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BACKGROUND: Bronchial artery embolization (BAE) is currently an important treatment for hemoptysis. However, there is no consensus in the efficacy and safety of BAE compared to conservative treatment for hemoptysis, which limits the widespread use of BAE in hemoptysis. The objective was to assess the clinical benefit of BAE versus conservative treatment in patients with hemoptysis. METHODS: A systematic search was conducted on the PubMed, Embase, ScienceDirect, CochraneLibrary, and ClinicalTrials up to March 2023. Both randomized controlled trials (RCTs) and cohort studies reporting rates of recurrent hemoptysis, clinical success, mortality, and complication by BAE and conservative treatment alone for hemoptysis were included. Data were pooled and compared by the use of odds ratio (OR) and 95% confidence interval (CI). RESULTS: Twelve studies (three RCTs, nine cohorts) involving 1231 patients met the eligibility criteria. Patients treated with BAE had lower recurrence rates of hemoptysis (26.5% vs. 34.6%; OR 0.37, 95% CI 0.14-0.98), higher clinical success rates (92.2% vs. 80.9%; OR 2.77, 95% CI 1.66-4.61), and lower hemoptysis-related mortality (0.8% vs. 3.2%; OR 0.20, 95% CI 0.05-0.84) compared with conservative treatment alone. There was no significant difference in all-cause mortality between the two groups. In terms of security, the incidence of major complications and minor complications in patients undergoing BAE treatment was 0.2% (1/422) and 15.6%, respectively. CONCLUSIONS: BAE was more effective than conservative treatment alone in controlling hemoptysis, reducing recurrence, and decreasing hemoptysis-related mortality, with an almost negligible risk of major complications.
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Arterias Bronquiales , Tratamiento Conservador , Embolización Terapéutica , Hemoptisis , Hemoptisis/terapia , Humanos , Embolización Terapéutica/métodos , Tratamiento Conservador/métodos , Resultado del Tratamiento , Recurrencia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIMS: This systematic review and meta-analysis aimed to investigate the association between serum uric acid (SUA) levels and the incidence rate and prognosis of heart failure (HF), as well as the impact of uric acid-lowering treatment on HF patients. METHODS AND RESULTS: PubMed and Embase were searched for original articles reporting on the association between SUA and HF incidence, adverse outcomes, and the effect of uric acid-lowering treatment in HF patients. Data were pooled using random effects or fixed effects models. Univariable meta-regression analysis assessed the influence of study characteristics on research outcomes. Statistical analyses were conducted using RevMan software and STATA software version 15.0. Eleven studies on HF incidence and 24 studies on adverse outcomes in HF patients were included. Higher SUA levels were associated with an increased risk of HF (RR: 1.81, 95% CI: 1.53-2.16), all-cause mortality (RR: 1.44, 95% CI: 1.25-1.66), cardiac death (RR: 1.56, 95% CI: 1.32-1.84), and HF rehospitalization (RR: 2.07, 95% CI: 1.37-3.13) in HF patients. Uric acid-lowering treatment was found to increase all-cause mortality in HF patients (RR: 1.15, 95% CI: 1.05-1.25). CONCLUSIONS: Uric acid is an independent predictor of heart failure occurrence and adverse prognosis. Targeting uric acid lowering as a therapeutic intervention does not improve the prognosis of patients with heart failure. It may not be advisable to use traditional urate-lowering drugs in young patients with heart failure, and elderly patients should exercise caution when using them.
