RESUMEN
BACKGROUND: Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking. METHODS: We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding. RESULTS: We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.).
RESUMEN
BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Insuficiencia Cardíaca , Insuficiencia de la Válvula Mitral , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia de la Válvula Mitral/tratamiento farmacológico , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/fisiopatología , Masculino , Femenino , Anciano , Método Doble Ciego , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Fragmentos de Péptidos/sangre , Función Ventricular Izquierda/efectos de los fármacos , Péptido Natriurético EncefálicoRESUMEN
BACKGROUND: Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. METHODS: PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. FINDINGS: Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). INTERPRETATION: In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. FUNDING: The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Placa Aterosclerótica , Humanos , Masculino , Femenino , Intervención Coronaria Percutánea/métodos , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/terapia , Resultado del Tratamiento , Nueva Zelanda , República de Corea , Taiwán/epidemiología , Japón , Infarto del Miocardio , Síndrome Coronario Agudo/terapiaRESUMEN
BACKGROUND: There are limited data from randomized trials to guide a specific follow-up surveillance approach after myocardial revascularization. Whether a follow-up strategy that includes routine functional testing improves clinical outcomes among high-risk patients who have undergone percutaneous coronary intervention (PCI) is uncertain. METHODS: We randomly assigned 1706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing (nuclear stress testing, exercise electrocardiography, or stress echocardiography) at 1 year after PCI or to standard care alone. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Key secondary outcomes included invasive coronary angiography and repeat revascularization. RESULTS: The mean age of the patients was 64.7 years, 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents. At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval [CI], 0.61 to 1.35; P = 0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, -0.01 to 5.99), and 8.1% and 5.8% of patients, respectively, had undergone repeat revascularization (difference, 2.23 percentage points; 95% CI, -0.22 to 4.68). CONCLUSIONS: Among high-risk patients who had undergone PCI, a follow-up strategy of routine functional testing, as compared with standard care alone, did not improve clinical outcomes at 2 years. (Funded by the CardioVascular Research Foundation and Daewoong Pharmaceutical; POST-PCI ClinicalTrials.gov number, NCT03217877.).
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Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Cuidados Posteriores , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Pruebas Diagnósticas de Rutina , Stents Liberadores de Fármacos/efectos adversos , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Nivel de Atención , Resultado del TratamientoRESUMEN
BACKGROUND: Intravascular imaging-guided percutaneous coronary intervention (PCI) with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) showed superior clinical outcomes compared with angiography-guided PCI. However, the comparative effectiveness of OCT-guided and IVUS-guided PCI regarding clinical outcomes is unknown. METHODS: In this prospective, multicenter, open-label, pragmatic trial, we randomly assigned 2008 patients with significant coronary artery lesions undergoing PCI in a 1:1 ratio to undergo either an OCT-guided or IVUS-guided PCI. The primary end point was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year, which was powered for noninferiority of the OCT group compared with the IVUS group. Safety outcomes were also assessed. RESULTS: At 1 year, primary end point events occurred in 25 of 1005 patients (Kaplan-Meier estimate, 2.5%) in the OCT group and in 31 of 1003 patients (Kaplan-Meier estimate, 3.1%) in the IVUS group (absolute difference, -0.6 percentage points; upper boundary of one-sided 97.5% CI, 0.97 percentage points; P<0.001 for noninferiority). The incidence of contrast-induced nephropathy was similar (14 patients [1.4%] in the OCT group versus 15 patients [1.5%] in the IVUS group; P=0.85). The incidence of major procedural complications was lower in the OCT group than in the IVUS group (22 [2.2%] versus 37 [3.7%]; P=0.047), although imaging procedure-related complications were not observed. CONCLUSIONS: In patients with significant coronary artery lesions, OCT-guided PCI was noninferior to IVUS-guided PCI with respect to the incidence of a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year. The selected study population and lower-than-expected event rates should be considered in interpreting the trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique number: NCT03394079.
