Parthanatos type programmed cell death and septic patient mortality / Muerte celular programada tipo Parthanatos y mortalidad de los pacientes sépticos

Objective: Parthanatos is a form of programmed cell death mediated by apoptosis-inducing factor (AIF). However, there are not data on parthanatos in septic patients. The objective of the current study was to explore whether parthanatos is associated with mortality of septic patients. Design: Observational and prospective study. Setting: Three Spanish Intensive Care Units during 2017. Patients: Patients with sepsis according to Sepsis-3 Consensus criteria. Interventions: Serum AIF concentrations were determined at moment of sepsis diagnosis. Main variable of interest: Mortality at 30 days. Results: There were included 195 septic patients, and non-surviving (n=72) had serum AIF levels (p<0.001), lactic acid (p<0.001) and APACHE-II (p<0.001) that surviving (n=123). Multiple logistic regression analysis showed that patients with serum AIF levels>55.6ng/mL had higher mortality risk (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlling for age, SOFA and lactic acid. Conclusions: Parthanatos is associated with mortality of septic patients. (AU)

Objetivo: Parthanatos es un tipo de muerte celular programada mediada por el factor inductor de apoptosis (AIF). Sin embargo, no hay datos sobre Parthanatos en pacientes sépticos. Por ello, el objetivo de este estudio fue explorar si Parthanatos está asociado con la morlaidad de los pacientes sépticos. Diseño: Estudio observacional y prospective. Ámbito: Tres Unidades de Cuidados Intensivos españolas durante 2017. Pacientes: Pacientes con sepsis en base a los criterios del Consenso Sepsis-3. Intervenciones: Se determinaron las concentraciones séricas de AIF en el momento del diagnóstico de la sepsis. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 195 pacientes sépticos, y los que fallecieron (n=72) presentaron mayores concentraciones séricas de AIF (p<0.001) y de ácido láctico (p<0.001), y mayor puntuación APACHE-II (p<0.001) que los pacientes supervivientes (n=123). El análisis de regresión logística múltiple mostró que los pacientes con concentraciones séricas de AIF>55.6ng/mL tuvieron mayor riesgo de fallecer (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlando por edad, SOFA y ácido láctico. Conclusiones: Parthanatos está asociado con la mortalidad de pacientes sépticos. (AU)

Parthanatos type programmed cell death and septic patient mortality.

OBJECTIVE: Parthanatos is a form of programmed cell death mediated by apoptosis-inducing factor (AIF). However, there are not data on parthanatos in septic patients. The objective of the current study was to explore whether parthanatos is associated with mortality of septic patients. DESIGN: Observational and prospective study. SETTING: Three Spanish Intensive Care Units during 2017. PATIENTS: Patients with sepsis according to Sepsis-3 Consensus criteria. INTERVENTIONS: Serum AIF concentrations were determined at moment of sepsis diagnosis. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: There were included 195 septic patients, and non-surviving (n=72) had serum AIF levels (p<0.001), lactic acid (p<0.001) and APACHE-II (p<0.001) that surviving (n=123). Multiple logistic regression analysis showed that patients with serum AIF levels>55.6ng/mL had higher mortality risk (OR=3.290; 95% CI=1.551-6.979; p=0.002) controlling for age, SOFA and lactic acid. CONCLUSIONS: Parthanatos is associated with mortality of septic patients.

Serum Fas levels during first week of sepsis are associated with severity and mortality.

INTRODUCTION: The aim of our study was to explore whether there is an association of serum sFas (cell death apoptosis receptor) concentrations during the first week of sepsis with sepsis severity and sepsis mortality. METHODS: In this observational study, septic patients were recruited. Serum sFas concentrations were determined on days 1, 4, and 8 of sepsis diagnosis. Thirty-day mortality was the outcome variable. RESULTS: Surviving patients (n = 181) compared to non-survivors (n = 101) presented lower serum sFas levels on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001), and lower SOFA on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001). Logistic regression analyses showed associations between 30-day mortality and serum sFas levels controlling for SOFA on day 1 (OR = 1.005; 95% CI = 1.003-1.007; p < 0.001), day 4 (OR = 1.044; 95% CI = 1.029-1.060; p < 0.001) and day 8 (OR = 1.012; 95% CI = 1.002-1.022; p = 0.02). CONCLUSIONS: The association of serum sFas concentrations during the first week of sepsis with sepsis severity and sepsis mortality were our new findings.

Association between blood caspase-9 concentrations and septic patient prognosis.

