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.

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.

The mitochondrial signature of cultured endothelial cells in sepsis: Identifying potential targets for treatment.

Sepsis is the most common cause of death from infection in the world. Unfortunately, there is no specific treatment for patients with sepsis, and management relies on infection control and support of organ function. A better understanding of the underlying pathophysiology of this syndrome will help to develop innovative therapies. In this regard, it has been widely reported that endothelial cell activation and dysfunction are major contributors to the development of sepsis. This review aims to provide a comprehensive overview of emerging findings highlighting the prominent role of mitochondria in the endothelial response in in vitro experimental models of sepsis. Additionally, we discuss potential mitochondrial targets that have demonstrated protective effects in preclinical investigations against sepsis. These promising findings hold the potential to pave the way for future clinical trials in the field.

Improving the performance of the Cleveland Clinic Score for predicting acute kidney injury after cardiac surgery: a prospective multicenter cohort study.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is associated with high short- and long-term mortality rates. The prediction of CSA-AKI is crucial for early detection and treatment. Current predictive models may be improved by potentially useful preoperative and intraoperative information. METHODS: This multicenter prospective cohort study recruited 261 consecutive patients at high risk for developing CSA-AKI, based on a Cleveland Clinical Score (CCS) of ≥4 points from July to December 2017 in 14 hospitals in Spain and the UK. Postoperative AKI occurred in 145 (55.5%) patients. The receiver operating characteristics curve (AUC) of a base model including only the CCS was compared with models including additional preoperative and intraoperative variables such as the estimated glomerular filtration rate (eGFR) instead of plasmatic creatinine, intraoperative urine output, baseline hemoglobin, nadir hemoglobin, and glycosylated hemoglobin (HbA1c) instead of diabetes mellitus. The performance of each model for AKI was compared. RESULTS: The CCS alone gave an AUC of 0.67 (95% CI, 0.56-0.78) for postoperative AKI. None of the single variables added to the base model CCS improve discrimination. The AUC for postoperative AKI was improved when baseline hemoglobin, eGFR instead of plasmatic creatinine, HbA1c, and nadir hemoglobin were added to the CCS (AUC=0.77; 95% CI, 0.67-0.87; P=0.02). CONCLUSIONS: The addition of baseline hemoglobin, eGFR, HbA1c, and nadir intraoperative hemoglobin may be useful for improving the discrimination of the clinical predictive risk scores for AKI.

Prevalence and cost of hospitalized patients with asymptomatic COVID-19 in 2020 in Spain.

Introduction: COVID-19 transmission has been characterized by the presence of asymptomatic patients. Additionally, most studies evaluating costs focus on symptomatic COVID-19 cases. Objective: To describe the prevalence, characteristics, and costs of asymptomatic COVID-19 cases at admission in Spanish hospitals in 2020. Methods: A nationwide study was performed, and data of hospitalized patients were collected of the Minimum Basic Data Set in Spain during 2020. Patients with COVID-19 codes as a primary and as a secondary diagnosis at admission were selected. Variables collected included age, sex, length of stay, in-hospital death, admission, length of stay and death in intensive care unit, mechanical ventilation and ventilatory assistance. COVID-19 related hospital costs were calculated using diagnosis-related groups from the Minimum Basic Data Set. Patients and costs were disaggregated by sex, age group, intensive care unit admission and epidemic wave (first or second) and main diagnosis. Results: A total of 14,742 patients were admitted with asymptomatic COVID-19 in Spanish hospitals representing 6.35% of all COVID-19 admitted patients. The total cost of admissions with asymptomatic COVID-19 was €105,933,677.6 with a mean cost per patient of €7,185.8 with higher mean cost in the first wave despite only 2.7% of cases were found during that time. Based on primary diagnosis, the higher number of cases of asymptomatic COVID-19 were found in "Pregnancy, childbirth and the puerperium" followed by "diseases of the circulatory system". Conclusions: There was a high prevalence of asymptomatic cases during screening at admission process in Spanish hospitals in 2020. The highest number of cases was found among the group of "pregnancy, childbirth, and puerperium" followed by "diseases of the circulatory system." The higher costs might be due not only to the main pathology at admission but to the associated healthcare provisions needed in case of positive COVID-19 testing.

