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1.
Biol Trace Elem Res ; 202(2): 454-465, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37198357

RESUMEN

The magnesium depletion score (MDS) is considered a new valuable and reliable predictor of body magnesium status. This study aimed to explore the association between MDS and congestive heart failure (CHF) among US adults. A total of 19,227 eligible participants from the 2007-2016 National Health and Nutrition Examination Survey were enrolled in this study and then divided into three groups according to the level of MDS (none to low: MDS=0-1, middle: MDS=2, high: MDS=3-5). Sample-weighted logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) exploring the independent relationship between MDS and CHF. The estimated prevalence of CHF increased with the increasing level of MDS (none to low: 0.86%, middle: 4.06%, high: 13.52%; P < 0.001). Compared to those in the none-to-low group, participants in the middle and high groups were at significantly higher risk of CHF after adjusting for various covariates (model 3: OR=1.55, 95%CI: 1.05-2.30, P < 0.001; OR=3.20, 95%CI: 2.07-4.96, P < 0.001; respectively). Subgroup analyses indicated that adequate dietary magnesium intake could reduce the risk of CHF in participants who did not meet the recommended dietary allowance (RDA) for magnesium. Besides, there was an interaction between coronary artery disease and MDS on CHF (P for interaction < 0.001). These findings indicated that MDS, a novel indicator estimating magnesium deficiency, is associated with the risk of CHF in non-institutionalized US civilians. Participants whose dietary magnesium intake reaches the RDA might be at lower risk.


Asunto(s)
Insuficiencia Cardíaca , Deficiencia de Magnesio , Adulto , Humanos , Magnesio , Dieta , Encuestas Nutricionales , Insuficiencia Cardíaca/epidemiología , Deficiencia de Magnesio/complicaciones , Deficiencia de Magnesio/epidemiología , Factores de Riesgo
2.
Heart Lung ; 64: 55-61, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38042097

RESUMEN

BACKGROUND: Redo aortic arch surgery is complex and associated with higher risks and mortality. Prolonged mechanical ventilation (PMV) after cardiac surgery is linked to early adverse outcomes and increased costs. OBJECTIVES: Identify specific risk factors and early complications associated with PMV following redo aortic arch surgery. METHODS: Retrospective study at Fuwai Hospital involving 203 patients. Data on patient characteristics, intraoperative factors, and outcomes were analyzed. RESULTS: A total of 203 patients were included, with 42.4 % requiring PMV. PMV patients had longer ICU stays (P < 0.001), lower discharge ADL scores (P < 0.001), and higher hospitalization costs (P < 0.001). While there was no significant difference in-hospital mortality between the two groups, the long-term survival rate in the PMV group was lower than that in the non-PMV group (P = 0.029). Multivariate analysis identified longer cardiopulmonary bypass time (OR 1.008, 95% CI, 1.002 - 1.014, P = 0.006), elevated intraoperative red blood cell transfusion(OR 1.214, 95% CI, 1.057 - 1.393, P = 0.006), higher PEEP (OR 1.296, 95% CI 1.089 - 1.542, P = 0.003), and total arch replacement (OR 3.241, 95% CI 1.392 - 7.543, P = 0.006) as independent risk factors for PMV. CONCLUSION: PMV following redo aortic arch surgery is linked to early adverse outcomes, increased healthcare costs, and reduced long-term survival, with longer cardiopulmonary bypass times, elevated intraoperative red blood cell transfusion, higher PEEP, and total arch replacement as independent risk factors.


Asunto(s)
Aorta Torácica , Respiración Artificial , Humanos , Respiración Artificial/efectos adversos , Estudios Retrospectivos , Aorta Torácica/cirugía , Factores de Riesgo , Hospitalización
3.
J Cardiothorac Surg ; 18(1): 298, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37875966

RESUMEN

Limited reports exist on the utilization of venoarterial extracorporeal membrane oxygenation (VA-ECMO) following aortic dissection surgery, possibly due to concerns regarding complications. This case series aimed to evaluate the effectiveness and safety of using VA-ECMO in combination with intra-aortic balloon pump (IABP) for managing postoperative cardiogenic shock in patients with type A aortic dissection (AAD). The study included nine patients with an average age of 57.0 ± 9.5 years. The patients underwent various surgical procedures, including coronary artery bypass grafting (CABG) and aortic root reconstruction. The results showed that the combined use of VA-ECMO and IABP was feasible and effective in managing postoperative cardiogenic shock in AAD patients. However, the in-hospital mortality rate was high, with six out of nine patients succumbing to the condition. Among the patients who received VA-ECMO plus IABP in the operating room, four were successfully weaned from VA-ECMO, and three survived with a mean follow-up of 20 months. The study also highlighted the potential risks of renal complications associated with VA-ECMO and IABP. The findings suggest that the combined therapy of VA-ECMO and IABP may be beneficial for patients who have difficulty weaning from cardiopulmonary bypass (CPB) after AAD surgery.