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Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Angiografía Coronaria/métodos , Tomografía de Coherencia Óptica/métodos , Estudios Prospectivos , Stents Liberadores de Fármacos/efectos adversos , Ultrasonografía Intervencional/efectos adversos , Ultrasonografía Intervencional/métodos , Resultado del Tratamiento , Infarto del Miocardio/etiología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugíaRESUMEN
BACKGROUND: Harsh temperature exposure has been associated with a high risk of cardiovascular events. We sought to investigate the influence of temperature change on long-term incidence of acute myocardial infarction (AMI) in Korean patients. METHODS: From the National Health Insurance Service (NHIS) customized health information database (from 2005 to 2014), data from a total of 192,567 AMI patients was assessed according to the International Classification of Disease 10th edition code and matched with temperature reports obtained from the Korea Meteorological Administration database. We analyzed data for a 10-year period on a monthly and seasonal basis. RESULTS: The incidence rate per 100,000 year of AMI exhibited a downward trend from 69.1 to 56.1 over the period 2005 to 2014 (P < 0.005), and the seasonal AMI incidence rate per 100,000 year was highest in spring (63.1), and winter (61.3) followed by autumn (59.5) and summer (57.1). On a monthly basis, the AMI incidence rate per 100,000 year was highest during March (64.4) and December (63.9). The highest incidence of AMI occurred during temperature differences of 8-10° in each season. Moreover, AMI incidence tended to increase as the mean temperature decreased (r = -0.233, P = 0.001), and when the mean daily temperature difference increased (r = 0.353, P < 0.001). CONCLUSION: The AMI incidence rate per 100,000 year has a decreasing trend over the 10-year period, derived from the Korean NHIS database. Modest daily temperature differences (8-10°) and the spring season are related to higher AMI incidence, indicating that daily temperature variation is more important than the mean daily temperature.
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Infarto del Miocardio , Humanos , Temperatura , Incidencia , Estaciones del Año , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Bases de Datos FactualesRESUMEN
BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stents and coronary artery bypass grafting (CABG) are limited in patients with multivessel coronary artery disease. METHODS: This prospective, multicenter, randomized controlled trial was conducted in 27 international heart centers and was designed to randomly assign 1776 patients with angiographic multivessel coronary artery disease to receive PCI with everolimus-eluting stents or CABG. After inclusion of 880 patients (438 in the PCI group and 442 in the CABG group) between July 2008 and September 2013, the study was terminated early because of slow enrollment. The primary end point was the composite of death from any cause, myocardial infarction, or target vessel revascularization. RESULTS: During a median follow-up of 11.8 years (interquartile range, 10.6-12.5 years; maximum, 13.7 years), the primary end point occurred in 151 patients (34.5%) in the PCI group and 134 patients (30.3%) in the CABG group (hazard ratio [HR], 1.18 [95% CI, 0.88-1.56]; P=0.26). No significant differences were seen in the occurrence of a safety composite of death, myocardial infarction, or stroke between groups (28.8% and 27.1%; HR, 1.07 [95% CI, 0.75-1.53]; P=0.70), as well as the occurrence of death from any cause (20.5% and 19.9%; HR, 1.04 [95% CI, 0.65-1.67]; P=0.86). However, spontaneous myocardial infarction (7.1% and 3.8%; HR, 1.86 [95% CI, 1.06-3.27]; P=0.031) and any repeat revascularization (22.6% and 12.7%; HR, 1.92 [95% CI, 1.58-2.32]; P<0.001) were more frequent after PCI than after CABG. CONCLUSIONS: In patients with multivessel coronary artery disease, there were no significant differences between PCI and CABG in the incidence of major adverse cardiac events, the safety composite end point, and all-cause mortality during the extended follow-up. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT05125367 and NCT00997828.
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Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Everolimus/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Stents Liberadores de Fármacos/efectos adversos , Estudios de Seguimiento , Estudios Prospectivos , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.
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Estenosis de la Válvula Aórtica , Tromboembolia , Trombosis , Reemplazo de la Válvula Aórtica Transcatéter , Anticoagulantes/uso terapéutico , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Piridinas , Factores de Riesgo , Tiazoles , Tromboembolia/diagnóstico por imagen , Tromboembolia/epidemiología , Tromboembolia/etiología , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Trombosis/epidemiología , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial. METHODS: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up. RESULTS: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years. CONCLUSIONS: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).
