COMPARISON OF THREE MIDAZOLAM-BASED SEDATION PROTOCOLS IN BUDGERIGARS (MELOPSITTACUS UNDULATUS) AND BLACK-CHEEKED LOVEBIRDS (AGAPORNIS NIGRIGENIS).

This randomized, crossover study evaluated three sedation protocols administered subcutaneously in nine budgerigars (Melopsittacus undulatus) and nine black-cheeked lovebirds (Agapornis nigrigenis). All protocols included midazolam (5 mg/kg), combined with butorphanol (5 mg/kg) (BM), medetomidine (20 lg/kg) (MM), or alfaxalone (13 mg/kg) (AM). Mortalities from suspected cardiorespiratory arrest were observed when AM was used in lovebirds, even after reduction of alfaxalone dosage to 3 mg/kg, and therefore this protocol was excluded from further use in this species. Induction and recovery times were recorded and their quality assessed. Sedation depth and heart and respiratory rates were measured every 5 min and radiographic positioning was attempted at 10 and 20 min. At 30 min, midazolam and medetomidine were reversed with flumazenil (0.05 mg/kg, SC), and atipamezole (0.2 mg/kg, SC), respectively. MM consistently provided deep sedation in both species, with successful radiographic positioning at every attempt. As expected, heart rate was often lower with MM than with other protocols, but no associated complications were noted. In budgerigars, BM had the lowest radiographic positioning success rate (10 min: 5/9, 20 min: 3/9), whereas in lovebirds it provided significantly deeper sedation (P < 0.001), allowing radiographic positioning in all subjects. In both species, BM provided the shortest recovery times. AM resulted in reliable radiographic positioning of all budgerigars at 10 min, but not at 20 min (5/ 9), and provided consistently poor recoveries. This study highlights how differently two psittacine species of similar size may react to the same sedation protocols. AM sedation cannot be fully reversed and produced significant undesirable effects, several of which have been previously reported with alfaxalone administration to avian species. The authors therefore caution against using alfaxalone-midazolam combinations in budgerigars and black-cheeked lovebirds. Both BM and MM provided reliable sedation in these species, and appear to be suitable alternatives to AM.

Combination of CNTs with Classical Drugs for Treatment in Human Colorectal Adenocarcinoma (HT-29) Cell Line.

Due to the increase in new types of cancer cells and resistance to drugs, conventional cancer treatments are sometimes insufficient. Therefore, an alternative is to apply nanotechnology to biomedical areas, minimizing side effects and drug resistance and improving treatment efficacy. This work aims to find a promising cancer treatment in the human colorectal adenocarcinoma cell line (HT-29) to minimize the viability of cells (IC50) by using carbon nanotubes (CNTs) combined with different drugs (5-fluorouracil (5-FU) and two repurposing drugs-tacrine (TAC) and ethionamide (ETA). Several CNT samples with different functional groups (-O, -N, -S) and textural properties were prepared and characterized by elemental and thermogravimetry analysis, size distribution, and textural and temperature programmed desorption. The samples that interacted most with the drugs and contributed to improving HT-29 cell treatment were samples doped with nitrogen and sulfur groups (CNT-BM-N and CNT-H2SO4-BM) with IC50 1.98 and 2.50 µmol∙dm-3 from 5-FU and 15.32 and 15.81 µmol∙dm-3 from TAC. On the other hand, ETA had no activity, even combined with the CNTs. These results allow us to conclude that the activity was improved for both 5-FU and TAC when combined with CNTs.

Combination Therapy With CD147-Targeted Nanoparticles Carrying Phenformin Decreases Lung Cancer Growth.

