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BACKGROUND: Insulin resistance (IR) is involved in the pathophysiological processes of arrhythmias. Increasing evidence suggests triglyceride and glucose (TyG) index, metabolic score for insulin resistance (METS-IR), triglyceride glucose-body mass index (TyG-BMI), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio are simple and reliable surrogates for IR. Although they have been associated with atrial fibrillation (AF), evidence supporting this is limited. Here, this is the first study to investigate the association between TyG-BMI index and AF recurrence following radiofrequency catheter ablation (RFCA). The performance of the four non-insulin-based IR indexes in predicting AF recurrence after ablation was explored. METHODS: A total of 2242 AF patients who underwent a de novo RFCA between June 2018 to January 2022 at two hospitals in China were included in this retrospective study. The predictive values of IR indexes for AF recurrence after ablation were assessed. RESULTS: During 1-year follow-up, 31.7% of patients experienced AF recurrence. The multivariable analysis revealed that TyG index, METS-IR, and TyG-BMI index were independent risk factors for AF recurrence. Restricted cubic spline analysis revealed a connection between METS-IR, TyG-BMI index, and AF recurrence (P < 0.001). Furthermore, incorporating the METS-IR or TyG-BMI index to the basic risk model with fully adjusted factors considerably enhanced the forecast of AF recurrence, as demonstrated by the C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: TyG index, METS-IR, and TyG-BMI index were independently associated with AF recurrence following ablation. Among the four non-insulin-based IR indexes, TyG-BMI had the highest predictive value, followed by METS-IR.
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Fibrilación Atrial , Resistencia a la Insulina , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Estudios Retrospectivos , Glucosa , Triglicéridos , Glucemia , BiomarcadoresRESUMEN
BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Hiperglucemia , Humanos , Femenino , Anciano , Masculino , Enfermedad de la Arteria Coronaria/diagnóstico , Estudios Retrospectivos , Glucemia/análisis , Factores de RiesgoRESUMEN
BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.
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Biomarcadores , Glucemia , Enfermedades Cardiovasculares , Causas de Muerte , Diabetes Mellitus , Resistencia a la Insulina , Encuestas Nutricionales , Triglicéridos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Glucemia/metabolismo , Medición de Riesgo , Triglicéridos/sangre , Biomarcadores/sangre , Estudios Transversales , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus/mortalidad , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Factores de Tiempo , Pronóstico , Anciano , Adulto , Estados Unidos/epidemiología , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
Many endogenous molecules, mostly proteins, purportedly activate the Toll-like receptor 4 (TLR4)-myeloid differentiation factor-2 (MD-2) complex, the innate immune receptor for lipopolysaccharide (LPS) derived from gram-negative bacteria. However, there is no structural evidence supporting direct TLR4-MD-2 activation by endogenous ligands. Sulfatides (3-O-sulfogalactosylceramides) are natural, abundant sulfated glycolipids that have variously been shown to initiate or suppress inflammatory responses. We show here that short fatty acid (FA) chain sulfatides directly activate mouse TLR4-MD-2 independent of CD14, trigger MyD88- and TRIF-dependent signaling, and stimulate tumor necrosis factor α (TNFα) and type I interferon (IFN) production in mouse macrophages. In contrast to the agonist activity toward the mouse receptor, the tested sulfatides antagonize TLR4-MD-2 activation by LPS in human macrophage-like cells. The agonistic and antagonistic activities of sulfatides require the presence of the sulfate group and are inversely related to the FA chain length. The crystal structure of mouse TLR4-MD-2 in complex with C16-sulfatide revealed that three C16-sulfatide molecules bound to the MD-2 hydrophobic pocket and induced an active dimer conformation of the receptor complex similar to that induced by LPS or lipid A. The three C16-sulfatide molecules partially mimicked the detailed interactions of lipid A to achieve receptor activation. Our results suggest that sulfatides may mediate sterile inflammation or suppress LPS-stimulated inflammation, and that additional endogenous negatively charged lipids with up to six lipid chains of limited length might also bind to TLR4-MD-2 and activate or inhibit this complex.
