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BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.
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Angioplastia com Balão , Artéria Femoral , Doença Arterial Periférica , Artéria Poplítea , Ultrassonografia de Intervenção , Grau de Desobstrução Vascular , Humanos , Ultrassonografia de Intervenção/métodos , Masculino , Angioplastia com Balão/métodos , Artéria Femoral/diagnóstico por imagem , Feminino , Artéria Poplítea/diagnóstico por imagem , Doença Arterial Periférica/terapia , Doença Arterial Periférica/diagnóstico por imagem , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Materiais Revestidos Biocompatíveis , Resultado do Tratamento , AngiografiaRESUMO
BACKGROUND AND OBJECTIVES: The K-ELUVIA study aimed to investigate the clinical effectiveness and safety of Eluvia™, a polymer-coated, paclitaxel-eluting stent, for femoropopliteal artery disease using data from a prospective Korean multicenter registry. METHODS: A total of 105 patients with femoropopliteal artery disease who received endovascular treatment (EVT) with Eluvia™ stents at 7 Korean sites were enrolled in a prospective cohort and followed for 2 years. The primary endpoint was the 2-year clinical patency. The secondary endpoint was 2-year freedom from clinically driven target lesion revascularization (TLR). RESULTS: Mean patient age was 68.2±10.4 years, and most patients (82.7%) were male. Mean lesion length was 168.3±117.6 mm. Chronic total occlusion was found in 57.7% of patients. Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) type C or D lesions were present in 46.1% of patients. Procedural success was achieved in 99.0% of patients. The clinical patency rate was 84.4% at 1 year after EVT and 76.3% at 2 years post-EVT. The freedom from TLR rate was 89.1% at 1 year after EVT and 79.1% at 2 years post-EVT. Chronic total occlusion (hazard ratio [HR], 3.53; 95% confidence interval [CI], 1.08-11.67; p=0.039) and smaller mean stent diameter (HR, 0.40; 95% CI, 0.16-0.98; p=0.044) were identified as independent predictors of loss of clinical patency at 2 years. CONCLUSIONS: The K-ELUVIA study demonstrated favorable 2-year clinical effectiveness and safety outcomes of Eluvia stent for femoropopliteal artery lesions in real-world practice.
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Background: Atherosclerotic cardiovascular disease (ASCVD) is a major health concern, and lipoprotein(a) (Lp(a)) is an independent risk factor. However, there is limited evidence regarding Lp(a) and the risk of ASCVD in Asian populations. This study aimed to assess the predictive value of changes in coronary artery calcification (CAC) for ASCVD risk associated with Lp(a) level. Methods: Participants (n=2,750) were grouped according to their Lp(a) levels, and the association between Lp(a) and CAC progression was examined. CAC progression was defined as the occurrence of incident CAC or a difference ≥2.5 between the square root (â) of baseline and follow-up coronary artery calcium scores (CACSs) (Δâtransformed CACS). To adjust for differences in follow-up periods, Δâtransformed CACS was divided by the follow- up period (in years). Results: Over an average follow-up of 3.07 years, 18.98% of participants experienced CAC progression. Those with disease progression had notably higher Lp(a) levels. Higher Lp(a) tertiles correlated with increased baseline and follow-up CACS, CAC progression (%), and Δâtransformed CACS. Even after adjustment, higher Lp(a) levels were associated with CAC progression. However, annualized Δâtransformed CACS analysis yielded no significant results. Conclusion: This study demonstrated an association between elevated Lp(a) levels and CAC progression in a general population without ASCVD. However, longer-term follow-up studies are needed to obtain meaningful results regarding CAC progression. Further research is necessary to utilize Lp(a) level as a predictor of cardiovascular disease and to establish clinically relevant thresholds specific to the Korean population.
