Therapeutic targets in inflammatory bowel disease | Revista Médica Clínica Las Condes

array:23 ["pii" => "S0716864019300616" "issn" => "07168640" "doi" => "10.1016/j.rmclc.2019.06.008" "estado" => "S300" "fechaPublicacion" => "2019-07-01" "aid" => "494" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Revista Médica Clínica Las Condes. 2019;30:315-22" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 357 "formatos" => array:3 [ "EPUB" => 51 "HTML" => 191 "PDF" => 115 ] ] "itemSiguiente" => array:18 [ "pii" => "S0716864019300604" "issn" => "07168640" "doi" => "10.1016/j.rmclc.2019.06.007" "estado" => "S300" "fechaPublicacion" => "2019-07-01" "aid" => "493" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Revista Médica Clínica Las Condes. 2019;30:323-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2487 "formatos" => array:3 [ "EPUB" => 29 "HTML" => 1882 "PDF" => 576 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original" "titulo" => "Cetoacidosis diabética como guía diagnóstica: Caso clínico" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "323" "paginaFinal" => "325" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Diabetic cetoacidosis as a diagnostic guide: Case report" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1119 "Ancho" => 1606 "Tamanyo" => 101589 ] ] "descripcion" => array:1 [ "es" => "Ecografía abdominal clínica Se evidencia lesión en glándula pancreática de 5.99cm x 5.80cm." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Javier Miguel Martín Guerra, Miguel Martín Asenjo, Pablo Tellería Gómez, Claudia Iglesias Pérez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Javier" "apellidos" => "Miguel Martín Guerra" ] 1 => array:2 [ "nombre" => "Miguel" "apellidos" => "Martín Asenjo" ] 2 => array:2 [ "nombre" => "Pablo" "apellidos" => "Tellería Gómez" ] 3 => array:2 [ "nombre" => "Claudia" "apellidos" => "Iglesias Pérez" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0716864019300604?idApp=UINPBA00004N" "url" => "/07168640/0000003000000004/v1_201908150631/S0716864019300604/v1_201908150631/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0716864019300549" "issn" => "07168640" "doi" => "10.1016/j.rmclc.2019.06.001" "estado" => "S300" "fechaPublicacion" => "2019-07-01" "aid" => "487" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Revista Médica Clínica Las Condes. 2019;30:305-14" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 615 "formatos" => array:3 [ "EPUB" => 43 "HTML" => 423 "PDF" => 149 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original" "titulo" => "Manifestaciones extraintestinales de enfermedad inflamatoria intestinal" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "305" "paginaFinal" => "314" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Extraintestinal manifestations of the inflammatory bowel disease" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1187 "Ancho" => 1615 "Tamanyo" => 147582 ] ] "descripcion" => array:1 [ "es" => "Entesitis." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Amaranta Luzoro, Pablo Sabat, Leonardo Guzmán, Francisca Frias" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Amaranta" "apellidos" => "Luzoro" ] 1 => array:2 [ "nombre" => "Pablo" "apellidos" => "Sabat" ] 2 => array:2 [ "nombre" => "Leonardo" "apellidos" => "Guzmán" ] 3 => array:2 [ "nombre" => "Francisca" "apellidos" => "Frias" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0716864019300549?idApp=UINPBA00004N" "url" => "/07168640/0000003000000004/v1_201908150631/S0716864019300549/v1_201908150631/es/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Therapeutic targets in inflammatory bowel disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "315" "paginaFinal" => "322" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Daniela Fluxa, Maria T. Abreu" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Daniela" "apellidos" => "Fluxa" "email" => array:1 [ 0 => "danifluxa@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Maria T." "apellidos" => "Abreu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, USA" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author. https://doi.org/10.1016/j.rmclc.2019.06.008. e-ISSN: 2531-0186/ ISSN: 0716-8640/© 2019 Revista Médica Clínica Las Condes. Este es un artículo Open Access bajo la licencia CC BY-NC-ND, (http://creativecommons.org/licenses/by-nc-nd/4.0/)." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Objetivos terapéuticos enfermedad inflamatoria intestinal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2454 "Ancho" => 2851 "Tamanyo" => 557145 ] ] "descripcion" => array:1 [ "en" => "Therapeutic Targets in Inflammatory Bowel Disease." ] ] ] "textoCompleto" => "1IntroductionThe use of anti-tumor necrosis factor (anti-TNF) therapies in the management of inflammatory bowel disease (IBD) has redefined treatment goals. Before these medications were introduced treatment was guided on clinical parameters and symptomatic control.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> However, anti-TNFs were able to demonstrate that healing the intestinal lining was possible,<a class="elsevierStyleCrossRef" href="#bib0010">2</a> and although mucosal healing can be achieved with several medications including corticosteroids, mesalamines and immunomodulators, data suggests that biologics may be more robust.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Several studies have shown that mucosal healing (MH) is associated with long term corticosteroid-free clinical remission use and protection from colectomy in ulcerative colitis,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> hence treatment goals have now evolved to include MH as a target. Recently, the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) initiated the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program whose objective it was to garner international expert consensus on evidence-based treatment targets for IBD.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The objective of this article is to review and discuss what has been proposed as therapeutic targets in IBD.2Therapeutic targets2.1SymptomsOver the years, different scoring systems have been developed and used to assess for disease activity in both ulcerative colitis (UC) and Crohńs disease (CD). The Mayo Score (MS) was described by Schroeder et al. in 1987 and has since become one of the most commonly used scoring systems in UC.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> The Mayo score does have an endoscopic component (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The most frequently used scoring systems in CD are the Crohńs Disease Activity Index (CDAI) which was described by Best at al. in 1976 <a class="elsevierStyleCrossRef" href="#bib0030">6</a>and the Harvey Bradshaw Index (HBI) which was created by Harvey and Bradshaw in 1980.<a class="elsevierStyleCrossRef" href="#bib0035">7</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>For UC, clinical remission has been defined as a total MS ≤2, with no subscore>1; in CD clinical remission has been defined as a CDAI score<150 or HBI score of ≤4 points.<a class="elsevierStyleCrossRefs" href="#bib0040">8,9</a> On the other hand, clinical response has been defined as a reduction in the MS of ≥3 points and ≥30% from baseline, with a decrease in the rectal bleeding subscore of ≥1 point or a subscore of ≤1 for a patient with UC.<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a> In CD, the definition for clinical response has varied by clinical trials. Some of the definitions proposed are ≥ 70-point decrease in CDAI,<a class="elsevierStyleCrossRefs" href="#bib0040">8,12</a> ≥100-point decrease in CDAI(8,12), or a ≥70-point decrease in CDAI plus a ≥25% baseline reduction in score.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> In regards to HBI, Vermeire et al conducted a study that determined that CDAI and HBI were positively correlated and concluded that clinical response was defined as a 3 point decrease in the HBI score.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>However, some studies have shown that symptoms do not correlate with mucosal activity, particularly in patients with CD.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> For example, in the SONIC trial which included patients with moderately active CD (CDAI score>220), 20% of the patients did not have ulcerations on ileocolonoscopy at baseline.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> This discrepancy between symptoms and absence of mucosal inflammation has several potential explanations. One explanation could be persistent histological inflammation in the setting of endoscopic remission causing persistent symptoms.<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a> Another possibility is the presence of irritable bowel syndrome like symptoms.<a class="elsevierStyleCrossRefs" href="#bib0090">18–20</a> Vivinus-Nébot et al.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> have proposed that the presence of IBS-like symptoms is related to persistent subclinical and ongoing inflammation which is associated with increased colonic paracellular permeability. In addition, chronic inflammation in both UC and CD may lead to significant structural damage of the bowel wall, which can manifest itself as decreased motility, narrowing of the colon and rectum and changes in the absorptive function<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Furthermore, inflammation may also produce direct damage to the enteric nervous system and alter motility.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>In addition, the CDAI score has several limitations. It is subjective as it assesses the patient's perception of their disease; it is difficult to obtain as the score is based on a diary which is completed by the patient for 7 days prior to evaluation, which precludes its use in clinical practice and also has interobserver variability. Furthermore, it is not accurate on patient with stenotic or fistulizing behavior.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Therefore, although assessment of clinical parameters is still necessary, resolution of symptoms alone is not a sufficient target.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Given that for now our therapies are directed at inflammatory pathways, patients are unlikely to respond to any current therapy if there is no evidence of intestinal inflammation. Patients with symptoms and no mucosal inflammation or persistent symptoms after resolution of intestinal inflammation must be evaluated for structural damage and other causes of symptoms such as bacterial overgrowth, irritable bowel syndrome, and bile salt diarrhea.2.2Mucosal healingOver the last few decades it has been recognized that the best outcomes have been observed in patients who achieve mucosal healing. Historically, endoscopic disease activity has been assessed by different scores in UC and CD.In UC, the STRIDE program group recommends the use of endoscopic Mayo score rather than the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) given its simplicity and well-established predictive value.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The Mayo scoring system goes from 0-3; 0 meaning there is no disease activity and the mucosa is normal; 1 mild disease (erythema, decreased vascular pattern and mild friability); 2 moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 severe disease (ulceration, spontaneous bleeding).<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Although achieving an endoscopic Mayo score of 0 sounds ideal, there is insufficient evidence to recommend this as a target for all patients but an endoscopic Mayo score of 1 should be the minimal target. Experts have recommended to assess endoscopic disease activity 3-6 months after the patient has been started on therapy and to consider an endoscopic Mayo score of 0-1 as endoscopic remission.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>For CD, 2 different validated scoring systems have been used in clinical trials to assess disease severity, the CD Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for CD (SES-CD). The CDEIS score divides the bowel in 5 segments (rectum, sigmoid and left colon, transverse colon, right colon and ileum), assesses the presence of deep and superficial ulceration in each segment plus the extent of surface area involved and/or ulcerated (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRef" href="#bib0115">23</a> The SES-CD was later developed and validated as a simpler scoring system by Daperno et al. This scoring system divides the bowel in the same 5 segments and ulcer size, the extent of ulcerated and affected surfaces, and the presence of stenosis are scored from 0-3 (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Although endoscopic remission has been commonly defined as a CDEIS<3 and SES-CD ≤2, currently there is no cutoff value to define MH and hence MH has been defined as absence of ulceration.<a class="elsevierStyleCrossRefs" href="#bib0020">4,14</a> In the case of CD, endoscopic remission should be assessed 6-9 months after starting a new therapy.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> For those patients in whom endoscopic assessment cannot be performed or is not informative, cross sectional imaging should be obtained.<a class="elsevierStyleCrossRef" href="#bib0020">4</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Several studies have addressed long-term outcomes of patient who achieve MH in UC and CD patients. A recent meta-analysis assessing the long-term effect of mucosal healing in patients with UC showed that MH was associated with higher rates of clinical remission, colectomy avoidance, sustained MH, and corticosteroid-free clinical remission.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> A meta-analysis in patients with CD showed that patients who achieved MH had higher rates of achieving long-term clinical remission, long-term MH, and a trend towards decreased rate of CD-related surgeries in comparison to those patients with active CD who did not achieve MH.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>2.3ImagingImaging techniques are a good alternative for those patients in which endoscopy cannot be performed or is not informative. Several imaging techniques are available, including ultrasonography, computed tomography (CT) and Magnetic Resonance Imaging (MRI). The latter has the advantage of avoiding the use of ionizing radiation and hence should be preferred over CT imaging specially in patient with CD who will undergo repeated examination due to the natural history of the disease.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> However, magnetic resonance enterography interpretation requires training; data suggests that diagnostic accuracy is accomplished when feedback is provided on 100 cases.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> On the contrary, cross-sectional imaging techniques in UC have a limited role.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>The most common used score is the Magnetic Resonance Index of Activity (MaRIA) which takes into account bowel wall thickness (mm), presence of mucosal ulceration, presence of mural edema, presence of pseudopolyps in the lumen, enlarged (>1cm) regional mesenteric lymph nodes, quantitative measurement of wall signal intensity and relative contrast enhancement of the intestinal wall in six different segments (distal ileum, ascending, transverse, descending, sigmoid colon and rectum).<a class="elsevierStyleCrossRef" href="#bib0135">27</a> This score has shown to be highly correlated with CDEIS. Some years later a similar index was created which used diffusion-weighted imaging (DWI) sequence instead of contrast enhancement called DWI-MaRIA.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>On the other hand, MRI is also useful in detecting disease related complications such as fistulas. The Van Assche index is the most frequently used index for perianal disease.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> The score takes into account the number of fistula tracts, location, extension, hyperintensity on T2 weight images, collections, rectal wall involvement.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> This index has been partially validated.Ultrasonography (US) is another accessible, non-invasive, inexpensive technique that can be used in the evaluation of IBD.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> This technique can assess bowel wall thickening, pseudostratification, inflammatory mass, loss of colonic haustration as well as complications such as strictures, abscesses and fistulas.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> In addition, the use of doppler US can be used to evaluate bowel wall vascularity, as increased vascularity is seen in inflammatory processes.<a class="elsevierStyleCrossRefs" href="#bib0110">22,29</a> The use of oral and/or intravenous contrast can help increase diagnostic accuracy and improve sensitivity.<a class="elsevierStyleCrossRefs" href="#bib0110">22,29</a> However, to date, there are no validated indexes for luminal activity based on US.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>The STRIDE program recommends to assess resolution of inflammation by cross-sectional imaging as target in patient with CD when endoscopy cannot evaluate inflammation adequately. In patients with UC, cross-sectional imaging is not a target.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>2.4Histological healingSeveral studies have assessed histological healing in patients with UC and have shown that persistent histologic inflammation have been associated with risk of relapse, hospitalization and surgery.<a class="elsevierStyleCrossRefs" href="#bib0080">16,30–34</a> The Geboes score and the Riley score are the most commonly used scores in UC.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> The Riley score was described by Riley at al.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> in 1991 and evaluates for acute inflammatory cell infiltrate, crypt abscesses, mucin depletion, surface epithelial integrity, chronic inflammatory cell infiltrate and crypt architectural irregularities. Grades range between none, mild, moderate, or severe, which makes it difficult to reproduce. The Geboes score was later created and evaluates architectural changes, chronic inflammatory infiltration, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction, and erosions or ulcerations.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Active histology is defined as Geboes score ≥3.1 (presence of neutrophils in the epithelium).<a class="elsevierStyleCrossRef" href="#bib0160">32</a> Basal plasmacytosis, defined as plasma cell infiltrate in the lower third of the lamina propria, has also been shown to be an independent factor of relapse in UC.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>Most recently Mosli et al.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> developed and alternative instrument called the Robarts Histopathology Index due to the fact that the previous scores mentioned lacked formal assessment of index reliability, responsiveness and validity. In their study biopsies were scored using the Geboes score, modified Riley score and a visual analogue scale global rating. Analysis of intra-rater and inter-rater reliability for each index and individual index items was performed. Only items with high reliability were used to develop the Robarts Histopathology Index which included: chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in the epithelium and erosion or ulceration. Total score ranges from 0 (no disease activity) to 33 (severe disease activity). However, the prognostic value of Robarts Histopathology Index has not been assessed and hence prospective cohort studies are needed in order to define potential application of the index.<a class="elsevierStyleCrossRef" href="#bib0180">36</a>On the other hand, in patients with CD, discontinuous and transmural inflammation may induce sampling error for histological assessment and hence histological healing will not necessarily represent quiescent disease.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> The Colonic and Ileal Global Histologic Disease Activity Score is one of the few scores described and the most widely used.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> The score assesses epithelial damage, architectural changes, mononuclear or polymorphonuclear cells in the lamina propria and epithelium, presence of erosions/ulcers and granulomata, as well as the number of segmental biopsy specimens affected.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> The score is not validated and its role is not yet defined.