Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients

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“Dr. José Eleuterio González”, Monterrey, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidad Autónoma de Nuevo León, Servicio de Gastroenterología, Departamento de Medicina Interna, Hospital Universitario “Dr. José Eleuterio González”, Monterrey, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Falta de asociación de síntomas esofágicos con la manometría de alta resolución en pacientes con esclerosis sistémica" ] ] "textoCompleto" => "IntroductionSystemic sclerosis (SSc) is an autoimmune disease of unknown cause characterized by microvasculopathy, fibroblast activation, and excessive production of collagen.<a class="elsevierStyleCrossRef" href="#bib0140">1</a>Involvement of the gastrointestinal (GI) tract in SSc is second in frequency only to the skin, and it is characterized by esophageal dysmotility in 75–90%, stomach involvement in 50%, small bowel involvement in 40–70%, colon involvement in 20–50%, and anorectal involvement in 50–70%.<a class="elsevierStyleCrossRef" href="#bib0145">2</a> The mortality rate attributable to GI involvement is 6–12%.<a class="elsevierStyleCrossRefs" href="#bib0150">3–7</a>The great impact of esophageal involvement in the morbi-mortality of SSc is related to its association with interstitial lung disease,<a class="elsevierStyleCrossRef" href="#bib0175">8</a> weight loss and malnutrition, Barrett's esophagus<a class="elsevierStyleCrossRefs" href="#bib0180">9,10</a> and its progression to adenocarcinoma.<a class="elsevierStyleCrossRef" href="#bib0190">11</a> Around 18–40% of patients are asymptomatic despite the objective documentation of esophageal disease.<a class="elsevierStyleCrossRef" href="#bib0185">10</a> Esophageal manometry is considered the method of choice for evaluation of esophageal motility in SSc patients, even when they are asymptomatic.A new technique called high resolution manometry (HRM) in which catheters with 36 pressure sensors separated by 1cm are used to measure intraesophageal pressure from the hypopharynx to the stomach, was introduced recently. The result is a color picture of the topography of esophageal pressure, where the duration, amplitude and velocity of esophageal contractions (including the function of the upper and lower esophageal sphincter) are plotted.<a class="elsevierStyleCrossRef" href="#bib0195">12</a> Traditionally, manometric findings were reported as rated by Spechler and Castell.<a class="elsevierStyleCrossRef" href="#bib0200">13</a> From 2008 onwards (and with the introduction of the HRM) a new classification (The Chicago classification) was described, and is currently the most widely used classification.<a class="elsevierStyleCrossRefs" href="#bib0205">14,15</a> The aim of this study was to categorize esophageal motor disorder in patients with SSc by HRM and to describe its association with upper GI symptomatology.Materials and methodsSetting and populationThis is an observational, descriptive and cross-sectional study, carried out between May and August 2013 in a Tertiary-care University Hospital. This study was approved by the ethics committee of our Institution. We selected patients >18 years old with SSc according to the American College Classification 1980 with or without esophageal symptoms who accepted to enter to the study with a signed informed consent. Also, we included only two patients other than SSc, one with morphea and other with scleroderma sine scleroderma, both of them with esophageal symptoms.We evaluated clinical and demographics variables including: age, gender, body mass index (BMI), SSc classification, auto-antibodies, previously use of nonsteroidal anti-inflammatory drug (NSAID), calcium channel blockers (CCB) and proton pump inhibitors (PPIs). We asked about esophageal symptoms using a semi-structured interview and recorded the frequency of: dysphagia, heartburn, regurgitation, cough, chest pain, nausea, vomiting. We also evaluated skin thickening, gastro esophageal reflux symptoms, and dysphagia symptoms.Modified Rodnan skin score (mRSS)The mRSS is a validated measure of skin thickening in SSc. In the mRSS, skin thickening is assessed at 17 body sites by palpation and rated on a scale with values of 0 (normal), 1 (mild), 2 (moderate) or 3 (severe skin thickening). The total skin score is the sum of the individual skin assessments in the 17 body areas, with a possible range of 0–51; higher scores indicate more severe skin thickening.Carlsson–Dent questionnaireWe applied a gastroesophageal reflux questionnaire (Carlsson–Dent) to all patients, which has been used in Spanish-speaking Mexican patients previously.<a class="elsevierStyleCrossRef" href="#bib0215">16</a> It is a self-administered questionnaire that focuses on the nature of the sensations experienced by the patient as well as provoking, exacerbating and relieving factors. Scores range from −7 to 20. Scores of −7 to −1 indicate ‘absent’ reflux symptoms, 0–5 ‘mild’, 6–11 ‘moderate’ and >11 ‘severe’ reflux symptoms.DysphagiaWe classified dysphagia in four stages according to patient self-report: no dysphagia, dysphagia to liquid food, dysphagia to normal solids, dysphagia to soft solids and inability to swallow.High resolution manometry (HRM)HRM was done by a certified gastroenterologist (GBT) with experience using HRM. Seven days prior to HRM, we withheld the following drugs: prokinetics, narcotics, anticholinergics, antiemetics, and anti-inflammatory drugs. We asked the patient to fast the night before the procedure. The day of the study the patient was placed supine. Subsequently, topical anesthetic is applied in nostril. The manometry catheter was placed in a site that allowed to identify areas of both sphincters, placing about 5 sensors in the stomach and finally the probe was attached to the back of the nose. After a stabilization period of 5min, 10 consecutive shots of 5ml of water were administered every 30s.