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Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Antígeno 96 de los Linfocitos/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Sulfoglicoesfingolípidos/farmacología , Receptor Toll-Like 4/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Animales , Línea Celular , Femenino , Humanos , Antígeno 96 de los Linfocitos/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Simulación de Dinámica Molecular , Factor 88 de Diferenciación Mieloide/genética , Sulfoglicoesfingolípidos/química , Receptor Toll-Like 4/genéticaRESUMEN
BACKGROUND: Epicardial adipose tissue (EAT) is recognized as a clinical diagnostic marker for cardiometabolic disease. Thicker EAT may be associated with recurrence of ventricular tachycardia after ablation. The association between EAT volume and recurrence of premature ventricular complexes (PVC) following ablation has not been clarified. We investigated the association between EAT volume and PVC recurrence following radiofrequency catheter ablation.MethodsâandâResults: This retrospective study included 401 patients with PVC undergoing catheter ablation with preprocedural non-contrast computed tomography between 2017 and 2022. The impact of EAT volume in predicting PVC recurrence after ablation was analyzed. The mean (±SD) age of patients was 50.2±13.3 years. Multivariable Cox analysis revealed that a large EAT volume was an independent predictor of PVC recurrence after ablation during a median follow-up of 16.3 months. Kaplan-Meier analysis showed a difference in postablation PVC recurrence between the 2 groups dichotomized around the EAT volume cut-off. The risk of recurrence increased with increasing EAT volume according to restricted cubic spline regression. Furthermore, PVC originating from epicardial locations had larger EAT volumes than those originating from the right ventricular outflow tract. CONCLUSIONS: A large EAT volume was independently associated with PVC recurrence following ablation. Patients with PVC originating from epicardial sites had large EAT volumes. EAT volume may help stratify patients according to their risk of PVC recurrence after ablation.
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BACKGROUND: Pre-procedure liver dysfunction was associated with acute kidney injury after percutaneous coronary intervention (PCI). The aim of this study is to assess and compare the predictive value of different liver function scoring systems for contrast-associated acute kidney injury (CA-AKI) in patients undergoing elective PCI.MethodsâandâResults:A total of 5,569 patients were retrospectively enrolled. The model for end-stage liver disease (MELD) including albumin (MELD-Albumin) score (AUC=0.661) had the strongest predictive value in comparison to the MELD score (AUC=0.627), the MELD excluding the international normalized ratio (MELD-XI) score (AUC=0.560), and the MELD including sodium (MELD-Na) score (AUC=0.652). In the fully adjusted logistic regression model, the MELD-Albumin score and the MELD-Na score were independently associated with CA-AKI regardless of whether they were treated as continuous or categorical variables; however, this was not the case for the MELD score and the MELD-XI score. Furthermore, the addition of the MELD-Albumin score significantly improved the reclassification beyond the fully adjusted logistic regression model. The study further explored the association between different versions of the MELD score and CA-AKI using restricted cubic splines and found a linear relationship between the MELD-Albumin score and the risk of CA-AKI. CONCLUSIONS: The MELD-Albumin score had the highest predictive value for CA-AKI in patients undergoing elective PCI. The addition of the MELD-Albumin score to the existing risk prediction model significantly improved the reclassification for CA-AKI.
