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Original
Concordancia entre la actividad clínica y los marcadores biológicos en la enfermedad inflamatoria intestinal
Evaluation of the concordance between biological markers and clinical activity in inflammatory bowel disease
Pablo Miranda Garcíaa,
Autor para correspondencia
pmpablomiranda@gmail.com

Autor para correspondencia.
, María Chaparrob, Javier P. Gisbertb
a Servicio de Aparato Digestivo, Hospital Universitario Quirón, Madrid, España
b Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, España
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el patr&#243;n oro para establecer la presencia de actividad de la EII son los hallazgos encontrados en la ileocolonoscopia<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; Lamentablemente&#44; se trata de una t&#233;cnica cara e invasiva&#44; por tanto&#44; no exenta de riesgos para el paciente&#44; y a veces poco accesible&#46; Por estos motivos&#44; desde hace a&#241;os se emplean los marcadores biol&#243;gicos serol&#243;gicos como indicadores indirectos para la monitorizaci&#243;n de la actividad de la EII<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; La mayor&#237;a de estos marcadores son reactantes de fase aguda inespec&#237;ficos&#44; que pueden verse elevados en procesos extradigestivos&#59; sin embargo&#44; tienen la ventaja de que son accesibles y baratos&#44; y por ello&#44; ampliamente utilizados<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; No obstante&#44; existen pocos estudios que hayan analizado simult&#225;neamente la utilidad de estos marcadores biol&#243;gicos en una poblaci&#243;n amplia de pacientes con EII&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">El objetivo de nuestro estudio fue evaluar la concordancia entre los diferentes marcadores biol&#243;gicos m&#225;s utilizados en la monitorizaci&#243;n de la EII &#40;prote&#237;na C reactiva &#91;PCR&#93;&#44; orosomucoide&#44; velocidad de sedimentaci&#243;n globular &#91;VSG&#93;&#44; fibrin&#243;geno&#44; plaquetas&#44; leucocitos&#44; neutr&#243;filos&#44; hemoglobina&#41; y la propia actividad cl&#237;nica de dicha enfermedad&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todo</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Pacientes</span><p id="par0020" class="elsevierStylePara elsevierViewall">Se realiz&#243; un estudio prospectivo y observacional en el que se incluyeron pacientes consecutivos que acudieron a las consultas de la Unidad de EII de nuestro hospital entre enero de 2010 y junio de 2011&#46; El estudio fue evaluado y aceptado por el Comit&#233; de &#201;tica de nuestro centro&#46; Se emple&#243; la clasificaci&#243;n de Montreal para definir las caracter&#237;sticas de la EC y la localizaci&#243;n de la CU&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Criterios de inclusi&#243;n</span><p id="par0025" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Diagn&#243;stico de EC o CU &#40;establecido en base a los criterios cl&#237;nicos&#44; radiol&#243;gicos&#44; histol&#243;gicos y endosc&#243;picos habituales&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Pacientes consecutivos que acudieron a consultas de EII de nuestro hospital desde enero de 2010 hasta junio de 2011&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Criterios de exclusi&#243;n</span><p id="par0040" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">1&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Ausencia de determinaciones anal&#237;ticas en la revisi&#243;n&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">2&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Negativa del paciente a participar en el estudio&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Recogida de datos&#58; actividad cl&#237;nica y marcadores biol&#243;gicos</span><p id="par0055" class="elsevierStylePara elsevierViewall">Durante la entrevista del m&#233;dico con el paciente se estableci&#243; la presencia y el grado de actividad cl&#237;nica en ese momento&#44; bas&#225;ndose en el &#237;ndice de Mayo parcial &#40;IMP&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41; para los pacientes con CU y en el &#237;ndice de Harvey-Bradshaw &#40;IHB&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41; para la EC&#46; Los pacientes hab&#237;an sido sometidos a determinaciones anal&#237;ticas entre 1 y 7 d&#237;as antes de la consulta&#44; de manera que los datos cl&#237;nicos y anal&#237;ticos &#40;PCR&#44; orosomucoide&#44; VSG&#44; fibrin&#243;geno&#44; plaquetas&#44; leucocitos&#44; neutr&#243;filos&#44; hemoglobina&#41; fueron recogidos prospectivamente en el momento de la entrevista con el paciente&#46; Se estim&#243; que los marcadores biol&#243;gicos se encontraban alterados si sus valores se hallaban por encima del l&#237;mite superior de la normalidad del laboratorio&#58; PCR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;08<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#59; VSG<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#59; orosomucoide<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>125<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; fibrin&#243;geno<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; leucocitos<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>12&#46;000&#47;mm<span