Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

Prognostic factors and combined use of tocilizumab and corticosteroids in a Spanish cohort of elderly COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection in elderly patients is more aggressive and treatments have shown limited efficacy. Our objective is to describe the clinical course and to analyze the prognostic factors associated with a higher risk of mortality of a cohort of patients older than 80 years. In addition, we assess the efficacy of immunosuppressive treatments in this population. We analyzed the data from 163 patients older than 80 years admitted to our institution for COVID-19, during March and April 2020. A Lasso regression model and subsequent multivariate Cox regression were performed to select variables predictive of death. We evaluated the efficacy of immunomodulatory therapy in three cohorts using adjusted survival analysis. The mortality rate was 43%. The mean age was 85.2 years. The disease was considered severe in 76.1% of the cases. Lasso regression and multivariate Cox regression indicated that factors correlated with hospital mortality were: age (hazard ratio [HR] 1.12, 95% confidence interval [CI]: 1.03-1.22), alcohol consumption (HR 3.15, 95% CI: 1.27-7.84), CRP > 10 mg/dL (HR 2.67, 95% CI: 1.36-5.24), and oxygen support with Venturi Mask (HR 6.37, 95% CI: 2.18-18.62) or reservoir (HR 7.87, 95% CI: 3.37-18.38). Previous treatment with antiplatelets was the only protective factor (HR 0.47, 95% CI: 0.23-0.96). In the adjusted treatment efficacy analysis, we found benefit in the combined use of tocilizumab (TCZ) and corticosteroids (CS) (HR 0.09, 95% CI: 0.01-0.74) compared to standard treatment, with no benefit of CS alone (HR 0.95, 95% CI: 0.53-1.71). Hospitalized elderly patients suffer from a severe and often fatal form of COVID-19 disease. In this regard, several parameters might identify high-risk patients upon admission. Combined use of TCZ and CS could improve survival.

Study of risk factors for healthcare-associated infections in acute cardiac patients using categorical principal component analysis (CATPCA).

Using categorical principal component analysis, we aimed to determine the relationship between health care-associated infections (HAIs) and diagnostic categories (DCs) in patients with acute heart disease using data collected in the Spanish prospective ENVIN-HELICS intensive care registry over a 10-year period (2005-2015). A total of 69,876 admissions were included, of which 5597 developed HAIs. Two 2-component CATPCA models were developed. In the first model, all cases were included; the first component was determined by the duration of the invasive devices, the ICU stay, the APACHE II score and the HAIs; the second component was determined by the type of admission (medical or surgical) and by the DCs. No clear association between DCs and HAIs was found. Cronbach's alpha was 0.899, and the variance accounted for (VAF) was 52.5%. The second model included only admissions that developed HAIs; the first component was determined by the duration of the invasive devices and the ICU stay; the second component was determined by the inflammatory response, the mortality in the ICU and the HAIs. Cronbach's alpha value was 0.855, and VAF was 46.9%. These findings highlight the role of exposure to invasive devices in the development of HAIS in patients with acute heart disease.

[Neurologic complications in the immediate postoperative period after cardiac surgery. Role of brain magnetic resonance imaging]. / Complicaciones neurológicas en el postoperatorio inmediato de la cirugía cardíaca. Aportación de la resonancia magnética cerebral.

INTRODUCTION AND OBJECTIVES: Neurologic complications still cause significant morbidity and mortality in the immediate postoperative period following cardiac surgery. Our understanding of the pathogenesis, prevention, and management of these lesions is constantly developing. MATERIAL AND METHOD: We describe neurologic complications and their course in a cardiac surgery cohort and analyze the value of brain magnetic resonance imaging (MRI), using T1-weighted, T2-weighted, and FLAIR sequences, in patients with postoperative stroke or encephalopathy in whom CT scanning revealed no abnormalities explaining their clinical condition. RESULTS: In 688 patients studied postoperatively, we observed 57 neurologic complications (8.3%): 25 strokes, 24 encephalopathies, 5 seizure disorders, 2 brain deaths, and 1 intracranial hemorrhage. Initial CT scanning failed to show significant findings in 70%. 18 patients underwent brain MRI. In all but 1 of the 11 with stroke, MRI showed areas of acute or subacute infarction (i.e., hyperintensity in FLAIR or T2-weighted sequences) in different locations, mainly in a watershed distribution. In 3 of the 4 patients with mild-to-moderate encephalopathy, MRI showed lesions similar to those previously described for stroke. In the remaining 3 patients, who had severe encephalopathy, MRI showed diffuse cortical necrosis. CONCLUSIONS: The incidence of neurologic complications in the postoperative period following cardiac surgery is significant. In a high percentage of patients, brain CT scanning may not show pathologic findings. In selected patients, MRI could help identify areas of infarction not detected by CT. These images could improve clinicians' understanding of the pathogenic, pathophysiologic, clinical, and prognostic characteristics of such neurologic complications.

