miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

The Overlooked Immune State in Candidemia: A Risk Factor for Mortality.

Lymphopenia has been related to increased mortality in septic patients. Nonetheless, the impact of lymphocyte count on candidemia mortality and prognosis has not been addressed. We conducted a retrospective study, including all admitted patients with candidemia from 2007 to 2016. We examined lymphocyte counts during the first 5 days following the diagnosis of candidemia. Multivariable logistic regression analysis was performed to determine the relationship between lymphocyte count and mortality. Classification and Regression Tree analysis was used to identify the best cut-off of lymphocyte count for mortality associated with candidemia. From 296 cases of candidemia, 115 died, (39.8% 30-day mortality). Low lymphocyte count was related to mortality and poor outcome (p < 0.001). Lymphocyte counts <0.703 × 109 cells/L at diagnosis (area under the curve (AUC)-ROC, 0.783 ± 0.042; 95% confidence interval (CI), 0.700-0.867, p < 0.001), and lymphocyte count <1.272 × 109 cells/L five days later (AUC-ROC, 0.791 ± 0.038; 95%CI, 0.716-0.866, p < 0.001) increased the odds of mortality five-fold (odds ratio (OR), 5.01; 95%CI, 2.39-10.93) at time of diagnosis, and three-fold (OR, 3.27; 95%CI, 1.24-8.62) by day 5, respectively. Low lymphocyte count is an independent predictor of mortality in patients with candidemia and might serve as a biomarker for predicting candidemia-associated mortality and poor outcome.

Impact of empirical treatment with antifungal agents on survival of patients with candidemia / Impacto del tratamiento antifúngico empírico en la supervivencia de pacientes con candidemia

Introduction: The objective of this study was to evaluate the impact of echinocandins and fluconazole) on mortality 7 and 30 days after candidemia onset and overall in-hospital mortality), in patients with candidemia at a Spanish tertiary hospital. Methods: A retrospective study was conducted that enrolled all non-neutropenic adult patients diagnosed with candidemia at Hospital Clínico Universitario de Valladolid between 2007 and 2016. A total of 179 patients were evaluated, they were divided into two sub-groups: surviving patients (n = 92) and non-surviving patients (n = 87). Results: The 7-day mortality was 25,1% (45), 30-day mortality was 46,9% (84), and overall in-hospital mortality was 48,6% (87). 40.8% of patients received no antifungal treatment (43.8% of surviving patients and 37.8% of non-surviving patients; p=0.15). A total of 106 (59.2%) patients were treated, of which 90 patients (50.3%) received empiric treatment. 19.6% and 47.8% of surviving patients were treated with echinocandins and fluconazole, respectively. By contrast, of non-surviving patients, 31.0% were treated with echinocandins and 47.1% received fluconazole. Survival for the first 7 days was significantly higher in treated with antifungal agents (log-rank = 0.029), however, there were not significant differences in 30-day survival. Factors linked to a significant increase in overall in-hospital mortality were age (OR 1.040), septic shock (OR 2.694) and need for mechanical ventilation > 48 h (OR 2.812). Conclusion: Patients who received antifungal treatment, regardless of whether they received fluconazole or echinocandins, had a significantly lower mortality rate after 7 days than untreated patients, although no significant differences in 30-day mortality were seen