Asunto(s)
Disección Aórtica , Oxigenación por Membrana Extracorpórea , Humanos , Persona de Mediana Edad , Anciano , Choque Cardiogénico/etiología , Choque Cardiogénico/cirugía , Oxigenación por Membrana Extracorpórea/métodos , Contrapulsador Intraaórtico/efectos adversos , Aorta , Disección Aórtica/cirugía
4.
J Card Surg ; 37(12): 4906-4918, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36378900

RESUMEN

BACKGROUND: The present study aimed to explore the relationship between serum anion gap (AG) and long-term mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS: Clinical variables were extracted among patients undergoing CABG from Medical Information Mart for Intensive Care III (MIMIC III) database. The primary outcome was 4-year mortality following CABG. An optimal cut-off value of AG was determined by the receiver operating characteristic (ROC) curve. The Kaplan-Meier (K-M) analysis and multivariate Cox hazard analysis were performed to investigate the prognostic value of AG in long-term mortality after CABG. To eliminate the bias between different groups, propensity score matching (PSM) was conducted to validate the findings. RESULTS: The optimal cut-off value of AG was 17.00 mmol/L. Then a total of 3162 eligible patients enrolled in this study were divided into a high AG group (≥17.00, n = 1022) and a low AG group (<17.00, n = 2,140). A lower survival rate was identified in the high AG group based on the K-M curve (p < .001). Compared with patients in the low AG group, patients in the high AG group had an increased risk of long-term mortality [1-year mortality: hazard ratio, HR: 2.309, 95% CI (1.672-3.187), p < .001; 2-year mortality: HR: 1.813, 95% CI (1.401-2.346), p < .001; 3- year mortality: HR: 1.667, 95% CI (1.341-2.097), p < .001; 4-year mortality: HR: 1.710, 95% CI (1.401-2.087), p < .001] according to multivariate Cox hazard analysis. And further validation of above results was consistent in the matched cohort after PSM. CONCLUSIONS: The AG is an independent predictive factor for long-term all-cause mortality in patients following CABG, where a high AG value is associated with an increased mortality.


Asunto(s)
Equilibrio Ácido-Base , Enfermedad de la Arteria Coronaria , Humanos , Puntaje de Propensión , Estudios Retrospectivos , Puente de Arteria Coronaria/métodos , Tasa de Supervivencia , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/etiología , Resultado del Tratamiento
6.
BMC Cardiovasc Disord ; 22(1): 195, 2022 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-35473483

RESUMEN

BACKGROUND: Calcific aortic valve stenosis (CAVS) represents a serious health threat to elderly patients. Post-stenotic aortic dilation, a common feature in CAVS patients, might progress into aneurysm and even dissection, potential consequences of CAVS, and predicts a poor prognosis. This study sought to investigate the association of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, with severe post-stenotic aortic dilation in a case-control study in Chinese population. MATERIALS AND METHODS: 208 consecutive patients with CAVS were recruited retrospectively in a case-control study in Chinese population, from July 1, 2015 to June 31, 2018. LMR was statistically analyzed using the ROC curve and binary logistic regression analyses for its prognostic value in severe post-stenotic aortic dilation. RESULTS: LMR was significantly reduced in patients with severe post-stenotic aortic dilation (2.72 vs. 3.53, p = 0.002 < 0.05) compared to patients without severe post-stenotic aortic dilation. There was an inverse correlation observed between the maximal diameter of ascending aorta and LMR in the overall patients (r = - 0.217, p = 0.002 < 0.05). For post-stenotic aortic dilation, the prevalence of high-LMR group was statistically lower than that of low-LMR group (19.7% vs. 43.9%, p < 0.001). The maximal diameter of ascending aorta was significantly reduced in the high-LMR group (4.35 vs. 4.76, p = 0.003 < 0.05) compared to low-LMR group. Additionally, LMR was identified in the multivariate analysis independently associated with severe post-stenotic aortic dilation (AUC 0.743, 95% CI: [0.573-0.964], p = 0.025). CONCLUSIONS: This study provided the evidence of an inverse correlation between severe post-stenotic aortic dilation and LMR. LMR is potentially independently associated with severe post-stenotic aortic dilation.