Complicaciones neurológicas en el postoperatorio inmediato de la cirugía cardíaca. Aportación de la resonancia magnética cerebral / Neurologic complications in the immediate postoperative period after cardiac surgery. Role of brain magnetic resonance imaging

Introducción y objetivos. Las complicaciones neurológicas (CN) causan una importante morbimortalidad en el postoperatorio inmediato de la cirugía cardíaca. La comprensión de la etiopatogenia, la prevención y el tratamiento de éstas están en constante evolución. Material y método. Se describen las CN y su evolución en una serie quirúrgica, y se analizan las aportaciones de la resonancia magnética cerebral (RMC) con secuencias T1, T2 y la supresión de líquido cefalorraquídeo, en los pacientes que presentan ictus o encefalopatía poscirugía y tomografía computarizada (TC) craneal sin hallazgos que justifiquen la situación clínica. Resultados. Se estudió a 688 postoperados; se observaron 57 CN (8,3%): 25 ictus, 24 encefalopatías, 5 pacientes con crisis convulsivas, 2 muertes cerebrales y una hemorragia intracerebral. La TC craneal inicial no mostró hallazgos relevantes en el 70% de las ocasiones. Se realizó RMC en 18 pacientes, 11 de ellos con ictus: excepto en un estudio, en la RMC encontramos áreas de infarto agudo o subagudo (hiperintensas en la secuencia T2 y FLAIR) en diferentes localizaciones. También se realizó en 4 pacientes con encefalopatía leve-moderada y mostró en 3 de ellos lesiones similares a las descritas en los ictus. En los restantes 3 casos con encefalopatía severa, la RMC mostró áreas con múltiples infartos corticales. Conclusiones. Las CN tras cirugía cardíaca se presentan con una incidencia no despreciable. La TC craneal puede no presentar hallazgos patológicos en un alto porcentaje. En pacientes seleccionados, la RMC puede presentar lesiones, y demostrar áreas isquémicas no detectadas en la TC que ayudan a comprender a los clínicos la etiopatogenia, la fisiopatología, la clínica y la evolución de estas complicaciones (AU)

Introduction and objectives. Neurologic complications still cause significant morbidity and mortality in the immediate postoperative period following cardiac surgery. Our understanding of the pathogenesis, prevention, and management of these lesions is constantly developing. Matherial and method. We describe neurologic complications and their course in a cardiac surgery cohort and analyze the value of brain magnetic resonance imaging (MRI), using T1-weighted, T2-weighted, and FLAIR sequences, in patients with postoperative stroke or encephalopathy in whom CT scanning revealed no abnormalities explaining their clinical condition. Results. In 688 patients studied postoperatively, we observed 57 neurologic complications (8.3%): 25 strokes, 24 encephalopathies, 5 seizure disorders, 2 brain deaths, and 1 intracranial hemorrhage. Initial CT scanning failed to show significant findings in 70%. 18 patients underwent brain MRI. In all but 1 of the 11 with stroke, MRI showed areas of acute or subacute infarction (i.e., hyperintensity in FLAIR or T2-weighted sequences) in different locations, mainly in a watershed distribution. In 3 of the 4 patients with mild-to-moderate encephalopathy, MRI showed lesions similar to those previously described for stroke. In the remaining 3 patients, who had severe encephalopathy, MRI showed diffuse cortical necrosis. Conclusions. The incidence of neurologic complications in the postoperative period following cardiac surgery is significant. In a high percentage of patients, brain CT scanning may not show pathologic findings. In selected patients, MRI could help identify areas of infarction not detected by CT. These images could improve clinicians' understanding of the pathogenic, pathophysiologic, clinical, and prognostic characteristics of such neurologic complications (AU)