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.

Impact of Aspergillus spp. isolation in the first 24 hours of admission in critically ill patients with severe influenza virus pneumonia.

OBJECTIVE: To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. DESIGN: Secondary analysis of an observational and prospective cohort study. SETTING: ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTS: Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS: 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONS: Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.

Prior influenza vaccine is not a risk factor for bacterial coinfection in patients admitted to the ICU due to severe influenza.

OBJECTIVE: To determine whether the prior usage of the flu vaccine is a risk factor for bacterial co-infection in patients with severe influenza. DESIGN: This was a retrospective observational cohort study of subjects admitted to the ICU. A propensity score matching, and logistic regression adjusted for potential confounders were carried out to evaluate the association between prior influenza vaccination and bacterial co-infection. SETTINGS: 184 ICUs in Spain due to severe influenza. PATIENTS: Patients included in the Spanish prospective flu registry. INTERVENTIONS: Flu vaccine prior to the hospital admission. RESULTS: A total of 4175 subjects were included in the study. 489 (11.7%) received the flu vaccine prior to develop influenza infection. Prior vaccinated patients were older 71 [61-78], and predominantly male 65.4%, with at least one comorbid condition 88.5%. Prior vaccination was not associated with bacterial co-infection in the logistic regression model (OR: 1.017; 95%CI 0.803-1.288; p=0.885). After matching, the average treatment effect of prior influenza vaccine on bacterial co-infection was not statistically significant when assessed by propensity score matching (p=0.87), nearest neighbor matching (p=0.59) and inverse probability weighting (p=0.99). CONCLUSIONS: No association was identified between prior influenza vaccine and bacterial coinfection in patients admitted to the ICU due to severe influenza. Post influenza vaccination studies are necessary to continue evaluating the possible benefits.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction / Asociación de niveles sanguíneos de caspasa-8 y mortalidad de pacientes con infarto maligno de la arteria cerebral media

Objective High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). Design Observational prospective study. Setting Five Intensive Care Units (ICU). Patients Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. Interventions Determination of serum caspase-8 levels when MMCAI was diagnosed. Main variables of interest Mortality at 30 days and time until this event. Results Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%–91%; p<0.001) by serum caspase-8 levels. Kaplan–Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4–28.4; p<0.001). Conclusions The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study (AU)

Objetivo Se han encontrado altas concentraciones de caspasa-8 (principal caspasa iniciadora de la vía extrínseca de apoptosis) en el tejido cerebral de pacientes con traumatismo craneoencefálico y en la sangre de pacientes con diferentes enfermedades. Sin embargo, no hay datos sobre las concentraciones sanguíneas de caspasa-8 en pacientes con ictus isquémico. Por tanto, el objetivo de este estudio fue determinar si existe una asociación entre las concentraciones sanguíneas de caspasa-8 y la probabilidad y velocidad de mortalidad a 30días en pacientes con infarto maligno de la arteria cerebral media (MMCAI). Diseño Observacional y prospectivo. Ámbito Cinco unidades de cuidados intensivos (UCI). Pacientes Pacientes con MMCAI grave definido como infarto agudo en más del 50% de ese territorio y escala de coma de Glasgow (GCS)<9. Intervenciones Determinación de niveles séricos de caspasa-8 cuando se diagnosticó el MMCAI grave. Variables de interés principal Mortalidad hasta los 30dias y tiempo hasta este evento. Resultados Los pacientes fallecidos (n=28) en comparación con los supervivientes (n=28) mostraron mayores concentraciones séricas de caspasa-8 (p<0,001), menor recuento plaquetario (p=0,01) y menor GCS (p=0,002). Encontramos un área bajo la curva para la predicción de mortalidad del 78% (IC 95%: 65-91%; p<0,001) por los niveles séricos de caspasa-8. El análisis de Kaplan-Meier encontró una mayor tasa de mortalidad en pacientes con niveles séricos de caspasa-8>62,8ng/mL (hazard ratio: 11,2; IC 95%: 4,4-28,4; p<0,001). Conclusiones La asociación de elevadas concentraciones sanguíneas de caspasa-8 con la tasa y velocidad de mortalidad a 30días en pacientes con MMCAI es el principal hallazgo nuevo de nuestro estudio (AU)