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Lesión Renal Aguda , Enfermedad Hepática en Estado Terminal , Intervención Coronaria Percutánea , Lesión Renal Aguda/inducido químicamente , Albúminas , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Humanos , Masculino , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
The outbreak of 2019 novel coronavirus disease (COVID-19) has posed a grave threat to the global public health. The COVID-19-induced infection is closely related to coagulation dysfunction in the affected patients. This paper attempts to conduct a meta-analysis and systematically review the blood coagulation indicators in patients with severe COVID-19. A meta-analysis of eligible studies was performed to compare the blood coagulation indicators in patients with severe and nonsevere COVID-19. PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between 1 December 2019 and 7 May 2020. A total of 13 studies with 1341 adult patients were enrolled in this analysis. Platelet (weighted mean difference [WMD] = -24.83, 95% confidence interval [CI]: -34.12 to -15.54; P < .001), d-dimer (WMD = 0.19, 95% CI: 0.09-0.29; P < .001), and fibrinogen (WMD = 1.02, 95% CI: 0.50-1.54; P < .001) were significantly associated with the severity in patients with COVID-19. The meta-analysis revealed that no correlation was evident between an increased severity risk of COVID-19 and activated partial thromboplastin time (WMD = -1.56, 95% CI: -5.77 to 2.64; P = .468) or prothrombin time (WMD = 0.19, 95% CI: -0.13 to 0.51; P = .243). The single arm meta-analysis showed that compared with the nonsevere group, the severe group had a lower pooled platelet (165.12 [95% CI: 157.38-172.85] vs 190.09 [95% CI: 179.45-200.74]), higher d-dimer (0.49 [95% CI: 0.33-0.64] vs 0.27 [95% CI: 0.20-0.34]), and higher fibrinogen (4.34 [95% CI: 1.98-6.70] vs 3.19 [95% CI: 1.13-5.24]). Coagulation dysfunction is closely related to the severity of patients with COVID-19, in which low platelet, high d-dimer, and fibrinogen upon admission may serve as risk indicators for increased aggression of the disease. These findings are of great clinical value for timely and effective treatment of the COVID-19 cases.
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Trastornos de la Coagulación Sanguínea/virología , COVID-19/complicaciones , Plaquetas , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Hospitalización , Humanos , Tiempo de Tromboplastina Parcial , Pronóstico , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: This study aimed to investigate the connection between malnutrition evaluated by the Controlling Nutritional Status (CONUT) score and the risk of contrast-associated acute kidney injury (CA-AKI) in elderly patients who underwent percutaneous coronary intervention (PCI). METHODS: A total of 1308 patients aged over 75 years undergoing PCI was included. Based on the CONUT score, patients were assigned to normal (0-1), mild malnutrition (2-4), moderate-severe malnutrition group (≥ 5). The primary outcome was CA-AKI (an absolute increase in ≥ 0.3 mg/dL or ≥ 50% relative serum creatinine increase 48 h after contrast medium exposure). RESULTS: Overall, the incidence of CA-AKI in normal, mild, moderate-severe malnutrition group was 10.8%, 11.0%, and 27.2%, respectively (p < 0.01). Compared with moderate-severe malnutrition group, the normal group and the mild malnutrition group showed significant lower risk of CA-AKI in models adjusting for risk factors for CA-AKI and variables in univariate analysis (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.26-0.89, p = 0.02; OR = 0.46, 95%CI: 0.26-0.82, p = 0.009, respectively). Furthermore, the relationship were consistent across the subgroups classified by risk factors for CA-AKI except anemia. The risk of CA-AKI related with CONUT score was stronger in patients with anemia. (overall interaction p by CONUT score = 0.012). CONCLUSION: Moderate-severe malnutrition is associated with higher risk of CA-AKI in elderly patients undergoing PCI.
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Lesión Renal Aguda/epidemiología , Medios de Contraste/efectos adversos , Desnutrición/complicaciones , Estado Nutricional , Lesión Renal Aguda/inducido químicamente , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Gravedad del Paciente , Intervención Coronaria Percutánea , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIM: We investigated whether perioperative urine pH was associated with contrast-associated acute kidney injury (CA-AKI) in patients undergoing emergency percutaneous coronary intervention (PCI). METHODS: The study enrolled 1109 consecutive patients undergoing emergency PCI. Patients were divided into three groups based on perioperative urine pH (5.0-6.0, 6.5- 7.0, 7.5-8.5). The primary endpoint was the development of CA-AKI, defined as an absolute increase ≥ 0.3 mg/dL or a relative increase ≥ 50% from baseline serum creatinine within 48 h after contrast medium exposure. RESULTS: Overall, 181 patients (16.3%) developed contrast-associated acute kidney injury. The incidences of CA-AKI in patients with urine pH 5.0-6.0, 6.5-7.0, and 7.5-8.5 were 19.7%, 9.8%, and 23.3%, respectively. After adjustment for potential confounding factors, perioperative urine pH 5.0-6.0 and 7.5-8.5 remained independently associated with CA-AKI [odds ratio (OR)1.86, 95% confidence interval (CI) 1.25-2.82, P = 0.003; OR 2.70, 95% CI 1.5-4.68, P < 0.001, respectively]. The association was consistent in subgroups of patients stratified by several CA-AKI risk predictors. However, the risk of CA-AKI associated with urine pH 7.5-8.5 was stronger in patients with worse renal function (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2) (HR 5.587, 95% CI 1.178-30.599 vs. HR 2.487, 95% CI 1.331-4.579; overall interaction P < 0.05). CONCLUSION: The urine pH and CA-AKI may underlie the V-shape relationship.
