The importance of calprotectin for differentiating organic inflammatory disease and avoiding unnecessary procedures in paediatrics

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Each box represents the interquartile range of the group, from 25% percentile (bottom side of the box) to the 75% one (upper part of the box). Each dash line shows the median value of the group. The horizontal dotted line indicates the cut-off value of 50μg/g. Different letters represent the statistical correlations between the respective groups." ] ] ] "textoCompleto" => "IntroductionA frequent challenge that gastroenterologists face at the time of diagnosis is the differentiation between functional and organic intestinal disorders.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> Intense abdominal pain, diarrhoea, and generalised malaise are symptoms frequently associated with functional gastrointestinal disorders, including functional abdominal pain, irritable bowel syndrome, functional dyspepsia, and abdominal migraine.<a class="elsevierStyleCrossRef" href="#bib0165">2</a> Nevertheless, patients with organic intestinal disorders (Crohn's disease and ulcerative colitis) also experience some of these symptoms.<a class="elsevierStyleCrossRef" href="#bib0170">3</a> Crohn's disease and ulcerative colitis are chronic disorders characterised by the inflammation of the gastrointestinal tract. Diagnosis and confirmation require invasive endoscopic or radiological procedures that have potential risks, especially in paediatrics.<a class="elsevierStyleCrossRef" href="#bib0175">4</a> In contrast, the diagnosis of irritable bowel syndrome is mainly based on symptoms.<a class="elsevierStyleCrossRef" href="#bib0180">5</a> Different acute-phase reactants such as ESR (erythrocyte sedimentation rate) and C-reactive protein (CRP) have been traditionally used as serological markers of inflammation. In the last few years, faecal calprotectin has become a biomarker for the diagnosis of IBD.<a class="elsevierStyleCrossRefs" href="#bib0185">6–8</a> Calprotectin is a protein of the S100 family that is released mainly by neutrophils, monocytes and macrophages.<a class="elsevierStyleCrossRefs" href="#bib0200">9,10</a> It constitutes the response generated by the innate immune system. Calprotectin also exerts antibacterial, pro-apoptotic, and chemotactic activity.<a class="elsevierStyleCrossRefs" href="#bib0210">11–13</a> Calprotectin has been measured in serum, plasma, saliva, urine, cerebrospinal fluid, and synovial fluid. The highest concentration has been found in faeces.<a class="elsevierStyleCrossRefs" href="#bib0225">14,15</a> Plasma calprotectin levels have been shown to increase about 5–40 fold under inflammatory and pathological conditions. Faecal levels are approximately 6 fold higher than plasma levels.<a class="elsevierStyleCrossRef" href="#bib0235">16</a> Calprotectin is stable in stools for >7 days due to its resistance to proteolytic degradation. Despite the number of studies characterising faecal calprotectin in recent years, data on paediatric populations are still incomplete.<a class="elsevierStyleCrossRefs" href="#bib0240">17–20</a> The objective of the study was to determine the ability of faecal calprotectin for differentiating between functional and organic (intestinal bowel disease, IBD, and non-IBD) diseases in paediatric patients, and to evaluate the correlation between traditional inflammatory parameters and levels of faecal calprotectin.Patients and methodsThis retrospective study involved clinical data from 129 paediatric patients presenting to the Department of Paediatric Gastroenterology at Miguel Servet University Hospital with symptoms of intestinal pathology, including intense abdominal pain, diarrhoea, weight loss and rectal bleeding, between August 2013 and January 2015. The primary endpoint included a differential diagnosis between functional disorder, organic IBD, and organic non-IBD by using faecal calprotectin. The second endpoint involved the analysis of correlation between clinical parameters and levels of calprotectin. Before establishing the final diagnosis, all patients underwent a complete evaluation of serological parameters, including ESR (mm/h), CRP (mg/dl), transferrin saturation (%), serum ferritin (ng/ml), albumin (g/dl), haemoglobin levels (g/dl), and platelet count/l. Faecal calprotectin was also determined in all patients. A stool sample was collected from each patient and frozen at −70°C until analysis. The quantitative determination of calprotectin levels in faeces was performed by Quantum Blue® immunoassay (Bühlmann Laboratories AG). Functional gastrointestinal disorders were diagnosed by following Rome II paediatric criteria.<a class="elsevierStyleCrossRef" href="#bib0260">21</a> Intestinal inflammation was evaluated in patients with cystic fibrosis as part of the annual nutritional and digestive monitoring. Procedures were performed in accordance with guidelines established by the hospital's Ethics Committee.Statistical analysisCategorical variables were expressed as absolute and relative (%) frequencies and continuous variables as median and interquartile range (IQR). Comparisons between diagnostic groups were performed by using Mann–Whitney U test and Bonferroni correction. The correlation between calprotectin levels and serological parameters was evaluated by performing a Spearman's rho test. The statistical significance was established for p≤0.05. All statistical procedures were performed with SPSS 15.0 software.ResultsAlthough the initial number of paediatric patients was 129, diagnostic information was not available for one of them and the total number of patients included in the analysis was therefore 128. The reasons for presenting to the specialist are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, the main ones being: abdominal pain (41 patients, 32.0%); cystic fibrosis (29, 22.7%); rectal bleeding (16, 12.5%); and diarrhoea (14 patients, 10.9%). According to the final diagnosis, patients were classified into three groups: functional (42 patients, 32.8%); organic non-IBD (69, 53.9%); and organic IBD (17, 13.3%) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Of the 129 patients, 70 were male (54.3%) and 59 female (45.7%), with a mean age of 9.1 years (SD 4.5). Demographic and clinical characteristics of patients according to final diagnosis are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. Median values of parameters at baseline were: ESR 11.0mm/h (IQR 4.0–26.0); CRP 0.11mg/dl (IQR 0.03–0.31); transferrin saturation 20.7% (IQR 15.0–25.5); ferritin 44.2ng/ml (IQR 23.5–77.5); albumin 4.4g/dl (IQR 4.2–4.7); haemoglobin 13.1g/dl (IQR 12.4–13.6); and platelet count 2.8×105/l (IQR 2.3–3.4×105). To establish the final diagnosis, specialists needed to perform an endoscopy in 52 patients (41.3%). Of these, 11 patients (26.8%) were finally diagnosed with a functional disease, 24 patients (35.3%) with an organic non-IBD, and 17 patients (100.0%) with an organic IBD. Calprotectin levels were significantly different among the three diagnostic groups (p<0.001) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Levels were higher in organic IBD (500μg/g, IQR 446–1800) than organic non-IBD (61μg/g, IQR 21–200), and functional disease (21μg/g, IQR 16–44). Eight out of 42 patients diagnosed with functional disease (19.0%) had calprotectin levels between 50 and 100μg/g. None