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BACKGROUND: Left ventricular hypertrabeculation (LVHT) is a heterogeneous entity with life-threatening complications and variable prognosis. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVHT is comparatively complex for clinical practice. This study aimed to develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVHT. METHODS: This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2009 and December 2020 at Fuwai Hospital (derivation cohort, n = 300; internal validation cohort, n = 129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort, n = 95). The derivation/internal validation cohorts and the external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors in the multivariable Cox regression predictive model for MACE, and underwent both internal and external validations to confirm its discrimination, calibration, and clinical applicability. RESULTS: A total of 524 LVHT patients (43.5 ± 16.6 years, 65.8% male) were included in the study. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement, and left ventricular ejection fraction ≤ 40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell's C-index of 0.821 [95% confidence interval (CI), 0.772-0.869], 0.786 (95%CI, 0.703-0.869), and 0.750 (95%CI, 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVHT. According to decision curve analysis, the ABLE-SCORE displayed greater net benefits than the existing risk score for LVHT, indicating its strength in clinical applicability. CONCLUSIONS: A simplified and efficient risk score for MACE was developed and validated using a large LVHT cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVHT.
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Enfermedades Cardiovasculares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Longitudinales , Medición de Riesgo/métodos , Anciano , Factores de Riesgo , Adulto , Pronóstico , Estudios de CohortesRESUMEN
BACKGROUND: The stress hyperglycemia ratio (SHR) has been demonstrated as an independent risk factor for acute kidney injury (AKI) in certain populations. However, this relationship in patients with congestive heart failure (CHF) remains unclear. Our study sought to elucidate the relationship between SHR and AKI in patients with CHF. METHODS: A total of 8268 patients with CHF were included in this study. We categorized SHR into distinct groups and evaluated its association with mortality through logistic or Cox regression analyses. Additionally, we applied the restricted cubic spline (RCS) analysis to explore the relationship between SHR as a continuous variable and the occurrence of AKI. The primary outcome of interest in this investigation was the incidence of AKI during hospitalization. RESULTS: Within this patient cohort, a total of 5,221 (63.1%) patients experienced AKI during their hospital stay. Upon adjusting for potential confounding variables, we identified a U-shaped correlation between SHR and the occurrence of AKI, with an inflection point at 0.98. When the SHR exceeded 0.98, for each standard deviation (SD) increase, the risk of AKI was augmented by 1.32-fold (odds ratio [OR]: 1.32, 95% CI: 1.22 to 1.46). Conversely, when SHR was below 0.98, each SD decrease was associated with a pronounced increase in the risk of AKI. CONCLUSION: Our study reveals a U-shaped relationship between SHR and AKI in patients with CHF. Notably, we identified an inflection point at an SHR value of 0.98, signifying a critical threshold for evaluating AKI in this population.
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Lesión Renal Aguda , Insuficiencia Cardíaca , Hiperglucemia , Humanos , Estudios Retrospectivos , Factores de Riesgo , Hiperglucemia/diagnóstico , Hiperglucemia/epidemiología , Hiperglucemia/complicaciones , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicacionesRESUMEN
AIMS: Advanced atrial fibrillation (AF) is currently a dilemma for electrophysiologists when choosing a minimally invasive treatment strategy. Previous studies have demonstrated the outcome of either catheter ablation or thoracoscopic surgical ablation (SA) is unsatisfactory in these patients. Whether hybrid ablation (HA) could improve outcomes in these patients is unknown. The purpose of this study was to evaluate the clinical efficacy of HA for the treatment of advanced AF. METHODS AND RESULTS: A randomized controlled trial was designed to enrol patients with persistent AF (PerAF) and enlarged left atrium or long-standing persistent AF (LSPAF) who were randomized to HA or thoracoscopic SA at a 1:1 ratio. The primary endpoint was freedom from any recurrence of AF off antiarrhythmic drugs (AADs) 12 months after operation. The primary endpoint was monitored by 7-day electrocardiogram monitoring devices. One hundred patients were enrolled. The mean age was 58.5 ± 7.6 years, and the mean left atrial diameter (LAD) was 50.1 ± 6.1â mm. At 12 months, freedom from AF off AADs was recorded in 71.4% (35/49) of patients in HA group and 45.8% (22/48) in SA group [odds ratio 2.955, 95% confidence interval (1.275-6.848), P = 0.014]. HA significantly reduced patients' AF burden (30.2% in SA group and 14.8% in HA group, P = 0.048) and the LAD (mean differences: -5.53 ± 4.97â mm in HA group and -3.27 ± 5.20â mm in SA group, P = 0.037) at 12 months after operation. CONCLUSION: In patients with PerAF and enlarged left atrium or LSPAF, HA achieved better freedom from AF after 1 year of follow-up compared with thoracoscopic SA.