<a class="elsevierStyleCrossRef" href="#bib0220">17</a> HRM results were reported according to the Chicago classification.<a class="elsevierStyleCrossRefs" href="#bib0205">14–18</a> Patients with normal EGJ pressure, normal EGJ relaxation, normal PFV, and a DCI <5000mm Hg s cm were reported as normal or abnormal if the gastroenterologist reported one of the following based in manometric parameters: Peristaltic dysfunction; aperistalsis, hypertensive peristalsis; rapidly propagated pressurization; abnormal LES tone (end expiratory); achalasia or functional obstruction.Statistical analysisContinuous variables with normal distribution were expressed with mean and standard deviation. Continuous variables without normal distribution were expressed with median and interquartile ranges. We categorized HRM results in two groups: Normal or abnormal HRM (any alteration), then, we used 2×2 contingency tables. In addition, chi-square or Fisher exact tests were used according to their distribution to assess whether there was an association between each variable and the HRM results. A value of p<0.05 was considered statistically significant. All statistical analyses were performed using the SPSS version 20.0 statistical software package. This work has been assessed and approved by the local IRB with registration: RE13-006.ResultsWe included 21 patients, 19 with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Seventeen patients (80.9%) had less than three years of being diagnosed. Most patients were female (95.2%) with mean age of 44.9 (SD 14) years, a mean weight of 61.9kg (SD 14.4) and height of 1.57 (SD 0.8) m; the other clinical and demographic variables are in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. We found 17 (80.9%) patients with limited SSc. The mean mRSS for all patients was 9.7 (SD 7.4). Raynaud's phenomenon was reported in 18 (85.7%) patients.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>We found a normal HRM in 6 (28.5%) patients and an abnormal HRM in 15 (71.4%) patients. Patients with an abnormal HRM were: 1 (6.6%) patient with distal esophageal spasm, 5 (33.3%) patients with absent peristalsis, 4 (26.6%) patients with weak peristalsis with small peristaltic defects, and 3 (20%) patients with frequent failed peristalsis. Only 2 (13.3%) patients in whom an abnormal HRM was found could not be classified.The association between upper GI symptoms and HRM results is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Dysphagia and heartburn were the most frequent symptoms reported by the patients, but in general, symptom frequency did not vary between groups with or without HRM abnormalities. Only regurgitation was found to be more frequent in patients with a normal HRM. Additionally, neither the Carlsson–Dent questionnaire nor dysphagia severity was different between groups. Two patients with limited SSc who were asymptomatic (one patient with absent peristalsis and the other with weak peristalsis with small peristaltic defects) showed an abnormal HRM. The two variant SSc patients (scleroderma sine scleroderma and morphea) had a normal HRM.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiscussionIn this cohort of SSc patients, an abnormal HRM was found in 71.4%. Dysphagia and heartburn were the most common esophageal symptoms reported, which is similar to other published series.<a class="elsevierStyleCrossRefs" href="#bib0175">8–10</a> We did not find any association between clinical-demographic variables and the outcome of the HRM, or between upper GI symptoms and HRM findings, except for regurgitation, which was found to be more frequent in patients with a normal HRM.There had been a previous study assessing the clinical features of Mexican scleroderma patients; Santos-Navarro et al.<a class="elsevierStyleCrossRef" href="#bib0230">19</a> studied 60 patients and found hypotensive lower esophageal sphincter (LES) in 95%. Aperistalsis (41%), slight hypomotility (30%), and severe hypomotility (27%) with different gastric manifestations as: early satiety 45%, abdominal pain 35%, nausea 20% and vomiting 10%. In contrast with our study they did not intent to correlate the clinical findings with manometry ones. Also they performed standard manometry versus high resolution in our patients. Even tough, they found a high prevalence of manometry alterations, maybe explained by age differences between cohorts, and the established disease by ten years of more.This is not the first study to find a lack of an association between esophageal dysmotility evaluated by HRM and upper GI symptomatology in patients with SSc. Roman et al. studied HRM findings in 51 patients with SSc, and found that 67.3% had HRM abnormalities (most commonly hypotensive esophagogastric junction). However, up to 87% of patients had esophageal symptoms that were not predictive of HRM alterations.