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BACKGROUND: Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA. METHODS: The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least 1 non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into 2 groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50%-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis was revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025. CONCLUSIONS: The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457.
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Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Masculino , Feminino , Angiografia Coronária , Fatores de Tempo , Revascularização Miocárdica/métodos , Tempo para o Tratamento , Pessoa de Meia-IdadeRESUMO
PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.
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Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Fatores de RiscoRESUMO
Background: Periprocedural myocardial infarction (PMI) occurs more frequently in patients with heavily calcified lesion and undergoing rotational atherectomy (RA). However, there are limited studies addressing prognostic impact of PMI in patients requiring RA due to severe coronary artery calcification (CAC). Therefore, the objective of this study was to determine the prognostic impact of PMI in patients who underwent percutaneous coronary intervention (PCI) using RA. Methods: A total of 540 patients (583 lesions) who received PCI using RA were enrolled between January 2010 and October 2019. PMI was defined as elevations of creatine kinase-myocardial band (CK-MB) > 10 times the upper limited normal. Patients were divided into a PMI group and a non-PMI group. Primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of cardiac death, target-vessel myocardial infarction, target-vessel revascularization, and cerebrovascular accident. Results: Although in-hospital events occurred more frequently in the PMI group than in the non-PMI group (15 [3.0%] vs. 6 [13.3%], p = 0.005), the incidence of MACCEs at 1 month, 1-12 months, or 12 months failed to show a significant difference between the two groups (1 month, 10 [2.0%] vs. 1 [2.2%], p > 0.999; 1-12 months, 39 [7.9%] vs. 7 [15.6%], p = 0.091; 12 months, 49 [9.9%] vs. 8 [17.8%], p = 0.123). Conclusions: This study shows that PMI after RA in patients with severe CAC was associated with more frequent in-hospital events and a nonsignificant trend for more events during 1 year follow-up.
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Background and Objectives: Although both rotational atherectomy (RA) and atrial fibrillation (AF) have a high thrombotic risk, there have been no previous studies on the prognostic impact of AF in patients who undergo percutaneous coronary intervention (PCI) using RA. Thus, the aim of the present study was to determine the prognostic impact of AF in patients undergoing PCI using RA. Materials and Methods: A total of 540 patients who received PCI using RA were enrolled between January 2010 and October 2019. Patients were divided into AF and sinus rhythm groups according to the presence of AF. The primary endpoint was net adverse clinical events (NACEs) defined as a composite outcome of all-cause death, myocardial infarction, target vessel revascularization, cerebrovascular accident, or total bleeding. Results: Although in-hospital adverse events showed no difference between those with AF and those without AF (in-hospital events, 54 (11.0%) vs. 6 (12.2%), p = 0.791), AF was strongly associated with an increased risk of NACE at 3 years (NACE: hazard ratio, 1.880; 95% confidence interval, 1.096-3.227; p = 0.022). Conclusions: AF in patients who underwent PCI using RA was strongly associated with poor clinical outcomes. Thus, more attention should be paid to thrombotic and bleeding risks.
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Aterectomia Coronária , Fibrilação Atrial , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Aterectomia Coronária/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Fibrilação Atrial/complicações , Prognóstico , Resultado do Tratamento , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: While fish oil (FO) has attracted great attention due to their health-enhancing properties, its potential to enhance benefits from resistance exercise training (RET) has not been fully elucidated yet. AIMS: The aim of this study was to investigate effects of FO administration during 12 weeks of programmed RET on muscular strength, resting metabolic rate (RMR), and systemic inflammation in healthy older adults. METHODS: Twenty-eight healthy older adults were randomly assigned to three experimental groups: sedentary control (CON), resistance exercise training (RET), or RET combined with FO (RET-FO). A one-repetition (1RM) of maximum muscle strength, RMR, substrate oxidation, and blood inflammatory biomarkers were assessed before and after the intervention. Statistical significance was set at p ≤ 0.05. RESULTS: 1RM muscle strength was significantly increased in RET and RET-FO while substantially decreased in CON. RMR greatly increased in RET and RET-FO with no change in CON. RET-FO exhibited significantly increased fatty acid oxidation, but no change was found in CON and RET. Systemic interleukin 6 (IL-6) and C-reactive protein (CRP) were significantly decreased from baseline in RET-FO while no change was observed in CON and RET. CONCLUSION: Our data indicate chronic RET reversed aging-induced loss of muscle strength and improved RMR, while FO administration combined with RET appears to enhance fat metabolism and mildly reduce some indicators of systemic inflammation.