had values over 100μg/g. In a subsequent analysis of calprotectin between 1 and 8 months later, none of these patients had levels over 50μg/g (data not shown). Calprotectin levels according to final diagnosis are shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>. Crohn's disease and ulcerative colitis had the highest median values, 497μg/g (IQR 446–1800) and 500μg/g (IQR 380–845) respectively, and functional abdominal pain (21μg/g, IQR 16–44) had the lowest. Calprotectin values for organic IBD were significantly different (p≤0.05) from functional disease and almost all diseases from organic non-IBD. Assuming a cut-off value of 50μg/g, sensibility and specificity of calprotectin, to differentiate patients with IBD from organic non-IBD and functional disease, were 100% (17 IBD cases with calprotectin >50μg/g)/17 total IBD cases), and 60.3% (67 cases with organic non-IBD and functional disease with calprotectin <50μg/g/111 total organic non-IBD and functional cases), respectively. Positive and negative predictive values were: 27.8% (17 IBD cases with calprotectin >50μg/g/61 total cases with calprotectin >50μg/g), and 100% (67 cases with organic non-IBD and functional disease with calprotectin <50μg/g/67 total cases with calprotectin <50μg/g). Similarly, sensibility and specificity of calprotectin, to differentiate patients with organic disease (both IBD and non-IBD) from functional disease, were 61.6% (53 organic cases with calprotectin >50μg/g)/86 total organic cases), and 80.9% (34 cases with functional disease with calprotectin <50μg/g/42 total functional cases), respectively. Positive and negative predictive values were: 86.9% (53 organic cases with calprotectin >50μg/g)/61 total cases with calprotectin >50μg/g), and 50.7% (34 cases with functional disease with calprotectin <50μg/g/67 total cases with calprotectin <50μg/g). Evaluating the correlation between calprotectin values and clinical parameters, with the exception of ferritin levels, all showed significant associations. Positive associations were found between high levels of calprotectin and ESR (rho=0.497), CRP (rho=0.460), and platelet count (rho=0.232). In contrast, an inverse correlation was found between high levels of calprotectin and transferrin saturation (rho=−0.310), albumin levels (rho=−0.412), and haemoglobin levels (rho=−0.309).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>DiscussionPerforming an accurate diagnosis and avoiding unnecessary invasive procedures are priorities for gastrointestinal specialists, especially when dealing with paediatric patients.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> Results from our study corroborate the effectiveness of faecal calprotectin for differentiating between functional and organic intestinal diseases, mainly IBD. In concordance with the literature, calprotectin levels for Crohn's disease and ulcerative colitis were significantly higher compared to functional disease.<a class="elsevierStyleCrossRefs" href="#bib0265">22,23</a> Indeed, a cut-off of 50μg/g (95–100% sensitivity and 44–93% specificity) has been proposed to distinguish diagnosis or relapse in IBD (level>50μg/g) from other non-inflammatory disorders in paediatric populations.<a class="elsevierStyleCrossRef" href="#bib0275">24</a> In our study, 19.0% of patients diagnosed with functional disease showed calprotectin levels ranging between 50 and 100μg/g. In a systematic review from 2014 analysing 6 prospective and 2 retrospective case-control studies and involving 394 paediatric IBD patients, and 321 non-IBD controls, aimed to evaluate the usefulness of faecal calprotectin for the diagnosis of IBD in children, revealed that its sensitivity and specificity were 0.978 and 0.682, respectively.<a class="elsevierStyleCrossRef" href="#bib0280">25</a> Endoscopy is the standard procedure for establishing an accurate diagnosis of IBD. Apart from being invasive, endoscopy is expensive and, in paediatric patients, requires general anaesthesia, which has potential risks.<a class="elsevierStyleCrossRef" href="#bib0175">4</a> It has been reported that more than 60% of colonoscopies performed in young patients showed no pathology, i.e. the procedure was not necessary.<a class="elsevierStyleCrossRef" href="#bib0275">24</a> In our study, 11 patients out of 42 who finally were diagnosed with functional abdominal pain (or 21.2% of total endoscopies) underwent an unnecessary procedure. Other organic pathologies, such as cystic fibrosis, infections, food allergies, polyps and neoplasms may also result in increased levels of calprotectin.<a class="elsevierStyleCrossRefs" href="#bib0285">26,27</a> Similarly, in our study, levels in organic IBD were also significantly higher compared with almost all organic non-IBD studied. Median calprotectin concentrations in cystic fibrosis, coeliac disease, fructose intolerance and infections (Helicobacter pylori) were within normal levels, suggesting that calprotectin may be used as a complementary biomarker during the follow-up of these conditions. The median value for polyps was a little higher than normal values. According to the literature, colonic polyposis has been shown to cause an increase in stool calprotectin.<a class="elsevierStyleCrossRef" href="#bib0295">28</a> Therefore, calprotectin might be used to identify affected patients; and it also suggests the presence of associated lesions. Although not analysed in the present study, different types of functional gastrointestinal disorders have been shown to present similar calprotectin levels.<a class="elsevierStyleCrossRef" href="#bib0300">29</a> Acute phase reactants such as ESR and CRP, however, have provided excellent results when used as inflammatory markers of IBD<a class="elsevierStyleCrossRef" href="#bib0305">30</a>; of all the markers, CRP has been the most studied and has been shown to provide the most reliable results, while ESR, leucocyte and platelet count and albumin have been studied less extensively in IBD.<a class="elsevierStyleCrossRef" href="#bib0310">31</a> Moreover, ESR and CRP offer low specificity and sensitivity for identifying an organic condition in the colon, while the specificity and sensitivity of faecal calprotectin are higher in the small bowel and colon. In our study, calprotectin levels showed positive correlation with both ESR and CRP; especially ESR. The inverse correlation found between faecal calprotectin and serum levels of albumin, haemoglobin, and transferrin saturation may be suggestive of an inverse relationship with the nutritional status of the patient (presumably deficient due to the inflammatory condition). The main limitation of the study was the retrospective nature of the data. Moreover, the low number of patients included in some of these pathologies did not allow a cut-off to be established for distinguishing between organic IBD and non-IBD, or even between functional and organic non-IBD. However, our results corroborate data published in the literature and encourage further prospective experiments involving larger cohorts of patients.In conclusion, the determination of faecal calprotectin is a necessary complementary tool in routine clinical practice for discriminating between functional and organic IBD, and avoiding unnecessary invasive procedures in paediatric patients.FundingNo funding to declare.