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Insuficiencia Cardíaca , Ácido Úrico , Humanos , Anciano , Biomarcadores , Pronóstico , Readmisión del PacienteRESUMEN
AIMS: The purpose of this study was to evaluate the role of the NLRP3-inflammasome in heart failure with preserved ejection fraction (HFpEF). MAIN METHODS: Serum inflammatory cytokines were detected in patients with heart failure. Correlation analysis was performed to investigate the relationship between serum inflammatory cytokines and left ventricular diastolic function. A 'two-hit' (metabolic stress and mechanical stress) mouse model of HFpEF was established. Furthermore, MCC950 was used to determine the role of NLRP3-inflammasome inhibition in cardiac and pulmonary artery remodelling in HFpEF mice. KEY FINDINGS: Compared with heart failure patients with reduced ejection fraction, patients with HFpEF have significantly elevated serum inflammatory cytokine levels. Serum NLRP3 and interleukin-1ß levels were positively correlated with the diastolic function of HFpEF. In the HFpEF mouse model, the inhibition of the NLRP3-inflammasome by MCC950 improved exercise intolerance, glucose intolerance, and left ventricular diastolic function, but had no significant effect on systolic function. Meanwhile, MCC950 attenuated the release of inflammatory cytokines, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, the potential protective effects of MCC950 are achieved by inhibiting activation of the NLRP3-IL-1ß pathway and cascade expansion of downstream inflammatory cytokines. Additionally, the inhibition of NLRP3-inflammasome by MCC950 reduced pulmonary artery pressure and improved pulmonary artery remodelling in HFpEF. SIGNIFICANCE: The NLRP3-inflammasome plays a considerable role in inflammation and cardiac and pulmonary artery remodelling in HFpEF by activating the cascade reaction of inflammatory cytokines. This study is the first to comprehensively elucidate the role of the NLRP3-inflammasome in HFpEF, and will provide reference for future study.
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Insuficiencia Cardíaca , Inflamasomas , Humanos , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Sulfonas/farmacología , Sulfonas/uso terapéutico , Volumen Sistólico/fisiología , Arteria Pulmonar/metabolismo , Sulfonamidas/farmacología , Modelos Animales de Enfermedad , CitocinasRESUMEN
Objective: As a new method of left ventricular-arterial coupling (VAC), the non-invasive myocardial work index (MWI) may provide more useful information than the classical methods of arterial elastance/left ventricular (LV) elastance index (the ratio of effective arterial elastance (Ea) over end-systolic elastance [Ea/Ees]). This research aims to investigate if MWI might be better associated with hypertension-mediated organ damage (HMOD) and diastolic dysfunction than Ea/Ees in hypertension. Methods: We prospectively enrolled 104 hypertensives and 69 normotensives. All subjects had speckle-tracking echocardiography for myocardial work, conventional echocardiography, and brachial-ankle pulse wave velocity (baPWV) measurements. The global work index (GWI) is a myocardial work component. The correlation between GWI and HMOD, as well as diastolic dysfunction, was analyzed. The receiver operating characteristic (ROC) curve was utilized for evaluating the GWI predicting efficacy. Results: The global work index was significantly higher in hypertensives than in normotensives (2,021.69 ± 348.02 vs. 1,757.45 ± 225.86 mmHg%, respectively, p < 0.001). Higher GWI was a risk factor on its own for increased baPWV, pulse pressure (PP), echocardiographic LV hypertrophy (LVH), and left atrial volume index (LAVI) (p = 0.030, p < 0.001, p = 0.018 p = 0.031, respectively), taking into account the sex, age, mean arterial pressure (MAP), body mass index (BMI), and antihypertensive therapy. However, no considerable associations were found between Ea/Ees and HMOD parameters and the diastolic dysfunction markers. The GWI area under the ROC curve for increased PP and baPWV, echocardiographic LVH, and increased LAVI were 0.799, 0.770, 0.674, and 0.679, respectively (p < 0.05). Conclusions: The global work index but not traditionally echocardiographic-derived Ea/Ees of VAC is independently related to HMOD and diastolic impairment in hypertensives with preserved LV ejection fraction. The GWI may be a potential marker for evaluating the VAC in hypertension.
