Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages.

BACKGROUND: Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures. METHODS: To investigate the effect of tibolone in macrophage enzymatic activity, gene expression of cytokines, and its effect on foam cells formation. We use phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells. The cells were incubated 24 h and 48 h using pre and post-treatment schemes. We evaluated total ROS determination by NBT assay, expression of cytokines (IL-1ß, IL-6, TNF-α, NOS2, ARG1, TGFß) by RT-qPCR and foam cell formation in THP-1 differentiated macrophages stimulated with PMA. RESULTS: It was observed that the minor levels of total ROS determination were obtained with tibolone at 48 h in post-treatment scheme. Also, in a long term we found decrease the proinflammatory cytokines (IL-1ß, IL-6 and TNF-α). Finally, with treatment for 24 h with P4 y Tb we observed fewer LDL vesicles into macrophages cytoplasm. CONCLUSIONS: These results suggest that tibolone reduces the inflammatory process, also inhibits the foam cells formation; suggesting a possible role in reducing cardiovascular risk.

Asociación de factores de riesgo independientes con fracaso posextubación en pacientes desconectados de la ventilación mecánica / Association of independent risk factors with post-extubation failure in patients undergoing mechanical ventilation weaning

Resumen Introducción: Aun con adecuado protocolo de desconexión de la ventilación mecánica (DVM), el procedimiento falla en 15 a 30 % de los casos. Objetivo: Evaluar la asociación entre factores de riesgo independientes y fracaso posextubación en pacientes con DVM en una unidad de cuidados intensivos. Método: Estudio de cohorte, longitudinal, prospectivo, analítico, que incluyó pacientes sometidos a ventilación mecánica por más de 24 horas y que fueron extubados. Se obtuvieron reportes preextubación de hemoglobina, albúmina, fósforo, índice cintura-cadera y puntuación SOFA. Se definió como fracaso de extubación al reinicio de la ventilación mecánica en 48 horas o menos. Resultados: Se extubaron 123 pacientes, 74 hombres (60 %); la edad promedio fue de 50 ± 18 años. Ocurrió fracaso de extubación en 37 (30 %). Como factores de riesgo independentes se asoció hipoalbuminemia en 29 (23.8 %, RR = 1.43, IC 95 % = 1.11-1.85) e hipofosfatemia en 18 (14.6 %, RR = 2.98, IC 95 % = 1.66-5.35); se observaron dos o más factores de riesgo independientes en 22.7 % (RR = 1.51, IC 95 % = 1.14-2.00). Conclusiones: Identificar los factores de riesgo independentes antes de la DVM puede ayudar a reducir el fracaso de la extubación y la morbimortalidad asociada.

Abstract Introduction: Even with an adequate mechanical ventilation weaning (MVW) protocol, the procedure fails in 15 to 30 % of cases. Objective: To assess the association between independent risk factors (IRFs) and post-extubation failure in patients undergoing MVW in an intensive care unit. Method: Longitudinal, prospective, analytical cohort study in patients on mechanical ventilation for more than 24 hours and who were extubated. Pre-extubation reports of hemoglobin, albumin, phosphorus, waist-hip ratio and SOFA score were obtained. Extubation failure was defined as resumption of mechanical ventilation within 48 hours or less. Results: 123 patients were extubated, out of whom 74 were males (60 %); average age was 50 ± 18 years. Extubation failure occurred in 37 (30 %). Hypoalbuminemia was associated as an independent risk factor in 29 (23.8 %, RR = 1.43, 95 % CI = 1.11-1.85) and hypophosphatemia was in 18 (14.6 %, RR = 2.98, 95 % CI = 1.66-5.35); two or more IRFs were observed in 22.7 % (RR = 1.51, 95 % CI = 1.14-2.00). Conclusions: Identifying independent risk factors prior to MVW can help reduce the risk of extubation failure and associated morbidity and mortality.

Association of independent risk factors with post-extubation failure in patients undergoing mechanical ventilation weaning.

