A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

[Inflammatory response in acute myocardial infarction. Predictive values]. / Respuesta inflamatoria en el infarto agudo de miocardio. Valores predictivos.

INTRODUCTION AND OBJECTIVES: Our purpose was to investigate the significance of inflammatory acute phase response early after myocardial infarction. We also observed how these indices were influenced by trombolytic therapy. METHOD: We examined the blood samples of 200 non consecutive patients at the first day of acute myocardial infarction (155 [77%] males; mean age 65 +/- 13 years) to characterize the proteins and proinflamatory reactants profile. Results were correlated with hospital mortality. Thrombolytic therapy was administrated to 117 patients on admission and in these patients the samples were taken after the procedure. RESULTS: Overall mortality was 8%. Serum C-reactive protein (69 vs 41 mg/l), haptoglobine (237 vs 190 mg/dl), gammaglobuline (0.93 vs 0.84 g/dl), alpha-1-globuline (0.28 vs 0.23 g/dl) and alpha-2-globuline (0.7 vs 0.6 g/dl) were significantly higher in patients without trombolytic therapy. Conversely, patients who had received lytic therapy, had higher plasma concentrations of interleukin-1 beta (104 vs 40 pg/dl). The only clinical variable which was associated with mortality was a Killip class > or = 2 on admission (mortality = 21%; odds ratio = 5.2; p = 0.02). Other biochemical variables associated with a higher mortality were a white blood cell count > 10/nl (mortality = 12%; odds ratio = 5.4; p = 0.01), increased activated neutrophils > 80% (mortality = 18%; odds ratio = 5.4; p = 0.004) and C-reactive protein > 20 mg/l (mortality = 11%; odds ratio = 6; p = 0.05). Only patients with activated neutrophils > 80% on admission had a higher probability of dying during hospital stay (Exp[B] = 3.6; B = 1.2; r = 0.29; p = 0.001). CONCLUSION: The acute phase reaction in early myocardial infarction is determined by thrombolytic treatment. A high increase of activated neutrophils on patient admission is the only biochemical predictive value for hospital mortality.

[Auricular fibrillation and stroke in patients with sick sinus syndromeusing permanent pacemakers]. / Fibrilación auricular y accidente vascular encefálico en pacientes con enfermedad del nodo sinusal portadores de marcapasos definitivos.

INTRODUCTION AND OBJECTIVES: Since physiological pacing systems have become available, a debate has raged about the merits of atrial versus ventricular pacing in the sick sinus syndrome. The goal of this retrospective report was to study the long term incidence and the independent predictors for atrial fibrillation and stroke in 153 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis. METHOD AND RESULTS: From 1980 to 1994, we implanted 32 dualchamber, 33 atrial, and 88 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 177 months (median 30 months for paroxismal atrial fibrillation, 45 months for chronic atrial fibrillation and 43,5 months for stroke) the actuarial incidence of paroximal atrial fibrillation was 7.8% at 1 year, 29% at 5 years and 42% at 10 years. The actuarial incidence of chronic atrial fibrillation was 1.3% at 1 year, 9.8% at 5 years and 22% at 10 years. Independent predictors for paroxismal AF from Cox's model was history of atrial tachyarrhythmias (p < 0.0001), chronic obstructive pulmonary disease (p = 0,006) and age (> 70 years-old) (p = 0.035). Only a history of atrial tachyarrhythmias before pacemaker implant was an independent predictor for chronic atrial fibrillation (p < 0.0001). The odd ratio for paroxismal atrial fibrillation in patients with previous atrial tachyarrhythmias and chronic atrial fibrillation were 6 (2.8-12) and 4 (1.6-9.7) (95% confiance limits). Actuarial incidence of stroke was 3% at 1 year, 10% at 5 years and 14% at 10 years. Independent predictors for stroke were history of peripheral vascular disease (p = 0.033) and hypertensive cardiomyopathy (p = 0.015). Development of paroxysmal and chronic atrial fibrillation during the follow-up were higher in patients with stroke (p < 0.001 and p < 0.05). CONCLUSIONS: Development of atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables. Preimplant paroxysmal atrial tachyarrhythmias is the most important predictor for atrial fibrillation in the follow-up.