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Objectives: Although myocardial fibrosis is a common pathophysiological process associated with many heart diseases, the molecular mechanisms regulating the development of fibrosis have not been fully determined. Recently, single cell RNA sequencing (scRNA-seq) analysis has been used to examine cellular fate and function during cellular differentiation and has contributed to elucidating the mechanisms of various diseases. The main purpose of this study was to characterize the fate of cardiac fibroblasts (CFs) and the dynamic gene expression patterns in a model of cardiac pressure overload using scRNA-seq analysis. Methods: The public scRNA-seq dataset of the transverse aortic coarctation (TAC) model in mice was downloaded from the GEO database, GSE155882. First, we performed quality control, dimensionality reduction, clustering, and annotation of the data through the Seurat R package (v4.0.5). Then, we constructed the pseudotime trajectory of cell development and identified key regulatory genes using the Monocle R package (v2.22.0). Different cell fates and groups were fully characterized by Gene Set Enrichment Analysis (GSEA) analysis and Transcription factor (TF) activity analysis. Finally, we used Cytoscape (3.9.1) to extensively examine the gene regulatory network related to cell fate. Results: Pseudotime analysis showed that CFs differentiated into two distinct cell fates, one of which produced activated myofibroblasts, and the other which produced protective cells that were associated with reduced fibrosis levels, increased antioxidative stress responses, and the ability to promote angiogenesis. In the TAC model, activated CFs were significantly upregulated, while protective cells were downregulated. Treatment with the bromodomain inhibitor JQ1 reversed this change and improved fibrosis. Analysis of dynamic gene expression revealed that Gpx3 was significantly upregulated during cell differentiation into protective cells. Gpx3 expression was affected by JQ1 treatment. Furthermore, Gpx3 expression levels were negatively correlated with the different levels of fibrosis observed in the various treatment groups. Finally, we found that transcription factors Jun, Fos, Atf3, and Egr1 were upregulated in protective cells, especially Egr1 was predicted to be involved in the regulation of genes related to antioxidant stress and angiogenesis, suggesting a role in promoting differentiation into this cell phenotype. Conclusions: The scRNA-seq analysis was used to characterize the dynamic changes associated with fibroblast differentiation and identified Gpx3 as a factor that might be involved in the regulation of myocardial fibrosis under cardiac pressure overload. These findings will help to further understanding of the mechanism of fibrosis and provide potential intervention targets.
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Cardiomiopatías , Animales , Cardiomiopatías/metabolismo , Diferenciación Celular , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Fibroblastos/metabolismo , Fibrosis , Glutatión Peroxidasa , Ratones , Miocardio/patologíaRESUMEN
BACKGROUND: The relationship between ambulatory arterial stiffness index (AASI) and left ventricular diastolic dysfunction (LVDD) in patients with heart failure with preserved ejection fraction (HFpEF) is unknown. We aimed to investigate the association between the AASI and LVDD in HFpEF. METHODS: We prospective enrolled consecutive patients with HFpEF in Chongqing, China. Twenty-four-hour ambulatory blood pressure monitoring (24 h-ABPM) and echocardiography were performed in each patient. AASI was obtained through individual 24 h-ABPM. The relationship between AASI and LVDD was analyzed. RESULTS: A total of 107 patients with HFpEF were included. The mean age was 68.45 ± 14.02 years and 63 (59%) were women. The patients were divided into two groups according to the upper normal border of AASI (0.55). AASI > 0.55 group were more likely to be older, to have higher mean systolic blood pressure and worsen left ventricular diastolic function than AASI group ≤ 0.55. AASI was closely positive related to the diastolic function parameters, including mean E/e' (r = 0.307, P = 0.001), septal E/e' (r = 0.290, P = 0.002), lateral E/e' (r = 0.276, P = 0.004) and E (r = 0.274, P = 0.004). After adjusting for conventional risk factors, AASI was still an independent risk factors of mean E/e' > 10 in patients with HFpEF (OR: 2.929, 95%CI: 1.214-7.064, P = 0.017), and the association between AASI and mean E/e' > 14 was reduced (OR: 2.457, 95%CI: 1.030-5.860, P = 0.043). AASI had a partial predictive value for mean E/e' > 10 (AUC = 0.691, P = 0.002), while the predictive value for mean E/e' > 14 was attenuated (AUC = 0.624, P = 0.034). CONCLUSION: AASI was positive related to E/e' in HFpEF and might be an independent risk factor for the increase of mean E/e'.