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BACKGROUND: Functional assessment using fractional flow reserve (FFR) and anatomical assessment using optical coherence tomography (OCT) are used in clinical practice for patients with intermediate coronary stenosis. Moreover, coronary computed tomography angiography (CTA) is a common noninvasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. This study aimed to investigate the association between FFR and plaque characteristics assessed using coronary CTA and OCT for intermediate coronary stenosis. METHODS: Based on a prospective multicenter registry, 159 patients having 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography, and both FFR measurements and OCT examinations were performed during angiography. A stenotic lesion identified with FFR ≤0.80 was deemed diagnostic of an ischemia-causing lesion. The predictive value of plaque characteristics assessed using coronary CTA and OCT for identifying lesions causing ischemia was analyzed. RESULTS: Stenosis severity and plaque characteristics on coronary CTA and OCT differed between lesions that caused ischemia and those that did not. In multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]=2.78; P=0.038), thrombus (OR=5.13; P=0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors of ischemic lesions. Increasing the number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. CONCLUSIONS: Comprehensive anatomical evaluation of coronary stenosis may provide additional supportive information for predicting the lesions causing ischemia.
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Angiografia Coronária , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Placa Aterosclerótica , Valor Preditivo dos Testes , Sistema de Registros , Tomografia de Coerência Óptica , Humanos , Masculino , Feminino , Placa Aterosclerótica/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Angiografia Coronária/métodos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Estenose Coronária/diagnóstico , Angiografia por Tomografia Computadorizada/métodos , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/diagnóstico , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnósticoRESUMO
The long-term outcome of first-line moderate-intensity statin with ezetimibe combination therapy for secondary prevention after percutaneous coronary intervention in patients with acute coronary syndrome (ACS) compared to high-intensity statin monotherapy remains elusive. The objective of this study was to compare the effectiveness of moderate-intensity statin and ezetimibe combination therapy with high-intensity statin monotherapy. We conducted a nationwide, population-based, retrospective, cohort study of patients with ACS from 2013 to 2019. The patients using combination therapy were matched (1:1) to those using monotherapy. The primary outcome was a composite of myocardial infarction, stroke and all-cause mortality. We estimated the hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards regression. After propensity score matching, 10,723 pairs were selected. Men accounted for 70% of the patients and 37% aged > 70 years. The primary endpoint occurred in 1297 patients (12.1%) in the combination group and in 1426 patients (13.3%) in the monotherapy group, and decreased risk (HR 0.85, 95% CI 0.78-0.92, P < 0.001) in the combination group. Among the patients with ACS, moderate-intensity statin with ezetimibe combination therapy was associated with decreased risk of adverse cardiovascular outcomes compared with high-intensity statin monotherapy in a nationwide population-based study representing routine clinical practice.
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Síndrome Coronariana Aguda , Inibidores de Hidroximetilglutaril-CoA Redutases , Masculino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Estudos de Coortes , Estudos Retrospectivos , Ezetimiba/uso terapêuticoRESUMO
BACKGROUND: Homeostasis model assessment for insulin resistance (HOMA-IR) is a biomarker for type 2 diabetes mellitus (T2DM). However, the role of HOMA-IR in the non-diabetic is unclear. This study aimed to determine whether IR measured HOMA-IR value is associated with new onset diabetes as well as vascular disease and can be used as an early predictor for diabetes and vascular diseases in non-diabetic participants. METHODS: From a prospective community-based cohort of 10,030 individuals, 4314 individuals younger than 65 years and without diabetes were enrolled and divided into three groups by baseline HOMA-IR tertiles: low (n = 1454), moderate (n = 1414), and high (n = 1446). The primary outcome was new onset T2DM. Secondary outcomes were chronic kidney disease (CKD) and a composite of coronary artery disease, myocardial infarction, and stroke as macrovascular events. RESULTS: The mean age was 51 years. The prevalence of hypertension and cholesterol and HbA1c were higher in the high HOMA-IR group. New onset T2DM (5.8%) and CKD (12.2%) incidence in the high HOMA-IR group was higher than that in the others. The prevalence of macrovascular events did not differ among groups. High-HOMA-IR was an independent risk factor for new onset T2DM (odds ratio 1.86 [1.17-2.96]; p = 0.01) and CKD (1.49 [1.12-1.98]; p = 0.01). CONCLUSIONS: High HOMA-IR was an early predictor of new onset T2DM and CKD, regardless of HbA1c in non-diabetic individuals. Further research on the specific cut off value will be needed.
