Enhanced HLA-DR expression on T-lymphocytes from patients in early stages of non-surgical sepsis

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Recio-Rodriguez, Manuel A. Gomez-Marcos, Maria C. Patino-Alonso, Cristina Agudo-Conde, Luis Garcia-Ortiz" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Jesus" "apellidos" => "Gonzalez-Sanchez" ] 1 => array:2 [ "nombre" => "Jose I." "apellidos" => "Recio-Rodriguez" ] 2 => array:2 [ "nombre" => "Manuel A." "apellidos" => "Gomez-Marcos" ] 3 => array:2 [ "nombre" => "Maria C." "apellidos" => "Patino-Alonso" ] 4 => array:2 [ "nombre" => "Cristina" "apellidos" => "Agudo-Conde" ] 5 => array:2 [ "nombre" => "Luis" "apellidos" => "Garcia-Ortiz" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619301135?idApp=UINPBA00004N" "url" => "/23870206/0000015200000009/v1_201904241408/S2387020619301135/v1_201904241408/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Brief report" "titulo" => "Enhanced HLA-DR expression on T-lymphocytes from patients in early stages of non-surgical sepsis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "346" "paginaFinal" => "349" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Esther Fernández-Grande, Carmen María Cabrera, Blanca González, Carolina Varela, José Miguel Urra" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Esther" "apellidos" => "Fernández-Grande" "email" => array:1 [ 0 => "e.fernandezgrande@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen María" "apellidos" => "Cabrera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Blanca" "apellidos" => "González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Carolina" "apellidos" => "Varela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "José Miguel" "apellidos" => "Urra" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Immunology, Hospital General Universitario de Ciudad Real, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Medicine Faculty-Ciudad Real, Universidad de Castilla La Mancha, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Immunology, Hospital Regional Universitario Carlos Haya, Málaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Preventive Medicine, Hospital General Universitario de Ciudad Real, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Elevada expresión de HLA-DR en linfocitos T de pacientes en fases tempranas de sepsis no quirúrgica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 712 "Ancho" => 1005 "Tamanyo" => 40226 ] ] "descripcion" => array:1 [ "en" => "Percentage of CD3+/DR+ T-lymphocytes into the group of patients with sepsis (SP), patients with SIRS (NSP) and healthy controls (HC). In the dot plots, horizontal bars represent the mean value." ] ] ] "textoCompleto" => "IntroductionSepsis is defined as the presence of infection, documented or suspected, together with systemic manifestations of infection.<a class="elsevierStyleCrossRef" href="#bib0050">1</a> The early identification of sepsis and implementation of early evidence-based therapies have been documented to improve outcomes and decrease sepsis-related mortality.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> Reducing the diagnostic time of severe sepsis it is thought to be a critical component for reducing mortality as well as multiple organ dysfunctions.<a class="elsevierStyleCrossRef" href="#bib0060">3</a>Different biomarkers have been employed to achieve an early diagnosis of sepsis, such as procalcitonin (PCT) and C-reactive protein (CRP) as the major traditional markers of bacterial sepsis.<a class="elsevierStyleCrossRef" href="#bib0065">4</a> Apart from white cell count, there is limited information concerning to the use of cellular markers in the diagnosis of sepsis. Thus, a decreased HLA-DR expression on monocytes from septic patients has been associated with the immunosuppression developed in the clinical course of sepsis, and consequently with an increased mortality rate.<a class="elsevierStyleCrossRef" href="#bib0065">4</a> Similarly, the expression of HLA-DR molecule on T-lymphocytes has been previously investigated in sepsis with contradictory results.<a class="elsevierStyleCrossRefs" href="#bib0070">5,6</a> Hence this study was determinate to evaluate the expression of HLA-DR on peripheral T-lymphocytes as a cellular marker of early diagnosis in non-surgical septic patients.Material and methodsA cross sectional study was conducted over a period of six months. The subjects were classified in three groups: (a) patients with confirmed sepsis (N=26) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>); (b) patients with SIRS and negative blood culture (N=4, with a median age 69.75±18.98 years), and (c) healthy individuals (N=18) matched in age to patients (50±8.75 years). The absence of infectious disease in the healthy controls was confirmed by serological tests.