Blood caspase-8 concentrations and mortality among septic patients

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"apellidos" => "Jiménez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Crta Rosario s/n., Santa Cruz Tenerife 38010, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Intensive Care Unit, Hospital General de La Palma, Buenavista de Arriba s/n, Breña Alta, La Palma 38713, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Laboratory Department, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Santa Cruz de Tenerife, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Laboratory Department, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Tenerife, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Intensive Care Unit, Hospital Universitario de Canarias, Ofra s/n., La Laguna, Santa Cruz de Tenerife 38320, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Research Unit, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Tenerife, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Niveles sanguíneos de caspasa-8 y mortalidad de los pacientes sépticos" ] ] "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" => 1355 "Ancho" => 1583 "Tamanyo" => 141845 ] ] "descripcion" => array:1 [ "en" => "Survival curves at 30 days using blood caspase-8 concentrations lower or equal vs higher than 43.5ng/mL." ] ] ] "textoCompleto" => "IntroductionSepsis contributes to many deaths and healthcare system costs.<a class="elsevierStyleCrossRefs" href="#bib0135">1,2</a> Apoptosis, the process in which cells are programmedly and actively eliminated, that occurs in physiological processes (during morphogenesis and tissue remodeling) and also in different diseases.<a class="elsevierStyleCrossRef" href="#bib0145">3</a> In addition, in animal models has been found an increase of apoptosis.<a class="elsevierStyleCrossRef" href="#bib0145">3</a> Apoptotic cell death occurs mainly through the extrinsic pathway (or death receptor pathway) and the intrinsic pathway (or mitochondrial pathway). The extrinsic pathway is activated when tumor necrosis factor membrane receptors superfamily (TNFRSF) binding to its ligands of the tumor necrosis factor ligand superfamily (TNFSF). The main ligands and receptors in this pathway are the ligand FasL (which bind to its Fas antigen) and the TNF-related apoptosis-inducing ligand (TRAIL) (which bind to its different receptors (TRAILR1–4). When TNFRSF and its ligand TNFSF binding is generated a death signal that adheres to pro-caspase-8 and appears active caspase-8 (initiator caspase), which activates caspase-3 (the main effector caspase) leading to cellular apoptotic changes.<a class="elsevierStyleCrossRef" href="#bib0145">3</a>The extrinsic pathway of apoptosis in septic patients has been scarcely explored and only in studies of small sample size.<a class="elsevierStyleCrossRefs" href="#bib0150">4,5</a> In one study higher blood Fas levels in septic patients than in controls and in non-survivor than in survivor septic patients,<a class="elsevierStyleCrossRef" href="#bib0150">4</a> and the same findings for TRAIL.<a class="elsevierStyleCrossRef" href="#bib0155">5</a> However, there are not data on blood caspase-8 concentrations in septic patients. Increased blood caspase-8 concentrations have been found in patients with systemic lupus erythematosus<a class="elsevierStyleCrossRefs" href="#bib0160">6,7</a> and with in patients with metabolic syndrome and non-alcoholic fatty liver disease.<a class="elsevierStyleCrossRef" href="#bib0170">8</a> We have chosen the study of blood caspase-8 concentrations in our research due to that the extrinsic pathway of apoptosis in septic patients has been scarcely explored and that caspase-8 is the initiator caspase of the extrinsic apoptosis pathway. We hypothesized that non-survivor septic patients could have higher blood caspase-8 concentrations than survivor ones. Therefore, the objectives of this study were to describe blood caspase-8 concentrations in survivor and non-survivor patients and to determine whether there is an association between blood caspase-8 concentrations and mortality in septic patients.Material and methodsDesign and subjectsThis prospective and observational study was conducted in the polyvalent Intensive Care Unit from 3 Spanish hospitals: H. Universitario de Canarias, H. Universitario Nuestra Señora de Candelaria and H. General de la Palma. The study was approved by the Ethics Committee of all hospitals. The informed and signed consent from patients or their relatives was obtained to participate in the study.The study was conducted between 2013 and 2014. We included patients with sepsis according to the Sepsis-3 Consensus criteria<a class="elsevierStyleCrossRef" href="#bib0175">9</a>; thus, the patients were recoded according to those sepsis criteria. We excluded patients with white solid tumor, blood cell count <1000/μl, hematological tumor, human immunodeficiency virus (HIV), immunosuppressive therapy, radiation therapy, steroid agents, breastfeeding, or pregnancy, or age <18 years.Age, sex, and the history of chronic renal failure, ischemic heart disease, diabetes mellitus, chronic obstructive pulmonary disease, sepsis focus and appropriateness of antimicrobial therapy were registered. We also registered creatinine, leukocytes, bilirubin, activated partial thromboplastin time, international normalized ratio, platelets, lactic acid, pressure of arterial oxygen, fraction inspired of oxygen, site of infection, Acute Physiology and Chronic Health Evaluation (APACHE)-II score<a class="elsevierStyleCrossRef" href="#bib0180">10</a> and Sepsis-related Organ Failure Assessment [SOFA] score.<a class="elsevierStyleCrossRef" href="#bib0185">11</a> Besides, we registered the appearance of bloodstream infection and septic shock. Mortality at 30 days was considered our endpoint study.Determination of serum caspase-8 concentrationsWe freeze patient sera at moment of sepsis diagnosis at −80°C until the determination of serum caspase-8 levels. We used the Human Caspase 8 ELISA Kit (Elabscience, Houston, Texas, United States) for the determination of serum caspase-8 concentrations. The detection limit of the assay was 0.10ng/mL, the intra-assay coefficient of variation (CV) was <6%, and the inter-assay CV was <8%.Statistical methodsWe used medians (percentile 25–75) and frequencies (percentages) to describe continuous and categorical variables. Mann–Whitney U test and chi-square test were used to compare continuous and categorical variables between surviving and non-surviving patients. We carried out receiver operating characteristic (ROC) analyses using 30-day mortality, serum caspase-8 concentrations, SOFA and APACHE-II. Comparison of ROC curves to test the statistical significance of the difference between the areas under curves (derived from the same cases) was carried out with the method of DeLong et al.<a class="elsevierStyleCrossRef" href="#bib0190">12</a> We reported sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values and its 95% confidence interval (CI) of serum caspase-8 levels cut-off selected in basis to Youden J index. We constructed Kaplan–Meier 30-day survival curves using survival at 30 days and the cut-off of serum caspase-8 concentrations estimated by Youden J index, and Hazard Ratio was calculated for this cut-off. To explore the association between serum caspase-8 concentrations and 30-day mortality controlling for possible confounds was performed a multiple logistic regression analysis; and to estimate the clinical impact of prognostic variables were reported odds ratio (OR) and its 95% confidence interval (CI). For statistical analyses were used the programs NCSS 2000 (Kaysville, Utah) and SPSS 17.0 (SPSS Inc., Chicago, IL, USA), and for the establishment of significant differences was used the point p<0.05ResultsWe included a total of 221 patients, 140 (63.3%) surviving at 30 days and 81 (36.7%) deaths in the following 30 days. The number of patients included in each hospital were 121, 68 and 32 patients respectively. There were not significant differences in the mortality rate between hospitals (47/121 (38.8%), 22/68 (32.4%) and 12/32 (37.5%); p=0.67). We found that non-surviving patients (n=81) compared to surviving patients (n=140) had higher SOFA (p<0.001), APACHE-II (p<0.001), age (p<0.001), rate of septic shock (p<0.001), lactic acid (p<0.001), creatinine (p=0.01), aPTT (p=0.01), INR (p=0.02), and lower platelet count (p<0.001). In addition, non-surviving patients had higher serum caspase-8 levels (p<0.001) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Patients with septic shock showed median lactate of 4.00mmol/L (percentile 25–75 of 2.70–6.35, and range of 2–20).