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Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Tratamiento Conservador , Anciano , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/terapia , Enfermedades Asintomáticas/terapia , Enfermedades Cardiovasculares/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Complicaciones Posoperatorias/mortalidadRESUMEN
BACKGROUND: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. METHODS: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H2O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. RESULTS: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H2O in the driving pressure group vs 9.2 cm H2O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H2O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H2O-1; P<0.001) and Pao2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. CONCLUSIONS: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. CLINICAL TRIAL REGISTRATION: NCT04260451.
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Cirugía Torácica , Procedimientos Quirúrgicos Torácicos , Humanos , Femenino , Persona de Mediana Edad , Masculino , Respiración con Presión Positiva/efectos adversos , Pulmón , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Torácicos/efectos adversos , Volumen de Ventilación PulmonarRESUMEN
BACKGROUND: Although pulmonary rehabilitation is helpful for patients following lung cancer surgery, rehabilitation is not widely available, due in part to a lack of medical resources. Recent developments in digital health care have overcome the space limitations associated with in-person health care. This study will evaluate and compare the efficacy of three different smartphone healthcare systems in patients with lung cancer. METHODS: This single center randomized controlled study is designed to evaluate the efficacy of digital healthcare applications for lung cancer patients after thoracoscopic lung resection. A total of 320 patients will be enrolled and randomized 1:1:1:1 into four different groups, with one group each using the smartphone applications NOOM, Walkon, and Efilcare and the fourth being the control group without intervention. Questionnaires will be administered to patients at baseline and after 3, 6, and 12 months. The primary endpoint will be the score on the EuroQol five-dimension index. Secondary endpoints will include other questionnaires about quality of life and dyspnea. DISCUSSION: This prospective randomized controlled study may allow assessments and comparisons of the efficacy of various smartphone applications in patients who undergo lung cancer surgery. This process may enable the introduction of healthcare interventions that maintain quality of life in patients with lung cancer. Trial registration CRIS, KCT0005447. Registered 06 October 2020, https://cris.nih.go.kr/cris/search/detailSearch.do/19346.
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Neoplasias Pulmonares , Calidad de Vida , Atención a la Salud , Humanos , Neoplasias Pulmonares/cirugía , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Teléfono InteligenteRESUMEN
BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents and coronary-artery bypass grafting (CABG) for left main coronary artery disease are highly debated. METHODS: In the PRECOMBAT trial (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), patients with unprotected left main coronary artery disease were randomly assigned to undergo PCI with sirolimus-eluting stents (n=300) or CABG (n=300) in 13 hospitals in Korea from April 2004 to August 2009. The follow-up was extended to at least 10 years for all patients (median, 11.3 years). The primary outcome was the incidence of major adverse cardiac or cerebrovascular events (composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization). RESULTS: At 10 years, a primary outcome event occurred in 29.8% of the PCI group and in 24.7% of the CABG group (hazard ratio [HR] with PCI vs CABG, 1.25 [95% CI, 0.93-1.69]). The 10-year incidence of the composite of death, myocardial infarction, or stroke (18.2% vs 17.5%; HR 1.00 [95% CI, 0.70-1.44]) and all-cause mortality (14.5% vs 13.8%; HR 1.13 [95% CI, 0.75-1.70]) were not significantly different between the PCI and CABG groups. Ischemia-driven target-vessel revascularization was more frequent after PCI than after CABG (16.1% vs 8.0%; HR 1.98 [95% CI, 1.21-3.21). CONCLUSIONS: Ten-year follow-up of the PRECOMBAT trial of patients with left main coronary artery disease randomized to PCI or CABG did not demonstrate significant difference in the incidence of major adverse cardiac or cerebrovascular events. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03871127 and NCT00422968.