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Fibrilación Atrial , Ablación por Catéter , Recurrencia , Toracoscopía , Humanos , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Masculino , Femenino , Ablación por Catéter/métodos , Persona de Mediana Edad , Estudios Prospectivos , Toracoscopía/métodos , Resultado del Tratamiento , Venas Pulmonares/cirugía , Venas Pulmonares/fisiopatología , Antiarrítmicos/uso terapéutico , Anciano , Factores de Tiempo , Electrocardiografía AmbulatoriaRESUMEN
INTRODUCTION: Sepsis-associated acute kidney injury (SA-AKI) is strongly associated with poor prognosis. We aimed to build a machine learning (ML)-based clinical model to predict 1-year mortality in patients with SA-AKI. METHODS: Six ML algorithms were included to perform model fitting. Feature selection was based on the feature importance evaluated by the SHapley Additive exPlanations (SHAP) values. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminatory ability of the prediction model. Calibration curve and Brier score were employed to assess the calibrated ability. Our ML-based prediction models were validated both internally and externally. RESULTS: A total of 12,750 patients with SA-AKI and 55 features were included to build the prediction models. We identified the top 10 predictors including age, ICU stay and GCS score based on the feature importance. Among the six ML algorithms, the CatBoost showed the best prediction performance with an AUROC of 0.813 and Brier score of 0.119. In the external validation set, the predictive value remained favorable (AUROC = 0.784). CONCLUSION: In this study, we developed and validated a ML-based prediction model based on 10 commonly used clinical features which could accurately and early identify the individuals at high-risk of long-term mortality in patients with SA-AKI.
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Lesión Renal Aguda , Aprendizaje Automático , Sepsis , Humanos , Lesión Renal Aguda/mortalidad , Sepsis/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , AlgoritmosRESUMEN
The polysilicate aluminum ferric (PSAF) was synthesized via copolymerization of polysilicic acid (PSi), AlCl3 and FeCl3 for treating oily wastewater from Daqing gas field. This study investigated the effects of key preparation factors such as the degree of PSi's preactivation and the ratio of (Fe + Al)/Si and Al/Fe on both polymerization and coagulation performance exhibited by PSAF. To determine the optimal timing for introducing Al3+ and Fe3+, zeta potential, viscosity and particle size were investigated. Additionally, infrared spectroscopy, X-ray powder diffraction, polarizing microscopy and scanning electron microscope analysis were employed to investigate the structure and morphology of PSAF. The results indicate that under conditions characterized by a SiO2 mass fraction of 2.5% and pH = 4.5, an optimal timing for introducing Al3+ and Fe3+ is at 100 min when PSi exhibits moderate polymerization along with sufficient stability. When considering molar ratios such as (Al + Fe)/Si being 6:4 and Al/Fe being 5:5, respectively, PSAF falls within a "stable zone" enabling storage period up to 32 days. Moreover, Jar test results demonstrate that at a dosage of 200 mg/L PSAF for oily wastewater treatment in gas fields could reach the maximum turbidity removal efficiency up to 99.5% while oil removal efficiency reach 88.6% without pH adjustment. The copolymerization facilitates the formation of larger PSAF aggregates with positive potential, thereby augmenting the coagulants' adsorption bridging and charge neutralization capabilities. As a result, PSAF has great potential as a practical coagulant for treating oil-containing wastewater in industrial settings.
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Aguas Residuales , Purificación del Agua , Aluminio/química , Dióxido de Silicio , Polímeros , Hierro/química , Purificación del Agua/métodos , Compuestos Férricos/químicaRESUMEN
Sepsis-induced acute respiratory distress syndrome (ARDS) is a devastating clinically severe respiratory disorder, and no effective therapy is available. Melatonin (MEL), an endogenous neurohormone, has shown great promise in alleviating sepsis-induced ARDS, but the underlying molecular mechanism remains unclear. Using a lipopolysaccharide (LPS)-treated mouse alveolar macrophage cell line (MH-S) model, we found that MEL significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation in LPS-treated macrophages, whereas this inhibitory effect of MEL was weakened in MH-S cells transfected with glucose transporter 1 (GLUT1) overexpressing lentivirus. Further experiments showed that MEL downregulated GLUT1 via inhibition of hypoxia-inducible factor 1 (HIF-1α). Notably, hydrogen peroxide (H2O2), a donor of reactive oxygen species (ROS), significantly increased the level of intracellular ROS and inhibited the regulatory effect of MEL on the HIF-1α/GLUT1 pathway. Interestingly, the protective effect of MEL was attenuated after the knockdown of melatonin receptor 1A (MT1) in MH-S cells. We also confirmed in vivo that MEL effectively downregulated the HIF-1α/GLUT1/NLRP3 pathway in the lung tissue of LPS-treated mice, as well as significantly ameliorated LPS-induced lung injury and improved survival in mice. Collectively, these findings revealed that MEL regulates the activation of the ROS/HIF-1α/GLUT1/NLRP3 pathway in alveolar macrophages via the MT1 receptor, further alleviating sepsis-induced ARDS.