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Insuficiencia Cardíaca , Hipertensión , Rigidez Vascular , Disfunción Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Volumen Sistólico , Rigidez Vascular/fisiología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiologíaRESUMEN
BACKGROUND: Cardiac fibrosis is the most important pathogenesis leading to cardiac remodeling and heart failure after myocardial infarction (MI). Tissue nonspecific alkaline phosphatase (TNAP) has recently been recognized as a potential prognostic factor for MI. Nevertheless, the role of TNAP in cardiac fibrosis after MI has not been explicitly delineated. METHODS: A systematic review and meta-analysis was conducted to assess the effect of serum TNAP levels on mortality in patients with ischemic heart disease (IHD). A correlation analysis was performed to investigate the relationship between serum levels of TNAP and biomarkers of fibrosis. Heart biopsies from patients with MI and a mouse model of MI were used to detect the expression and distribution of TNAP. Furthermore, we established adenovirus-mediated knockdown and overexpression of TNAP, using a combination of in vivo and in vitro studies in mice, to determine the role and mechanism of TNAP in cardiac fibrosis after MI. In the in vitro studies, cardiac fibroblasts were cultured on soft plates. FINDINGS: After searching the main databases and performing a detailed assessment of the full-text articles, eight studies with 14,816 individuals were included in the quantitative analysis. We found that a high serum TNAP level was associated with an increased risk of mortality in patients with IHD and MI. The correlation analysis revealed a positive correlation between serum TNAP levels and the concentration of fibrosis biomarkers (PICP/PIIINP). The expression of TNAP was upregulated in the myocardium of patients with MI and in a mouse model of MI, accompanied by fibroblast activation and the deposition of collagen fibers. In the in vivo study, TNAP knockdown ameliorated cardiac fibrosis and improved cardiac function in mice. TNAP overexpression aggravated cardiac fibrosis and worsened cardiac function. In the in vitro study, TNAP promoted cardiac fibroblast differentiation, migration and proliferation. Mechanistically, the pro-fibrotic effect of TNAP on cardiac fibroblasts was at least partially achieved by activating the TGF-ß1/Smads and ERK1/2 signaling pathways. INTERPRETATION: Based on these findings, TNAP plays an important pro-fibrotic role in cardiac fibrosis after MI by activating TGF-ß/Smads and ERK1/2 signaling, indicating that it functions as a potential regulator of and therapeutic target in cardiac fibrosis. FUNDING: This work was supported by the National Natural Science Foundation of China.
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Fosfatasa Alcalina/metabolismo , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miofibroblastos/metabolismo , Fosfatasa Alcalina/genética , Animales , Células Cultivadas , Fibrosis , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Miocitos Cardíacos/patología , Miofibroblastos/patología , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients. METHODS: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. RESULTS: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235-57.671] and CD8+T [HR: 10.883; 95%CI: 3.277-36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients. CONCLUSIONS: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient's disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients. TRIAL REGISTRATION: Prognostic Factors of Patients With COVID-19, NCT04292964 . Registered 03 March 2020. Retrospectively registered.
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Linfocitos T CD4-Positivos/citología , COVID-19/sangre , SARS-CoV-2/inmunología , Adulto , Anciano , Linfocitos T CD8-positivos/citología , COVID-19/diagnóstico , COVID-19/mortalidad , COVID-19/terapia , Comorbilidad , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Pandemias , Alta del Paciente , Pronóstico , Estudios Retrospectivos , SARS-CoV-2/genéticaRESUMEN
AIMS: Abnormal expression of long non-coding RNAs (lncRNAs) occurs in several diseases including renal fibrosis. Notably, growth arrest-specific 5 (Gas5) is a lncRNA, which functions as an essential modulator of cell proliferation and growth. However, the role and expression of lncRNA Gas5 associated with renal fibrosis remains controversial. Herein, we investigate the effect of lncRNA Gas5 deficiency in renal fibrosis induced by the operation of unilateral ureteric obstruction (UUO) in mice. MAIN METHODS: Sera and urine of mice were used to detect markers of renal function. Further, Masson and immunohistochemical staining, western blotting as well as qRT-PCR were performed to observe the distribution and expression of fibrosis marker in the kidney tissue of the mice. KEY FINDINGS: Unlike the wild type mice, the obstructed kidney in Gas5+/- mice showed more severe renal fibrosis and collagen deposition. In the UUO-Gas5+/- group, the serum levels of uric acid, serum creatinine, and the urine levels of albumin-to-creatinine ratio were higher. Moreover, the expression of mRNA and protein of α-smooth muscle actin (α-SMA), vimentin, collagen IV, fibronectin, and matrix metalloproteinase 9 (MMP9) were higher, whereas that of phosphatase and tensin homolog (PTEN) were lower with the difference being statistically significant (p < 0.05). SIGNIFICANCE: lncRNA Gas5 was up-regulated in renal fibrosis tissues, and its deficiency exacerbated renal fibrosis in the UUO mice model.