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Treinamento Resistido , Humanos , Óleos de Peixe/farmacologia , Metabolismo Basal , Força Muscular , Inflamação , Músculo EsqueléticoRESUMO
The aim of this study was to investigate the impact of chronic total occlusion (CTO) on clinical outcomes in patients with calcified coronary lesions receiving rotational atherectomy (RA). This multi-center registry enrolled consecutive patients with calcified coronary artery disease who underwent RA during percutaneous coronary intervention (PCI) from 9 tertiary centers in Korea between January 2010 and October 2019. The primary outcome was target-vessel failure (TVF) which included the composite of cardiac death, target-vessel myocardial infarction (TVMI), and target-vessel revascularization (TVR). A total of 583 lesions were enrolled in this registry and classified as CTO (n = 42 lesions, 7.2%) and non-CTO (n = 541 lesions, 92.8%). The CTO group consisted of younger patients who were more likely to have a history of previous percutaneous coronary intervention or coronary artery bypass graft surgery. The incidence of the primary outcome was 14.1% and 16.7% for the non-CTO group and CTO group, respectively. The primary outcomes observed in the two groups were not significantly different (log-rank p = 0.736). The 18-month clinical outcomes of the CTO group were comparable to those of the non-CTO group in multivariate analysis. About 7% of patients requiring RA have CTO lesions and these patients experience similar clinical outcomes compared with those having non-CTO lesions. Use of RA for CTO lesions was safe despite higher procedural complexity.
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Aterectomia Coronária , Doença da Artéria Coronariana , Oclusão Coronária , Intervenção Coronária Percutânea , Aterectomia Coronária/efeitos adversos , Doença Crônica , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Oclusão Coronária/diagnóstico , Oclusão Coronária/cirurgia , Humanos , Sistema de Registros , Fatores de Risco , Resultado do TratamentoRESUMO
Background and Objectives: Data is still limited regarding clinical outcomes of rotational atherectomy (RA) after percutaneous coronary intervention. We sought to evaluate clinical outcomes of RA. Materials and Methods: This multi-center registry enrolled patients who underwent RA during PCI from nine tertiary centers in Korea between January 2010 and October 2019. The primary endpoint was target-vessel failure (TVF; the composite outcome of cardiac death, target-vessel spontaneous myocardial infarction, or target-vessel revascularization). Results: Of 540 patients (583 lesions), the mean patient age was 71.4 ± 0.4 years, 323 patients (59.8%) were men, and 305 patients (56.5%) had diabetes mellitus. Technical success rate was 96.4%. In-hospital major adverse cerebral and cardiac events occurred in 63 cases (10.8%). At 1.5 years, 72 (16.0%) of TVFs were occurred. We evaluated independent predictors of TVF, which included current smoker (hazard ratio (HR), 1.92; 95% confidence interval (CI), 1.17-3.16; p = 0.01), chronic renal disease (HR, 1.87; 95% CI, 1.14-3.08; p = 0.013), history of cerebrovascular attack (HR, 2.14; 95% CI, 1.24-3.68; p = 0.006), left ventricle ejection fraction (HR, 0.98; 95% CI, 0.97-0.999; p = 0.037), and left main disease (HR, 1.94; 95% CI, 1.11-3.37; p = 0.019). Conclusions: From this registry, we demonstrated acceptable success rates, in-hospital and mid-term clinical outcomes of RA in the DES era.