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>All the patients included were diagnosed of non-surgical sepsis according to the International Guidelines for Management of Severe Sepsis and Septic Shock<a class="elsevierStyleCrossRef" href="#bib0055">2</a> and met at least two of the following criteria for SIRS: body temperature greater than 38°C or less than 36°C; heart rate of greater than 90beats/min; respiratory rate of greater than 20breaths/min or PaCO2 of less than 32mmHg; and white blood cell count of greater than 12,000cells/μL or less than 4000cells/μL.The microbiological infection was confirmed by isolation of the pathogenic bacteria from the blood cultures. And the clinical course of sepsis was determined by the quantification of the serum levels of CRP, PCT and fibrinogen as acute phase reactants. All participants in the study were adequately informed and consented to participate in the study.The analysis of the HLA-DR expression on T-lymphocytes and monocytes was carried out at the first day upon admission to the Infectious Disease Unit of the General University Hospital of Ciudad Real by collecting 4mL of peripheral blood samples per patient.To study the surface expression by flow cytometry, the following monoclonal antibodies were used: fluorescein isothiocyanate (FITC) conjugated anti-human CD3 (clone SK7) and phycoerythrin anti-human HLA-DR (PE clone L243) purchased from Becton Dickinson (BD San José, USA). Lymphocytes were acquired in a FACScan cytometer (BD) and analysed with the CellQuest Pro software (BD) as described in Cabrera et al.<a class="elsevierStyleCrossRef" href="#bib0080">7</a> For each sample, a negative control was defined adding the same isotype-matched mouse anti-human monoclonal antibody.Data on HLA-DR expression were analysed by the non-parametric Mann–Whitney U-test after a significant result for the Kruskal–Wallis analysis when comparing the three populations. The relationships between the percentage of lymphocytes and serum levels of CRP and PCT were analysed by the Spearman correlation coefficient. Statistical Package for the Social Sciences (SPSS Chicago, USA) version 22.0 was used for statistical analysis. The differences were considered statistically significant at p values of less than 0.05.ResultsTwenty three out of 26 septic patients (88.4%) showed serum levels of CRP above the upper threshold of normal range (<1mg/dL). The mean value was of 10.2±1.35mg/dL.The mean value of fibrinogen was of 628.1±37.2mg/dL, 18 out of 24 patients (75%) showed values above the upper threshold of normal range (200–500mg/dL). In 14 out of 18 of septic patients (77.8%) the serum levels of PCT were above the normal limit (PCT <0.5ng/mL) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Regarding to the aetiology of the isolated bacteria in the septic patients, gram-negative sepsis was found in 59.25% and 40.74% for gram-positive sepsis (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Escherichia coli (12/27, 44.4%) and Staphylococcus aureus (4/27, 14.8%) were the most frequent gram-negative and gram-positive bacterial infection, respectively. No differences were found in serum levels of CRP, PCT or fibrinogen among the type of sepsis (gram-positive and gram-negative) (p=0.75, p=0.18, and p>0.05 respectively).The control group of patients with SIRS had serum levels of CRP above the normality upper threshold, with a mean value for CRP of 14.6±6.6mg/dL and fibrinogen of 615.2±92.3mg/dL. Moreover, in 2 out of 4 patients with SIRS the serum levels of PCT were above the normal limit. Healthy individuals did not show any alteration in these parameters.Lymphocyte counts in peripheral blood samples showed a significant decrement (lymphopenia) in the septic patients (1250±561cells/μL) and patients with SIRS (1200±361cells/μL) in contrast to the healthy individuals (2360±288cells/μL) (p<0.05). However, no differences were evidenced in the number of monocytes in septic patients (583±297cells/μL), patients with SIRS (720±311cells/μL) and healthy individuals (440±194cells/μL).As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> the septic patients showed increased percentage of CD3+/DR+ T-lymphocytes compared to healthy individuals (20.37±9.42 vs. 6.58±3.89; p<0.005) and to patients with SIRS (20.37±9.42 vs. 8.7±2.9; p<0.005). However, the degree of HLA-DR expression on CD3+ T-cells, determined by mean fluorescence intensity (MFI), did not show significant differences between groups (166.42±91.6 for septic patients; 181.3±70.1 for SIRS patients and 161.65±42.52 in healthy controls). No correlations were found between the CD3+/DR+ T-lymphocytes and serum levels of CRP or PCT in septic patients.