High serum nitrates levels in non-survivor COVID-19 patients / Altas concentraciones séricas de nitratos en pacientes fallecidos por COVID-19

Objective: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. Design: A prospective observation study was carried out. Setting: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). Patients: COVID-19 patients admitted to the ICU. Interventions: Determination of serum nitrate levels at ICU admission. Main variable of interest: Mortality at 30 days. Results: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006–1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006–1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73–92%; p<0.001), APACHE II (AUC=85%; 95%CI=75–96%; p<0.001) and SOFA (AUC=78%; 95%CI=63–92%; p=0.005) based on the DeLong method. The Kaplan–Meier analysis found patients with serum nitrates levels>68.4μmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3–863.9; p<0.001). Conclusions: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation (AU)

Objetivo: Se han encontrado niveles más elevados de nitratos en la sangre de pacientes con enfermedad del coronavirus 2019 (COVID-19) que en sujetos sanos. Por lo tanto, el objetivo de estudio consistió en explorar la posible asociación entre los niveles séricos de nitratos y la mortalidad de pacientes por COVID-19. Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI. Intervenciones: Se midieron los niveles séricos de nitratos al ingreso en la UCI. Variable de interés principal: Mortalidad a los 30 días. Resultados: Los pacientes fallecidos (n=11) comparados con los supervivientes (n=42) presentaron mayores APACHE-II (p<0,001), SOFA (p=0,004) y niveles séricos de nitratos (p=0,001). Los análisis de regresión logística mostraron una asociación entre los niveles séricos de nitratos al ingreso en la UCI y la mortalidad a los 30 días controlando por SOFA (OR:1.021; IC 95%:1.006-1.036; p=0,01) o APACHE-II (OR:1.023; IC 95%:1.006-1.041; p=0,01). No encontramos diferencias en el área bajo la curva (ABC) para la predicción de mortalidad entre los niveles séricos de nitratos (ABC:83%; IC 95%:73-92%; p<0,001), APACHE-II (ABC:85%; IC 95%:75-96%; p<0,001) y SOFA (ABC:78%; IC 95%:63-92%; p=0,005) con el método de DeLong. El análisis de Kaplan-Meier mostró que los pacientes que tenían niveles séricos de nitratos al ingreso en la UCI>68,4μmol/l presentaban mayor riesgo de fallecer (hazard ratio:138,8; IC 95%:22,3-863,9; p<0,001). Conclusiones: El principal nuevo hallazgo fue la asociación entre los niveles séricos de nitratos y la mortalidad de pacientes COVID-19 controlando por SOFA o APACHE-II; pero estudios de mayor tamaño muestral son necesarios para confirmar este resultado (AU)

High serum nitrates levels in non-survivor COVID-19 patients.

OBJECTIVE: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. DESIGN: A prospective observation study was carried out. SETTING: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). PATIENTS: COVID-19 patients admitted to the ICU. INTERVENTIONS: Determination of serum nitrate levels at ICU admission. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006-1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006-1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73-92%; p<0.001), APACHE II (AUC=85%; 95%CI=75-96%; p<0.001) and SOFA (AUC=78%; 95%CI=63-92%; p=0.005) based on the DeLong method. The Kaplan-Meier analysis found patients with serum nitrates levels>68.4µmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3-863.9; p<0.001). CONCLUSIONS: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation.

Prior influenza vaccine is not a risk factor for bacterial coinfection in patients admitted to the ICU due to severe influenza.

