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

Lorente, L.; Martín, M.M.; Pérez-Cejas, A.; González-Rivero, A.F.; Argueso, M.; Ramos, L.; Solé-Violán, J.; Cáceres, J.J.; Jiménez, A.; García-Marín, V.

doi:10.1016/j.medin.2019.09.005

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"apellidos" => "García-Marín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "j" "identificador" => "aff0050" ] ] ] ] "afiliaciones" => array:10 [ 0 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Laboratory Department, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Laboratory Department, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Clínico Universitario de Valencia, Valencia, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Intensive Care Unit, Hospital General de La Palma, Breña Alta, La Palma, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Universitario Dr. Negrín, CIBERES, Las Palmas de Gran Canaria, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Insular, Las Palmas de Gran Canaria, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Research Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Department of Neurosurgery, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Niveles séricos de caspasa-3 durante la primera semana de un traumatismo craneoencefálico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 947 "Ancho" => 2919 "Tamanyo" => 148710 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic (ROC) curves of serum caspase-3 levels at day 1, 4 and 8 of traumatic brain injury for 30-day mortality prediction." ] ] ] "textoCompleto" => "IntroductionMany disabilities, deaths, and health resource consumption are due to traumatic brain injury (TBI).<a class="elsevierStyleCrossRefs" href="#bib0170">1–3</a> In TBI appears a cerebral damage due to the primary brain injury produced by the physical forces in the moment of trauma, and also a cerebral damage due to the secondary brain injury produced by the activation in the following hours or days of different physiopathological ways such as apoptosis.<a class="elsevierStyleCrossRefs" href="#bib0185">4–7</a> The programed cell death by apoptosis occurs mainly through the activation of the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway, and both pathways (intrinsic and extrinsic) activate caspase-3 which motivate the cell changes that leads to death cell.<a class="elsevierStyleCrossRefs" href="#bib0185">4–7</a>There have been found increased caspase-3 in brain tissues of TBI animal models,<a class="elsevierStyleCrossRefs" href="#bib0205">8–20</a> in cerebrospinal fluid (CSF) of TBI patients,<a class="elsevierStyleCrossRefs" href="#bib0270">21–23</a> and in brain tissues of TBI patients.<a class="elsevierStyleCrossRefs" href="#bib0285">24,25</a> In addition, higher brain tissue caspase-3 concentrations in non-surviving than in surviving TBI patients have been found.<a class="elsevierStyleCrossRef" href="#bib0290">25</a> Besides, higher serum caspase-3 on day 1 of TBI have been found in 30-day non-survivor compared to survivor patients.<a class="elsevierStyleCrossRef" href="#bib0295">26</a> Thus, the objectives of this study were to determine whether serum caspase-3 levels are maintainly higher in non-survivor than in survivor patients and whether those levels could be used to predict 30-day mortality.MethodsDesign and subjectsSix spanish hospitals participated in this observational and prospective study. The Institutional Board of all hospitals approved the protocol before to start the study: H. General of La Palma, H. Universitario de Canarias of La Laguna, H. Insular of Las Palmas de Gran Canaria, H. Clínico Universitario of Valencia, H. Universitario Nuestra Señora de Candelaria of Santa Cruz de Tenerife, and H. Universitario Dr. Negrín of Las Palmas de Gran Canaria. A relative of each patient signed the written informed consent for the inclusion of the patient in the study.We included patients with a severe isolated TBI. The criteria used for the definition of isolated was <10 points in non-cranial aspects of Injury Severity Score (ISS),<a class="elsevierStyleCrossRef" href="#bib0300">27</a> and the criteria for used for the definition of severe was <9 points in Glasgow Coma Scale (GCS).<a class="elsevierStyleCrossRef" href="#bib0305">28</a> We excluded patients with inflammatory disease, pregnancy, age less than 18 years, malignant disease, or comfort measures only.We registered sex, age, temperature, GCS, ISS, glycemia, creatinine, lactic acid, bilirrubin, fraction inspired oxygen (FIO2), pressure of arterial oxygen (PaO2), sodium, leukocytes, platelets, hemoglobin, activated partial thromboplastin time (aPTT), fibrinogen, international normalized ratio (INR), cerebral perfusion pressure (CPP), intracranial pressure (ICP), Acute Physiology and Chronic Health Evaluation II (APACHE II) score,<a class="elsevierStyleCrossRef" href="#bib0310">29</a> and brain lesions according to Marshall computer tomography classification (CT).<a class="elsevierStyleCrossRef" href="#bib0315">30</a> Thirty-day mortality from the ICU admission was considered as the end-point study. Clinical variables, CT findings and blood parameters were taken on admission, and ICP and CPP correspond to the values peak and small in the first 24h, respectively.Determinations of caspase-3 serum levelsWe obtained and frozen at −80°C until the moment of determination, serum samples on day 1, day 4 and day 8 of TBI. Serum caspase-3 levels on day 1 of TBI had been previously determined by our team in some of those patients<a class="elsevierStyleCrossRef" href="#bib0295">26</a>; and in this study we determined serum caspase-3 levels on day 1, day 4 and day 8 of TBI. Caspase-3 levels determination were performed in the Laboratory Department of the Hospital Universitario de Canarias (La Laguna Spain) by means of Human Caspase-3 Elisa BlueGene Biotech® (Shanghai, China). The assay detection limit was 0.10ng/mL, the intra-assay variation coefficient (VC) was <5.6%, and the inter-assay VC was <7.9%.Statistical methodsWe reported continuous variables as medians (and percentile 25 and 75) and were compared between both groups of patients (30-day survivor and non-survivor) using Wilcoxon–Mann–Whitney test. We reported categorical variables as frequencies (and percentages) and were compared between both groups of patients using chi-square test. To test the capacity of serum caspase-3 levels at day 1, 4 and 8 of TBI to predict 30-day mortality were performed receiver operating characteristic (ROC) analyses. We reported area under curve (AUC) and its 95% confidence intervals (CI). In addition, we reported sensitivity and specificity, negative and positive likelihood ratios, and negative and positive predicted values and its 95% CI for the cut-offs of serum caspase-3 levels at days 1, 4 and 8 of TBI (which were selected according to Youden J index). Multiple logistic regression was used to determine the association between serum caspase-3 levels and 30 day-mortality controlling for APACHE-II, CT, sex, age and CGS. For statistical analyses, we used the programs SPSS 17.0 (SPSS Inc., Chicago, IL, USA), NCSS 2000 (Kaysville, Utah), and LogXact 4.1 (Cytel Co., Cambridge, MA). To consider a difference as statistically significant, we used the cut-off of p-value <0.05.ResultsThirty-day survivor TBI patients (n=90) and non-survivors patients (n=34) were not statistically different in temperature, lactic acid, sodium, glycemia, bilirubin, PaO2, PaO2/FIO2 ratio, hemoglobin, creatinine, platelets, leukocytes, INR, fibrinogen, aPTT, ISS, ICP, and CPP. We found that survivor and non-survivor patients showed different brain computer tomography findings, and that survivor compared to non-survivor patients showed lower female rate, lower age, higher GCS, and lower APACHE-II score (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). All patients were undergoing to mechanical ventilation and monitorization of ICP. The causes of death were brain death in 25 patients, cardiac arrest in 5 patients, and nosocomial pneumonia in 4 patients.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>We found that survivor patients in comparison with non-survivors showed lower serum caspase-3 levels at days 1 (p=0.001), 4 (p<0.001), and 8 (p<0.001) of TBI (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). We found that non-survivor patients showed higher serum caspase-3 levels at day 1 than at day 4 (p=0.005) and at day 8 (p<0.001) of TBI, and that survivor patients showed higher serum caspase-3 levels at day 1 than at day 4 (p=0.005) but not at day 8 (p=0.15) of TBI.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>ROC curve analyses showed that serum caspase-3 concentrations at days 1, 4, and 8 of TBI had an AUC (95% CI) to predict 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 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> showed sensitivity and specificity, negative and positive likelihood ratios, and negative and positive predicted values of cut-offs of serum caspase-3 levels at day 1 (>0.20ng/mL), day 4 (>0.11ng/mL) and day 8 (>0.11ng/mL) for 30-day mortality prediction.<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>We found an AUC for 30-day mortality prediction from GCS of 0.75 (0.66–0.83), age of 0.74 (0.65–0.81) and APACHE-II of 0.86 (0.79–0.92). We did not find significant differences in the comparison of AUC for 30-day mortality prediction of serum caspase-3 levels with GCS (p=0.59) and with age (p=0.75); but the AUC was lower with serum caspase-3 levels that with APACHE-II (p=0.04).In multiple logistic regression we found an association between serum caspase-3 concentrations >20ng/mL and mortality controlling for sex, CT and APACHE-II (OR=9.76; 95% CI=2.819–33.794; p<0.001), and controlling for age, CT and CGS (OR=11.52; 95% CI=3.150–42.118; p<0.001) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). We found a mortality rate of 15.8% (6/38) in patients with CT on admission type 5, 16.7% (5/30) with type 2, 28.6% (6/21) with type 3, 40.9% (9/22) with type 4, and 61.5% (8/13) with type 6. Therefore, we recoded the patients according to CT findings in death low risk (including CT types 2 and 5) and death high risk (including CT types 3, 4 and 6), and that variable was included in logistic regression analyses.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionThe novel findings of our study were that non-surviving TBI patients showed higher serum caspase-3 levels during the first week of TBI than survivors, and that those levels could be used to predict 30-day mortality.In a previous study by our team were determined serum caspase-3 levels on day 1 of TBI, and we found higher serum caspase-3 levels in non-surviving than in surviving patients.<a class="elsevierStyleCrossRef" href="#bib0265">20</a> The novel aspect of the current study was that those levels have been not only measured on day 1 of TBI but also on days 4 and 8 of TBI, and we found that serum caspase-3 levels at different moments of the first week of TBI could be used as biomarkers for the prediction of 30-day mortality according the results of ROC analyses. However, we think that the findings of our study do not imply a causal relationship between serum caspase-3 levels and mortality.We have not found differences in the capacity of mortality prediction between serum caspase-3 levels and age and GCS, and was higher with APACHE-II than with serum caspase-3 levels; however, the main objective of this study was to determine whether serum caspase-3 levels could play a role in the mortality prediction and not whether its potential capacity of mortality prediction is better than that of other biomarkers such as age, GCS and APACHE-II.<a class="elsevierStyleCrossRefs" href="#bib0320">31,32</a>We found in the bivariate analysis that women showed higher mortality rate that men; however, there we did not find an association between sex and mortality in multiple logistic regression. In a recent review has been found that the most of studies showed worse outcomes in females than males, in other better outcomes in females, and in other no sex differences. The authors concluded that sex differences in mitochondrial function might contribute to possible sex differences in TBI outcomes.<a class="elsevierStyleCrossRef" href="#bib0330">33</a>Apoptotic cell death can occur mainly through the extrinsic or death receptor pathway (type I cells) and the intrinsic or mitochondrial pathway (type II cells).<a class="elsevierStyleCrossRefs" href="#bib0175">2–5</a> The intrinsic pathway is initiated in type II cells by action of oxygen free radicals and of cytokines such as interleukin (IL)-1 and IL-6; all of them releasing cytochrome c from mitochondria to cytoplasma and then activating caspase-3. The extrinsic pathway is initiated in type I cells by the action of tumor necrosis factor superfamily (TNFSF) that activates a surface death receptor of tumor necrosis factor receptor superfamily (TNFRSF), then a death signal is created and caspase-8 activates caspase-3. Therefore, intrinsic and extrinsic apoptosis pathways come together to caspase-3 which motivate death cell. We found that serum caspase-3 levels decreased from day 1 to day 4 and day 8 of TBI in non-survivor patients, and also from day 1 to day 4 in survivor patients. We think that this decreased in serum caspase-3 levels could be due to a decrease in apoptosis degree with the time.We must to recognize as limitations of our study that we have not analyze brain apoptosis and levels of the potential activator agents of apoptosis pathways (such as TNFSF, IL-1, IL-6 or oxygen free radicals). Besides, we have registered some variables only on admission and not also the worst value, and we have not registered the patients excluded and the exclusion cause. Another limitation was that we did not establish a protocol for patient management and we cannot ensure that patients were treated homogeneously in all hospitals, in fact one of the hospitals has not neurosurgery and some of its patients had to move to other hospitals that do have it; however, these patients were excluded from the study and we do not find differences in the mortality rate between different hospitals (p=0.99). Another limitation was that the assay detection limit was 0.10ng/mL, the percentile 25 of serum caspase-3 levels in non-surviving and surviving patients was 0.10ng/mL, and the range of serum caspase-3 levels in non-surviving and surviving patients were 0.10–1.21 and 0.10–0.59, respectively. Besides, we have not validated our findings in other patients cohort.The sample size of our study could be relatively small; however, we have found higher caspase-3 levels in non-surviving than in surviving patients in the three moments that were determined (days 1, 4 and 8 of TBI) and we believe that this consistence in the findings is a strength of our study. Thus, we think that those levels could help in the mortality prediction together with other markers (as age, GCS, APACHE-II) and that additional studies are needed to confirm our findings.We think that the interest of our study lies in that is the first one reporting higher serum caspase-3 levels during the first week of TBI in non-survivor than in survivor TBI patients. Those results could originate more research to determine the role of serum caspase-3 levels for TBI mortality prediction. In addition, in TBI rat models have been found a reduction of caspase-3 activity and apoptosis in brain tissues with the administration of caspase-3 inhibitors.<a class="elsevierStyleCrossRefs" href="#bib0230">13–20</a> Thus, the results of our study and those in animal models could originate more research to explore the use of caspase-3 inhibitors in TBI patients.ConclusionsThe novels findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivor patients and could predict 30-day mortality.Author contributionsLL conceived, designed and coordinated the study, participated in acquisition of data, and drafted the manuscript.MMM, MA, LR, JSV, JJC, VGM participated in acquisition of data and provided useful suggestions.APC and AGR carried out the immunoassays and provided useful suggestions.AJ interpreted the data and provided useful suggestions.All authors read and approved the final version of the manuscript.FundingsThis study was supported by a grant (OA18/011) from Fundación DISA a la Investigación Médica 2017 (Santa Cruz de Tenerife, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Conflicts of interestsThe authors declare that they have no competing interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1489473" "titulo" => "Abstract" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Interventions" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Main variables of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1352574" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1489472" "titulo" => "Resumen" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Pacientes" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Intervenciones" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Variables de interés principales" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1352573" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design and subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Determinations of caspase-3 serum levels" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical methods" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Author contributions" ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Fundings" ] 11 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interests" ] 12 => array:2 [ "identificador" => "xack521441" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-07-02" "fechaAceptado" => "2019-09-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1352574" "palabras" => array:5 [ 0 => "Caspase-3" 1 => "Patients" 2 => "Mortality" 3 => "Traumatic" 4 => "Brain injury" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1352573" "palabras" => array:5 [ 0 => "Caspasa-3" 1 => "Pacientes" 2 => "Mortalidad" 3 => "Trauma" 4 => "Craneoencefálico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveConfluence 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." "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Interventions" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Main variables of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoLa 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." "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Pacientes" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Intervenciones" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Variables de interés principales" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1424 "Ancho" => 1663 "Tamanyo" => 98776 ] ] "descripcion" => array:1 [ "en" => "Serum caspase-3 levels at day 1, 4 and 8 of traumatic brain injury in 30-day surviving and non-surviving patients." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 947 "Ancho" => 2919 "Tamanyo" => 148710 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic (ROC) curves of serum caspase-3 levels at day 1, 4 and 8 of traumatic brain injury for 30-day mortality prediction." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "aPTT=activated partial thromboplastin time; INR=international normalized ratio; PaO2=pressure of arterial oxygen; FIO2=fraction inspired oxygen; ISS=Injury Severity Score; APACHE II=Acute Physiology and Chronic Health Evaluation; ICP=intracranial pressure; CPP=cerebral perfusion pressure; p25–75=percentile 25th–75th." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-surviving (n=34) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Surviving (n=90) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender female – n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (38.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 (55–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (28–62) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glasgow Coma Scale – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (3–7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (5–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Temperature (°C) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.0 (35.0–37.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.0 (36.0–37.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Marshall computer tomography – n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (14.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (27.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (17.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (26.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (14.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (17.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (35.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (23.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (5.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CT with high risk of death (types 3,4,6) – n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (67.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (36.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ISS – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (25–25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (25–34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Platelets – median ×103mm−3(p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">172 (125–232) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">182 (135–238) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.49 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">aPTT (s) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (25–37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (25–31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fibrinogen (mg/dl) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">348 (300–475) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">371 (286–471) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.70 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INR – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12 (1.03–1.48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.11 (1.00–1.24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leukocytes – median ×103mm−3(p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.9 (9.7–21.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.9 (10.1–19.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.47 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemoglobin (g/dL) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.9 (10.0–13.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.2 (10.0–13.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PaO2(mmHg) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">142 (97–195) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">148 (110–242) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PaO2/FIO2ratio – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">294 (167–395) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">336 (246–400) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sodium (mEquiv./L) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">141 (136–147) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140 (138–143) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine (mg/dL) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.80 (0.70–1.10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.80 (0.70–1.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lactic acid (mmol/L) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.30 (1.25–4.58) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.75 (1.10–2.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilirubin (mg/dL) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.70 (0.53–1.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.60 (0.40–0.80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glycemia (g/dL) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">160 (125–191) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">139 (121–167) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">APACHE-II score – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (23–28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (14–22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ICP peak in first 24h (mmHg) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (11–30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (14–20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.36 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CPP small in first 24h (mmHg) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 (52–70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 (57–70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Caspase-3 on admission (ng/mL) – median (p25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 (0.11–0.41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 (0.10–0.17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2558379.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics on admission of 30-day surviving and non-surviving patients." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 4 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 8 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cut-off of caspase-3 (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Specificity and 95% CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56% (38%–73%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56% (45%–66%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67% (56%–76%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sensitivity and 95% CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83% (74%–90%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94% (71%–99%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92% (64%–99%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative likelihood ratio and 95% CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.5 (0.4–0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 (0.02–0.70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12 (0.02–0.80) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive likelihood ratio and 95% CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.4 (1.9–5.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.1 (1.6–2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.8 (2.0–3.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative predicted value and 95% CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83% (77%–88%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98% (88%–99%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98% (91%–99%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive predicted value and 95% CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56% (42%–69%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29% (24%–34%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29% (22%–36%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2558380.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Thirty-day mortality prognostic capability of serum caspase-3 levels at day 1, 4 and 8 of trauma brain injury." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "APACHE II=Acute Physiology and Chronic Health Evaluation; CT=computed tomography; GCS=Glasgow Coma Scale." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Odds ratio \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95% Confidence interval \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First model</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum caspase-3 levels >0.20ng/mL (yes vs. no) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.819–33.794 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">APACHE-II score (points) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.166–1.539 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CT classification (high vs. low risk of death) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.290–14.511 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex (female vs. male) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.756–10.117 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Second model</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum caspase-3 levels>0.20ng/mL (yes vs. no) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.150–42.118 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CT classification (high vs. low risk of death) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.009–25.402 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.034–1.111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GCS score (points) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.446–0.795 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2558378.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Multiple logistic regression analysis to predict 30-day mortality." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0170" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for the management of severe traumatic brain injury" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Brain Trauma Foundation; 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          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic &#40;ROC&#41; curves of serum caspase-3 levels at day 1&#44; 4 and 8 of traumatic brain injury for 30-day mortality prediction&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Many disabilities&#44; deaths&#44; and health resource consumption are due to traumatic brain injury &#40;TBI&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">1&#8211;3</span></a> In TBI appears a cerebral damage due to the primary brain injury produced by the physical forces in the moment of trauma&#44; and also a cerebral damage due to the secondary brain injury produced by the activation in the following hours or days of different physiopathological ways such as apoptosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4&#8211;7</span></a> The programed cell death by apoptosis occurs mainly through the activation of the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway&#44; and both pathways &#40;intrinsic and extrinsic&#41; activate caspase-3 which motivate the cell changes that leads to death cell&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4&#8211;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">There have been found increased caspase-3 in brain tissues of TBI animal models&#44;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">8&#8211;20</span></a> in cerebrospinal fluid &#40;CSF&#41; of TBI patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">21&#8211;23</span></a> and in brain tissues of TBI patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">24&#44;25</span></a> In addition&#44; higher brain tissue caspase-3 concentrations in non-surviving than in surviving TBI patients have been found&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> Besides&#44; higher serum caspase-3 on day 1 of TBI have been found in 30-day non-survivor compared to survivor patients&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a> Thus&#44; the objectives of this study were to determine whether serum caspase-3 levels are maintainly higher in non-survivor than in survivor patients and whether those levels could be used to predict 30-day mortality&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Design and subjects</span><p id="par0015" class="elsevierStylePara elsevierViewall">Six spanish hospitals participated in this observational and prospective study&#46; The Institutional Board of all hospitals approved the protocol before to start the study&#58; H&#46; General of La Palma&#44; H&#46; Universitario de Canarias of La Laguna&#44; H&#46; Insular of Las Palmas de Gran Canaria&#44; H&#46; Cl&#237;nico Universitario of Valencia&#44; H&#46; Universitario Nuestra Se&#241;ora de Candelaria of Santa Cruz de Tenerife&#44; and H&#46; Universitario Dr&#46; Negr&#237;n of Las Palmas de Gran Canaria&#46; A relative of each patient signed the written informed consent for the inclusion of the patient in the study&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We included patients with a severe isolated TBI&#46; The criteria used for the definition of isolated was &#60;10 points in non-cranial aspects of Injury Severity Score &#40;ISS&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a> and the criteria for used for the definition of severe was &#60;9 points in Glasgow Coma Scale &#40;GCS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a> We excluded patients with inflammatory disease&#44; pregnancy&#44; age less than 18 years&#44; malignant disease&#44; or comfort measures only&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We registered sex&#44; age&#44; temperature&#44; GCS&#44; ISS&#44; glycemia&#44; creatinine&#44; lactic acid&#44; bilirrubin&#44; fraction inspired oxygen &#40;FIO<span class="elsevierStyleInf">2</span>&#41;&#44; pressure of arterial oxygen &#40;PaO<span class="elsevierStyleInf">2</span>&#41;&#44; sodium&#44; leukocytes&#44; platelets&#44; hemoglobin&#44; activated partial thromboplastin time &#40;aPTT&#41;&#44; fibrinogen&#44; international normalized ratio &#40;INR&#41;&#44; cerebral perfusion pressure &#40;CPP&#41;&#44; intracranial pressure &#40;ICP&#41;&#44; Acute Physiology and Chronic Health Evaluation II &#40;APACHE II&#41; score&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a> and brain lesions according to Marshall computer tomography classification &#40;CT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> Thirty-day mortality from the ICU admission was considered as the end-point study&#46; Clinical variables&#44; CT findings and blood parameters were taken on admission&#44; and ICP and CPP correspond to the values peak and small in the first 24<span class="elsevierStyleHsp" style=""></span>h&#44; respectively&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Determinations of caspase-3 serum levels</span><p id="par0030" class="elsevierStylePara elsevierViewall">We obtained and frozen at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C until the moment of determination&#44; serum samples on day 1&#44; day 4 and day 8 of TBI&#46; Serum caspase-3 levels on day 1 of TBI had been previously determined by our team in some of those patients<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a>&#59; and in this study we determined serum caspase-3 levels on day 1&#44; day 4 and day 8 of TBI&#46; Caspase-3 levels determination were performed in the Laboratory Department of the Hospital Universitario de Canarias &#40;La Laguna Spain&#41; by means of Human Caspase-3 Elisa BlueGene Biotech&#174; &#40;Shanghai&#44; China&#41;&#46; The assay detection limit was 0&#46;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; the intra-assay variation coefficient &#40;VC&#41; was &#60;5&#46;6&#37;&#44; and the inter-assay VC was &#60;7&#46;9&#37;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Statistical methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">We reported continuous variables as medians &#40;and percentile 25 and 75&#41; and were compared between both groups of patients &#40;30-day survivor and non-survivor&#41; using Wilcoxon&#8211;Mann&#8211;Whitney test&#46; We reported categorical variables as frequencies &#40;and percentages&#41; and were compared between both groups of patients using chi-square test&#46; To test the capacity of serum caspase-3 levels at day 1&#44; 4 and 8 of TBI to predict 30-day mortality were performed receiver operating characteristic &#40;ROC&#41; analyses&#46; We reported area under curve &#40;AUC&#41; and its 95&#37; confidence intervals &#40;CI&#41;&#46; In addition&#44; we reported sensitivity and specificity&#44; negative and positive likelihood ratios&#44; and negative and positive predicted values and its 95&#37; CI for the cut-offs of serum caspase-3 levels at days 1&#44; 4 and 8 of TBI &#40;which were selected according to Youden J index&#41;&#46; Multiple logistic regression was used to determine the association between serum caspase-3 levels and 30 day-mortality controlling for APACHE-II&#44; CT&#44; sex&#44; age and CGS&#46; For statistical analyses&#44; we used the programs SPSS 17&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#44; NCSS 2000 &#40;Kaysville&#44; Utah&#41;&#44; and LogXact 4&#46;1 &#40;Cytel Co&#46;&#44; Cambridge&#44; MA&#41;&#46; To consider a difference as statistically significant&#44; we used the cut-off of <span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">Thirty-day survivor TBI patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&#41; and non-survivors patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#41; were not statistically different in temperature&#44; lactic acid&#44; sodium&#44; glycemia&#44; bilirubin&#44; PaO<span class="elsevierStyleInf">2</span>&#44; PaO<span class="elsevierStyleInf">2</span>&#47;FIO<span class="elsevierStyleInf">2</span> ratio&#44; hemoglobin&#44; creatinine&#44; platelets&#44; leukocytes&#44; INR&#44; fibrinogen&#44; aPTT&#44; ISS&#44; ICP&#44; and CPP&#46; We found that survivor and non-survivor patients showed different brain computer tomography findings&#44; and that survivor compared to non-survivor patients showed lower female rate&#44; lower age&#44; higher GCS&#44; and lower APACHE-II score &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; All patients were undergoing to mechanical ventilation and monitorization of ICP&#46; The causes of death were brain death in 25 patients&#44; cardiac arrest in 5 patients&#44; and nosocomial pneumonia in 4 patients&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">We found that survivor patients in comparison with non-survivors showed lower serum caspase-3 levels at days 1 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; 4 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and 8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; of TBI &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; We found that non-survivor patients showed higher serum caspase-3 levels at day 1 than at day 4 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41; and at day 8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; of TBI&#44; and that survivor patients showed higher serum caspase-3 levels at day 1 than at day 4 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41; but not at day 8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;15&#41; of TBI&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">ROC curve analyses showed that serum caspase-3 concentrations at days 1&#44; 4&#44; and 8 of TBI had an AUC &#40;95&#37; CI&#41; to predict 30-day mortality of 0&#46;70 &#40;0&#46;61&#8211;0&#46;78&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; 0&#46;83 &#40;0&#46;74&#8211;0&#46;89&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and 0&#46;87 &#40;0&#46;79&#8211;0&#46;93&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; respectively &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> showed sensitivity and specificity&#44; negative and positive likelihood ratios&#44; and negative and positive predicted values of cut-offs of serum caspase-3 levels at day 1 &#40;&#62;0&#46;20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#44; day 4 &#40;&#62;0&#46;11<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; and day 8 &#40;&#62;0&#46;11<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; for 30-day mortality prediction&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">We found an AUC for 30-day mortality prediction from GCS of 0&#46;75 &#40;0&#46;66&#8211;0&#46;83&#41;&#44; age of 0&#46;74 &#40;0&#46;65&#8211;0&#46;81&#41; and APACHE-II of 0&#46;86 &#40;0&#46;79&#8211;0&#46;92&#41;&#46; We did not find significant differences in the comparison of AUC for 30-day mortality prediction of serum caspase-3 levels with GCS &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;59&#41; and with age &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;75&#41;&#59; but the AUC was lower with serum caspase-3 levels that with APACHE-II &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In multiple logistic regression we found an association between serum caspase-3 concentrations &#62;20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and mortality controlling for sex&#44; CT and APACHE-II &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;76&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;819&#8211;33&#46;794&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and controlling for age&#44; CT and CGS &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#46;52&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;150&#8211;42&#46;118&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; We found a mortality rate of 15&#46;8&#37; &#40;6&#47;38&#41; in patients with CT on admission type 5&#44; 16&#46;7&#37; &#40;5&#47;30&#41; with type 2&#44; 28&#46;6&#37; &#40;6&#47;21&#41; with type 3&#44; 40&#46;9&#37; &#40;9&#47;22&#41; with type 4&#44; and 61&#46;5&#37; &#40;8&#47;13&#41; with type 6&#46; Therefore&#44; we recoded the patients according to CT findings in death low risk &#40;including CT types 2 and 5&#41; and death high risk &#40;including CT types 3&#44; 4 and 6&#41;&#44; and that variable was included in logistic regression analyses&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">The novel findings of our study were that non-surviving TBI patients showed higher serum caspase-3 levels during the first week of TBI than survivors&#44; and that those levels could be used to predict 30-day mortality&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In a previous study by our team were determined serum caspase-3 levels on day 1 of TBI&#44; and we found higher serum caspase-3 levels in non-surviving than in surviving patients&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a> The novel aspect of the current study was that those levels have been not only measured on day 1 of TBI but also on days 4 and 8 of TBI&#44; and we found that serum caspase-3 levels at different moments of the first week of TBI could be used as biomarkers for the prediction of 30-day mortality according the results of ROC analyses&#46; However&#44; we think that the findings of our study do not imply a causal relationship between serum caspase-3 levels and mortality&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We have not found differences in the capacity of mortality prediction between serum caspase-3 levels and age and GCS&#44; and was higher with APACHE-II than with serum caspase-3 levels&#59; however&#44; the main objective of this study was to determine whether serum caspase-3 levels could play a role in the mortality prediction and not whether its potential capacity of mortality prediction is better than that of other biomarkers such as age&#44; GCS and APACHE-II&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">31&#44;32</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">We found in the bivariate analysis that women showed higher mortality rate that men&#59; however&#44; there we did not find an association between sex and mortality in multiple logistic regression&#46; In a recent review has been found that the most of studies showed worse outcomes in females than males&#44; in other better outcomes in females&#44; and in other no sex differences&#46; The authors concluded that sex differences in mitochondrial function might contribute to possible sex differences in TBI outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Apoptotic cell death can occur mainly through the extrinsic or death receptor pathway &#40;type I cells&#41; and the intrinsic or mitochondrial pathway &#40;type II cells&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">2&#8211;5</span></a> The intrinsic pathway is initiated in type II cells by action of oxygen free radicals and of cytokines such as interleukin &#40;IL&#41;-1 and IL-6&#59; all of them releasing cytochrome c from mitochondria to cytoplasma and then activating caspase-3&#46; The extrinsic pathway is initiated in type I cells by the action of tumor necrosis factor superfamily &#40;TNFSF&#41; that activates a surface death receptor of tumor necrosis factor receptor superfamily &#40;TNFRSF&#41;&#44; then a death signal is created and caspase-8 activates caspase-3&#46; Therefore&#44; intrinsic and extrinsic apoptosis pathways come together to caspase-3 which motivate death cell&#46; We found that serum caspase-3 levels decreased from day 1 to day 4 and day 8 of TBI in non-survivor patients&#44; and also from day 1 to day 4 in survivor patients&#46; We think that this decreased in serum caspase-3 levels could be due to a decrease in apoptosis degree with the time&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">We must to recognize as limitations of our study that we have not analyze brain apoptosis and levels of the potential activator agents of apoptosis pathways &#40;such as TNFSF&#44; IL-1&#44; IL-6 or oxygen free radicals&#41;&#46; Besides&#44; we have registered some variables only on admission and not also the worst value&#44; and we have not registered the patients excluded and the exclusion cause&#46; Another limitation was that we did not establish a protocol for patient management and we cannot ensure that patients were treated homogeneously in all hospitals&#44; in fact one of the hospitals has not neurosurgery and some of its patients had to move to other hospitals that do have it&#59; however&#44; these patients were excluded from the study and we do not find differences in the mortality rate between different hospitals &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;99&#41;&#46; Another limitation was that the assay detection limit was 0&#46;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; the percentile 25 of serum caspase-3 levels in non-surviving and surviving patients was 0&#46;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; and the range of serum caspase-3 levels in non-surviving and surviving patients were 0&#46;10&#8211;1&#46;21 and 0&#46;10&#8211;0&#46;59&#44; respectively&#46; Besides&#44; we have not validated our findings in other patients cohort&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The sample size of our study could be relatively small&#59; however&#44; we have found higher caspase-3 levels in non-surviving than in surviving patients in the three moments that were determined &#40;days 1&#44; 4 and 8 of TBI&#41; and we believe that this consistence in the findings is a strength of our study&#46; Thus&#44; we think that those levels could help in the mortality prediction together with other markers &#40;as age&#44; GCS&#44; APACHE-II&#41; and that additional studies are needed to confirm our findings&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We think that the interest of our study lies in that is the first one reporting higher serum caspase-3 levels during the first week of TBI in non-survivor than in survivor TBI patients&#46; Those results could originate more research to determine the role of serum caspase-3 levels for TBI mortality prediction&#46; In addition&#44; in TBI rat models have been found a reduction of caspase-3 activity and apoptosis in brain tissues with the administration of caspase-3 inhibitors&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">13&#8211;20</span></a> Thus&#44; the results of our study and those in animal models could originate more research to explore the use of caspase-3 inhibitors in TBI patients&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">The novels findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivor patients and could predict 30-day mortality&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Author contributions</span><p id="par0110" class="elsevierStylePara elsevierViewall">LL conceived&#44; designed and coordinated the study&#44; participated in acquisition of data&#44; and drafted the manuscript&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">MMM&#44; MA&#44; LR&#44; JSV&#44; JJC&#44; VGM participated in acquisition of data and provided useful suggestions&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">APC and AGR carried out the immunoassays and provided useful suggestions&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">AJ interpreted the data and provided useful suggestions&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">All authors read and approved the final version of the manuscript&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Fundings</span><p id="par0135" class="elsevierStylePara elsevierViewall">This study was supported by a grant &#40;<span class="elsevierStyleGrantNumber" refid="gs1">OA18&#47;011</span>&#41; from <span class="elsevierStyleGrantSponsor" id="gs1">Fundaci&#243;n DISA a la Investigaci&#243;n M&#233;dica</span> 2017 &#40;Santa Cruz de Tenerife&#44; Spain&#41;&#46; The funders had no role in study design&#44; data collection and analysis&#44; decision to publish&#44; or preparation of the manuscript&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflicts of interests</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that they have no competing interests&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation&#44; which induces death cell&#46; Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury &#40;TBI&#41; in 30-day non-survivors compared to survivors&#46; The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors&#44; and whether these levels may be used to predict 30-day mortality&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective observational study was carried out&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Setting</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Six Spanish Intensive Care Units&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patients</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Patients with severe isolated TBI &#40;defined as Glasgow Coma Scale &#60;9 points and non-cranial Injury Severity Score &#60;10 points&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Interventions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Serum caspase-3 concentrations were measured on days 1&#44; 4 and 8 of TBI&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Main variables of interest</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Thirty-day mortality was considered as the study endpoint&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In comparison with non-survivors &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#41;&#44; 30-day survivors &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&#41; showed lower serum caspase-3 levels on days 1 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; 4 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and 8 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; of TBI&#46; Analysis of the ROC curves showed serum caspase-3 concentrations on days 1&#44; 4 and 8 of TBI to have an AUC &#40;95&#37; CI&#41; in predicting 30-day mortality of 0&#46;70 &#40;0&#46;61&#8211;0&#46;78&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; 0&#46;83 &#40;0&#46;74&#8211;0&#46;89&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and 0&#46;87 &#40;0&#46;79&#8211;0&#46;93&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; respectively&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">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&#46;</p></span>"
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        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La v&#237;a intr&#237;nseca y extr&#237;nseca de la apoptosis confluyen en la activaci&#243;n de caspasa-3&#46; Se han encontrado mayores niveles s&#233;ricos de caspasa-3 en el d&#237;a 1 del traumatismo craneoencef&#225;lico &#40;TCE&#41; en los pacientes que fallecen en los primeros 30&#160;d&#237;as que en supervivientes&#46; Por tanto&#44; los objetivos de este estudio es determinar si los niveles s&#233;ricos de caspasa-3 se mantienen superiores en los pacientes fallecidos que en los supervivientes&#44; y si podr&#237;an utilizarse para predecir la mortalidad a 30 d&#237;as&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Dise&#241;o</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional y prospectivo&#46;</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">&#193;mbito</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Seis unidades de cuidados intensivos espa&#241;olas&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Enfermos con un TCE grave y aislado &#40;definido como escala de coma de Glasgow &#60;<span class="elsevierStyleHsp" style=""></span>9 y puntuaci&#243;n de gravedad de la lesi&#243;n <span class="elsevierStyleItalic">Score</span> en lesiones no craneales &#60;<span class="elsevierStyleHsp" style=""></span>10&#41;&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intervenciones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se midieron los niveles s&#233;ricos de caspasa-3 en los d&#237;as 1&#44; 4 y 8 del TCE&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variables de inter&#233;s principales</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Mortalidad a los 30 d&#237;as&#46;</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Los pacientes supervivientes a los 30 d&#237;as &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&#41; presentan menores niveles s&#233;ricos de caspasa-3 en los d&#237;as 1 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; 4 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y 8 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; del TCE que los fallecidos &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#41;&#46; Los niveles s&#233;ricos de caspasa-3 en los d&#237;as 1&#44; 4 y 8 del TCE ten&#237;an un &#225;rea bajo la curva &#40;intervalo de confianza del 95&#37;&#41; para predecir la mortalidad de 0&#44;70 &#40;0&#44;61-0&#44;78&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; 0&#44;83 &#40;0&#44;74-0&#44;89&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y 0&#44;87 &#40;0&#44;79-0&#44;93&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; respectivamente&#46;</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Los nuevos hallazgos de nuestro estudio fueron que los niveles s&#233;ricos de caspasa-3 durante la primera semana del TCE fueron menores en los pacientes supervivientes&#44; y que pueden predecir la mortalidad a los 30 d&#237;as&#46;</p></span>"