INTRODUCTION: Even with an adequate mechanical ventilation weaning (MVW) protocol, the procedure fails in 15 to 30 % of cases. OBJECTIVE: To assess the association between independent risk factors (IRFs) and post-extubation failure in patients undergoing MVW in an intensive care unit. METHOD: Longitudinal, prospective, analytical cohort study in patients on mechanical ventilation for more than 24 hours and who were extubated. Pre-extubation reports of hemoglobin, albumin, phosphorus, waist-hip ratio and SOFA score were obtained. Extubation failure was defined as resumption of mechanical ventilation within 48 hours or less. RESULTS: 123 patients were extubated, out of whom 74 were males (60 %); average age was 50 ± 18 years. Extubation failure occurred in 37 (30 %). Hypoalbuminemia was associated as an independent risk factor in 29 (23.8 %, RR = 1.43, 95 % CI = 1.11-1.85) and hypophosphatemia was in 18 (14.6 %, RR = 2.98, 95 % CI = 1.66-5.35); two or more IRFs were observed in 22.7 % (RR = 1.51, 95 % CI = 1.14-2.00). CONCLUSIONS: Identifying independent risk factors prior to MVW can help reduce the risk of extubation failure and associated morbidity and mortality. INTRODUCCIÓN: Aun con adecuado protocolo de desconexión de la ventilación mecánica (DVM), el procedimiento falla en 15 a 30 % de los casos. OBJETIVO: Evaluar la asociación entre factores de riesgo independientes y fracaso posextubación en pacientes con DVM en una unidad de cuidados intensivos. MÉTODO: Estudio de cohorte, longitudinal, prospectivo, analítico, que incluyó pacientes sometidos a ventilación mecánica por más de 24 horas y que fueron extubados. Se obtuvieron reportes preextubación de hemoglobina, albúmina, fósforo, índice cintura-cadera y puntuación SOFA. Se definió como fracaso de extubación al reinicio de la ventilación mecánica en 48 horas o menos. RESULTADOS: Se extubaron 123 pacientes, 74 hombres (60 %); la edad promedio fue de 50 ± 18 años. Ocurrió fracaso de extubación en 37 (30 %). Como factores de riesgo independentes se asoció hipoalbuminemia en 29 (23.8 %, RR = 1.43, IC 95 % = 1.11-1.85) e hipofosfatemia en 18 (14.6 %, RR = 2.98, IC 95 % = 1.66-5.35); se observaron dos o más factores de riesgo independientes en 22.7 % (RR = 1.51, IC 95 % = 1.14-2.00). CONCLUSIONES: Identificar los factores de riesgo independentes antes de la DVM puede ayudar a reducir el fracaso de la extubación y la morbimortalidad asociada.

The Effects of Ketamine on Cognitive Function in Elderly Patients Undergoing Ophthalmic Surgery: A Pilot Study.

BACKGROUND: Acute postoperative cognitive dysfunction is characterized by neurocognitive dysfunction and confusion. In this study, we compared the cognitive status of a geriatric population undergoing ophthalmic surgery, as assessed by the Short Portable Mental Status Questionnaire (SPMSQ) before and after ketamine administration. METHODS: Eighty patients were enrolled and randomly assigned in a double-blind study to receive either ketamine (0.3 mg/kg dose) or physiologic solution (control group). Sixty-five (control, n = 32; ketamine, n = 33) patients completed the trial. Cognitive performance was assessed with an abbreviated version of the SPMSQ. Measurements of analgesia, sedation, intraocular pressure, and hemodynamic variables were recorded. RESULTS: With respect to cognitive performance, the baseline evaluation was similar for the control and ketamine groups. Postoperative evaluation showed an improvement only in the ketamine group. No increase in intraocular pressure or a secondary nystagmus was observed. The average dose of midazolam was higher in the control group, but the difference was not clinically significant. After surgery, analgesic behavior was better in the ketamine group than in the control group. There were no differences between groups in the sedation scale or in hemodynamic variables. CONCLUSIONS: The administration of 0.3 mg/kg ketamine during ophthalmic surgery in geriatric patients changed their cognitive status as assessed by the SPMSQ, decreased the required dose of anesthetics, and produced no increase in intraocular pressure or in hemodynamic variables. However, because the evaluation only analyzed the immediate effects of the administered drug, further research will be required to examine the impact of ketamine on the postoperative cognitive performance of geriatric patients before the drug can be formally recommended for this purpose.