Lung cancer is one of the most fatal cancers worldwide. Resistance to conventional therapies remains a hindrance to patient treatment. Therefore, the development of more effective anti-cancer therapeutic strategies is imperative. Solid tumors exhibit a hyperglycolytic phenotype, leading to enhanced lactate production; and, consequently, its extrusion to the tumor microenvironment. Previous data reveals that inhibition of CD147, the chaperone of lactate transporters (MCTs), decreases lactate export in lung cancer cells and sensitizes them to phenformin, leading to a drastic decrease in cell growth. In this study, the development of anti-CD147 targeted liposomes (LUVs) carrying phenformin is envisioned, and their efficacy is evaluated to eliminate lung cancer cells. Herein, the therapeutic effect of free phenformin and anti-CD147 antibody, as well as the efficacy of anti-CD147 LUVs carrying phenformin on A549, H292, and PC-9 cell growth, metabolism, and invasion, are evaluated. Data reveals that phenformin decreases 2D and 3D-cancer cell growth and that the anti-CD147 antibody reduces cell invasion. Importantly, anti-CD147 LUVs carrying phenformin are internalized by cancer cells and impaired lung cancer cell growth in vitro and in vivo. Overall, these results provide evidence for the effectiveness of anti-CD147 LUVs carrying phenformin in compromising lung cancer cell aggressiveness.

Efficient clinical-grade γ-retroviral vector purification by high-speed centrifugation for CAR T cell manufacturing.

γ-Retroviral vectors (γ-RV) are powerful tools for gene therapy applications. Current clinical vectors are produced from stable producer cell lines which require minimal further downstream processing, while purification schemes for γ-RV produced by transient transfection have not been thoroughly investigated. We aimed to develop a method to purify transiently produced γ-RV for early clinical studies. Here, we report a simple one-step purification method by high-speed centrifugation for γ-RV produced by transient transfection for clinical application. High-speed centrifugation enabled the concentration of viral titers in the range of 107-108 TU/mL with >80% overall recovery. Analysis of research-grade concentrated vector revealed sufficient reduction in product- and process-related impurities. Furthermore, product characterization of clinical-grade γ-RV by BioReliance demonstrated two-logs lower impurities per transducing unit compared with regulatory authority-approved stable producer cell line vector for clinical application. In terms of CAR T cell manufacturing, clinical-grade γ-RV produced by transient transfection and purified by high-speed centrifugation was similar to γ-RV produced from a clinical-grade stable producer cell line. This method will be of value for studies using γ-RV to bridge vector supply between early- and late-stage clinical trials.

Age-adjusted Charlson Comorbidity Index Does Not Predict Outcomes in Patients Submitted to Noninvasive Ventilation / El índice de comorbilidad de Charlson ajustado por edad no predice los resultados de pacientes sometidos a ventilación no invasiva

Introduction: Comorbidities are thought to have prognostic impact on outcomes of patients submitted to noninvasive ventilation (NIV). Our goal was to determine if age-adjusted Charlson comorbidity index (ACCI) could predict outcomes in patients undergoing NIV due to acute respiratory failure. Methods:Patients in respiratory failure submitted to NIV were prospective evaluated comparing patien's characteristics and outcomes according to ACCI ≤ median vs. ACCI > median. Each comorbidity composing the index was tested as predictor of NIV failure and readmission/mortality risk at 30 and 90 days, using logistic regression analysis. NIV failure was defined as need for invasive mechanical ventilation and/or death. Results: 177 patients were enrolled. Median ACCI score was 5 points. Comparing patients with ACCI > 5 with ACCI ≤ 5, the former group was older but APACHE II was similar. Time to first NIV disconnection was inferior for ACCI > 5 patients (OR 0.46, 95% CI 0.23-0.89, p = 0.021), after gender and age adjustment. No differences were found in length of stay, time on NIV, NIV complications or failure, and 30 and 90-day hospital readmission or death, before and after adjustment. None of the single comorbidities was predictive of NIV failure and readmission risk, when adjusted to sex and age. Conclusion: ACCI is not a good predictor for short and medium-term outcomes in patients submitted to NIV