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Lesión Renal Aguda/inducido químicamente , Medios de Contraste/efectos adversos , Tasa de Filtración Glomerular , Orina/química , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/orina , Anciano , Creatinina/sangre , Urgencias Médicas , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Periodo Perioperatorio , Estudios Prospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Liver fibrosis scores have been demonstrated to be associated with poor prognosis after percutaneous coronary intervention (PCI). However, no studies have compared the prognostic value of these scores in acute myocardial infarction (AMI) patients with and without diabetes. We retrospectively enrolled 1576 AMI patients who underwent PCI. There were 177 all-cause deaths and 111 cardiac deaths during follow-up (median 3.8 years). The non-alcoholic fatty liver disease fibrosis score (NFS) showed a better prognostic value than the fibrosis-8 (FIB-8) score (Harrell's C-index: 0.703 vs 0.671, P = .014) and the fibrosis-4 (FIB-4) score (Harrell's C-index: 0.703 vs 0.648, P < .001) in the overall population. In the time-dependent receiver operating characteristic analysis, the NFS also had the highest area under the curve across all time points. Consistent results were observed in diabetic and non-diabetic populations. Adding the NFS to traditional cardiovascular risk factors significantly improved the prediction both for all-cause mortality (Harrell's C-index: 0.806 vs 0.771, P < .001) and cardiac death (Harrell's C-index: 0.800 vs 0.771, P = .014). The NFS showed a better prognostic value than the FIB-8 score and the FIB-4 score in patients with AMI undergoing PCI, which might be preferable for estimating the risk of mortality regardless of the presence or absence of diabetes.
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Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Enfermedad del Hígado Graso no Alcohólico , Intervención Coronaria Percutánea , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Pronóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Estudios Retrospectivos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapiaRESUMEN
AIMS: Variability of metabolic parameters, such as glycemic variability (GV) and systolic blood pressure variability (SBPV), are associated with adverse cardiovascular outcomes. However, whether these parameters have additive effects on mortality in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU) remains unclear. METHODS: We retrospectively enrolled patients with CAD from the Medical Information Mart for Intensive Care-IV database. The highest tertile of variability was defined as high variability. A variability scoring system was established, which assigned 0 points to tertile 1, 1 point to tertile 2, and 2 points to tertile 3 for GV and SBPV. RESULTS: Among 4237 patients with CAD, 400 patients died in hospital, and 967 patients died during 1-year follow-up. High GV and high SBPV were associated with an increased risk of mortality. The effects of GV and SBPV on in-hospital mortality were partially mediated by ventricular arrhythmias (18.0 % and 6.6 %, respectively). The risk of mortality gradually increased with the number of high-variability parameters and increasing variability scores. CONCLUSIONS: GV and SBPV have additive effects on the risk of mortality in patients with CAD hospitalized in the ICU. Ventricular arrhythmias partially mediate the effects of GV and SBPV on in-hospital mortality.