<a class="elsevierStyleCrossRef" href="#bib0185">37</a>To date there is no clear definition for histological healing or consensus in which histologic score should be used,<a class="elsevierStyleCrossRef" href="#bib0070">14</a> hence histological healing is currently not recommended as a target in both clinical practice or clinical trials.<a class="elsevierStyleCrossRefs" href="#bib0020">4,14</a>2.5BiomarkersThe identification and utilization of noninvasive biomarkers has become of great interest over the last decades as they might be able to assist in the monitoring of mucosal inflammation in patients with IBD and potentially reduce the use of colonoscopy. To date, the most commonly used tests are C-reactive protein (CRP) and fecal calprotectin (FC). CRP is a widely available and inexpensive tool in the management of IBD, however its production is enhanced in a variety of systemic inflammatory diseases and is not exclusive to intestinal inflammation.<a class="elsevierStyleCrossRef" href="#bib0190">38</a>CRP lacks sensitivity. In a prospective study, 71% and 25% of patients with UC and Crohn's disease, respectively, had normal CRP levels at diagnosis.<a class="elsevierStyleCrossRef" href="#bib0195">39</a> Active ileal disease in particular can be associated with a normal CRP.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> In addition, a CRP+1059 G/C polymorphism in CRP gene was found to be associated with decreased serum CRP levels in patient with CD.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> In this study, homozygous and heterozygous carriers of the CRP+1059G/C polymorphism had lower mean serum CRP levels compared to wildtype carriers. The genotype frequencies were noted to be 0.1%, 8.4% and 91.5% respectively for homozygous, heterozygous and wildtype carriers in the single nucleotide polymorphism database of the National Center of Biotechnology Information (NCBI), which has the largest population data on the+1059 G/C polymorphism (1016 individuals).<a class="elsevierStyleCrossRef" href="#bib0205">41</a>On the other hand, FC has shown to be one of the most reliable, non-invasive diagnostic tools for management of IBD.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> Calprotectin is a calcium and zinc binding protein considered to be neutrophil-specific, and accounts for around 60% of total soluble proteins in the cytoplasm of neutrophils.<a class="elsevierStyleCrossRef" href="#bib0215">43</a> Therefore, the amount of calprotectin in stool is proportional to the neutrophil migration to the gastrointestinal mucosa.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> A recent meta-analysis showed that FC is a highly sensitive tool for assessing endoscopic activity with a pooled sensitivity of 85% and specificity of 75%.<a class="elsevierStyleCrossRef" href="#bib0225">45</a>D’Haens et al. proposed a level of 250μg/g as cutoff to predict mucosal inflammation in both CD and UC. In their study, they found a positive predictive value (PPV) 48.5% and negative predictive value (NPV) of 96.6% in predicting endoscopic remission in patients with CD (CDEIS<3) and a PPV of 100.0% and NPV of 47.1% for active mucosal disease activity in patients with UC (Mayo>0).<a class="elsevierStyleCrossRef" href="#bib0230">46</a> Fecal calprotectin is best used as a test for following individual patient's response to therapy rather than across populations of patients.New noninvasive tests are being developed. One such test, Monitr, is a serum test that assesses MH by evaluating levels of 13 biomarkers associated with angiogenesis, cell adhesion, cell proliferation and repair, extracellular matrix remodeling, inflammation and immune cell recruitment in patients with CD.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The testing provides a MH index score that reflects disease severity. Validation of the test showed an overall accuracy of 90%, with a negative predictive value of 92% and a positive predictive value of 87% for identifying patients with endoscopic activity.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Currently, biomarkers are not considered a target for treatment per se, but are considered helpful tools in monitoring disease. CRP and FC may reflect residual intestinal inflammation, hence objective evaluation of the mucosa with endoscopy should be pursued if values fail to normalize.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>3Patient reported outcomes (PROs)Patient-reported outcomes (PROs) are self-administered tools that come directly from the patient without being interpreted by a physician or anyone else.<a class="elsevierStyleCrossRef" href="#bib0235">47</a> PROs are now becoming important endpoints in clinical trials,<a class="elsevierStyleCrossRef" href="#bib0240">48</a> as approval of IBD pharmacotherapy by the United States Food and Drug administration (FDA) now requires evaluation of PROs and objective measures of disease.<a class="elsevierStyleCrossRefs" href="#bib0070">14,47</a> To date, there are no PRO instruments created under the guidance of the FDA,<a class="elsevierStyleCrossRef" href="#bib0245">49</a> however interim PROs derived from the CDAI and Mayo score have been created <a class="elsevierStyleCrossRef" href="#bib0020">4</a>and have been included in the 12 recommendations to treat to target by the STRIDE group.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The primary PRO for UC has been defined as resolution of rectal bleeding and normalization of bowel habits while primary PRO for CD has been defined as abdominal pain resolution and normalization of bowel habits; in addition, patient's individual goals should also be assessed.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The STRIDE group recommends to assess PROs every 3 months until symptom resolution and every 6–12 months thereafter.3.1Composite end-pointThe STRIDE program has recommended to achieve a composite target of clinical/PRO remission and endoscopic remission in both UC and CD. Recommendations made by the STRIDE program are summarized in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>4ConclusionTherapeutic targets have evolved from clinical response to a composite end point including MH and PRO remission. Therapeutic interventions should be guided by periodic assessment of MH/PRO. Biomarkers are useful in monitoring the disease but are not a target for treatment per se. Although HH is associated with improved outcomes in UC, there is not consensus on best index and best way to minimize inter-observer variability. Ongoing research on new biomarkers and assessment of HH might change treatment paradigms in the future.5Declaración conflicto de interesesDr. Daniela Fluxa has no disclosures.Dr Abreu is a member of the scientific advisory boards of AbbVie Laboratories, Celgene Corporation, Shire Pharmaceuticals, Roche Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, AMGEN and GILEAD. She is on the advisory boards of Allergan, SERES and Nestle Health Science. She is a consultant for Prometheus Laboratories; Takeda; UCB, Inc.; Pfizer; Janssen and Eli Lilly Pharmaceuticals, Inc. She has performed training/consulting for Focus Medical Communications. She has performed lecturing/teaching for Imedex, Inc. She has lectured for CME Outfitters." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1230310" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1143078" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1230309" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1143077" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Therapeutic targets" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Symptoms" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Mucosal healing" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Imaging" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Histological healing" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Biomarkers" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Patient reported outcomes (PROs)" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Composite end-point" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Declaración conflicto de intereses" ] 9 => array:1 [ "titulo" => "Referencias" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-02-06" "fechaAceptado" => "2019-06-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1143078" "palabras" => array:5 [ 0 => "Biomarkers" 1 => "Crohn Disease" 2 => "Colitis" 3 => "Ulcerative" 4 => "Inflammatory Bowel Disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1143077" "palabras" => array:4 [ 0 => "Biomarcadores" 1 => "Colitis ulcerosa" 2 => "Enfermedad de Crohn" 3 => "Enfermedad inflamatoria intestinal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Therapeutic goals in inflammatory bowel disease (IBD) have evolved with the introduction of biologic therapies. These medications have demonstrated that resolution of mucosal inflammation was feasible. Mucosal healing has been associated with fewer complications and better patient outcomes. Hence, symptomatic control, which was considered the primary treatment goal, is no longer sufficient. Mucosal healing is now the principal target. Several biomarkers of inflammation have been studied, including C-reactive protein and fecal calprotectin. Although they are helpful in monitoring disease activity, they are still not considered therapeutic targets at this time. Ongoing research is evaluating new biomarkers as potential future targets. Resolution of histological inflammation has also been associated with better outcomes, however, the evidence is limited and the definition of histologic healing is still not clear. Ultimately, restoring quality of life is essential. In recognition of the patient's goals in wellness, patient reported outcomes are part of the therapeutic goals. When combined with mucosal healing endpoints, patient reported outcomes serve as a composite endpoint in IBD clinical trials and now patient care." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La introducción de terapias biológicas para el tratamiento de la Enfermedad Inflamatoria Intestinal (EII) demostró que la resolución de la inflamación mucosa era factible. Subsecuentemente, se ha demostrado que la curación de la mucosa se asocia a remisión clínica prolongada, menor tasa de cirugías, menor tasa de hospitalizaciones y mejor calidad de vida. Por lo tanto, el control sintomático que hasta entonces se consideraba como objetivo terapéutico principal ya se no considera suficiente. Estudios recientes han demostrado que la resolución de la inflamación histológica también se ha asociado con mejores resultados, sin embargo, la evidencia es limitada y la definición de curación histológica aún no está clara. En adición, múltiples biomarcadores han sido estudiados con el fin de encontrar un método alternativo a la endoscopía, entre ellos la proteína C reactiva y la calprotectina fecal. Sin embargo, aunque éstos son útiles para monitorear la actividad de la enfermedad, no son considerados objetivos terapéuticos. Nuevos biomarcadores están bajo investigación. A pesar de que la resolución sintomática no es considerada como el objetivo terapéutico principal, el reconocimiento de la percepción del paciente respecto a su enfermedad, mejor conocido como resultados comunicados por el paciente, forman parte de los objetivos terapéuticos junto con la curación mucosa." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2454 "Ancho" => 2851 "Tamanyo" => 557145 ] ] "descripcion" => array:1 [ "en" => "Therapeutic Targets in Inflammatory Bowel Disease." ] ] 1 => 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" => "Reference: Schroeder KW, Tremaine WJ, IIstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317(26):1625–9." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameters \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Subscores 0-3 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stool frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0=normal number of stools for the patient1=1-2 stools more than normal2=3-4 stools more than normal3=5 or more stools more than normal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rectal bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0=no bleeding1=streaks of blood with stool less than half of the time2=obvious blood with stool most of the time3=blood alone passed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Findings of flexible proctosigmoidoscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0=normal or inactive1=mild disease (erythema, decreased vascular pattern, mild friability)2=moderate disease (marked erythema, absent vascular pattern, friability, erosions)3=severe disease (spontaneous bleeding, ulceration) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Physician's global assessment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0=normal1=mild disease2=moderate disease3=severe disease \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2101773.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Mayo Score." ] ] 2 => 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:3 [ "leyenda" => "Total 1+Total 2+Total 3+Total 4=Total A Numbers (n) of segments totally or partially explored (1-5)=n Total A divided by n=Total B Quote 3 if ulcerated stenosis anywhere, 0 if not=Total C Quote 3 if non-ulcerated stenosis anywhere, 0 if not=Total D Total B+C+D=CDEIS" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ileum \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Right Colon \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Transverse \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Left/Sigmoid Colon \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rectum \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sum \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Deep ulceration (0 points if none, 12 points if present) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total 1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Superficial ulceration (0 points if none, 6 points if present) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total 2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Surface involved by disease in cm (0-10 points)<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total 3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Surface involved by ulceration in cm (0-10 points)<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total 4 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2101774.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "The 10cm scale represents the surface effectively explored. Reference: Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d’Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989;30(7):983–9." ] ] ] "descripcion" => array:1 [ "en" => "CDEIS." ] ] 3 => 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" => "Total SES-CD=sum of the 4 variables in the 5 bowel segments (rectum, sigmoid/left colon, transverse colon, right colon and ileum).Reference: Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-12." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Simple Endoscopic Score for Crohńs Disease values</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Size of ulcers \t\t\t\t\t\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">None \t\t\t\t\t\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">Aphthous ulcer (diameter 0.1-0.5 cm) \t\t\t\t\t\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">Large ulcer (diameter 0.5-2 cm) \t\t\t\t\t\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">Very large ulcer (diameter>2 cm) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulcerated surface \t\t\t\t\t\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">None \t\t\t\t\t\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"><10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10-30% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>30% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Affected surface \t\t\t\t\t\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">Unaffected segment \t\t\t\t\t\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"><50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50-75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>75% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of narrowings \t\t\t\t\t\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">None \t\t\t\t\t\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">Single, can be passed \t\t\t\t\t\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">Multiple, can be passed \t\t\t\t\t\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">Cannot be passed \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2101775.png" ] ] ] ] "descripcion" => array:1 [ "en" => "SES-CD." ] ] ] "bibliografia" => array:2 [ "titulo" => "Referencias" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:49 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treat to Target in Inflammatory Bowel Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Bossuyt" 1 => "S. Vermeire" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11938-016-0077-z" "Revista" => array:6 [ "tituloSerie" => "Curr Treat Options Gastroenterol." "fecha" => "2016" "volumen" => "14" "paginaInicial" => "61" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26864745" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A Noninvasive Method to Assess Mucosal Healing in Patients With Crohn's Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W.J. Sandborn" 1 => "M.T. Abreu" 2 => "M.C. Dubinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterol Hepatol (NY)." "fecha" => "2018" "volumen" => "14" "numero" => "5 Suppl 2" "paginaInicial" => "1" "paginaFinal" => "12" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis: A Systematic Review and Meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.C. Shah" 1 => "J.F. Colombel" 2 => "B.E. Sands" 3 => "N. Narula" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2016.01.015" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol." "fecha" => "2016" "volumen" => "14" "paginaInicial" => "1245" "paginaFinal" => "1255" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26829025" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Peyrin-Biroulet" 1 => "W. Sandborn" 2 => "B.E. Sands" 3 => "W. Reinisch" 4 => "W. Bemelman" 5 => "R.V. Bryant" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ajg.2015.233" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol." "fecha" => "2015" "volumen" => "110" "paginaInicial" => "1324" "paginaFinal" => "1338" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26303131" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.W. Schroeder" 1 => "W.J. Tremaine" 2 => "D.M. IIstrup" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM198712243172603" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "1987" "volumen" => "317" "paginaInicial" => "1625" "paginaFinal" => "1629" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3317057" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of a Crohn's Disease Activity Index: National Cooperative Crohn's Disease Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "W.R. Best" 1 => "J.M. Becktel" 2 => "J.W. Singleton" 3 => "F. Kern Jr." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology." "fecha" => "1976" "volumen" => "70" "paginaInicial" => "439" "paginaFinal" => "444" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1248701" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A simple index of Crohn's-disease activity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.F. Harvey" 1 => "J.M. Bradshaw" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(13)70190-5" "Revista" => array:5 [ "tituloSerie" => "Lancet." "fecha" => "1980" "volumen" => "1" "paginaInicial" => "514" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24461611" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Defining the optimal response criteria for the Crohn's disease activity index for induction studies in patients with mildly to moderately active Crohn's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.T. Thia" 1 => "W.J. Sandborn" 2 => "J.D. Lewis" 3 => "E.V. Loftus Jr." 4 => "B.G. Feagan" 5 => "A.H. Steinhart" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2008.02176.