OBJECTIVE: To determine whether the prior usage of the flu vaccine is a risk factor for bacterial co-infection in patients with severe influenza. DESIGN: This was a retrospective observational cohort study of subjects admitted to the ICU. A propensity score matching, and logistic regression adjusted for potential confounders were carried out to evaluate the association between prior influenza vaccination and bacterial co-infection. SETTINGS: 184 ICUs in Spain due to severe influenza. PATIENTS: Patients included in the Spanish prospective flu registry. INTERVENTIONS: Flu vaccine prior to the hospital admission. RESULTS: A total of 4175 subjects were included in the study. 489 (11.7%) received the flu vaccine prior to develop influenza infection. Prior vaccinated patients were older 71 [61-78], and predominantly male 65.4%, with at least one comorbid condition 88.5%. Prior vaccination was not associated with bacterial co-infection in the logistic regression model (OR: 1.017; 95%CI 0.803-1.288; p=0.885). After matching, the average treatment effect of prior influenza vaccine on bacterial co-infection was not statistically significant when assessed by propensity score matching (p=0.87), nearest neighbor matching (p=0.59) and inverse probability weighting (p=0.99). CONCLUSIONS: No association was identified between prior influenza vaccine and bacterial coinfection in patients admitted to the ICU due to severe influenza. Post influenza vaccination studies are necessary to continue evaluating the possible benefits.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

Serum caspase-3 levels during the first week of traumatic brain injury / Niveles séricos de caspasa-3 durante la primera semana de un traumatismo craneoencefálico

Objective: Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality.DesignA prospective observational study was carried out.SettingSix Spanish Intensive Care Units.PatientsPatients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points).InterventionsSerum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI.Main variables of interestThirty-day mortality was considered as the study endpoint.ResultsIn comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61–0.78; p=0.001), 0.83 (0.74–0.89; p<0.001) and 0.87 (0.79–0.93; p<0.001), respectively.ConclusionsThe novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality. (AU)

Objetivo: La vía intrínseca y extrínseca de la apoptosis confluyen en la activación de caspasa-3. Se han encontrado mayores niveles séricos de caspasa-3 en el día 1 del traumatismo craneoencefálico (TCE) en los pacientes que fallecen en los primeros 30 días que en supervivientes. Por tanto, los objetivos de este estudio es determinar si los niveles séricos de caspasa-3 se mantienen superiores en los pacientes fallecidos que en los supervivientes, y si podrían utilizarse para predecir la mortalidad a 30 días.DiseñoEstudio observacional y prospectivo.ÁmbitoSeis unidades de cuidados intensivos españolas.PacientesEnfermos con un TCE grave y aislado (definido como escala de coma de Glasgow <9 y puntuación de gravedad de la lesión Score en lesiones no craneales <10).IntervencionesSe midieron los niveles séricos de caspasa-3 en los días 1, 4 y 8 del TCE.Variables de interés principalesMortalidad a los 30 días.ResultadosLos pacientes supervivientes a los 30 días (n=90) presentan menores niveles séricos de caspasa-3 en los días 1 (p=0,001), 4 (p<0,001) y 8 (p<0,001) del TCE que los fallecidos (n=34). Los niveles séricos de caspasa-3 en los días 1, 4 y 8 del TCE tenían un área bajo la curva (intervalo de confianza del 95%) para predecir la mortalidad de 0,70 (0,61-0,78; p=0,001), 0,83 (0,74-0,89; p<0,001) y 0,87 (0,79-0,93; p<0,001), respectivamente.ConclusionesLos nuevos hallazgos de nuestro estudio fueron que los niveles séricos de caspasa-3 durante la primera semana del TCE fueron menores en los pacientes supervivientes, y que pueden predecir la mortalidad a los 30 días. (AU)

HLA genetic polymorphisms and prognosis of patients with COVID-19 / Polimorfismos genéticos de los HLA y pronóstico de pacientes con COVID-19

OBJECTIVE: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. DESIGN: Observational and prospective study. SETTING: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). PATIENTS: COVID-19 patients admitted in ICU and healthy subjects. INTERVENTIONS: Determination of HLA genetic polymorphisms. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063-55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524-92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053-118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629-190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235-80.358; p = 0.03). CONCLUSIONS: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn

OBJETIVO: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19). DISEÑO: Estudio observacional y prospectivo. ÁMBITO: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). PACIENTES: Pacientes COVID-19 ingresados en la UCI y sujetos sanos. INTERVENCIONES: Se determinaron los polimorfismos genéticos de los HLA. VARIABLE DE INTERÉS PRINCIPAL: Mortalidad a los 30 días. RESULTADOS: Se incluyeron 3.886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p = 0,004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p = 0,02) y HLA-C*16 (p = 0,02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR = 7.693; IC del 95% = 1.063-55.650; p = 0,04) o APACHE-II (OR = 11.858; IC del 95% = 1.524-92.273; p = 0,02), el alelo HLA-C*01 controlando por SOFA (OR = 11.182; IC del 95% = 1.053-118.700; p = 0,04) o APACHE-II (OR = 17.604; IC del 95% = 1.629-190.211; p = 0,02) y el alelo HLA-DQB1*04 controlando por SOFA (OR = 9.963; IC del 95% = 1.235-80.358; p = 0,03). CONCLUSIONES: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de los HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, son necesarios estudios de mayor tamaño muestral para concluirlo definitivamente

DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction / El daño oxidativo del ADN y ARN se asocian con la mortalidad en los pacientes con inf0arto cerebral

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p < 0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p = 0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients

OBJETIVO: En el infarto cerebral puede aparecer una lesión cerebral secundaria debido a la oxidación del ácido desoxirribonucleico (ADN) y del ácido ribonucleico (ARN). Se han encontrado concentraciones sanguíneas de 8-hidroxi-2'-desoxiguanosina (8-OHdG) (por la oxidación de la guanosina del ADN) más altas en pacientes con infarto cerebral que en individuos sanos, y en pacientes con depresión tras un infarto cerebral. El objetivo de nuestro estudio fue determinar si existe una asociación entre el daño oxidativo del ADN y del ARN, y la mortalidad de los pacientes con infarto cerebral. MÉTODOS: Estudio prospectivo, observacional y multicéntrico realizado en unidades de cuidados intensivos de 6 hospitales españoles. Se incluyeron pacientes con un infarto maligno grave de la arteria cerebral media (MMCAI), definido como la presencia de cambios isquémicos en la tomografía en más del 50% del territorio de la arteria cerebral media y menos de 9 puntos en la escala Glasgow Coma Scale (GCS). Se determinaron los niveles séricos de las 3 especies oxidadas de la nucleobase guanina (OGS) (8-hidroxiguanina del ADN o ARN, 8-hidroxiguanosina del ARN y 8-OHdG del ADN) en el día del diagnóstico del MMCAI. La variable principal fue la mortalidad a 30 días. RESULTADOS: Encontramos concentraciones séricas de OGS (p < 0,001) más altas en los pacientes fallecidos (n=34) que en los supervivientes (n=34). La regresión logística mostró que los niveles séricos de OGS se asociaban con la mortalidad a los 30 días controlando por ácido láctico, GCS y recuento plaquetario (odds ratio=1,568; IC 95%=1,131-2,174; p = 0,01). CONCLUSIONES: El nuevo hallazgo de nuestro estudio fue la asociación entre los niveles séricos de OGS globales y la mortalidad de los pacientes con infarto cerebral

[HLA genetic polymorphisms and prognosis of patients with COVID-19]. / Polimorfismos genéticos de los HLA y pronóstico de pacientes con COVID-19.

OBJECTIVE: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. DESIGN: Observational and prospective study. SETTING: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). PATIENTS: COVID-19 patients admitted in ICU and healthy subjects. INTERVENTIONS: Determination of HLA genetic polymorphisms. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p=0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p=0.02) and HLA-C*16 (p=0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR=7.693; 95% CI=1.063-55.650; p=0.04) or APACHE-II (OR=11.858; 95% CI=1.524-92.273; p=0.02), the allele HLA-C*01 after controlling for SOFA (OR=11.182; 95% CI=1.053-118.700; p=0.04) or APACHE-II (OR=17.604; 95% CI=1.629-190.211; p=0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR=9.963; 95% CI=1.235-80.358; p=0.03). CONCLUSIONS: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Serum caspase-3 levels during the first week of traumatic brain injury.

OBJECTIVE: Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality. DESIGN: A prospective observational study was carried out. SETTING: Six Spanish Intensive Care Units. PATIENTS: Patients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points). INTERVENTIONS: Serum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI. MAIN VARIABLES OF INTEREST: Thirty-day mortality was considered as the study endpoint. RESULTS: In comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61-0.78; p=0.001), 0.83 (0.74-0.89; p<0.001) and 0.87 (0.79-0.93; p<0.001), respectively. CONCLUSIONS: The novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality.

DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction.

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p<0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p=0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients.

HLA genetic polymorphisms and prognosis of patients with COVID-19.

Objective: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. Design: Observational and prospective study. Setting: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). Patients: COVID-19 patients admitted in ICU and healthy subjects. Interventions: Determination of HLA genetic polymorphisms. Main variable of interest: Mortality at 30 days. Results: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063-55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524-92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053-118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629-190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235-80.358; p = 0.03). Conclusions: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Objetivo: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19). Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI y sujetos sanos. Intervenciones: Se determinaron los polimorfismos genéticos de los HLA. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 3.886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p = 0,004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p = 0,02) y HLA-C*16 (p = 0,02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR= 7.693; IC del 95%= 1.063-55.650; p = 0,04) o APACHE-II (OR= 11.858; IC del 95%= 1.524-92.273; p = 0,02), el alelo HLA-C*01 controlando por SOFA (OR= 11.182; IC del 95%= 1.053-118.700; p = 0,04) o APACHE-II (OR= 17.604; IC del 95%= 1.629-190.211; p = 0,02) y el alelo HLA-DQB1*04 controlando por SOFA (OR= 9.963; IC del 95%= 1.235-80.358; p = 0,03). Conclusiones: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de los HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, son necesarios estudios de mayor tamaño muestral para concluirlo definitivamente.

High serum nitrates levels in non-survivor COVID-19 patients.

OBJECTIVE: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. DESIGN: A prospective observation study was carried out. SETTING: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). PATIENTS: COVID-19 patients admitted to the ICU. INTERVENTIONS: Determination of serum nitrate levels at ICU admission. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006-1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006-1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73-92%; p<0.001), APACHE II (AUC=85%; 95%CI=75-96%; p<0.001) and SOFA (AUC=78%; 95%CI=63-92%; p=0.005) based on the DeLong method. The Kaplan-Meier analysis found patients with serum nitrates levels>68.4µmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3-863.9; p<0.001). CONCLUSIONS: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation.

Relationship between acute kidney injury and serum procalcitonin (PCT) concentration in critically ill patients with influenza infection / Relación entre disfunción renal aguda y valores séricos de procalcitonina en pacientes críticos con infección por gripe

INTRODUCTION: Serum procalcitonin (PCT) concentration could be increased in patients with renal dysfunction in the absence of bacterial infection. OBJECTIVE: To determine the interactions among serum renal biomarkers of acute kidney injury (AKI) and serum PCT concentration, in patients admitted to the intensive care unit (ICU) due to lung influenza infection. DESIGN: Secondary analysis of a prospective multicentre observational study. SETTING: 148 Spanish ICUs. PATIENTS: ICU patients admitted with influenza infection without bacterial co-infection. Clinical, laboratory and hemodynamic variables were recorded. AKI was classified as AKI I or II based on creatinine (Cr) concentrations (≥1.60-2.50mg/dL and Cr≥2.51-3.99mg/dL, respectively). Patients with chronic renal disease, receiving renal replacement treatment or with Cr>4mg/dL were excluded. Spearman's correlation, simple and multiple linear regression analysis were performed. INTERVENTIONS: None. RESULTS: Out of 663 patients included in the study, 52 (8.2%) and 10 (1.6%) developed AKI I and II, respectively. Patients with AKI were significantly older, had more comorbid conditions and were more severally ill. PCT concentrations were higher in patients with AKI (2.62 [0.60-10.0]ng/mL vs. 0.40 [0.13-1.20]ng/mL, p = 0.002). Weak correlations between Cr/PCT (rho=0.18) and Urea (U)/PCT (rho=0.19) were identified. Simple linear regression showed poor interaction between Cr/U and PCT concentrations (Cr R2=0.03 and U R2=0.018). Similar results were observed during multiple linear regression analysis (Cr R2=0.046 and U R2=0.013). CONCLUSIONS: Although PCT concentrations were slightly higher in patients with AKI, high PCT concentrations are not explained by AKI and could be warning sign of a potential bacterial infection

