miRNome Profiling of Extracellular Vesicles in Patients With Severe COVID-19 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 patients with severe COVID-19 vs controls, identifying potential mortality predictors. METHODS: This prospective study included 36 patients with severe COVID-19 and 33 controls without COVID-19. EV-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of patients with severe COVID-19 (n = 32) and controls (n = 12) was used to compare with our data. Survival analysis identified potential mortality predictors among the significantly differentially expressed (SDE) miRNAs in EVs. RESULTS: Patients with severe COVID-19 showed 50 SDE miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EV miRNAs were SDE in the plasma of severe cases vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an area under the receiver operating characteristic curve of 0.938. CONCLUSIONS: This research provides insights into the role of miRNAs within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

Post-operative sepsis-induced acute respiratory distress syndrome: risk factors for a life-threatening complication.

Introduction: Prevalence and mortality of the acute respiratory distress syndrome (ARDS) in intensive care units (ICU) are unacceptably high. There is scarce literature on post-operative sepsis-induced ARDS despite that sepsis and major surgery are conditions associated with ARDS. We aimed to examine the impact of post-operative sepsis-induced ARDS on 60-day mortality. Methods: We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups depending on whether they met criteria for ARDS. Primary outcome was 60-day mortality of post-operative sepsis-induced ARDS. Secondary outcome measures were potential risk factors for post-operative sepsis-induced ARDS, and for 60-day mortality. Results: Higher SOFA score (OR 1.1, 95% CI 1.0-1.3, p = 0.020) and higher lactate (OR 1.9, 95% CI 1.2-2.7, p = 0.004) at study inclusion were independently associated with ARDS. ARDS patients (n = 45) had higher ICU stay [14 (18) vs. 5 (11) days, p < 0.001] and longer need for mechanical ventilation [6 (14) vs. 1 (5) days, p < 0.001] than non-ARDS patients (n = 409). Sixty-day mortality was higher in ARDS patients (OR 2.7, 95% CI 1.1-6.3, p = 0.024). Chronic renal failure (OR 4.0, 95% CI 1.2-13.7, p = 0.026), elevated lactate dehydrogenase (OR 1.7, 95% CI 1.1-2.7, p = 0.015) and higher APACHE II score (OR 2.7, 95% CI 1.3-5.4, p = 0.006) were independently associated with 60-day mortality. Conclusion: Post-operative sepsis-induced ARDS is associated with higher 60-day mortality compared to non-ARDS post-operative septic patients. Post-operative septic patients with higher severity of illness have a greater risk of ARDS and worse outcomes. Further investigation is needed in post-operative sepsis-induced ARDS to prevent ARDS.

COVID-19-associated pulmonary aspergillosis (CAPA) in hematological patients: Could antifungal prophylaxis be necessary? A nationwide study.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. METHODS: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. FINDINGS: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p < 0.001). Candida spp. showed higher rate in non-COVID-19 (74.2 % vs. 66.8 %; p = 0.015), meanwhile Aspergillus spp. confirmed its predominance in COVID-19 hematological patients (35.4 % vs. 19.1 %; p < 0.001). IPA was diagnosed in 703 patients and 11.2 % (79 cases) were CAPA. The multivariate logistic regression analysis found that the diagnosis of COVID-19 disease at hospital admission increased more than two-fold IPA development [OR: 2.5, 95CI (1.9-3.1), p < 0.001]. B-cell malignancies - specifically B-cell non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia and acute lymphoblastic leukemia - showed between four- and six-fold higher CAPA development and 90-day mortality rates ranging between 50 % and 72 %. However, myeloid malignancies did not show higher CAPA rates compared to IPA in non-COVID-19 patients. CONCLUSION: COVID-19 constitutes an independent risk factor for developing aspergillosis in B-cell hematological malignancies and the use of antifungal prophylaxis during hospitalizations may be warranted.

Impact of Oxygen Delivery on the Development of Acute Kidney Injury in Patients Undergoing Valve Heart Surgery.

One of the strongest risk factors for death in individuals undergoing cardiac surgery is Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI). Although the minimum kidney oxygen delivery index (DO2i) during cardiopulmonary bypass (CPB) has been reported, the optimal threshold value has not yet been established. A prospective study was conducted from June 2012 to January 2016 to asses how DO2i influences the pathogenesis of CSA-AKI, as well as its most favorable cut-off value. DO2 levels were recorded at the beginning, middle, and end of the CPB. The association between DO2i and CSA-AKI was investigated using multivariable logistic regression analysis. The optimal cut-off of DO2i as a predictor of CSA-AKI was determined using Classification and Regression Tree (CART) analysis. A total of 782 consecutive patients were enrolled. Of these, 231 (29.5%) patients developed AKI. Optimal DO2i thresholds of 303 mL/min/m2 during the CPB and 295 mL/min/m2 at the end of the intervention were identified, which increased the odds of CSA-AKI almost two-fold (Odds Ratio (OR), 1.90; 95% CI, 1.12-3.24) during the surgery and maintained that risk (OR 1.94; 95% CI, 1.15-3.29) until the end. Low DO2i during cardiopulmonary bypass is a risk factor for CSA-AKI that cannot be ruled out. Continuous renal oxygen supply monitoring for adult patients could be a promising method for predicting AKI during CPB.

Influence of Renal Dysfunction on the Differential Behaviour of Procalcitonin for the Diagnosis of Postoperative Infection in Cardiac Surgery.

Background: procalcitonin is a valuable marker in the diagnosis of bacterial infections; however, the impairment of renal function can influence its diagnostic precision. The objective of this study is to evaluate the differential behaviour of procalcitonin, as well as its usefulness in the diagnosis of postoperative pulmonary infection after cardiac surgery, depending on the presence or absence of impaired renal function. Materials and methods: A total of 805 adult patients undergoing cardiac surgery with extracorporeal circulation (CBP) were prospectively recruited, comparing the behaviour of biomarkers between the groups with and without postoperative pneumonia and according to the presence or absence of renal dysfunction. Results: Pulmonary infection was diagnosed in 42 patients (5.21%). In total, 228 patients (28.32%) presented postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, even in the presence of renal dysfunction. The optimal procalcitonin threshold differed markedly in patients with renal dysfunction compared to patients without renal dysfunction (1 vs. 0.78 ng/mL p < 0.05). The diagnostic accuracy of procalcitonin increased significantly when the procalcitonin threshold was adapted to renal function. Conclusions: Procalcitonin is an accurate marker of postoperative infection in cardiac surgery, even in the presence of renal dysfunction. Renal function is an important determinant of procalcitonin levels and, therefore, its diagnostic thresholds must be adapted in the presence of renal dysfunction.