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In addition, no significant differences were found between the percentage of HLA-DR expression on T-lymphocytes from patients with sepsis caused by gram-positive (N=10) or patients with sepsis caused by gram-negative bacteria (N=16) (19.76±7.57 vs. 20.75±10.63; p>0.05). In contrast, the degree of HLA-DR expression was higher in gram-positive than in gram-negative bacteria (216.61±131.35 vs. 135.05±31, 82; p=0.041) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>There were no differences in the expression of HLA-DR in terms of overall survival in the patients (survivors 19.7±3.8 vs. non-survivors 25.0±5.4; p=0.594).Finally, HLA-DR expression on monocytes did not show significant differences between the septic patients and control groups: healthy individuals (88.60±5.55 vs. 89.98±5.59; p=0.535) and patients with SIRS (110±10.7; p=0.317).ROC curve analysis for HLA-DR expression in septic patients and healthy controls had an area under the curve (AUC) of 0.962. We found a cut-off value for HLA-DR expression of 10.91%, being the sensitivity and specificity of 0.95 and 0.95, respectively. The positive predictive value (PPV) was of 0.96 and the negative predictive value (NPV) of 0.94. The MFI of HLA-DR in the 26 septic patients had an AUC of 0.471.DiscussionOur study shows evidences regarding the use of surface expression of HLA-DR molecule on T-lymphocytes as a quick and effective marker for the early detection of non-surgical sepsis. Likewise, our data are consistent with those described in post-surgical patients who developed severe sepsis.<a class="elsevierStyleCrossRef" href="#bib0085">8</a> We found lymphopenia and increased HLA-DR expression on T-lymphocytes at the first day upon admission in ICU. Conversely, we did not find any change in the number of peripheral monocytes. However, there are conflicting results in previous reports about the percentage of CD3+/DR+ lymphocytes in non-surgical sepsis.<a class="elsevierStyleCrossRefs" href="#bib0070">5,6</a> Holub et al. did not find significant differences of HLA-DR expression on CD3+ T-lymphocytes in early stages of non-surgical sepsis.<a class="elsevierStyleCrossRefs" href="#bib0070">5,8</a> However, they described an increment in the count of CD3+/DR+ lymphocytes at the seventh day after admission.<a class="elsevierStyleCrossRef" href="#bib0070">5</a> These differences between our results and those described by Holub et al. could be explained, at least in part, for the main type of sepsis in the enrolled patients, purulent meningitis caused by Neisseria meningitides and Streptococcus pneumoniae<a class="elsevierStyleCrossRef" href="#bib0070">5</a> in contrast to the main type sepsis found in our study (E. coli and S. aureus). In the monocyte compartment, we did not find signs of immunosuppression since HLA-DR expression in patients with sepsis was similar to the control groups.<a class="elsevierStyleCrossRef" href="#bib0090">9</a>ConclusionsThese results suggest that increased expression of HLA-DR on T-lymphocytes is a phenomenon that occurs early and enables and early identification of sepsis at least in non-surgical patients. Although there is a limitation is the low number of patients enrolled, and therefore further studies will bee necessary to support our findings.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Conflict of interestThe authors declare no financial or commercial conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1182825" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1103482" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1182824" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1103481" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-01-17" "fechaAceptado" => "2018-07-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1103482" "palabras" => array:3 [ 0 => "Sepsis" 1 => "HLA-DR" 2 => "T-lymphocytes" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1103481" "palabras" => array:3 [ 0 => "Sepsis" 1 => "HLA-DR" 2 => "Linfocitos T" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionEarly detection of sepsis is a critical step to improve patient's survival and cellular markers effective diagnosis tools. The aim of this work was to evaluate HLA-DR expression on peripheral T-lymphocytes (CD3+), a marker associate to T-cell activation, as an early sepsis detection tool. Patients and methodsA cross-sectional study was conducted in twenty-six patients with confirmed sepsis by blood culture, eighteen healthy individuals and four patients with systemic inflammatory response syndrome. The analysis of the HLA-DR expression was carried by flow cytometry. ResultsThe patients with confirmed sepsis had significantly higher percentage of CD3+/HLA-DR+ lymphocytes compared with both, patients with SIRS (20.37±9.42 vs. 8.7±2.9; p<0.005) and healthy individuals (20.37±9.42 vs. 6.58±3.89; p<0.005). Moreover, the average amount of HLA-DR expressed was higher when caused by gram-positive than by gram-negative bacterias (216.61±131.35 vs. 135.05±31.82; p=0.041). A ROC curve analysis showed the utility of HLA-DR expression on T-cells to identify patients with sepsis. DiscussionOur results suggest that surface expression of HLA-DR on T-lymphocytes could be an early marker for the presence of sepsis in non-surgical septic patients." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa detección temprana de la sepsis es un paso crítico para mejorar la supervivencia del paciente. Nuestro objetivo fue evaluar la expresión de HLA-DR en linfocitos T periféricos (CD3+), marcador asociado a la activación de células T, como herramienta de detección temprana de la sepsis. Pacientes y métodosSe realizó un estudio en 26 pacientes con sepsis confirmada, 18 sanos y 4 con síndrome de respuesta inflamatoria sistémica(SIRS). La expresión de HLA-DR se midió por citometría de flujo. ResultadosLos pacientes con sepsis tenían un porcentaje significativamente mayor de linfocitos CD3+/HLA-DR+ en comparación con los otros grupos, pacientes con SIRS (20,37±9,42 vs. 8,7±2,9; p<0,005) y sanos (20,37±9,42 vs. 6,58±3,89; p<0,005). La cantidad media de HLA-DR fue mayor cuando la sepsis estaba causada por bacterias gram-positivas que por gram-negativas (216,61±131,35 vs. 135,05±31,82; p=0,041). El análisis mediante curva ROC mostró la utilidad de la expresión de HLA-DR en células T para identificar pacientes con sepsis. DiscusiónNuestros resultados sugieren que la expresión de HLA-DR en linfocitos T podría ser un marcador temprano de sepsis en pacientes sépticos no quirúrgicos." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 712 "Ancho" => 1005 "Tamanyo" => 40226 ] ] "descripcion" => array:1 [ "en" => "Percentage of CD3+/DR+ T-lymphocytes into the group of patients with sepsis (SP), patients with SIRS (NSP) and healthy controls (HC). In the dot plots, horizontal bars represent the mean value." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 724 "Ancho" => 2504 "Tamanyo" => 71599 ] ] "descripcion" => array:1 [ "en" => "(A) Degree of HLA-DR expression in CD3+ T-cells according to the type of sepsis (gram-positive, N=10; and gram-negative, N=16). (B) Data are represented as the mean±SD of HLA-DR expression degree in gram-positive and gram-negative groups. *p<0.041." ] ] 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" => "Abbreviations: CRP, C-reactive protein; F, female; M, male; NA, not available; NS, non-survivor; PCT, procalcitonin; S, survivor." "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (years), sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Aetiology \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CRP (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCT (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fibrinogen (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">88, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">720 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. aureus, E. faecalis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">574 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. epidermidis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">864 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. epidermidis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">83, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">910 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">78, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. aeroginosa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">654 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. epidermidis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">440 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Klebsiella spp. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">607 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">784 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">81, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. faecium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">793 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">78, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">675 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. pyogenes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">785 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. mirabilis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">351 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">582 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. capitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">555 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">703 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">830 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">764 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47, M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S. aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">230 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18, F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E. coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">552 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" 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Brief report

Enhanced HLA-DR expression on T-lymphocytes from patients in early stages of non-surgical sepsis

Elevada expresión de HLA-DR en linfocitos T de pacientes en fases tempranas de sepsis no quirúrgica

Esther Fernández-Grandea,

Corresponding author

e.fernandezgrande@gmail.com

Corresponding author.

