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BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.
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The goal of constrained multiobjective evolutionary optimization is to obtain a set of well-converged and well-distributed feasible solutions. To achieve this goal, a delicate tradeoff must be struck among feasibility, diversity, and convergence. However, balancing these three elements simultaneously through a single tradeoff model is nontrivial, mainly because the significance of each element varies in different evolutionary phases. As an alternative approach, we adapt distinct tradeoff models in various phases and introduce a novel algorithm named adaptive tradeoff model with reference points (ATM-R). In the infeasible phase, ATM-R takes the tradeoff between diversity and feasibility into account, aiming to move the population toward feasible regions from diverse search directions. In the semi-feasible phase, ATM-R promotes the transition from "the tradeoff between feasibility and diversity" to "the tradeoff between diversity and convergence." This transition is instrumental in discovering an adequate number of feasible regions and accelerating the search for feasible Pareto optima in succession. In the feasible phase, ATM-R places an emphasis on balancing diversity and convergence to obtain a set of feasible solutions that are both well-converged and well-distributed. It is worth noting that the merits of reference points are leveraged in ATM-R to accomplish these tradeoff models. Also, in ATM-R, a multiphase mating selection strategy is developed to generate promising solutions beneficial to different evolutionary phases. Systemic experiments on a diverse set of benchmark test functions and real-world problems demonstrate that ATM-R is effective. When compared to eight state-of-the-art constrained multiobjective optimization evolutionary algorithms, ATM-R consistently demonstrates its competitive performance.
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A growing body of research suggests that short-chain fatty acids (SCFAs), metabolites produced by intestinal symbiotic bacteria that ferment dietary fibers (DFs), play a crucial role in the health status of symbiotes. SCFAs act on a variety of cell types to regulate important biological processes, including host metabolism, intestinal function, and immune function. SCFAs also affect the function and fate of immune cells. This finding provides a new concept in immune metabolism and a better understanding of the regulatory role of SCFAs in the immune system, which impacts the prevention and treatment of disease. The mechanism by which SCFAs induce or regulate the immune response is becoming increasingly clear. This review summarizes the different mechanisms through which SCFAs act in cells. According to the latest research, the regulatory role of SCFAs in the innate immune system, including in NLRP3 inflammasomes, receptors of TLR family members, neutrophils, macrophages, natural killer cells, eosinophils, basophils and innate lymphocyte subsets, is emphasized. The regulatory role of SCFAs in the adaptive immune system, including in T-cell subsets, B cells, and plasma cells, is also highlighted. In addition, we discuss the role that SCFAs play in regulating allergic airway inflammation, colitis, and osteoporosis by influencing the immune system. These findings provide evidence for determining treatment options based on metabolic regulation.
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Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Interacciones Microbiota-Huesped , Inmunidad , Ácidos Grasos Volátiles/biosíntesis , Ácidos Grasos Volátiles/química , Ácidos Grasos Volátiles/metabolismo , Inmunidad Innata , Humanos , Animales , Transducción de Señal , Inflamación/inmunología , Inflamación/metabolismoRESUMEN
Constrained multiobjective optimization problems (CMOPs) involve both conflicting objective functions and various constraints. Due to the presence of constraints, CMOPs' Pareto-optimal solutions are very likely lying on constraint boundaries. The experience from the constrained single-objective optimization has shown that to quickly obtain such an optimal solution, the search should surround the boundary of the feasible region from both the feasible and infeasible sides. In this article, we extend this idea to cope with CMOPs and, accordingly, we propose a novel constrained multiobjective evolutionary algorithm with bidirectional coevolution, called BiCo. BiCo maintains two populations, that is: 1) the main population and 2) the archive population. To update the main population, the constraint-domination principle is equipped with an NSGA-II variant to move the population into the feasible region and then to guide the population toward the Pareto front (PF) from the feasible side of the search space. While for updating the archive population, a nondominated sorting procedure and an angle-based selection scheme are conducted in sequence to drive the population toward the PF within the infeasible region while maintaining good diversity. As a result, BiCo can get close to the PF from two complementary directions. In addition, to coordinate the interaction between the main and archive populations, in BiCo, a restricted mating selection mechanism is developed to choose appropriate mating parents. Comprehensive experiments have been conducted on three sets of CMOP benchmark functions and six real-world CMOPs. The experimental results suggest that BiCo can obtain quite competitive performance in comparison to eight state-of-the-art-constrained multiobjective evolutionary optimizers.