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Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Presión Sanguínea/fisiología , Glucemia , Estudios Retrospectivos , Mortalidad HospitalariaRESUMEN
AIMS: The stress hyperglycemia ratio (SHR) is significantly associated with short-term adverse cardiovascular events. However, the association between SHR and mortality after the acute phase of acute coronary syndrome (ACS) remains controversial. METHODS: This study used data from the Medical Information Mart for Intensive Care-IV database. Patients with ACS hospitalized in the intensive care unit (ICU) were retrospectively enrolled. RESULTS: A total of 2668 ACS patients were enrolled. The incidence of in-hospital and 1-year mortality was 4.7 % and 13.2 %, respectively. The maximum SHR had a higher prognostic value for predicting both in-hospital and 1-year mortality than the first SHR. Adding the maximum SHR to the SOFA score could significantly improve the prognostic prediction. In the landmark analysis at 30 days, the maximum SHR was a risk factor for mortality within 30 days regardless of whether patients had diabetes. However, it was no longer associated with mortality after 30 days in patients with diabetes after adjustment (HR = 1.237 per 1-point increment, 95 % CI 0.854-1.790). CONCLUSIONS: The maximum SHR was significantly associated with mortality in patients with ACS hospitalized in the ICU. However, caution is warranted if it is used for predicting mortality after 30 days in patients with diabetes.
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Síndrome Coronario Agudo , Diabetes Mellitus , Hiperglucemia , Humanos , Estudios Retrospectivos , Síndrome Coronario Agudo/complicaciones , Hiperglucemia/complicaciones , Hospitalización , PronósticoRESUMEN
Diabetic cardiomyopathy (DCM) is a cardiac microvascular complication caused by metabolic disorders. It is characterized by myocardial remodeling and dysfunction. The pathogenesis of DCM is associated with abnormal cellular metabolism and organelle accumulation. Autophagy is thought to play a key role in the diabetic heart, and a growing body of research suggests that modulating autophagy may be a potential therapeutic strategy for DCM. Here, we have summarized the major signaling pathways involved in the regulation of autophagy in DCM, including Adenosine 5'-monophosphate-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), Forkhead box subfamily O proteins (FOXOs), Sirtuins (SIRTs), and PTEN-inducible kinase 1 (PINK1)/Parkin. Given the significant role of autophagy in DCM, we further identified natural products and chemical drugs as regulators of autophagy in the treatment of DCM. This review may help to better understand the autophagy mechanism of drugs for DCM and promote their clinical application.
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Autofagia , Cardiomiopatías Diabéticas , Transducción de Señal , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Humanos , Autofagia/efectos de los fármacos , Animales , Transducción de Señal/efectos de los fármacosRESUMEN
The model for end-stage liver disease (MELD) and the model for end-stage liver disease excluding international normalized ratio (INR) (MELD-XI) scores, which reflect dysfunction of liver and kidneys, have been reported to be related to the prognosis of patients with right-sided "backward" failure. However, the relationship between the MELD/MELD-XI score and the in-hospital adverse events in pulmonary embolism (PE) patients was unknown. Normotensive PE patients were retrospectively enrolled at China-Japan friendship hospital from January 2017 to February 2020. The primary outcome was defined as death and clinical deterioration during hospitalization. Multivariate logistic analysis was used to explore the association between the MELD and MELD-XI scores for in-hospital adverse events. We also compared the accuracy of the MELD, MELD-XI, and the pulmonary embolism severity index (PESI) score using the time-dependent receiver operating characteristic curve and corresponding areas under the curve (AUC). A total of 222 PE patients were analyzed. Logistic regression analysis showed that the MELD score was independently associated with in-hospital adverse events (odds ratio = 1.115, 95% confidential interval = 1.022-1.217, P = .014). The MELD score has an AUC of 0.731 and was better than PESI (AUC of 0.629) in predicting in-hospital adverse events. Among PE patients with normal blood pressure on admission, the MELD score was associated with increased in-hospital adverse events.
