Association between septic patient mortality and blood survivin concentrations / Asociación entre la mortalidad de pacientes sépticos y las concentraciones sanguíneas de survivina

Objective Survivin is a member of inhibitors of apoptosis proteins family. There are not data about the association between mortality of septic patients and blood survivin concentrations. Therefore, the objective of this study was to determine whether exist that association. Design Observational and prospective study. Setting Three Spanish Intensive Care Units. Patient Patients with sepsis or septic shock according to Sepsis-3 Consensus criteria. Interventions Serum survivin concentrations were determined at moment of sepsis diagnosis. Main variable of interest Mortality at 30 days. Results A total of 204 patients were included in the study, of which 75 (36.8%) died in the first 30 days. Lower age (p<0.001), serum lactic acid levels (p=0.001), rate of septic shock (p=0.001) and SOFA (p<0.001), and higher serum survivin levels (p=0.001) exhibited surviving (n=129) than non-surviving patients (n=75). We found in multiple logistic regression analysis an association between serum survivin concentrations and mortality independently of SOFA, lactic acid, age, INR, activated partial thromboplastin time (aPTT) and empiric antimicrobial treatment adequate (OR=0.968; 95% CI=0.946–0.990; p=0.005), and also independently of APACHE-II, lactic acid, platelet, INR, aPTT and empiric antimicrobial treatment adequate (OR=0.966; 95% CI=0.943–0.989; p=0.004). Conclusions There is an association between septic patient mortality and low blood survivin concentrations (AU)

Objetivo Survivina es un miembro de la familia de proteínas inhibidoras de apoptosis. No existen datos sobre la asociación entre la mortalidad de los pacientes sépticos y las concentraciones de survivina en sangre. Por tanto, el objetivo de este estudio fue determinar si existe esa asociación. Diseño Estudio observacional y prospectivo. Ámbito Tres Unidades de Cuidados Intensivos españolas. Pacientes Pacientes con sepsis o shock séptico según criterios del Consenso Sepsis-3. Intervenciones Se determinaron las concentraciones séricas de survivina en el momento del diagnóstico de la sepsis. Variable de interés principal Mortalidad a los 30 días. Resultados Un total de 204 pacientes se incluyeron en el estudio, 75 (36,8%) de los cuales fallecieron en los primeros 30 días. Menor edad (p<0,001), niveles séricos de ácido láctico (p=0,001), tasa de shock séptico (p=0,001) y SOFA (p<0,001), y mayores niveles de survivina en suero (p=0,001) exhibieron los pacientes supervivientes (n=129) en comparación con los fallecidos (n=75). El análisis de regresión logística múltiple mostró una asociación entre las concentraciones séricas de survivina y la mortalidad independientemente del SOFA, ácido láctico, edad, INR, tiempo de tromboplastina parcial activada (aPTT) y tratamiento antimicrobiano empírico adecuado (OR=0,968; IC 95%=0,946-0,990; p=0,005), y también independientemente del APACHE-II, ácido láctico, plaquetas, INR, aPTT y tratamiento antimicrobiano empírico adecuado (OR=0,966; IC 95%=0,943-0,989; p=0,004). Conclusiones Existe una asociación entre la mortalidad de los pacientes sépticos y las concentraciones bajas de survivina en sangre (AU)

Association between septic patient mortality and blood survivin concentrations.

OBJECTIVE: Survivin is a member of inhibitors of apoptosis proteins family. There are not data about the association between mortality of septic patients and blood survivin concentrations. Therefore, the objective of this study was to determine whether exist that association. DESIGN: Observational and prospective study. SETTING: Three Spanish Intensive Care Units. PATIENTS: Patients with sepsis or septic shock according to Sepsis-3 Consensus criteria. INTERVENTIONS: Serum survivin concentrations were determined at moment of sepsis diagnosis. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 204 patients were included in the study, of which 75 (36.8%) died in the first 30 days. Lower age (p<0.001), serum lactic acid levels (p=0.001), rate of septic shock (p=0.001) and SOFA (p<0.001), and higher serum survivin levels (p=0.001) exhibited surviving (n=129) than non-surviving patients (n=75). We found in multiple logistic regression analysis an association between serum survivin concentrations and mortality independently of SOFA, lactic acid, age, INR, activated partial thromboplastin time (aPTT) and empiric antimicrobial treatment adequate (OR=0.968; 95% CI=0.946-0.990; p=0.005), and also independently of APACHE-II, lactic acid, platelet, INR, aPTT and empiric antimicrobial treatment adequate (OR=0.966; 95% CI=0.943-0.989; p=0.004). CONCLUSIONS: There is an association between septic patient mortality and low blood survivin concentrations.

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.