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Penile squamous cell carcinoma (PSCC) is a rare malignancy with poor survival after standard treatment. Although genomic alterations of PSCC have been characterized in several latest studies, the association between the formation of somatic landscape and regional lymph node metastasis (LNM), an important predictor for patient survival, has not been comprehensively investigated. Here, we collected formalin-fixed paraffin-embedded tumor tissue and matched normal samples of 32 PSCC patients, including 14 LNM patients and 18 clinically node-negative patients, to implement a whole-exome sequencing. Comparison of genomic features among different lymph node status subgroups was conducted after genomic profiling and its effects on patient survival were explored. Top-ranked recurrent gene mutants in our PSCC cohort were TP53 (13/32), NOTCH1 (12/32), CDKN2A (11/32), TTN (9/32) and FAT1 (8/32), mainly identified in the Notch, Hippo, cell cycle, TP53, RTK-RAS and PI3K pathways. While CDKN2A was confirmed to be the driver gene in all PSCC patients, certain gene mutants were significantly enriched in LNM involved patients, including TP53 (9/14 vs. 4/18, p = 0.029) and GBF1 (4/14 vs. 0/18, p = 0.028). Overall survival stratification of PSCC patients were found to be significantly correlated with mutations of three genes, including PIK3CA (Hazard ratio [HR] = 4.15, p = 0.029), CHD7 (HR = 4.82, p = 0.032) and LAMC3 (HR = 15.9, p < 0.001). PIK3CA and LAMC3 held a higher prevalence in patients with LNM compared to those without LNM (PIK3CA: 3/14 vs. 1/18, LAMC3: 2/14 vs. 1/18). Our finding demonstrated that genomic divergence exists across PSCC patients with different lymph node statuses, and it may be correlated with their survival outcome. It helps delineate somatic evolution during tumor progression and perfect potential therapeutic intervention in this disease.
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OBJECTIVES: The aim of this study was to explore the difference in target vessel failure (TVF) 3 years after intravascular ultrasound (IVUS) guidance versus angiographic guidance among all comers undergoing second-generation drug-eluting stent (DES) implantation. BACKGROUND: The multicenter randomized ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions) trial showed a lower incidence of 1-year TVF after IVUS-guided DES implantation among all comers compared with angiographic guidance. However, the 3-year clinical outcomes of the ULTIMATE trial remain unknown. METHODS: A total of 1,448 all comers undergoing DES implantation who were randomly assigned to either IVUS guidance or angiographic guidance in the ULTIMATE trial were followed for 3 years. The primary endpoint was the risk for TVF at 3 years. The safety endpoint was definite or probable stent thrombosis (ST). RESULTS: At 3 years, TVF occurred in 47 patients (6.6%) in the IVUS-guided group and in 76 patients (10.7%) in the angiography-guided group (p = 0.01), driven mainly by the decrease in clinically driven target vessel revascularization (4.5% vs. 6.9%; p = 0.05). The rate of definite or probable ST was 0.1% in the IVUS-guided group and 1.1% in the angiography-guided group (p = 0.02). Notably, the IVUS-defined optimal procedure was associated with a significant reduction in 3-year TVF relative to that with the suboptimal procedure. CONCLUSIONS: IVUS-guided DES implantation was associated with significantly lower rates of TVF and ST during 3-year follow-up among all comers, particularly those who underwent the IVUS-defined optimal procedure compared with those with angiographic guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions; NCT02215915).
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Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Angiografía Coronaria , Humanos , Intervención Coronaria Percutánea , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.