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol." "fecha" => "2008" "volumen" => "103" "paginaInicial" => "3123" "paginaFinal" => "3131" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18786111" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation Between the Crohn's Disease Activity and Harvey-Bradshaw Indices in Assessing Crohn's Disease Severity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Vermeire" 1 => "S. Schreiber" 2 => "W.J. Sandborn" 3 => "C. Dubois" 4 => "P. Rutgeerts" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2010.01.001" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol." "fecha" => "2010" "volumen" => "8" "paginaInicial" => "357" "paginaFinal" => "363" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20096379" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.J. Sandborn" 1 => "G. van Assche" 2 => "W. Reinisch" 3 => "J.F. Colombel" 4 => "G. D’Haens" 5 => "D.C. Wolf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2011.10.032" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology." "fecha" => "2012" "volumen" => "142" "paginaInicial" => "257" "paginaFinal" => "265" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22062358" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.J. Sandborn" 1 => "B.G. Feagan" 2 => "D.C. Wolf" 3 => "G. D’Haens" 4 => "S. Vermeire" 5 => "S.B. Hanauer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1513248" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2016" "volumen" => "374" "paginaInicial" => "1754" "paginaFinal" => "1762" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27144850" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adalimumab for maintenance treatment of Crohn's disease: Results of the CLASSIC II trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.J. Sandborn" 1 => "S.B. Hanauer" 2 => "P. Rutgeerts" 3 => "R.N. Fedorak" 4 => "M. Lulcas" 5 => "D.G. MacIntosh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2006.106781" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "2007" "volumen" => "56" "paginaInicial" => "1232" "paginaFinal" => "1239" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17299059" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.B. Hanauer" 1 => "B.G. Feagan" 2 => "G.R. Lichtenstein" 3 => "L.F. Mayer" 4 => "S. Schreiber" 5 => "J.F. Colombel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(02)08512-4" "Revista" => array:6 [ "tituloSerie" => "Lancet." "fecha" => "2002" "volumen" => "359" "paginaInicial" => "1541" "paginaFinal" => "1549" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12047962" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What Are the Targets of Inflammatory Bowel Disease Management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Lega" 1 => "M.C. Dubinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ibd/izy064" "Revista" => array:6 [ "tituloSerie" => "Inflamm Bowel Dis." "fecha" => "2018" "volumen" => "24" "paginaInicial" => "1670" "paginaFinal" => "1675" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29697788" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:5 [ 0 => "J.F. Colombel" 1 => "W.J. Sandborn" 2 => "W. Reinisch" 3 => "G.J. Mantzaris" 4 => "A. Kornbluth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0904492" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2010" "volumen" => "362" "paginaInicial" => "1383" "paginaFinal" => "1395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20393175" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microscopic activity in ulcerative colitis: what does it mean?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.A. Riley" 1 => "V. Mani" 2 => "M.J. Goodman" 3 => "S. Dutt" 4 => "M.E. Herd" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.32.2.174" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "1991" "volumen" => "32" "paginaInicial" => "174" "paginaFinal" => "178" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1864537" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.F. Colombel" 1 => "M.E. Keir" 2 => "A. Scherl" 3 => "R. Zhao" 4 => "G. de Hertogh" 5 => "W.A. Faubion" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2016-312307" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "2017" "volumen" => "66" "paginaInicial" => "2063" "paginaFinal" => "2068" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27590995" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IBS-like symptoms in patients with inflammatory bowel disease in remission; relationships with quality of life and coping behavior" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "I.M. Minderhoud" 1 => "B. Oldenburg" 2 => "J.A. Wismeijer" 3 => "G.P. van Berge Henegouwen" 4 => "A.J. Smout" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1023/b:ddas.0000020506.84248.f9" "Revista" => array:6 [ "tituloSerie" => "Dig Dis Sci." "fecha" => "2004" "volumen" => "49" "paginaInicial" => "469" "paginaFinal" => "474" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15139501" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of irritable bowel syndrome-like symptoms in ulcerative colitis patients with clinical and endoscopic evidence of remission: prospective multicenter study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Fukuba" 1 => "S. Ishihara" 2 => "Y. Tada" 3 => "N. Oshima" 4 => "I. Moriyama" 5 => "T. Yuki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/00365521.2014.898084" "Revista" => array:6 [ "tituloSerie" => "Scand J Gastroenterol." "fecha" => "2014" "volumen" => "49" "paginaInicial" => "674" "paginaFinal" => "680" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24646420" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Functional bowel symptoms in quiescent inflammatory bowel diseases: Role of epithelial barrier disruption and low-grade inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Vivinus-Nébot" 1 => "G. Frin-Mathy" 2 => "H. Bzioueche" 3 => "R. Dainese" 4 => "G. Bernard" 5 => "R. Anty" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2012-304066" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "2014" "volumen" => "63" "paginaInicial" => "744" "paginaFinal" => "752" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23878165" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunohistochemical analysis of myenteric ganglia and interstitial cells of Cajal in ulcerative colitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Bernardini" 1 => "C. Segnani" 2 => "C. Ippolito" 3 => "R. De Giorgio" 4 => "R. Colucci" 5 => "M.S. Faussone-Pellegrini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1582-4934.2011.01298.x" "Revista" => array:7 [ "tituloSerie" => "J Cell Mol Med." "fecha" => "2012" "volumen" => "16" "paginaInicial" => "318" "paginaFinal" => "327" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21426484" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1590865810605087" "estado" => "S300" "issn" => "15908658" ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2: IBD scores and general principales and technical aspects" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Sturm" 1 => "C. Maaser" 2 => "E. Calabrese" 3 => "V. Annese" 4 => "G. Fiorino" 5 => "T. Kucharzik" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "J Crohns Colitis." "fecha" => "2018" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d’Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.Y. Mary" 1 => "R. Modigliani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.30.7.983" "Revista" => array:7 [ "tituloSerie" => "Gut." "fecha" => "1989" "volumen" => "30" "paginaInicial" => "983" "paginaFinal" => "989" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2668130" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022347608001054" "estado" => "S300" "issn" => "00223476" ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Daperno" 1 => "G. D’Haens" 2 => "G. Van Assche" 3 => "F. Baert" 4 => "P. Bulois" 5 => "V. Maunoury" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0016-5107(04)01878-4" "Revista" => array:6 [ "tituloSerie" => "Gastrointest Endosc." "fecha" => "2004" "volumen" => "60" "paginaInicial" => "505" "paginaFinal" => "512" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15472670" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.C. Shah" 1 => "J.F. Colombel" 2 => "B.E. Sands" 3 => "N. Narula" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/apt.13475" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther." "fecha" => "2016" "volumen" => "43" "paginaInicial" => "317" "paginaFinal" => "333" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26607562" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diffusion-weighted magnetic resonance imaging for detecting and assessing ileal inflammation in Crohn's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Buisson" 1 => "A. Joubert" 2 => "P.F. Montoriol" 3 => "D. Da Ines" 4 => "C. Hordonneau" 5 => "B. Pereira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/apt.12201" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther." "fecha" => "2013" "volumen" => "37" "paginaInicial" => "537" "paginaFinal" => "545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23289713" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Rimola" 1 => "S. Rodriguez" 2 => "O. García-Bosch" 3 => "I. Ordás" 4 => "E. Ayala" 5 => "M. Aceituno" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2008.167957" "Revista" => array:7 [ "tituloSerie" => "Gut." "fecha" => "2009" "volumen" => "58" "paginaInicial" => "1113" "paginaFinal" => "1120" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19136510" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673609613040" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Van Assche" 1 => "D. Vanbeckevoort" 2 => "D. Bielen" 3 => "G. Coremans" 4 => "I. Aerden" 5 => "M. Noman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2003.07241.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol." "fecha" => "2003" "volumen" => "98" "paginaInicial" => "332" "paginaFinal" => "339" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12591051" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Up-to-date overview of imaging techniques in the diagnosis and management of inflammatory bowel diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.B. Biernacka" 1 => "D. Barańska" 2 => "P. Grzelak" 3 => "E. Czkwianianc" 4 => "K. Szabelska-Zakrzewska" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5114/pg.2019.83423" "Revista" => array:6 [ "tituloSerie" => "Prz Gastroenterol." "fecha" => "2019" "volumen" => "14" "paginaInicial" => "19" "paginaFinal" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30944674" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Bitton" 1 => "M.A. Peppercorn" 2 => "D.A. Antonioli" 3 => "J.L. Niles" 4 => "S. Shah" 5 => "A. Bousvaros" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/gast.2001.20912" "Revista" => array:7 [ "tituloSerie" => "Gastroenterology." "fecha" => "2001" "volumen" => "120" "paginaInicial" => "13" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11208709" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1474442207702673" "estado" => "S300" "issn" => "14744422" ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission: A Prospective Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Zenlea" 1 => "E.U. Yee" 2 => "L. Rosenberg" 3 => "M. Boyle" 4 => "K.S. Nanda" 5 => "J.L. Wolf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ajg.2016.50" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol." "fecha" => "2016" "volumen" => "111" "paginaInicial" => "685" "paginaFinal" => "690" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26977756" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Bessissow" 1 => "B. Lemmens" 2 => "M. Ferrante" 3 => "R. Bisschops" 4 => "K. Van Steen" 5 => "K. Geboes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ajg.2012.301" "Revista" => array:7 [ "tituloSerie" => "Am J Gastroenterol." "fecha" => "2012" "volumen" => "107" "paginaInicial" => "1684" "paginaFinal" => "1692" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23147523" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673616307759" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Histologic Normalization Occurs in Ulcerative Colitis and Is Associated With Improved Clinical Outcomes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Christensen" 1 => "S.B. Hanauer" 2 => "J. Erlich" 3 => "O. Kassim" 4 => "P.R. Gibson" 5 => "J.R. Turner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2017.02.016" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol." "fecha" => "2017" "volumen" => "15" "paginaInicial" => "1557" "paginaFinal" => "1564" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28238954" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.V. Bryant" 1 => "D.C. Burger" 2 => "J. Delo" 3 => "A.J. Walsh" 4 => "S. Thomas" 5 => "A. von Herbay" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2015-309598" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "2016" "volumen" => "65" "paginaInicial" => "408" "paginaFinal" => "414" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25986946" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A reproducible grading scale for histological assessment of inflammation in ulcerative colitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Geboes" 1 => "R. Riddell" 2 => "A. Ost" 3 => "B. Jensfelt" 4 => "T. Persson" 5 => "R. Löfberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.47.3.404" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "2000" "volumen" => "47" "paginaInicial" => "404" "paginaFinal" => "409" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10940279" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development and validation of a histological index for UC" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.H. Mosli" 1 => "B.G. Feagan" 2 => "G. Zou" 3 => "W.J. Sandborn" 4 => "G. D’Haens" 5 => "R. Khanna" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2015-310393" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "2017" "volumen" => "66" "paginaInicial" => "50" "paginaFinal" => "58" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26475633" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review: histological remission in inflammatory bowel disease, Is “complete” remission the new treatment paradigm?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.V. Bryant" 1 => "S. Winer" 2 => "S.P. Travis" 3 => "R.H. Riddell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.crohns.2014.08.011" "Revista" => array:6 [ "tituloSerie" => "An IOIBD initiative. J Crohns Colitis." "fecha" => "2014" "volumen" => "8" "paginaInicial" => "1582" "paginaFinal" => "1597" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25267173" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C-reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: A systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.H. Mosli" 1 => "G. Zou" 2 => "S.K. Garg" 3 => "S.G. Feagan" 4 => "J.K. MacDonald" 5 => "N. Chande" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ajg.2015.120" "Revista" => array:7 [ "tituloSerie" => "Am J Gastroenterol." "fecha" => "2015" "volumen" => "110" "paginaInicial" => "802" "paginaFinal" => "819" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25964225" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673614605390" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C-reactive protein: A predictive factor and marker of inflammation in inflammatory bowel disease, Results from a prospective population-based study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Henriksen" 1 => "J. Jahnsen" 2 => "I. Lygren" 3 => "N. Stray" 4 => "J. Sauar" 5 => "M.H. Vatn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2007.146357" "Revista" => array:6 [ "tituloSerie" => "Gut." "fecha" => "2008" "volumen" => "57" "paginaInicial" => "1518" "paginaFinal" => "1523" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18566104" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinically active Crohn's disease in the presence of a low C-reactive protein" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "T.H. Florin" 1 => "E.W. Paterson" 2 => "E.V. Fowler" 3 => "G.L. Radford-Smith" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/00365520500217118" "Revista" => array:6 [ "tituloSerie" => "Scand J Gastroenterol." "fecha" => "2006" "volumen" => "41" "paginaInicial" => "306" "paginaFinal" => "311" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16497618" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The+1059G/C polymorphism in the C-reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Thalmaier" 1 => "J. Dambacher" 2 => "J. Seiderer" 3 => "A. Konrad" 4 => "V. Schachinger" 5 => "S. Pfennig" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Aliment Pharmacol Ther." "fecha" => "2006" "volumen" => "24" "paginaInicial" => "1105" "paginaFinal" => "1115" ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.G. Mumolo" 1 => "L. Bertani" 2 => "L. Ceccarelli" 3 => "G. Laino" 4 => "G. Di Fluri" 5 => "E. Albano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v24.i33.3681" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol." "fecha" => "2018" "volumen" => "24" "paginaInicial" => "3681" "paginaFinal" => "3694" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30197475" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Use of Fecal Calprotectin in Inflammatory Bowel Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "I. Bjarnason" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Gastroenterol Hepatol (NY)." "fecha" => "2017" "volumen" => "13" "paginaInicial" => "53" "paginaFinal" => "56" ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Discriminating IBD from IBS: Comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.M. Schoepfer" 1 => "M. Trummler" 2 => "P. Seeholzer" 3 => "B. Seibold-Schmid" 4 => "F. Seibold" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ibd.20275" "Revista" => array:6 [ "tituloSerie" => "Inflamm Bowel Dis." "fecha" => "2008" "volumen" => "14" "paginaInicial" => "32" "paginaFinal" => "39" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17924558" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fecal calprotectin in assessing inflammatory bowel disease endoscopic activity: A diagnostic accuracy meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T. Rokkas" 1 => "P. Portincasa" 2 => "I.E. Koutroubakis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Gastrointest Liver Dis." "fecha" => "2018" "volumen" => "27" "paginaInicial" => "299" "paginaFinal" => "306" ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fecal Calprotectin is a Surrogate Marker for Endoscopic Lesions in Inflammatory Bowel Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. D’Haens" 1 => "M. Ferrante" 2 => "S. Vermeire" 3 => "F. Baert" 4 => "M. Noman" 5 => "L. Moortgat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ibd.22917" "Revista" => array:6 [ "tituloSerie" => "Inflamm Bowel Dis." "fecha" => "2012" "volumen" => "18" "paginaInicial" => "2218" "paginaFinal" => "2224" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22344983" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PROMises Made, PROMises To Be Kept: Patient-Reported Outcome Measures in Inflammatory Bowel Diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Singh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2018.01.032" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol." "fecha" => "2018" "volumen" => "16" "paginaInicial" => "624" "paginaFinal" => "626" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29409805" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patient reported-outcomes in a French nationwide survey of inflammatory bowel disease patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Williet" 1 => "H. Sarter" 2 => "C. Gower-Rousseau" 3 => "C. Adrianjafy" 4 => "A. Olympie" 5 => "A. Buisson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ecco-jcc/jjw145" "Revista" => array:6 [ "tituloSerie" => "J Crohns Colitis." "fecha" => "2017" "volumen" => "11" "paginaInicial" => "165" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27516406" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Converging goals of treatment of inflammatory bowel disease from clinical trials and practice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B.G. Levesque" 1 => "W.J. Sandborn" 2 => "J. Ruel" 3 => "B.G. Feagan" 4 => "B.E. Sands" 5 => "J.F. Colombel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2014.08.003" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology." "fecha" => "2015" "volumen" => "148" "paginaInicial" => "37" "paginaFinal" => "51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25127678" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/07168640/0000003000000004/v1_201908150631/S0716864019300616/v1_201908150631/en/main.assets" "Apartado" => array:4 [ "identificador" => "78900" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Tema Central: Enfermedad Inflamatoria Intestinal I" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/07168640/0000003000000004/v1_201908150631/S0716864019300616/v1_201908150631/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0716864019300616?idApp=UINPBA00004N"]