BACKGROUND: There are few data on caspase­9 (intrinsic apoptosis pathway initiating caspase) in septic patients. Higher serum caspase­9 levels in septic patients than in healthy subjects have been found. However, there are no data on the prognosis of septic patients and blood caspase­9 concentrations. Therefore, the objective of this study was to analyze the potential association between blood caspase­9 concentrations and prognosis in septic patients. METHODS: Three Spanish hospitals participated in the recruitment of septic patients admitted to intensive care units in this observational and prospective study. Serum caspase­9 concentrations were determined at the time of sepsis diagnosis. The 30-day mortality was the outcome variable. RESULTS: Higher Acute Phisiology and Chronic Health Evaluation(APACHE)-II (p < 0.001), Sepsis-related Organ Failure Assessment score (SOFA) (p < 0.001), serum lactic acid levels (p = 0.001), serum caspase­9 levels (p < 0.001), age (p < 0.001), International normalized ratio (INR) (p = 0.001), rate of septic shock (p = 0.001), Activated partial thromboplastin time (aPTT) (p = 0.03), rate of diabetes mellitus (p = 0.04), and lower platelet counts (p = 0.01) were found in non-surviving (n = 80) than in surviving patients (n = 134). Multiple logistic regression analysis showed an association between serum caspase­9 concentrations and mortality (Odds Ratio (OR) = 1.985; 95% Confidence Interval (CI) = 1.359-2.900; p < 0.001) regardless of age, SOFA, lactic acid and septic shock and history of diabetes mellitus. No significant differences were found when we compared area under ROC curves of serum caspase­9 with SOFA (p = 0.92) and with lactic acid (p = 0.59). CONCLUSIONS: The main novel finding of our study was the association between blood caspase­9 concentrations and septic patient prognosis. However, our study showed some limitations (for example, the absence of data in respect to execution of Surviving Sepsis Campaign bundles); thus, more research could be interesting to confirm our preliminary findings.

Association between neutrophil-to-lymphocyte ratio in the first seven days of sepsis and mortality.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity. METHODS: This observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity. RESULTS: Thirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p<0.001), fourth (p<0.001), and eighth (p<0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p<0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days. CONCLUSIONS: The new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

Association between neutrophil-to-lymphocyte ratio in the first seven days of sepsis and mortality / Asociación entre la relación neutrófilos/linfocitos durante los primeros siete días de sepsis y mortalidad

IntroductionThe neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity.MethodsThis observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity.ResultsThirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p<0.001), fourth (p<0.001), and eighth (p<0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p<0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days.ConclusionsThe new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

IntroducciónSe ha objetivado que la relación neutrófilos/linfocitos (NLR) en el momento del diagnóstico de la sepsis es mayor en fallecidos que en supervivientes y que está asociada con la mortalidad. En dos estudios, se ha reportado mayor NLR en fallecidos durante la evolución; sin embargo, NLR no se controló por la gravedad de la sepsis. Por lo tanto, el objetivo de este estudio consistió en determinar si existe una asociación entre NLR durante los primeros siete días y mortalidad, controlando por gravedad de la sepsis.MétodosEste estudio observacional, incluyendo pacientes sépticos, fue realizado en las Unidades de Cuidados Intensivos de tres hospitales españoles. Se registró NLR en los días 1, 4 y 8 del diagnóstico de la sepsis. Se realizó regresión logística múltiple para determinar la asociación entre NLR durante los primeros siete días y mortalidad (a los 30 días), controlando por gravedad de la sepsis.ResultadosLos pacientes fallecidos en los primeros 30 días (n = 68), comparados con los supervivientes (n = 135), tuvieron mayor NLR en los días 1 (p < 0,001), 4 (p < 0,001) y 8 (p < 0,001) del diagnóstico de la sepsis. La regresión logística múltiple mostró la asociación entre NLR en los días 1 (p < 0,001), 4 (p = 0,004) y 8 (p = 0,01) del diagnóstico de la sepsis y mortalidad, controlando por SOFA y lactatemia en esos días.ConclusionesEl nuevo hallazgo de nuestro estudio fue la asociación entre NLR durante los primeros siete días de la sepsis y la mortalidad, controlando por gravedad de la sepsis.

High mortality rate of septic patients with high blood granzyme B concentrations.