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Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea/instrumentación , Anciano , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , República de Corea , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
We investigated the association between herpes zoster (HZ) and dementia, and the effects of antiviral therapy on the risk of dementia. We used the National Health Insurance Service-National Sample Cohort in South Korea to identify individuals that were followed from January 1, 2002, to December 31, 2013. Occurrences of HZ and dementia were identified using the relevant diagnostic codes. Dementia was defined as the presence of diagnostic codes and history of anti-dementia drug prescription. Propensity score matching (1:1) was carried out among HZ patients according to antiviral therapy. A total of 229,594 individuals aged ≥50 years were analyzed. The incidences of the first-diagnosed HZ and dementia were 16.69 and 4.67 per 1000 person-years (PY), respectively. HZ patients had a higher risk of dementia (incidence rate ratio [IRR], 1.94 [95% CI 1.83-2.06]; adjusted hazard ratio [HR], 1.12 [95% CI 1.05-1.19]). Of the 34,505 patients with HZ, 28,873 (84%) had received antiviral treatment. The crude incidence rates of subsequent dementia in the treated and untreated groups were 7.79 and 12.27 per 1000 PY, respectively, resulting in an IRR of 0.64 (95% CI 0.56-0.72) and covariate-adjusted HR of 0.79 (95% CI 0.69-0.90). After propensity score matching, the treated group showed a significantly lower risk of dementia (HR 0.76; 95% CI 0.65-0.90). In this large population-based cohort study, HZ was associated with a higher risk of dementia. The use of antiviral agents in HZ patients was associated with lower risks of dementia.
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Antivirales , Demencia , Herpes Zóster , Antivirales/uso terapéutico , Estudios de Cohortes , Demencia/epidemiología , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Medición de RiesgoRESUMEN
BACKGROUND: The morbidity and mortality of patients with functional mitral regurgitation (MR) remain high, but no pharmacological therapy has been proven effective. The hypothesis of this study was that sacubitril/valsartan would be superior to valsartan alone in improving functional MR via dual inhibition of the renin-angiotensin system and neprilysin. METHODS: In this double-blind trial, we randomly assigned 118 patients with heart failure with chronic functional MR secondary to left ventricular (LV) dysfunction to receive either sacubitril/valsartan or valsartan, in addition to standard medical therapy for heart failure. The primary end point was the change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume, and incomplete mitral leaflet closure area. RESULTS: The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group than in the valsartan group (-0.058±0.095 versus -0.018±0.105 cm2; P=0.032) in an intention-to-treat analysis including 117 (99%) patients. Regurgitant volume was also significantly decreased in the sacubitril/valsartan group in comparison with the valsartan group (mean difference, -7.3 mL; 95% CI, -12.6 to -1.9; P=0.009). There were no significant between-group differences regarding the changes in incomplete mitral leaflet closure area and LV volumes, with the exception of LV end-diastolic volume index ( P=0.044). We noted no significant difference in the change of blood pressure between the treatment groups, and 7 patients (12%) in the sacubitril/valsartan group and 9 (16%) in the valsartan group had ≥1 serious adverse events ( P=0.54). CONCLUSIONS: Among patients with secondary functional MR, sacubitril/valsartan reduced MR to a greater extent than did valsartan. Our findings suggest that an angiotensin receptor-neprilysin inhibitor might be considered for optimal medical therapy of patients with heart failure and functional MR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02687932.
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Aminobutiratos/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Insuficiencia de la Válvula Mitral/tratamiento farmacológico , Válvula Mitral/efectos de los fármacos , Neprilisina/antagonistas & inhibidores , Inhibidores de Proteasas/uso terapéutico , Tetrazoles/uso terapéutico , Disfunción Ventricular Izquierda/tratamiento farmacológico , Función Ventricular Izquierda/efectos de los fármacos , Anciano , Aminobutiratos/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Compuestos de Bifenilo , Enfermedad Crónica , Método Doble Ciego , Combinación de Medicamentos , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/fisiopatología , Estudios Prospectivos , Inhibidores de Proteasas/efectos adversos , Recuperación de la Función , República de Corea , Tetrazoles/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Valsartán , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. METHODS: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. RESULTS: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P=0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P=0.04) and fatal bleeding (1% [4/400] vs 0%, P=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. CONCLUSIONS: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.
