Surveillance and prevention of healthcare-associated infections: best practices to prevent ventilator-associated events.

INTRODUCTION: Ventilator associated pneumonia (VAP) leads to an increase in morbidity, mortality, and healthcare costs. In addition to increased evidence from the latest European and American guidelines (published in 2017 and 2022, respectively), in the last two years, several important clinical experiences have added new prevention tools to be included to improve the management of VAP. AREAS COVERED: This paper is a narrative review of new evidence on VAP prevention. We divided VAP prevention measures into pharmacological, non-pharmacological, and ventilator care bundles. EXPERT OPINION: Most of the effective strategies that have been shown to decrease the incidence of complications are easy to implement and inexpensive. The implementation of care bundles, accompanied by educational measures and a multidisciplinary team should be part of optimal management. In addition to ventilator care bundles for the prevention of VAP, it could possibly be beneficial to use ventilator care bundles for the prevention of noninfectious ventilator associated events.

Adding vortexing to the Maki technique provides no benefit for the diagnosis of catheter colonization or catheter-related bacteremia.

BACKGROUND: A previous study compared vortexing and Maki techniques for the diagnosis of catheter-related bloodstream infection (CRBSI), and concluded that vortexing was not superior to Maki method. AIM: To determine whether the combined use of vortexing and Maki techniques provides profitability versus the Maki technique for the diagnosis of catheter tip colonization (CTC) and CRBSI. METHODS: Observational and prospective study carried out in an Intensive Care Unit. Patients with suspected catheter-related infection (CRI) and with one central venous catheter for at least 7 days were included. The area under the curve (AUC) of the Maki technique, the vortexing technique and the combination of both techniques for the diagnosis of CTC and CRBSI were compared. RESULTS: We included 136 episodes of suspected CRI. We found 21 cases of CTC of which 10 were also CRBSI cases. Of the 21 CTC episodes, 18 (85.7%) were diagnosed by Maki technique and vortexing technique, 3 (14.3%) only by the technique of Maki, and none only by technique of vortexing. Of the 10 CRBSI episodes, 9 (90.0%) were diagnosed by the techniques of Maki and vortexing, 1 (10.0%) was diagnosed only by the technique of Maki, and none only by the technique of vortexing. We no found differences in the comparison of AUC between the technique of Maki and the combination of Maki and vortexing techniques for the diagnosis of CTC (P = 0.99) and CRBSI (P = 0.99). CONCLUSION: The novel finding of our study was that the combined use of vortexing and Maki techniques did not provide profitability to the technique of Maki alone to CRBSI diagnosis of.

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.

Elevated soluble fas blood concentrations in patients dying from spontaneous intracerebral hemorrhage.

BACKGROUND: Several studies of spontaneous intracerebral hemorrhage (SICH) patients have shown apoptotic changes in brain samples after hematoma evacuation. However, there have been no data on the association between blood concentrations of soluble fas (sFas) (the main surface death receptor of the extrinsic apoptosis pathway) and the prognosis of spontaneous intracranial hypotension (SIH) patients. AIM: To determine whether there is an association between blood sFas concentrations and SICH patient mortality. METHODS: We included patients with severe and supratentorial SIH. Severe was defined as having Glasgow Coma Scale < 9. We determined serum sFas concentrations at the time of severe SICH diagnosis. RESULTS: We found that non-surviving patients (n = 36) compared to surviving patients (n = 39) had higher ICH score (P = 0.001), higher midline shift (P = 0.004), higher serum sFas concentrations (P < 0.001), and lower rate of early hematoma evacuation (P = 0.04). Multiple logistic regression analysis showed an association between serum sFas concentrations and 30-d mortality (odds ratio = 1.070; 95% confidence interval = 1.014-1.129; P = 0.01) controlling for ICH score, midline shift, and early hematoma evacuation. CONCLUSION: The association of blood sFas concentrations and SICH patient mortality is a novel finding in our study.

Patients with hepatocellular carcinoma that die during the first year of liver transplantation have high blood sFasL concentrations.

BACKGROUND: Fas ligand (FasL) is one ligand that activates extrinsic apoptosis pathway. High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation (LT). No high blood concentrations of soluble FasL (sFasL) have been found in patients with acute LT rejection; however, the samples size of those studies was small. AIM: To determine whether patients with hepatocellular carcinoma (HCC) that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size. METHODS: Patients underwent LT due to HCC were included in this retrospective study. Serum sFasL levels prior to LT were measured and one-year LT mortality was registered. RESULTS: Non-surviving patients (n = 14) showed higher serum sFasL levels [477 (269-496) vs 85 (44-382) pg/mL; P < 0.001] than surviving patients (n = 113). Serum sFasL levels (pg/mL) were associated with mortality (OR = 1.006; 95%CI = 1.003-1.010; P = 0.001) independently of age of LT donor in the logistic regression analysis. CONCLUSION: We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.