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BACKGROUND: Delayed heart rate (HR) and blood pressure recovery after exercise test is known as the reliable indexes of autonomic dysfunction. Here we tried to evaluate the serial changes in various indicators during exercise test and correlations with recovery of HR and blood pressure in a normotensive healthy middle-aged group. METHODS: A total of 122 patients without hypertension or diabetes was enrolled (mean age, 55.6 ± 11.0; male, 56.6%; mean blood pressure, 124.8 ± 16.6 / 81.5 ± 9.6 mmHg). Treadmill test was performed for evaluation of chest pain. Patients with coronary artery disease, positive treadmill test result, left ventricular dysfunction or renal failure were excluded. Heart rate recovery was calculated by subtracting the HR in the first or second minute of recovery period from the HR of peak exercise (HRR1 or HRR2). Systolic blood pressure in the 4th minute of recovery stage (SBPR4) was used to show delayed blood pressure recovery. RESULTS: Metabolic equivalents (METs) and HR in stage 2 to 4 were significantly correlated with both HRR1 and HRR2. Multiple regression analysis of HRR revealed significant correlation of METs and SBPR4. SBPR4 was significantly correlated with both HRR1 and HRR2 (HRR1, r = -0.376, p<0.001; HRR2, r = -0.244, p = 0.008) as well as SBP in the baseline to stage 3 and pulse pressure (r = 0.406, p<0.001). CONCLUSIONS: Delayed BP recovery after peak exercise test revealed significant association with autonomic dysfunction and increased pulse pressure in normotensive middle-aged healthy group. It can be a simple and useful marker of autonomic dysfunction and arterial stiffness.
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Hipertensão , Disautonomias Primárias , Pessoa de Meia-Idade , Humanos , Masculino , Adulto , Idoso , Teste de Esforço , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologiaRESUMO
AIMS: The prevalence and incidence rate of heart failure (HF) continues to increase along with the aging of the population and the increase of ischaemic heart disease. The morbidity and mortality of HF are also on the rise in the industrialized countries; it can be a great public health problem. A detailed and accurate analysis of the demographical incidence and prevalence of HF is an important first step in predicting the occurrence of the disease in the future and proper preparing for prevention. Here, we aimed to analyse the annual prevalence and incidence of HF by gender and age using long-term national health insurance service data in the Republic of Korea. METHODS AND RESULTS: A total of 47 243 patients newly diagnosed with HF between 2006 and 2015 among nationally representative random subjects of 1 000 000 were included. The data of age and gender were analysed by year, and the total population information of the Ministry of Land, Infrastructure, and Transport of Korea was referred to compare the data of HF patients with the total population (2008-15). Over the decade from 2006 to 2015, the prevalence of HF patients showed tendency of increase (P < 0.001). The overall incidence rate was also gradually increasing (P < 0.001), but in women, it tended to decrease gradually. Women significantly accounted higher than the male group in incidence of HF over the period (54.6% vs. 45.4%, P < 0.001). The mean age at the time of diagnosis gradually increased (P = 0.002 for total, P = 0.001 for each gender). Total incidence was highest in 70s (27.22%), but males were the most in their 60s and females were in their 70s. Analysis of annual trend by age and gender distribution of HF incidence in men presented highest in the 50s-70s with a similar pattern annually, and the incidence is increasing more recently. Different from that of men, in the case of women, the incidence gradually increased with age in a similar annual pattern, peaking in their 70s and gradually decreasing in recent years. CONCLUSIONS: The prevalence and incidence of HF are gradually increasing. It increased rapidly in their 50s and older. It showed an increased incidence of HF especially in men between their 50s and 70s, and more observation and caution for the management of the risk factors may be needed to prevent HF in the male group.