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Melatonina , Síndrome de Dificultad Respiratoria , Sepsis , Ratones , Animales , Inflamasomas/metabolismo , Macrófagos Alveolares/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Melatonina/farmacología , Melatonina/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Proteínas NLR/metabolismo , Lipopolisacáridos/farmacología , Transportador de Glucosa de Tipo 1 , Peróxido de Hidrógeno/metabolismo , Síndrome de Dificultad Respiratoria/tratamiento farmacológicoRESUMEN
AIMS: The aim of this study was to investigate the outcomes of catheter ablation (CA) in preventing arrhythmic events among patients with symptomatic Brugada syndrome (BrS) who declined implantable cardioverter defibrillator (ICD) implantation. METHODS AND RESULTS: A total of 40 patients with symptomatic BrS were included in the study, of which 18 refused ICD implantation and underwent CA, while 22 patients received ICD implantation. The study employed substrate modification (including endocardial and epicardial approaches) and ventricular fibrillation (VF)-triggering pre-mature ventricular contraction (PVC) ablation strategies. The primary outcomes were a composite endpoint consisting of episodes of VF and sudden cardiac death during the follow-up period. The study population had a mean age of 43.8 ± 9.6 years, with 36 (90.0%) of them being male. All patients exhibited the typical Type 1 BrS electrocardiogram pattern, and 16 (40.0%) were carriers of an SCN5A mutation. The Shanghai risk scores were comparable between the CA and the ICD groups (7.05 ± 0.80 vs. 6.71 ± 0.86, P = 0.351). Ventricular fibrillation-triggering PVCs were ablated in 3 patients (16.7%), while VF substrates were ablated in 15 patients (83.3%). Epicardial ablation was performed in 12 patients (66.7%). During a median follow-up of 46.2 (17.5-73.7) months, the primary outcomes occurred more frequently in the ICD group than in the CA group (5.6 vs. 54.5%, Log-rank P = 0.012). CONCLUSION: Catheter ablation is an effective alternative therapy for improving arrhythmic outcomes in patients with symptomatic BrS who decline ICD implantation. Our findings support the consideration of CA as an alternative treatment option in this population.
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Síndrome de Brugada , Ablación por Catéter , Desfibriladores Implantables , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Síndrome de Brugada/complicaciones , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/cirugía , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/etiología , Fibrilación Ventricular/cirugía , China , Electrocardiografía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodosRESUMEN
BACKGROUND: Neuroinflammation plays a vital role in the development and maintenance of neuropathic pain. Recent evidence has proved that bone marrow mesenchymal stem cells (BMSCs) can inhibit neuropathic pain and possess potent immunomodulatory and immunosuppressive properties via secreting a variety of bioactive molecules, such as TNF-α-stimulated gene 6 protein (TSG-6). However, it is unknown whether BMSCs exert their analgesic effect against neuropathic pain by secreting TSG-6. Therefore, the present study aimed to evaluate the analgesic effects of TSG-6 released from BMSCs on neuropathic pain induced by chronic constriction injury (CCI) in rats and explored the possible underlying mechanisms in vitro and in vivo. METHODS: BMSCs were isolated from rat bone marrow and characterized by flow cytometry and functional differentiation. One day after CCI surgery, about 5 × 106 BMSCs were intrathecally injected into spinal cerebrospinal fluid. Behavioral tests, including mechanical allodynia, thermal hyperalgesia, and motor function, were carried out at 1, 3, 5, 7, 14 days after CCI surgery. Spinal cords were processed for immunohistochemical analysis of the microglial marker Iba-1. The mRNA and protein levels of pro-inflammatory cytokines (IL-1ß, TNFα, IL-6) were detected by real-time RT-PCR and ELISA. The activation of the TLR2/MyD88/NF-κB signaling pathway was evaluated by Western blot