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1080407" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1025665" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1080406" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1025664" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack366279" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-07-10" "fechaAceptado" => "2017-11-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1025665" "palabras" => array:5 [ 0 => "Calprotectin" 1 => "Diagnosis" 2 => "Functional" 3 => "Organic" 4 => "Inflammatory bowel disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1025664" "palabras" => array:5 [ 0 => "Calprotectina" 1 => "Diagnóstico" 2 => "Funcional" 3 => "Orgánico" 4 => "Enfermedad inflamatoria intestinal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Background and objectiveThe objective of the study was to determine the ability of faecal calprotectin to differentiate functional and organic intestinal diseases in paediatric patients, and to evaluate the correlation between inflammatory parameters and levels of faecal calprotectin. Patients and methodsThis retrospective study involved clinical data from 129 paediatric patients with symptoms of intestinal pathology. Faecal calprotectin was determined by quantitative immunoassay. Patients were classified into three groups: functional (32.8% of patients); organic non-inflammatory bowel disease (IBD, 53.9%); and organic IBD (13.3%). ResultsCalprotectin levels were significantly different among the three groups; between patients with IBD and the others, and also between patients with non-organic IBD and functional. Positive associations were found between high levels of calprotectin and higher erythrocyte sedimentation rate (rho=0.497), C-reactive protein (rho=0.460), and platelet count (rho=0.232). Nevertheless, an inverse correlation was found between high levels of calprotectin and transferrin saturation (rho=−0.310), albumin (rho=−0.412), and haemoglobin levels (rho=−0.309). DiscussionDetermination of faecal calprotectin is a complementary tool in clinical practice for discriminating between functional and organic IBD, avoiding, according to the levels of calprotectin, unnecessary invasive procedures in paediatric patients." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Antecedentes y objetivoEl objetivo de este estudio fue determinar la capacidad de la calprotectina fecal para diferenciar las enfermedades funcionales y orgánicas en los pacientes pediátricos, y evaluar la correlación entre los parámetros inflamatorios y los niveles de calprotectina fecal. Pacientes y métodosEste estudio retrospectivo incluyó los datos clínicos de 129 pacientes pediátricos con síntomas de enfermedad intestinal. Se determinaron los valores de calprotectina fecal mediante inmunoensayo cuantitativo. Se clasificaron los pacientes en 3 grupos: funcionales (32,8% de pacientes), enfermedad intestinal inflamatoria no orgánica (EII, 53,9%) e EII orgánica (13,3%). ResultadosLos niveles de calprotectina fueron significativamente diferentes entre los 3 grupos; entre los pacientes con EII y el resto, y también entre los pacientes con EII no orgánica e EII funcional. Se encontraron asociaciones positivas entre los niveles altos de calprotectina y la tasa de sedimentación eritrocítica alta (Rho=0,497), proteína C reactiva (Rho=0,460) y recuento plaquetario (Rho=0,232). Sin embargo, se encontró una correlación inversa entre los niveles altos de calprotectina y la saturación de transferrina (Rho=−0,310), albúmina (Rho=−0,412) y niveles de hemoglobina (Rho=−0,309). DiscusiónLa determinación de la calprotectina fecal es una herramienta complementara en la práctica clínica para discriminar entre EII funcional y EII orgánica, y evitar con arreglo a los niveles de calprotectina, los procedimientos invasivos innecesarios en pacientes pediátricos." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1033 "Ancho" => 1529 "Tamanyo" => 55573 ] ] "descripcion" => array:1 [ "en" => "Representation of calprotectin levels in the three diagnostic groups. Each box represents the interquartile range of the group, from 25% percentile (bottom side of the box) to the 75% one (upper part of the box). Each dash line shows the median value of the group. The horizontal dotted line indicates the cut-off value of 50μg/g. Different letters represent the statistical correlations between the respective diagnostic groups." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1392 "Ancho" => 2521 "Tamanyo" => 140167 ] ] "descripcion" => array:1 [ "en" => "Representation of calprotectin levels regarding the final diagnosis. Each box represents the interquartile range of the group, from 25% percentile (bottom side of the box) to the 75% one (upper part of the box). Each dash line shows the median value of the group. The horizontal dotted line indicates the cut-off value of 50μg/g. Different letters represent the statistical correlations between the respective groups." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reasons for presenting to the specialist, n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total (N=128) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abdominal pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 (32.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abdominal pain and weight loss \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (3.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cystic fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 (22.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (10.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diarrhoea and weight loss \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rectal bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rectal bleeding and diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (5.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rectal bleeding and constipation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Crohn's disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fistula \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hirschsprung's disease, colostomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Underweight \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melaena \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pallor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melaena and haematemesis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Raised markers for coeliac disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitamin B12 deficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Iron-deficiency anaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1844501.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Reasons for presenting to the specialist for the total number of paediatric patients." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Final diagnosis, n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total (N=128) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Functional abdominal pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 (32.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cystic fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 (22.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Crohn's disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (7.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Helicobacter pylori \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (7.