Asunto(s)
Aorta , Monocitos , Anciano , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica , Calcinosis , Estudios de Casos y Controles , Dilatación , Dilatación Patológica , Humanos , Linfocitos , Estudios Retrospectivos
7.
Front Surg ; 9: 801708, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35252328

RESUMEN

BACKGROUND: This study examined the role of blood urea nitrogen-to-albumin ratio (BAR) in predicting long-term mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS: In this retrospective cohort study, patients undergoing CABG were enrolled from the Medical Information Mart for Intensive Care III (MIMIC III) database. Patients were divided into the three groups according to the optimal cutoff values of BAR determined by X-tile software. The survival curve was constructed by the Kaplan-Meier method and multivariate Cox regression analysis was performed to explore the independent prognostic factors of 1- and 4-year mortality after CABG. The receiver operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were calculated to estimate the accuracy of BAR in predicting the outcomes. Subgroup analyses were also carried out. RESULTS: A total of 1,462 patients at 4-year follow-up were included, of which 933, 293, and 236 patients were categorized into the group 1 (≤ 6.45 mg/g), group 2 (>6.45 and ≤ 10.23 mg/g), and group 3 (>10.23 mg/g), respectively. Non-survivors showed an increased level of BAR at both 1- (p < 0.001) and 4-year (p < 0.001) follow-up compared with the survivors. The patients with a higher BAR had a higher risk of 1- and 4-year mortality following CABG (33.05 vs. 14.33 vs. 5.14%, p < 0.001 and 52.97 vs. 30.72 vs. 13.08%, p < 0.001, respectively). Cox proportional hazards regression model suggested a higher BAR as an independent risk factor of 1-year mortality (HR 3.904; 95% CI 2.559-5.956; P < 0.001) and 4-year mortality (HR 2.895; 95% CI 2.138-3.921; P < 0.001) after adjusting for confounders. Besides, the receiver operating characteristic (ROC) curves showed the better predictive ability of BAR compared to other grading scores at both 1- (0.7383, 95% CI: 0.6966-0.7800) and 4-year mortality (0.7189, 95% CI: 0.6872-0.7506). Subgroup analysis demonstrated no heterogeneous results of BAR in 4-year mortality in particular groups of patient. CONCLUSION: This report provided evidence of an independent association between 1- and 4-year mortality after CABG and BAR. A higher BAR was associated with a higher risk of long-term mortality and could serve as a prognostic predictor in patients following CABG.

8.
Int J Gen Med ; 15: 2247-2259, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35256854

RESUMEN

Background: Blood urea nitrogen to albumin ratio (BAR) has been implicated in predicting outcomes of various inflammatory-related diseases. However, the predictive value of BAR in long-term mortality in patients with acute myocardial infarction (AMI) has not yet been evaluated. Methods: In this retrospective cohort study, the patients were recruited from the Medical Information Mart for Intensive Care III (MIMIC III) database and categorized into two groups by a cutoff value of BAR. Kaplan-Meier (K-M) analysis and Cox proportional hazard model were performed to determine the predictive value of BAR in long-term mortality following AMI. In order to adjust the baseline differences, a 1:1 propensity score matching (PSM) was carried out and the results were further validated. Results: A total of 1827 eligible patients were enrolled. The optimal cutoff value of BAR for four-year mortality was 7.83 mg/g. Patients in the high BAR group tended to have a longer intensive care unit (ICU) stay and a higher rate of one-, two-, three- and four-year mortality (all p<0.001) compared with those in the low BAR group. K-M curves indicated a significant difference in four-year survival (p<0.001) between low and high BAR groups. The Cox proportional hazards model showed that higher BAR (>7.83) was independently associated with increased four-year mortality in the entire cohort, with a hazard ratio (HR) of 1.478 [95% CI (1.254-1.740), p<0.001]. After PSM, the baseline characteristics of 312 pairs of patients in the high and low BAR groups were well balanced, and similar results were observed in K-M curve (p=0.003). Conclusion: A higher BAR (>7.83) was associated with four-year mortality in patients with AMI. As an easily available biomarker, BAR can predict the long-term mortality in AMI patients independently.