class="elsevierStyleSup">3</span>&#59; neutr&#243;filos<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>7&#46;500&#47;mm<span class="elsevierStyleSup">3</span>&#59; plaquetas<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>400&#46;000&#47;mm<span class="elsevierStyleSup">3</span>&#59; hemoglobina<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>g&#47;dl en mujeres y<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>13<span class="elsevierStyleHsp" style=""></span>g&#47;dl en varones&#46; Se consider&#243; ausencia de actividad cl&#237;nica presentar un IHB<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>4 puntos y un IMP de 0 puntos&#59; brote leve&#44; un IHB de 5 puntos y un IMP entre 1-3 puntos&#59; brote moderado&#44; un IHB entre 6-12 puntos y un IMP entre 4-6 puntos&#59; y brote grave&#44; un IHB<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>12 puntos y un IMP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>6 puntos&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;stico</span><p id="par0060" class="elsevierStylePara elsevierViewall">Las variables cuantitativas se expresaron como media y desviaci&#243;n est&#225;ndar&#44; o mediana y rango intercuart&#237;lico&#44; dependiendo de si segu&#237;an o no una distribuci&#243;n normal<span class="elsevierStyleItalic">&#46;</span> Las variables cuantitativas se compararon mediante el test de la <span class="elsevierStyleItalic">t</span> de Student o un test no param&#233;trico en el caso de variables que no segu&#237;an una distribuci&#243;n normal&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Se determin&#243; el estad&#237;stico kappa &#40;y su error est&#225;ndar&#41; para establecer el grado de concordancia entre la presencia de actividad cl&#237;nica de la EII y la elevaci&#243;n de cada marcador biol&#243;gico por encima del valor normal de laboratorio&#46; Para interpretar los resultados obtenidos al calcular el estad&#237;stico kappa nos basamos en la clasificaci&#243;n de Landis y Koch<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Para realizar el an&#225;lisis estad&#237;stico se utiliz&#243; el paquete estad&#237;stico SPSS<span class="elsevierStyleSup">&#174;</span> 15&#46;0&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resultados</span><p id="par0075" class="elsevierStylePara elsevierViewall">Se incluyeron 350 pacientes&#44; con una edad media de 46 a&#241;os &#40;rango de 17 a 91 a&#241;os&#41;&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> se describen las caracter&#237;sticas de los pacientes del estudio&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">En cuanto a la localizaci&#243;n de la enfermedad&#44; de los pacientes con CU&#44; un 20&#37; padec&#237;a una proctitis&#44; el 45&#37; presentaba una colitis izquierda y un 35&#37; ten&#237;an pancolitis&#46; La localizaci&#243;n m&#225;s frecuente en la EC fue la ileoc&#243;lica &#40;43&#37;&#41;&#44; seguida de la afectaci&#243;n exclusivamente ileal &#40;29&#37;&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Un 11&#37; de los pacientes presentaba actividad cl&#237;nica de la EII&#46; De los pacientes con CU&#44; 18 ten&#237;an actividad&#46; La media del IMP fue de 4&#44;2 puntos &#40;rango de 2 a 9&#41;&#44; presentando un 50&#37; de los pacientes actividad leve&#44; un 42&#37; actividad moderada y un 8&#37; actividad grave&#46; La media del IHB fue de 7 puntos &#40;rango de 5 a 13&#41; en los 22 pacientes con actividad cl&#237;nica de la EC&#58; el 44&#37; ten&#237;a un brote leve&#44; otro 44&#37; un brote moderado&#44; y un 12&#37; padec&#237;a un brote grave&#44; seg&#250;n el IHB&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Al comparar las medias de los valores de los marcadores biol&#243;gicos entre los pacientes sin actividad y con actividad cl&#237;nica&#44; obtuvimos los resultados que se muestran en las <a class="elsevierStyleCrossRefs" href="#tbl0020">tablas 4 y 5</a>&#46; En la mayor&#237;a de los marcadores biol&#243;gicos evaluados&#44; la media de los valores fue significativamente m&#225;s alta en los pacientes con actividad cl&#237;nica que en aquellos en remisi&#243;n&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">En las <a class="elsevierStyleCrossRefs" href="#tbl0030">tablas 6 y 7</a> se muestra la concordancia de cada marcador biol&#243;gico con la actividad cl&#237;nica en la EC y la CU&#44; respectivamente&#44; medida mediante el coeficiente kappa y su correspondiente error est&#225;ndar&#46; En el caso de la CU&#44; los marcadores con mayor &#237;ndice kappa fueron la hemoglobina&#44; la PCR y el orosomucoide &#40;valores k de 0&#44;28&#44; 0&#44;24 y 0&#44;21&#44; respectivamente&#41;&#46; En la EC&#44; fueron los neutr&#243;filos &#40;k<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;25&#41;&#44; los leucocitos &#40;k<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;22&#41; y la hemoglobina &#40;k<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;22&#41; los marcadores que obtuvieron mejores