Statistics

Review

Therapeutic targets in inflammatory bowel disease

Objetivos terapéuticos enfermedad inflamatoria intestinal

Daniela Fluxaa,

Corresponding author

danifluxa@gmail.com

Corresponding author. https://doi.org/10.1016/j.rmclc.2019.06.008. e-ISSN: 2531-0186/ ISSN: 0716-8640/© 2019 Revista Médica Clínica Las Condes. Este es un artículo Open Access bajo la licencia CC BY-NC-ND, (http://creativecommons.org/licenses/by-nc-nd/4.0/).

, Maria T. Abreub

a Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, USA

b Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA

Read

4075

Times
was read the article

911

Total PDF

3164

Total HTML

Share statistics

 array:23 [
  "pii" => "S0716864019300616"
  "issn" => "07168640"
  "doi" => "10.1016/j.rmclc.2019.06.008"
  "estado" => "S300"
  "fechaPublicacion" => "2019-07-01"
  "aid" => "494"
  "copyrightAnyo" => "2019"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "rev"
  "cita" => "Revista M&#233;dica Cl&#237;nica Las Condes. 2019;30:315-22"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 357
    "formatos" => array:3 [
      "EPUB" => 51
      "HTML" => 191
      "PDF" => 115
    ]
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S0716864019300604"
    "issn" => "07168640"
    "doi" => "10.1016/j.rmclc.2019.06.007"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-01"
    "aid" => "493"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Revista M&#233;dica Cl&#237;nica Las Condes. 2019;30:323-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 2487
      "formatos" => array:3 [
        "EPUB" => 29
        "HTML" => 1882
        "PDF" => 576
      ]
    ]
    "es" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
      "titulo" => "Cetoacidosis diab&#233;tica como gu&#237;a diagn&#243;stica&#58; Caso cl&#237;nico"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "323"
          "paginaFinal" => "325"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Diabetic cetoacidosis as a diagnostic guide&#58; Case report"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1119
              "Ancho" => 1606
              "Tamanyo" => 101589
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Ecograf&#237;a abdominal cl&#237;nica</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se evidencia lesi&#243;n en gl&#225;ndula pancre&#225;tica de 5&#46;99<span class="elsevierStyleHsp" style=""></span>cm x 5&#46;80<span class="elsevierStyleHsp" style=""></span>cm&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Javier Miguel Mart&#237;n Guerra, Miguel Mart&#237;n Asenjo, Pablo Teller&#237;a G&#243;mez, Claudia Iglesias P&#233;rez"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Javier"
              "apellidos" => "Miguel Mart&#237;n Guerra"
            ]
            1 => array:2 [
              "nombre" => "Miguel"
              "apellidos" => "Mart&#237;n Asenjo"
            ]
            2 => array:2 [
              "nombre" => "Pablo"
              "apellidos" => "Teller&#237;a G&#243;mez"
            ]
            3 => array:2 [
              "nombre" => "Claudia"
              "apellidos" => "Iglesias P&#233;rez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0716864019300604?idApp=UINPBA00004N"
    "url" => "/07168640/0000003000000004/v1_201908150631/S0716864019300604/v1_201908150631/es/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S0716864019300549"
    "issn" => "07168640"
    "doi" => "10.1016/j.rmclc.2019.06.001"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-01"
    "aid" => "487"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Revista M&#233;dica Cl&#237;nica Las Condes. 2019;30:305-14"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 615
      "formatos" => array:3 [
        "EPUB" => 43
        "HTML" => 423
        "PDF" => 149
      ]
    ]
    "es" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
      "titulo" => "Manifestaciones extraintestinales de enfermedad inflamatoria intestinal"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "305"
          "paginaFinal" => "314"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Extraintestinal manifestations of the inflammatory bowel disease"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1187
              "Ancho" => 1615
              "Tamanyo" => 147582
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Entesitis&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Amaranta Luzoro, Pablo Sabat, Leonardo Guzm&#225;n, Francisca Frias"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Amaranta"
              "apellidos" => "Luzoro"
            ]
            1 => array:2 [
              "nombre" => "Pablo"
              "apellidos" => "Sabat"
            ]
            2 => array:2 [
              "nombre" => "Leonardo"
              "apellidos" => "Guzm&#225;n"
            ]
            3 => array:2 [
              "nombre" => "Francisca"
              "apellidos" => "Frias"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0716864019300549?idApp=UINPBA00004N"
    "url" => "/07168640/0000003000000004/v1_201908150631/S0716864019300549/v1_201908150631/es/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Therapeutic targets in inflammatory bowel disease"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "315"
        "paginaFinal" => "322"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Daniela Fluxa, Maria T&#46; Abreu"
        "autores" => array:2 [
          0 => array:4 [
            "nombre" => "Daniela"
            "apellidos" => "Fluxa"
            "email" => array:1 [
              0 => "danifluxa@gmail.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Maria T&#46;"
            "apellidos" => "Abreu"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; University of Miami Miller School of Medicine&#44; Miami&#44; USA"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Division of Gastroenterology&#44; Department of Medicine&#44; University of Miami Miller School of Medicine&#44; Miami&#44; USA"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46; https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;rmclc&#46;2019&#46;06&#46;008&#46; e-ISSN&#58; 2531-0186&#47; ISSN&#58; 0716-8640&#47;&#169; 2019 Revista M&#233;dica Cl&#237;nica Las Condes&#46; Este es un art&#237;culo Open Access bajo la licencia CC BY-NC-ND&#44; &#40;http&#58;&#47;&#47;creativecommons&#46;org&#47;licenses&#47;by-nc-nd&#47;4&#46;0&#47;&#41;&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Objetivos terap&#233;uticos enfermedad inflamatoria intestinal"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2454
            "Ancho" => 2851
            "Tamanyo" => 557145
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Therapeutic Targets in Inflammatory Bowel Disease&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The use of anti-tumor necrosis factor &#40;anti-TNF&#41; therapies in the management of inflammatory bowel disease &#40;IBD&#41; has redefined treatment goals&#46; Before these medications were introduced treatment was guided on clinical parameters and symptomatic control&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; anti-TNFs were able to demonstrate that healing the intestinal lining was possible&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and although mucosal healing can be achieved with several medications including corticosteroids&#44; mesalamines and immunomodulators&#44; data suggests that biologics may be more robust&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Several studies have shown that mucosal healing &#40;MH&#41; is associated with long term corticosteroid-free clinical remission use and protection from colectomy in ulcerative colitis&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> hence treatment goals have now evolved to include MH as a target&#46; Recently&#44; the International Organization for the Study of Inflammatory Bowel Diseases &#40;IOIBD&#41; initiated the Selecting Therapeutic Targets in Inflammatory Bowel Disease &#40;STRIDE&#41; program whose objective it was to garner international expert consensus on evidence-based treatment targets for IBD&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The objective of this article is to review and discuss what has been proposed as therapeutic targets in IBD&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="sect0030">Therapeutic targets</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0035">Symptoms</span><p id="par0010" class="elsevierStylePara elsevierViewall">Over the years&#44; different scoring systems have been developed and used to assess for disease activity in both ulcerative colitis &#40;UC&#41; and Crohn&#769;s disease &#40;CD&#41;&#46; The Mayo Score &#40;MS&#41; was described by Schroeder et al&#46; in 1987 and has since become one of the most commonly used scoring systems in UC&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The Mayo score does have an endoscopic component &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The most frequently used scoring systems in CD are the Crohn&#769;s Disease Activity Index &#40;CDAI&#41; which was described by Best at al&#46; in 1976 <a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>and the Harvey Bradshaw Index &#40;HBI&#41; which was created by Harvey and Bradshaw in 1980&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">For UC&#44; clinical remission has been defined as a total MS &#8804;2&#44; with no subscore<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">&#62;</span><span class="elsevierStyleHsp" style=""></span>1&#59; in CD clinical remission has been defined as a CDAI score<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">&#60;</span><span class="elsevierStyleHsp" style=""></span>150 or HBI score of &#8804;4 points&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> On the other hand&#44; clinical response has been defined as a reduction in the MS of &#8805;3 points and &#8805;30&#37; from baseline&#44; with a decrease in the rectal bleeding subscore of &#8805;1 point or a subscore of <span class="elsevierStyleSmallCaps">&#8804;</span>1 for a patient with UC&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> In CD&#44; the definition for clinical response has varied by clinical trials&#46; Some of the definitions proposed are &#8805; 70-point decrease in CDAI&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;12</span></a> &#8805;100-point decrease in CDAI&#40;8&#44;12&#41;&#44; or a &#8805;70-point decrease in CDAI plus a &#8805;25&#37; baseline reduction in score&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In regards to HBI&#44; Vermeire et al conducted a study that determined that CDAI and HBI were positively correlated and concluded that clinical response was defined as a 3 point decrease in the HBI score&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">However&#44; some studies have shown that symptoms do not correlate with mucosal activity&#44; particularly in patients with CD&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> For example&#44; in the SONIC trial which included patients with moderately active CD &#40;CDAI score<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">&#62;</span><span class="elsevierStyleHsp" style=""></span>220&#41;&#44; 20&#37; of the patients did not have ulcerations on ileocolonoscopy at baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> This discrepancy between symptoms and absence of mucosal inflammation has several potential explanations&#46; One explanation could be persistent histological inflammation in the setting of endoscopic remission causing persistent symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> Another possibility is the presence of irritable bowel syndrome like symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;20</span></a> Vivinus-N&#233;bot et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> have proposed that the presence of IBS-like symptoms is related to persistent subclinical and ongoing inflammation which is associated with increased colonic paracellular permeability&#46; In addition&#44; chronic inflammation in both UC and CD may lead to significant structural damage of the bowel wall&#44; which can manifest itself as decreased motility&#44; narrowing of the colon and rectum and changes in the absorptive function<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Furthermore&#44; inflammation may also produce direct damage to the enteric nervous system and alter motility&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In addition&#44; the CDAI score has several limitations&#46; It is subjective as it assesses the patient&#39;s perception of their disease&#59; it is difficult to obtain as the score is based on a diary which is completed by the patient for 7 days prior to evaluation&#44; which precludes its use in clinical practice and also has interobserver variability&#46; Furthermore&#44; it is not accurate on patient with stenotic or fistulizing behavior&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Therefore&#44; although assessment of clinical parameters is still necessary&#44; resolution of symptoms alone is not a sufficient target&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Given that for now our therapies are directed at inflammatory pathways&#44; patients are unlikely to respond to any current therapy if there is no evidence of intestinal inflammation&#46; Patients with symptoms and no mucosal inflammation or persistent symptoms after resolution of intestinal inflammation must be evaluated for structural damage and other causes of symptoms such as bacterial overgrowth&#44; irritable bowel syndrome&#44; and bile salt diarrhea&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0040">Mucosal healing</span><p id="par0035" class="elsevierStylePara elsevierViewall">Over the last few decades it has been recognized that the best outcomes have been observed in patients who achieve mucosal healing&#46; Historically&#44; endoscopic disease activity has been assessed by different scores in UC and CD&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In UC&#44; the STRIDE program group recommends the use of endoscopic Mayo score rather than the Ulcerative Colitis Endoscopic Index of Severity &#40;UCEIS&#41; given its simplicity and well-established predictive value&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The Mayo scoring system goes from 0-3&#59; 0 meaning there is no disease activity and the mucosa is normal&#59; 1 mild disease &#40;erythema&#44; decreased vascular pattern and mild friability&#41;&#59; 2 moderate disease &#40;marked erythema&#44; absent vascular pattern&#44; friability&#44; erosions&#41;&#59; 3 severe disease &#40;ulceration&#44; spontaneous bleeding&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Although achieving an endoscopic Mayo score of 0 sounds ideal&#44; there is insufficient evidence to recommend this as a target for all patients but an endoscopic Mayo score of 1 should be the minimal target&#46; Experts have recommended to assess endoscopic disease activity 3-6 months after the patient has been started on therapy and to consider an endoscopic Mayo score of 0-1 as endoscopic remission&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">For CD&#44; 2 different validated scoring systems have been used in clinical trials to assess disease severity&#44; the CD Endoscopic Index of Severity &#40;CDEIS&#41; and the Simple Endoscopic Score for CD &#40;SES-CD&#41;&#46; The CDEIS score divides the bowel in 5 segments &#40;rectum&#44; sigmoid and left colon&#44; transverse colon&#44; right colon and ileum&#41;&#44; assesses the presence of deep and superficial ulceration in each segment plus the extent of surface area involved and&#47;or ulcerated &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The SES-CD was later developed and validated as a simpler scoring system by Daperno et al&#46; This scoring system divides the bowel in the same 5 segments and ulcer size&#44; the extent of ulcerated and affected surfaces&#44; and the presence of stenosis are scored from 0-3 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Although endoscopic remission has been commonly defined as a CDEIS<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">&#60;</span><span class="elsevierStyleHsp" style=""></span>3 and SES-CD &#8804;2&#44; currently there is no cutoff value to define MH and hence MH has been defined as absence of ulceration&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;14</span></a> In the case of CD&#44; endoscopic remission should be assessed 6-9 months after starting a new therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> For those patients in whom endoscopic assessment cannot be performed or is not informative&#44; cross sectional imaging should be obtained&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Several studies have addressed long-term outcomes of patient who achieve MH in UC and CD patients&#46; A recent meta-analysis assessing the long-term effect of mucosal healing in patients with UC showed that MH was associated with higher rates of clinical remission&#44; colectomy avoidance&#44; sustained MH&#44; and corticosteroid-free clinical remission&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> A meta-analysis in patients with CD showed that patients who achieved MH had higher rates of achieving long-term clinical remission&#44; long-term MH&#44; and a trend towards decreased rate of CD-related surgeries in comparison to those patients with active CD who did not achieve MH&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0045">Imaging</span><p id="par0055" class="elsevierStylePara elsevierViewall">Imaging techniques are a good alternative for those patients in which endoscopy cannot be performed or is not informative&#46; Several imaging techniques are available&#44; including ultrasonography&#44; computed tomography &#40;CT&#41; and Magnetic Resonance Imaging &#40;MRI&#41;&#46; The latter has the advantage of avoiding the use of ionizing radiation and hence should be preferred over CT imaging specially in patient with CD who will undergo repeated examination due to the natural history of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> However&#44; magnetic resonance enterography interpretation requires training&#59; data suggests that diagnostic accuracy is accomplished when feedback is provided on 100 cases&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> On the contrary&#44; cross-sectional imaging techniques in UC have a limited role&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The most common used score is the Magnetic Resonance Index of Activity &#40;MaRIA&#41; which takes into account bowel wall thickness &#40;mm&#41;&#44; presence of mucosal ulceration&#44; presence of mural edema&#44; presence of pseudopolyps in the lumen&#44; enlarged &#40;<span class="elsevierStyleSmallCaps">&#62;</span>1<span class="elsevierStyleHsp" style=""></span>cm&#41; regional mesenteric lymph nodes&#44; quantitative measurement of wall signal intensity and relative contrast enhancement of the intestinal wall in six different segments &#40;distal ileum&#44; ascending&#44; transverse&#44; descending&#44; sigmoid colon and rectum&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> This score has shown to be highly correlated with CDEIS&#46; Some years later a similar index was created which used diffusion-weighted imaging &#40;DWI&#41; sequence instead of contrast enhancement called DWI-MaRIA&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">On the other hand&#44; MRI is also useful in detecting disease related complications such as fistulas&#46; The Van Assche index is the most frequently used index for perianal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The score takes into account the number of fistula tracts&#44; location&#44; extension&#44; hyperintensity on T2 weight images&#44; collections&#44; rectal wall involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> This index has been partially validated&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Ultrasonography &#40;US&#41; is another accessible&#44; non-invasive&#44; inexpensive technique that can be used in the evaluation of IBD&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> This technique can assess bowel wall thickening&#44; pseudostratification&#44; inflammatory mass&#44; loss of colonic haustration as well as complications such as strictures&#44; abscesses and fistulas&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In addition&#44; the use of doppler US can be used to evaluate bowel wall vascularity&#44; as increased vascularity is seen in inflammatory processes&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;29</span></a> The use of oral and&#47;or intravenous contrast can help increase diagnostic accuracy and improve sensitivity&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;29</span></a> However&#44; to date&#44; there are no validated indexes for luminal activity based on US&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The STRIDE program recommends to assess resolution of inflammation by cross-sectional imaging as target