiation marker genes in vitro. In a rat calvaria defect model, KR-MgP scaffolds enhanced bone regeneration and increased bone volume compared with MgP scaffolds, as assessed by micro-computed tomography and histological analyses. In conclusion, we developed a method for producing osteoinductive MgP scaffolds incorporating a bioactive organic compound, without high temperature sintering. The KR-MgP scaffolds enhanced osteoblast activation in vitro and bone regeneration in vivo.
Psoriasis is a chronic inflammatory skin disease accompanied by excessive keratinocyte proliferation. Corticosteroids, vitamin D3 analogs, and calcineurin inhibitors, which are used to treat ...psoriasis, have diverse adverse effects, whereas natural products are popular due to their high efficiency and relatively low toxicity. The roots of the Cudrania tricuspidata (C. tricuspidata) are known to have diverse pharmacological effects, among which the anti-inflammatory effect is reported as a potential therapeutic agent in skin cells. Nevertheless, its effectiveness against skin diseases, especially psoriasis, is not fully elucidated. Here, we investigated the effect of cudraxanthone D (CD), extracted from the roots the C. tricuspidata Bureau, on psoriasis using an imiquimod (IMQ)-induced mouse model and the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-activated keratinocytes. IMQ was topically applied to the back skin of C57BL/6 mice for seven consecutive days, and the mice were orally administered with CD. This resulted in reduced psoriatic characteristics, such as the skin thickness and Psoriasis Area Severity Index score, and the infiltration of neutrophils in IMQ-induced skin. CD inhibited the serum levels of TNF-α, immunoglobulin G2a, and myeloperoxidase, and the expression of Th1/Th17 cells in splenocytes. In TNF-α/IFN-γ-activated keratinocytes, CD reduced the expressions of CCL17, IL-1β, IL-6, and IL-8 by inhibiting the phosphorylation of STAT1 and the nuclear translocation of NF-kB. Taken together, these results suggest that CD could be a potential drug candidate for the treatment of psoriasis.
Receptor-interacting protein kinase (RIP) family 1 signaling has complex effects on inflammatory processes and cell death, but little is known concerning allergic skin diseases. We examined the role ...of RIP1 in
extract (DFE)-induced atopic dermatitis (AD)-like skin inflammation. RIP1 phosphorylation was increased in HKCs treated with DFE. Nectostatin-1, a selective and potent allosteric inhibitor of RIP1, inhibited AD-like skin inflammation and the expression of histamine, total IgE, DFE-specific IgE, IL-4, IL-5, and IL-13 in an AD-like mouse model. The expression of RIP1 was increased in ear skin tissue from a DFE-induced mouse model with AD-like skin lesions and in the lesional skin of AD patients with high house dust mite sensitization. The expression of IL-33 was down-regulated after RIP1 inhibition, and the levels of IL-33 were increased by over-expression of RIP1 in keratinocytes stimulated with DFE. Nectostatin-1 reduced IL-33 expression in vitro and in the DFE-induced mouse model. These results suggest that RIP1 can be one of the mediators that regulate IL-33-mediated atopic skin inflammation by house dust mites.
Discontinuing aspirin after short-term dual antiplatelet therapy (DAPT) was evaluated as a bleeding reduction strategy. However, the strategy of ticagrelor monotherapy has not been exclusively ...evaluated in patients with acute coronary syndromes (ACS).
To determine whether switching to ticagrelor monotherapy after 3 months of DAPT reduces net adverse clinical events compared with ticagrelor-based 12-month DAPT in patients with ACS treated with drug-eluting stents.
A randomized multicenter trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea. Follow-up was completed in October 2019.
Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529).
The primary outcome was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization). Prespecified secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events.
Among 3056 patients who were randomized (mean age, 61 years; 628 women 20%; 36% ST-elevation myocardial infarction), 2978 patients (97.4%) completed the trial. The primary outcome occurred in 59 patients (3.9%) receiving ticagrelor monotherapy after 3-month DAPT and in 89 patients (5.9%) receiving ticagrelor-based 12-month DAPT (absolute difference, -1.98% 95% CI, -3.50% to -0.45%; hazard ratio HR, 0.66 95% CI, 0.48 to 0.92; P = .01). Of 10 prespecified secondary outcomes, 8 showed no significant difference. Major bleeding occurred in 1.7% of patients with ticagrelor monotherapy after 3-month DAPT and in 3.0% of patients with ticagrelor-based 12-month DAPT (HR, 0.56 95% CI, 0.34 to 0.91; P = .02). The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the ticagrelor monotherapy after 3-month DAPT group (2.3%) vs the ticagrelor-based 12-month DAPT group (3.4%) (HR, 0.69 95% CI, 0.45 to 1.06; P = .09).
Among patients with acute coronary syndromes treated with drug-eluting stents, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year. The study population and lower than expected event rates should be considered in interpreting the trial.
ClinicalTrials.gov Identifier: NCT02494895.
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