Introducción: El objetivo del estudio es evaluar el impacto del tratamiento antifúngico en la mortalidad hospitalaria a los 7 y 30 días en pacientes con candidemia en un hospital terciario español. Métodos: Se realizó un estudio retrospectivo que incluyó los pacientes adultos no neutropénicos diagnosticados de candidemia en el Hospital Clínico Universitario entre 2007 y 2016. Se evaluaron 179 pacientes, se dividieron en grupo de supervivientes (n=92) y no supervivientes (n=87). Resultados: La mortalidad a 7 días fue 25,1% (45), a los 30 días 46,9% (84) y la hospitalaria 48,6% (87). El 40,8% no recibieron antifúngico (43,8% de supervivientes y 37,8% de no supervivientes; p=0,15). El 50,3% (90) recibieron tratamiento empírico. De los supervivientes el 19,6% y 47,8% se trataron con equinocandinas y fluconazol, respectivamente. De los no supervivientes el 31% recibió equinocandinas y el 47,1% fluconazol. La supervivencia a los 7 días fue significativamente mayor en los tratados (log-rank = 0.029), no hubo diferencias a los 30 días. Los factores asociados a mortalidad hospitalaria fueron edad (OR: 1.040), shock séptico (OR: 2.694) y ventilación mecánica> 48 h (OR: 2.812). Conclusión: Los pacientes tratados con antifúngicos (ya sean equinocandinas o fluconazol) tienen una tasa de mortalidad inferior a los 7 días que los no tratados, sin embargo no hallamos diferencias a los 30 días

Antifungal treatment with echinocandins: a 10-year clinical experience / Tratamiento antifúngico con equinocandinas: 10 años de experiencia clínica

Introduction. The number of studies evaluating the use of echinocandins, whether or not its indication meets international guidelines, in clinical practice is limited. The objective of the present study was to determine the use of echinocandins in a tertiary Spanish hospital in 10 years of clinical practice, and to evaluate its impact on prognosis. Methods. This retrospective study involved adult nonneutropenic ill patients with suspicion of fungal invasion who started treatment with echinocandins between 2006 and 2015. Results. The number of patients treated with echinocandins was 153, and candidemia was detected thereafter in 25.5%. Factors associated with in-hospital mortality in patients receiving echinocandins were: sex male, septic shock, Charlson comorbidity index, and total stay at the hospital. In-hospital mortality after 7, 30 and 90 days was 13.7%, 24.8%, and 56.8%, respectively. From patients receiving echinocandins, 98 did no show multifocal colonization, 50 had Candida score <2.5, and 49 did not meet Ostrosky-Zeichner prediction rule. A total of 19 patients did not show any of these 3 potential risk factors for candidemia. Conclusions. The use of echinocandins in 10 years of clinical practice in our tertiary hospital has been performed according to international guidelines; however, candidemia was only diagnosed thereafter in only 25.5% of cases. Furthermore, according to our results, the adequate use of echinocandins seems not to be associated with reduced mortality rates. Further studies, involving a large cohort of patients and more hospitals, are required to corroborate these results (AU)

Introducción. El número de estudios que evalúan la utilización de equinocandinas de acuerdo con las guías internacionales es limitado. El objetivo de este estudio es evaluar la utilización de equinocandinas en un hospital terciario español en los últimos 10 años y evaluar su impacto en el pronóstico del paciente. Métodos. Este estudio retrospectivo incluye pacientes adultos no neutropénicos con sospecha de infección fúngica invasora a los que se indicaron equinocandinas entre 2006 y 2015. Resultados. El número de tratados con equinocandinas fue 153, la candidemia se confirmó en un 25,5% de estos pacientes. La mortalidad hospitalaria a los 7, 30 y 90 días fue 13,7%, 24,8% y 56,8% respectivamente. De los pacientes a los que se indicó equinocandina 98 no sufrían colonización multifocal, 50 tenían un Candida score <2,5 y 49 no cumplían la regla de Ostrosky-Zeichner. En 19 pacientes no concurrían ninguno de estos 3 factores de riesgo de candidemia. Los factores de riesgo de mortalidad hospitalaria fueron: varón, shock séptico, índice de Charlson y estancia hospitalaria. Conclusiones. El uso de equinocandinas durante 10 años en nuestro hospital terciario se realizó de acuerdo con las guías internacionales; sin embargo solo se detectó candidemia en un 25,5% de los pacientes. Incluso, de acuerdo a nuestros resultados la indicación adecuada de equinocandinas no se asocia con disminución de la mortalidad. Se requieren estudios multicéntricos que incluyan una cohorte más grande de pacientes para corroborar estos resultados (AU)