in patient with CD when endoscopy cannot evaluate inflammation adequately&#46; In patients with UC&#44; cross-sectional imaging is not a target&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0050">Histological healing</span><p id="par0080" class="elsevierStylePara elsevierViewall">Several studies have assessed histological healing in patients with UC and have shown that persistent histologic inflammation have been associated with risk of relapse&#44; hospitalization and surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;30&#8211;34</span></a> The Geboes score and the Riley score are the most commonly used scores in UC&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The Riley score was described by Riley at al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> in 1991 and evaluates for acute inflammatory cell infiltrate&#44; crypt abscesses&#44; mucin depletion&#44; surface epithelial integrity&#44; chronic inflammatory cell infiltrate and crypt architectural irregularities&#46; Grades range between none&#44; mild&#44; moderate&#44; or severe&#44; which makes it difficult to reproduce&#46; The Geboes score was later created and evaluates architectural changes&#44; chronic inflammatory infiltration&#44; lamina propria neutrophils and eosinophils&#44; neutrophils in epithelium&#44; crypt destruction&#44; and erosions or ulcerations&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Active histology is defined as Geboes score &#8805;3&#46;1 &#40;presence of neutrophils in the epithelium&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Basal plasmacytosis&#44; defined as plasma cell infiltrate in the lower third of the lamina propria&#44; has also been shown to be an independent factor of relapse in UC&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Most recently Mosli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> developed and alternative instrument called the Robarts Histopathology Index due to the fact that the previous scores mentioned lacked formal assessment of index reliability&#44; responsiveness and validity&#46; In their study biopsies were scored using the Geboes score&#44; modified Riley score and a visual analogue scale global rating&#46; Analysis of intra-rater and inter-rater reliability for each index and individual index items was performed&#46; Only items with high reliability were used to develop the Robarts Histopathology Index which included&#58; chronic inflammatory infiltrate&#44; lamina propria neutrophils&#44; neutrophils in the epithelium and erosion or ulceration&#46; Total score ranges from 0 &#40;no disease activity&#41; to 33 &#40;severe disease activity&#41;&#46; However&#44; the prognostic value of Robarts Histopathology Index has not been&#160;assessed and hence prospective cohort studies are needed in order to&#160;define potential application of the index&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">On the other hand&#44; in patients with CD&#44; discontinuous and transmural inflammation may induce sampling error for histological assessment and hence histological healing will not necessarily represent quiescent disease&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The&#160;Colonic and Ileal Global Histologic Disease Activity Score&#160;is one of the few scores described and the most widely used&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The score assesses epithelial damage&#44; architectural changes&#44; mononuclear or&#160;polymorphonuclear cells&#160;in the lamina propria and epithelium&#44; presence of erosions&#47;ulcers and granulomata&#44; as well as the number of segmental biopsy specimens affected&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The score is not validated and its role&#160;is not yet defined&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">To date there is no clear definition for histological healing or consensus in which histologic score should be used&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> hence histological healing is currently not recommended as a target in both clinical practice or clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;14</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;5</span><span class="elsevierStyleSectionTitle" id="sect0055">Biomarkers</span><p id="par0100" class="elsevierStylePara elsevierViewall">The identification and utilization of noninvasive biomarkers has become of great interest over the last decades as they might be able to assist in the monitoring of mucosal inflammation in patients with IBD and potentially reduce the use of colonoscopy&#46; To date&#44; the most commonly used tests are C-reactive protein &#40;CRP&#41; and fecal calprotectin &#40;FC&#41;&#46; CRP is a widely available and inexpensive tool in the management of IBD&#44; however its production is enhanced in a variety of systemic inflammatory diseases and is not exclusive to intestinal inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">CRP lacks sensitivity&#46; In a prospective study&#44; 71&#37; and 25&#37; of patients with UC and Crohn&#39;s disease&#44; respectively&#44; had normal CRP levels at diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Active ileal disease in particular can be associated with a normal CRP&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> In addition&#44; a CRP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1059 G&#47;C polymorphism in CRP gene was found to be associated with decreased serum CRP levels in patient with CD&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> In this study&#44; homozygous and heterozygous carriers of the&#160;CRP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1059G&#47;C&#160;polymorphism had lower mean serum CRP levels compared to wildtype carriers&#46; The genotype frequencies were noted to be 0&#46;1&#37;&#44; 8&#46;4&#37; and 91&#46;5&#37; respectively for homozygous&#44; heterozygous and wildtype carriers in the single nucleotide polymorphism database of the National Center of Biotechnology Information &#40;NCBI&#41;&#44; which&#160;has the largest population data&#160;on the<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1059 G&#47;C polymorphism &#40;1016 individuals&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">On the other hand&#44; FC has shown to be one of the most reliable&#44; non-invasive diagnostic tools for management of IBD&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Calprotectin is a calcium and zinc binding protein considered to be neutrophil-specific&#44; and accounts for around 60&#37; of total soluble proteins in the cytoplasm of neutrophils&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> Therefore&#44; the amount of calprotectin in stool is proportional to the neutrophil migration to the gastrointestinal mucosa&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> A recent meta-analysis showed that FC is a highly sensitive tool for assessing endoscopic activity with a pooled sensitivity of 85&#37; and specificity of 75&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">D&#8217;Haens et al&#46; proposed a level of 250<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g as cutoff to predict mucosal inflammation in both CD and UC&#46; In their study&#44; they found a positive predictive value &#40;PPV&#41; 48&#46;5&#37; and negative predictive value &#40;NPV&#41; of 96&#46;6&#37; in predicting endoscopic remission in patients with CD &#40;CDEIS<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">&#60;</span><span class="elsevierStyleHsp" style=""></span>3&#41; and a PPV of 100&#46;0&#37; and NPV of 47&#46;1&#37; for active mucosal disease activity in patients with UC &#40;Mayo<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> Fecal calprotectin is best used as a test for following individual patient&#39;s response to therapy rather than across populations of patients&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">New noninvasive tests are being developed&#46; One such test&#44; Monitr&#44; is a serum test that assesses MH by evaluating levels of 13 biomarkers associated with angiogenesis&#44; cell adhesion&#44; cell proliferation and repair&#44; extracellular matrix remodeling&#44; inflammation and immune cell recruitment in patients with CD&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The testing provides a MH index score that reflects disease severity&#46; Validation of the test showed an overall accuracy of 90&#37;&#44; with a negative predictive value of 92&#37; and a positive predictive value of 87&#37; for identifying patients with endoscopic activity&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Currently&#44; biomarkers are not considered a target for treatment per se&#44; but are considered helpful tools in monitoring disease&#46; CRP and FC may reflect residual intestinal inflammation&#44; hence objective evaluation of the mucosa with endoscopy should be pursued if values fail to normalize&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="sect0060">Patient reported outcomes &#40;PROs&#41;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Patient-reported outcomes &#40;PROs&#41; are self-administered tools that come directly from the patient without being interpreted by a physician or anyone else&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> PROs are now becoming important endpoints in clinical trials&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> as approval of IBD pharmacotherapy by the United States Food and Drug administration &#40;FDA&#41; now requires evaluation of PROs and objective measures of disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;47</span></a> To date&#44; there are no PRO instruments created under the guidance of the FDA&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> however interim PROs derived from the CDAI and Mayo score have been created <a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>and have been included in the 12 recommendations to treat to target by the STRIDE group&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The primary PRO for UC has been defined as resolution of rectal bleeding and normalization of bowel habits while primary PRO for CD has been defined as abdominal pain resolution and normalization of bowel habits&#59; in addition&#44; patient&#39;s individual goals should also be assessed&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The STRIDE group recommends to assess PROs every 3 months until symptom resolution and every 6&#8211;12 months thereafter&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0065">Composite end-point</span><p id="par0135" class="elsevierStylePara elsevierViewall">The STRIDE program has recommended to achieve a composite target of clinical&#47;PRO remission and endoscopic remission in both UC and CD&#46; Recommendations made by the STRIDE program are summarized in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="sect0070">Conclusion</span><p id="par0140" class="elsevierStylePara elsevierViewall">Therapeutic targets have evolved from clinical response to a composite end point including MH and PRO remission&#46; Therapeutic interventions should be guided by periodic assessment of MH&#47;PRO&#46; Biomarkers are useful in monitoring the disease but are not a target for treatment per se&#46; Although HH is associated with improved outcomes in UC&#44; there is not consensus on best index and best way to minimize inter-observer variability&#46; Ongoing research on new biomarkers and assessment of HH might change treatment paradigms in the future&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">5</span><span class="elsevierStyleSectionTitle" id="sect0075">Declaraci&#243;n conflicto de intereses</span><p id="par0145" class="elsevierStylePara elsevierViewall">Dr&#46; Daniela Fluxa has no disclosures&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Dr Abreu is a member of the scientific advisory boards of AbbVie Laboratories&#44; Celgene Corporation&#44; Shire Pharmaceuticals&#44; Roche Pharmaceuticals&#44; Boehringer Ingelheim Pharmaceuticals&#44; AMGEN and GILEAD&#46; She is on the advisory boards of Allergan&#44; SERES and Nestle Health Science&#46; She is a consultant for Prometheus Laboratories&#59; Takeda&#59; UCB&#44; Inc&#46;&#59; Pfizer&#59; Janssen and Eli Lilly Pharmaceuticals&#44; Inc&#46; She has performed training&#47;consulting for Focus Medical Communications&#46; She has performed lecturing&#47;teaching for Imedex&#44; Inc&#46; She has lectured for CME Outfitters&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:10 [
        0 => array:3 [
          "identificador" => "xres1230310"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1143078"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1230309"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1143077"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Therapeutic targets"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Symptoms"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Mucosal healing"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Imaging"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Histological healing"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Biomarkers"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Patient reported outcomes &#40;PROs&#41;"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Composite end-point"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conclusion"
        ]
        8 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Declaraci&#243;n conflicto de intereses"
        ]
        9 => array:1 [
          "titulo" => "Referencias"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-02-06"
    "fechaAceptado" => "2019-06-09"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1143078"
          "palabras" => array:5 [
            0 => "Biomarkers"
            1 => "Crohn Disease"
            2 => "Colitis"
            3 => "Ulcerative"
            4 => "Inflammatory Bowel Disease"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1143077"
          "palabras" => array:4 [
            0 => "Biomarcadores"
            1 => "Colitis ulcerosa"
            2 => "Enfermedad de Crohn"
            3 => "Enfermedad inflamatoria intestinal"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Therapeutic goals in inflammatory bowel disease &#40;IBD&#41; have evolved with the introduction of biologic therapies&#46; These medications have demonstrated that resolution of mucosal inflammation was feasible&#46; Mucosal healing has been associated with fewer complications and better patient outcomes&#46; Hence&#44; symptomatic control&#44; which was considered the primary treatment goal&#44; is no longer sufficient&#46; Mucosal healing is now the principal target&#46; Several biomarkers of inflammation have been studied&#44; including C-reactive protein and fecal calprotectin&#46; Although they are helpful in monitoring disease activity&#44; they are still not considered therapeutic targets at this time&#46; Ongoing research is evaluating new biomarkers as potential future targets&#46; Resolution of histological inflammation has also been associated with better outcomes&#44; however&#44; the evidence is limited and the definition of histologic healing is still not clear&#46; Ultimately&#44; restoring quality of life is essential&#46; In recognition of the patient&#39;s goals in wellness&#44; patient reported outcomes are part of the therapeutic goals&#46; When combined with mucosal healing endpoints&#44; patient reported outcomes serve as a composite endpoint in IBD clinical trials and now patient care&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La introducci&#243;n de terapias biol&#243;gicas para el tratamiento de la Enfermedad Inflamatoria Intestinal &#40;EII&#41; demostr&#243; que la resoluci&#243;n de la inflamaci&#243;n mucosa era factible&#46; Subsecuentemente&#44; se ha demostrado que la curaci&#243;n de la mucosa se asocia a remisi&#243;n cl&#237;nica prolongada&#44; menor tasa de cirug&#237;as&#44; menor tasa de hospitalizaciones y mejor calidad de vida&#46; Por lo tanto&#44; el control sintom&#225;tico que hasta entonces se consideraba como objetivo terap&#233;utico principal ya se no considera suficiente&#46; Estudios recientes han demostrado que la resoluci&#243;n de la inflamaci&#243;n histol&#243;gica tambi&#233;n se ha asociado con mejores resultados&#44; sin embargo&#44; la evidencia es limitada y la definici&#243;n de curaci&#243;n histol&#243;gica a&#250;n no est&#225; clara&#46; En adici&#243;n&#44; m&#250;ltiples biomarcadores han sido estudiados con el fin de encontrar un m&#233;todo alternativo a la endoscop&#237;a&#44; entre ellos la prote&#237;na C reactiva y la calprotectina fecal&#46; Sin embargo&#44; aunque &#233;stos son &#250;tiles para monitorear la actividad de la enfermedad&#44; no son considerados objetivos terap&#233;uticos&#46; Nuevos biomarcadores est&#225;n bajo investigaci&#243;n&#46; A pesar de que la resoluci&#243;n sintom&#225;tica no es considerada como el objetivo terap&#233;utico principal&#44; el reconocimiento de la percepci&#243;n del paciente respecto a su enfermedad&#44; mejor conocido como resultados comunicados por el paciente&#44; forman parte de los objetivos terap&#233;uticos junto con la curaci&#243;n mucosa&#46;</p></span>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2454
            "Ancho" => 2851
            "Tamanyo" => 557145
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Therapeutic Targets in Inflammatory Bowel Disease&#46;</p>"
        ]
      ]
      1 => 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="spar0030" class="elsevierStyleSimplePara elsevierViewall">Reference&#58; Schroeder KW&#44; Tremaine WJ&#44; IIstrup DM&#46; Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis&#46; A randomized study&#46; N Engl J Med&#46; 1987&#59;317&#40;26&#41;&#58;1625&#8211;9&#46;</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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Subscores 0-3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stool frequency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>normal number of stools for the patient1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1-2 stools more than normal2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3-4 stools more than normal3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5 or more stools more than normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rectal bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>no bleeding1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>streaks of blood with stool less than half of the time2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>obvious blood with stool most of the time3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>blood alone passed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Findings of flexible proctosigmoidoscopy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>normal or inactive1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>mild disease &#40;erythema&#44; decreased vascular pattern&#44; mild friability&#41;2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>moderate disease &#40;marked erythema&#44; absent vascular pattern&#44; friability&#44; erosions&#41;3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>severe disease &#40;spontaneous bleeding&#44; ulceration&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Physician&#39;s global assessment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>normal1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>mild disease2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>moderate disease3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>severe disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2101773.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Mayo Score&#46;</p>"
        ]
      ]
      2 => 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:3 [
          "leyenda" => "<p id="spar0031" class="elsevierStyleSimplePara elsevierViewall">Total 1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Total 2<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Total 3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Total 4<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Total A Numbers &#40;n&#41; of segments totally or partially explored &#40;1-5&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>n Total A divided by n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Total B Quote 3 if ulcerated stenosis anywhere&#44; 0 if not<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Total C Quote 3 if non-ulcerated stenosis anywhere&#44; 0 if not<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Total D Total B<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>C<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>D<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>CDEIS</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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ileum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Right Colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Transverse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Left&#47;Sigmoid Colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rectum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deep ulceration &#40;0 points if none&#44; 12 points if present&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Superficial ulceration &#40;0 points if none&#44; 6 points if present&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Surface involved by disease in cm &#40;0-10 points&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Surface involved by ulceration in cm &#40;0-10 points&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2101774.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The 10<span class="elsevierStyleHsp" style=""></span>cm scale represents the surface effectively explored&#46; Reference&#58; Mary JY&#44; Modigliani R&#46; Development and validation of an endoscopic index of the severity for Crohn&#39;s disease&#58; a prospective multicentre study&#46; Groupe d&#8217;Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif &#40;GETAID&#41;&#46; Gut&#46; 1989&#59;30&#40;7&#41;&#58;983&#8211;9&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">CDEIS&#46;</p>"