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Aterectomia Coronária , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Calcificação Vascular , Idoso , Doença da Artéria Coronariana/cirurgia , Humanos , Masculino , Sistema de Registros , República da Coreia/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The influence of intensive glucose control in diabetic patients on the macrovascular outcomes is controversial. Thus, this study aimed to elucidate the effect of preprocedural hemoglobin A1c (HbA1c) on clinical outcomes after endovascular therapy for lower extremity artery disease (LEAD) in diabetic patients. METHODS: Diabetic patients were enrolled from the retrospective cohorts of a Korean multicenter endovascular therapy registry and were divided according to the HbA1c level during index admission into the optimal (< 7.0%) or suboptimal (≥ 7.0%) glycemic control groups. The primary endpoints were major adverse limb events (MALE, a composite of major amputation, minor amputation, and reintervention). RESULTS: Of the 1103 patients enrolled (897 men, mean age 68.2 ± 8.9 years), 432 (39.2%) were classified into the optimal glycemic control group and 671 (60.8%) into the suboptimal glycemic control group. In-hospital events and immediate procedural complications were not different between the two groups. The suboptimal group showed a trend towards a higher incidence of MALE than the optimal group (log-rank p = 0.072). Although no significant differences were found between the two groups in terms of overall survival or amputation, the risk of reintervention was significantly higher in the suboptimal group (log-rank p = 0.048). In the multivariate Cox regression model, suboptimal glycemic control was one of the independent predictors for reintervention. When our data were analyzed according to the initial presentation, suboptimal preprocedural HbA1c significantly increased the incidence of MALE compared with optimal preprocedural HbA1c only in patients with intermittent claudication. CONCLUSION: In diabetic patients undergoing endovascular therapy for LEAD, suboptimal preprocedural HbA1c is associated with an increased risk of adverse limb events, especially in patients with intermittent claudication. Further prospective research will be required to validate the role of more intensive glycemic control on the reduction of adverse limb events in diabetic patients undergoing endovascular therapy for LEAD.
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Glicemia/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Procedimentos Endovasculares , Hipoglicemiantes/uso terapêutico , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Idoso , Amputação Cirúrgica , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Sistema de Registros , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Although chronic kidney disease (CKD) and diabetes are important prognostic factors in patients with peripheral artery disease, there are limited data regarding the outcomes of endovascular treatment (EVT) according to the severity of CKD, especially in the presence of diabetes. This study sought to compare clinical outcomes of lower limb EVT between patients with and patients without CKD according to the presence of diabetes. METHODS: Patients were enrolled from the Korean multicenter EVT registry and were divided according to the presence of diabetes, then further stratified by CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). The primary outcome was major adverse limb events (MALEs; a composite of reintervention for target limb, reintervention for target vessel, and unplanned major amputation) at 2 years. RESULTS: A total of 3045 patients were eligible for analysis: 1277 nondiabetic patients (944 without CKD, 333 with CKD) and 1768 diabetic patients (951 without CKD, 817 with CKD). CKD was associated with a significantly increased risk of MALEs after EVT in diabetic patients (14.4% vs 9.9%; adjusted hazard ratio, 1.60; 95% confidence interval, 1.28-2.01; P < .001) but not in nondiabetic patients (7.6% vs 9.7%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.53-1.14; P = .203; interaction P = .018). In analysis stratified by the severity of CKD among diabetic patients, end-stage renal disease was significantly associated with an increased risk of MALE. CONCLUSIONS: CKD was associated with a significantly higher risk of MALEs after EVT in diabetic patients but not in nondiabetic patients. The increased risk of MALEs was mainly driven by patients with end-stage renal disease.
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Diabetes Mellitus/epidemiologia , Procedimentos Endovasculares , Taxa de Filtração Glomerular , Rim/fisiopatologia , Doença Arterial Periférica/terapia , Insuficiência Renal Crônica/epidemiologia , Idoso , Amputação Cirúrgica , Diabetes Mellitus/diagnóstico , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/fisiopatologia , Sistema de Registros , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Aucklandia lappa Decne., known as "Mok-hyang" in Korea, has been used for the alleviation of abdominal pain, vomiting, diarrhea, and stress gastric ulcers in traditional oriental medicine. We investigated the anti-inflammatory and antioxidative effects of the ethanol extract of Aucklandia lappa Decne. (ALDE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. ALDE significantly inhibited the LPS-induced nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. The production of other proinflammatory mediators, including COX-2, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, was reduced by ALDE in LPS-stimulated RAW 264.7 cells. The mechanism underlying the anti-inflammatory effects of ALDE was elucidated to be the suppression of LPS-induced nuclear translocation of p65, followed by the degradation of IκB and the inhibition of the phosphorylation of mitogen-activated protein kinases (MAPK). In addition, ALDE showed enhanced radical scavenging activity. The antioxidant effect of ALDE was caused by the enhanced expression of heme oxygenase (HO-1) via stabilization of the expression of the nuclear transcription factor E2-related factor 2 (Nrf2) pathway. Collectively, these results indicated that ALDE not only exerts anti-inflammatory effects via the suppression of the NF-κB and MAPK pathways but also has an antioxidative effect through the activation of the Nrf2/HO-1 pathway.