Gene Co-Expression Networks Offer New Perspectives on Sepsis Pathophysiology.

Sepsis is among the most common causes of death in intensive care units. Septic shock is a type of circulatory shock that shows signs and symptoms that are similar to non-septic shock. Despite the impact of shock on patients and the economic burden, knowledge of the pathophysiology of septic shock is scarce. In this context, weighted gene co-expression network analysis can help to elucidate the molecular mechanisms of this condition. The gene expression dataset used in this study was downloaded from the Gene Expression Omnibus, which contains 80 patients with septic shock, 33 patients with non-septic shock, and 15 healthy controls. Our novel analysis revealed five gene modules specific for patients with septic shock and three specific gene modules for patients with non-septic shock. Interestingly, genes related to septic shock were mainly involved in the immune system and endothelial cells, while genes related to non-septic shock were primarily associated with endothelial cells. Together, the results revealed the specificity of the genes related to the immune system in septic shock. The novel approach developed here showed its potential to identify critical pathways for the occurrence and progression of these conditions while offering new treatment strategies and effective therapies.

Environmental factors are associated to hospital outcomes in COVID-19 patients during lockdown and post-lockdown in 2020: A nationwide study.

OBJECTIVE: This study analyzed, at a postcode detailed level, the relation-ship between short-term exposure to environmental factors and hospital ad-missions, in-hospital mortality, ICU admission, and ICU mortality due to COVID-19 during the lockdown and post-lockdown 2020 period in Spain. METHODS: We performed a nationwide population-based retrospective study on 208,744 patients admitted to Spanish hospitals due to COVID-19 based on the Minimum Basic Data Set (MBDS) during the first two waves of the pandemic in 2020. Environmental data were obtained from Copernicus Atmosphere Monitoring Service. The association was assessed by a generalized additive model. RESULTS: PM2.5 was the most critical environmental factor related to hospital admissions and hospital mortality due to COVID-19 during the lockdown in Spain, PM10, NO2, and SO2and also showed associations. The effect was considerably reduced during the post-lockdown period. ICU admissions in COVID-19 patients were mainly associated with PM2.5, PM10, NO2, and SO2 during the lockdown as well. During the lockdown, exposure to PM2.5 and PM10 were the most critical environmental factors related to ICU mortality in COVID-19. CONCLUSION: Short-term exposure to air pollutants impacts COVID-19 out-comes during the lockdown, especially PM2.5, PM10, NO2, and SO2. These pollutants are associated with hospital admission, hospital mortality and ICU admission, while ICU mortality is mainly associated with PM2.5 and PM10. Our findings reveal the importance of monitoring air pollutants in respiratory infectious diseases.

Economic Burden of the 2020 COVID-19 Hospitalizations in Spain.

This economic evaluation reports the total and per patient costs of inpatient care for COVID-19 in Spain in 2020.

Postoperative delirium: An independent risk factor for poorer quality of life with long-term cognitive and functional decline after cardiac surgery.

STUDY OBJECTIVE: To evaluate the influence of delirium on the functional and cognitive capacity of patients included in the DELIPRECAS study, as well as on their quality of life, in the 3-4 years after cardiac surgery. DESIGN: Prospective observational study. SETTING: Assessment of cognitive and functional status from hospital discharge to the present, 3 years after cardiac surgery. PATIENTS: 313 patients undergoing cardiac surgery consecutively, aged 18 years or over. MEASUREMENTS: The primary outcome measure was the cognitive and functional status of the patients 3 years after cardiac surgery, evaluated by telephone interview, and the possible influence on them of delirium diagnosed by the Confusion Assessment Method in Intensive Care Units (CAM-ICU) during their stay in the intensive care unit after cardiac surgery. MAIN RESULTS: Postoperative delirium acts as an independent risk factor for the long-term development of memory problems (OR 6.11, 95% CI 2.54 to 14.68, p < 0.001), concentration (OR 11.20, 95% CI 3.58 to 35.09, p > 0.001), confusion/disorientation (OR 10.93, 95% CI 3.61 to 33.12, p > 0.001), sleep problems (OR 5.21, 95% CI 2 0.29 to 11.84, p < 0.001), nightmares (OR 8.99, 95% CI 1.98 to 40.90, p = 0.004), emotional problems (OR 4.30, 95% CI 1.87 to 9.91, p = 0.001) and poorer mobility after hospital discharge (OR 2.436, 95% CI 1.06 to 5.61, p = 0.037). The number of hospital readmissions was also significantly higher in those patients who developed delirium after cardiac surgery (27% vs 13.8%, p = 0.022). CONCLUSION: Postoperative delirium is a risk factor for decreased quality of life in patients 3 years after heart surgery, being associated with greater cognitive and functional deterioration, as well as greater risk of hospital readmission. Therefore, emphasis should be placed on both prevention and early recognition and treatment of delirium to improve long-term outcomes for patients after cardiac surgery.