        ]
      ]
      3 => 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="spar0040" class="elsevierStyleSimplePara elsevierViewall">Total SES-CD<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>sum of the 4 variables in the 5 bowel segments &#40;rectum&#44; sigmoid&#47;left colon&#44; transverse colon&#44; right colon and ileum&#41;&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Reference&#58; Daperno M&#44; D&#8217;Haens G&#44; Van Assche G&#44; Baert F&#44; Bulois P&#44; Maunoury V&#44; et al&#46; Development and validation of a new&#44; simplified endoscopic activity score for Crohn&#39;s disease&#58; the SES-CD&#46; Gastrointest Endosc&#46; 2004&#59;60&#40;4&#41;&#58;505-12&#46;</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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Simple Endoscopic Score for Crohn&#769;s Disease values</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" 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><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Size of ulcers&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">None&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">Aphthous ulcer &#40;diameter 0&#46;1-0&#46;5 cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Large ulcer &#40;diameter 0&#46;5-2 cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Very large ulcer &#40;diameter<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2 cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ulcerated surface&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">None&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">&#60;<span class="elsevierStyleHsp" style=""></span>10&#37;&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">10-30&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>30&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Affected surface&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">Unaffected segment&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">&#60;<span class="elsevierStyleHsp" style=""></span>50&#37;&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">50-75&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>75&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presence of narrowings&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">None&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">Single&#44; can be passed&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">Multiple&#44; can be passed&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">Cannot be passed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2101775.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">SES-CD&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Referencias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:49 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treat to Target in Inflammatory Bowel Disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Bossuyt"
                            1 => "S&#46; Vermeire"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11938-016-0077-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Treat Options Gastroenterol&#46;"
                        "fecha" => "2016"
                        "volumen" => "14"
                        "paginaInicial" => "61"
                        "paginaFinal" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26864745"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A Noninvasive Method to Assess Mucosal Healing in Patients With Crohn&#39;s Disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "W&#46;J&#46; Sandborn"
                            1 => "M&#46;T&#46; Abreu"
                            2 => "M&#46;C&#46; Dubinsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterol Hepatol &#40;NY&#41;&#46;"
                        "fecha" => "2018"
                        "volumen" => "14"
                        "numero" => "5 Suppl 2"
                        "paginaInicial" => "1"
                        "paginaFinal" => "12"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis&#58; A Systematic Review and Meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;C&#46; Shah"
                            1 => "J&#46;F&#46; Colombel"
                            2 => "B&#46;E&#46; Sands"
                            3 => "N&#46; Narula"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2016.01.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol&#46;"
                        "fecha" => "2016"
                        "volumen" => "14"
                        "paginaInicial" => "1245"
                        "paginaFinal" => "1255"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26829025"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selecting Therapeutic Targets in Inflammatory Bowel Disease &#40;STRIDE&#41;&#58; Determining Therapeutic Goals for Treat-to-Target"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Peyrin-Biroulet"
                            1 => "W&#46; Sandborn"
                            2 => "B&#46;E&#46; Sands"
                            3 => "W&#46; Reinisch"
                            4 => "W&#46; Bemelman"
                            5 => "R&#46;V&#46; Bryant"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ajg.2015.233"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol&#46;"
                        "fecha" => "2015"
                        "volumen" => "110"
                        "paginaInicial" => "1324"
                        "paginaFinal" => "1338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26303131"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis&#46; A randomized study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46;W&#46; Schroeder"
                            1 => "W&#46;J&#46; Tremaine"
                            2 => "D&#46;M&#46; IIstrup"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM198712243172603"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "1987"
                        "volumen" => "317"
                        "paginaInicial" => "1625"
                        "paginaFinal" => "1629"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3317057"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of a Crohn&#39;s Disease Activity Index&#58; National Cooperative Crohn&#39;s Disease Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "W&#46;R&#46; Best"
                            1 => "J&#46;M&#46; Becktel"
                            2 => "J&#46;W&#46; Singleton"
                            3 => "F&#46; Kern Jr&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology&#46;"
                        "fecha" => "1976"
                        "volumen" => "70"
                        "paginaInicial" => "439"
                        "paginaFinal" => "444"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1248701"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A simple index of Crohn&#39;s-disease activity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;F&#46; Harvey"
                            1 => "J&#46;M&#46; Bradshaw"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(13)70190-5"
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "1980"
                        "volumen" => "1"
                        "paginaInicial" => "514"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24461611"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Defining the optimal response criteria for the Crohn&#39;s disease activity index for induction studies in patients with mildly to moderately active Crohn&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;T&#46; Thia"
                            1 => "W&#46;J&#46; Sandborn"
                            2 => "J&#46;D&#46; Lewis"
                            3 => "E&#46;V&#46; Loftus Jr&#46;"
                            4 => "B&#46;G&#46; Feagan"
                            5 => "A&#46;H&#46; Steinhart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1572-0241.2008.02176.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol&#46;"
                        "fecha" => "2008"
                        "volumen" => "103"
                        "paginaInicial" => "3123"
                        "paginaFinal" => "3131"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18786111"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation Between the Crohn&#39;s Disease Activity and Harvey-Bradshaw Indices in Assessing Crohn&#39;s Disease Severity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Vermeire"
                            1 => "S&#46; Schreiber"
                            2 => "W&#46;J&#46; Sandborn"
                            3 => "C&#46; Dubois"
                            4 => "P&#46; Rutgeerts"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2010.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol&#46;"
                        "fecha" => "2010"
                        "volumen" => "8"
                        "paginaInicial" => "357"
                        "paginaFinal" => "363"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20096379"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;J&#46; Sandborn"
                            1 => "G&#46; van Assche"
                            2 => "W&#46; Reinisch"
                            3 => "J&#46;F&#46; Colombel"
                            4 => "G&#46; D&#8217;Haens"
                            5 => "D&#46;C&#46; Wolf"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2011.10.032"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology&#46;"
                        "fecha" => "2012"
                        "volumen" => "142"
                        "paginaInicial" => "257"
                        "paginaFinal" => "265"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22062358"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;J&#46; Sandborn"
                            1 => "B&#46;G&#46; Feagan"
                            2 => "D&#46;C&#46; Wolf"
                            3 => "G&#46; D&#8217;Haens"
                            4 => "S&#46; Vermeire"
                            5 => "S&#46;B&#46; Hanauer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1513248"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "2016"
                        "volumen" => "374"
                        "paginaInicial" => "1754"
                        "paginaFinal" => "1762"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27144850"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adalimumab for maintenance treatment of Crohn&#39;s disease&#58; Results of the CLASSIC II trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;J&#46; Sandborn"
                            1 => "S&#46;B&#46; Hanauer"
                            2 => "P&#46; Rutgeerts"
                            3 => "R&#46;N&#46; Fedorak"
                            4 => "M&#46; Lulcas"
                            5 => "D&#46;G&#46; MacIntosh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2006.106781"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2007"
                        "volumen" => "56"
                        "paginaInicial" => "1232"
                        "paginaFinal" => "1239"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17299059"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maintenance infliximab for Crohn&#39;s disease&#58; the ACCENT I randomised trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;B&#46; Hanauer"
                            1 => "B&#46;G&#46; Feagan"
                            2 => "G&#46;R&#46; Lichtenstein"
                            3 => "L&#46;F&#46; Mayer"
                            4 => "S&#46; Schreiber"
                            5 => "J&#46;F&#46; Colombel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(02)08512-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2002"
                        "volumen" => "359"
                        "paginaInicial" => "1541"
                        "paginaFinal" => "1549"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12047962"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "What Are the Targets of Inflammatory Bowel Disease Management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46; Lega"
                            1 => "M&#46;C&#46; Dubinsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ibd/izy064"
                      "Revista" => array:6 [
                        "tituloSerie" => "Inflamm Bowel Dis&#46;"
                        "fecha" => "2018"
                        "volumen" => "24"
                        "paginaInicial" => "1670"
                        "paginaFinal" => "1675"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29697788"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Infliximab&#44; Azathioprine&#44; or Combination Therapy for Crohn&#39;s Disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:5 [
                            0 => "J&#46;F&#46; Colombel"
                            1 => "W&#46;J&#46; Sandborn"
                            2 => "W&#46; Reinisch"
                            3 => "G&#46;J&#46; Mantzaris"
                            4 => "A&#46; Kornbluth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0904492"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "2010"
                        "volumen" => "362"
                        "paginaInicial" => "1383"
                        "paginaFinal" => "1395"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20393175"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microscopic activity in ulcerative colitis&#58; what does it mean&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46;A&#46; Riley"
                            1 => "V&#46; Mani"
                            2 => "M&#46;J&#46; Goodman"
                            3 => "S&#46; Dutt"
                            4 => "M&#46;E&#46; Herd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.32.2.174"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "1991"
                        "volumen" => "32"
                        "paginaInicial" => "174"
                        "paginaFinal" => "178"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1864537"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Discrepancies between patient-reported outcomes&#44; and endoscopic and histological appearance in UC"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;F&#46; Colombel"
                            1 => "M&#46;E&#46; Keir"
                            2 => "A&#46; Scherl"
                            3 => "R&#46; Zhao"
                            4 => "G&#46; de Hertogh"
                            5 => "W&#46;A&#46; Faubion"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gutjnl-2016-312307"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2017"
                        "volumen" => "66"
                        "paginaInicial" => "2063"
                        "paginaFinal" => "2068"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27590995"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IBS-like symptoms in patients with inflammatory bowel disease in remission&#59; relationships with quality of life and coping behavior"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46;M&#46; Minderhoud"
                            1 => "B&#46; Oldenburg"
                            2 => "J&#46;A&#46; Wismeijer"
                            3 => "G&#46;P&#46; van Berge Henegouwen"
                            4 => "A&#46;J&#46; Smout"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1023/b:ddas.0000020506.84248.f9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dig Dis Sci&#46;"
                        "fecha" => "2004"
                        "volumen" => "49"
                        "paginaInicial" => "469"
                        "paginaFinal" => "474"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15139501"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of irritable bowel syndrome-like symptoms in ulcerative colitis patients with clinical and endoscopic evidence of remission&#58; prospective multicenter study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Fukuba"
                            1 => "S&#46; Ishihara"
                            2 => "Y&#46; Tada"
                            3 => "N&#46; Oshima"
                            4 => "I&#46; Moriyama"
                            5 => "T&#46; Yuki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/00365521.2014.898084"
                      "Revista" => array:6 [
                        "tituloSerie" => "Scand J Gastroenterol&#46;"
                        "fecha" => "2014"
                        "volumen" => "49"
                        "paginaInicial" => "674"
                        "paginaFinal" => "680"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24646420"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Functional bowel symptoms in quiescent inflammatory bowel diseases&#58; Role of epithelial barrier disruption and low-grade inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Vivinus-N&#233;bot"
                            1 => "G&#46; Frin-Mathy"
                            2 => "H&#46; Bzioueche"
                            3 => "R&#46; Dainese"
                            4 => "G&#46; Bernard"
                            5 => "R&#46; Anty"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gutjnl-2012-304066"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2014"
                        "volumen" => "63"
                        "paginaInicial" => "744"
                        "paginaFinal" => "752"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23878165"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunohistochemical analysis of myenteric ganglia and interstitial cells of Cajal in ulcerative colitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Bernardini"
                            1 => "C&#46; Segnani"
                            2 => "C&#46; Ippolito"
                            3 => "R&#46; De Giorgio"
                            4 => "R&#46; Colucci"
                            5 => "M&#46;S&#46; Faussone-Pellegrini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1582-4934.2011.01298.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Cell Mol Med&#46;"
                        "fecha" => "2012"
                        "volumen" => "16"
                        "paginaInicial" => "318"
                        "paginaFinal" => "327"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21426484"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1590865810605087"
                          "estado" => "S300"
                          "issn" => "15908658"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2&#58; IBD scores and general principales and technical aspects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Sturm"
                            1 => "C&#46; Maaser"
                            2 => "E&#46; Calabrese"
                            3 => "V&#46; Annese"
                            4 => "G&#46; Fiorino"
                            5 => "T&#46; Kucharzik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "J Crohns Colitis&#46;"
                        "fecha" => "2018"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development and validation of an endoscopic index of the severity for Crohn&#39;s disease&#58; a prospective multicentre study&#46; Groupe d&#8217;Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif &#40;GETAID&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;Y&#46; Mary"
                            1 => "R&#46; Modigliani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.30.7.983"
                      "Revista" => array:7 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "1989"
                        "volumen" => "30"
                        "paginaInicial" => "983"
                        "paginaFinal" => "989"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2668130"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0022347608001054"
