RESUMEN
The 'cancer cell fusion' theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynamics and properties of tumor-hybrid cells (THC), as well as the molecular mechanisms beneath this fusion process by several techniques: electron-microscopy, karyotyping, CRISPR-Cas9, RNA-seq, immunostaining, signaling blockage, among others. Moreover, mice models were assessed for in vivo characterization of hybrids colonization and invasiveness. Then, the presence of THCs in bloodstream and samples from primary and metastatic lesions were detected by FACS and immunofluorescence protocols, and their correlations with TNM stages established. Our data indicate that the generation of THCs depends on the expression of CD36 on tumor stem cells and the oxidative state and polarization of monocytes, the latter being strongly influenced by microenvironmental fluctuations. Highly oxidized M2-like monocytes show the strongest affinity to fuse with tumor stem cells. THCs are able to proliferate, colonize and invade organs. THC-specific cell surface signature CD36+CD14+PANK+ allows identifying them in matched primary tumor tissues and metastases as well as in bloodstream from patients with lung cancer, thus functioning as a biomarker. THCs levels in circulation correlate with TNM classification. Our results suggest that THCs are involved in both origin and spread of metastatic cells. Furthermore, they might set the bases for future therapies to avoid or eradicate lung cancer metastasis.
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Neoplasias Pulmonares , Monocitos , Células Madre Neoplásicas , Animales , Fusión Celular , Humanos , Células Híbridas , RatonesRESUMEN
BACKGROUND: To assess the efficacy and safety of intramyocardial autologous bone marrow mononuclear stem cells (BMMNC) grafting combined with coronary artery bypass grafting (CABG) on ventricular remodeling and global and regional wall motion after acute transmural myocardial infarction (AMI). METHODS: Randomized controlled trial including 20 patients with non-revascularized transmural AMI, left ventricular ejection fraction (LVEF) lower than 50% and surgical indication for CABG. The stem cell group was treated with BMMNC grafting by direct intramyocardial injection between the 10th and 15th days after AMI (subacute phase) combined with CABG under cardiopulmonary bypass; the control group was only treated with CABG. Magnetic resonance imaging with gadolinium and stress echocardiography were performed presurgery and 9 months postsurgery. RESULTS: Seventeen patients completed the follow-up. The baseline characteristics of both groups were homogeneous. No significant differences were found in the increase in LVEF (control: 6.99±4.60, cells: 7.47±6.61, P=0.876) or in the decrease in global (control: 0.28±0.39, cells: 0.22±0.28, P=0.759) or regional (control: 0.52±0.38, cells: 0.74±0.60, P=0.415) wall motion indices between the control and stem cell groups of AMI patients. No differences were found in the recovered non-viable segments (control: 1.29±1.11, cells: 2.50±1.41, P=0.091) or in the decrease in end-diastolic (control: 14.05±19.72, cells: 18.40±29.89, P=0.725) or end-systolic (control: 15.42±13.93, cells: 23.06±25.03, P=0.442) volumes. No complications from stem cell grafting were observed. CONCLUSIONS: The results from our study reported herein suggest that intramyocardial BMMNC administration during CABG in patients with AMI causes no medium- to long-term improvement in ventricular remodeling.