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Síndrome Coronario Agudo/terapia , Aspirina , Duración de la Terapia , Hemorragia , Intervención Coronaria Percutánea , Complicaciones Posoperatorias/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ticlopidina , Adulto , Aspirina/administración & dosificación , Aspirina/efectos adversos , Angiografía Coronaria/métodos , Stents Liberadores de Fármacos , Terapia Antiplaquetaria Doble/métodos , Femenino , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Humanos , Masculino , Estudios Multicéntricos como Asunto/métodos , Evaluación de Procesos y Resultados en Atención de Salud , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Complicaciones Posoperatorias/etiología , Ajuste de Riesgo/métodos , Cirugía Asistida por Computador/métodos , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.
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Angiografía Coronaria/métodos , Enfermedad Coronaria/terapia , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea/métodos , Ultrasonografía Intervencional/métodos , Causas de Muerte , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/patología , Reestenosis Coronaria/etiología , Trombosis Coronaria/etiología , Stents Liberadores de Fármacos/efectos adversos , Humanos , Infarto del Miocardio/etiología , Revascularización Miocárdica , Estudios ProspectivosRESUMEN
Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.
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Criopreservación/métodos , Espermatozoides , Vitrificación , Reacción Acrosómica , Adulto , Humanos , Masculino , Manejo de Especímenes/métodos , Motilidad Espermática , Adulto JovenRESUMEN
This paper studies a multiuser cooperative mobile edge computing offloading (called CoMECO) system in a multiuser interference environment, in which delay-sensitive tasks may be executed on local devices, cooperative devices, or the primary MEC server. In this system, we jointly optimize the offloading decision and computation resource allocation for minimizing the total energy consumption of all mobile users under the delay constraint. If this problem is solved directly, the offloading decision and computation resource allocation are generally generated separately at the same time. Note, however, that they are closely coupled. Therefore, under this condition, their dependency is not well considered, thus leading to poor performance. We transform this problem into a bilevel optimization problem, in which the offloading decision is generated in the upper level, and then the optimal allocation of computation resources is obtained in the lower level based on the given offloading decision. In this way, the dependency between the offloading decision and computation resource allocation can be fully taken into account. Subsequently, a bilevel optimization approach, called BiJOR, is proposed. In BiJOR, candidate modes are first pruned to reduce the number of infeasible offloading decisions. Afterward, the upper-level optimization problem is solved by ant colony system (ACS). Furthermore, a sorting strategy is incorporated into ACS to construct feasible offloading decisions with a higher probability and a local search operator is designed in ACS to accelerate the convergence. For the lower-level optimization problem, it is solved by the monotonic optimization method. In addition, BiJOR is extended to deal with a complex scenario with the channel selection. Extensive experiments are carried out to investigate the performance of BiJOR on two sets of instances with up to 400 mobile users. The experimental results demonstrate the effectiveness of BiJOR and the superiority of the CoMECO system.