                          "estado" => "S300"
                          "issn" => "00223476"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development and validation of a new&#44; simplified endoscopic activity score for Crohn&#39;s disease&#58; the SES-CD"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Daperno"
                            1 => "G&#46; D&#8217;Haens"
                            2 => "G&#46; Van Assche"
                            3 => "F&#46; Baert"
                            4 => "P&#46; Bulois"
                            5 => "V&#46; Maunoury"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0016-5107(04)01878-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastrointest Endosc&#46;"
                        "fecha" => "2004"
                        "volumen" => "60"
                        "paginaInicial" => "505"
                        "paginaFinal" => "512"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15472670"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review with meta-analysis&#58; mucosal healing is associated with improved long-term outcomes in Crohn&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;C&#46; Shah"
                            1 => "J&#46;F&#46; Colombel"
                            2 => "B&#46;E&#46; Sands"
                            3 => "N&#46; Narula"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/apt.13475"
                      "Revista" => array:6 [
                        "tituloSerie" => "Aliment Pharmacol Ther&#46;"
                        "fecha" => "2016"
                        "volumen" => "43"
                        "paginaInicial" => "317"
                        "paginaFinal" => "333"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26607562"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diffusion-weighted magnetic resonance imaging for detecting and assessing ileal inflammation in Crohn&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Buisson"
                            1 => "A&#46; Joubert"
                            2 => "P&#46;F&#46; Montoriol"
                            3 => "D&#46; Da Ines"
                            4 => "C&#46; Hordonneau"
                            5 => "B&#46; Pereira"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/apt.12201"
                      "Revista" => array:6 [
                        "tituloSerie" => "Aliment Pharmacol Ther&#46;"
                        "fecha" => "2013"
                        "volumen" => "37"
                        "paginaInicial" => "537"
                        "paginaFinal" => "545"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23289713"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Rimola"
                            1 => "S&#46; Rodriguez"
                            2 => "O&#46; Garc&#237;a-Bosch"
                            3 => "I&#46; Ord&#225;s"
                            4 => "E&#46; Ayala"
                            5 => "M&#46; Aceituno"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2008.167957"
                      "Revista" => array:7 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2009"
                        "volumen" => "58"
                        "paginaInicial" => "1113"
                        "paginaFinal" => "1120"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19136510"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673609613040"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Van Assche"
                            1 => "D&#46; Vanbeckevoort"
                            2 => "D&#46; Bielen"
                            3 => "G&#46; Coremans"
                            4 => "I&#46; Aerden"
                            5 => "M&#46; Noman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1572-0241.2003.07241.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol&#46;"
                        "fecha" => "2003"
                        "volumen" => "98"
                        "paginaInicial" => "332"
                        "paginaFinal" => "339"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12591051"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Up-to-date overview of imaging techniques in the diagnosis and management of inflammatory bowel diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46;B&#46; Biernacka"
                            1 => "D&#46; Bara&#324;ska"
                            2 => "P&#46; Grzelak"
                            3 => "E&#46; Czkwianianc"
                            4 => "K&#46; Szabelska-Zakrzewska"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5114/pg.2019.83423"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prz Gastroenterol&#46;"
                        "fecha" => "2019"
                        "volumen" => "14"
                        "paginaInicial" => "19"
                        "paginaFinal" => "25"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30944674"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical&#44; biological&#44; and histologic parameters as predictors of relapse in ulcerative colitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Bitton"
                            1 => "M&#46;A&#46; Peppercorn"
                            2 => "D&#46;A&#46; Antonioli"
                            3 => "J&#46;L&#46; Niles"
                            4 => "S&#46; Shah"
                            5 => "A&#46; Bousvaros"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/gast.2001.20912"
                      "Revista" => array:7 [
                        "tituloSerie" => "Gastroenterology&#46;"
                        "fecha" => "2001"
                        "volumen" => "120"
                        "paginaInicial" => "13"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11208709"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1474442207702673"
                          "estado" => "S300"
                          "issn" => "14744422"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission&#58; A Prospective Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Zenlea"
                            1 => "E&#46;U&#46; Yee"
                            2 => "L&#46; Rosenberg"
                            3 => "M&#46; Boyle"
                            4 => "K&#46;S&#46; Nanda"
                            5 => "J&#46;L&#46; Wolf"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ajg.2016.50"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol&#46;"
                        "fecha" => "2016"
                        "volumen" => "111"
                        "paginaInicial" => "685"
                        "paginaFinal" => "690"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26977756"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Bessissow"
                            1 => "B&#46; Lemmens"
                            2 => "M&#46; Ferrante"
                            3 => "R&#46; Bisschops"
                            4 => "K&#46; Van Steen"
                            5 => "K&#46; Geboes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ajg.2012.301"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Gastroenterol&#46;"
                        "fecha" => "2012"
                        "volumen" => "107"
                        "paginaInicial" => "1684"
                        "paginaFinal" => "1692"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23147523"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673616307759"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Histologic Normalization Occurs in Ulcerative Colitis and Is Associated With Improved Clinical Outcomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Christensen"
                            1 => "S&#46;B&#46; Hanauer"
                            2 => "J&#46; Erlich"
                            3 => "O&#46; Kassim"
                            4 => "P&#46;R&#46; Gibson"
                            5 => "J&#46;R&#46; Turner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2017.02.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "15"
                        "paginaInicial" => "1557"
                        "paginaFinal" => "1564"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28238954"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Beyond endoscopic mucosal healing in UC&#58; histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;V&#46; Bryant"
                            1 => "D&#46;C&#46; Burger"
                            2 => "J&#46; Delo"
                            3 => "A&#46;J&#46; Walsh"
                            4 => "S&#46; Thomas"
                            5 => "A&#46; von Herbay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gutjnl-2015-309598"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2016"
                        "volumen" => "65"
                        "paginaInicial" => "408"
                        "paginaFinal" => "414"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25986946"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A reproducible grading scale for histological assessment of inflammation in ulcerative colitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "K&#46; Geboes"
                            1 => "R&#46; Riddell"
                            2 => "A&#46; Ost"
                            3 => "B&#46; Jensfelt"
                            4 => "T&#46; Persson"
                            5 => "R&#46; L&#246;fberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.47.3.404"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2000"
                        "volumen" => "47"
                        "paginaInicial" => "404"
                        "paginaFinal" => "409"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10940279"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development and validation of a histological index for UC"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;H&#46; Mosli"
                            1 => "B&#46;G&#46; Feagan"
                            2 => "G&#46; Zou"
                            3 => "W&#46;J&#46; Sandborn"
                            4 => "G&#46; D&#8217;Haens"
                            5 => "R&#46; Khanna"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gutjnl-2015-310393"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2017"
                        "volumen" => "66"
                        "paginaInicial" => "50"
                        "paginaFinal" => "58"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26475633"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review&#58; histological remission in inflammatory bowel disease&#44; Is &#8220;complete&#8221; remission the new treatment paradigm&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46;V&#46; Bryant"
                            1 => "S&#46; Winer"
                            2 => "S&#46;P&#46; Travis"
                            3 => "R&#46;H&#46; Riddell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.crohns.2014.08.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "An IOIBD initiative&#46; J Crohns Colitis&#46;"
                        "fecha" => "2014"
                        "volumen" => "8"
                        "paginaInicial" => "1582"
                        "paginaFinal" => "1597"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25267173"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C-reactive protein&#44; fecal calprotectin&#44; and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients&#58; A systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;H&#46; Mosli"
                            1 => "G&#46; Zou"
                            2 => "S&#46;K&#46; Garg"
                            3 => "S&#46;G&#46; Feagan"
                            4 => "J&#46;K&#46; MacDonald"
                            5 => "N&#46; Chande"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ajg.2015.120"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Gastroenterol&#46;"
                        "fecha" => "2015"
                        "volumen" => "110"
                        "paginaInicial" => "802"
                        "paginaFinal" => "819"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25964225"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673614605390"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C-reactive protein&#58; A predictive factor and marker of inflammation in inflammatory bowel disease&#44; Results from a prospective population-based study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Henriksen"
                            1 => "J&#46; Jahnsen"
                            2 => "I&#46; Lygren"
                            3 => "N&#46; Stray"
                            4 => "J&#46; Sauar"
                            5 => "M&#46;H&#46; Vatn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2007.146357"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut&#46;"
                        "fecha" => "2008"
                        "volumen" => "57"
                        "paginaInicial" => "1518"
                        "paginaFinal" => "1523"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18566104"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinically active Crohn&#39;s disease in the presence of a low C-reactive protein"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "T&#46;H&#46; Florin"
                            1 => "E&#46;W&#46; Paterson"
                            2 => "E&#46;V&#46; Fowler"
                            3 => "G&#46;L&#46; Radford-Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/00365520500217118"
                      "Revista" => array:6 [
                        "tituloSerie" => "Scand J Gastroenterol&#46;"
                        "fecha" => "2006"
                        "volumen" => "41"
                        "paginaInicial" => "306"
                        "paginaFinal" => "311"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16497618"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1059G&#47;C polymorphism in the C-reactive protein &#40;CRP&#41; gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn&#39;s disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Thalmaier"
                            1 => "J&#46; Dambacher"
                            2 => "J&#46; Seiderer"
                            3 => "A&#46; Konrad"
                            4 => "V&#46; Schachinger"
                            5 => "S&#46; Pfennig"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Aliment Pharmacol Ther&#46;"
                        "fecha" => "2006"
                        "volumen" => "24"
                        "paginaInicial" => "1105"
                        "paginaFinal" => "1115"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "From bench to bedside&#58; Fecal calprotectin in inflammatory bowel diseases clinical setting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;G&#46; Mumolo"
                            1 => "L&#46; Bertani"
                            2 => "L&#46; Ceccarelli"
                            3 => "G&#46; Laino"
                            4 => "G&#46; Di Fluri"
                            5 => "E&#46; Albano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3748/wjg.v24.i33.3681"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Gastroenterol&#46;"
                        "fecha" => "2018"
                        "volumen" => "24"
                        "paginaInicial" => "3681"
                        "paginaFinal" => "3694"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30197475"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Use of Fecal Calprotectin in Inflammatory Bowel Disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "I&#46; Bjarnason"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Gastroenterol Hepatol &#40;NY&#41;&#46;"
                        "fecha" => "2017"
                        "volumen" => "13"
                        "paginaInicial" => "53"
                        "paginaFinal" => "56"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Discriminating IBD from IBS&#58; Comparison of the test performance of fecal markers&#44; blood leukocytes&#44; CRP&#44; and IBD antibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;M&#46; Schoepfer"
                            1 => "M&#46; Trummler"
                            2 => "P&#46; Seeholzer"
                            3 => "B&#46; Seibold-Schmid"
                            4 => "F&#46; Seibold"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ibd.20275"
                      "Revista" => array:6 [
                        "tituloSerie" => "Inflamm Bowel Dis&#46;"
                        "fecha" => "2008"
                        "volumen" => "14"
                        "paginaInicial" => "32"
                        "paginaFinal" => "39"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17924558"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fecal calprotectin in assessing inflammatory bowel disease endoscopic activity&#58; A diagnostic accuracy meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46; Rokkas"
                            1 => "P&#46; Portincasa"
                            2 => "I&#46;E&#46; Koutroubakis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Gastrointest Liver Dis&#46;"
                        "fecha" => "2018"
                        "volumen" => "27"
                        "paginaInicial" => "299"
                        "paginaFinal" => "306"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fecal Calprotectin is a Surrogate Marker for Endoscopic Lesions in Inflammatory Bowel Disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; D&#8217;Haens"
                            1 => "M&#46; Ferrante"
                            2 => "S&#46; Vermeire"
                            3 => "F&#46; Baert"
                            4 => "M&#46; Noman"
                            5 => "L&#46; Moortgat"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ibd.22917"
                      "Revista" => array:6 [
                        "tituloSerie" => "Inflamm Bowel Dis&#46;"
                        "fecha" => "2012"
                        "volumen" => "18"
                        "paginaInicial" => "2218"
                        "paginaFinal" => "2224"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22344983"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PROMises Made&#44; PROMises To Be Kept&#58; Patient-Reported Outcome Measures in Inflammatory Bowel Diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Singh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2018.01.032"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol&#46;"
                        "fecha" => "2018"
                        "volumen" => "16"
                        "paginaInicial" => "624"
                        "paginaFinal" => "626"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29409805"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Patient reported-outcomes in a French nationwide survey of inflammatory bowel disease patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Williet"
                            1 => "H&#46; Sarter"
                            2 => "C&#46; Gower-Rousseau"
                            3 => "C&#46; Adrianjafy"
                            4 => "A&#46; Olympie"
                            5 => "A&#46; Buisson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ecco-jcc/jjw145"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Crohns Colitis&#46;"
                        "fecha" => "2017"
                        "volumen" => "11"
                        "paginaInicial" => "165"
                        "paginaFinal" => "174"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27516406"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Converging goals of treatment of inflammatory bowel disease from clinical trials and practice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B&#46;G&#46; Levesque"
                            1 => "W&#46;J&#46; Sandborn"
                            2 => "J&#46; Ruel"
                            3 => "B&#46;G&#46; Feagan"
                            4 => "B&#46;E&#46; Sands"
                            5 => "J&#46;F&#46; Colombel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2014.08.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology&#46;"
                        "fecha" => "2015"
                        "volumen" => "148"
                        "paginaInicial" => "37"
                        "paginaFinal" => "51"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25127678"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/07168640/0000003000000004/v1_201908150631/S0716864019300616/v1_201908150631/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "78900"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Tema Central&#58; Enfermedad Inflamatoria Intestinal I"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/07168640/0000003000000004/v1_201908150631/S0716864019300616/v1_201908150631/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0716864019300616?idApp=UINPBA00004N"
]