, Carmen María Cabrerac, Blanca Gonzáleza, Carolina Varelad, José Miguel Urraa,b

a Immunology, Hospital General Universitario de Ciudad Real, Spain

b Medicine Faculty-Ciudad Real, Universidad de Castilla La Mancha, Spain

c Immunology, Hospital Regional Universitario Carlos Haya, Málaga, Spain

d Preventive Medicine, Hospital General Universitario de Ciudad Real, Spain

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        "titulo" => "Elevada expresi&#243;n de HLA-DR en linfocitos T de pacientes en fases tempranas de sepsis no quir&#250;rgica"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Percentage of CD3<span class="elsevierStyleSup">&#43;</span>&#47;DR<span class="elsevierStyleSup">&#43;</span> T-lymphocytes into the group of patients with sepsis &#40;SP&#41;&#44; patients with SIRS &#40;NSP&#41; and healthy controls &#40;HC&#41;&#46; In the dot plots&#44; horizontal bars represent the mean value&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Sepsis is defined as the presence of infection&#44; documented or suspected&#44; together with systemic manifestations of infection&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> The early identification of sepsis and implementation of early evidence-based therapies have been documented to improve outcomes and decrease sepsis-related mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> Reducing the diagnostic time of severe sepsis it is thought to be a critical component for reducing mortality as well as multiple organ dysfunctions&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Different biomarkers have been employed to achieve an early diagnosis of sepsis&#44; such as procalcitonin &#40;PCT&#41; and C-reactive protein &#40;CRP&#41; as the major traditional markers of bacterial sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> Apart from white cell count&#44; there is limited information concerning to the use of cellular markers in the diagnosis of sepsis&#46; Thus&#44; a decreased HLA-DR expression on monocytes from septic patients has been associated with the immunosuppression developed in the clinical course of sepsis&#44; and consequently with an increased mortality rate&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> Similarly&#44; the expression of HLA-DR molecule on T-lymphocytes has been previously investigated in sepsis with contradictory results&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5&#44;6</span></a> Hence this study was determinate to evaluate the expression of HLA-DR on peripheral T-lymphocytes as a cellular marker of early diagnosis in non-surgical septic patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">A cross sectional study was conducted over a period of six months&#46; The subjects were classified in three groups&#58; &#40;a&#41; patients with confirmed sepsis &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#59; &#40;b&#41; patients with SIRS and negative blood culture &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; with a median age 69&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;98 years&#41;&#44; and &#40;c&#41; healthy individuals &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#41; matched in age to patients &#40;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;75 years&#41;&#46; The absence of infectious disease in the healthy controls was confirmed by serological tests&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">All the patients included were diagnosed of non-surgical sepsis according to the International Guidelines for Management of Severe Sepsis and Septic Shock<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> and met at least two of the following criteria for SIRS&#58; body temperature greater than 38<span class="elsevierStyleHsp" style=""></span>&#176;C or less than 36<span class="elsevierStyleHsp" style=""></span>&#176;C&#59; heart rate of greater than 90<span class="elsevierStyleHsp" style=""></span>beats&#47;min&#59; respiratory rate of greater than 20<span class="elsevierStyleHsp" style=""></span>breaths&#47;min or PaCO<span class="elsevierStyleInf">2</span> of less than 32<span class="elsevierStyleHsp" style=""></span>mmHg&#59; and white blood cell count of greater than 12&#44;000<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L or less than 4000<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The microbiological infection was confirmed by isolation of the pathogenic bacteria from the blood cultures&#46; And the clinical course of sepsis was determined by the quantification of the serum levels of CRP&#44; PCT and fibrinogen as acute phase reactants&#46; All participants in the study were adequately informed and consented to participate in the study&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The analysis of the HLA-DR expression on T-lymphocytes and monocytes was carried out at the first day upon admission to the Infectious Disease Unit of the General University Hospital of Ciudad Real by collecting 4<span class="elsevierStyleHsp" style=""></span>mL of peripheral blood samples per patient&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">To study the surface expression by flow cytometry&#44; the following monoclonal antibodies were used&#58; fluorescein isothiocyanate &#40;FITC&#41; conjugated anti-human CD3 &#40;clone SK7&#41; and phycoerythrin anti-human HLA-DR &#40;PE clone L243&#41; purchased from Becton Dickinson &#40;BD San Jos&#233;&#44; USA&#41;&#46; Lymphocytes were acquired in a FACScan cytometer &#40;BD&#41; and analysed with the CellQuest Pro software &#40;BD&#41; as described in Cabrera et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> For each sample&#44; a negative control was defined adding the same isotype-matched mouse anti-human monoclonal antibody&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Data on HLA-DR expression were analysed by the non-parametric Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span>-test after a significant result for the Kruskal&#8211;Wallis analysis when comparing the three populations&#46; The relationships between the percentage of lymphocytes and serum levels of CRP and PCT were analysed by the Spearman correlation coefficient&#46; Statistical Package for the Social Sciences &#40;SPSS Chicago&#44; USA&#41; version 22&#46;0 was used for statistical analysis&#46; The differences were considered statistically significant at <span class="elsevierStyleItalic">p</span> values of less than 