and immunofluorescence staining. The analgesic effect of exogenous recombinant TSG-6 on CCI-induced mechanical allodynia and heat hyperalgesia was observed by behavioral tests. In the in vitro experiments, primary cultured microglia were stimulated with the TLR2 agonist Pam3CSK4, and then co-cultured with BMSCs or recombinant TSG-6. The protein expression of TLR2, MyD88, p-p65 was evaluated by Western blot. The mRNA and protein levels of IL-1ß, TNFα, IL-6 were detected by real-time RT-PCR and ELISA. BMSCs were transfected with the TSG-6-specific shRNA and then intrathecally injected into spinal cerebrospinal fluid in vivo or co-cultured with Pam3CSK4-treated primary microglia in vitro to investigate whether TSG-6 participated in the therapeutic effect of BMSCs on CCI-induced neuropathic pain and neuroinflammation. RESULTS: We found that CCI-induced mechanical allodynia and heat hyperalgesia were ameliorated by intrathecal injection of BMSCs. Moreover, intrathecal administration of BMSCs inhibited CCI-induced neuroinflammation in spinal cord tissues. The analgesic effect and anti-inflammatory property of BMSCs were attenuated when TSG-6 expression was silenced. We also found that BMSCs inhibited the activation of the TLR2/MyD88/NF-κB pathway in the ipsilateral spinal cord dorsal horn by secreting TSG-6. Meanwhile, we proved that intrathecal injection of exogenous recombinant TSG-6 effectively attenuated CCI-induced neuropathic pain. Furthermore, in vitro experiments showed that BMSCs and TSG-6 downregulated the TLR2/MyD88/NF-κB signaling and reduced the production of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in primary microglia treated with the specific TLR2 agonist Pam3CSK4. CONCLUSIONS: The present study demonstrated a paracrine mechanism by which intrathecal injection of BMSCs targets the TLR2/MyD88/NF-κB pathway in spinal cord dorsal horn microglia to elicit neuroprotection and sustained neuropathic pain relief via TSG-6 secretion.
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Moléculas de Adhesión Celular/metabolismo , Células Madre Mesenquimatosas/metabolismo , Microglía/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Neuralgia/metabolismo , Transducción de Señal/fisiología , Receptor Toll-Like 2/metabolismo , Animales , Células de la Médula Ósea/metabolismo , Moléculas de Adhesión Celular/farmacología , Masculino , Trasplante de Células Madre Mesenquimatosas , Microglía/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismoRESUMEN
AIMS: The study aims to describe the long-term outcome of radiofrequency catheter ablation for ventricular tachycardia (VT) in a large cohort arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. METHODS AND RESULTS: Radiofrequency catheter ablation was performed in 284 ARVC patients due to VT between July 2000 and January 2019. An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation. Activation, entrainment, pace and substrate mapping strategies were used with regional ablation applied. A total of 393 ablation procedures were performed including endocardial approach only (n = 377) and endo and epicardial combined (n = 16). Right ventricular basal free wall was accounted as the primary substrate of VT in 258 (65.6%) patients. There were 81 patients underwent redo ablation procedure (second time = 81; ≥3 times = 28). New targets were observed in 68.8% of redo procedures. There were 171 VT recurrences and 19 deaths occurred during the follow-up. Ventricular tachycardia-free survival rate of the first, second, and last ablation procedure was 56.7%, 73.2%, and 78.1%, respectively. Multivariate analysis showed ≥3 induced VTs in the procedure was correlated with rehospitalized VT recurrence [hazard ratio (HR) 1.467, 95% confidence interval (CI) 1.052-2.046; P = 0.024]. For all-cause mortality, rehospitalized VT and ≥3 induced VTs were the independent risk factors (HR 2.954, 95% CI 1.8068.038; P = 0.034; HR 3.189, 95% CI 1.073-9.482; P = 0.037). CONCLUSION: Endocardial ablation is effective to ARVC VT though it may require repeated procedures. Induced multiple VTs was correlated with worse outcomes.