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Riñón/patología , ARN Largo no Codificante/metabolismo , Obstrucción Ureteral/genética , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Regulación de la Expresión Génica , Riñón/fisiopatología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Fosfohidrolasa PTEN/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal , Obstrucción Ureteral/fisiopatologíaRESUMEN
The aim of this study is to investigate clinical characteristics and fatal outcomes of hypertension as well as the role of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) use in patients with severe coronavirus disease 2019 (COVID-19). A total of 220 (female: 51.8%) patients with severe COVID-19 were included. The mean age of included patients was 59.5 years and 70 (31.8%) patients had a history of hypertension. There were 23 patients (32.9%) receiving ACEI/ARB therapy. Patients with hypertension were older and had more comorbidities, and were more likely to suffer from severe inflammatory response and acute cardiac injury. Moreover, patients with hypertension were associated with significantly higher risk of in-hospital mortality than patients without hypertension. After adjustment of potential confounders, the independent correlation was still observed. In addition, ACEI/ARB users were associated with lower level of high-sensitivity cardiac troponin I and creatinine kinase-myocardial band, and lower risk of acute cardiac injury than ACEI/ARB non-users. In conclusion, patients with hypertension were more likely to suffer from severe inflammatory response, acute cardiac injury and had high risk of in-hospital mortality in severe COVID-19. The use of ACEI/ARB may protect patients with COVID-19 from acute cardiac injury.
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COVID-19/complicaciones , Hipertensión/complicaciones , Hipertensión/mortalidad , SARS-CoV-2 , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/virología , Comorbilidad , Manejo de la Enfermedad , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Mortalidad , Índice de Severidad de la Enfermedad , Evaluación de SíntomasRESUMEN
BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.
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Infecciones por Coronavirus , Mortalidad Hospitalaria , Péptido Natriurético Encefálico/análisis , Pandemias , Fragmentos de Péptidos/análisis , Neumonía Viral , Adulto , Anciano , Betacoronavirus , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Valor Predictivo de las Pruebas , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: In this study, we aimed to investigate the preoperative serum carcinoembryonic antigen (CEA) in the diagnosis of positive lymph node metastasis (LNM), and to evaluated the relationship between CEA and survival in patients with locally advanced gastric cancer (LAGC). METHODS: The significance of the preoperative serum CEA level for the diagnose of LAGC and prediction of LNM was determined using the receiver operating characteristic (ROC) curve. The areas under the ROC of CEA were compared with those of other tumor markers or imaging examination including CT and MRI. Logistic regression was utilized to identify the risk factors predicting positive LNM. Independent prognosis factors were evaluated using univariate and multivariate COX regression analyses. RESULTS: The ROC curves showed that the AUCs of CEA, CA199, and CA125 for diagnosing LAGC were 0.727, 0.594, and 0.566. When used to predict LNM, the AUC of CEA, CA199 and CA125 were 0.696, 0.531, and 0.588. Logistic regression analysis demonstrated that preoperative serum CEA were significantly associated with positive LNM. On combining imaging examination with CEA, the sensitivity and specificity were 85.3 and 79.4%, respectively, with the AUC equal to 0.853. The combination of CEA and imaging examination preformed the highest levels of AUC and sensitivity for diagnosing LNM, which is significantly higher than using either of them alone. Although patients with abnormal CEA have a poor prognosis, two models of multivariate analysis showed that CEA was not the independent prognosis factor for survival. CONCLUSIONS: CEA can be used to diagnose gastric cancer and determine whether it has LNM. Moreover, combined with CEA could improve the diagnostic sensitivity of imaging examination for lymph node involvement.
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Adenocarcinoma/patología , Adenocarcinoma/cirugía , Antígeno Carcinoembrionario/sangre , Gastrectomía , Metástasis Linfática , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Adenocarcinoma/sangre , Adenocarcinoma/mortalidad , Adulto , Anciano , Área Bajo la Curva , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Preoperatorios/métodos , Periodo Preoperatorio , Pronóstico , Curva ROC , Estudios Retrospectivos , Neoplasias Gástricas/sangre , Neoplasias Gástricas/mortalidad , Análisis de SupervivenciaRESUMEN
Tissue nonspecific alkaline phosphatase (TNAP) is expressed widely in different tissues, modulating functions of metabolism and inflammation. However, the effect of TNAP on cardiac fibrosis remains controversial and needs to be further studied. The present study aims to investigate the role of TNAP on myocardial infarction (MI)-induced fibrosis and its mechanism. TNAP was upregulated in patients with MI, both in serum and injured hearts, and predicted in-hospital mortality. TNAP was also significantly upregulated after MI in rats, mostly in the border zone of the infarcted hearts combined with collagen synthesis. Administration of TNAP inhibitor, tetramisole, markedly improved cardiac function and fibrosis after MI. In the primary cultures of neonatal rat cardiac fibroblasts (CFs), TNAP inhibition significantly attenuated migration, differentiation, and expression of collagen-related genes. The TGF-ß1/Smads signaling suppression, and p-AMPK and p53 upregulation were involved in the process. When p53 inhibitor was administered, the antifibrotic effect of TNAP inhibition can be blocked. This study provides a direct evidence that inhibition of TNAP might be a novel regulator in cardiac fibrosis and exert an antifibrotic effect mainly through AMPK-TGF-ß1/Smads and p53 signals.