Granzyme B could be released from cytotoxic T lymphocytes producing apoptosis activation. The objective of our study was to determine whether an association between septic patient mortality and blood granzyme B concentrations exist. We recruited septic patients admitted in 3 Intensive Care Units. We recorded mortality at 30 days and we determined serum granzyme B concentrations at moment of sepsis diagnosis. We found higher rate of history of diabetes mellitus (P = 0.02), serum granzyme B concentrations (P < 0.001), age (P = 0.001), serum lactic acid levels (P = 0.001) and sepsis-related organ failure assessment (P < 0.001) exhibited non-surviving patients (n = 67) than surviving ones (n = 110). We found in multiple logistic regression analysis an association of serum granzyme B concentrations with mortality (odds ratio = 1.223; 95% confidence interval = 1.104-1.355; P < 0.001) controlling for diabetes mellitus, sepsis-related organ failure assessment, lactic acid and age. That we know, our study is the first reporting the existence of an association of high serum granzyme B concentrations with high septic patients mortality.

Blood Bcl-2 levels to predict the mortality of septic patients.

Aim: To determine whether blood concentrations of Bcl-2 during the 1st week of sepsis could help predict mortality. Methods: Serum Bcl-2 concentrations were determined at the 1st, 4th and 8th days of sepsis diagnosis. Results: Thirty-day surviving patients (n = 168) showed higher serum Bcl-2 levels at the 1st (p = 0.002), 4th (p < 0.001) and 8th days (p < 0.001) of sepsis diagnosis than non-surviving patients (n = 91). An association between serum Bcl-2 concentrations at the 1st (p = 0.003), 4th (p < 0.001) and 8th days (p = 0.01) and 30-day mortality after controlling for diabetes mellitus, Sepsis-related Organ Failure Assessment, lactic acid and age was found in the multiple logistic regression analysis. Conclusions: The novel finding is that blood Bcl-2 concentrations at any time in the 1st week of sepsis are associated with mortality.

Mortality prediction of septic patients by blood caspase-8 levels.

We have not found data about blood caspase-8 concentrations (initiator caspase in the extrinsic pathway of apoptosis) during follow-up of sepsis and this was the objective of our study. We included septic patients. Serum caspase-8 concentrations were determined at days 1, 4, and 8 of sepsis diagnosis. We registered mortality at 30 days. Nonsurviving patients (n = 89) in respect to surviving patients (n = 160) showed higher serum caspase-8 levels at days 1 (P < 0.001), 4 (P <0.001), and 8 (P <0.001) of sepsis diagnosis. Serum caspase-8 levels on day 1, day 4, and day 8 had an area under curve for the prediction of 30-day mortality of 68% (60%-75%, P<0.001), 72% (62%-82%, P<0.001), and 81% (73%-90%, P<0.001). Thus, that blood caspase-8 concentrations at any time during the first week of sepsis were higher in non-survivor than in survivor patients and that were able to predict mortality were new findings in our study.

Association of serum soluble Fas concentrations and mortality of septic patients.

INTRODUCTION: Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists. METHODS: We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination. RESULTS: Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p<0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002-1.006; p<0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002-1.006; p<0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65-71%; p<0.001). Kaplan-Meier analysis showed higher mortality rate in patients with serum sFas levels>83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1-5.0; p<0.001). CONCLUSIONS: That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.

Association of serum soluble Fas concentrations and mortality of septic patients / Asociación de concentraciones séricas de soluble Fas y mortalidad de pacientes sépticos

Introduction: Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists. Methods: We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination. Results: Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p<0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002–1.006; p<0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002–1.006; p<0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65–71%; p<0.001). Kaplan–Meier analysis showed higher mortality rate in patients with serum sFas levels>83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1–5.0; p<0.001). Conclusions: That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.(AU)