Blood caspase-8 concentrations and mortality among septic patients.

OBJECTIVE: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DESIGN: A prospective observational study was carried out. SETTING: Three Spanish Intensive Care Units. PATIENTS: Septic patients. INTERVENTIONS: Serum caspase-8 concentrations were determined at the diagnosis of sepsis. MAIN VARIABLE OF INTEREST: Mortality after 30 days. RESULTS: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001). CONCLUSIONS: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients.

Blood caspase-8 concentrations and mortality among septic patients / Niveles sanguíneos de caspasa-8 y mortalidad de los pacientes sépticos

Objective: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients.Design: A prospective observational study was carried out.Setting: Three Spanish Intensive Care Units.Patients: Septic patients.Interventions: Serum caspase-8 concentrations were determined at the diagnosis of sepsis.Main variable of interest: Mortality after 30 days.Results: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001).Conclusions: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients (AU)

Objetivo: No existen datos publicados sobre los niveles sanguíneos de caspasa-8 (la caspasa iniciadora en la vía extrínseca de apoptosis) en pacientes sépticos. Por lo tanto, los objetivos del estudio fueron describir los niveles sanguíneos de caspasa-8 en pacientes supervivientes y fallecidos y determinar si existe una asociación entre los niveles sanguíneos de caspasa-8 y la mortalidad de los pacientes sépticos.DiseñoEstudio observacional y prospectivo.ÁmbitoTres unidades de cuidados intensivos españolas.PacientesPacientes sépticos.IntervencionesSe determinaron las concentraciones séricas de caspasa-8 al diagnóstico de la sepsis.Variable de interés principalMortalidad a los 30 días.ResultadosEncontramos que los pacientes fallecidos en los primeros 30 días (n=81) comparados con los pacientes supervivientes (n=140) presentaban niveles séricos mayores de caspasa-8 (p<0,001). En el análisis de regresión logística múltiple encontramos una asociación entre los niveles séricos de caspasa-8>43,5ng/ml y la mortalidad (OR: 3,306; IC 95%: 1,619-6,753; p=0,001). El área bajo la curva para predecir la mortalidad por los niveles séricos de caspasa-8 fue del 67% (IC 95%: 60-73%; p<0,001).ConclusionesLos nuevos hallazgos de nuestro estudio fueron que los niveles séricos mayores de caspasa-8 eran superiores en los pacientes fallecidos en los primeros 30 días, y que existe una asociación entre los niveles séricos de caspasa-8 y la mortalidad (AU)

Treatment success after rhinosurgery: an evaluation of subjective and objective parameters.

PURPOSE: Septal deviation and nose deformities are widely prevalent. As a consequence, patients may complain about difficulties in nasal breathing leading to a perception of diminished disease-specific quality of life. In a prospective randomized trial, we aimed to analyse the outcome of septoplasty (SPL) and septorhinoplasty (SRP) on patient satisfaction. METHODS: Patients with functional indication for SPL (n = 19) or SRP (n = 54) were included and randomized for additional turbinoplasty. Preoperative clinical symptoms were collected with SNOT-20 GAV (Sinu-nasal outcome test-20-German adapted version) and NOSE© (nasal obstruction symptom evaluation) questionnaires. The final evaluation of treatment success was performed 9 months after surgery with SNOT-20 GAV, NOSE© and a self-established feedback questionnaire. Nasal breathing and obstruction were objectively measured with rhinomanometry and acoustic rhinometry [minimum cross-sectional area 2 (MCA2)]. RESULTS: Minimum cross-sectional area 2 was statistically improved compared to the pre-treatment value in SPL (p = 0.0004) and SRP (p = 0.0001). Regarding MCA2 values of matched patient groups, similar findings were detected (SPL: p = 0.0013, SRP: p < 0.0001). Sinu-nasal outcome test-20 GAV and NOSE© scores were significantly reduced after both surgical procedures (NOSE©: SPL: p < 0.0001, SRP: p < 0.0001; SNOT-20 GAV: SPL: p = 0.0068, SRP: p < 0.0001). Evaluation of patient satisfaction in a self-established feedback questionnaire revealed a motivation of 81% of patients to redo the surgery (SPL 13/16, SRP 34/42) and a notably general satisfaction of 86% for SPL and 80% for SRP. CONCLUSION: Rhinosurgery leads to quantitative better nasal breathing and increased disease-specific satisfaction. However, this study implies the importance of the right selection of patients and the correct indication of the surgical technique.

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

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)

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.

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.

[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.

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.

Blood caspase-8 concentrations and mortality among septic patients.

OBJECTIVE: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DESIGN: A prospective observational study was carried out. SETTING: Three Spanish Intensive Care Units. PATIENTS: Septic patients. INTERVENTIONS: Serum caspase-8 concentrations were determined at the diagnosis of sepsis. MAIN VARIABLE OF INTEREST: Mortality after 30 days. RESULTS: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001). CONCLUSIONS: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients.

[Functional connectivity derived from an electroencephalogram during non-REM sleep in autism spectrum disorders]. / Conectividad funcional derivada del electroencefalograma durante el sueño no REM en los trastornos del espectro autista.

AIM: To know the differences in the patterns of functional connectivity, the topological characteristics of the network and the relationship between these latter and the interictal epileptiform anomalies in children with primary and secondary autism spectrum disorder (ASD). PATIENTS AND METHODS: A retrospective study was conducted with 27 children aged between 3 and 13 years diagnosed with ASD. Subjects were submitted to an electroencephalogram in a functional state of spontaneous sleep. Functional connectivity and the properties of the network were analysed using data obtained from the electroencephalogram during the N2 stage of non-REM sleep. The frequency of discharge of the interictal epileptiform activity (FDIEA) was determined and was correlated with the topological properties of the network. RESULTS: Synchronisation was diminished in patients with secondary ASD for the alpha frequency and increased for the theta and delta frequency compared with patients with primary ASD. Local alpha efficiency was higher in patients who presented interictal epileptiform activity. Additionally, in patients with secondary ASD there was a statistically significant positive and negative correlation between FDIEA and the topological properties of the network. CONCLUSIONS: Patients with secondary ASD display patterns of functional connectivity that are weaker for the alpha frequency and stronger for theta and delta than patients with primary ASD. In patients with secondary ASD, the interictal epileptiform activity is related to local and global connectivity of the network for the alpha and beta bands during non-REM sleep.

TITLE: Conectividad funcional derivada del electroencefalograma durante el sueño no REM en los trastornos del espectro autista.Objetivo. Conocer las diferencias en los patrones de conectividad funcional, las caracteristicas topologicas de la red y la relacion de estas con las anomalias epileptiformes interictales en niños con trastorno del espectro autista (TEA) primario y secundario. Pacientes y metodos. Se realizo un estudio retrospectivo con 27 niños de 3-13 años diagnosticados con TEA, a los que se les realizo un electroencefalograma en estado funcional de sueño espontaneo. Se analizo la conectividad funcional y las propiedades de la red a partir de los datos obtenidos del electroencefalograma durante la etapa N2 del sueño no REM. Se determino la frecuencia de descarga de la actividad epileptiforme interictal (FDAEI) y se correlaciono con las propiedades topologicas de la red. Resultados. Los pacientes con TEA secundario tenian una disminucion de la sincronizacion para la frecuencia alfa y un incremento para la frecuencia theta y delta en comparacion con los pacientes con TEA primario. La eficiencia local alfa fue mayor en los pacientes que presentaban actividad epileptiforme interictal. Ademas, en los pacientes con TEA secundario, existia una correlacion positiva y negativa estadisticamente significativa entre la FDAEI y las propiedades topologicas de red. Conclusiones. Los pacientes con TEA secundario muestran patrones de conectividad funcional mas debiles para la frecuencia alfa y mas fuerte para la theta y delta que los pacientes con TEA primario. En pacientes con TEA secundario, la actividad epileptiforme interictal se relaciona con la conectividad local y global de la red para las bandas de frecuencia alfa y beta durante el sueño no REM.

Sustained high serum caspase-3 concentrations and mortality in septic patients.

Caspase-3 is the main executor of the apoptotic process. Higher serum caspase-3 concentrations in non-survivor compared to survivor septic patients have been found. The objectives of this work (with the increase of sample size to 308 patients, and the determination of serum caspase-3 concentrations also on days 4 and 8 of diagnosis of severe sepsis) were to know whether an association between serum caspase-3 concentrationss during the first week, degree of apoptosis, sepsis severity, and sepsis mortality exists. We collected serum samples of 308 patients with severe sepsis from eight intensive care units on days 1, 4 and 8 to measure concentrations of caspase-3 and caspase-cleaved cytokeratin (CCCK)-18 (to assess degree of apoptosis). End point was 30-day mortality. We found higher serum concentrations of caspase-3 and CCCK-18 in non-survivors compared to survivors on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). We found an association between serum caspase-3 concentrations on days 1, 4 and 8 of severe sepsis diagnosis and serum CCCK-18 concentrations (p < 0.001), SOFA (p < 0.001), serum acid lactic concentrations (p < 0.001), and 30-day sepsis mortality (p < 0.001). The new findings of this work were that an association between serum caspase-3 concentrations during the first week, apoptosis degree, sepsis severity, and sepsis mortality exists.