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BACKGROUND: To explore the association of platelet activation markers, vitamin D, and antiplatelet drugs resistance in ischemic stroke patients. METHODS: A total of 230 patients with ischemic stroke were enrolled in this study. Platelet aggregation, platelet activation marker (CD62p), and vitamin D were measured after 7-14 days of dual antiplatelet treatment (aspirinâ¯+â¯clopidogrel). All individuals were divided into a drug resistance group and a drug sensitive group according to the platelet maximum aggregation rate induced by antagonist adenosine diphosphate or arachidonic acid. RESULTS: In this study, the prevalence of aspirin resistance was low (1.2%), while the prevalence of clopidogrel resistance (CR) was 24.8%, so we focused on CR. The percentage of CD62p on activated platelet [(25.74 ± 4.61) versus (12.41 ± 3.93), P < .001] and the prevalence of hypertension [93.0% (53) versus 79.8% (138), Pâ¯=â¯.021] in CR group were significantly higher than those in clopidogrel sensitive (CS) group, while the vitamin D concentration [(8.96 ± 4.41) versus (13.9 ± 4.84) ng/mL, Pâ¯=â¯.003] in CR group was significantly lower compared with the CS group. No significant difference was found in soluble P-selectin between these 2 groups [(56.2 ± 16.13) versus (54.2 ± 14.87) ng/mL, Pâ¯=â¯.258], neither in calcium [(2.29 ± .12) versus (2.33 ± .13) mmol/L, Pâ¯=â¯.821]. Logistic regression analysis showed that hypertension (odds ratio [OR] = 5.348, 95% confidence intervals [CI] 1.184-23.350, Pâ¯=â¯.026), expression of platelet CD62p (ORâ¯=â¯1.095, 95% CI 1.052-1.201, Pâ¯=â¯.018) and vitamin D level (ORâ¯=â¯.832, 95% CI .763-.934, Pâ¯=â¯.005) were associated with CR in ischemic stroke patients. CONCLUSIONS: CR in ischemic stroke patients is associated with several independent predictors, including increased platelet activation marker CD62p, decreased vitamin D level, and hypertension.
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Plaquetas/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Clopidogrel/uso terapéutico , Resistencia a Medicamentos , Selectina-P/sangre , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Deficiencia de Vitamina D/sangre , Vitamina D/análogos & derivados , Anciano , Pueblo Asiatico , Aspirina/uso terapéutico , Biomarcadores/sangre , Plaquetas/metabolismo , Isquemia Encefálica/sangre , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnología , China , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/sangre , Hipertensión/etnología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etnología , Resultado del Tratamiento , Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/etnologíaRESUMEN
The performance of many nature-inspired optimization algorithms (NIOAs) depends strongly on their implemented coordinate system. However, the commonly used coordinate system is fixed and not well suited for different function landscapes, NIOAs thus might not search efficiently. To overcome this shortcoming, in this paper we propose a framework, named ACoS, to adaptively tune the coordinate systems in NIOAs. In ACoS, an Eigen coordinate system is established by making use of the cumulative population distribution information, which can be obtained based on a covariance matrix adaptation strategy and an additional archiving mechanism. Since the population distribution information can reflect the features of the function landscape to some extent, NIOAs in the Eigen coordinate system have the capability to identify the modality of the function landscape. In addition, the Eigen coordinate system is coupled with the original coordinate system, and they are selected according to a probability vector. The probability vector aims to determine the selection ratio of each coordinate system for each individual, and is adaptively updated based on the collected information from the offspring. ACoS has been applied to two of the most popular paradigms of NIOAs, i.e., particle swarm optimization and differential evolution, for solving 30 test functions with 30D and 50D at the 2014 IEEE Congress on Evolutionary Computation. The experimental studies demonstrate its effectiveness.
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Type 2 diabetes correlates with clinical events after the implantation of a second-generation drug-eluting stent (DES). The rate and prognostic value of stent fracture (SF) in patients with diabetes who underwent DES implantation remain unknown. A total of 1160 patients with- and 2251 without- diabetes, who underwent surveillance angiography at 1 year after DES implantation between June 2004 and August 2014, were prospectively studied. The primary endpoints included the incidence of SF and a composite major adverse cardiac event [MACE, including myocardial infarction (MI), cardiac death, and target-vessel revascularization (TVR)] at 1-year follow-up and at the end of follow-up for overall patients, and target lesion failure [TLF, including cardiac death, target vessel myocardial infarction (TVMI) and target lesion revascularization (TLR)] at the end of study for SF patients. In general, diabetes was associated with a higher rate of MACE at 1-year (18.4 vs. 12.9%) and end of follow-up (24.0 vs. 18.6%, all p < 0.001), compared with those in patients who did not have diabetes. The 1-year SF rate was comparable among patients with diabetes (n = 153, 13.2%) and non-diabetic patients (n = 273, 12.1%, p > 0.05). Diabetic patients with SF had a 2.6-fold increase of SF-related cardiac death at the end of study and threefold increase of re-repeat TLR when compared with non-diabetic patients with SF (5.9 vs. 2.2%, p = 0.040; 6.5 vs. 2.2%, p = 0.032), respectively. Given the fact that diabetes is correlated with increased MACE rate, SF in diabetic patients translates into differences in mortality and re-repeat TLR compared with the non-diabetic group.