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.

Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

Role of Oxidative Stress and Lipid Peroxidation in the Pathophysiology of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is characterised by an excess of hepatic fat that can progress to steatohepatitis, fibrosis, cirrhosis and hepatocarcinoma. The imbalance between lipid uptake/lipogenesis and lipid oxidation/secretion in the liver is a major feature of NAFLD. Given the lack of a non-invasive and reliable methods for the diagnosis of non-alcoholic steatohepatitis (NASH), it is important to find serum markers that are capable of discriminating or defining patients with this stage of NASH. Blood samples were obtained from 152 Caucasian subjects with biopsy-proven NAFLD due to persistently elevated liver enzyme levels. Metabolites representative of oxidative stress were assessed. The findings derived from this work revealed that NAFLD patients with a NASH score of ≥ 4 showed significantly higher levels of lipid peroxidation (LPO). Indeed, LPO levels above the optimal operating point (OOP) of 315.39 µM are an independent risk factor for presenting a NASH score of ≥ 4 (OR: 4.71; 95% CI: 1.68−13.19; p = 0.003). The area under the curve (AUC = 0.81, 95% CI = 0.73−0.89, p < 0.001) shows a good discrimination ability of the model. Therefore, understanding the molecular mechanisms underlying the basal inflammation present in these patients is postulated as a possible source of biomarkers and therapeutic targets in NASH.

A genome-wide association study of survival in patients with sepsis.

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

Time evolution of cytokine profiles associated with mortality in COVID-19 hospitalized patients.

Background: High cytokine levels have been associated with severe COVID-19 disease. Although many cytokine studies have been performed, not many of them include combinatorial analysis of cytokine profiles through time. In this study we investigate the association of certain cytokine profiles and its evolution, and mortality in SARS-CoV2 infection in hospitalized patients. Methods: Serum concentration of 45 cytokines was determined in 28 controls at day of admission and in 108 patients with COVID-19 disease at first, third and sixth day of admission. A principal component analysis (PCA) was performed to characterize cytokine profiles through time associated with mortality and survival in hospitalized patients. Results: At day of admission non-survivors present significantly higher levels of IL-1α and VEGFA (PC3) but not through follow up. However, the combination of HGF, MCP-1, IL-18, eotaxine, and SCF (PC2) are significantly higher in non-survivors at all three time-points presenting an increased trend in this group through time. On the other hand, BDNF, IL-12 and IL-15 (PC1) are significantly reduced in non-survivors at all time points with a decreasing trend through time, though a protective factor. The combined mortality prediction accuracy of PC3 at day 1 and PC1 and PC2 at day 6 is 89.00% (p<0.001). Conclusions: Hypercytokinemia is a hallmark of COVID-19 but relevant differences between survivors and non-survivors can be early observed. Combinatorial analysis of serum cytokines and chemokines can contribute to mortality risk assessment and optimize therapeutic strategies. Three clusters of cytokines have been identified as independent markers or risk factors of COVID mortality.

Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge.

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4-), and, to a lower extent, in B-cells from healthy controls. Notably, IDE's surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE's surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4- T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4- T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.

PCR-based diagnosis of respiratory virus in postsurgical septic patients: A preliminary study before SARS-CoV-2 pandemic.