0&#46;05&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">Twenty three out of 26 septic patients &#40;88&#46;4&#37;&#41; showed serum levels of CRP above the upper threshold of normal range &#40;&#60;1<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; The mean value was of 10&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;35<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The mean value of fibrinogen was of 628&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>37&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; 18 out of 24 patients &#40;75&#37;&#41; showed values above the upper threshold of normal range &#40;200&#8211;500<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; In 14 out of 18 of septic patients &#40;77&#46;8&#37;&#41; the serum levels of PCT were above the normal limit &#40;PCT &#60;0&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Regarding to the aetiology of the isolated bacteria in the septic patients&#44; gram-negative sepsis was found in 59&#46;25&#37; and 40&#46;74&#37; for gram-positive sepsis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; <span class="elsevierStyleItalic">Escherichia coli</span> &#40;12&#47;27&#44; 44&#46;4&#37;&#41; and <span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;4&#47;27&#44; 14&#46;8&#37;&#41; were the most frequent gram-negative and gram-positive bacterial infection&#44; respectively&#46; No differences were found in serum levels of CRP&#44; PCT or fibrinogen among the type of sepsis &#40;gram-positive and gram-negative&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;75&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;18&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05 respectively&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The control group of patients with SIRS had serum levels of CRP above the normality upper threshold&#44; with a mean value for CRP of 14&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and fibrinogen of 615&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>92&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; Moreover&#44; in 2 out of 4 patients with SIRS the serum levels of PCT were above the normal limit&#46; Healthy individuals did not show any alteration in these parameters&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Lymphocyte counts in peripheral blood samples showed a significant decrement &#40;lymphopenia&#41; in the septic patients &#40;1250<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>561<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L&#41; and patients with SIRS &#40;1200<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>361<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L&#41; in contrast to the healthy individuals &#40;2360<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>288<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; However&#44; no differences were evidenced in the number of monocytes in septic patients &#40;583<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>297<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L&#41;&#44; patients with SIRS &#40;720<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>311<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L&#41; and healthy individuals &#40;440<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>194<span class="elsevierStyleHsp" style=""></span>cells&#47;&#956;L&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> the septic patients showed increased percentage of CD3<span class="elsevierStyleSup">&#43;</span>&#47;DR<span class="elsevierStyleSup">&#43;</span> T-lymphocytes compared to healthy individuals &#40;20&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;42 <span class="elsevierStyleItalic">vs&#46;</span> 6&#46;58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;89&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41; and to patients with SIRS &#40;20&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;42 <span class="elsevierStyleItalic">vs</span>&#46; 8&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;9&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; However&#44; the degree of HLA-DR expression on CD3<span class="elsevierStyleSup">&#43;</span> T-cells&#44; determined by mean fluorescence intensity &#40;MFI&#41;&#44; did not show significant differences between groups &#40;166&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>91&#46;6 for septic patients&#59; 181&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>70&#46;1 for SIRS patients and 161&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#46;52 in healthy controls&#41;&#46; No correlations were found between the CD3<span class="elsevierStyleSup">&#43;</span>&#47;DR<span class="elsevierStyleSup">&#43;</span> T-lymphocytes and serum levels of CRP or PCT in septic patients&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In addition&#44; no significant differences were found between the percentage of HLA-DR expression on T-lymphocytes from patients with sepsis caused by gram-positive &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41; or patients with sepsis caused by gram-negative bacteria &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; &#40;19&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;57 <span class="elsevierStyleItalic">vs</span>&#46; 20&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;63&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; In contrast&#44; the degree of HLA-DR expression was higher in gram-positive than in gram-negative bacteria &#40;216&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>131&#46;35 <span class="elsevierStyleItalic">vs&#46;</span> 135&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#44; 82&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;041&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">There were no differences in the expression of HLA-DR in terms of overall survival in the patients &#40;survivors 19&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;8 <span class="elsevierStyleItalic">vs&#46;</span> non-survivors 25&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;4&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;594&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Finally&#44; HLA-DR expression on monocytes did not show significant differences between the septic patients and control groups&#58; healthy individuals &#40;88&#46;60<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;55 <span class="elsevierStyleItalic">vs</span>&#46; 89&#46;98<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;59&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;535&#41; and patients with SIRS &#40;110<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;7&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;317&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">ROC curve analysis for HLA-DR expression in septic patients and healthy controls had an area under the curve &#40;AUC&#41; of 0&#46;962&#46; We found a cut-off value for HLA-DR expression of 10&#46;91&#37;&#44; being the sensitivity and specificity of 0&#46;95 and 0&#46;95&#44; respectively&#46; The positive predictive value &#40;PPV&#41; was of 0&#46;96 and the negative predictive value &#40;NPV&#41; of 0&#46;94&#46; The MFI of HLA-DR in the 26 septic patients had an AUC of 0&#46;471&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">Our study shows evidences regarding the use of surface expression of HLA-DR molecule on T-lymphocytes as a quick and effective marker for the early detection of non-surgical sepsis&#46; Likewise&#44; our data are consistent with those described in post-surgical patients who developed severe sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> We found lymphopenia and increased HLA-DR expression on T-lymphocytes at the first day upon admission in ICU&#46; Conversely&#44; we did not find any change in the number of peripheral monocytes&#46; However&#44; there are conflicting results in previous reports about the percentage of CD3<span class="elsevierStyleSup">&#43;</span>&#47;DR<span class="elsevierStyleSup">&#43;</span> lymphocytes in non-surgical sepsis&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5&#44;6</span></a> Holub et al&#46; did not find significant differences of HLA-DR expression on CD3<span class="elsevierStyleSup">&#43;</span> T-lymphocytes in early stages of non-surgical sepsis&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5&#44;8</span></a> However&#44; they described an increment in the count of CD3<span class="elsevierStyleSup">&#43;</span>&#47;DR<span class="elsevierStyleSup">&#43;</span> lymphocytes at the seventh day after admission&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> These differences between our results and those described by Holub et al&#46; could be explained&#44; at least in part&#44; for the main type of sepsis in the enrolled patients&#44; purulent meningitis caused by <span class="elsevierStyleItalic">Neisseria meningitides</span> and <span class="elsevierStyleItalic">Streptococcus pneumoniae</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> in contrast to the main type sepsis found in our study &#40;<span class="elsevierStyleItalic">E&#46; coli</span> and <span class="elsevierStyleItalic">S&#46; aureus</span>&#41;&#46; In the monocyte compartment&#44; we did not find signs of immunosuppression since HLA-DR expression in patients with sepsis was similar to the control groups&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">These results suggest that increased expression of HLA-DR on T-lymphocytes is a phenomenon that occurs early and enables and early identification of sepsis at least in non-surgical patients&#46; Although there is a limitation is the low number of patients enrolled&#44; and therefore further studies will bee necessary to support our findings&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare no financial or commercial conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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              "identificador" => "abst0025"
              "titulo" => "Introducci&#243;n"
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              "titulo" => "Pacientes y m&#233;todos"
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              "titulo" => "Resultados"
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          "titulo" => "Palabras clave"
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    "fechaRecibido" => "2018-01-17"
    "fechaAceptado" => "2018-07-16"
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            0 => "Sepsis"
            1 => "HLA-DR"
            2 => "T-lymphocytes"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Early detection of sepsis is a critical step to improve patient&#39;s survival and cellular markers effective diagnosis tools&#46; The aim of this work was to evaluate HLA-DR expression on peripheral T-lymphocytes &#40;CD3<span class="elsevierStyleSup">&#43;</span>&#41;&#44; a marker associate to T-cell activation&#44; as an early sepsis detection tool&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional study was conducted in twenty-six patients with confirmed sepsis by blood culture&#44; eighteen healthy individuals and four patients with systemic inflammatory response syndrome&#46; The analysis of the HLA-DR expression was carried by flow cytometry&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The patients with confirmed sepsis had significantly higher percentage of CD3<span class="elsevierStyleSup">&#43;</span>&#47;HLA-DR<span class="elsevierStyleSup">&#43;</span> lymphocytes compared with both&#44; patients with SIRS &#40;20&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;42 <span class="elsevierStyleItalic">vs&#46;</span> 8&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;9&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41; and healthy individuals &#40;20&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;42 <span class="elsevierStyleItalic">vs&#46;</span> 6&#46;58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;89&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; Moreover&#44; the average amount of HLA-DR expressed was higher when caused by gram-positive than by gram-negative bacterias &#40;216&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>131&#46;35 <span class="elsevierStyleItalic">vs&#46;</span> 135&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#46;82&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;041&#41;&#46; A ROC curve analysis showed the utility of HLA-DR expression on T-cells to identify patients with sepsis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our results suggest that surface expression of HLA-DR on T-lymphocytes could be an early marker for the presence of sepsis in non-surgical septic