resultados&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0035"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0100" class="elsevierStylePara elsevierViewall">Los resultados del presente estudio muestran que&#44; de forma global&#44; la concordancia entre los marcadores biol&#243;gicos evaluados y la actividad cl&#237;nica de la EII es baja&#44; tanto en pacientes con CU como en aquellos con EC&#44; ya que el &#237;ndice kappa en ning&#250;n caso super&#243; el valor de 0&#44;3&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Es posible que se obtengan resultados diferentes en la concordancia entre cl&#237;nica y marcadores biol&#243;gicos si elegimos puntos de corte m&#225;s elevados para considerar que existe actividad cl&#237;nica&#46; Sin embargo&#44; en la pr&#225;ctica es necesario identificar a todos los pacientes con posibilidades de tener actividad de la EII&#44; por lo que precisamos m&#233;todos diagn&#243;sticos sensibles&#59; es decir&#44; debemos sospechar actividad cl&#237;nica ante la presencia de s&#237;ntomas leves&#44; aunque estos sean poco espec&#237;ficos&#46; Se eligieron esos puntos de corte para definir actividad cl&#237;nica bas&#225;ndonos en estudios previos que utilizaron estos &#237;ndices para determinar el grado de actividad cl&#237;nica<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">En la EC&#44; la concentraci&#243;n de neutr&#243;filos y leucocitos y la cifra de hemoglobina fueron los marcadores que mejor concordancia presentaron con la actividad cl&#237;nica&#44; alcanzando los &#237;ndices kappa valores cercanos al 0&#44;25&#44; lo que supone una concordancia tan solo discreta&#46; El resto de los marcadores obtuvieron &#237;ndices kappa inferiores a 0&#44;20&#44; mostrando&#44; por tanto&#44; una concordancia insignificante&#46; En el caso de la CU los resultados fueron similares&#44; siendo la cifra de hemoglobina el marcador con un mayor &#237;ndice kappa &#40;0&#44;28&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">La concordancia entre la PCR y la actividad cl&#237;nica en nuestros pacientes con CU fue discreta &#40;&#237;ndice kappa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;24&#41;&#46; Sin embargo&#44; este marcador ha sido propuesto en otros estudios como un buen predictor de la necesidad de colectom&#237;a en pacientes con brotes graves de CU<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a>&#44; y ha presentado una buena correlaci&#243;n con la actividad cl&#237;nica si la CU no se limita al recto y si la actividad es grave<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; Es posible que en nuestro estudio no se confirmen estos resultados debido al no desde&#241;able n&#250;mero de proctitis incluidas &#40;20&#37;&#41;&#44; en los que la respuesta inflamatoria sist&#233;mica no es suficiente para producir una elevaci&#243;n de los marcadores biol&#243;gicos&#46; Por otro lado&#44; en nuestra muestra hay pocos pacientes con actividad grave de la CU&#46; No obstante&#44; otros autores han observado&#44; al igual que nosotros&#44; que la PCR no se eleva de forma significativa en los pacientes con CU activa<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;15</span></a>&#46; Estos &#250;ltimos resultados en la CU podr&#237;an explicarse en base a que&#44; en teor&#237;a&#44; la afectaci&#243;n en la CU se limita a la mucosa&#44; lo que no generar&#237;a mediadores inflamatorios suficientes para inducir un aumento en la s&#237;ntesis de PCR<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">M&#225;s sorprendentes fueron los resultados de la PCR en nuestros pacientes con EC&#44; pues este marcador biol&#243;gico tuvo una correlaci&#243;n insignificante con la actividad cl&#237;nica &#40;k<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;18&#41;&#46; Resultados similares a los nuestros se han obtenido en pacientes con afectaci&#243;n ileal y patr&#243;n estenosante de la EC<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; Sin embargo&#44; en los &#250;ltimos a&#241;os se ha considerado que la PCR es m&#225;s &#250;til para estimar la actividad de la EC que de la CU<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;17</span></a>&#46; En este sentido&#44; en algunos estudios la PCR ha mostrado una buena correlaci&#243;n con la actividad endosc&#243;pica en pacientes con EC<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#44; si bien existen otros estudios con datos contradictorios<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;23</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Del resto de marcadores estudiados cabe destacar la hemoglobina como el par&#225;metro con mejor correlaci&#243;n con la actividad cl&#237;nica en pacientes con CU&#46; La presencia de anemia se ha asociado a un peor pron&#243;stico en pacientes con CU&#44; y a una mayor tasa de colectom&#237;a<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46; En cualquier caso&#44; el &#237;ndice kappa en nuestro estudio no super&#243; siquiera el valor de 0&#44;30&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Por su parte&#44; la VSG obtuvo una concordancia insignificante con la actividad cl&#237;nica&#44; tanto en los pacientes con CU &#40;k<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;16&#41; como