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Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/efectos adversos , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Ticagrelor/efectos adversos , Síndrome Coronario Agudo/etnología , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/terapia , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Causas de Muerte , Clopidogrel/uso terapéutico , Terapia Combinada , Susceptibilidad a Enfermedades , Femenino , Estudios de Seguimiento , Hemorragia/epidemiología , Hemorragia/mortalidad , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Premedicación , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , República de Corea/epidemiología , Tamaño de la Muestra , Ticagrelor/uso terapéuticoRESUMEN
BACKGROUND: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials. METHODS: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator. The primary end point was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life was assessed at baseline and at 1, 6, 12, 24, and 36 months. Because of slow recruitment, the trial was stopped before completion of the 1284 planned enrollments. RESULTS: Between March 2010 and September 2016, 834 patients were randomly assigned to the CTO-PCI (n=417) or no CTO-PCI (n=398) strategy. Among the patients assigned to the no CTO-PCI strategy, 78 (19.6%) crossed over to receive staged CTO-PCI within 3 days of randomization. The overall CTO-PCI success rate was 90.6%. Serious nonfatal complications associated with CTO-PCI occurred in 3 patients (1 stroke, 1 cardiac tamponade, and 1 patient with recurrent episodes of ventricular tachyarrhythmia induced by intracoronary thrombus). Approximately half of the patients in each group underwent PCI for an average of 1.3 non-CTO lesions, resulting in a comparable residual SYNTAX score (Synergy Between PCI With TAXUS and Cardiac Surgery; 3.7±5.4 versus 4.0±5.9, P=0.42) confined to non-CTO vessels. During a median follow-up of 4.0 years (interquartile range, 2.4 to 5.1 years), there was no significant difference between the CTO-PCI and the no CTO-PCI strategies in the incidence of the primary end point (22.3% versus 22.4%, hazard ratio, 1.03; 95% CI, 0.77 to 1.37; P=0.86). Both CTO-PCI and no CTO-PCI strategy were associated with significant improvements but without between-group differences in disease-specific health status that was sustained through 36 months. CONCLUSIONS: CTO-PCI was feasible with high success rates. There was no difference in the incidence of major adverse cardiovascular events with CTO-PCI versus no CTO-PCI, but the study was limited by low power for clinical end points and high crossover rates between groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01078051.
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Oclusión Coronaria/terapia , Intervención Coronaria Percutánea , Anciano , Asia/epidemiología , Enfermedad Crónica , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/mortalidad , Stents Liberadores de Fármacos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Calidad de Vida , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Taquicardia Ventricular/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) is etiologically associated with ~ 10% of all gastric carcinomas. However, the molecular mechanisms and roles of EBV miRNAs in gastric carcinoma oncogenesis are yet to be elucidated. METHODS: MicroRNA microarray and TaqMan quantitative real-time RT-PCR were conducted. RT-PCR and luciferase reporter assay for PIAS3, western blotting for 20 proteins, immunofluorescence for STAT3, transfection with miRBART5-5p-plasmid, STAT3-plasmid, miRBART5-5p mimic, or PIAS3-siRNA, and in vitro assays for biological effects of PD-L1 were implemented. In situ hybridization for EBV-encoded small RNAs and immunohistochemistry were performed on gastric carcinoma tissues. RESULTS: Transfecting miR-BART5-5p into EBV(-) gastric carcinoma cell lines caused a decrease in PIAS3 3'-UTR reporter activity, PIAS3 downregulation, and subsequent STAT3 activation followed by PIAS3/pSTAT3-dependent PD-L1 upregulation. Interestingly, due to PD-L1 knockdown, apoptosis was increased, while the rate of cell proliferation, invasion capacity, and migration were decreased in miR-BART5-5p-transfected cells. In EBV(+) gastric carcinoma cells, anti-miR-BART5-5p reduced PD-L1 levels through PIAS3/pSTAT3 control. Among 103 patients with EBV-associated gastric carcinomas, overall survival was significantly shortened for those with PD-L1(+) tumors compared to those with PD-L1(-) tumors (P = 0.049). CONCLUSIONS: Our findings imply that miR-BART5-5p directly targets PIAS3 and augments PD-L1 through miR-BART5/PIAS3/pSTAT3/PD-L1 axis control. This contributes to antiapoptosis, tumor cell proliferation, invasion and migration, as well as immune escape, furthering gastric carcinoma progression and worsening the clinical outcome, especially in the PD-L1(+) group of patients with EBV-associated gastric carcinomas. miR-BART5-5p may, therefore, be amenable to PD-1/PD-L1 immune checkpoint inhibitor therapy.