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Fosfatasa Alcalina/metabolismo , Proteínas de la Membrana/metabolismo , Miocardio/enzimología , Miocardio/patología , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adenilato Quinasa/metabolismo , Fosfatasa Alcalina/antagonistas & inhibidores , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/genética , Animales , Diferenciación Celular , Hipoxia de la Célula/efectos de los fármacos , Colágeno/metabolismo , Ciclina E/metabolismo , Fibroblastos/patología , Fibrosis , Mortalidad Hospitalaria , Humanos , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/sangre , Proteínas de la Membrana/genética , Infarto del Miocardio/sangre , Infarto del Miocardio/mortalidad , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Fosforilación , Ratas Sprague-Dawley , Regulación hacia Arriba/genética , Remodelación VascularRESUMEN
Primary synovial sarcoma of the duodenal bulb is a rare mesenchymal tumor with special morphological features. It usually originates from the major joints or tendon sheaths of the extremities and mostly seen in young population, but rarely found in gastrointestinal tract. In this manuscript, we reported the first case of synovial sarcoma arising between the intestinal wall of the duodenal bulb with a concomitant SYT/SSX type of the t(X;18) translocation. A 49-year-old male presented to our hospital with a 2-month history of upper abdominal pain along with a 4-day amply jaundice. Tumor marker testing showed only a slight increase of carbohydrate antigen 19-9 (CA19-9). A computed tomography scan of his abdomen showed that indeterminate tissue occupied the duodenal bulb wall, compressed the surrounding tissues, and measured roughly 5.0 cm × 7.7 cm × 8.7 cm. Since the sarcoma grows between the intestinal wall, which cannot be detected by endoscopy, an initial diagnosis of duodenal wall stromal tumor was made at that time. Postoperative Immunohistochemistry results showed that the tumor was positive for the expression of transducin-like enhancer of split 1, B-cell lymphoma 2, and Vimentin. These pathological findings were indicative of the diagnosis of synovial sarcoma, but still did not provide sufficient diagnostic evidence. Finally we confirmed the diagnosis by using fluorescence in situ hybridization (FISH) with detection of the t(X;18) (SYT-SSX) translocation. No such lesions were found on preoperative examination, so a diagnosis of primary duodenal synovial sarcoma was made. After literature review, we found four reports of duodenal synovial sarcomas, all of which could be detected endoscopically, but there were no results of long-term follow-up. This case is the first reported case of synovial sarcoma arising between the intestinal walls of the duodenal bulb treated twice with ifosfamide and followed up for 13 months without recurrence.
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OBJECTIVE: To assess the efficacy and safety of catheter-based renal denervation (RDN) for the treatment of uncontrolled hypertension by conducting a systematic review and a meta-analysis. METHODS: The Medline, Cochrane Library, and Embase databases were searched for clinical studies between January 1, 2009, and July 16, 2018. Studies that evaluated the effect of RDN on uncontrolled hypertension were identified. The primary endpoints were changes in 24-hour ambulatory systolic blood pressure (BP) and office systolic BP. The secondary endpoints included changes in 24-hour ambulatory diastolic BP, office diastolic BP, and major adverse events. RESULTS: After a literature search and detailed evaluation, 12 randomized controlled trials with a total of 1539 individuals were included in the quantitative analysis. Pooled analyses indicated that RDN was associated with a significantly greater reduction of 24-hour systolic BP (mean difference [MD], -4.02 mm Hg; 95% CI, -5.49 to -2.56; P<.001) and office systolic BP (MD, -8.93 mm Hg; 95% CI, -14.03 to -3.83; P<.001) than controls. Similarly, RDN significantly reduced 24-hour diastolic BP (MD, -2.05 mm Hg; 95% CI, -3.05 to -1.05; P<.001) and office diastolic BP (MD, -4.49 mm Hg; 95% CI, -6.46 to -2.52; P<.001). RDN was not associated with an increased risk of major adverse events (relative risk, 1.06; 95% CI, 0.72 to 1.57; P=.76). CONCLUSIONS: Catheter-based RDN was associated with a significant BP-lowering benefit without increasing major adverse events.
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Desnervación Autonómica/métodos , Ablación por Catéter/métodos , Hipertensión/diagnóstico , Hipertensión/cirugía , Riñón/cirugía , Adulto , Anciano , Electrocardiografía Ambulatoria/métodos , Femenino , Humanos , Riñón/inervación , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
AIMS: The sex-related differences in the clinical outcomes of rhythm and safety after catheter ablation remain unclear. The purpose of this study was to compare the clinical outcomes of catheter ablation for atrial fibrillation (AF) in women and men. METHODS AND RESULTS: The Medline and EMBASE databases were searched for published articles up to December 2018. Studies that met our predefined inclusion criteria were included. The primary endpoints were freedom from AF/atrial tachycardia (AT) recurrence, stroke/transient ischaemic attack (TIA), and all-cause mortality. After literature search and detailed assessment, 19 observational studies (151 370 patients; 34% women) were identified. Our analyses showed that the rate of freedom from AF/AT recurrence was lower in women than men at the 2.4-year follow-up [odds ratio (OR): 0.75, 95% confidence interval (CI) 0.69-0.81; P < 0.0001]. Moreover, women had an increased risk of stroke/TIA (OR: 1.42, 95% CI 1.21-1.67; P < 0.0001) and all-cause mortality (OR: 1.53, 95% CI 1.02-2.28; P = 0.04). Nevertheless, for the endpoint of all-cause mortality, there was no significant difference between the two genders in the subgroup of prospective studies (OR: 1.19, 95% CI 0.69-2.05; P = 0.53). Additionally, women were more likely to experience major complications compared with men (pericardial effusion/tamponade, major bleeding requiring transfusion, and pacemaker implantation). CONCLUSIONS: Women who underwent catheter ablation of AF might experience lower efficacy and a higher risk of stroke/TIA and major complications than men. The reasons for these sex-related differences need to be further studied.
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Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Accidente Cerebrovascular/prevención & control , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Salud Global , Humanos , Incidencia , Pronóstico , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
Introduction: Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric cancer (LAGC); however, evidence for its use as a standard treatment has not been established in China. The aim of this study was to investigate the effectiveness, safety, and feasibility of the FLOT regimen as neoadjuvant chemotherapy in Chinese patients with resectable LAGC. Methods: We conducted an observational study to compare the effectiveness of FLOT regimen consisting of docetaxel (60 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), and 5-fluorouracil (2,600 mg/m2 as a 24 hr infusion), all given on day 1 and administered every 2 weeks versus initial surgery followed by chemotherapy in patients with clinical T3-4 LAGC. OS was compared by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) and propensity score-matched (PSM) analysis. In addition, we performed subgroup analyses to determine the effectiveness of the FLOT regimen in clinically relevant patient subsets. Results: Overall, 47 patients who received initial FLOT chemotherapy and 269 patients who received initial surgery were enrolled in this study. In the PSM analysis, the FLOT-first group showed favorable OS compared with the surgery-first group (41 vs 41 [HR, 0.416; 95% CI, 0.218-0.794; P=0.008]), and 3-year survival rates were 58.7% and 30.9% in the FLOT-first group and surgery-first group, respectively. IPTW analysis showed similar results. However, the effect of FLOT was low (HR, 0.868; 95 CI%, 0.215-3.504) in patients without lymph node metastasis. Conclusion: Our study suggests that preoperative FLOT chemotherapy is safe and feasible. In terms of OS, FLOT may be superior to initial surgery followed by chemotherapy in reducing morbidity with resectable LAGC.
