RESUMO
BACKGROUND: The criteria for the selection of COVID-19 patients that could benefit most from ECMO organ support are yet to be defined. In this study, we evaluated the predictive performance of ECMO mortality predictive models in patients with COVID-19. We also performed a cost-benefit analysis depending on the mortality predicted probability. We conducted a retrospective cohort study in COVID-19 patients who received ECMO at two tertiary care hospitals between March 2020 to July 2021. MATERIALS AND METHODS: We evaluated the discrimination (C-statistic), calibration (Cox calibration), and accuracy of the prediction of death due to severe ARDS in V-V ECMO score (PRESERVE), the Respiratory Extracorporeal Membrane Oxygenation Survival Score (RESP) score, and the PREdiction of Survival on ECMO Therapy-Score (PRESET) score. In addition, we compared the RESP score with Plateau pressure instead of Peak pressure. RESULTS: We included a total of 36 patients, 29 (80%) of them male and with a median (IQR) APACHE of 10 (8-15). The PRESET score had the highest discrimination (AUROCs 0.81 [95%CI 0.67-0.94]) and calibration (calibration-in-the-large 0.5 [95%CI -1.4 to 0.3]; calibration slope 2.2 [95%CI 0.7/3.7]). The RESP score with Plateau pressure had higher discrimination than the conventional RESP score. The cost per QALY in the USA, adjusted to life expectancy, was higher than USD 100 000 in patients older than 45 years with a PRESET > 10. CONCLUSION: The PRESET score had the highest predictive performance and could help in the selection of patients that benefit most from this resource-demanding and highly invasive organ support.
Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Estudos Retrospectivos , Calibragem , Curva ROC , COVID-19/terapiaRESUMO
AIM: To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosyl-methionine (AdoMet). METHODS: Primary hepatocyte cultures were pretreated with 100 micromol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined by the TUNEL and DNA ladder assays. JNK activity and its inhibition by SP600125 and AdoMet were determined by Western blot analysis of c-jun phosphorylation and Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway were determined by Western blot analysis of cytochrome c release and pro-caspase 3 fragmentation. The AdoMet effect on glutathione levels was measured by Ellman's method and reactive oxygen species (ROS) generation by cell cytometry. RESULTS: The exposure of hepatocytes to ethanol induced JNK activation, c-jun phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3 cleavage; these effects were diminished by SP600125, and caused a significant decrease in ethanol-induced apoptosis (P< 0.05). AdoMet exerted an antioxidant effect maintaining glutathione levels and decreasing ROS generation, without a significant effect on JNK activity, and prevented cytochrome c release and pro-caspase 3 cleavage. CONCLUSION: The JNK signaling cascade is a key component of the proapoptotic signaling pathway induced by ethanol. JNK activation may be independent from ROS generation, since AdoMet which exerted antioxidant properties did not have a significant effect on JNK activity. JNK pathway modulator agents and AdoMet may be components of promising therapies for alcoholic liver disease (ALD) treatment.