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute gastroenteritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (7.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ulcerative colitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (6.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bacterial overgrowth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (4.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Polyps \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (3.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Coeliac disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (2.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Diagnostic groups, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Functional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 (32.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Organic non-IBD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69 (53.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Organic IBD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (13.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1844502.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Final diagnosis and groups for the total number of paediatric patients." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SD, standard deviation; ESR, erythrocyte sedimentation rate; IQR, interquartile range; CRP, C-reactive protein" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total (N=128) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Functional (n=42) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Organic, non-IBD (n=69) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Organic, IBD (n=17) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male gender, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70 (54.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 (54.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (50.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (70.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, mean years (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.1 (4.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.2 (2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.3 (4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.9 (4.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Clinical parameters at baseline</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESR, median mm/h (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.0 (4.0–26.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.5 (3.0–15.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.0 (4.0–21.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.0 (29.5–48.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CRP, median mg/dl (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.11 (0.03–0.31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.06 (0.03–0.18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.06 (0.02–0.21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.40 (0.17–2.63) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transferrin saturation, median % (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.7 (15.0–25.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.2 (15.5–25.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.1 (17.3–27.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.9 (8.3–16.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ferritin, median ng/ml (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.2 (23.5–77.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59.2 (33.4–85.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.3 (23.3–66.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22.7 (15.0–68.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin, median g/dl (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.4 (4.2–4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.6 (4.4–4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.4 (4.3–4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.2 (4.0–4.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haemoglobin, median g/dl (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.1 (12.4–13.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.4 (12.7–13.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.2 (12.2–13.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.3 (11.3–12.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelet count×105/l, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.8 (2.3–3.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.4 (2.2–2.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.9 (2.3–3.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.8 (3.3–4.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Endoscopy requirement, n/N available (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52/126 (41.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11/41 (26.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24/68 (35.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 (100.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gastroscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13/49 (26.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/10 (50.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8/22 (36.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/17 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Colonoscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/49 (12.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/10 (10.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/22 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/17 (17.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gastroscopy and colonoscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30/49 (61.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/10 (40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12/22 (54.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14/17 (82.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1844503.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic and clinical characteristics of paediatric patients according to the final diagnosis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0160" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differential diagnosis between functional and organic intestinal disorders: is there a role for non-invasive tests?" 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The importance of calprotectin for differentiating organic inflammatory disease and avoiding unnecessary procedures in paediatrics

Importancia de la calprotectina para la diferenciación de la enfermedad inflamatoria orgánica y la evitación de procedimientos innecesarios en pediatría

Ruth García Romero

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ruthgarciaromero@yahoo.es

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, Marta López Ubeda, Lidia Cardiel Valiente, Ignacio Ros Arnal