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Insuficiência Cardíaca , Humanos , Masculino , Feminino , Criança , Idoso , Morbidade , Incidência , Prevalência , República da Coreia/epidemiologia , Insuficiência Cardíaca/diagnósticoRESUMO
Background: Popliteal artery entrapment syndrome (PAES) is an underreported and underdiagnosed condition that affects the lower extremities. Previous case reports mainly presented young and uncomplicated PAES. Here, we report the cases of complicated PAES in middle-aged patients. Furthermore, we discuss the importance of a multidisciplinary team approach from diagnosis to treatment to obtain favourable clinical outcomes against this rare disease. Case summary: Two middle-aged patients presented with recent claudication and were diagnosed with popliteal artery obstruction due to a complicated PAES. At the multidisciplinary meeting, the decided treatment plan was to prioritize the gastrocnemius tendon accessory transfer and surgical thromboendarterectomy. In case the popliteal artery patency was unsatisfactory, an additional on-site percutaneous intervention was planned. Follow-up lower extremity computed tomographic angiography showed a patent popliteal artery without any claudication in both two cases. Discussion: Popliteal artery entrapment syndrome is a rare vascular disorder. Clinical suspicion and advanced imaging modalities can lead to an accurate diagnosis. A multidisciplinary team approach helps in obtaining favourable clinical results using minimally invasive hybrid surgical and interventional treatments.
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Purpose: This study aimed to assess the effectiveness and safety of a fixed-dose combination of rosuvastatin and valsartan (Rovatitan®) in Korean patients with concomitant hypertension and hyperlipidemia. Patients and Methods: A total of 1008 eligible patients with concomitant hypertension and hyperlipidemia were enrolled and treated for 12 weeks. Both upward and downward drug dose titrations were allowed based on the investigator's discretion. This study evaluated the effectiveness of the study drug, defined by the percentage of patients achieving the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) treatment targets. Additionally, regression analyses were conducted to evaluate the factors associated with the effectiveness and safety of the study drug. Of the 1008 patients enrolled in the study, 911 were analyzed for clinical effectiveness. Results: At 12 weeks, 84.6% and 75.9% of patients treated with the study drug achieved their BP and LDL-C targets, respectively, and 64.8% of patients achieved both targets simultaneously. Furthermore, the percentage of patients who achieved their BP and LDL-C treatment targets demonstrated a trend across the respective risk groups; the higher the risk group, the lower the success of attaining the respective target. This trend was also observed regardless of the prior antihypertensive and/or lipid-lowering treatments. According to regression analysis, poor metabolic profiles, including a higher body mass index (BMI) and higher BP and LDL-C levels at baseline, were significantly associated with treatment failure for BP. Among the 1005 patients included in the safety analysis, 17 patients (1.7%) experienced serious adverse events; however, none were considered related to the study drug. Conclusion: The study drug used for the treatment of concomitant hypertension and hyperlipidemia in a real-world setting was effective and was well tolerated. Therefore, the study drug is suggested as a good alternative to increase patient convenience and compliance, particularly in those taking multiple medications.