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Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saussurea/química , Animais , Antioxidantes/metabolismo , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas I-kappa B/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The relationship of LPA single nucleotide polymorphisms (SNPs), apolipoprotein(a) isoforms, and lipoprotein(a) [Lp(a)] levels with major adverse cardiovascular events (MACE) in different ethnic groups is not well known. METHODS: LPA SNPs, apolipoprotein(a) isoforms, Lp(a), and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) levels were measured in 1792 black, 1030 white, and 597 Hispanic subjects enrolled in the Dallas Heart Study. Their interdependent relationships and prospective association with MACE after median 9.5-year follow-up were determined. RESULTS: LPA SNP rs3798220 was most prevalent in Hispanics (42.38%), rs10455872 in whites (14.27%), and rs9457951 in blacks (32.92%). The correlation of each of these SNPs with the major apolipoprotein(a) isoform size was highly variable and in different directions among ethnic groups. In the entire cohort, Cox regression analysis with multivariable adjustment revealed that quartiles 4 of Lp(a) and OxPL-apoB were associated with hazard ratios (95% confidence interval) for time to MACE of 2.35 (1.50-3.69, P<0.001) and 1.89 (1.26-2.84, P=0.003), respectively, versus quartile 1. Addition of the major apolipoprotein(a) isoform and the 3 LPA SNPs to these models attenuated the risk, but significance was maintained for both Lp(a) and OxPL-apoB. Evaluating time to MACE in specific ethnic groups, Lp(a) was a positive predictor and the size of the major apolipoprotein(a) isoform was an inverse predictor in blacks, the size of the major apolipoprotein(a) isoform was an inverse predictor in whites, and OxPL-apoB was a positive predictor in Hispanics. CONCLUSIONS: The prevalence and association of LPA SNPs with size of apolipoprotein(a) isoforms, Lp(a), and OxPL-apoB levels are highly variable and ethnicity-specific. The relationship to MACE is best explained by elevated plasma Lp(a) or OxPL-apoB levels, despite significant ethnic differences in LPA genetic markers.
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Doenças Cardiovasculares/sangue , Lipoproteína(a)/sangue , Polimorfismo de Nucleotídeo Único/genética , Adulto , Etnicidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: There are limited data comparing the outcomes of subintimal vs. intraluminal approach in the treatment of long femoropopliteal artery occlusions. The objective of this study was to investigate the efficacy and safety of the subintimal approach for long femoropopliteal artery occlusions.MethodsâandâResults:From a multicenter retrospective registry cohort, we included a total of 461 patients with 487 femoropopliteal artery occlusions classified as Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) II C/D for this analysis. We compared the immediate and mid-term outcomes of subintimal vs. intraluminal approaches. There were 228 patients with 243 limbs in the subintimal group, and 233 patients with 244 limbs in the intraluminal group. Baseline clinical and lesion characteristics were comparable between the 2 groups. The technical success rate was significantly higher in the subintimal group than in the intraluminal group (95.1% vs. 89.8%, P=0.041). The clinical primary patency (67.5% vs. 73.4% at 12 months, 54.0% vs. 61.3% at 24 months; P=0.086) and target lesion revascularization (TLR)-free survival (89.5% vs. 86.3% at 12 months, 77.6% vs. 76.0% at 24 months; P=0.710) did not differ significantly between the subintimal and the intraluminal groups. CONCLUSIONS: In long femoropopliteal occlusions, the subintimal approach achieved a higher technical success rate and similar mid-term primary patency and TLR-free survival compared with intraluminal approach.