Introducción: Las comorbilidades parecen tener un impacto en el pronóstico de los resultados de pacientes sometidos a ventilación no invasiva (VNI). Nuestro objetivo fue determinar si el ajuste por edad del índice de comorbilidad de Charlson (ICC) podía predecir los resultados de aquellos pacientes sometidos a VNI por insuficiencia respiratoria aguda. Métodos: Se evaluaron de forma prospectiva pacientes con insuficiencia respiratoria sometidos a VNI, comparando las características de los pacientes y sus resultados valorados como ICCmediana. Mediante un análisis de regresión logística, cada comorbilidad incluida en el índice se evaluó como predictor de fracaso de VNI y de riesgo de reingreso/mortalidad a los 30 y 90 días. Se definió fracaso de VNI como la necesidad de ventilación mecánica asistida y/o muerte. Resultados: Se incluyeron 177 pacientes. La mediana del valor del ICC fue de 5 puntos. En la comparación de pacientes con ICC>5 frente a pacientes con ICC≤5, el primer grupo resultó ser el de mayor edad, aunque la clasificación por APACHE II fue similar. El tiempo hasta la primera desconexión de VNI fue inferior en pacientes con ICC>5 (OR: 0,46; IC 95%: 0,23-0,89; p=0,021), tras el ajuste por género y edad. No se encontraron diferencias en la duración de la hospitalización, el tiempo con VNI, complicaciones o fracaso de la VNI y el reingreso hospitalario o la muerte a los 30 y 90 días, antes y después del ajuste. Ninguna de las comorbilidades analizadas era predictora de fracaso de la VNI o del riesgo de reingreso cuando se ajustaron por sexo edad. Conclusión: El ICC no es un buen predictor de los resultados a corto y medio plazo de pacientes sometidos a VNI

Age-adjusted Charlson Comorbidity Index Does Not Predict Outcomes in Patients Submitted to Noninvasive Ventilation.

INTRODUCTION: Comorbidities are thought to have prognostic impact on outcomes of patients submitted to noninvasive ventilation (NIV). Our goal was to determine if age-adjusted Charlson comorbidity index (ACCI) could predict outcomes in patients undergoing NIV due to acute respiratory failure. METHODS: Patients in respiratory failure submitted to NIV were prospective evaluated comparing patient's characteristics and outcomes according to ACCI≤median vs. ACCI>median. Each comorbidity composing the index was tested as predictor of NIV failure and readmission/mortality risk at 30 and 90 days, using logistic regression analysis. NIV failure was defined as need for invasive mechanical ventilation and/or death. RESULTS: 177 patients were enrolled. Median ACCI score was 5 points. Comparing patients with ACCI>5 with ACCI≤5, the former group was older but APACHE II was similar. Time to first NIV disconnection was inferior for ACCI>5 patients (OR 0.46, 95% CI 0.23-0.89, p=0.021), after gender and age adjustment. No differences were found in length of stay, time on NIV, NIV complications or failure, and 30 and 90-day hospital readmission or death, before and after adjustment. None of the single comorbidities was predictive of NIV failure and readmission risk, when adjusted to sex and age. CONCLUSION: ACCI is not a good predictor for short and medium-term outcomes in patients submitted to NIV.

Characteristics and outcomes of heart failure hospitalization before implementation of a heart failure clinic: The PRECIC study.

OBJECTIVE: This study aims to characterize patients hospitalized for acute heart failure (HF) in an internal medicine department and their one-year mortality and rate of rehospitalization for decompensated HF. METHODS: This retrospective observational study enrolled all patients discharged in 2012 after hospitalization for acute HF. Discharge summaries, clinical records and telephone interviews were analysed. The data reports to the year before implementation of a heart failure clinic. RESULTS: Four hundred and twenty-nine patients were enrolled, with a mean age of 79 years, 62.5% female. The most prevalent comorbidity and etiology was hypertension (86.7%) and the most frequent decompensation trigger was infection. HF with preserved ejection fraction (HFpEF) was present in 70.5%. In-hospital mortality was 7.9%. At discharge more than half of the patients were prescribed beta-blockers (52.8%) and angiotensin-converting enzyme inhibitors (52%). Women presented a significantly higher proportion of HFpEF than men (75.3% vs. 62.7%, p=0.01). Patients with diabetes and those with ischemic etiology had significantly higher proportions of HF with reduced ejection fraction (HFrEF) (34.8% vs. 24.3% in non-diabetic patients, p=0.027, and 56.2% vs. 15.6% for other etiologies, p<0.001). The HFrEF group were more frequently discharged under beta-blockers and spironolactone (75.2% vs. 46.4% in the HFpEF group, p<0.001 and 31.2% vs. 12.6% in the HFpEF group, p<0.001, respectively). Mortality was 34.3% and rehospitalization for HF was 30.5% in one-year follow-up. CONCLUSIONS: The population characterized is an elderly one, mainly female and with HFpEF. Nearly a third of patients died and/or were rehospitalized in the year following discharge.