Introducción: Existen pocos datos sobre Fas, uno de los principales receptores que activan la vía extrínseca de la apoptosis, en pacientes septicos. En estudios de pequeño tamaño muestral se han encontrado altas concentraciones sanguíneas de soluble Fas (sFas) en pacientes sépticos fallecidos en comparación con supervivientes; sin embargo, no ha sido establecida la asociación de concentraciones sanguíneas de sFas con mortalidad controlando por la gravedad de la sepsis. Por lo tanto, el principal objetivo de nuestro estudio fue determinar si existe una asociación entre concentraciones sanguíneas de sFas y la mortalidad en sepsis controlando por la gravedad. Métodos: Incluímos pacientes sépticos en este estudio observacional y prospectivo realizado en tres Unidades de Cuidados Intensivos españolas. Obtuvimos muestras de suero en el momento del diagnóstico de la sepsis para la determinación de concentraciones de sFas. Resultados: Los pacientes fallecidos durante los primeros treinta días (n=85) comparados con los supervivientes (n=151) tuvieron mayores concentraciones séricas de sFas (p<0,001). Se encontró una asociación de concentraciones séricas de sFas con mortalidad controlando por edad y SOFA (OR=1,004; 95% IC=1,002-1,006; p < 0,001), y por edad y APACHE-II (OR=1,004; 95% IC=1,002-1,006; p < 0,001). Las concentraciones séricas de sFas mostraron un área bajo la curva para la predicción de mortalidad del 71% (IC 95%=65%-71%; p < 0,001). El análisis Kaplan-Meier mostró una mayor mortalidad en los pacientes con concentraciones séricas de sFas > 83,5 ng/mL (Hazard ratio=3,2; 95% IC=2,1-5,0; p < 0,001). Conclusiones: La asociación entre concentraciones sanguíneas de sFas y la mortalidad en sepsis controlando por la gravedad fue el principal nuevo hallazgo de nuestro estudio.(AU)

Circulating Bcl-2 concentrations and septic patient mortality.

INTRODUCTION: There are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction. METHODS: Intensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable. RESULTS: We found that 30-day non-surviving patients (n=81) showed lower serum Bcl-2 levels (p=0.003) than surviving patients (n=140). We found that serum concentrations of Bcl-2<4.4ng/mL were associated with mortality (OR=3.228; 95% CI=1.406-7.415; p=0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI=55-68%; p=0.003). CONCLUSIONS: In our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.

Circulating Bcl-2 concentrations and septic patient mortality / Concentraciones sanguíneas de Bcl-2 y mortalidad de los pacientes con sepsis

Introduction: There are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction. Methods: Intensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable. Results: We found that 30-day non-surviving patients (n=81) showed lower serum Bcl-2 levels (p=0.003) than surviving patients (n=140). We found that serum concentrations of Bcl-2<4.4ng/mL were associated with mortality (OR=3.228; 95% CI=1.406–7.415; p=0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI=55–68%; p=0.003). Conclusions: In our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.(AU)

Introducción: No hemos encontrado datos publicados sobre las concentraciones sanguíneas de B-cell lymphoma 2 (Bcl-2) (una de las moléculas antiapoptóticas de la familia Bcl-2 de la vía intrínseca de la apoptosis) en pacientes con sepsis. Por lo cual, este estudio se realizó con los propósitos de explorar las concentraciones sanguíneas de Bcl-2 en el momento del diagnóstico de la sepsis en los pacientes supervivientes y fallecidos, analizar si se asocian con la supervivencia y determinar si son útiles para predecir el fallecimiento. Métodos: Las unidades de Cuidados Intensivos de 3 hospitales españoles participaron en este estudio observacional y prospectivo de pacientes con sepsis, y se determinaron las concentraciones sanguíneas de Bcl-2 al diagnosticar la sepsis. La mortalidad a 30 días fue nuestra variable resultado. Resultados: Los pacientes que fallecían en los primeros 30 días (n=81) presentaron menores concentraciones sanguíneas de Bcl-2 (p=0,003) que los supervivientes (n=140). Encontramos que las concentraciones sanguíneas de Bcl-2<4,4 ng/ml se asociaban con la mortalidad en el análisis de regresión logística múltiple (OR=3,228; IC del 95%=1,406-7,415; p=0,006). Encontramos que las concentraciones sanguíneas de Bcl-2 tenían un área bajo la curva del 62% (IC del 95%=55%-68%; p=0,003) para la predicción del fallecimiento. Conclusiones: En nuestro estudio aparecieron nuevos hallazgos como que las concentraciones sanguíneas de Bcl-2 fueron superiores en los supervivientes, se asociaban con la supervivencia y podían predecir la mortalidad.(AU)

Association between serum sFasL concentrations and sepsis mortality.