INTRODUCCIÓN: Los niveles de procalcitonina (PCT) pueden elevarse en pacientes con disfunción renal aún en ausencia de infección bacteriana. OBJETIVOS: Determinar la interacción entre los biomarcadores de disfunción renal aguda (AKI) y las concentraciones séricas de PCT en pacientes ingresados en cuidados intensivos (UCI) debido a infección por gripe. DISEÑO: Análisis secundario de un estudio prospectivo, multicéntrico observacional. Lugar: Ciento cuarenta y ocho UCI. PACIENTES: Con infección por gripe sin co-infección bacteriana. Se registraron las variables clínicas, de laboratorio y hemodinámicas. El nivel de AKI fue definido como AKI I y II basado en la creatinina (Cr) sérica (>1,60-2,50mg/dl y >2,51-3,99mg/dl), respectivamente. Pacientes con insuficiencia renal crónica, técnicas de reemplazo renal o Cr>4mg/dl fueron excluidos. El análisis estadístico se realizó mediante correlación de Spearman y regresión linear simple y múltiple. INTERVENCIONES: Ninguna. RESULTADOS: De los 663 pacientes incluidos, 52 (8,2%) y 10 (1,6%) desarrollaron AKI I y II, respectivamente. Pacientes con AKI fueron más añosos, presentaron más comorbilidades y mayor nivel de gravedad. Los niveles de PCT fueron mayores en pacientes con AKI (2,62 [0,60-10,0] ng/ml vs. 0,40 [0,13-1,20] ng/ml; p = 0,002). Se observaron correlaciones débiles entre Cr/PCT (rho=0,18) y PCT/U (rho=0,19). La regresión linear simple evidenció una pobre contribución tanto de Cr (R2=0,03) como de U (R2=0,018) sobre los niveles de PCT. Resultados similares fueron obtenidos con la regresión linear múltiple para Cr (R2=0,046) y U (R2=0,013). CONCLUSIONES: Aunque los valores de PCT pueden estar elevados en pacientes con AKI, altos niveles de PCT no pueden ser explicados por la disfunción renal y podrían ser un signo de alarma de una potencial infección bacteriana

Relationship between acute kidney injury and serum procalcitonin (PCT) concentration in critically ill patients with influenza infection.

INTRODUCTION: Serum procalcitonin (PCT) concentration could be increased in patients with renal dysfunction in the absence of bacterial infection. OBJECTIVE: To determine the interactions among serum renal biomarkers of acute kidney injury (AKI) and serum PCT concentration, in patients admitted to the intensive care unit (ICU) due to lung influenza infection. DESIGN: Secondary analysis of a prospective multicentre observational study. SETTING: 148 Spanish ICUs. PATIENTS: ICU patients admitted with influenza infection without bacterial co-infection. Clinical, laboratory and hemodynamic variables were recorded. AKI was classified as AKI I or II based on creatinine (Cr) concentrations (≥1.60-2.50mg/dL and Cr≥2.51-3.99mg/dL, respectively). Patients with chronic renal disease, receiving renal replacement treatment or with Cr>4mg/dL were excluded. Spearman's correlation, simple and multiple linear regression analysis were performed. INTERVENTIONS: None. RESULTS: Out of 663 patients included in the study, 52 (8.2%) and 10 (1.6%) developed AKI I and II, respectively. Patients with AKI were significantly older, had more comorbid conditions and were more severally ill. PCT concentrations were higher in patients with AKI (2.62 [0.60-10.0]ng/mL vs. 0.40 [0.13-1.20]ng/mL, p=0.002). Weak correlations between Cr/PCT (rho=0.18) and Urea (U)/PCT (rho=0.19) were identified. Simple linear regression showed poor interaction between Cr/U and PCT concentrations (Cr R2=0.03 and U R2=0.018). Similar results were observed during multiple linear regression analysis (Cr R2=0.046 and U R2=0.013). CONCLUSIONS: Although PCT concentrations were slightly higher in patients with AKI, high PCT concentrations are not explained by AKI and could be warning sign of a potential bacterial infection.