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Trasplante de Médula Ósea , Infarto del Miocardio/cirugía , Miocardio/patología , Regeneración , Trasplante de Células Madre , Función Ventricular Izquierda , Remodelación Ventricular , Anciano , Trasplante de Médula Ósea/efectos adversos , Puente de Arteria Coronaria , Método Doble Ciego , Ecocardiografía de Estrés , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Contracción Miocárdica , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Estudios Prospectivos , Recuperación de la Función , España , Trasplante de Células Madre/efectos adversos , Factores de Tiempo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
INTRODUCTION: The risk of mortality in cardiac surgery is generally evaluated using preoperative risk-scale models. However, intraoperative factors may change the risk factors of patients, and the organism functionality parameters determined upon ICU admittance could therefore be more relevant in deciding operative mortality. The goals of this study were to find associations between the general parameters of organism functionality upon ICU admission and the operative mortality following cardiac operations, to develop a Post Cardiac Surgery (POCAS) Scale to define operative risk categories and to validate an operative mortality risk score. METHODS: We conducted a prospective study, including 920 patients who had undergone cardiac surgery with cardiopulmonary bypass. Several parameters recorded on their ICU admission were explored, looking for a univariate and multivariate association with in-hospital mortality (90 days). In-hospital mortality was 9%. Four independent factors were included in the POCAS mortality risk model: mean arterial pressure, bicarbonate, lactate and the International Normalized Ratio (INR). The POCAS scale was compared with four other risk scores in the validation series. RESULTS: In-hospital mortality (90 days) was 9%. Four independent factors were included in the POCAS mortality risk model: mean arterial pressure, bicarbonate ratio, lactate ratio and the INR. The POCAS scale was compared with four other risk scores in the validation series. Discriminatory power (accuracy) was defined with a receiver-operating characteristics (ROC) analysis. The best accuracy in predicting in-hospital mortality (90 days) was achieved by POCAS. The areas under the ROC curves of the different systems analyzed were 0.890 (POCAS), followed by 0.847 (Simplified Acute Physiology Score (SAP II)), 0.825 (Sepsis-related Organ Failure Assessment (SOFA)), 0.768 (Acute Physiology and Chronic Health Evaluation (APACHE II)), 0.754 (logistic EuroSCORE), 0.714 (standard EuroSCORE) and 0.699 (Age, Creatinine, Ejection Fraction (ACEF) score). CONCLUSIONS: Our new system to predict the operative mortality risk of patients undergoing cardiac surgery is better than others used for this purpose (SAP II, SOFA, APACHE II, logistic EuroSCORE, standard EuroSCORE, and ACEF score). Moreover, it is an easy-to-use tool since it only requires four risk factors for its calculation.
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Procedimientos Quirúrgicos Cardíacos/mortalidad , Procedimientos Quirúrgicos Cardíacos/tendencias , Mortalidad Hospitalaria/tendencias , Complicaciones Posoperatorias/mortalidad , Índice de Severidad de la Enfermedad , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/diagnóstico , Estudios ProspectivosRESUMEN
Mediastinitis due to Klebsiella pneumoniae, related to thoracic wall contamination after cardiac surgery, has rarely been described. We aim to report a case of fulminant mediastinitis due to extended-spectrum beta-lactamase-producing K. pneumoniae, secondary to a disseminated concomitant pulmonary infection. The patient remained pauci-symptomatic until clinical manifestations of sepsis acutely appeared.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Infección Hospitalaria/microbiología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/enzimología , Mediastinitis/microbiología , Infecciones del Sistema Respiratorio/microbiología , Esternotomía/efectos adversos , Infección de la Herida Quirúrgica/microbiología , Resistencia betalactámica , beta-Lactamasas/metabolismo , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/terapia , Resultado Fatal , Femenino , Humanos , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/terapia , Mediastinitis/diagnóstico , Mediastinitis/terapia , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/terapia , Sepsis/microbiología , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/terapia , Insuficiencia del TratamientoRESUMEN
OBJECTIVES: Preoperative anemia has been related with adverse outcomes in elective valve replacement and CABG surgery. Impact of preoperative anemia on outcome in octogenarians submitted to cardiopulmonary bypass (CPB) has not yet been precisely described. METHODS: We analyzed association between preoperative hemoglobin level, minimum intraoperative and immediate postoperative hematocrit (HCT), and other co-morbidities and occurrence of adverse outcomes in 227 octogenarians who underwent cardiac surgery. RESULTS: Frequency of preoperative anemia was 41.9% (40.4% in male and 43.5% in female patients). Postoperative mortality was 13.2% (9% in non-anemic patients vs. 18.9% in anemic). 44.5% of patients suffered at least one postoperative adverse outcome (43.1% non-anemic vs. 46.3% anemic). In multivariate analysis (after adjusting independent preoperative risk factors for operative mortality and EuroSCORE) preoperative creatinine level [odds ratio (OR), 2.29; 95% confidence interval (CI), 1.06-4.98; P=0.035], immediate postoperative HCT <24% (OR, 2.78; 95% CI, 1.04-7.38; P=0.039), perioperative red blood cell (RBC) transfusion (OR, 1.58; 95% CI, 1.24-2.00; P=0.0001), peripheral vascular disease (OR, 4.92; 95% CI, 1.45-16.69; P=0.012) and urgent surgery (OR, 10.57; 95% CI, 2.54-43.91; P=0.0001) were identified as independent predictors for in-hospital mortality. CONCLUSIONS: Mortality and adverse postoperative outcome increase in anemic octogenarians undergoing cardiac surgery. Although mortality is directly related to immediate postoperative anemia, adverse outcomes mainly depend on associated co-morbidities.