Respiratory viruses are part of the normal microbiota of the respiratory tract, which sometimes cause infection with/without respiratory insufficiency and the need for hospital or ICU admission. The aim of this study is to determine the prevalence of respiratory viruses in nontransplanted postoperative septic patients as well as lymphocyte count influence in their presence and its relationship to mortality. 223 nontransplanted postsurgical septic patients were recruited on the Intensive Care Unit (ICU) at Hospital Clínico Universitario de Valladolid prior to the SARS-COV-2 pandemic. Patients were split into 2 groups according to the presence/absence of respiratory viruses. Multivariate logistic regression analysis was used to identify independent factors related to positive respiratory virus PCR test. Respiratory viruses were isolated in 28.7% of patients. 28-day mortality was not significantly different between virus-positive and virus-negative groups. Logistic regression analysis revealed that lymphocyte count ≤ 928/µl is independently associated with a positive PCR result [OR 3.76, 95% CI (1.71-8.26), P = .001] adjusted by platelet count over 128,500/µL [OR 4.27, 95% CI (1.92-9.50) P < .001] and the presence of hypertension [OR 2.69, 95% CI (1.13-6.36) P = .025] as confounding variables. Respiratory viruses' detection by using PCR in respiratory samples of nontransplanted postoperative septic patients is frequent. These preliminary results revealed that the presence of lymphopenia on sepsis diagnosis is independently associated to a positive virus result, which is not related to a higher 28-day mortality.

Diagnosis of Cardiac Surgery-Associated Acute Kidney Injury: State of the Art and Perspectives.

Diagnosis of cardiac surgery-associated acute kidney injury (CSA-AKI), a syndrome of sudden renal dysfunction occurring in the immediate post-operative period, is still sub-optimal. Standard CSA-AKI diagnosis is performed according to the international criteria for AKI diagnosis, afflicted with insufficient sensitivity, specificity, and prognostic capacity. In this article, we describe the limitations of current diagnostic procedures and of the so-called injury biomarkers and analyze new strategies under development for a conceptually enhanced diagnosis of CSA-AKI. Specifically, early pathophysiological diagnosis and patient stratification based on the underlying mechanisms of disease are presented as ongoing developments. This new approach should be underpinned by process-specific biomarkers including, but not limited to, glomerular filtration rate (GFR) to other functions of renal excretion causing GFR-independent hydro-electrolytic and acid-based disorders. In addition, biomarker-based strategies for the assessment of AKI evolution and prognosis are also discussed. Finally, special focus is devoted to the novel concept of pre-emptive diagnosis of acquired risk of AKI, a premorbid condition of renal frailty providing interesting prophylactic opportunities to prevent disease through diagnosis-guided personalized patient handling. Indeed, a new strategy of risk assessment complementing the traditional scores based on the computing of risk factors is advanced. The new strategy pinpoints the assessment of the status of the primary mechanisms of renal function regulation on which the impact of risk factors converges, namely renal hemodynamics and tubular competence, to generate a composite and personalized estimation of individual risk.

Hospitalized COVID-19 Patients with Severe Acute Respiratory Syndrome: A Population-Based Registry Analysis to Assess Clinical Findings, Pharmacological Treatment and Survival.

Background and Objectives: One of the most serious clinical outcomes in hospitalized patients with COVID-19 is severe acute respiratory syndrome (SARS). The aim is to analyze pharmacological treatment, survival and the main mortality predictors. Materials and Methods: A real-world data study from COVID-19-hospitalized patients with SARS from 1 March to 31 May 2020 has been carried out. Variables such as hospital length of stay, ventilation type and clinical outcomes have been taken into account. Results: In Castile and Leon, 14.03% of the 7307 in-hospital COVID-19 patients developed SARS, with a mortality rate of 42.53%. SARS prevalence was doubled in males compared to females, and 78.54% had an age of 65 years or more. The most commonly used medicines were antibiotics (89.27%), antimalarials (68.1%) and corticosteroids (55.9%). Survival of patients developing SARS was lower compared to patients without this complication (12 vs. 13 days). The main death predictors were disseminated intravascular coagulation (DIC) (OR: 13.87) and age (>65 years) (OR: 7.35). Conclusions: Patients older than 65 years who develop DIC have a higher probability of hospital death. Tocilizumab and steroids have been linked to a lower incidence of hospital death, being the main treatment for COVID-19 hospitalized patients with SARS.