Ruxolitinib as a treatment strategy for SARS-CoV-2 pneumonia: clinical experience in a real-world setting.

INTRODUCTION: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. METHODOLOGY: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. RESULTS: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. CONCLUSIONS: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

[Levosimendan in patients with acute cardiac failure]. / Uso de levosimendan en enfermos con falla cardíaca aguda.

OBJECTIVE: To assess levosimendan efficacy in acute cardiac failure. METHODS: We included 25 patients with acute cardiac failure and partial conventional therapy response defined as persistence of low cardiac output with inotropic support. We started levosimendan at loading dose and continuous infusion for 24 hours, recording hemodynamic data, as well as clinical variables. RESULTS: All patients showed clinical and hemodynamic improvement. Pulmonary wedge capillary pressure (PWCP) decreased from 18 cmH2O (11-30 cmH2O) to 14 cmH2O (8-15 cmH2O) at 12 hours (p = 0.3) and to 13 cmH2O (8-12 cmH2O) at the end of the infusion period (p = 0.2). Cardiac index increased from 2.1 L/min/m2 (1.8-3.5 L/ min/m2) to 2.86 L/min/m2 (2-4.3 L/min/m2) at 12 hours (p = 0.03) and to 3.08 L/min/m2 at the end of the infusion period (p = 0.02). Tachycardia higher than 120 bpm was present in six patients. No major hypotensive events were present. Mortality to the present is of eight patients. CONCLUSION: Levosimendan infusion improved hemodynamics and clinical variables in acute cardiac failure with few side effects in this small series of patients.

Uso de levosimendan en enfermos con falla cardíaca aguda / Levosimendan in patients with acute cardiac failure

Objetivo: Valorar el uso de levosimendan en el contexto de la falla cardíaca aguda. Material y métodos: Se incluyeron 25 pacientes que ingresaron o desarrollaron insuficiencia cardíaca aguda, con respuesta parcial al manejo habitual definida como la presencia de bajo gasto cardíaco a pesar de tratamiento inotrópico. Se inició levosimendan administrando una dosis de carga y se continuó con una infusión durante 24 horas, monitorizándose a los pacientes con un catéter de flotación pulmonar y registrándose los parámetros hemodinámicos, así como las variables clínicas de frecuencia cardíaca (FC) y presión arterial media (PAM). Resultados: Observamos mejoría clínica en todos los pacientes. Hemodinámicamente se documentó disminución de la presión capilar pulmonar (PCP) de 18 cmH2O (11-30 cmH2O) a 14 cmH2O (8-15 cmH2O) (p = 0.3) para las 12 horas de haberse iniciado la infusión y al final de 13 cmH2O (8-12 cmH2O) (p = 0.2.) Igualmente se observó mejoría en cuanto al índice cardíaco (IC) 2.1 L/min/m² (1.8-3.5 L/min/m²), a 2.86 L/min/m² (2-4.3 L/min/m²) (p = 0.03) a las 12 h de la infusión y manteniéndose de 3.08 L/min/m² (2.4-3.9 L/min/m²) al término de la infusión (p = 0.02.). Sólo 6 pacientes mostraron como complicación taquicardia con FC mayor de 120 x min, que fue transitoria y que no requirió manejo adicional. En ningún caso requirió iniciar infusión de algún vasopresor. La mortalidad hasta el momento es de 8 pacientes. Conclusión: El uso de levosimendan en pacientes con falla cardíaca aguda mejora las variables hemodinámicas y clínicas con pocos efectos adversos en esta población de estudio.

Objective: To assess levosimendan efficacy in acute cardiac failure. Methods: We included 25 patients with acute cardiac failure and partial conventional therapy response defined as persistence of low cardiac output with inotropic support. We started levosimendan at loading dose and continuous infusion for 24 hours, recording hemodynamic data, as well as clinical variables. Results: All patients showed clinical and hemodynamic improvement. Pulmonary wedge capillary pressure (PWCP) decreased from 18 cmH2O (11 -30 cmH2O) to 14 cmH2O (8-15 cmH2O) at 12 hours (p = 0.3) and to 13 cmH2O (8-12 cmH2O) at the end of the infusion period (p = 0.2). Cardiac index increased from 2.1 L/min/m² (1.8-3.5 L/ min/m²) to 2.86 L/min/m² (2-4.3 L/min/m²) at 12 hours (p = 0.03) and to 3.08 L/min/m² at the end of the infusion period (p = 0.02). Tachycardia higherthan 120 bpm was present in six patients. No major hypotensive events were present. Mortality to the present is of eight patients. Conclusion: Levosimendan infusion improved hemodynamics and clinical variables in acute cardiac failure with few side effects in this small series of patients.