con EC &#40;k<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;08&#41;&#46; Lo mismo sucedi&#243; con el resto de marcadores estudiados&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">La baja concordancia entre los marcadores biol&#243;gicos evaluados y la actividad cl&#237;nica podr&#237;a deberse a que diversos s&#237;ntomas atribuidos a la EII&#44; como por ejemplo el dolor abdominal&#44; la fatiga o la diarrea&#44; no siempre son secundarios a la actividad inflamatoria&#44; sino que pueden ser consecuencia de procesos intercurrentes o enfermedad funcional concomitante<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46; Parece demostrado que existe una pobre correlaci&#243;n entre la remisi&#243;n cl&#237;nica &#40;evaluada mediante el <span class="elsevierStyleItalic">Crohn Disease Activity Index</span>&#41; y la mejor&#237;a endosc&#243;pica &#40;valorada por el <span class="elsevierStyleItalic">Crohn&#39;s Disease Endoscopic Index of Severity</span>&#41; en pacientes con EC tratados con corticoides<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46; Asimismo&#44; podr&#237;an existir inflamaci&#243;n y lesiones en la mucosa que no se tradujesen en s&#237;ntomas y que&#44; sin embargo&#44; s&#237; produjesen una reacci&#243;n inflamatoria evidenciable mediante la medici&#243;n de los marcadores biol&#243;gicos s&#233;ricos&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">En la actualidad&#44; el objetivo del tratamiento de la EII es el control de la actividad inflamatoria en el tubo digestivo&#44; ya que la curaci&#243;n de la mucosa es el factor que se ha asociado de forma m&#225;s consistente con una mejor evoluci&#243;n en los pacientes&#44; al modificar la historia natural de la enfermedad&#44; disminuyendo las tasas de hospitalizaci&#243;n y las intervenciones quir&#250;rgicas tanto en la EC como en la CU<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#8211;31</span></a>&#46; Adem&#225;s&#44; el da&#241;o que se genera por la inflamaci&#243;n persistente de la mucosa puede producir cambios anat&#243;micos y funcionales irreversibles&#46; Por todo lo anterior&#44; se ha planteado que para evaluar la respuesta a los tratamientos y tomar decisiones cl&#237;nicas es necesario determinar de forma objetiva la presencia de inflamaci&#243;n activa en el tubo digestivo&#44; siendo inadecuado el abordaje terap&#233;utico basado &#250;nicamente en la presencia o ausencia de s&#237;ntomas<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#44; como evidencian nuestros resultados&#46; No obstante&#44; debemos ser cautos al interpretar los resultados del presente estudio&#44; pues el valor kappa se ve afectado por la prevalencia del rasgo estudiado y en nuestra muestra la prevalencia de actividad fue baja&#46; Otra limitaci&#243;n de nuestro estudio es que tiene un dise&#241;o transversal&#44; por lo que no podemos inferir si la actividad cl&#237;nica o los marcadores biol&#243;gicos pueden desempe&#241;ar otros papeles en el abordaje de la enfermedad&#44; como predecir el curso de esta o valorar una posible respuesta al tratamiento&#46; Por otro lado&#44; dadas las limitaciones ya comentadas de la endoscopia&#44; es preciso disponer de marcadores biol&#243;gicos que estimen de manera indirecta&#44; pero objetiva&#44; la actividad de la EII y que se correlacionen estrechamente con el grado de inflamaci&#243;n intestinal<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;33</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; la concordancia entre los marcadores biol&#243;gicos s&#233;ricos evaluados y la actividad cl&#237;nica de la EII es notablemente baja&#59; no obstante&#44; para conocer la exactitud diagn&#243;stica de los mencionados marcadores biol&#243;gicos se precisan estudios que determinen su correlaci&#243;n con la actividad inflamatoria medida mediante el patr&#243;n oro&#58; la ileocolonoscopia&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicto de intereses</span><p id="par0150" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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              "titulo" => "Recogida de datos&#58; actividad cl&#237;nica y marcadores biol&#243;gicos"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "An&#225;lisis estad&#237;stico"
            ]
          ]
        ]
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          "identificador" => "sec0040"
          "titulo" => "Resultados"
        ]
        7 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Discusi&#243;n"
        ]
        8 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conflicto de intereses"
        ]
        9 => array:1 [
          "titulo" => "Bibliograf&#237;a"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-05-16"
    "fechaAceptado" => "2013-09-05"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec368860"
          "palabras" => array:5 [
            0 => "Enfermedad de Crohn"
            1 => "Colitis ulcerosa"
            2 => "Marcadores biol&#243;gicos"
            3 => "Actividad cl&#237;nica"
            4 => "Prote&#237;na C reactiva"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec368859"
          "palabras" => array:5 [
            0 => "Crohn&#39;s disease"
            1 => "Ulcerative colitis"
            2 => "Serological biomarkers"
            3 => "Clinical activity"
            4 => "C reactive protein"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Fundamento y objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La ileocolonoscopia es el patr&#243;n oro para determinar el grado de actividad de la enfermedad inflamatoria intestinal&#46; Sin embargo&#44; es una t&#233;cnica invasiva&#46; La actividad cl&#237;nica y los marcadores biol&#243;gicos se han empleado como indicadores indirectos para determinar&#44; de forma no invasiva&#44; el grado de actividad inflamatoria&#46; El objetivo de este estudio fue determinar la concordancia entre los marcadores biol&#243;gicos s&#233;ricos m&#225;s utilizados &#40;prote&#237;na C reactiva&#44; orosomucoide&#44; velocidad de sedimentaci&#243;n globular&#44; fibrin&#243;geno&#44; plaquetas&#44; leucocitos&#44; neutr&#243;filos&#44; hemoglobina&#41; y la actividad cl&#237;nica de la enfermedad inflamatoria intestinal&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron prospectivamente pacientes consecutivos en los que se evalu&#243; la actividad cl&#237;nica medida mediante el &#237;ndice de Harvey-Bradshaw en la enfermedad de Crohn&#44; y mediante el &#237;ndice de Mayo parcial en la colitis ulcerosa&#46; Se cuantificaron los valores de los diversos marcadores biol&#243;gicos&#46; Se determin&#243; la concordancia de la actividad cl&#237;nica con la elevaci&#243;n de los marcadores biol&#243;gicos mediante el estad&#237;stico kappa&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 350 pacientes &#40;edad media 46 a&#241;os&#44; enfermedad de Crohn 59&#37;&#41;&#46; El 11&#37; presentaba actividad cl&#237;nica&#46; De los pacientes con enfermedad de Crohn&#44; el 44&#37; ten&#237;a un brote leve&#44; un 44&#37; un brote moderado y un 12&#37; un brote grave&#46; Los pacientes con colitis ulcerosa presentaban actividad leve&#44; moderada y grave en un 50&#44; 42 y 8&#37; de los casos&#44; respectivamente&#46; Ninguno de los marcadores biol&#243;gicos estudiados se correlacion&#243; aceptablemente con la actividad cl&#237;nica &#40;&#237;ndices kappa<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#44;30 en todos los casos&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La concordancia de los marcadores biol&#243;gicos con la actividad cl&#237;nica de la enfermedad inflamatoria intestinal es notablemente baja&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Background and objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Endoscopy is the gold standard to assess disease severity in inflammatory bowel disease&#44; although it is an invasive procedure&#46; Clinical activity and biological markers have been routinely used to determine disease activity in a non-invasive manner&#46; The aim of this study was to determine concordance between common biological markers &#40;C reactive protein&#44; orosomucoid&#44; erythrocyte sedimentation rate&#44; fibrinogen&#44; platelets&#44; leukocytes&#44; neutrophils and haemoglobin&#41; and clinical activity in inflammatory bowel disease&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Patients and method</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Consecutive patients with inflammatory bowel disease were included&#46; Clinical activity was evaluated according to the Harvey-Bradshaw index in Crohn&#39;s disease and to the partial Mayo score in ulcerative colitis&#46; Serum concentrations of the different biomarkers were analysed&#46; Concordance between clinical activity and elevation of the serological biomarkers was determined using the kappa statistic&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In total&#44; 350 patients were included &#40;median age 46 years&#44; Crohn&#39;s disease 59&#37;&#41;&#46; Eleven percent of patients had clinical activity&#46; Crohn&#39;s disease patients had mild clinical activity in 44&#37; of cases&#44; moderate disease in 44&#37; and only 12&#37; of patients had severe clinical activity&#46; In ulcerative colitis&#44; patients had mild&#44; moderate and severe clinical activity in 50&#44; 42 and 8&#37; of cases&#44; respectively&#46; None of the biomarkers included had an acceptable concordance with clinical activity &#40;kappa statistic<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;30&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Concordance between serological biomarkers and clinical activity in inflammatory bowel disease is remarkably low&#46;</p>"
      ]
    ]
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>no se observa sangre&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>resto de sangre en las heces menos de la mitad de las veces&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>sangre evidente en las heces la mayor parte del tiempo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>solo sale sangre&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#205;ndice de Mayo parcial para determinar la actividad cl&#237;nica en pacientes con colitis ulcerosa</p>"
        ]
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Estado general</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Muy bueno<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Intenso<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero de deposiciones l&#237;quidas diarias</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Un punto cada deposici&#243;n l&#237;quida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dudosa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Definida<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Definida y dolorosa<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Otros s&#237;ntomas asociados &#40;un punto por cada complicaci&#243;n&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Artritis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Uve&#237;tis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Eritema nudoso&#47;pioderma&#47;aftas bucales&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>F&#237;stula&#47;fisura&#47;absceso perianal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Otras f&#237;stulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#205;ndice de Harvey-Bradshaw para determinar la actividad cl&#237;nica en la enfermedad de Crohn</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edad media &#40;desviaci&#243;n est&#225;ndar&#41;&#44; a&#241;os</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Enfermedad de Crohn&#47;colitis ulcerosa</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">206&#47;144 &#40;59&#47;41&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo masculino</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">182 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Localizaci&#243;n de enfermedad de Crohn</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Intestino delgado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Colon&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Intestino delgado y colon&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tracto gastrointestinal superior&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Localizaci&#243;n de colitis ulcerosa</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Proctitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Colitis izquierda&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Colitis extensa&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patr&#243;n &#40;enfermedad de Crohn&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inflamatorio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">115 &#40;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Estenosante&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fistulizante&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56 &#40;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Presencia de actividad cl&#237;nica</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Gravedad de la actividad cl&#237;nica</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Enfermedad de Crohn leve&#47;moderada&#47;grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#47;9&#47;4 &#40;44&#47;44&#47;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Colitis ulcerosa leve&#47;moderada&#47;grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#47;8&#47;1 &#40;50&#47;42&#47;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Manifestaciones extraintestinales</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas de los pacientes incluidos en el estudio &#40;N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>350&#41;</p>"
        ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">PCR&#58; prote&#237;na C reactiva&#59; VSG&#58; velocidad de sedimentaci&#243;n globular&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Datos expresados como media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desviaci&#243;n est&#225;ndar&#46;</p>"
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Enfermedad de Crohn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Pacientes sin actividad cl&#237;nica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Pacientes con actividad cl&#237;nica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Pacientes sin actividad cl&#237;nica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Pacientes con actividad cl&#237;nica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">p &#40;<span class="elsevierStyleItalic">t</span> de Student&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mediana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">M&#225;ximo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">M&#237;nimo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PCR &#40;mg&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VSG &#40;mm&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Orosomucoide &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">108<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>34&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">251&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrin&#243;geno &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">441<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>94&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">379&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">713&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;528<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;851&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;812<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;007&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">6&#46;440&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;004&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">PCR&#58; prote&#237;na C reactiva&#59; VSG&#58; velocidad de sedimentaci&#243;n globular&#46;</p>"
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neutr&#243;filos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#44;13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leucocitos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#44;22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Hemoglobina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PCR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;09&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Orosomucoide&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrin&#243;geno&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">VSG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leucocitos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">-0&#44;03&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Fibrin&#243;geno&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:33 [
            0 => array:3 [
              "identificador" => "bib0005"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D deficiency and bone mineral density in Crohn&#39;s disease"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D&#46; S&#225;nchez-Cano"
                            1 => "R&#46; Ruiz-Villaverde"
                            2 => "J&#46;L&#46; Callejas-Rubio"
                            3 => "C&#46;C&#46; P&#233;rez"
                            4 => "M&#46;G&#46; Garc&#237;a"
                            5 => "N&#46; Ortego Centeno"
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin &#40;Barc&#41;"
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                        "volumen" => "137"
                        "paginaInicial" => "62"
                        "paginaFinal" => "65"
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              "identificador" => "bib0010"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "What predicts mucosal inflammation in Crohn&#39;s disease patients&#63;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "I&#46;M&#46; Minderhoud"
                            1 => "M&#46; Samsom"
                            2 => "B&#46; Oldenburg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ibd.20233"
                      "Revista" => array:6 [
                        "tituloSerie" => "Inflamm Bowel Dis"
                        "fecha" => "2007"
                        "volumen" => "13"
                        "paginaInicial" => "1567"
                        "paginaFinal" => "1572"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17663422"
                            "web" => "Medline"
                          ]
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                      ]
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            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Laboratory markers in IBD&#58; Useful&#44; magic&#44; or unnecessary toys"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Vermeire"
                            1 => "G&#46; van Assche"
                            2 => "P&#46; Rutgeerts"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2005.069476"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2006"
                        "volumen" => "55"
                        "paginaInicial" => "426"
                        "paginaFinal" => "431"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16474109"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
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              "identificador" => "bib0020"
              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biomarkers in inflammatory bowel disease&#58; Current practices and recent advances"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46;N&#46; Iskandar"
                            1 => "M&#46;A&#46; Ciorba"
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.trsl.2012.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Transl Res"
                        "fecha" => "2012"
                        "volumen" => "159"
                        "paginaInicial" => "313"
                        "paginaFinal" => "325"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22424434"
                            "web" => "Medline"
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              "identificador" => "bib0025"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Role of biological markers in inflammatory bowel disease"
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                        0 => array:2 [
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Información del artículo
ISSN: 00257753
Idioma original: Español
DOI:10.1016/j.medcli.2013.09.047
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