Department of Paediatric Gastroenterology, Miguel Servet University Hospital, Paseo Isabel La Católica, 1-3, 50009, Zaragoza, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">A frequent challenge that gastroenterologists face at the time of diagnosis is the differentiation between functional and organic intestinal disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> Intense abdominal pain&#44; diarrhoea&#44; and generalised malaise are symptoms frequently associated with functional gastrointestinal disorders&#44; including functional abdominal pain&#44; irritable bowel syndrome&#44; functional dyspepsia&#44; and abdominal migraine&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">2</span></a> Nevertheless&#44; patients with organic intestinal disorders &#40;Crohn&#39;s disease and ulcerative colitis&#41; also experience some of these symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a> Crohn&#39;s disease and ulcerative colitis are chronic disorders characterised by the inflammation of the gastrointestinal tract&#46; Diagnosis and confirmation require invasive endoscopic or radiological procedures that have potential risks&#44; especially in paediatrics&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">4</span></a> In contrast&#44; the diagnosis of irritable bowel syndrome is mainly based on symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">5</span></a> Different acute-phase reactants such as ESR &#40;erythrocyte sedimentation rate&#41; and C-reactive protein &#40;CRP&#41; have been traditionally used as serological markers of inflammation&#46; In the last few years&#44; faecal calprotectin has become a biomarker for the diagnosis of IBD&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">6&#8211;8</span></a> Calprotectin is a protein of the S100 family that is released mainly by neutrophils&#44; monocytes and macrophages&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">9&#44;10</span></a> It constitutes the response generated by the innate immune system&#46; Calprotectin also exerts antibacterial&#44; pro-apoptotic&#44; and chemotactic activity&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">11&#8211;13</span></a> Calprotectin has been measured in serum&#44; plasma&#44; saliva&#44; urine&#44; cerebrospinal fluid&#44; and synovial fluid&#46; The highest concentration has been found in faeces&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">14&#44;15</span></a> Plasma calprotectin levels have been shown to increase about 5&#8211;40 fold under inflammatory and pathological conditions&#46; Faecal levels are approximately 6 fold higher than plasma levels&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a> Calprotectin is stable in stools for &#62;7 days due to its resistance to proteolytic degradation&#46; Despite the number of studies characterising faecal calprotectin in recent years&#44; data on paediatric populations are still incomplete&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">17&#8211;20</span></a> The objective of the study was to determine the ability of faecal calprotectin for differentiating between functional and organic &#40;intestinal bowel disease&#44; IBD&#44; and non-IBD&#41; diseases in paediatric patients&#44; and to evaluate the correlation between traditional inflammatory parameters and levels of faecal calprotectin&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">This retrospective study involved clinical data from 129 paediatric patients presenting to the Department of Paediatric Gastroenterology at Miguel Servet University Hospital with symptoms of intestinal pathology&#44; including intense abdominal pain&#44; diarrhoea&#44; weight loss and rectal bleeding&#44; between August 2013 and January 2015&#46; The primary endpoint included a differential diagnosis between functional disorder&#44; organic IBD&#44; and organic non-IBD by using faecal calprotectin&#46; The second endpoint involved the analysis of correlation between clinical parameters and levels of calprotectin&#46; Before establishing the final diagnosis&#44; all patients underwent a complete evaluation of serological parameters&#44; including ESR &#40;mm&#47;h&#41;&#44; CRP &#40;mg&#47;dl&#41;&#44; transferrin saturation &#40;&#37;&#41;&#44; serum ferritin &#40;ng&#47;ml&#41;&#44; albumin &#40;g&#47;dl&#41;&#44; haemoglobin levels &#40;g&#47;dl&#41;&#44; and platelet count&#47;l&#46; Faecal calprotectin was also determined in all patients&#46; A stool sample was collected from each patient and frozen at &#8722;70<span class="elsevierStyleHsp" style=""></span>&#176;C until analysis&#46; The quantitative determination of calprotectin levels in faeces was performed by Quantum Blue<span class="elsevierStyleSup">&#174;</span> immunoassay &#40;B&#252;hlmann Laboratories AG&#41;&#46; Functional gastrointestinal disorders were diagnosed by following Rome II paediatric criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">21</span></a> Intestinal inflammation was evaluated in patients with cystic fibrosis as part of the annual nutritional and digestive monitoring&#46; Procedures were performed in accordance with guidelines established by the hospital&#39;s Ethics Committee&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0015" class="elsevierStylePara elsevierViewall">Categorical variables were expressed as absolute and relative &#40;&#37;&#41; frequencies and continuous variables as median and interquartile range &#40;IQR&#41;&#46; Comparisons between diagnostic groups were performed by using Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test and Bonferroni correction&#46; The correlation between calprotectin levels and serological parameters was evaluated by performing a Spearman&#39;s rho test&#46; The statistical significance was established for <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; All statistical procedures were performed with SPSS 15&#46;0 software&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0020" class="elsevierStylePara elsevierViewall">Although the initial number of paediatric patients was 129&#44; 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To establish the final diagnosis&#44; specialists needed to perform an endoscopy in 52 patients &#40;41&#46;3&#37;&#41;&#46; Of these&#44; 11 patients &#40;26&#46;8&#37;&#41; were finally diagnosed with a functional disease&#44; 24 patients &#40;35&#46;3&#37;&#41; with an organic non-IBD&#44; and 17 patients &#40;100&#46;0&#37;&#41; with an organic IBD&#46; Calprotectin levels were significantly different among the three diagnostic groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Levels were higher in organic IBD &#40;500<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#44; IQR 446&#8211;1800&#41; than organic non-IBD &#40;61<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#44; IQR 21&#8211;200&#41;&#44; and functional disease &#40;21<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#44; IQR 16&#8211;44&#41;&#46; Eight out of 42 patients diagnosed with functional disease &#40;19&#46;0&#37;&#41; had calprotectin levels between 50 and 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#46; None had values over 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#46; In a subsequent analysis of calprotectin between 1 and 8 months later&#44; none of these patients had levels over 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g &#40;data not shown&#41;&#46; Calprotectin levels according to final diagnosis are shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; Crohn&#39;s disease and ulcerative colitis had the highest median values&#44; 497<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g &#40;IQR 446&#8211;1800&#41; and 500<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g &#40;IQR 380&#8211;845&#41; respectively&#44; and functional abdominal pain &#40;21<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#44; IQR 16&#8211;44&#41; had the lowest&#46; Calprotectin values for organic IBD were significantly different &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; from functional disease and almost all diseases from organic non-IBD&#46; Assuming a cut-off value of 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#44; sensibility and specificity of calprotectin&#44; to differentiate patients with IBD from organic non-IBD and functional disease&#44; were 100&#37; &#40;17 IBD cases with calprotectin &#62;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#47;17 total IBD cases&#41;&#44; and 60&#46;3&#37; &#40;67 cases with organic non-IBD and functional disease with calprotectin &#60;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#47;111 total organic non-IBD and functional cases&#41;&#44; respectively&#46; Positive and negative predictive values were&#58; 27&#46;8&#37; &#40;17 IBD cases with calprotectin &#62;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#47;61 total cases with calprotectin &#62;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#44; and 100&#37; &#40;67 cases with organic non-IBD and functional disease with calprotectin &#60;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#47;67 total cases with calprotectin &#60;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#46; Similarly&#44; sensibility and specificity of calprotectin&#44; to differentiate patients with organic disease &#40;both IBD and non-IBD&#41; from functional disease&#44; were 61&#46;6&#37; &#40;53 organic cases with calprotectin &#62;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#47;86 total organic cases&#41;&#44; and 80&#46;9&#37; &#40;34 cases with functional disease with calprotectin &#60;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#47;42 total functional cases&#41;&#44; respectively&#46; Positive and negative predictive values were&#58; 86&#46;9&#37; &#40;53 organic cases with calprotectin &#62;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#47;61 total cases with calprotectin &#62;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#44; and 50&#46;7&#37; &#40;34 cases with functional disease with calprotectin &#60;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#47;67 total cases with calprotectin &#60;50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#46; Evaluating the correlation between calprotectin values and clinical parameters&#44; with the exception of ferritin levels&#44; all showed significant associations&#46; Positive associations were found between high levels of calprotectin and ESR &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;497&#41;&#44; CRP &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;460&#41;&#44; and platelet count &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;232&#41;&#46; In contrast&#44; an inverse correlation was found between high levels of calprotectin and transferrin saturation &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;310&#41;&#44; albumin levels &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;412&#41;&#44; and haemoglobin levels &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;309&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Performing an accurate diagnosis and avoiding unnecessary invasive procedures are priorities for gastrointestinal specialists&#44; especially when dealing with paediatric patients&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> Results from our study corroborate the effectiveness of faecal calprotectin for differentiating between functional and organic intestinal diseases&#44; mainly IBD&#46; In concordance with the literature&#44; calprotectin levels for Crohn&#39;s disease and ulcerative colitis were significantly higher compared to functional disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">22&#44;23</span></a> Indeed&#44; a cut-off of 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g &#40;95&#8211;100&#37; sensitivity and 44&#8211;93&#37; specificity&#41; has been proposed to distinguish diagnosis or relapse in IBD &#40;level<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41; from other non-inflammatory disorders in paediatric populations&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">24</span></a> In our study&#44; 19&#46;0&#37; of patients diagnosed with functional disease showed calprotectin levels ranging between 50 and 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#46; In a systematic review from 2014 analysing 6 prospective and 2 retrospective case-control studies and involving 394 paediatric IBD patients&#44; and 321 non-IBD controls&#44; aimed to evaluate the usefulness of faecal calprotectin for the diagnosis of IBD in children&#44; revealed that its sensitivity and specificity were 0&#46;978 and 0&#46;682&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">25</span></a> Endoscopy is the standard procedure for establishing an accurate diagnosis of IBD&#46; Apart from being invasive&#44; endoscopy is expensive and&#44; in paediatric patients&#44; requires general anaesthesia&#44; which has potential risks&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">4</span></a> It has been reported that more than 60&#37; of colonoscopies performed in young patients showed no pathology&#44; i&#46;e&#46; the procedure was not necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">24</span></a> In our study&#44; 11 patients out of 42 who finally were diagnosed with functional abdominal pain &#40;or 21&#46;2&#37; of total endoscopies&#41; underwent an unnecessary procedure&#46; Other organic pathologies&#44; such as cystic fibrosis&#44; infections&#44; food allergies&#44; polyps and neoplasms may also result in increased levels of calprotectin&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">26&#44;27</span></a> Similarly&#44; in our study&#44; levels in organic IBD were also significantly higher compared with almost all organic non-IBD studied&#46; Median calprotectin concentrations in cystic fibrosis&#44; coeliac disease&#44; fructose intolerance and infections &#40;<span class="elsevierStyleItalic">Helicobacter pylori</span>&#41; were within normal levels&#44; suggesting that calprotectin may be used as a complementary biomarker during the follow-up of these conditions&#46; The median value for polyps was a little higher than normal values&#46; According to the literature&#44; colonic polyposis has been shown to cause an increase in stool calprotectin&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">28</span></a> Therefore&#44; calprotectin might be used to identify affected patients&#59; and it also suggests the presence of associated lesions&#46; Although not analysed in the present study&#44; different types of functional gastrointestinal disorders have been shown to present similar calprotectin levels&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">29</span></a> Acute phase reactants such as ESR and CRP&#44; however&#44; have provided excellent results when used as inflammatory markers of IBD<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">30</span></a>&#59; of all the markers&#44; CRP has been the most studied and has been shown to provide the most reliable results&#44; while ESR&#44; leucocyte and platelet count and albumin have been studied less extensively in IBD&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">31</span></a> Moreover&#44; ESR