9.
Int J Gen Med ; 14: 9747-9760, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34934349

RESUMEN

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is one of the most complex congenital cardiac malformations, and the molecular mechanism of heart failure (HF) in HLHS is still elusive. METHODS: Integrative bioinformatics analysis was performed to unravel the underlying genes and mechanisms involved in HF in HLHS. Microarray dataset GSE23959 was screened out for the differentially expressed genes (DEGs), after which the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out using the Metascape. The protein-protein interaction (PPI) network was generated, and the modules and hub genes were identified with the Cytoscape-plugin. And the integrated network of transcription factor (TF)-DEGs and miRNA-DEGs was constructed, respectively. RESULTS: A total of 210 DEGs were identified, including 135 up-regulated and 75 down-regulated genes. The functional enrichment analysis of DEGs pointed towards the mitochondrial-related biological processes, cellular components, molecular functions and signaling pathways. A PPI network was constructed including 155 nodes as well as 363 edges. And 15 hub genes, such as NDUFB6, UQCRQ, SDHD, ATP5H, were identified based on three topological analysis methods and mitochondrial components and functions were the most relevant. Furthermore, by integrating network interaction construction, 23 TFs (NFKB1, RELA, HIF1A, VHL, GATA1, PPAR-γ, etc.) as well as several miRNAs (hsa-miR-155-5p, hsa-miR-191-5p, hsa-mir-124-3p, hsa-miR-1-3p, etc.) were detected and indicated the possible involvement of NF-κB signaling pathways in mitochondrial dysfunction in HLHS. CONCLUSION: The present study applied the integrative bioinformatics analysis and revealed the mitochondrial-related key genes, regulatory pathways, TFs and miRNAs underlying the HF in HLHS, which improved the understanding of disease mechanisms and the development of novel therapeutic targets.

11.
Front Surg ; 8: 704345, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34458315

RESUMEN

Background: The post-operative acute kidney injury (AKI) represents a common complication in the Acute Debakey Type I Aortic Dissection (ADTIAD) and predicts a poorer prognosis. The clinical evidence is scarce supporting the predictive value of the pre-operative lymphocyte-to-monocyte ratio (LMR) in post-operative AKI in ADTIAD. Methods: In this retrospective cohort study, 190 consecutive patients with ADTIAD enrolled for surgical treatment between January 1, 2013, and December 31, 2018. The diagnosis of AKI followed the Kidney Disease: Improving Global Outcomes guidelines (KDIGO). Pre-operative LMR and other possible risk factors were analyzed for their prognostic value in the post-operative AKI in ADTIAD. Results: The subjects were assigned to the low-LMR and high-LMR groups according to the median value of pre-operative LMR. For post-operative AKI, the incidence and the severity in the low-LMR group were statistically different from that of the high-LMR group. Besides, the lower LMR was statistically associated with the more extended ICU stay and intubation time and higher incidences of ischemic stroke and in-hospital mortality. Additionally, in the multivariable analysis, the pre-operative LMR was an independent predictor for post-operative AKI in ADTIAD. A predictive model for post-operative AKI in ADTIAD was established incorporating LMR. Conclusions: LMR is an independent prognostic indicator incorporated into the predictive model with other risk factors to predict the post-operative AKI in ADTIAD.

12.
Biomark Med ; 14(14): 1329-1339, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33064019

RESUMEN

Aim: This study examined the role of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, in predicting the severity of calcific aortic valve stenosis (CAVS) in a Chinese case-control study. Results: The LMR significantly decreased in the patients with CAVS compared with healthy controls. An inverse correlation was observed between the severity of stenosis and LMR in the patients. Additionally, the LMR was identified in the multivariate analysis as an independent predictor of severe CAVS. Conclusion: This study provides evidence of an inverse correlation between the severity of CAVS and LMR. LMR could potentially be applied as an independent predictor of severe CAVS and could be incorporated into a novel predictive model.