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/mL (OR=3.306; 95% CI=1.619–6.753; p=0.001) after controlling for age, lactic acid, septic shock, SOFA, aPTT and INR (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The Hosmer and Lemeshow goodness test of the logistic model had a chi-square of 11.4 and a p-value of 0.18.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The area under the curve for mortality prediction was of 67% (95% CI=60–73%; p<0.001) by serum caspase-8 levels (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), of 69% (95% CI=63–77%; p<0.001) by SOFA, and of 71% (95% CI=65–77%; p<0.001) by APACHE-II score. No significant differences were found in the area under the curve between serum caspase-8 levels and SOFA (p=0.64), serum caspase-8 levels and APACHE-II score (p=0.38), and SOFA and APACHE-II (p=0.57). We found that the point of serum caspase-8 levels>43.5ng/mL showed a sensitivity of 49% (38–61%), specificity 82% (75–88%), positive likelihood ratio 2.8 (1.8–4.2), negative likelihood ratio 0.6 (0.5–0.8), positive predictive value 62% (51–71%) and negative predictive value 74% (69–78%) for mortality prediction.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In Kaplan–Meier analysis was found that patients with serum caspase-8 levels>43.5ng/mL had a higher mortality rate (Hazard ratio=4.4; 95% CI=2.6–7.3; p<0.001) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>DiscussionThat we know this is the study reporting data on blood caspase-8 concentrations in septic patients and the main novelty of our study is that blood caspase-8 concentrations could have a role in the mortality prediction of septic patients.We found in the multiple logistic regression analysis an association between serum caspase-8 levels and mortality after controlling for age, lactic acid, septic shock, SOFA, aPTT and INR. We did not include in the regression model APACHE due to that we included SOFA, other severity score. In addition, we neither include creatinine and platelet count due that both are included in SOFA.There are different types of programmed cell death, as apoptosis,<a class="elsevierStyleCrossRef" href="#bib0145">3</a> autophagy,<a class="elsevierStyleCrossRefs" href="#bib0195">13–15</a> and Pyroptosis.<a class="elsevierStyleCrossRefs" href="#bib0210">16–18</a> Autophagy is induced by pro-inflammatory cytokines that produce the activation of Toll-like receptor (TLR)-2 and TLR-4, then 5′ adenosine monophosphate-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) are activated and produce the inhibition of mammalian target of rapamycin complex 1 (mTORC1) that lead to cell death by autophagy.<a class="elsevierStyleCrossRefs" href="#bib0195">13–15</a> Pyroptosis is an inflammatory form of programmed cell death, in which participate caspase-1, caspase-4, caspase-5 and caspase-11, and is characterized by the release of inflammatory cytokines as IL-1β and IL-18.<a class="elsevierStyleCrossRefs" href="#bib0210">16–18</a>Apoptotic cell death occurs through death receptor pathway or mitochondrial pathway. The apoptotic extrinsic pathway is activated when some membrane receptor superfamily binding to its ligand superfamily generating a death signal that active caspase-8. Afterwards, caspase-8 will activate caspase-3, the main effector caspase of cellular changes by apoptosis.<a class="elsevierStyleCrossRef" href="#bib0145">3</a> Therefore, our findings could mean that the non-surviving patients showed a higher activation of apoptosis extrinsic pathway that lead to higher activation of effector caspases and finally to a higher apoptotic state.The blockade of extrinsic apoptosis pathway in septic mice has been associated with reduction of apoptosis and improvement of survival.<a class="elsevierStyleCrossRefs" href="#bib0225">19–23</a> Treatment with small interfering RNA (siRNA) against caspase-8 or Fas increased survival and decreased active caspase-3 and apoptosis in the liver and spleen.<a class="elsevierStyleCrossRef" href="#bib0225">19</a> Treatment with caspase-8 or caspase-3 siRNA reduced apoptosis in aortic endothelium and increased survival.<a class="elsevierStyleCrossRef" href="#bib0230">20</a> Treatment with Fas-associated death domain (FADD) siRNA increased survival and reduced acute lung injury<a class="elsevierStyleCrossRef" href="#bib0235">21</a> and caspase-3 activation and apoptosis in aortic endothelium.<a class="elsevierStyleCrossRef" href="#bib0240">22</a> Treatment with a caspase-8 inhibitor increased survival, and decreased monocyte activation, induced necroptotic cell death of activated monocytes, and release of interleukin-1.<a class="elsevierStyleCrossRef" href="#bib0245">23</a> Thus, in all those studies with septic mice has been found a reduction of apoptosis and an increase of survival decreasing extrinsic apoptosis pathway by the block of caspase-8, the main executor caspase of that apoptosis pathway. Thus, it is possible that according the results of our study (association between blood caspase-8 levels and mortality in septic patients) and those in animal models (increase of survival with the agents that block caspase-8 activation) could be interesting to research about the use of agents that block extrinsic apoptosis pathway in septic patients.We must recognize some limitations of our study. First, we have not assessed cellular damage by apoptosis with some biochemical (Annexin V) or histological assay as terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL), and neither proinflammatory cytokines (as IL-1). Second, we have not data about compliance of sepsis bundle, nor a validation patient cohort. Third, we have not determined blood anti-caspase-8 antibodies, which have been described in patients with type 1 diabetes,<a class="elsevierStyleCrossRef" href="#bib0250">24</a> patients with systemic sclerosis, systemic lupus erythematosus, silicosis, as well as in healthy individuals.<a class="elsevierStyleCrossRef" href="#bib0255">25</a> Fourth, we do not know whether the mortality prognostic ability of serum caspase-8 levels is generalizable to all septic patients due to exclusion criteria. In addition, although the AUC was statistically significant; however, the AUC (67%) and the lower limit of 95% CI (60%) were low.