Article information

ISSN: 07168640
Original language: English

DOI:10.1016/j.rmclc.2019.06.008

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	6	2	8
2024 October	68	15	83
2024 September	95	17	112
2024 August	52	15	67
2024 July	75	13	88
2024 June	69	21	90
2024 May	67	13	80
2024 April	70	8	78
2024 March	99	12	111
2024 February	89	16	105
2024 January	76	10	86
2023 December	67	16	83
2023 November	104	38	142
2023 October	129	27	156
2023 September	110	17	127
2023 August	48	11	59
2023 July	24	12	36
2023 June	41	7	48
2023 May	67	10	77
2023 April	56	7	63
2023 March	48	8	56
2023 February	32	4	36
2023 January	16	5	21
2022 December	17	13	30
2022 November	19	9	28
2022 October	36	12	48
2022 September	34	18	52
2022 August	45	16	61
2022 July	43	7	50
2022 June	25	7	32
2022 May	27	18	45
2022 April	55	8	63
2022 March	45	12	57
2022 February	55	4	59
2022 January	69	11	80
2021 December	55	14	69
2021 November	37	14	51
2021 October	65	15	80
2021 September	55	18	73
2021 August	80	12	92
2021 July	52	15	67
2021 June	45	12	57
2021 May	55	26	81
2021 April	92	52	144
2021 March	45	14	59
2021 February	29	9	38
2021 January	31	21	52
2020 December	19	11	30
2020 November	29	7	36
2020 October	21	20	41
2020 September	39	20	59
2020 August	50	11	61
2020 July	44	14	58
2020 June	40	9	49
2020 May	34	18	52
2020 April	32	9	41
2020 March	33	16	49
2020 February	32	5	37
2020 January	21	10	31
2019 December	35	22	57
2019 November	29	15	44
2019 October	31	13	44
2019 September	33	26	59
2019 August	23	24	47

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter