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All <span class="elsevierStyleItalic">p</span>-values lower than 0.012 were statistically significant after Bonferroni correction.</p>" ] ] ] "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 associated with considerable resource consumption, and mortality.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">1,2</span></a> Findings as the presence of elevated tissue oxygen concentrations in skeletal muscle of septic patients<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">3,4</span></a> and that non-survivor septic patients did not response with an increase in tissue oxygen consumption following to the increase of oxygen delivery<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">5</span></a> rise the theory that during sepsis there is a mitochondrial dysfunction leading to a cellular inability to use oxygen.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">6</span></a> Most of oxygen delivered to tissues is consumed by the mitochondrial respiratory chain of the oxidative phosphorylation (OXPHOS) system to produce adenosine triphosphate (ATP), and the respiratory complex IV (CIV) or cytochrome c oxidase is the highest responsible of this oxygen consumption.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The mitochondrial dysfunction has been scarcely analyzed in patients with sepsis, and the most of studies with small sample size.<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">7–27</span></a> In addition, the influence of mitochondrial deoxyribonucleic acid (mtDNA) haplogroup on survival of septic patients has been scarcely studied.<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">28–32</span></a> Previously, our team found that non-surviving septic patients showed lower platelet respiratory complex IV (CIV) specific activity than survivors at the time of severe sepsis diagnosis<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">25</span></a> and during the first week of severe sepsis,<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">26</span></a> and that septic patients showed lower platelet CIV specific activity than healthy controls.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">27</span></a> In addition, our team found that patients with mtDNA haplogroup JT compared with other haplogropus showed higher survival at 1 month<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">30</span></a> and 6 months,<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">31</span></a> and higher platelet CIV specific activity.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a> However, the comparison on mitochondrial function between severe septic patients and healthy control subjects according to mtDNA haplogroup has been not previously reported; and this was the objective of the current study.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design and subjects</span><p id="par0015" class="elsevierStylePara elsevierViewall">This prospective, multicenter, and observational study was carried our in six Intensive Care Units (ICUs) from Spain. The study was approved by the Institutional Ethic Review Boards of all hospitals: San Jorge (Huesca), Clínico Universitario de Valencia (Valencia), Universitario de Canarias (La Laguna. Tenerife), Insular (Las Palmas de Gran Canaria), Universitario Dr. Negrín (Las Palmas de Gran Canaria), Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife). Patients or family members signed the informed consent to participate in the study.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We included 198 patients with severe sepsis diagnosed according to the International Sepsis Definitions Conference criteria.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">33</span></a> We excluded patients with white blood cell count <1000<span class="elsevierStyleHsp" style=""></span>cells/μl, human immunodeficiency virus (HIV), solid or hematological tumor, steroid or immunosuppressive or radiation therapy, age <18 years, lactation, pregnancy and platelet transfusion. We also included 96 sex- and age-matched healthy subject controls.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The same cohort of severe septic patients was used in previous publications by our team to compare platelet CIV specific activity between surviving and non-surviving severe septic patients and between septic patients and healthy controls, and to compare severe sepsis survival and platelet CIV specific activity according to mtDNA.<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">25,30–32</span></a> In the current analysis, we compare mitochondrial function between severe septic patients and healthy control subjects according to mtDNA haplogroup due to it has not been previously reported.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Determination of mtDNA haplogroup and platelet CIV specific activity</span><p id="par0030" class="elsevierStylePara elsevierViewall">We recollected blood samples from healthy controls and from severe septic patients at days 1, 4 and 8 of the diagnois of severe sepsis, and then were frozen at −80<span class="elsevierStyleHsp" style=""></span>°C. The determination of mtDNA haplogroup and platelet CIV specific activity was centralized in the Departamento de Bioquímica y Biología Molecular y Celular of the Centro de Investigaciones Biomédicas En Red de Enfermedades Raras (CIBERER) e Instituto de Investigación Sanitaria de Aragón (Universidad de Zaragoza. Zaragoza. Spain).</p><p id="par0035" class="elsevierStylePara elsevierViewall">For the determination of mtDNA haplogroup determination was used real time-polymerase chain reaction. In all blood samples were genotyped three single nucleotide polymorphisms (m.4216C, m.7028C and m.12308G) that define very frequent haplogroups (JT, H and U). We analyzed other 14 mtDNA single nucleotide polymorphisms (m.15693C, m.15257A, m.15218G, m.14798C, m.14793G, m.14766C, m.13708A, m.10873C, m.9477A, m.4769A, m.4580A, m.4336C, m.3010A, m.1811G) by an hierarchic approach to determine each particular haplogroup.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">34</span></a> We considered patients with mtDNA haplogroup non-JT to those patients with a mtDNA haplogroup different to JT.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In respect to platelet CIV specific activity, first we obtained platelets according to a protocol previously described.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">35</span></a> We determined protein levels using a protocol previously described,<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">36</span></a> and CIV activity by means of Mitoprofile Human Complex IV Activity kit (Mitosciences, Invitrogen, Carlsbad, CA). CIV specific activity was expressed as milli-optic density/min/mg multiplied by 100.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">We reported categorical variables in form of frequencies and percentages, and continuous variables in form of medians and interquartile ranges. We compared categorical variables between groups using chi-square test, and continuous variables by Wilcoxon–Mann–Whitney test. All <span class="elsevierStyleItalic">P</span> values lower than 0.05 were considered statistically significant; and Bonferroni correction was used to correct multiple comparisons in repeated measures. The statistical analyses were performed with SPSS v. 17.0 (SPSS Inc., Chicago, IL, USA) and Med Calc v. 10.1.3.0 (Mariakerke, Belgium) programs.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">We included 198 severe septic patients, 38 with mtDNA haplogroup JT and 160 with mtDNA haplogroup non-JT (80 HV, 51 U and 29 Non-R). We also included 96 healthy control subjects, 16 with DNAmt haplogroup JT and 80 with mtDNA haplogroup non-JT (26 HV, 42 U and 12 Non-R).</p><p id="par0055" class="elsevierStylePara elsevierViewall">There were not statistically significant differences in age, sex and platelet CIV specific activity between healthy control subjects with mtDNA haplogroup JT and other mtDNA haplogroups (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">We no found statistically significant differences in age and sex between healthy control subjects and severe septic patients with mtDNA haplogroup JT; however, severe septic patients showed lower platelet CIV specific activity (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.006) than healthy control subjects (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">There were not statistically significant differences in age and sex between healthy control subjects and severe septic patients with mtDNA haplogroup non-JT; however, severe septic patients showed lower platelet CIV specific activity (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) than healthy control subjects (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows platelet CIV specific activity in healthy controls, and survivor and non-survivor severe septic patients during follow up according to mtDNA haplogroup. We found that healthy control subjects with mtDNA haplogroup non-JT showed higher platelet CIV specific activity than survivor and non-survivor severe septic patients with mtDNA haplogroup non-JT at days 1, 4 and 8 of severe sepsis diagnosis. We found that healthy control subjects with mtDNA haplogroup JT showed higher platelet CIV specific activity than non-survivor severe septic patients with mtDNA haplogroup JT at days 1, 4 and 8 of severe sepsis diagnosis; however, we have no found statistically significant differences in platelet CIV specific activity between healthy control subjects and survivor severe septic patients with mtDNA haplogroup JT at days 1, 4 and 8 of severe sepsis diagnosis.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first study reporting the comparison on mitochondrial function between severe septic patients and healthy control subjects according to mtDNA haplogroup. The novel findings of our study were the following: 1) Healthy control subjects with mtDNA haplogroup non-JT showed higher platelet CIV specific activity than survivors and non-survivors severe septic patients with mtDNA haplogroup non-JT during the first week of severe sepsis diagnosis; 2) Healthy control subjects with mtDNA haplogroup JT showed higher platelet CIV specific activity than non-survivors severe septic patients with mtDNA haplogroup JT during the first week of severe sepsis diagnosis; 3) There were not found differences in platelet CIV specific activity between healthy control subjects and survivor severe septic patients with mtDNA haplogroup JT during the first week of severe sepsis diagnosis.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Previously, there was reported a lower OXPHOS function in septic patients compared to healthy control subjects in muscle,<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">7–11</span></a> in peripheral blood mononuclear cells<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">13,15–17</span></a> and in circulating platelets.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">20,21,23,24,27</span></a> In addition, there was found a lower OXPHOS function in circulating platelets in non-survivor than in survivor septic patients.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">21,25,26</span></a> Besides, there was found an association between mtDNA haplogroup and survival rate in septic patients,<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">28–32</span></a> and an association between mtDNA haplogroup and platelet CIV specific activity.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a> Thus, the more important and new finding of our study was that survivor severe septic patients with mtDNA haplogroup jt showed no different platelet Civ specific activity than healthy control subjects with mtDNA haplogroup jt; and that the remaining severe septic patients showed lower platelet CIV specific activity than healthy control subjects with the same mtDNA haplogroup. Then, it is possible that in some patients the mtDNA haplogroup jt could helps them to maintain the OXPHOS function and survive to severe sepsis; however, in other patients with mtDNA haplogroup jt, the apparently beneficial mtDNA haplogroup cannot compensate the sepsis process and the patients do not survive to sepsis. Finally, we think that is biologically plausible that patients with mtDNA haplogroup JT (polymorphism) have lower mitochondrial dysfunction during sepsis (intermediate phenotype) and lower risk of death during sepsis (clinical phenotype).</p><p id="par0085" class="elsevierStylePara elsevierViewall">We think that the findings of our study could have clinical implication in respect to prognosis and treatment of septic patients. We think that the findings of our study could suggest that the determination of the mtDNA haplogroup could help in the estimation of septic patients who have more risk of death, could increase the interest for research on how improve mitochondrial function in septic patients with unfavorable mtDNA haplogroup and could help in the selection of patients who may benefit of agents used with that intention.