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.

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.

DNA and RNA oxidative damage in hepatocellular carcinoma patients and mortality during the first year of liver transplantation.

BACKGROUND: Oxidative damage of DNA and RNA has been associated with mortality of patients with different diseases. However, there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). AIM: To determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis. METHODS: Patients with HCC who underwent LT were included in this observational and retrospective study. Serum levels of all three oxidized guanine species (OGS) were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation. LT mortality at 1 year was the end-point study. RESULTS: Surviving patients (n = 101) showed lower serum OGS levels (P = 0.01) and lower age of the liver donor (P = 0.03) than non-surviving patients (n = 13). An association between serum OGS levels prior to LT and 1-year LT (odds ratio = 2.079; 95% confidence interval = 1.356-3.189; P = 0.001) was found in the logistic regression analysis. CONCLUSION: The main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.

High blood Fas concentrations in non-survivor patients with traumatic brain injury.

Fas is one of the main death receptors of the extrinsic pathway of apoptosis. A study has reported higher Fas expression in brain samples of non-surviving TBI patients than in survivors. The objective of our current study was to determine whether there is an association between Fas concentrations in blood and mortality of isolated TBI patients. Patients with severe TBI [< 9 points in Glasgow Coma Scale (GCS)] and isolated TBI (< 10 non-cranial aspects points on the Injury Severity Score) were included from 5 Intensive Care Units. We measured serum Fas concentrations on the day of TBI. Non-surviving (n = 23) compared to surviving patients (n = 57) had higher age (p = 0.01), lower GCS (p = 0.001), higher APACHE-II score (p < 0.001), higher ICP (p = 0.01), higher CT findings with high risk of death (p = 0.02) and higher serum Fas concentrations (p < 0.001). We found in regression analyses an association between serum Fas levels and mortality of TBI patients after controlling for CT findings, age and CGS (OR = 1.006; 95% CI 1.001-1.011; p = 0.02), and after controlling for CT findings, ICP and APACHE-II (OR = 1.007; 95% CI 1.001-1.012; p = 0.02). Thus, the most interesting and novel finding in this study is the association between high blood Fas concentrations and mortality in TBI patients.

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.

Sonication did not provide reliability to Maki technique for catheter related bloodstream infection diagnosis / La sonicación no proporciona rentabilidad a la técnica de Maki para el diagnóstico de bacteriemia relacionada con catéter

Objective. The aim of our study was to analyze sonicationand Maki techniques for diagnosis of catheter tip colonizationand catheter-related bloodstream infection (CRBSI) on patientsadmitted to ICU.Material and methods. Observational and prospectivestudy in one Intensive Care Unit. Patients with some centralvenous catheter (CVC) at least for 7 days and catheter-relatedinfection (CRI) suspicion (new episode of fever or sepsis) wereincluded. We performed Maki technique followed by sonication of catheter tip. We compared area under the curve (AUC)of Maki, sonication, and techniques combination to diagnosiscatheter tip colonization and CRBSI.Results. We included 94 CVC from 87 CRI suspicion episodes. We found 14 cases of catheter tip colonization and 10cases of CRBSI. Of the 14 catheter tip colonization cases, 7(50.0%) were detected by Maki and sonication techniques, 6(42.9%) were detected only by Maki technique, and 1 (7.1%)was detected only by sonication technique. Of the 10 CRBSI,6 (60.0%) were detected by Maki and sonication techniques,4 (40.0%) were detected only by Maki technique, and anyonly by sonication technique. We found higher AUC in Makitechnique than in sonication technique to diagnosis of CRBSI(p=0.02) and to diagnosis of catheter tip colonization (p=0.03).No significant differences were found in AUC between Makitechnique and combination techniques for diagnosis of catheter tip colonization (p=0.32) and of CRBSI (p=0.32).Conclusion.: Sonication did not provide reliability to Makitechnique for diagnosis of catheter tip colonization and CRBSI. (AU)