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Displasia Ventricular Derecha Arritmogénica , Ablación por Catéter , Taquicardia Ventricular , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/cirugía , Endocardio/cirugía , Humanos , Recurrencia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Whether intraoperative positive end-expiratory pressure (PEEP) can reduce the risk of postoperative pulmonary complications remains controversial. We performed a systematic review of currently available literature to investigate whether intraoperative PEEP decreases pulmonary complications in anesthetized patients undergoing surgery. METHODS: We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) that compared intraoperative PEEP versus zero PEEP (ZEEP) for postoperative pulmonary complications in adults. The prespecified primary outcome was postoperative pulmonary atelectasis. RESULTS: Fourteen RCTs enrolling 1238 patients met the inclusion criteria. Meta-analysis using a random-effects model showed a decrease in postoperative atelectasis (relative risk [RR], 0.51; 95% confidence interval [CI], 0.35-0.76; trial sequential analyses [TSA]-adjusted CI, 0.10-2.55) and postoperative pneumonia (RR, 0.48; 95% CI, 0.27-0.84; TSA-adjusted CI, 0.05-4.86) in patients receiving PEEP ventilation. However, TSA showed that the cumulative Z-curve of 2 outcomes crossed the conventional boundary but did not cross the trial sequential monitoring boundary, indicating a possible false-positive result. We observed no effect of PEEP versus ZEEP ventilation on postoperative mortality (RR, 1.78; 95% CI, 0.55-5.70). CONCLUSIONS: The evidence that intraoperative PEEP reduces postoperative pulmonary complications is suggestive but too unreliable to allow definitive conclusions to be drawn.
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Anestesia/métodos , Lesión Pulmonar/prevención & control , Respiración con Presión Positiva/métodos , Complicaciones Posoperatorias/prevención & control , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Data regarding the correlations of biomarkers and AF in HCM patients are rather limited. We sought to explore the associations between the presence of AF and circulating biomarkers reflecting cardiovascular function (N-terminal pro-brain natriuretic peptide, NT-pro BNP), endothelial function (big endothelin-1, big ET-1), inflammation (high-sensitivity C-reactive protein), and myocardial damage (cardiac troponin I, cTnI) in HCM patients with and without left ventricular outflow tract obstruction (LVOTO).In all, 375 consecutive HCM in-hospital patients were divided into an AF group (n = 90) and a sinus rhythm (SR) group (n = 285) according to their medical history and electrocardiogram results.In comparison with the SR group, peripheral concentrations of big ET-1, NT-pro BNP, and cTnI were significantly higher in patients with AF. Only the biomarker of big ET-1, together with palpitation and left atrial diameter (LAD), was independently associated with AF in HCM patients. Ln big ET-1 was positively related to Ln NT-pro BNP, LAD, and heart rate, but negatively related to left ventricular ejection fraction. Combined measurements of big ET-1 ≥ 0.285 pmol/L and LAD ≥ 44.5 mm indicated good predictive values in the presence of AF, with a specificity of 94% and a sensitivity of 85% in HCM patients.Big ET-1 has been identified as an independent determinant of AF, regardless of LVOTO, and is significantly related to parameters representing cardiac function and remodeling in HCM. Big ET-1 might be a valuable index to evaluate the clinical status of AF in HCM patients.
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Fibrilación Atrial/sangre , Cardiomiopatía Hipertrófica/sangre , Endotelina-1/sangre , Volumen Sistólico , Obstrucción del Flujo Ventricular Externo/sangre , Remodelación Ventricular , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , China , Correlación de Datos , Ecocardiografía/métodos , Electrocardiografía/métodos , Femenino , Atrios Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Estudios Retrospectivos , Troponina I/sangre , Obstrucción del Flujo Ventricular Externo/diagnósticoRESUMEN
The transcription factor nuclear factor E2-related factor 2 (Nrf2) is known to control the expression of antioxidant response elements and cytoprotective genes and modulate inflammatory response, helping to ameliorate damage in many diseases. Exactly how Nrf2 regulates innate inflammatory homeostasis remains unclear. In this study, we provide in vitro and in vivo evidence that Nrf2 plays a crucial role in macrophage polarization and acute respiratory distress syndrome (ARDS). We conducted in vitro experiments using a mouse alveolar macrophage cell line as well as primary cultures of macrophages in which cells were exposed to lipopolysaccharide (LPS) or interferon-γ in order to mimic ARDS, in the presence or absence of the Nrf2 activator tert-butylhydroquinone (tBHQ). Using siRNA-mediated Nrf2 knockdown, we showed that Nrf2 inhibited the inflammatory response by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization. At the same time, tBHQ activated Nrf2-mediated inhibition of the p65 nuclear factor-κB pathway and activation of peroxisome proliferator-activated receptor-γ, which play important roles in regulating macrophage polarization. We also conducted in vivo experiments in which mice were given tBHQ with or without intratracheal LPS, then their survival was monitored, lung injury was assessed using histology, and levels of pro- and anti-inflammatory cytokines were assayed in the lungs and serum. Activation of Nrf2 with tBHQ dramatically reduced LPS-induced mortality and lung injury, down-regulated pro-inflammatory mediators and up-regulated anti-inflammatory mediators. These results suggest that Nrf2 can help prevent ARDS progression by promoting M2 polarization of macrophages. Interfering with Nrf2 may be an effective strategy for reprogramming macrophage polarization in order to treat ARDS.