patients&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0005"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La detecci&#243;n temprana de la sepsis es un paso cr&#237;tico para mejorar la supervivencia del paciente&#46; Nuestro objetivo fue evaluar la expresi&#243;n de HLA-DR en linfocitos T perif&#233;ricos &#40;CD3<span class="elsevierStyleSup">&#43;</span>&#41;&#44; marcador asociado a la activaci&#243;n de c&#233;lulas T&#44; como herramienta de detecci&#243;n temprana de la sepsis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio en 26 pacientes con sepsis confirmada&#44; 18 sanos y 4 con s&#237;ndrome de respuesta inflamatoria sist&#233;mica&#40;SIRS&#41;&#46; La expresi&#243;n de HLA-DR se midi&#243; por citometr&#237;a de flujo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con sepsis ten&#237;an un porcentaje significativamente mayor de linfocitos CD3<span class="elsevierStyleSup">&#43;</span>&#47;HLA-DR<span class="elsevierStyleSup">&#43;</span> en comparaci&#243;n con los otros grupos&#44; pacientes con SIRS &#40;20&#44;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;42 <span class="elsevierStyleItalic">vs&#46;</span> 8&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;9&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;005&#41; y sanos &#40;20&#44;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;42 <span class="elsevierStyleItalic">vs&#46;</span> 6&#44;58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;89&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;005&#41;&#46; La cantidad media de HLA-DR fue mayor cuando la sepsis estaba causada por bacterias gram-positivas que por gram-negativas &#40;216&#44;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>131&#44;35 <span class="elsevierStyleItalic">vs</span>&#46; 135&#44;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#44;82&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;041&#41;&#46; El an&#225;lisis mediante curva ROC mostr&#243; la utilidad de la expresi&#243;n de HLA-DR en c&#233;lulas T para identificar pacientes con sepsis&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestros resultados sugieren que la expresi&#243;n de HLA-DR en linfocitos T podr&#237;a ser un marcador temprano de sepsis en pacientes s&#233;pticos no quir&#250;rgicos&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Percentage of CD3<span class="elsevierStyleSup">&#43;</span>&#47;DR<span class="elsevierStyleSup">&#43;</span> T-lymphocytes into the group of patients with sepsis &#40;SP&#41;&#44; patients with SIRS &#40;NSP&#41; and healthy controls &#40;HC&#41;&#46; In the dot plots&#44; horizontal bars represent the mean value&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Degree of HLA-DR expression in CD3&#43; T-cells according to the type of sepsis &#40;gram-positive&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#59; and gram-negative&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#46; &#40;B&#41; Data are represented as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD of HLA-DR expression degree in gram-positive and gram-negative groups&#46; &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;041&#46;</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; CRP&#44; C-reactive protein&#59; F&#44; female&#59; M&#44; male&#59; NA&#44; not available&#59; NS&#44; non-survivor&#59; PCT&#44; procalcitonin&#59; S&#44; survivor&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age &#40;years&#41;&#44; sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Aetiology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CRP &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCT &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fibrinogen &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">720&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; aureus</span>&#44; <span class="elsevierStyleItalic">E&#46; faecalis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">574&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; epidermidis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">864&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; epidermidis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">83&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">910&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">78&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P&#46; aeroginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">654&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; epidermidis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">440&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Klebsiella</span> spp&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">607&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">784&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">81&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; faecium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">793&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">78&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">675&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; pyogenes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">785&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P&#46; mirabilis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">351&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">582&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; capitis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">555&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">703&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">830&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">72&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">764&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">230&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">552&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">M&#46; morganii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">576&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">83&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">S&#46; aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">486&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85&#44; F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">402&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&#44; M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">E&#46; coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">704&nbsp;\t\t\t\t\t\t\n
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