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Embolia Pulmonar , Humanos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Valor Predictivo de las Pruebas , Pronóstico , Enfermedad AgudaRESUMEN
BACKGROUND: The Age-D-dimer-Albumin (ADA), the CREDO-Kyoto, and the PARIS scores have been established to predict thrombotic events. However, the prognostic performance of these scores compared to the GRACE score in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) has not been reported. METHODS: Consecutive AMI patients treated with PCI were retrospectively enrolled at a teaching hospital in China from January 2016 to December 2019. The primary endpoint was all-cause mortality and the secondary endpoint was cardiac death. Harrell's C-index and net reclassification improvement (NRI) were used to compare the prognostic value of these scores with the GRACE score for mortality. RESULTS: Of the 1,578 patients enrolled, the mean age was 62.5 years, and 23.5% were female. During a median follow-up of 3.8 years, 146 all-cause deaths and 80 cardiac deaths occurred. The ADA score showed a better prognostic performance than the GRACE (Harrell's C-index: 0.800 vs. 0.749; p = 0.003), the CREDO-Kyoto (Harrell's C-index: 0.800 vs. 0.765; NRI = 0.348, p < 0.001), and the PARIS scores (Harrell's C-index: 0.800 vs. 0.694; NRI = 0.556, p < 0.001). In the multivariable Cox regression analysis, the ADA score was independently associated with all-cause mortality (hazard ratio [HR] = 1.641 per 10-point increment, 95% confidence interval [CI]: 1.397-1.929) and cardiac death (HR = 1.636 per 10-point increment, 95% CI: 1.325-2.020). The risk of all-cause mortality and cardiac death increased with the rising of the ADA score. CONCLUSION: The ADA score showed a better prognostic performance than the GRACE, the CREDO-Kyoto, and the PARIS scores in patients with AMI undergoing PCI, which was a potential predictive tool for mortality.
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Síndrome Coronario Agudo , Productos de Degradación de Fibrina-Fibrinógeno , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Femenino , Persona de Mediana Edad , Masculino , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Infarto del Miocardio/etiología , Muerte , Síndrome Coronario Agudo/terapiaRESUMEN
There are currently two main treatment strategies mainly for high-risk patients: percutaneous transluminal angioplasty and stenting (PTAS) and aggressive medical management (AMM). However, the choice between PTAS or AMM remains controversial for patients with stroke or intracranial atherosclerotic stenosis (ICAS). The investigators searched the PubMed, Web of Science, Embase, Scopus, and Cochrane library databases. Randomized controlled trial (RCT) comparing PTAS and AMM for patients with stroke or ICAS were selected. RevMan 5.3 was used to analyze the results and assess risk of bias. The primary endpoints are stroke and death within 30 days after enrollment, or ischemic stroke in the territory of the qualifying artery beyond 30 days, and entire follow-up endpoints. The secondary outcomes were the disabling or fatal stroke, and incidence of death within 3 years. Four studies, 989 patients were included in this article. The AMM group was superior in the entire follow-up endpoint (OR 0.56; 95% CI 0.40, 0.79). The AMM also better in primary endpoint within 30 days (OR 0.32; 95% CI 0.17, 0.61). There was no significant difference beyond 30 days (OR 1.08; 95% CI 0.63, 1.86). The remaining outcomes, such as stroke and death, were not significantly different (P > 0.05). This meta-analysis shows AMM is significantly more effective than PTAS in subjects with ICAS due to the high rate of periprocedural stroke (OR 0.32; 95% CI 0.17, 0.61) and stroke during the entire follow-up (OR 0.56; 95% CI 0.40, 0.79) associated with PTAS. Furthermore, PTAS offers no additional benefits over AMM beyond 30 days (OR 1.08; 95% CI 0.63, 1.86).
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Arteriosclerosis Intracraneal , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Constricción Patológica/terapia , Accidente Cerebrovascular/terapia , Angioplastia , Accidente Cerebrovascular Isquémico/terapia , Arteriosclerosis Intracraneal/terapiaRESUMEN
AIMS: Left ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling. METHODS AND RESULTS: This prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end-diastolic volume (LVEDV), a 15% increase in LV end-systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long-term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long-term mortality (hazard ratio = 2.78, 95% confidence interval 1.41-5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N-terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model. CONCLUSIONS: LV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long-term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all-cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling.