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Antígeno B7-H1/metabolismo , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , MicroARNs/genética , Chaperonas Moleculares/metabolismo , Proteínas Inhibidoras de STAT Activados/metabolismo , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/mortalidad , Apoptosis , Antígeno B7-H1/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/virología , Regulación Neoplásica de la Expresión Génica , Humanos , Chaperonas Moleculares/genética , Pronóstico , Proteínas Inhibidoras de STAT Activados/genética , Factor de Transcripción STAT3/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/virología , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
BACKGROUND AND AIM: The purpose of this study was to investigate the long-term oncologic outcomes after stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC). METHODS: A total of 290 patients with HCC were registered between March 2007 and July 2013. A dose of 10-15 Gy per fraction was given over three to four consecutive days, resulting in a total dose of 30-60 Gy. Overall and recurrence-free survivals were estimated from the date of the start of SBRT to the date of death, the last follow-up examination, or to the date of tumor recurrence. RESULTS: The median follow-up period of all patients was 38.2 months, and the median tumor size was 1.7 cm. Overall survival (OS) rate at 5 years was 44.9%. Multivariate analyses revealed that age, Child-Pugh class, tumor size, and albumin levels were significant factors for OS. The 5-year local control rate was 91.3%. In multivariate analysis, tumor size and albumin were significantly associated with local tumor control. However, there was a negative correlation between total dose and tumor size in Pearson's correlation analysis (r = -0.111, P = 0.046). CONCLUSIONS: Stereotactic body radiation therapy was an excellent ablative treatment option for patients with small HCC. Tumor size was a significant factor for local tumor control after SBRT, although the total dose was negatively correlated with tumor size. Considering the low OS rates and the high local tumor control rates, the combined SBRT and systemic therapies may be beneficial for improving survival outcomes.
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Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiocirugia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radiocirugia/efectos adversos , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Both environmental and genetic factors interact and play a critical role in the pathogenesis of endometriosis. We analyzed the plasma levels of 12 polychlorinated biphenyl (PCB) congeners with genetic polymorphisms of glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and aryl hydrocarbon receptor repressor (AhRR) codon 185. Total sum of the 12 congeners was significantly higher in the controls compared with endometriosis group. Women without C/C genotype in AhRR codon 185 had a significantly increased risk of endometriosis compared with those with C/C genotype. Total sum of the 12 congeners was significantly higher in women without C/C genotype compared with those with C/C genotype. Adjusting for age and AhRR codon 185 genotype, there was no significant association between exposure to PCBs and the risk of endometriosis. These findings suggest a possible presence of gene-environment interaction, however, we could not see any clear association between exposure to PCBs and the risk of endometriosis.
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Endometriosis , Enfermedades del Ovario , Bifenilos Policlorados/sangre , Polimorfismo Genético , Adulto , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Estudios de Casos y Controles , Progresión de la Enfermedad , Endometriosis/sangre , Endometriosis/epidemiología , Endometriosis/genética , Endometriosis/patología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Predisposición Genética a la Enfermedad , Glutatión Transferasa/genética , Humanos , Enfermedades del Ovario/sangre , Enfermedades del Ovario/epidemiología , Enfermedades del Ovario/genética , Enfermedades del Ovario/patología , Bifenilos Policlorados/efectos adversos , Proteínas Represoras/genética , República de Corea/epidemiología , Factores de RiesgoRESUMEN
The high abundance of mitochondria and the expression of mitochondrial uncoupling protein 1 (UCP1) confer upon brown adipose tissue (BAT) the unique capacity to convert chemical energy into heat at the expense of ATP synthesis. It was long believed that BAT is present only in infants, and so, it was not considered as a potential therapeutic target for metabolic syndrome; however, the discovery of metabolically active BAT in adult humans has re-stimulated interest in the contributions of BAT metabolic regulation and dysfunction to health and disease. Here we demonstrate that brown adipocyte autophagy plays a critical role in the regulation BAT activity and systemic energy metabolism. Mice deficient in brown adipocyte autophagy due to BAT-specific deletion of Atg7-a gene essential for autophagosome generation-maintained higher mitochondrial content due to suppression of mitochondrial clearance and exhibited improved insulin sensitivity and energy metabolism. Autophagy was upregulated in BAT of older mice compared to younger mice, suggesting its involvement in the age-dependent decline of BAT activity and metabolic rate. These findings suggest that brown adipocyte autophagy plays a crucial role in metabolism and that targeting this pathway may be a potential therapeutic strategy for metabolic syndrome.