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Hiperlipidemias , Hipertensão , Humanos , Rosuvastatina Cálcica/efeitos adversos , Valsartana/uso terapêutico , LDL-Colesterol , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/induzido quimicamente , Resultado do TratamentoRESUMO
Contrast sensitivity (CS) is closely associated with vision-related quality of life in glaucoma patients. This cross-sectional study was performed to determine the relationship between CS and visual field (VF) sensitivity (VFS) according to the hemifield location of VF defects in 238 patients with primary open-angle glaucoma (POAG) who underwent 24-2 standard automated perimetry and CS measurement on the same day. Of the 238 eyes, 83, 58, and 47 eyes had VF defects in the superior, inferior and both hemifields, respectively, and 50 had no VF defects in either hemifield. Significant correlations between CS and VFS in all sectors were observed in the entire cohort (R2 = 0.103-0.315, all P < 0.001). However, CS poorly represented VF defects in eyes with single superior (R2 = 0.037-0.086) or inferior (R2 = 0.107-0.222) hemifield defects. Eyes with bi-hemifield VF defects showed significant correlations between VFS and CS at 0.3 m in all sectors (R2 = 0.200-0.406), but the correlation between VFS and CS at 5 m was significant only in the inferior sector (R2 = 0.224-0.348 vs. 0.081-0.126 in the inferior and superior sectors, respectively). Correlations between CS and VFS were dependent on CS distances and the presence of bi-hemifield VF defects. Although CS may not correlate with VFS in eyes with single-hemifield VF defects, it may reflect visual disability in eyes with bi-hemifield defects.
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Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Testes de Campo Visual , Campos Visuais , Sensibilidades de Contraste , Qualidade de Vida , Estudos Transversais , Pressão Intraocular , Transtornos da VisãoRESUMO
Background: Coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) provide additional functional information beyond the anatomy by applying computational fluid dynamics (CFD). This study sought to evaluate a novel approach for estimating computational fractional flow reserve (FFR) from coronary CTA-OCT fusion images. Methods: Among patients who underwent coronary CTA, 148 patients who underwent both pressure wire-based FFR measurement and OCT during angiography to evaluate intermediate stenosis in the left anterior descending artery were included from the prospective registry. Coronary CTA-OCT fusion images were created, and CFD was applied to estimate computational FFR. Based on pressure wire-based FFR as a reference, the diagnostic performance of Fusion-FFR was compared with that of CT-FFR and OCT-FFR. Results: Fusion-FFR was strongly correlated with FFR (r = 0.836, P < 0.001). Correlation between FFR and Fusion-FFR was stronger than that between FFR and CT-FFR (r = 0.682, P < 0.001; z statistic, 5.42, P < 0.001) and between FFR and OCT-FFR (r = 0.705, P < 0.001; z statistic, 4.38, P < 0.001). Area under the receiver operating characteristics curve to assess functionally significant stenosis was higher for Fusion-FFR than for CT-FFR (0.90 vs. 0.83, P = 0.024) and OCT-FFR (0.90 vs. 0.83, P = 0.043). Fusion-FFR exhibited 84.5% accuracy, 84.6% sensitivity, 84.3% specificity, 80.9% positive predictive value, and 87.5% negative predictive value. Especially accuracy, specificity, and positive predictive value were superior for Fusion-FFR than for CT-FFR (73.0%, P = 0.007; 61.4%, P < 0.001; 64.0%, P < 0.001) and OCT-FFR (75.7%, P = 0.021; 73.5%, P = 0.020; 69.9%, P = 0.012). Conclusion: CFD-based computational FFR from coronary CTA-OCT fusion images provided more accurate functional information than coronary CTA or OCT alone. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03298282].
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In this study, we aimed to propose a novel diabetes index for the risk classification based on machine learning techniques with a high accuracy for diabetes mellitus. Upon analyzing their demographic and biochemical data, we classified the 2013-16 Korea National Health and Nutrition Examination Survey (KNHANES), the 2017-18 KNHANES, and the Korean Genome and Epidemiology Study (KoGES), as the derivation, internal validation, and external validation sets, respectively. We constructed a new diabetes index using logistic regression (LR) and calculated the probability of diabetes in the validation sets. We used the area under the receiver operating characteristic curve (AUROC) and Cox regression analysis to measure the performance of the internal and external validation sets, respectively. We constructed a gender-specific diabetes prediction model, having a resultant AUROC of 0.93 and 0.94 for men and women, respectively. Based on this probability, we classified participants into five groups and analyzed cumulative incidence from the KoGES dataset. Group 5 demonstrated significantly worse outcomes than those in other groups. Our novel model for predicting diabetes, based on two large-scale population-based cohort studies, showed high sensitivity and selectivity. Therefore, our diabetes index can be used to classify individuals at high risk of diabetes.