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Our study showed some limitations. First, there were not analyzed ATP synthesis, other mitochondrial respiratory complexes, <span class="elsevierStyleItalic">mixed venous oxygen saturation</span> (SvO<span class="elsevierStyleInf">2</span>), mitochondrial inner membrane potential, or reactive oxygen species (ROS) to explore the function of OXPHOS system. Second, there was not analyzed mitochondrial function in other cells. Third, as the study was developed before to the new criteria of sepsis,<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">37</span></a> we used the previous sepsis criteria.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0095" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first study reporting the comparison on mitochondrial function between severe septic patients and healthy control subjects according to mtDNA haplogroup. The more important and new finding of our study was that survivor severe septic patients and healthy control subjects with mtDNA haplogroup jt showed no different platelet CIV specific activity; and that the remaining severe septic patients showed lower platelet CIV specific activity than healthy control subjects with the same mtDNA haplogroup.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0100" class="elsevierStylePara elsevierViewall">This study was supported by grants from <span class="elsevierStyleGrantSponsor" id="gs1">Instituto de Salud Carlos III</span> (<span class="elsevierStyleGrantNumber" refid="gs1">PI-14-00005</span>, <span class="elsevierStyleGrantNumber" refid="gs1">PI-14-00070</span>, and <span class="elsevierStyleGrantNumber" refid="gs1">INT16/00165</span>) (Madrid, Spain) and co-financed with Fondo Europeo de Desarrollo Regional (<span class="elsevierStyleGrantSponsor" id="gs2">FEDER</span>).</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have no competing interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1100751" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1041676" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1100750" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1041677" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design and subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Determination of mtDNA haplogroup and platelet CIV specific activity" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interests" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-28" "fechaAceptado" => "2017-08-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1041676" "palabras" => array:5 [ 0 => "Mitochondria" 1 => "mtDNA" 2 => "Cytochrome c oxidase" 3 => "Sepsis" 4 => "Mortality" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1041677" "palabras" => array:5 [ 0 => "Mitocondria" 1 => "ADNmt" 2 => "Citocromo c oxidasa" 3 => "Sepsis" 4 => "Mortalidad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The comparison on mitochondrial function between severe septic patients and healthy control subjects according to mitochondrial deoxyribonucleic acid (mtDNA) haplogroup has not been previously reported; and this was the objective of the current study.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective, multicenter, observational study. We obtained blood samples from 198 severe septic patients at days 1, 4 and 8 of severe sepsis diagnosis and from 96 sex- and age-matched healthy controls to determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific activity. The endpoint of the study was 30-day mortality.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We included 198 severe septic patients (38 with mtDNA haplogroup JT and 160 with mtDNA haplogroup non-JT) and 96 healthy control subjects (16 with mtDNA haplogroup JT and 80 with mtDNA haplogroup non-JT). We have no found statistically significant differences in platelet CIV specific activity between healthy controls and survivor severe septic patients with mtDNA haplogroup JT at days 1, 4 and 8 of severe sepsis diagnosis; and the remaining severe septic patients showed lower platelet CIV specific activity than healthy controls with the same mtDNA haplogroup.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The new finding of our study was that survivor severe septic patients and healthy controls with mtDNA haplogroup JT showed no different platelet Civ specific activity.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La comparación en la función mitocondrial entre pacientes con sepsis grave y sujetos sanos según el haplogrupo del ácido desoxirribonucleico mitocondrial (ADNmt) no se ha reportado previamente; y este fue el objetivo del estudio.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo, multicéntrico y observacional. Obtuvimos muestras sanguíneas de 198 pacientes con sepsis grave en los días 1, 4 y 8 del diagnóstico de la sepsis grave y de 96 sujetos sanos para determinar el haplogrupo del ADNmt y la actividad del complejo respiratorio mitocondrial IV (CIV) en plaquetas circulantes. La variable resultado principal del estudio fue la mortalidad a los 30 días.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 198 pacientes con sepsis grave (38 con haplogrupo JT del ADNmt y 160 con otro haplogrupo del ADNmt) y 96 sujetos sanos (16 con haplogrupo JT del ADNmt y 80 con otro haplogrupo del ADNmt). No encontramos diferencias estadísticamente significativas en la actividad de CIV plaquetaria entre los sujetos sanos y los pacientes sépticos supervivientes con haplogrupo JT del ADNmt en los días 1, 4 y 8 del diagnóstico de la sepsis grave; y el resto de los pacientes sépticos presentaron menor actividad de CIV plaquetaria que los sujetos sanos con su mismo haplogrupo del ADNmt.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El nuevo hallazgo de nuestro estudio fue que los pacientes sépticos y sujetos sanos con haplogrupo JT del ADNmt no tenían diferencias en la actividad de CIV plaquetaria.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">These authors equally contributed to this article.</p>" "identificador" => "fn1" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1282 "Ancho" => 1669 "Tamanyo" => 104545 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Platelet respiratory complex IV (CIV) specific activity in healthy controls and severe septic patients according to mtDNA haplogroup. All <span class="elsevierStyleItalic">p</span>-values lower than 0.012 were statistically significant after Bonferroni correction.