<a class="elsevierStyleCrossRef" href="#bib0260">26</a> Besides, there were no differences in the prediction of mortality between serum caspase-8 levels, SOFA and APACHE-II score; however, the objective of our study was to determine whether serum caspase-8 levels could add in the mortality prediction and not replace other severity scores.ConclusionsTo the best of our knowledge, our study is the first series reporting data on blood caspase-8 concentrations in septic patients. The new findings from our study were that blood caspase-8 concentrations were higher in non-survivor than in survivor patients and there is an association between blood caspase-8 concentrations and mortality in septic patients.Authors’ contributionsLLo conceived, designed and coordinated the study, participated in acquisition and interpretation of data, and drafted the manuscript.MMM, RO, MM, VG, AP and MR participated in acquisition of data.AGC and APC carried out the determinations of serum caspase-8 concentrations.AJ participated in the interpretation of data.All authors revised the manuscript critically for important intellectual content and made the final approval of the version to be published.FundingThis study was supported by a grant from Instituto de Salud Carlos III (PI-18-00500) (Madrid, Spain) and co-financed with Fondo Europeo de Desarrollo Regional (FEDER).Conflicts of interestThe authors declare that they have no competing interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1640792" "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 variable of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1462858" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1640791" "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" => "Variable de interés principal" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1462857" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design and subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Determination of serum caspase-8 concentrations" ] 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" => "Authors’ contributions" ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-04-19" "fechaAceptado" => "2020-06-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1462858" "palabras" => array:5 [ 0 => "Apoptosis" 1 => "Caspase-8" 2 => "Sepsis" 3 => "Mortality" 4 => "Outcome" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1462857" "palabras" => array:5 [ 0 => "Apoptosis" 1 => "Caspasa-8" 2 => "Sepsis" 3 => "Mortalidad" 4 => "Resultado" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveNo data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DesignA prospective observational study was carried out. SettingThree Spanish Intensive Care Units. PatientsSeptic patients. InterventionsSerum caspase-8 concentrations were determined at the diagnosis of sepsis. Main variable of interestMortality after 30 days. ResultsPatients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619–6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60–73%; p<0.001). ConclusionsThe novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients." "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 variable of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoNo existen datos publicados sobre los niveles sanguíneos de caspasa-8 (la caspasa iniciadora en la vía extrínseca de apoptosis) en pacientes sépticos. Por lo tanto, los objetivos del estudio fueron describir los niveles sanguíneos de caspasa-8 en pacientes supervivientes y fallecidos y determinar si existe una asociación entre los niveles sanguíneos de caspasa-8 y la mortalidad de los pacientes sépticos. DiseñoEstudio observacional y prospectivo. ÁmbitoTres unidades de cuidados intensivos españolas. PacientesPacientes sépticos. IntervencionesSe determinaron las concentraciones séricas de caspasa-8 al diagnóstico de la sepsis. Variable de interés principalMortalidad a los 30 días. ResultadosEncontramos que los pacientes fallecidos en los primeros 30 días (n=81) comparados con los pacientes supervivientes (n=140) presentaban niveles séricos mayores de caspasa-8 (p<0,001). En el análisis de regresión logística múltiple encontramos una asociación entre los niveles séricos de caspasa-8>43,5ng/ml y la mortalidad (OR: 3,306; IC 95%: 1,619-6,753; p=0,001). El área bajo la curva para predecir la mortalidad por los niveles séricos de caspasa-8 fue del 67% (IC 95%: 60-73%; p<0,001). ConclusionesLos nuevos hallazgos de nuestro estudio fueron que los niveles séricos mayores de caspasa-8 eran superiores en los pacientes fallecidos en los primeros 30 días, y que existe una asociación entre los niveles séricos de caspasa-8 y la mortalidad." "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" => "Variable de interés principal" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1534 "Ancho" => 1623 "Tamanyo" => 144630 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic analysis using blood caspase-8 concentrations for prediction of mortality at 30 days." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1355 "Ancho" => 1583 "Tamanyo" => 141845 ] ] "descripcion" => array:1 [ "en" => "Survival curves at 30 days using blood caspase-8 concentrations lower or equal vs higher than 43.5ng/mL." ] ] 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" => "APACHE, Acute Physiology and Chronic Health Evaluation; SOFA, Sepsis-related Organ Failure Assessment; COPD, Chronic Obstructive Pulmonary Disease; PaO2/FIO2, pressure of arterial oxygen/fraction inspired oxygen; aPTT, activated partial thromboplastin time; INR, international normalized ratio." "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">Surviving(n=140) \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=81) \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">Sex 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 (35.0) \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">27 (33.3) \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">0.88 \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 – median years (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 (45–68) \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">64 (56–74) \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 – median (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (14–23) \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">23 (18–28) \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="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">SOFA score – median (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (7–11) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (9–14) \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"><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">Chronic renal failure – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (5.7) \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">8 (9.9) \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">0.29 \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">COPD – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (11.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (16.0) \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">0.41 \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">Diabetes mellitus – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (27.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (38.3) \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">0.10 \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">Ischemic heart disease – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (7.9) \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">6 (7.