Objetivo. El objetivo de nuestro estudio fue analizar lastécnicas de sonicación y Maki para el diagnóstico de la colonización de la punta del catéter y la bacteriemia relacionada conel catéter (CRBSI) en pacientes ingresados en UCI.Material y método. Estudio observacional y prospectivoen una Unidad de Cuidados Intensivos. Se incluyeron pacientescon algún catéter venoso central (CVC) insertado al menos durante 7 días y sospecha de sospecha de infección relacionadacon el catéter (IRC) (nuevo episodio de fiebre o sepsis). Se realizó técnica de Maki y posteriormente sonicación de la puntadel catéter. Comparamos áreas bajo la curva (AUC) de Maki,sonicación y combinación de técnicas para el diagnóstico decolonización de la punta del catéter y de CRBSI.Resultados. Se incluyeron 94 CVC de 87 episodios de sospecha de IRC. Encontramos 14 casos de colonización de la puntadel catéter y 10 casos de CRBSI. De los 14 casos de colonizaciónde la punta del catéter, 7 (50,0%) fueron detectados por Maki ytécnicas de sonicación, 6 (42,9%) fueron detectados solo por latécnica de Maki y 1 (7,1%) fue detectado solo por la técnica desonicación. De los 10 CRBSI, 6 (60,0%) fueron detectados portécnicas de Maki y sonicación, 4 (40,0%) fueron detectados solopor la técnica de Maki, y ninguno solo por la técnica de sonicación. Encontramos mayor AUC con Maki que en la sonicaciónpara el diagnóstico de CRBSI (p=0.02) y para el diagnóstico decolonización de la punta del catéter (p=0.03). No encontramosdiferencias significativas en AUC entre Maki technique y combinación de técnicas para el diagnóstico de CRBSI (p=0.32) y parael diagnóstico de colonización de la punta del catéter (p=0.32).Conclusiones. La sonicación no proporcionó rentabilidada la técnica de Maki para el diagnóstico de colonización de lapunta del catéter y CRBSI. (AU)

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.

Blood soluble Fas concentrations and ischemic stroke patient mortality.

BACKGROUND: Fas is a major receptor for cell death by apoptosis. Higher blood concentrations of soluble Fas (sFas) have been reported in patients with ischemic stroke compared to control subjects. The aim of this study was to explore the existence or not of an association between blood sFas concentrations and mortality in patients with ischemic stroke. METHODS: This study included patients admitted to Intensive Care Units with severe and malignant middle cerebral artery infarction (MCAI), defined as acute infarction, in more than 50% of this territory on computed tomography and less than 9 points on the Glasgow Coma Scale (GCS). Serum sFas levels were determined at the time of diagnosis of MMCAI. RESULTS: Non-surviving severe MMCAI patients (n = 27) showed lower platelet count (p = 0.004), higher serum sFas (p < 0.001), and lower GCS (p = 0.001) compared to surviving patients (n = 27). Multiple logistic regression found an association of serum sFas levels and mortality at 30 days (OR = 1.015; 95% CI = 1.002-1.027; p = 0.02) after control for CGS and platelet count. CONCLUSIONS: The main novelty of our study was the existence of an association between high blood sFas concentrations and mortality in patients with ischemic stroke.

Mortality prediction of patients with spontaneous intracerebral hemorrhage by serum soluble Fas ligand concentrations.

BACKGROUND: A study of patients with spontaneous intracerebral hemorrhage (SIH) found a higher content of Fas ligand in the perihematomic brain area compared to healthy brain areas. The objective of this study was to analyze whether blood soluble Fas ligand (sFasL) concentrations could be used to estimate the prognosis of SIH patients. METHODS: Observational and prospective study performed in five Spanish Intensive Care Units. Patients with severe supratentorial SIH, defined as Glasgow Coma Scale (GCS) <9, were included. Serum sFasL levels were determined at the time of diagnosis of severe SIH. Mortality at 30 days was the end-point study. RESULTS: Surviving SIH patients (n = 41) compared to nonsurvivors (n = 38) showed lower serum sFasL levels (p < 0.001). The area under curve of mortality prediction for serum sFasL levels was 0.79 (95% CI = 0.70-0.89; p < 0.001). Multiple logistic regression analysis found an association of serum sFasL concentrations with 30-day mortality (ORo = 1,034; 95% CI = 1,010-1,058; p = 0,006) after controlling for midline shift, early hematoma evacuation, and intracerebral hemorrhage score. CONCLUSIONS: The capability of serum sFasL to predict SIH patient mortality is the main novel finding of our study. ABBREVIATIONS: APACHE II: Acute Physiology and Chronic Health Evaluation; aPTT: activated partial thromboplastin time; FIO2: fraction of inspired oxygen; GCS: Glasgow Coma Scale; ICU: Intensive Care Unit; INR: international normalized ratio; PaO2: pressure of arterial oxygen.