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Enfermedad de la Arteria Coronaria/terapia , Diabetes Mellitus Tipo 2/mortalidad , Intervención Coronaria Percutánea/instrumentación , Falla de Prótesis , Stents , Anciano , Distribución de Chi-Cuadrado , China , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Reestenosis Coronaria/etiología , Reestenosis Coronaria/mortalidad , Reestenosis Coronaria/terapia , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Oportunidad Relativa , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Estudios Prospectivos , Diseño de Prótesis , Retratamiento , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The association of platelet reactivity and clinical outcomes, especially stent thrombosis, was not so clear. We sought to investigate whether high platelet reactivity affects clinical outcomes of patients with drug eluting stents (DESs) implantation. METHODS: All enrolled individuals treated with DESs implantation were evaluated by PL-11, using sequentially platelet counting method. The primary end point was the occurrence of definite and probable stent thrombosis at 2 years. The secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all cause death, spontaneous myocardial infarction (MI), target vessel revascularization (TVR), and ischemic stroke. RESULTS: A total of 1331consecutive patients were enrolled at our center. There were 91 patients (6.8 %) identified with high platelet reactivity (HPR) on aspirin, and 437 patients (32.9 %) with HPR on clopidogrel. At 2-year follow-up, the incidence of stent thrombosis was significantly higher in patients with HPR on aspirin (9.9 % vs. 0.4 %, p < 0.001), and HPR on clopidogrel (3.0 % vs. 0.1 %, p < 0.001). There were increased MACCE in the HPR on aspirin group (16.5 % vs. 8.5 %, p = 0.021), mainly driven by the higher all cause death (7.7 % vs. 1.6 %, p = 0.002) and MI (9.9 % vs. 1.9 %, p < 0.001) in the HPR on aspirin group. Similarly, the rate of MACCE was higher in the HPR on clopidogrel group (12.4 % vs. 7.4 %, p = 0.004). No differences in all bleeding and hemorrhagic stroke were observed. CONCLUSIONS: The present study demonstrated that high platelet reactivity on both aspirin and clopidogrel were associated with incremental stent thrombosis following DESs implantation.
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Plaquetas/fisiología , Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos , Oclusión de Injerto Vascular/prevención & control , Intervención Coronaria Percutánea , Agregación Plaquetaria/fisiología , Anciano , Aspirina/uso terapéutico , Clopidogrel , Enfermedad de la Arteria Coronaria/sangre , Femenino , Estudios de Seguimiento , Oclusión de Injerto Vascular/sangre , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Factores de TiempoRESUMEN
OBJECTIVES: The present study aimed to analyze the incidence of SF and its correlation with clinical events after DES implantation and the outcome of re-intervention for symptomatic in-stent restenosis (ISR) induced by stent fracture (SF). BACKGROUND: SF is associated with a high rate of clinical events after the implantation of drug-eluting stents (DES). However, the chronological rate of SF and the effect of SF on clinical outcomes from a large patient population remain underreported. METHODS: A total of 6,555 patients with 16482 DES in 10751 diseased vessels and surveillance angiography between November 2003 and January 2014 were prospectively studied. The primary endpoints included the incidence of SF, in-stent restenosis (ISR), target lesion revascularization (TLR), and definite stent thrombosis (ST) at the end of follow-up before and after propensity score matching. Clinical outcomes after TLR were also followed up. RESULTS: The SF rate was detected in 803 (12.3%) patients, 3,630 (22.0%) stents, and 1,852 (17.2%) diseased vessels. SF increased over time. SF was associated with higher unadjusted rates of ISR (42.1%), TLR (24.8%, n = 379), and definite ST (4.6%) compared with stents without fracture (10.7%, 6.6%, and 1.03%, all p < 0.001), and the differences remained significant after propensity score matching (all p < 0.05). There was no significant difference in any-cause or cardiac mortality between patients with and without SF. After 1,523 days of follow-up since the first surveillance angiography, repeat ISR was detected in 90 of 379 (23.8%) stents after reintervention, and 6 (7.5%) stents required repeat TLR. CONCLUSIONS: SF is more frequently observed after DES implantation. TLR was required in almost one-fourth of fractured stents. Increased events in the SF group did not translate into a difference in mortality compared with the non-SF group. Reintervention was associated with acceptable clinical results.