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Polaridad Celular , Macrófagos/patología , Factor 2 Relacionado con NF-E2/metabolismo , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/prevención & control , Tráquea/metabolismo , Animales , Línea Celular , Polaridad Celular/efectos de los fármacos , Citocinas/metabolismo , Hidroquinonas/farmacología , Hidroquinonas/uso terapéutico , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/metabolismoRESUMEN
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable myocardium disorder that predominantly affects the ventricle. Little is known about atrial involvement. This study aimed to assess atrial involvement, especially the role of genotype on atrium in ARVC. METHODS: The incidence, characterization and predictors of atrial involvement were investigated. Nine known ARVC-causing genes were screened and the correlation between genotype and atrial involvement was assessed. RESULTS: Right atrium (RA) dilation, left atrium (LA) dilation, and sustained atrial tachyarrhythmias (ATa) were found in 45, 16 and 3 patients, respectively. Gene mutations were identified in 64 (64.0%) patients. Mutation carriers showed more RA dilation than noncarriers (54.7% vs. 27.8%, P = 0.009), and no difference in LA dilation and ATa. Multivariate analysis showed tricuspid regurgitation (OR: 18.867; 95% CI: 1.466-250.000; P = 0.024) increased the risk of RA dilation and decreased left ventricular ejection fraction (LVEF) (OR: 1.134; 95% CI: 1.002-1.272; P = 0.031) correlated with LA dilation, whereas genotype showed no significant effect. At a median follow-up time of 91 months, 7 patients died and 1 patient accepted heart transplantation. New-onset RA dilation, LA dilation, and sustained ATa were found in 8, 7, and 6 patients, respectively. Atrial involvement was not associated with the long-term survival. Despite mutation carriers showing more RA dilation, Kaplan-Meier analysis showed genotype was not associated with atrial involvement. CONCLUSION: Atrial involvement was common in ARVC. Tricuspid regurgitation and decreased LVEF increased the risk for atrial dilation. Genotype was not associated with atrial involvement.
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Displasia Ventricular Derecha Arritmogénica/genética , Fibrilación Atrial/etiología , Aleteo Atrial/etiología , Función del Atrio Izquierdo , Función del Atrio Derecho , Ablación por Catéter , Atrios Cardíacos/fisiopatología , Mutación , Taquicardia Supraventricular/etiología , Potenciales de Acción , Adulto , Antiarrítmicos/uso terapéutico , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Aleteo Atrial/diagnóstico , Aleteo Atrial/fisiopatología , Aleteo Atrial/terapia , Remodelación Atrial , Femenino , Predisposición Genética a la Enfermedad , Atrios Cardíacos/cirugía , Frecuencia Cardíaca , Trasplante de Corazón , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Derivación y Consulta , Factores de Riesgo , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatología , Taquicardia Supraventricular/terapia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with systolic heart failure. Unlike conventional biventricular pacing (BIP), the left ventricular multipoint pacing (MPP) can increase the number of left ventricular pacing sites via a quadripolar lead positioned in the coronary sinus. This synthetic study was conducted to integratively and quantitatively evaluate the clinical outcome of MPP in comparison with BIP. We systematically searched the databases of EMBASE, Ovid medline, and Cochrane Library through May 2018 for studies comparing the clinical outcome of MPP with BIP in the patients who accepted CRT. Hospitalization for reason of heart failure, left ventricular eject fraction (LVEF), CRT response, all-cause morbidity, and cardiovascular death rate was collected for meta-analysis. A total of 11 studies with 29,606 participants were included in this meta-analysis. Compared with BIP group, MPP decreased heart failure hospitalization (OR, 0.41; 95% CI, 0.33 to 0.50; P < 0.00001), improved LVEF (mean difference, 4.97; 95% CI, 3.11 to 6.83; P < 0.00001), increased CRT response (OR, 3.64; 95% CI, 1.68 to 7.87; P = 0.001), and decreased all-cause morbidity (OR, 0.41; 95% CI, 0.26-0.66; P = 0.0002) and cardiovascular death rate (OR, 0.21; 95% CI, 0.11-0.40; P < 0.00001). The published literature demonstrates that MPP was more effective than BIP in the heart failure patients who accepted cardiac resynchronization therapy.