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Diabetes Mellitus/classificação , Diabetes Mellitus/epidemiologia , Aprendizado de Máquina , Idade de Início , Idoso , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , República da Coreia/epidemiologiaRESUMO
At present, it remains difficult to deconvolute serum in order to identify the cell or tissue origin of a given circulating protein. Here, by exploiting the properties of proximity biotinylation, we describe a mouse model that enables the elucidation of the in vivo tissue-specific secretome. As an example, we demonstrate how we can readily identify in vivo endothelial-specific secretion as well as how this model allows for the characterization of muscle-derived serum proteins that either increase or decrease with exercise. This genetic platform should, therefore, be of wide utility in understanding normal and disease physiology and for the rational design of tissue-specific disease biomarkers.
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Proteínas Sanguíneas/genética , Especificidade de Órgãos/genética , Proteoma/genética , Proteômica , Animais , Biotinilação , Humanos , Camundongos , Proteínas Musculares/sangue , Proteínas Musculares/genéticaRESUMO
PURPOSE: Determining the optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an important clinical issue. We evaluated the effects of ischemia (by DAPT score) and bleeding (by PRECISE-DAPT score), as well as the impact of DAPT duration, on clinical outcomes. METHODS: From pooled analysis of four randomized clinical trials, 5131 patients undergoing second-generation DES implantation were randomized to short-duration (n = 2575; ≤ 6 months) or standard-duration (n = 2556; ≥ 12 months) DAPT groups. This population was further divided into four subgroups according to PRECISE-DAPT (high bleeding risk ≥ 25) and DAPT (high ischemic risk ≥ 2) scores. RESULTS: Net clinical outcomes (1.3% vs. 1.3%; p = 0.89) and ischemic events (5.0% vs. 4.5%; p = 0.44) did not differ between the two duration groups, although bleeding events were more frequent in patients with standard-duration DAPT (0.4% vs. 0.9%; p = 0.04). Standard-duration DAPT was associated with fewer ischemic events (6.9% vs. 4.0%; p = 0.02) and no increase in bleeding events only among patients at low bleeding risk and high ischemic risk. The other groups show no differences in net clinical outcomes, ischemic events, or bleeding events according to DAPT duration. CONCLUSION: Compared with short-duration DAPT, standard-duration DAPT was associated with similar net clinical outcomes and ischemic events, but more bleeding events at 12 months after second-generation DES implantation. However, standard-duration DAPT reduced ischemic events without increasing bleeding events among patients at low bleeding and high ischemic risk. When determining DAPT duration, considering both ischemic and bleeding risk can help optimize patient benefits. CLINICAL TRIAL REGISTRATION: EXCELLENT (NCT00698607), RESET (NCT01145079), IVUS-XPL (NCT01308281), OPTIMA-C (NCT03056118).
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Stents Farmacológicos/estatística & dados numéricos , Terapia Antiplaquetária Dupla/métodos , Idoso , Comorbidade , Esquema de Medicação , Terapia Antiplaquetária Dupla/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Isquemia Miocárdica/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Bacteria and their toxins are associated with significant human morbidity and mortality. While a few bacterial toxins are well characterized, the mechanism of action for most toxins has not been elucidated, thereby limiting therapeutic advances. One such example is the highly potent pore-forming toxin, hemolysin BL (HBL), produced by the gram-positive pathogen Bacillus cereus. However, how HBL exerts its effects and whether it requires any host factors is unknown. Here, we describe an unbiased genome-wide CRISPR-Cas9 knockout screen that identified LPS-induced TNF-α factor (LITAF) as the HBL receptor. Using LITAF-deficient cells, a second, subsequent whole-genome CRISPR-Cas9 screen identified the LITAF-like protein CDIP1 as a second, alternative receptor. We generated LITAF-deficient mice, which exhibit marked resistance to lethal HBL challenges. This work outlines and validates an approach to use iterative genome-wide CRISPR-Cas9 screens to identify the complement of host factors exploited by bacterial toxins to exert their myriad biological effects.
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Proteínas Reguladoras de Apoptose/fisiologia , Bacillus cereus/patogenicidade , Proteínas de Bactérias/fisiologia , Proteínas de Ligação a DNA/fisiologia , Proteínas Hemolisinas/fisiologia , Receptores de Enterotoxina/fisiologia , Fatores de Transcrição/fisiologia , Animais , Proteínas Reguladoras de Apoptose/genética , Células CHO , Linhagem Celular , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Cricetulus , Proteínas de Ligação a DNA/genética , Células Endoteliais , Feminino , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno , Humanos , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Enterotoxina/genética , Fatores de Transcrição/genética , Fatores de VirulênciaRESUMO
BACKGROUND: Isolated true aneurysms in the superficial femoral artery (SFA) have rarely been reported. Most cases are undiagnosed until rupture or the occurrence of complications. CASE SUMMARY: A 36-year-old woman presented with a palpable, pulsating mass on her right thigh which had increased in size over 2 months. She also had a swollen right leg and mild claudication (Stage II in Rutherford classification). For 2 months, the patient was treated by manual massage, acupuncture, and extracorporeal shock wave therapy in local clinics. Bed-side ultrasonography identified a 3.4-cm sized true aneurysm of the right SFA. There were no other aneurysms in arteries from head to toe. There was no evidence of atherosclerotic risk factors or connective tissue disease. The patient was successfully treated by a covered stent graft implantation without any complications. DISCUSSION: Isolated true aneurysm in the SFA is rare and tends to go undiagnosed especially in young women. Ultrasonography is an easy and useful diagnostic tool for differential diagnosis of thigh mass. In this case, endovascular treatment was safely applied for a true aneurysm without rupture.
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BACKGROUND: Evaluate the safety and efficacy of guideline-recommended risk score-directed dual antiplatelet therapy (GD-DAPT) based on THE PRECISE-DAPT score after 2nd-generation drug-eluting stent (DES) implantation.MethodsâandâResults:We analyzed 5,131 patients pooled from 4 clinical trials. Patients were divided into 3 groups according to current recommendations on the duration of DAPT and their actual DAPT duration: GD-DAPT (n=2,183), shorter DAPT (n=1,540), longer DAPT (n=1,408). The primary endpoint was the rate of net adverse clinical events (NACE) during the first 12 months. The secondary endpoints were ischemic or bleeding events. Overall, GD-DAPT did not affect NACE (1.2% vs. 1.2% for shorter DAPT and 1.7% for longer DAPT) or bleeding events (0.6% vs. 0.5% and 0.9%), and there were fewer ischemic events (2.8% vs. 4.4% and 4.0%, P=0.03) than with shorter DAPT. Especially in acute coronary syndrome (ACS) patients, GD-DAPT had fewer NACE (1.5% vs. 1.4% and 4.2%; P=0.006) and bleeding events (0.8% vs. 0.5% and 2.8%; P=0.001) than longer DAPT as well as fewer ischemic events (2.8% vs. 4.4% and 4.7%; P=0.03) than shorter DAPT. CONCLUSIONS: GD-DAPT did not affect NACE or bleeding events and reduced the number of ischemic events at 12 months compared with shorter DAPT. For ACS, GD-DAPT was associated with favorable outcomes compared with non-GD-DAPT. Therefore, GD-DAPT may optimize efficacy and safety.