Asunto(s)
Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico , Calcinosis/complicaciones , Monocitos/citología , Estenosis de la Válvula Aórtica/inmunología , Estudios de Casos y Controles , China , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad
13.
J Cardiothorac Surg ; 15(1): 213, 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32767994

RESUMEN

BACKGROUND: The acute kidney injury (AKI) remains a frequent complication following open thoracic aortic surgery (OTAS) and worsens the postoperative prognosis. It remains unclear that whether the predictors of AKI following OTAS are different in the patients with or without acute aortic syndrome (AAS). METHODS: Preoperative and intraoperative variables were compared between the patients with or without AKI, and were further analyzed for identifying the potential predictors of postoperative AKI. Subgroup analysis was conducted in the patients with or without AAS, respectively. RESULTS: AKI after OTAS occurred in 57.6% of the overall cohort, 70.1% of the patients with AAS and 46.7% of the patients without AAS. In the multivariate analysis, history of hypertension (OR 1.011, 95% CI: [1.001-1.022], p = 0.04), preoperative platelet (OR 0.995, 95% CI: [0.991-0.999], p = 0.006) and operation time (OR 1.572, 95% CI: [1.355-1.823], p < 0.001) were identified as independent predictors of postoperative AKI for the overall cohort; CPB time (OR 1.020, 95% CI: [1.009-1.031], p < 0.001) and preoperative LMR (OR 0.823, 95% CI: [0.701-0.966], p = 0.02) as independent predictors for the patients with AAS; age (OR 1.045, 95% CI: [1.015-1.076], p = 0.003), preoperative platelet (OR 0.993, 95% CI: [0.988-0.998], p = 0.04) and operation time (OR 1.496, 95% CI: [1.166-1.918], p = 0.002) as independent predictors for the patients without AAS. CONCLUSIONS: The patients with AAS carry a higher risk for postoperative AKI compared with those without AAS. The predictive factors for postoperative AKI after OTAS are different for AAS- and non-AAS subgroups and operation time, CPB time and preoperative platelet are modifiable predictors of AKI.


Asunto(s)
Lesión Renal Aguda/etiología , Aorta Torácica/cirugía , Enfermedades de la Aorta/complicaciones , Enfermedades de la Aorta/cirugía , Procedimientos Quirúrgicos Vasculares/efectos adversos , Enfermedad Aguda , Adulto , Anciano , Puente Cardiopulmonar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tempo Operativo , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Síndrome , Factores de Tiempo
14.
Acta Cardiol Sin ; 36(3): 183-194, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32425433

RESUMEN

Calcific aortic valve disease (CAVD) represents a significant threat to cardiovascular health worldwide, and the incidence of this sclerocalcific valve disease has rapidly increased along with a rise in life expectancy. Compelling evidence has suggested that CAVD is an actively and finely regulated pathophysiological process even though it has been referred to as "degenerative" for decades. A striking similarity has been noted in the etiopathogenesis between CAVD and atherosclerosis, a classical proliferative sclerotic vascular disease.1 Nevertheless, pharmaceutical trials that attempted to target inflammation and dyslipidemia have produced disappointing results in CAVD. While senescence is a well-documented risk factor, the sophisticated regulatory networks have not been adequately explored underlying the aberrant calcification and osteogenesis in CAVD. Valvular endothelial cells (VECs), a type of resident effector cells in aortic leaflets, are crucial in maintaining valvular integrity and homeostasis, and dysfunctional VECs are a major contributor to disease initiation and progression. Accumulating evidence suggests that VECs undergo a phenotypic and functional transition to mesenchymal or fibroblast-like cells in CAVD, a process known as the endothelial-to-mesenchymal transition (EndMT) process. The relevance of this transition in CAVD has recently drawn great interest due to its importance in both valve genesis at an embryonic stage and CAVD development at an adult stage. Hence EndMT might be a valuable diagnostic and therapeutic target for disease prevention and treatment. This mini-review summarized the relevant literature that delineates the EndMT process and the underlying regulatory networks involved in CAVD.

15.
Medicine (Baltimore) ; 99(16): e19766, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32311980

RESUMEN

BACKGROUND: Chronic liver disease is traditionally conceived as a risk factor for cardiovascular surgery. Transcatheter aortic valve implantation (TAVI) has recently burgeoned to precede surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis at intermediate to high surgical risk. The evidence regarding TAVI in the patients with chronic liver disease is currently scarce. METHODS: This article aims to assess the application of TAVI technique in the patients with chronic liver disease. RESULTS: TAVI in the patients with chronic liver disease produced acceptable postoperative results. The post-TAVI outcomes were comparable between the patients with or without chronic liver disease, except for a lower rate of pacemaker implantation in the patients with chronic liver disease (OR, 0.49[0.27-0.87], P = .02). In the patients with chronic liver disease, compared to SAVR, TAVI led to a decrease in the in-hospital mortality (OR, 0.43[0.22-0.86], P = .02) and need for transfusion (OR, 0.39[0.25-0.62], P < .0001). The rest outcomes were similar between the 2 groups. CONCLUSIONS: This systematic review and meta-analysis supported that TAVI is a reliable therapeutic option for treating severe aortic stenosis in the patients with chronic liver disease. Future large-scale randomized controlled trials investigating the mid-term and long-term prognosis are needed to further verify these results.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Enfermedad Hepática en Estado Terminal/complicaciones , Reemplazo de la Válvula Aórtica Transcatéter , Estenosis de la Válvula Aórtica/complicaciones , Humanos
16.
J Cardiovasc Surg (Torino) ; 60(5): 624-632, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31486613

RESUMEN

INTRODUCTION: Recently transcatheter aortic valve replacement (TAVR) has emerged as a feasible alternative for traditional surgical aortic valve replacement (SAVR) in patients with intermediate to high risk. There is currently no clear consensus regarding the optimal antiplatelet strategy after TAVR. The primary objective of this updated meta-analyses was to compare the outcomes of dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT) following TAVR. EVIDENCE ACQUISITION: A meta-analysis of eligible studies of patients undergoing TAVR which reported our outcomes of postoperative DAPT in comparison with SAPT, was carried out. The outcomes included the all-cause mortality, stroke, major/life-threatening bleeding, myocardial infarction and a composite endpoint of mortality, stroke, bleeding and myocardial infarction. EVIDENCE SYNTHESIS: Three randomized controlled trials (RCTs, N.=421) and 5 observational studies (N.=6683) were included in this updated meta-analysis. All-cause mortality was comparable between the two groups (OR 1.13 [95% CI: 0.70-1.81], P=0.619). Besides, DAPT resulted in an augmented risk of major/life-threatening bleeding (OR 2.45 [95% CI: 1.08-5.59], P=0.032). No statistically significant difference was found between the two groups in the rates of stroke (OR 0.83 [95% CI: 0.62-1.10], P=0.212) and myocardial infarction (OR 1.17 [95% CI: 0.47-2.91], P=0.728). And DAPT led to an increased rate of the composite endpoint (OR 2.39 [95% CI: 1.63-3.50], P<0.0001). CONCLUSIONSː The updated meta-analysis presents the evidence that post-TAVR DAPT increases bleeding events, with no benefit in survival and ischemic events, in comparison with SAPT. Nevertheless, it is currently difficult to evaluate by a meta-analysis the effectiveness of DAPT versus SAPT to prevent the valve thrombosis resulting in leaflet dysfunction, due to a limited number of existing publications. Additional RCTs are needed to determine the optimal antiplatelet strategy after TAVR.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/mortalidad , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Humanos , Masculino , Infarto del Miocardio/mortalidad , Infarto del Miocardio/prevención & control , Inhibidores de Agregación Plaquetaria/efectos adversos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Trombosis/mortalidad , Trombosis/prevención & control , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Resultado del Tratamiento
17.
Eur J Med Chem ; 150: 719-728, 2018 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-29573707

RESUMEN

Lung cancer continues to be a leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for more than 80% of lung cancer cases. Current therapies for NSCLC have only limited effect and treatment resistance develops rapidly. In a previous study, we have shown that C1-phenylethynyl tetrahydroisoquinoline (THIQ) analogue 4 has anti-proliferative activity against PC3 human prostate cancer cells. However, this anticancer effect was achieved with relatively high IC50 in A549 lung cancer cells. To improve the potency of the drug, in the present study, a series of novel THIQ analogues (analogues 5a-d) were prepared by using an oxidative C-H functionalization strategy, and their potential anticancer activities on A549 lung cancer cells were investigated. Among these analogues, analogue 5c can markedly inhibit A549 cell proliferation in a dose-dependent manner with a reasonable IC50 of 14.61 ±â€¯1.03 µM. This effect was mediated by analogue 5c-induced G0/G1 phase arrest and cell apoptosis. Treatment with analogue 5c was shown to induce reactive oxygen species (ROS) accumulation, disruption of mitochondrial membrane potential, reduction of glutathione, elevation of intracellular calcium ion (Ca2+), and activation of Caspase-3. Furthermore, analogue 5c can lead to DNA double-strand break and the activation of p53 pathway in A549 cells. In conclusion, the oxidative C-H functionalization strategy to generate analogue 5c could improve the drug anticancer efficacy by inducing mitochondria-dependent apoptosis in A549 cells.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Tetrahidroisoquinolinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Mitocondrias/metabolismo , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Tetrahidroisoquinolinas/síntesis química , Tetrahidroisoquinolinas/química
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