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1625 "Ancho" => 2345 "Tamanyo" => 193672 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Platelet respiratory complex IV (CIV) specific activity in healthy controls, and survivor and non-survivor severe septic patients during follow up according to mtDNA haplogroup. The <span class="elsevierStyleItalic">p</span>-values for the comparisons on platelet CIV specific activities between healthy controls and severe septic patients were the following: <span class="elsevierStyleSup">‡</span><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04, <span class="elsevierStyleSup">**</span><span class="elsevierStyleItalic">p</span><<span class="elsevierStyleHsp" style=""></span>0.001, <span class="elsevierStyleSup">¶</span><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.15, <span class="elsevierStyleSup">*</span><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01. All <span class="elsevierStyleItalic">p</span>-values lower than 0.004 were statistically significant after Bonferroni correction.</p>" ] ] 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" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Platelet respiratory complex IV (CIV) specific activity is expressed as milli optical density/min/mg of protein.</p>" "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">JT haplogroup (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16) \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">Other haplogroup (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>80) \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"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex female – <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (50.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (33.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) – median (<span class="elsevierStyleItalic">p</span> 25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 (51–65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 (51–69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.92 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelet CIV activity – median (<span class="elsevierStyleItalic">p</span> 25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05 (0.80–1.23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.94 (0.78–1.07) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1883297.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Demografic variables in healthy controls subjects according to DNAmt haplogroup.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Platelet respiratory complex IV (CIV) specific activity is expressed as milli optical density/min/mg of protein.</p>" "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">JT haplogroup healthy controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16) \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">JT haplogroup septic patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>38) \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"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex female – n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (50.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (44.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) – median (<span class="elsevierStyleItalic">p</span> 25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 (51–65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 (49–71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.98 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelet CIV activity – median (<span class="elsevierStyleItalic">p</span> 25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05 (0.80–1.23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.49 (0.13–0.96) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1883298.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Demografic variables in healthy controls and severe septic patients with mtDNA haplogroup JT.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Platelet respiratory complex IV (CIV) specific activity is expressed as milli optical density/min/mg of protein.</p>" "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Non-JT haplogroup healthy controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>80) \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">Non-JT haplogroup septic patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>160) \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"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex female – n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (33.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 (31.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) – median (<span class="elsevierStyleItalic">p</span> 25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 (61–69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 (49–69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.66 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelet CIV activity – median (<span class="elsevierStyleItalic">p</span> 25–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.94 (0.78–1.07) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.17 (0.07–0.56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1883299.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Demografic variables in healthy controls and severe septic patients with mtDNA haplogroup non-JT.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0190" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sepsis in European intensive care units: results of the SOAP study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.L. 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Original article
Lower mitochondrial dysfunction in survivor septic patients with mitochondrial DNA haplogroup JT
Menor disfunción mitocondrial en pacientes septicos supervivientes con haplogrupo JT del ADN mitocondrial
Leonardo Lorentea,1,
, María M. Martínb, Ester López-Gallardoc, José Ferreresd, Jordi Solé-Violáne, Lorenzo Labartaf, César Díazg, Alejandro Jiménezh, Julio Montoyac, Eduardo Ruiz-Pesinii,1
Autor para correspondencia
a Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
b Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz de Tenerife, Spain
c Departamento de Bioquímica y Biología Molecular y Celular, Centro de Investigaciones Biomédicas En Red de Enfermedades Raras (CIBERER) e Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, Zaragoza, Spain
d Intensive Care Unit, Hospital Clínico Universitario de Valencia, Valencia, Spain
e Intensive Care Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain
f Intensive Care Unit, Hospital San Jorge de Huesca, Huesca, Spain
g Intensive Care Unit, Hospital Insular, Las Palmas de Gran Canaria, Spain
h Research Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
i Departamento de Bioquímica y Biología Molecular y Celular, Centro de Investigaciones Biomédicas En Red de Enfermedades Raras (CIBERER), Instituto de Investitación Sanitaria de Aragón y Fundación ARAID, Universidad de Zaragoza, Zaragoza, Spain
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