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Reestenosis Coronaria/epidemiología , Trombosis Coronaria/epidemiología , Intervención Coronaria Percutánea/instrumentación , Falla de Prótesis , Stents , Anciano , China/epidemiología , Angiografía Coronaria , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/mortalidad , Reestenosis Coronaria/terapia , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/mortalidad , Trombosis Coronaria/terapia , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Prevalencia , Sistema de Registros , Retratamiento , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Many molecular, epidemiological studies have been performed to explore the association between MTHFR A1298C polymorphism and cancer risk. However, the results were inconsistent or even contradictory. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR A1298C (81,040 cases and 114,975 controls from 265 studies) polymorphism. Overall, significant association was observed between MTHFR A1298C polymorphism and cancer risk when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased cervical cancer (dominant model: OR 1.46, 95 % CI 1.13-1.90; AC vs. AA: OR 1.48, 95 % CI 1.13-1.92) and lymphoma (dominant model: OR 1.22, 95 % CI 1.04-1.44; recessive model: OR 1.66, 95 % CI 1.15-2.39; CC vs. AA: OR 1.75, 95 % CI 1.21-2.53) risk were observed in Asians, and significantly decreased colorectal cancer risk was found in Asians (recessive model: OR 0.75, 95 % CI 0.59-0.96; CC vs. AA: OR 0.77, 95 % CI 0.60-1.00). In summary, this meta-analysis suggests that MTHFR A1298C polymorphism is associated with increased cervical cancer and lymphoma risk in Asians, and MTHFR A1298C polymorphism is associated with decreased colorectal cancer risk in Asians. Moreover, this meta-analysis also points out the importance of new studies, such as oral cancer and chronic myeloid leukemia, because they had high heterogeneity in this meta-analysis (I (2) > 75 %).
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Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Neoplasias/genética , Polimorfismo Genético/genética , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , RiesgoRESUMEN
Many molecular epidemiological studies have been performed to explore the association between MTHFR C677T polymorphism and cancer risk in diverse populations. However, the results were inconsistent. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR C677T (150,086 cases and 200,699 controls from 446 studies) polymorphism. Overall, significantly increased cancer risk was found when all eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significantly increased breast cancer risk was found in Asians and Indians, significantly decreased colon cancer risk was found, significantly decreased colorectal cancer risk was found in male population, significantly increased gastric cancer risk was found in Caucasians and Asians, significantly increased hepatocellular cancer risk was found in Asians, significantly decreased adult acute lymphoblastic leukemia (AALL) risk was found in Caucasians, significantly decreased childhood acute lymphoblastic leukemia (CALL) risk was found in Asians, and significantly increased multiple myeloma and NHL risk was found in Caucasians. In summary, this meta-analysis suggests that MTHFR C677T polymorphism is associated with increased breast cancer, gastric cancer, and hepatocellular cancer risk in Asians, is associated with increased gastric cancer, multiple myeloma, and NHL risk in Caucasians, is associated with decreased AALL risk in Caucasians, is associated with decreased CALL risk in Asians, is associated with increased breast cancer risk in Asians, is associated with decreased colon cancer risk, and is associated with decreased colorectal cancer risk in male population. Moreover, this meta-analysis also points out the importance of new studies, such as Asians of HNC, Asians of lung cancer, and Indians of breast cancer, because they had high heterogeneity in this meta-analysis (I(2) > 75%).
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Neoplasias/genética , Alelos , Genotipo , Humanos , Neoplasias/clasificación , Neoplasias/patología , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
AIMS: This study sought to compare angiographic endpoints at one-year follow-up after a drug-eluting stent implantation guided by either intravascular ultrasound (IVUS) or angiography in patients with chronic total occlusion (CTO) lesions. METHODS AND RESULTS: Patients with at least one CTO lesion recanalised successfully were randomly assigned to the IVUS-guided or the angiography-guided group. The use of IVUS for penetration of the true lumen and optimisation of stent expansion was only done in the IVUS-guided group. The primary endpoint was in-stent late lumen loss (LLL) at one-year follow-up. A total of 230 patients with CTO lesions after successful recanalisation were enrolled and followed with office visits or telephone contact up to 24 months. In-stent LLL in the IVUS-guided group was significantly lower compared to the angiography-guided group at one-year follow-up (0.28±0.48 mm vs. 0.46±0.68 mm, p=0.025), with a significant difference in restenosis of the "in-true-lumen" stent between the two groups (3.9% vs.13.7%, p=0.021). The minimal lumen diameter and minimal stent cross-section area significantly and negatively correlated with LLL (all p<0.001). The rates of adverse clinical events were comparable between the IVUS- and angiography-guided groups at two-year follow-up (21.7% vs. 25.2%, p=0.641). CONCLUSIONS: The IVUS-guided stenting of the CTO lesion was associated with less LLL and a lower incidence of "in-true-lumen" stent restenosis. Additional study is required to identify the clinical benefit of the IVUS-guided procedure for CTO lesions. [ChiCTR-TRC-10000996].
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Oclusión Coronaria/cirugía , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea/métodos , Anciano , Enfermedades Cardiovasculares/mortalidad , Angiografía Coronaria , Oclusión Coronaria/diagnóstico por imagen , Reestenosis Coronaria/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Trombosis/epidemiología , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
OBJECTIVES: This study sought to compare the outcomes of fractional flow reserve (FFR)-guided and angiography (Angio)-guided provisional side-branch (SB) stenting for true coronary bifurcation lesions. BACKGROUND: Angio-guided provisional SB stenting after stenting of the main vessel provides favorable outcomes for the majority of coronary bifurcation lesions. Whether an FFR-guided provisional stenting approach is superior has not been studied. METHODS: A total of 320 patients with single Medina 1,1,1 and 0,1,1 coronary bifurcation lesions undergoing stenting with a provisional SB approach were randomly assigned 1:1 to Angio-guided and FFR-guided groups. SB stenting was performed for Thrombolysis In Myocardial Infarction flow grade<3, ostial SB stenosis>70%, or greater than type A dissection after main vessel stenting in the Angio-guided group and for SB-FFR<0.80 in the FFR-guided group. The primary endpoint was the 1-year composite rate of major adverse cardiac events (cardiac death, myocardial infarction, and clinically driven target vessel revascularization). RESULTS: Comparing the Angio-guided and FFR-guided groups, treatment of the SB (balloon or stenting) was performed in 63.1% and 56.3% of lesions respectively (p=0.07); stenting of the SB was attempted in 38.1% and 25.9%, respectively (p=0.01); and, when attempted, stenting was successful in 83.6% and 73.3% of SBs, respectively (p=0.01). The 1-year composite major adverse cardiac event rate was 18.1% in both groups (hazard ratio: 0.91, 95% confidence interval: 0.48 to 1.88; p=1.00). The 1-year target vessel revascularization and stent thrombosis rates were 6.9% and 5.6% (p=0.82) and 1.3% and 0.6% (p=0.56) in the Angio-guided and FFR-guided groups, respectively. CONCLUSIONS: In this multicenter, randomized trial, angiographic and FFR guidance of provisional SB stenting of true coronary bifurcation lesions provided similar 1-year clinical outcomes. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChiCTR-TRC-07000015).