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Terapia de Resincronización Cardíaca/métodos , Insuficiencia Cardíaca/terapia , Disfunción Ventricular Izquierda/terapia , Función Ventricular Izquierda , Terapia de Resincronización Cardíaca/efectos adversos , Dispositivos de Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/fisiopatología , Hospitalización , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Volumen Sistólico , Resultado del Tratamiento , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
This study aimed to prospectively evaluate the safety and efficacy of a new developed method that uses percutaneous ultrasound-guided hematoma aspiration followed by targeted localized manual compression for treatment of femoral artery pseudoaneurysm after cardiac catheterization, which obviates thrombin use, surgery, and long-time compression.From January 2007 to July 2014, 32 patients (17 women; mean age, 55.3 ± 11.5 years) out of 8,725 consecutive cases undergoing cardiac catheterization via femoral access developed one pseudoaneurysm each ranging in size from 21 × 11 mm to 72 × 39 mm. Under ultrasound guidance, blood within the pseudoaneurysm was aspirated percutaneously using an 18-gauge needle, while the pseudoaneurysm neck and a nearby site over the pseudoaneurysm were manually compressed for 15 min. All patients underwent repeat ultrasound examination 24 hours later.Of the 32 pseudoaneurysms, 31 were successfully occluded, and 1 recurred in a patient with coexisting arteriovenous fistula, yielding an overall success rate of 96.9% (31/32). No further recurrence or procedure related complications were observed. The treatment approach is unlike open surgical repair with hematoma evacuation and arterial defect suturing, in that it entails hematoma aspiration and feeding flow blockage at the pseudoaneurismal neck.In this preliminary experience, combining percutaneous ultrasound-guided hematoma aspiration and manual compression appears safe and effective in treating femoral artery pseudoaneurysms after catheterization and avoids thrombin use, long-time compression, and surgery.
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Aneurisma Falso/cirugía , Cateterismo Cardíaco/efectos adversos , Arteria Femoral , Hematoma/diagnóstico por imagen , Hematoma/cirugía , Succión , Adulto , Anciano , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Femenino , Hematoma/etiología , Humanos , Masculino , Persona de Mediana Edad , Palpación , UltrasonografíaRESUMEN
BACKGROUND: Whether patients with asymptomatic atrial fibrillation (AF) could benefit from radiofrequency catheter ablation (RFCA) remains unclear. This study aimed to compare the outcomes of RFCA between asymptomatic and symptomatic AF. METHODS: Sixty-six patients with asymptomatic persistent AF who underwent the primary ablation for AF were enrolled; 132 patients with symptomatic persistent AF were matched using propensity score matching. All patients underwent circumferential pulmonary vein isolation in combination with linear ablation using AF termination as the primary procedural endpoint. RESULTS: Sinus rhythm (SR) was restored by ablation in 18 (27.3%) patients in the asymptomatic group and 93 (70.5%) in the symptomatic group (P < 0.001). Combined with intravenous infusion of ibutilide (1 mg), the numbers were 45 (68.2%) and 116 (87.8%), respectively (P = 0.001). At 1-year follow-up, SR was present in 23 (34.8%) patients in the asymptomatic group and 78 (59.1%) in the symptomatic group without any antiarrhythmic medication after a single procedure (P = 0.001). Of the 43 patients experiencing recurrence in the asymptomatic group, 16 (37.2%) had recurrent atrial tachycardia (AT)-related symptoms. Multivariate analysis showed that asymptomatic AF was independently associated with AF failed to be terminated by ablation (OR: 7.1; 95% CI: 3.4 to 14.9; P < 0.001) and recurrence (OR: 2.2; 95% CI: 1.1 to 4.4; P = 0.018). Patients with asymptomatic AF showed less improvement in quality of life postablation than those with symptoms. CONCLUSION: Current catheter ablation techniques showed worse outcomes in asymptomatic AF patients than in those with symptoms. Recurrent AT could cause significant symptoms in previously asymptomatic patients.