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Arteriopatias Oclusivas/terapia , Procedimentos Endovasculares/métodos , Idoso , Arteriopatias Oclusivas/mortalidade , Estudos de Coortes , Procedimentos Endovasculares/normas , Feminino , Artéria Femoral/patologia , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Artéria Poplítea/patologia , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
BACKGROUND: The safety and clinical effectiveness data of peramivir in the real clinical field are limited. A prospective observational study was conducted based on the post-marketing surveillance data to evaluate the post-marketing safety and effectiveness of peramivir in Korean adults with seasonal influenza. METHODS: Among adults aged 20 years or older who were diagnosed with influenza A or B, patients who started peramivir within 48 hours from the initial symptoms of influenza were enrolled. All adverse events (AEs) that occurred within 7 days after administration of peramivir were checked. For the evaluation of effectiveness, changes in the severity of influenza symptoms and daily living performance were examined before and 7 days after the administration of peramivir. The date on which influenza related symptoms disappeared was checked. RESULTS: A total of 3,024 patients were enrolled for safety evaluation and 2,939 patients were for effectiveness evaluation. In the safety evaluation, 42 AEs were observed in 35 (1.16%) patients. The most common AE was fever. AEs were mostly rated as mild in severity. Serious AEs were observed in 10 patients and two of them died. However, both deaths were considered to be less relevant to peramivir. In the effectiveness evaluation, the severity of influenza symptoms decreased by 10.68 ± 4.01 points and daily living performance was improved 5.59 ± 2.16 points. Influenza related symptoms disappeared on average 3.02 ± 2.39 days after peramivir administration. CONCLUSION: Peramivir showed a tolerable safety profile and acceptable effectiveness in Korean adult patients with seasonal influenza.
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Antivirais/uso terapêutico , Ciclopentanos/uso terapêutico , Guanidinas/uso terapêutico , Influenza Humana/tratamento farmacológico , Ácidos Carbocíclicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Ciclopentanos/efeitos adversos , Feminino , Guanidinas/efeitos adversos , Humanos , Masculino , Marketing , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Adulto JovemRESUMO
To access antitumor effects of a combined Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and interleukin-18 (IL-18), cDNA fusion of murine GM-CSF and mature IL-18 (GMIL-18) was constructed and transfected in mammalian cells. GMIL-18 fusion protein was highly secreted and displayed bifunctional activities, possessing immune response initiation and cytokine roles, including IFN-γ induction in mouse splenocytes and increased proliferation of GM-CSF-dependent cells, M-NSF-60. The GMIL-18 secreting tumor vaccine was generated and it strongly stimulated differentiation of dendrite cells (DCs) and effusive CD8+ and CD4+ cell infiltration into tumor mice. Moreover, growth of CT26 mouse colon cancer cells was significantly retarded by GMIL-18 (CT26GMIL-18), but not by CT26GM-CSF- or CT26IL-18. The efficiency of prophylactic vaccination was greater than that of therapeutic vaccination in terms of tumor size and its inhibitory role in proliferation. In micrometastasis analysis of tumor models, γ-ray irradiated GMIL-18 tumor vaccine showed a smaller number of liver-meta tumor nodules in mouse liver cells. We concluded that bifunctional GMIL-18 fusion protein could be applied as an immune therapy for cancer treatments.
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Vacinas Anticâncer/farmacologia , Fator Estimulador de Colônias de Granulócitos/imunologia , Interleucina-18/imunologia , Neoplasias Experimentais/terapia , Vacinação , Animais , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Fator Estimulador de Colônias de Granulócitos/genética , Interleucina-18/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologiaRESUMO
NEW FINDINGS: What is the central question of this study? This study examined the effects of 20 weeks of administration of conjugated linoleic acids/omega-3 fatty acids with or without programed resistance exercise training on body composition, skeletal muscle properties and functional capacity in middle-aged mice fed a high-fat diet. What is the main finding and its importance? Chronic daily administration of conjugated linoleic acids/omega-3 fatty acids with resistance exercise training can help to blunt fat gain, alleviate loss of myogenic capacity and sensorimotor function and lower tissue inflammation in middle-aged mice during chronic high-fat diet-induced catabolism. This study investigated the effects of 20 weeks of combined conjugated linoleic acid (CLA)/omega-3 fatty acid (n-3) administration independently or combined with resistance exercise training (RET) on skeletal muscle in middle-aged mice consuming a high-fat diet (HFD). Nine-month-old C57BL/6 mice were randomly assigned into four experimental groups (H, high-fat diet; HE, H + RET; HCN, H + CLA/n-3; and HECN, H + CLA/n3 + RET). Body composition and functional capacity were assessed pre- and post-intervention. Muscle tissues were collected at 14 months of age. ANOVA was used, with significance set at P ≤ 0.05. Fat mass significantly increased in H (+74%), HE (+142%) and HECN (+43%) but not in HCN. Muscle wet weights were significantly lower in H and HCN than in HE and HECN. Grip strength substantially declined in H (-15%) and HCN (-17%), whereas sensorimotor function significantly declined only in H (-11%). HECN exhibited improvement in strength (+22%) and sensorimotor coordination (+17%). In comparison to H, muscle tumour necrosis factor-α mRNA expression was significantly lower in HE (-39%), HCN (-24%) and HECN (-21%), respectively. Mean myofibre cross-sectional areas were markedly lower in H and HCN than in HE and HECN. H showed significantly lower satellite cell abundance and numbers of myonuclei than all other groups. Our findings suggest that long-term daily CLA/n-3 intake with resistance training improved sensorimotor function, ameliorated fat gain and prevented loss of myogenic capacity while lowering tumour necrosis factor-α expression during chronic HFD.
Assuntos
Dieta Hiperlipídica , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Linoleicos Conjugados/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Obesidade/prevenção & controle , Treinamento Resistido , Adiposidade/efeitos dos fármacos , Fatores Etários , Animais , Caspase 3/genética , Caspase 3/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Força Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia , Desempenho Psicomotor/efeitos dos fármacos , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add-on to fibrate (n = 26), treated for 85 days and followed for 176 days. Compared with placebo, volanesorsen was associated with an 82.3 ± 11.7%, 81.3 ± 15.7%, and 80.8 ± 13.6% reduction in apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoA-I, respectively (300 mg dose;P< 0.001 for all), at day 92. Strong correlations in all assay measures were noted with total plasma apoC-III, chylomicron-apoC-III, and VLDL-apoC-III. In conclusion, novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the first time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a), and apoA-I lipoproteins, and may be a potent agent to reduce triglycerides and cardiovascular risk mediated by apoC-III.
Assuntos
Apolipoproteína C-III/sangue , Apolipoproteína C-III/genética , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/uso terapêutico , Apolipoproteína C-III/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Triglicerídeos/sangueRESUMO
Backscatter-difference measurements may be used to detect changes in bone caused by osteoporosis. The backscatter-difference technique measures the power difference between two portions of an ultrasonic backscatter signal. The goal of this study is to evaluate the feasibility of using an ultrasonic imaging system to perform backscatter-difference measurements of bone. Ultrasonic images and backscatter signals were acquired from 24 specimens of human cancellous bone. The signals were analyzed in the frequency domain to determine the normalized mean backscatter-difference (nMBD) and in the time domain to determine the normalized backscatter amplitude ratio (nBAR). The images were analyzed to determine the normalized pixel value difference (nPVD), which measures the difference in average pixel brightness between regions of interest placed at two different depths in the image. All three parameters were found to increase with bone mineral density. The signal-based parameters, nMBD and nBAR, correlated well with bone mineral density, yielding linear correlation coefficients that ranged from 0.74 to 0.87. The image based parameter, nPVD, performed somewhat less well, yielding correlation coefficients that ranged from 0.42 to 0.81. These results suggest that ultrasonic imaging systems may be used to perform backscatter-difference measurements for the purpose of ultrasonic bone assessment.
Assuntos
Osso Esponjoso/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Osteoporose/diagnóstico por imagem , Processamento de Sinais Assistido por Computador , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espalhamento de RadiaçãoRESUMO
The primary aim of this study was to compare 2 daily undulating periodization (DUP) models on one-repetition maximum (1RM) strength in the squat, bench press, deadlift, total volume (TV) lifted, and temporal hormone response. Eighteen male, college-aged (21.1 ± 1.9 years) powerlifters participated in this study and were assigned to one of 2 groups: (a) traditional DUP training with a weekly training order: hypertrophy-specific, strength-specific, and power-specific training (HSP, n = 9) or (b) modified DUP training with a weekly training order: hypertrophy-specific, power-specific, and strength-specific training (HPS, n = 9). Both groups trained 3 nonconsecutive days per week for 6 weeks and performed the squat, bench press, and deadlift exercises. During hypertrophy and power sessions, subjects performed a fixed number of sets and repetitions but performed repetitions until failure at a given percentage during strength sessions to compare TV. Testosterone and cortisol were measured at pretesting and posttesting and before each strength-specific day. Hypertrophy, power, and strength produced greater TV in squat and bench press (p ≤ 0.05) than HSP, but not for deadlift (p > 0.05). For squat and deadlift, there was no difference between groups for 1RM (p > 0.05); however, HPS exhibited greater increases in 1RM bench press than HSP (p ≤ 0.05). Effect sizes (ES) showed meaningful differences (ES > 0.50) in favor of HPS for squat and bench press 1RM. Testosterone decreased (p ≤ 0.05) at weeks 5 and 6 and cortisol decline at weeks 3 and 4. However, neither hormone was different at posttesting compared with pretesting (p > 0.05). Our findings suggest that an HPS configuration of DUP has enhanced performance benefits compared with HSP.
Assuntos
Força Muscular , Treinamento Resistido/métodos , Levantamento de Peso/fisiologia , Adulto , Teste de Esforço , Humanos , Hidrocortisona/sangue , Masculino , Modelos Biológicos , Testosterona/sangue , Adulto JovemRESUMO
BACKGROUND AND AIMS: Increased adipose tissue may promote catabolic events in skeletal muscle. The aim of this study was to test whether high-fat diet (HFD)-induced obesity would accelerate the onset of muscle wasting in middle-aged mice. METHODS: Muscle was collected from C57BL/6 mice at 9 months of age (baseline) and 14 months of age after consuming a control (C) or HFD. Mice in C and HFD were also subjected to evaluations of body composition and function before and after their respective diets. RESULTS: HFD demonstrated significant (p < 0.05) losses of grip strength (-15 %) and sensorimotor coordination (-11 %), whereas C did not. Lean mass decreased to a greater degree in HFD although not significantly (C: -20.69 ± 7.94 vs. HFD: -31.14 ± 5.49 %, p > 0.05). Gastrocnemius, quadriceps, and hamstrings mass in C and HFD were significantly reduced from baseline (-27 to 43 and -39 to 47 %, respectively, p < 0.05) with no differences between the two; however, soleus mass was lower only in HFD (-24 %, p = 0.03). Myofiber area, satellite cells, and myonuclei of the gastrocnemius were lower only in HFD (-23, -19, and -16 %, respectively, p < 0.05) compared to baseline. CONCLUSIONS: HFD-induced obesity adversely affected function in middle-aged mice. Atrophy of the soleus in HFD but not C suggests sensitivity of oxidative muscle to HFD-dependent catabolism more so than aging. In the muscles containing fast/mixed fibers, aging effects may have concealed the catabolic nature of HFD; however, morphological changes in the gastrocnemius including decreased fiber area, satellite cells, and myonuclei are consistent with an atrophic phenotype related to HFD.
Assuntos
Tecido Adiposo , Dieta Hiperlipídica/efeitos adversos , Metabolismo/fisiologia , Músculo Esquelético , Atrofia Muscular , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Composição Corporal , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/patologia , Músculo Esquelético/fisiologia , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Obesidade/etiologia , Obesidade/patologia , Tamanho do Órgão , OxirreduçãoRESUMO
Ultrasonic backscatter techniques are being developed to diagnose osteoporosis. Tissues that lie between the transducer and the ultrasonically interrogated region of bone may produce errors in backscatter measurements. The goal of this study is to investigate the effects of intervening tissues on ultrasonic backscatter measurements of bone. Measurements were performed on 24 cube shaped specimens of human cancellous bone using a 5 MHz transducer. Measurements were repeated after adding a 1 mm thick plate of cortical bone to simulate the bone cortex and a 3 cm thick phantom to simulate soft tissue at the hip. Signals were analyzed to determine three apparent backscatter parameters (apparent integrated backscatter, frequency slope of apparent backscatter, and frequency intercept of apparent backscatter) and three backscatter difference parameters [normalized mean backscatter difference (nMBD), normalized slope of the backscatter difference, and normalized intercept of the backscatter difference]. The apparent backscatter parameters were impacted significantly by the presence of intervening tissues. In contrast, the backscatter difference parameters were not affected by intervening tissues. However, only one backscatter difference parameter, nMBD, demonstrated a strong correlation with bone mineral density. Thus, among the six parameters tested, nMBD may be the best choice for in vivo backscatter measurements of bone when intervening tissues are present.