BACKGROUND: There are scarce data on soluble Fas Ligand (sFasL), one of the main ligands that activate the apoptosis extrinsic pathway, in septic patients. In a small study of septic children were found higher plasma sFasL levels in non-survivors compared with survivors; however, an association between blood sFasL levels and mortality controlling for sepsis severity was not stablished due to the small sample size of the study. Therefore, the main objective of this study was to determine whether there is an association between blood sFasL concentrations and mortality in septic patients controlling for sepsis severity. Methods: Septic patients were included in this observational and prospective study conducted in three Spanish Intensive Care Units. Serum samples at diagnosis of sepsis were obtained for serum sFasL levels determination. RESULTS: Thirty-day non-surviving patients (n = 85) with respect to surviving patients (n = 151) showed higher serum sFasL levels (p<.001). Multiple logistic regression analysis found an association between serum sFasL levels and mortality (odds ratio [OR] = 1.007; 95% confidence interval [CI] = 1.003-1.010; p<.001) after controlling for age, septic shock, SOFA, INR and aPTT. The area under the curve (AUC) for mortality prediction by serum sFasL levels was of 62% (95% CI = 56-69%; p=.003). In Kaplan-Meier analysis was found that patients with serum sFasL levels >109 pg/mL had a higher mortality rate (hazard ratio = 3.6; 95% CI = 1.93-6.78; p<.001). CONCLUSIONS: The main new finding from our study was that serum sFasL concentrations were associated with mortality in septic patients controlling for sepsis severity. Highlights Blood sFasL concentrations were higher in non-survivor than in survivor patients. There is an association between blood sFasL concentrations and mortality in septic patients. Blood sFasL concentrations could predict mortality of septic patients.

Association between red blood cell distribution width and mortality of COVID-19 patients.

PURPOSE: We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. METHODS: Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. RESULTS: We found that patients who did not survive (n=25) compared to surviving patients (n=118) were older (p=0.004), showed higher RDW (p=0.001), urea (p<0.001), APACHE-II (p<0.001) and SOFA (p<0.001), and lower platelet count (p=0.007) and pH (p=0.008). Multiple binomial logistic regression analysis showed that RDW was associated with 30-day mortality after controlling for: SOFA and age (OR=1.659; 95% CI=1.130-2.434; p=0.01); APACHE-II and platelet count (OR=2.062; 95% CI=1.359-3.129; p=0.001); and pH and urea (OR=1.797; 95% CI=1.250-2.582; p=0.002). The area under the curve (AUC) of RDW for mortality prediction was of 71% (95% CI=63-78%; p<0.001). We did not find significant differences in the predictive capacity between RDW and SOFA (p=0.66) or between RDW and APACHE-II (p=0.12). CONCLUSIONS: Our study provides new information regarding the ability to predict mortality in patients with COVID-19. There is an association between high RDW and mortality. RDW has a good performance to predict 30-day mortality, similar to other severity scores (such as APACHE II and SOFA) but easier and faster to obtain.

Association of serum soluble Fas concentrations and mortality of septic patients.

INTRODUCTION: Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists. METHODS: We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination. RESULTS: Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p<0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002-1.006; p<0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002-1.006; p<0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65-71%; p<0.001). Kaplan-Meier analysis showed higher mortality rate in patients with serum sFas levels>83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1-5.0; p<0.001). CONCLUSIONS: That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.

Association between neutrophil-to-lymphocyte ratio in the first seven days of sepsis and mortality.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity. METHODS: This observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity. RESULTS: Thirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p<0.001), fourth (p<0.001), and eighth (p<0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p<0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days. CONCLUSIONS: The new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

Association between DNA and RNA oxidative damage and mortality in septic patients.

PURPOSE: DNA and RNA oxidative damage occurs during sepsis. Higher urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels (from oxidation of guanosine from DNA) have been found in non-surviving patients than in surviving septic patients. However, the relation between DNA and RNA oxidative damage and mortality in septic patients has never been published; thus, the objective of this study was to determine the existence of this association. METHODS: This prospective and observational study including septic patients was conducted in 8 Spanish Intensive Care Units. Serum concentrations of the three oxidizied guanine species (OGS) (8-OHdG from DNA, 8-hydroxyguanosine from RNA, and 8-hydroxyguanine from DNA or RNA) were determined, and malondialdehyde (to estimate lipid peroxidation) in the diagnosis of sepsis. Mortality at 30 days was the end-point study. RESULTS: Non-surviving patients (n = 78) compared to surviving patients (n = 139) showed higher serum concentrations of OGS (p = .004) and malondialdehyde (p < .001). Simultaneously, an association between serum OGS concentrations and mortality in logistic regression analysis was found (OR = 1.105; 95% CI = 1.024-1.193; p = .01), and a positive correlation between serum levels of OGS and malondialdehyde (rho = 0.21; p = .002). CONCLUSIONS: The new findings from our study were that oxidative DNA and RNA damage in septic patients was associated with mortality and lipid peroxidation.