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OBJECTIVE: The aim of this meta-analysis was to compare the clinical outcomes of transcatheter aortic valve replacement (TAVR) with those of surgical aortic valve replacement (SAVR) in patients with chronic kidney disease (CKD). DESIGN: Meta-analysis of 10 observational studies. SETTING: Hospital. PARTICIPANTS: Patients with CKD (9,619) undergoing aortic valve replacement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Medline, Cochrane Library, and Embase databases were searched for clinical studies published from January 2000 to October 2018. Studies that fulfilled the predefined inclusion criteria were included. The primary clinical outcomes included early all-cause mortality and postoperative stroke. Random-effects modeling was used to calculate odds ratio (OR) and 95% CI. After a literature search of the major databases, 10 observational cohort studies with a total of 9,619 patients were identified. Pooled analysis indicated that, when compared with SAVR, TAVR was associated with a lower risk of early all-cause mortality (6.1% v 10.2%; OR: 0.71; 95% CI: 0.51-0.98) and stroke (1.1% v 2.2%; OR: 0.53; 95% CI: 0.37-0.75). Although TAVR increased the risk of pacemaker implantation (OR: 2.06; 95% CI: 1.16-3.66), it reduced the risk of blood transfusion (OR: 0.50; 95% CI: 0.39-0.65), infection (OR: 0.30; 95% CI: 0.13-0.70), acute kidney injury (AKI) (OR: 0.46; 95% CI: 0.38-0.55), and AKI requiring dialysis (OR: 0.66; 95% CI: 0.58-0.75). There were not significant differences in the incidence rates of cardiac tamponade (OR: 0.60; 95% CI: 0.26-1.36) and major vascular damage (OR: 1.12; 95% CI: 0.81-1.55) between the 2 groups. CONCLUSION: Transcatheter aortic valve replacement might be a preferable approach to SAVR in patients with CKD. A large, prospective, randomized controlled trial is warranted.
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Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/cirugía , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Humanos , Mortalidad/tendencias , Estudios Observacionales como Asunto/métodos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in renal transplant recipients. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register from the inception to March 2015 for relevant studies. Data concerning publication information, population characteristics, and transplant information were extracted. Odds ratios (ORs) was calculated for the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. RESULTS: This meta-analysis included 22 case-control studies including 2779 cases of renal transplant recipients. The pooled estimate showed that the IL-10-1082 GG genotype was not significantly associated with AR risk (ORrandom=1.07, 95% CI 0.80-1.43, p = 0.64). Similarly, the pooled estimate showed that the IL-10-1082 G allele was not significantly associated with AR risk (ORfixed=1.02, 95% CI 0.90-1.16, p = 0.74). None of subgroup analyses yielded significant results in the association between IL-10-1082 GG genotype (or IL-10-1082 G allele) and AR risk. Meta-regression confirmed that there was no significant correlation between the pre-selected trial characteristics and our study results. CONCLUSIONS: This meta-analysis suggests that IL-10-1082 G/A polymorphism is not significantly associated with AR risk in renal transplant recipients.
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Rechazo de Injerto/genética , Interleucina-10/genética , Trasplante de Riñón , HumanosRESUMEN
OBJECTIVE: The purpose of this meta-analysis was to assess the role of preoperative statin therapy on adverse cardiovascular events in patients undergoing valve surgery. DESIGN: Meta-analysis of 10 observational studies. SETTING: Hospital. PARTICIPANTS: 22,158 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Medline, Cochrane, and Embase databases were searched for clinical studies published up to June 2014. Studies that evaluated the effects of preoperative statin therapy on valve surgery were included. After a literature search in the major databases, 10 observational studies with 22,518 patients were identified. Pool analysis indicated that preoperative statin therapy was associated with a significantly lower risk of early all-cause mortality (Odds ratio [OR]: 0.69; 95% confidence interval [CI] 0.50-0.95, p = 0.03). The benefits of preoperative statin therapy were more obvious in studies with isolated valve surgery, resulting in a 1.9% absolute risk and a 38% odds reduction of early mortality (2.4 v 4.3%; OR: 0.62; 95% CI 0.49-0.77, p<0.0001). A significant reduction by statin therapy also was observed for atrial fibrillation (OR 0.88, 95% CI: 0.80-0.98, p = 0.02). However, statin therapy was not associated with a lower risk of postoperative stroke (OR: 0.74; 95% CI 0.46-1.19, p = 0.21), myocardial infarction (OR: 1.02; 95% CI 0.78-1.34, p = 0.87), and renal failure (OR: 0.91; 95% CI 0.57-1.44, p = 0.68). CONCLUSIONS: Preoperative statin therapy was associated with a significantly lower risk of early mortality in patients undergoing isolated valve surgery. A prospective, randomized, controlled trial is warranted.