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Fibrilación Atrial/cirugía , Ablación por Catéter , Venas Pulmonares/cirugía , Enfermedades Asintomáticas , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Ablación por Catéter/efectos adversos , Distribución de Chi-Cuadrado , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Puntaje de Propensión , Venas Pulmonares/fisiopatología , Calidad de Vida , Recuperación de la Función , Recurrencia , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: This study was aimed to report the characteristics and treatment of ventricular tachycardia (VT) following surgical treatment of pulmonary stenosis with intact ventricular septum. METHODS AND RESULTS: Five patients underwent radiofrequency catheter ablation for sustained monomorphic left bundle branch block (LBBB) type VT who previously underwent surgical treatment of pulmonary stenosis. Except stimulation, voltage and activation mapping was performed using three-dimensional (3D) electro-anatomic mapping and ablation was applied accordingly. Four VTs were induced during EP study. Two VTs were focal and the earliest activity was targeted in the right ventricular apex (RVA). The other two VTs were reentrant and the critical isthmus located in the mid-lateral wall and anterior wall of right ventricle, respectively. Ablation abolished all inducible VTs in four patients. In the patient whose VT was non-inducible, radiofrequency (RF) energy was delivered to the RVA where pacing mapping matched the clinical VT. One focal VT recurred 60 months after the initial RF ablation. Repeat mapping and ablation was performed and no VT recurred over a 24-month period. CONCLUSIONS: The mechanism of VT following surgical treatment of pulmonary stenosis can be either focal or reentrant. Ablation of this subgroup of VT is feasible.
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Estimulación Cardíaca Artificial/métodos , Ablación por Catéter/métodos , Complicaciones Posoperatorias/terapia , Estenosis de la Válvula Pulmonar/cirugía , Taquicardia Ventricular/terapia , Procedimientos Quirúrgicos Torácicos/efectos adversos , Adulto , Antiarrítmicos/uso terapéutico , Bloqueo de Rama/fisiopatología , Electrocardiografía , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Taquicardia Ventricular/etiologíaRESUMEN
Herein is reported a study of asymmetric decarboxylative Mannich addition reactions between (Ss)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine and Schiff bases derived from various aldehydes and lithium 2,2-diphenylglycinate. These reactions proceed with excellent diastereoselectivities and good chemical yields, providing a practical method for preparation of trifluoromethyl-containing vicinal diamines. The procedures can be conducted under convenient conditions, rendering this approach of high synthetic value.
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Diaminas/síntesis química , Hidrocarburos Fluorados/química , Descarboxilación , Diaminas/química , Estructura MolecularRESUMEN
A Cu-catalyzed asymmetric detrifluoroacetylative aldol addition reaction of 2-fluoro-1,3-diketones/hydrates to aldehydes in the presence of base and chiral bidentate ligand was developed. The reaction was carried out under convenient conditions and tolerated a wide range of substrates, resulting in fluorinated quaternary stereogenic α-fluoro-ß-hydroxy ketone products with good chemical yields, diastereo- and enantioselectivities. This catalytic asymmetric detrifluoroacetylative aldol addition reaction provides a new approach for the preparation of biologically relevant products containing C-F quaternary stereogenic centers.
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Aldehídos/química , Aldehídos/síntesis química , Cobre/química , Hidrocarburos Fluorados/síntesis química , Cetonas/química , Compuestos Organometálicos/química , Catálisis , Halogenación , Hidrocarburos Fluorados/química , Modelos Moleculares , Estructura MolecularRESUMEN
BACKGROUND: The long-term outcome of radiofrequency catheter ablation in persistent atrial fibrillation (AF) patients remains controversial due to different procedural strategies. This study aimed to present the clinical outcome of a pure linear ablation approach without circumferential pulmonary vein isolation (CPVI) over an extended (>5 years) follow-up period. METHODS: From January 2005 to December 2009, 120 consecutive patients (94 men; age, 53.6 ± 10.3 years) with drug-refractory persistent AF that underwent pure linear ablation using AF termination as the desired procedural endpoint were enrolled. RESULTS: In the primary procedure, sinus rhythm was restored by ablation in 75 (62.5%) patients, and the remaining 45 patients in whom AF could not be terminated by ablation received electrical cardioversion. During a median follow-up period of 5.1 (range 3.2-7.5) years, sinus rhythm was maintained in 48 (40.0%) patients without any antiarrhythmic drugs after a single procedure. There was a higher long-term success in the patients in whom AF was terminated by ablation than in those requiring cardioversion (49.3 vs. 24.4%; P = 0.007). CONCLUSION: Linear catheter ablation without CPVI is effective for persistent AF. Patients with AF terminated by ablation were associated with a better long-term outcome than those requiring cardioversion.