and CRP offer low specificity and sensitivity for identifying an organic condition in the colon&#44; while the specificity and sensitivity of faecal calprotectin are higher in the small bowel and colon&#46; In our study&#44; calprotectin levels showed positive correlation with both ESR and CRP&#59; especially ESR&#46; The inverse correlation found between faecal calprotectin and serum levels of albumin&#44; haemoglobin&#44; and transferrin saturation may be suggestive of an inverse relationship with the nutritional status of the patient &#40;presumably deficient due to the inflammatory condition&#41;&#46; The main limitation of the study was the retrospective nature of the data&#46; Moreover&#44; the low number of patients included in some of these pathologies did not allow a cut-off to be established for distinguishing between organic IBD and non-IBD&#44; or even between functional and organic non-IBD&#46; However&#44; our results corroborate data published in the literature and encourage further prospective experiments involving larger cohorts of patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; the determination of faecal calprotectin is a necessary complementary tool in routine clinical practice for discriminating between functional and organic IBD&#44; and avoiding unnecessary invasive procedures in paediatric patients&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0035" class="elsevierStylePara elsevierViewall">No funding to declare&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Background and objective"
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          "titulo" => "Resumen"
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              "titulo" => "Antecedentes y objetivo"
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    "fechaRecibido" => "2017-07-10"
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          "palabras" => array:5 [
            0 => "Calprotectin"
            1 => "Diagnosis"
            2 => "Functional"
            3 => "Organic"
            4 => "Inflammatory bowel disease"
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          "palabras" => array:5 [
            0 => "Calprotectina"
            1 => "Diagn&#243;stico"
            2 => "Funcional"
            3 => "Org&#225;nico"
            4 => "Enfermedad inflamatoria intestinal"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The objective of the study was to determine the ability of faecal calprotectin to differentiate functional and organic intestinal diseases in paediatric patients&#44; and to evaluate the correlation between inflammatory parameters and levels of faecal calprotectin&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This retrospective study involved clinical data from 129 paediatric patients with symptoms of intestinal pathology&#46; Faecal calprotectin was determined by quantitative immunoassay&#46; Patients were classified into three groups&#58; functional &#40;32&#46;8&#37; of patients&#41;&#59; organic non-inflammatory bowel disease &#40;IBD&#44; 53&#46;9&#37;&#41;&#59; and organic IBD &#40;13&#46;3&#37;&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Calprotectin levels were significantly different among the three groups&#59; between patients with IBD and the others&#44; and also between patients with non-organic IBD and functional&#46; Positive associations were found between high levels of calprotectin and higher erythrocyte sedimentation rate &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;497&#41;&#44; C-reactive protein &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;460&#41;&#44; and platelet count &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;232&#41;&#46; Nevertheless&#44; an inverse correlation was found between high levels of calprotectin and transferrin saturation &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;310&#41;&#44; albumin &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;412&#41;&#44; and haemoglobin levels &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;309&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Determination of faecal calprotectin is a complementary tool in clinical practice for discriminating between functional and organic IBD&#44; avoiding&#44; according to the levels of calprotectin&#44; unnecessary invasive procedures in paediatric patients&#46;</p></span>"
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          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio fue determinar la capacidad de la calprotectina fecal para diferenciar las enfermedades funcionales y org&#225;nicas en los pacientes pedi&#225;tricos&#44; y evaluar la correlaci&#243;n entre los par&#225;metros inflamatorios y los niveles de calprotectina fecal&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Este estudio retrospectivo incluy&#243; los datos cl&#237;nicos de 129 pacientes pedi&#225;tricos con s&#237;ntomas de enfermedad intestinal&#46; Se determinaron los valores de calprotectina fecal mediante inmunoensayo cuantitativo&#46; Se clasificaron los pacientes en 3 grupos&#58; funcionales &#40;32&#44;8&#37; de pacientes&#41;&#44; enfermedad intestinal inflamatoria no org&#225;nica &#40;EII&#44; 53&#44;9&#37;&#41; e EII org&#225;nica &#40;13&#44;3&#37;&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los niveles de calprotectina fueron significativamente diferentes entre los 3 grupos&#59; entre los pacientes con EII y el resto&#44; y tambi&#233;n entre los pacientes con EII no org&#225;nica e EII funcional&#46; Se encontraron asociaciones positivas entre los niveles altos de calprotectina y la tasa de sedimentaci&#243;n eritroc&#237;tica alta &#40;Rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;497&#41;&#44; prote&#237;na C reactiva &#40;Rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;460&#41; y recuento plaquetario &#40;Rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;232&#41;&#46; Sin embargo&#44; se encontr&#243; una correlaci&#243;n inversa entre los niveles altos de calprotectina y la saturaci&#243;n de transferrina &#40;Rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#44;310&#41;&#44; alb&#250;mina &#40;Rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#44;412&#41; y niveles de hemoglobina &#40;Rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#44;309&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La determinaci&#243;n de la calprotectina fecal es una herramienta complementara en la pr&#225;ctica cl&#237;nica para discriminar entre EII funcional y EII org&#225;nica&#44; y evitar con arreglo a los niveles de calprotectina&#44; los procedimientos invasivos innecesarios en pacientes pedi&#225;tricos&#46;</p></span>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reasons for presenting to the specialist&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abdominal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41 &#40;32&#46;0&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abdominal pain and weight loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;3&#46;1&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cystic fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29 &#40;22&#46;7&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;10&#46;9&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diarrhoea and weight loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;1&#46;6&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rectal bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;12&#46;5&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rectal bleeding and diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;5&#46;5&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rectal bleeding and constipation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Crohn&#39;s disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;1&#46;6&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fistula&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;1&#46;6&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hirschsprung&#39;s disease&#44; colostomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;1&#46;6&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Underweight&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;1&#46;6&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Melaena&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pallor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Melaena and haematemesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Raised markers for coeliac disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vitamin B12 deficiency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Iron-deficiency anaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at2"
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          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Final diagnosis&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Functional abdominal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42 &#40;32&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cystic fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29 &#40;22&#46;7&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Crohn&#39;s disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;7&#46;0&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Helicobacter pylori</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;7&#46;0&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute gastroenteritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;7&#46;0&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ulcerative colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;6&#46;3&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bacterial overgrowth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;4&#46;7&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Polyps&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;3&#46;9&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Coeliac disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Diagnostic groups&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Functional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42 &#40;32&#46;8&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Organic non-IBD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69 &#40;53&#46;9&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Organic IBD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">SD&#44; standard deviation&#59; ESR&#44; erythrocyte sedimentation rate&#59; IQR&#44; interquartile range&#59; CRP&#44; C-reactive protein</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Functional &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Organic&#44; non-IBD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>69&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Organic&#44; IBD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male gender&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70 &#40;54&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;54&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35<br>&#40;50&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12<br>&#40;70&#46;6&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age&#44; mean years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;1 &#40;4&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;2 &#40;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;3<br>&#40;4&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;9<br>&#40;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Clinical parameters at baseline</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ESR&#44; median mm&#47;h &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;0<br>&#40;4&#46;0&#8211;26&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;5<br>&#40;3&#46;0&#8211;15&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;0<br>&#40;4&#46;0&#8211;21&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#46;0<br>&#40;29&#46;5&#8211;48&#46;5&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CRP&#44; median mg&#47;dl &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;11<br>&#40;0&#46;03&#8211;0&#46;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;06<br>&#40;0&#46;03&#8211;0&#46;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;06<br>&#40;0&#46;02&#8211;0&#46;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;40<br>&#40;0&#46;17&#8211;2&#46;63&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Transferrin saturation&#44; median &#37; &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#46;7<br>&#40;15&#46;0&#8211;25&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;2<br>&#40;15&#46;5&#8211;25&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;1<br>&#40;17&#46;3&#8211;27&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;9<br>&#40;8&#46;3&#8211;16&#46;0&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ferritin&#44; median ng&#47;ml &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;2<br>&#40;33&#46;4&#8211;85&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#46;3<br>&#40;23&#46;3&#8211;66&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#46;7<br>&#40;15&#46;0&#8211;68&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;6<br>&#40;4&#46;4&#8211;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;4<br>&#40;4&#46;3&#8211;4&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;2<br>&#40;4&#46;0&#8211;4&#46;4&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Haemoglobin&#44; median g&#47;dl &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;3<br>&#40;11&#46;3&#8211;12&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;9<br>&#40;2&#46;3&#8211;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#47;126 &#40;41&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;41 &#40;26&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;68 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17<br>&#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;10<br>&#40;50&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#47;22<br>&#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Colonoscopy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#47;10<br>&#40;10&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;22<br>&#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#47;17<br>&#40;17&#46;6&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gastroscopy and colonoscopy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#47;49<br>&#40;61&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;10<br>&#40;40&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#47;22 &#40;54&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#47;17<br>&#40;82&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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