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                  \t\t\t\t">5 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25 &#40;27&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13 &#40;14&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;23&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23 &#40;67&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;36&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25 &#40;25&#8211;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;25&#8211;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Platelets &#8211; median &#215;10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#8722;3</span></span><span class="elsevierStyleItalic">&#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">172 &#40;125&#8211;232&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">182 &#40;135&#8211;238&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">aPTT &#40;s&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;25&#8211;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;25&#8211;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fibrinogen &#40;mg&#47;dl&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">348 &#40;300&#8211;475&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">371 &#40;286&#8211;471&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">INR &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;12 &#40;1&#46;03&#8211;1&#46;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;11 &#40;1&#46;00&#8211;1&#46;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leukocytes &#8211; median &#215;10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#8722;3</span></span><span class="elsevierStyleItalic">&#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;9 &#40;9&#46;7&#8211;21&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;9 &#40;10&#46;1&#8211;19&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hemoglobin &#40;g&#47;dL&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;9 &#40;10&#46;0&#8211;13&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;2 &#40;10&#46;0&#8211;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PaO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#40;mmHg&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">142 &#40;97&#8211;195&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">148 &#40;110&#8211;242&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PaO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#47;FIO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">ratio &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">294 &#40;167&#8211;395&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">336 &#40;246&#8211;400&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sodium &#40;mEquiv&#46;&#47;L&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">141 &#40;136&#8211;147&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">140 &#40;138&#8211;143&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Creatinine &#40;mg&#47;dL&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;80 &#40;0&#46;70&#8211;1&#46;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;80 &#40;0&#46;70&#8211;1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Lactic acid &#40;mmol&#47;L&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;30 &#40;1&#46;25&#8211;4&#46;58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;75 &#40;1&#46;10&#8211;2&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Bilirubin &#40;mg&#47;dL&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;70 &#40;0&#46;53&#8211;1&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;60 &#40;0&#46;40&#8211;0&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Glycemia &#40;g&#47;dL&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">160 &#40;125&#8211;191&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139 &#40;121&#8211;167&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">APACHE-II score &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;23&#8211;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;14&#8211;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ICP peak in first 24</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h &#40;mmHg&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;11&#8211;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;14&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">CPP small in first 24</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h &#40;mmHg&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61 &#40;52&#8211;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;57&#8211;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Caspase-3 on admission &#40;ng&#47;mL&#41; &#8211; median &#40;p25&#8211;75&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;25 &#40;0&#46;11&#8211;0&#46;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;11 &#40;0&#46;10&#8211;0&#46;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Characteristics on admission of 30-day surviving and non-surviving patients&#46;</p>"
        ]
      ]
      3 => array:8 [
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cut-off of caspase-3 &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Specificity and 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#37; &#40;38&#37;&#8211;73&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#37; &#40;45&#37;&#8211;66&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#37; &#40;56&#37;&#8211;76&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sensitivity and 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#37; &#40;74&#37;&#8211;90&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&#37; &#40;71&#37;&#8211;99&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#37; &#40;64&#37;&#8211;99&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative likelihood ratio and 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5 &#40;0&#46;4&#8211;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;11 &#40;0&#46;02&#8211;0&#46;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12 &#40;0&#46;02&#8211;0&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive likelihood ratio and 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;4 &#40;1&#46;9&#8211;5&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;1 &#40;1&#46;6&#8211;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;8 &#40;2&#46;0&#8211;3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative predicted value and 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#37; &#40;77&#37;&#8211;88&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&#37; &#40;88&#37;&#8211;99&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&#37; &#40;91&#37;&#8211;99&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive predicted value and 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#37; &#40;42&#37;&#8211;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#37; &#40;24&#37;&#8211;34&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#37; &#40;22&#37;&#8211;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Thirty-day mortality prognostic capability of serum caspase-3 levels at day 1&#44; 4 and 8 of trauma brain injury&#46;</p>"
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        "etiqueta" => "Table 3"
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          0 => array:3 [
            "identificador" => "at3"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">APACHE II<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Acute Physiology and Chronic Health Evaluation&#59; CT<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>computed tomography&#59; GCS<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Glasgow Coma Scale&#46;</p>"
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Odds ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; Confidence interval&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">First model</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Serum caspase-3 levels &#62;0&#46;20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;yes vs&#46; no&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;819&#8211;33&#46;794&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>APACHE-II score &#40;points&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;166&#8211;1&#46;539&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CT classification &#40;high vs&#46; low risk of death&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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