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.99 \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">Bilirubin (mg/dl) – median (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.90 (0.43–1.45) \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">0.85 (0.50–2.17) \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">0.49 \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">Leukocytes (cells/mm3) – median*103(p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.0 (10.2–19.6) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.3 (8.5–20.7) \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">0.84 \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 (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">173 (120–263) \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">172 (101–239) \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">0.32 \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 (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.10 (0.80–1.90) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.45 (0.93–2.95) \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">aPTT (seconds) – median (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (28–40) \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">36 (30–46) \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">INR – median (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.27 (1.10–1.54) \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">1.41 (1.13–1.91) \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">Platelets (cells/mm3) – median*103(p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">197 (135–296) \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">136 (76–223) \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">Lactic acid (mmol/L) – median (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.80 (1.08–3.50) \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">3.50 (1.55–6.00) \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"><0.001 \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">Septic shock – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 (44.3) \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">56 (69.1) \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="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">Bloodstream infection – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (15.7) \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">10 (12.3) \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">0.56 \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-8 (ng/mL) – median (p 25–75) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.8 (4.2–35.8) \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">39.7 (6.7–206.5) \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="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" 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">Sepsis focus \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">0.75 \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">Respiratory – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 (56.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 (59.3) \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="" 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">Abdominal – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (26.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (25.9) \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">Neurological \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 (1.4) \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="char" 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">Urinary – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (5.7) \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">4 (4.9) \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">Skin – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (5.7) \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">3 (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="" 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">Endocarditis – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (4.3) \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">4 (4.9) \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">Osteomyelitis – 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="char" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.2) \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="" 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">Empiric antimicrobial treatment adequate \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">0.91 \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">Unknown due to negative cultures – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 (52.9) \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">44 (54.3) \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="" 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">Adequate – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 (40.7) \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">30 (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="" 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">Inadequate – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (2.9) \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 (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="" 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">Unknown due to antigenuria diagnosis – 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (3.6) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (4.9) \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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2795249.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparisons between non-surviving and surviving septic patients on demographic and clinical characteristics at moment of sepsis diagnosis." ] ] 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:2 [ "leyenda" => "SOFA, Sepsis-related Organ Failure Assessment; aPTT, activated partial thromboplastin time; INR, international normalized ratio." "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">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-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">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">1.034 \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">1.009–1.060 \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">SOFA 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">1.188 \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">1.071–1.317 \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">Lactic acid (mmol/L) \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">1.120 \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">0.963–1.303 \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">0.14 \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">Septic shock (yes vs non) \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">1.483 \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">0.614–3.584 \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">0.38 \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">Serum caspase-8 level>43.5ng/mL (yes vs non) \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">3.306 \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">1.619–6.753 \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">aPTT (seconds) \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">1.017 \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">0.991–1.043 \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">0.21 \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 \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">0.879 \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">0.551–1.404 \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">0.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2795248.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Multiple logistic regression analyses to predict mortality at 30 days." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0135" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.C. Angus" 1 => "W.T. Linde-Zwirble" 2 => "J. Lidicker" 3 => "G. Clermont" 4 => "J. Carcillo" 5 => "M.R. Pinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00003246-200107000-00002" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2001" "volumen" => "29" "paginaInicial" => "1303" "paginaFinal" => "1310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11445675" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0140" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sepsis occurrence in acutely ill patients investigators sepsis in European intensive care units: results of the SOAP study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.L. Vincent" 1 => "Y. Sakr" 2 => "C.L. Sprung" 3 => "V.M. Ranieri" 4 => "K. Reinhart" 5 => "H. 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Estadísticas

Original

Blood caspase-8 concentrations and mortality among septic patients

Niveles sanguíneos de caspasa-8 y mortalidad de los pacientes sépticos

L. Lorentea,

Autor para correspondencia

lorentemartin@msn.com

Corresponding author.

, M.M. Martínb, R. Ortiz-Lópezc, A.F. González-Riverod, A. Pérez-Cejase, M. Martínf, V. Gonzalezf, A. Pérezf, M. Rodinf, A. Jiménezg

a Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Tenerife, Spain

b Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Crta Rosario s/n., Santa Cruz Tenerife 38010, Spain

c Intensive Care Unit, Hospital General de La Palma, Buenavista de Arriba s/n, Breña Alta, La Palma 38713, Spain

d Laboratory Department, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Santa Cruz de Tenerife, Spain

e Laboratory Department, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Tenerife, Spain

f Intensive Care Unit, Hospital Universitario de Canarias, Ofra s/n., La Laguna, Santa Cruz de Tenerife 38320, Spain

g Research Unit, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Tenerife, Spain

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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">Sepsis contributes to many deaths and healthcare system costs&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#44;2</span></a> Apoptosis&#44; the process in which cells are programmedly and actively eliminated&#44; that occurs in physiological processes &#40;during morphogenesis and tissue remodeling&#41; and also in different diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> In addition&#44; in animal models has been found an increase of apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> Apoptotic cell death occurs mainly through the extrinsic pathway &#40;or death receptor pathway&#41; and the intrinsic pathway &#40;or mitochondrial pathway&#41;&#46; The extrinsic pathway is activated when tumor necrosis factor membrane receptors superfamily &#40;TNFRSF&#41; binding to its ligands of the tumor necrosis factor ligand superfamily &#40;TNFSF&#41;&#46; The main ligands and receptors in this pathway are the ligand FasL &#40;which bind to its Fas antigen&#41; and the TNF-related apoptosis-inducing ligand &#40;TRAIL&#41; &#40;which bind to its different receptors &#40;TRAILR1&#8211;4&#41;&#46; When TNFRSF and its ligand TNFSF binding is generated a death signal that adheres to pro-caspase-8 and appears active caspase-8 &#40;initiator caspase&#41;&#44; which activates caspase-3 &#40;the main effector caspase&#41; leading to cellular apoptotic changes&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The extrinsic pathway of apoptosis in septic patients has been scarcely explored and only in studies of small sample size&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;5</span></a> In one study higher blood Fas levels in septic patients than in controls and in non-survivor than in survivor septic patients&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> and the same findings for TRAIL&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> However&#44; there are not data on blood caspase-8 concentrations in septic patients&#46; Increased blood caspase-8 concentrations have been found in patients with systemic lupus erythematosus<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;7</span></a> and with in patients with metabolic syndrome and non-alcoholic fatty liver disease&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a> We have chosen the study of blood caspase-8 concentrations in our research due to that the extrinsic pathway of apoptosis in septic patients has been scarcely explored and that caspase-8 is the initiator caspase of the extrinsic apoptosis pathway&#46; We hypothesized that non-survivor septic patients could have higher blood caspase-8 concentrations than survivor ones&#46; Therefore&#44; the objectives of this study were to describe blood caspase-8 concentrations in survivor and non-survivor patients and to determine whether there is an association between blood caspase-8 concentrations and mortality in septic patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Design and subjects</span><p id="par0015" class="elsevierStylePara elsevierViewall">This prospective and observational study was conducted in the polyvalent Intensive Care Unit from 3 Spanish hospitals&#58; H&#46; Universitario de Canarias&#44; H&#46; Universitario Nuestra Se&#241;ora de Candelaria and H&#46; General de la Palma&#46; The study was approved by the Ethics Committee of all hospitals&#46; The informed and signed consent from patients or their relatives was obtained to participate in the study&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study was conducted between 2013 and 2014&#46; We included patients with sepsis according to the Sepsis-3 Consensus criteria<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a>&#59; thus&#44; the patients were recoded according to those sepsis criteria&#46; We excluded patients with white solid tumor&#44; blood cell count &#60;1000&#47;&#956;l&#44; hematological tumor&#44; human immunodeficiency virus &#40;HIV&#41;&#44; immunosuppressive therapy&#44; radiation therapy&#44; steroid agents&#44; breastfeeding&#44; or pregnancy&#44; or age &#60;18 years&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Age&#44; sex&#44; and the history of chronic renal failure&#44; ischemic heart disease&#44; diabetes mellitus&#44; chronic obstructive pulmonary disease&#44; sepsis focus and appropriateness of antimicrobial therapy were registered&#46; We also registered creatinine&#44; leukocytes&#44; bilirubin&#44; activated partial thromboplastin time&#44; international normalized ratio&#44; platelets&#44; lactic acid&#44; pressure of arterial oxygen&#44; fraction inspired of oxygen&#44; site of infection&#44; Acute Physiology and Chronic Health Evaluation &#40;APACHE&#41;-II score<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> and Sepsis-related Organ Failure Assessment &#91;SOFA&#93; score&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a> Besides&#44; we registered the appearance of bloodstream infection and septic shock&#46; Mortality at 30 days was considered our endpoint study&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Determination of serum caspase-8 concentrations</span><p id="par0030" class="elsevierStylePara elsevierViewall">We freeze patient sera at moment of sepsis diagnosis at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C until the determination of serum caspase-8 levels&#46; We used the Human Caspase 8 ELISA Kit &#40;Elabscience&#44; Houston&#44; Texas&#44; United States&#41; for the determination of serum caspase-8 concentrations&#46; The detection limit of the assay was 0&#46;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; the intra-assay coefficient of variation &#40;CV&#41; was &#60;6&#37;&#44; and the inter-assay CV was &#60;8&#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 used medians &#40;percentile 25&#8211;75&#41; and frequencies &#40;percentages&#41; to describe continuous and categorical variables&#46; Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test and chi-square test were used to compare continuous and categorical variables between surviving and non-surviving patients&#46; We carried out receiver operating characteristic &#40;ROC&#41; analyses using 30-day mortality&#44; serum caspase-8 concentrations&#44; SOFA and APACHE-II&#46; Comparison of ROC curves&#160;to test the statistical significance of the difference between the areas&#160;under curves &#40;derived from the same cases&#41; was carried out with the method of DeLong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> We reported sensitivity&#44; specificity&#44; positive and negative likelihood ratios&#44; and positive and negative predictive values and its 95&#37; confidence interval &#40;CI&#41; of serum caspase-8 levels cut-off selected in basis to Youden J index&#46; We constructed Kaplan&#8211;Meier 30-day survival curves using survival at 30 days and the cut-off of serum caspase-8 concentrations estimated by Youden J index&#44; and Hazard Ratio was calculated for this cut-off&#46; To explore the association between serum caspase-8 concentrations and 30-day mortality controlling for possible confounds was performed a multiple logistic regression analysis&#59; and to estimate the clinical impact of prognostic variables were reported odds ratio &#40;OR&#41; and its 95&#37; confidence interval &#40;CI&#41;&#46; For statistical analyses were used the programs NCSS 2000 &#40;Kaysville&#44; Utah&#41; and SPSS 17&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#44; and for the establishment of significant differences was used the point <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">We included a total of 221 patients&#44; 140 &#40;63&#46;3&#37;&#41; surviving at 30 days and 81 &#40;36&#46;7&#37;&#41; deaths in the following 30 days&#46; The number of patients included in each hospital were 121&#44; 68 and 32 patients respectively&#46; There were not significant differences in the mortality rate between hospitals &#40;47&#47;121 &#40;38&#46;8&#37;&#41;&#44; 22&#47;68 &#40;32&#46;4&#37;&#41; and 12&#47;32 &#40;37&#46;5&#37;&#41;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;67&#41;&#46; We found that non-surviving patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>81&#41; compared to surviving patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>140&#41; had higher SOFA &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; APACHE-II &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; age &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; rate of septic shock &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; lactic acid &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; creatinine &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; aPTT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; INR &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; and lower platelet count &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In addition&#44; non-surviving patients had higher serum caspase-8 levels &#40;<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="#tbl0005">Table 1</a>&#41;&#46; Patients with septic shock showed median lactate of 4&#46;00<span class="elsevierStyleHsp" style=""></span>mmol&#47;L &#40;percentile 25&#8211;75 of 2&#46;70&#8211;6&#46;35&#44; and range of 2&#8211;20&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Multiple logistic regression analysis found an association between serum caspase-8 levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>43&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;306&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;619&#8211;6&#46;753&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; after controlling for age&#44; lactic acid&#44; septic shock&#44; SOFA&#44; aPTT and INR &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The Hosmer and Lemeshow goodness test of the logistic model had a chi-square of 11&#46;4 and a <span class="elsevierStyleItalic">p</span>-value of 0&#46;18&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The area under the curve for mortality prediction was of 67&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#8211;73&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; by serum caspase-8 levels &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; of 69&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#8211;77&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; by SOFA&#44; and of 71&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>65&#8211;77&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; by APACHE-II score&#46; No significant differences were found in the area under the curve between serum caspase-8 levels and SOFA &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;64&#41;&#44; serum caspase-8 levels and APACHE-II score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;38&#41;&#44; and SOFA and APACHE-II &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;57&#41;&#46; We found that the point of serum caspase-8 levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>43&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;mL showed a sensitivity of 49&#37; &#40;38&#8211;61&#37;&#41;&#44; specificity 82&#37; &#40;75&#8211;88&#37;&#41;&#44; positive likelihood ratio 2&#46;8 &#40;1&#46;8&#8211;4&#46;2&#41;&#44; negative likelihood ratio 0&#46;6 &#40;0&#46;5&#8211;0&#46;8&#41;&#44; positive predictive value 62&#37; &#40;51&#8211;71&#37;&#41; and negative predictive value 74&#37; &#40;69&#8211;78&#37;&#41; for mortality prediction&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In Kaplan&#8211;Meier analysis was found that patients with serum caspase-8 levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>43&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;mL had a higher mortality rate &#40;Hazard ratio<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;4&#59; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#8211;7&#46;3&#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="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">That we know this is the study reporting data on blood caspase-8 concentrations in septic patients and the main novelty of our study is that blood caspase-8 concentrations could have a role in the mortality prediction of septic patients&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">We found in the multiple logistic regression analysis an association between serum caspase-8 levels and mortality after controlling for age&#44; lactic acid&#44; septic shock&#44; SOFA&#44; aPTT and INR&#46; We did not include in the regression model APACHE due to that we included SOFA&#44; other severity score&#46; In addition&#44; we neither include creatinine and platelet count due that both are included in SOFA&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">There are different types of programmed cell death&#44; as apoptosis&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> autophagy&#44;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">13&#8211;15</span></a> and Pyroptosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">16&#8211;18</span></a> Autophagy is induced by pro-inflammatory cytokines that produce the activation of Toll-like receptor &#40;TLR&#41;-2 and TLR-4&#44; then 5&#8242; adenosine monophosphate-activated protein kinase &#40;MAPK&#41; and c-Jun&#160;<span class="elsevierStyleItalic">N</span>-terminal kinase &#40;JNK&#41; are activated and produce the inhibition of mammalian target of rapamycin complex 1 &#40;mTORC1&#41; that lead to cell death by autophagy&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">13&#8211;15</span></a> Pyroptosis is an inflammatory form of programmed cell death&#44; in which participate caspase-1&#44; caspase-4&#44; caspase-5 and caspase-11&#44; and is characterized by the release of inflammatory cytokines as IL-1&#946; and IL-18&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">16&#8211;18</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Apoptotic cell death occurs through death receptor pathway or mitochondrial pathway&#46; The apoptotic extrinsic pathway is activated when some membrane receptor superfamily binding to its ligand superfamily generating a death signal that active caspase-8&#46; Afterwards&#44; caspase-8 will activate caspase-3&#44; the main effector caspase of cellular changes by apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> Therefore&#44; our findings could mean that the non-surviving patients showed a higher activation of apoptosis extrinsic pathway that lead to higher activation of effector caspases and finally to a higher apoptotic state&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The blockade of extrinsic apoptosis pathway in septic mice has been associated with reduction of apoptosis and improvement of survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">19&#8211;23</span></a> Treatment with small interfering RNA &#40;siRNA&#41; against caspase-8 or Fas increased survival and decreased active caspase-3 and apoptosis in the liver and spleen&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a> Treatment with caspase-8 or caspase-3 siRNA reduced apoptosis in aortic endothelium and increased survival&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">20</span></a> Treatment with Fas-associated death domain &#40;FADD&#41; siRNA increased survival and reduced acute lung injury<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> and caspase-3 activation and apoptosis in aortic endothelium&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> Treatment with a caspase-8 inhibitor increased survival&#44; and decreased monocyte activation&#44; induced necroptotic cell death of activated monocytes&#44; and release of interleukin-1&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">23</span></a> Thus&#44; in all those studies with septic mice has been found a reduction of apoptosis and an increase of survival decreasing extrinsic apoptosis pathway by the block of caspase-8&#44; the main executor caspase of that apoptosis pathway&#46; Thus&#44; it is possible that according the results of our study &#40;association between blood caspase-8 levels and mortality in septic patients&#41; and those in animal models &#40;increase of survival with the agents that block caspase-8 activation&#41; could be interesting to research about the use of agents that block extrinsic apoptosis pathway in septic patients&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We must recognize some limitations of our study&#46; First&#44; we have not assessed cellular damage by apoptosis with some biochemical &#40;Annexin V&#41; or histological assay as terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling &#40;TUNEL&#41;&#44; and neither proinflammatory cytokines &#40;as IL-1&#41;&#46; Second&#44; we have not data about compliance of sepsis bundle&#44; nor a validation patient cohort&#46; Third&#44; we have not determined blood anti-caspase-8 antibodies&#44; which have been described in patients with type 1 diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">24</span></a> patients with systemic sclerosis&#44; systemic lupus erythematosus&#44; silicosis&#44; as well as in healthy individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a> Fourth&#44; we do not know whether the mortality prognostic ability of serum caspase-8 levels is generalizable to all septic patients due to exclusion criteria&#46; In addition&#44; although the AUC was statistically significant&#59; however&#44; the AUC &#40;67&#37;&#41; and the lower limit of 95&#37; CI &#40;60&#37;&#41; were low&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a> Besides&#44; there were no differences in the prediction of mortality between serum caspase-8 levels&#44; SOFA and APACHE-II score&#59; however&#44; the objective of our study was to determine whether serum caspase-8 levels could add in the mortality prediction and not replace other severity scores&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0090" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; our study is the first series reporting data on blood caspase-8 concentrations in septic patients&#46; The new findings from our study were that blood caspase-8 concentrations were higher in non-survivor than in survivor patients and there is an association between blood caspase-8 concentrations and mortality in septic patients&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Authors&#8217; contributions</span><p id="par0095" class="elsevierStylePara elsevierViewall">LLo conceived&#44; designed and coordinated the study&#44; participated in acquisition and interpretation of data&#44; and drafted the manuscript&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">MMM&#44; RO&#44; MM&#44; VG&#44; AP and MR participated in acquisition of data&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">AGC and APC carried out the determinations of serum caspase-8 concentrations&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">AJ participated in the interpretation of data&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">All authors revised the manuscript critically for important intellectual content and made the final approval of the version to be published&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par0120" class="elsevierStylePara elsevierViewall">This study was supported by a grant from <span class="elsevierStyleGrantSponsor" id="gs1">Instituto de Salud Carlos III</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs1">PI-18-00500</span>&#41; &#40;Madrid&#44; Spain&#41; and co-financed with <span class="elsevierStyleGrantSponsor" id="gs2">Fondo Europeo de Desarrollo Regional &#40;FEDER&#41;</span>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflicts of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have no competing interests&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "identificador" => "sec0015"
              "titulo" => "Design and subjects"
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            1 => array:2 [
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              "titulo" => "Determination of serum caspase-8 concentrations"
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              "titulo" => "Statistical methods"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2020-04-19"
    "fechaAceptado" => "2020-06-27"
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            0 => "Apoptosis"
            1 => "Caspase-8"
            2 => "Sepsis"
            3 => "Mortality"
            4 => "Outcome"
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            1 => "Caspasa-8"
            2 => "Sepsis"
            3 => "Mortalidad"
            4 => "Resultado"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">No data are available on blood caspase-8 concentrations &#40;the initiator caspase in the extrinsic apoptosis pathway&#41; in septic patients&#46; The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors&#44; and examines the possible association between blood caspase-8 concentrations and mortality in septic patients&#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">Three 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">Septic patients&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Interventions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Serum caspase-8 concentrations were determined at the diagnosis of sepsis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Main variable of interest</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Mortality after 30 days&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Patients not surviving at day 30 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>81&#41; compared to surviving patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>140&#41; showed higher serum caspase-8 levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Multiple logistic regression analysis found an association between serum caspase-8 levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>43&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and mortality &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;306&#59; 95&#37;CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;619&#8211;6&#46;753&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The area under the curve &#40;AUC&#41; for mortality predicted by serum caspase-8 levels was 67&#37; &#40;95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#8211;73&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#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 blood caspase-8 concentrations are higher in non-survivors than in survivors&#44; and that there is an association between blood caspase-8 concentrations and mortality in septic patients&#46;</p></span>"
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            "titulo" => "Design"
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            "titulo" => "Main variable of interest"
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        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">No existen datos publicados sobre los niveles sangu&#237;neos de caspasa-8 &#40;la caspasa iniciadora en la v&#237;a extr&#237;nseca de apoptosis&#41; en pacientes s&#233;pticos&#46; Por lo tanto&#44; los objetivos del estudio fueron describir los niveles sangu&#237;neos de caspasa-8 en pacientes supervivientes y fallecidos y determinar si existe una asociaci&#243;n entre los niveles sangu&#237;neos de caspasa-8 y la mortalidad de los pacientes s&#233;pticos&#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">Tres 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">Pacientes s&#233;pticos&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intervenciones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se determinaron las concentraciones s&#233;ricas de caspasa-8 al diagn&#243;stico de la sepsis&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variable de inter&#233;s principal</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">Encontramos que los pacientes fallecidos en los primeros 30 d&#237;as &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>81&#41; comparados con los pacientes supervivientes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>140&#41; presentaban niveles s&#233;ricos mayores de caspasa-8 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En el an&#225;lisis de regresi&#243;n log&#237;stica m&#250;ltiple encontramos una asociaci&#243;n entre los niveles s&#233;ricos de caspasa-8<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>43&#44;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml y la mortalidad &#40;OR&#58; 3&#44;306&#59; IC 95&#37;&#58; 1&#44;619-6&#44;753&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; El &#225;rea bajo la curva para predecir la mortalidad por los niveles s&#233;ricos de caspasa-8 fue del 67&#37; &#40;IC 95&#37;&#58; 60-73&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#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 mayores de caspasa-8 eran superiores en los pacientes fallecidos en los primeros 30 d&#237;as&#44; y que existe una asociaci&#243;n entre los niveles s&#233;ricos de caspasa-8 y la mortalidad&#46;</p></span>"