Predictores e indicadores de vía aérea difícil en pacientes con diferentes índices de masa corporal / Predictors and indicators of difficult airway in patients with different body mass indexes

Objetivo: Identificar la relación entre diferentes predictores e indicadores de vía aérea difícil con el índice de masa corporal (IMC). Metodología: Estudio descriptivo y transversal realizado en pacientes que cumplieron los criterios de inclusión y exclusión durante un año. Evaluamos los predictores: antecedentes de roncar (AR), alteraciones de la articulación temporomandibular (ATM), clasificaciñon de Mallampati (CM) y clasificación de Cormack-Lehane (CCL); los indicadores: intentos de intubación (IE), compresión externa de la tráquea (CET) y uso de estilete (UE). La información se correlacionó y generó un modelo de regresión múltiple. Los resultados se expresaron en proporciones, gráficos de barras y dispersión. Resultados: ATM y CM fueron mas en los pacientes obesos, lo cual fue estadísticamente significativo (ATMp<0.05, CM p<0.001). No se encontró relación entre AR y CCL con el IMC. La CET fue más utilizada en pacientes con mayor IMC, lo cual fue estadísticamente significativo (p < 0.05). No evidenciamos relación entre IE y UE con obesidad. La regresión múltiple para predicción de intubación difícil arrojó la siguiente ecuación: 0.18IQ+0.32AR-0.60ATM+0.04CM+0.15CCL-1.26.R²=0.05 (F=0.65, alfa=0.67). Conclusiones: No todos los predictores de intubación difícil guardan relación con el IMC. Ninguna de las variables demostró tener influencia como preditor de vía aérea difícil. La obesidad por sí misma no es un predictor de vía aérea difícil.

Capacitación en soporte vital básico en la clínica central Cira García: resultados preliminares / Training in Basic Life Support in the Central Clinical Cira Garcia: preliminary results

En promedio los pacientes que sobreviven al PCR son aquellos en que la reanimación se inicia durante los primeros cuatro minutos. Determinar los conocimientos, habilidades y nivel de capacitación del personal de enfermería en soporte vital básico antes y después de un proceso educativo. Durante un periodo de 4 meses se impartió un curso-taller de 20 horas a 66 enfermeras del área de hospitalización, con una evaluación al inicio y al final del proceso educativo. La variable fue capacitación con 3 criterios: conocimiento con valor de 50 puntos, habilidad 50 puntos y competencia. Durante un periodo de 4 meses se impartió este curso de 20 horas organizado con 30 minutos para la evaluación inicial teórico-práctica, 2 horas de conferencias orientadoras, 17 horas de actividad práctica y 30 minutos para la evaluación teórica-práctica final. Éste fue impartido por profesores del servicio de anestesiología con experiencia en esta temática La fase teórica incluyó además el estudio individual de los contenidos por un manual elaborado para ello siguiendo las normas internacionales establecidas por el comité de enlace internacional. (ILCOR). Muestreo por conveniencia, instrumentos validados y calificados por el propio investigador. Se consideró capacitada, a la persona que logró aprobar los 2 criterios. En la evaluación inicial ninguna enfermera logró calificar como capacitada y en la evaluación final 100 por ciento. El resultado después del proceso educativo se consideró de bueno a excelente pues el nivel de competencia, habilidad y conocimiento fue alto. Recomendamos realizar investigaciones dirigidas a medir el impacto de la intervención educativa sobre la política de salud hospitalaria. Aún más, si se considera que actualmente la capacitación en RCPC están contenidas en la carpetas de evaluación para la acreditación de hospitales(AU)