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Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Nomogramas , Remodelación Ventricular/fisiología , Estudios Prospectivos , Insuficiencia Cardíaca/diagnósticoRESUMEN
The model for end-stage liver disease (MELD) score, which can reflect liver and renal function, is associated with poor prognosis. However, the prognostic performance of the modified MELD score in patients undergoing elective percutaneous coronary intervention (PCI) has not been fully evaluated and compared. This study retrospectively enrolled 5324 patients. During a median follow-up of 2.85 years, 412 patients died. Time-dependent receiver operating characteristic curves at 3 years indicated that the MELD including albumin (MELD-Albumin) score had the highest prognostic performance (AUC = .721) than the MELD score (AUC = .630), the MELD excluding the international normalized ratio (MELD-XI) score (AUC = .606), and the MELD including sodium (MELD-Na) score (AUC = .656) (all P < .001). The MELD-Albumin score, the MELD score, and the MELD-Na score were independent predictors of long-term mortality; however, the MELD-XI score was not when treated as a categorical variable (P = .254). Adding the MELD-Albumin score to the model of clinical risk factors could improve the prognostic performance. For the subgroup analysis, the association between the MELD-Albumin score and long-term mortality was more pronounced in patients ≤75 years (interaction P value = .005). The MELD-Albumin score showed the strongest prognostic performance than the other versions of the MELD score in patients undergoing elective PCI.
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Enfermedad Hepática en Estado Terminal , Intervención Coronaria Percutánea , Humanos , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/cirugía , Pronóstico , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , AlbúminasRESUMEN
Previous studies have demonstrated that non-invasive liver fibrosis scores (LFSs) are associated with kidney function deterioration. This study aimed to assess the predictive performance of LFSs in contrast-associated acute kidney injury (CA-AKI) in coronary artery disease (CAD) patients undergoing elective percutaneous coronary intervention (PCI). This retrospective study involved 5627 patients. The frequency of CA-AKI was 6.3% (n = 353). In a multivariate logistic analysis after adjustment, non-invasive LFSs, including fibrosis-5 score (FIB-5), fibrosis-4 score (FIB-4), aspartate aminotransferase to alanine aminotransferase ratio (AAR), and aspartate aminotransferase to platelet ratio index were independent risk factors for CA-AKI (all P < .05), whereas the Forns score was not (P > .05). The highest predictive performance was observed for FIB-5 (area under the curve [AUC] = .644) compared to other LFSs. A restricted cubic spline analysis confirmed approximately linear relationships between LFSs and risks of CA-AKI. Furthermore, adding FIB-5 (AUC = .747; net reclassification improvement [NRI] = .441, P < .001; integrated discrimination improvement [IDI] = .008, P < .001) or AAR (AUC = .747; NRI = .419, P < .001; IDI = .006, P = .010) to an established clinical risk model could significantly improve the prediction of CA-AKI. The LFSs were significantly associated with CA-AKI, possibly serving as predictive tools for early identification of CAD patients undergoing elective PCI that are at high risk of CA-AKI.
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Lesión Renal Aguda , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Medios de Contraste/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Valor Predictivo de las Pruebas , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Factores de Riesgo , Enfermedad de la Arteria Coronaria/cirugía , Cirrosis Hepática , Aspartato Aminotransferasas , FibrosisRESUMEN
Genetic lineage tracing is indispensable to unraveling the origin, fate, and plasticity of cells. However, the intrinsic leakiness in the CreER-loxP system raises concerns on data interpretation. Here, we reported the generation of a novel dual inducible CreER-loxP system with superior labeling characteristics. This two-component system consists of membrane localized CreER (mCreER: CD8α-FRB-CS-CreER) and TEV protease (mTEVp: CD8α-FKBP-TEVp), which are fusion proteins incorporated with the chemically induced dimerization machinery. Rapamycin and tamoxifen induce sequential dimerization of FKBP and FRB, cleavage of CreER from the membrane, and translocation into the nucleus. The labeling leakiness in Ad293 cells reduced dramatically from more than 70% to less than 5%. This tight labeling feature depends largely on the association of mCreER with HSP90, which conceals the TEV protease cutting site between FRB and CreER and thus preventing uninduced cleavage of the membrane-tethering CreER. Membrane-bound CreER also diminished significantly cytotoxicity. Our studies showed mCreER under the control of the rat insulin promoter increased labeling specificity in MIN6 islet beta-cells. Viability and insulin secretion of MIN6 cells remained intact. Our results demonstrate that this novel system can provide more stringent temporal and spatial control of gene expression and will be useful in cell fate probing.