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                  \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;29&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">COPD</span> &#8211; <span class="elsevierStyleItalic">n &#40;&#37;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;11&#46;4&#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">13 &#40;16&#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;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">Diabetes mellitus</span> &#8211; <span class="elsevierStyleItalic">n &#40;&#37;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;27&#46;1&#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">31 &#40;38&#46;3&#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;10&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">Ischemic heart disease</span> &#8211; <span class="elsevierStyleItalic">n &#40;&#37;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;7&#46;9&#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">6 &#40;7&#46;4&#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;99&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;</span> &#8211; <span class="elsevierStyleItalic">median &#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;90 &#40;0&#46;43&#8211;1&#46;45&#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;85 &#40;0&#46;50&#8211;2&#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;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">Leukocytes &#40;cells&#47;mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span><span class="elsevierStyleItalic">&#41;</span> &#8211; <span class="elsevierStyleItalic">median&#42;10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span><span class="elsevierStyleItalic">&#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;0 &#40;10&#46;2&#8211;19&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;3 &#40;8&#46;5&#8211;20&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;84&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</span> &#8211; <span class="elsevierStyleItalic">median &#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">173 &#40;120&#8211;263&#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">172 &#40;101&#8211;239&#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;32&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;</span> &#8211; <span class="elsevierStyleItalic">median &#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;10 &#40;0&#46;80&#8211;1&#46;90&#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;45 &#40;0&#46;93&#8211;2&#46;95&#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;01&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;seconds&#41;</span> &#8211; <span class="elsevierStyleItalic">median &#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;28&#8211;40&#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">36 &#40;30&#8211;46&#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;01&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</span> &#8211; <span class="elsevierStyleItalic">median &#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;27 &#40;1&#46;10&#8211;1&#46;54&#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;41 &#40;1&#46;13&#8211;1&#46;91&#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;02&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 &#40;cells&#47;mm</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span><span class="elsevierStyleItalic">&#41;</span> &#8211; <span class="elsevierStyleItalic">median&#42;10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">3</span></span><span class="elsevierStyleItalic">&#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">197 &#40;135&#8211;296&#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">136 &#40;76&#8211;223&#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">Lactic acid &#40;mmol&#47;L&#41;</span> &#8211; <span class="elsevierStyleItalic">median &#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;80 &#40;1&#46;08&#8211;3&#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">3&#46;50 &#40;1&#46;55&#8211;6&#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">&#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">Septic shock</span> &#8211; <span class="elsevierStyleItalic">n &#40;&#37;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;44&#46;3&#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">56 &#40;69&#46;1&#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">Bloodstream infection</span> &#8211; <span class="elsevierStyleItalic">n &#40;&#37;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;15&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;12&#46;3&#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;56&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-8 &#40;ng&#47;mL&#41;</span> &#8211; <span class="elsevierStyleItalic">median &#40;p 25</span>&#8211;<span class="elsevierStyleItalic">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;8 &#40;4&#46;2&#8211;35&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;7 &#40;6&#46;7&#8211;206&#46;5&#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" 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="elsevierStyleVsp" style="height:0.5px"></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="elsevierStyleItalic">Sepsis focus</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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="" valign="\n
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                  \t\t\t\t">&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;75&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>Respiratory &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79 &#40;56&#46;4&#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">48 &#40;59&#46;3&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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>Abdominal &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;26&#46;4&#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">21 &#40;25&#46;9&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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>Neurological&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 &#40;1&#46;4&#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&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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>Urinary &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;5&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;4&#46;9&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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>Skin &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;5&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;3&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \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>Endocarditis &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;4&#46;3&#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 &#40;4&#46;9&#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="" valign="\n
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                  \t\t\t\t">&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>Osteomyelitis &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;2&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \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">Empiric antimicrobial treatment adequate</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="" valign="\n
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                  \t\t\t\t">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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
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                  \t\t\t\t">0&#46;91&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Unknown due to negative cultures &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">74 &#40;52&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">44 &#40;54&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \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>Adequate &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#40;40&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;37&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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>Inadequate &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;2&#46;9&#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">3 &#40;3&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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>Unknown due to antigenuria diagnosis &#8211; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">4 &#40;4&#46;9&#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="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#46;01&nbsp;\t\t\t\t\t\t\n
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Información del artículo

ISSN: 02105691
Idioma original: Inglés

DOI:10.1016/j.medin.2020.06.016

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