<a class="elsevierStyleCrossRef" href="#bib0235">20</a> Later, Tang et al. associated HRM findings with phenotypic and GI symptoms in 28 patients with SSc, and could not find a clear association between dysphagia and HRM findings.<a class="elsevierStyleCrossRef" href="#bib0240">21</a> Recently, Raja et al. reported the finding of a study on 31 patients with SSc who underwent HRM.<a class="elsevierStyleCrossRef" href="#bib0245">22</a> They found that upper GI symptoms were absent in the majority of their patients, even when they had severe esophageal involvement according to HRM findings. The same basic results were reported in another recent study involving 79 patients with SSc.<a class="elsevierStyleCrossRef" href="#bib0250">23</a>It has been known for some time that the severity of upper GI symptoms does not always correlate with objective measures of esophageal dysmotility, and this may include HRM. In a retrospective study of over 250 patients who underwent HRM due to upper GI symptoms, these were not found to be related to abnormal motor function defined by HRM during liquid, viscous or solid bolus swallows in the upright position.<a class="elsevierStyleCrossRef" href="#bib0255">24</a> The discordance that we observed in our study might not be limited to patients with SSc. Other studies on populations with systemic diseases that usually involve the esophagus, such as Chagas disease, have similarly found a lack of an association between HRM findings and upper GI symptomatology.<a class="elsevierStyleCrossRef" href="#bib0260">25</a> Additionally, in our study, 95.2% of patients at the time of evaluation were treated with proton pump inhibitors (PPIs). The lack of association between the symptoms and the results of HRM may be also partly explained by the high percentage of patients using PPIs at the time of evaluation, or even the use of other non-prescription medications for heartburn that could mask the symptoms evaluated. This limitation was also seen in other study.<a class="elsevierStyleCrossRef" href="#bib0240">21</a>On the other hand, there are certain features of SSc that have been more consistently associated with HRM alterations. Patients with SSc and Raynaud phenomenon have been found to have lower amplitude of distal esophageal contractions<a class="elsevierStyleCrossRef" href="#bib0240">21</a> as well as with more hypotensive lower esophageal sphincter<a class="elsevierStyleCrossRef" href="#bib0245">22</a> compared to those without. Degree of skin involvement has also been positively correlated with esophageal dysmotility according to HRM as well as with more severe dysphagia.<a class="elsevierStyleCrossRefs" href="#bib0240">21,23</a> The latter were not found in our cohort. The presence of pulmonary fibrosis in SSc patients was also found to be associated with more absent contractility in HRM as well as with more symptoms of gastroesophageal reflux.<a class="elsevierStyleCrossRefs" href="#bib0245">22,23</a> At least one study found that alterations in HRM were correlated to presence of Scl70 and absence of anti-centromere antibodies,<a class="elsevierStyleCrossRef" href="#bib0235">20</a> but these findings were not replicated in another recent study.<a class="elsevierStyleCrossRef" href="#bib0250">23</a> In our study we did not assess lung function, and neither the severity of skin involvement or presence of Raynaud phenomenon was significantly associated with HRM abnormalities, although there was a trend toward more alterations in patients with Raynaud phenomenon.The patients with morphea and scleroderma sine scleroderma we included both had a normal HRM. Recently, Arif et al. evaluated SSc and morphea patients with upper gastrointestinal endoscopy, esophageal manometry and 24-h pH monitoring, and found that of the 31 patients with morphea, none had manometric findings, although only four patients had symptoms. The authors concluded that in morphea, an assessment of GI manifestations is not necessary, unlike SSc.<a class="elsevierStyleCrossRef" href="#bib0265">26</a> We also observed two patients with SSc without esophageal symptoms but with an abnormal HRM. Previously, Thonhofer et al. conducted a retrospective study, where they evaluated patients with SSc and Mixed Connective Tissue Disease (MCTD) without GI symptoms. The patients underwent a baseline evaluation and follow-up at three to six months. In all thirteen SSc patients, significant pathology of the upper GI-tract was found. In patients with esophageal abnormalities, starting treatment led to favorable results, which was confirmed in the follow-up study. The authors suggest that the GI evaluation must be performed early in patients diagnosed with SSc, even if they do not report typical symptoms,<a class="elsevierStyleCrossRef" href="#bib0270">27</a> an opinion that we share considering our results.We consider that the strengths of the study are: a population with a relatively early diagnosis of SSc, the use of HRM and the Chicago classification. The limitations include: cross-sectional study design, small cohort of patients, heterogeneity in the treatment of patients, lack of description of other comorbidities that could affect the outcome of the HRM, as well as lack of further studies to complement the manometry result, such as pH monitoring or endoscopy.In conclusion, we found a high prevalence of esophageal symptoms but a lack of association between these and the presence of an abnormal HRM, which is in accordance to other published, studies.<a class="elsevierStyleCrossRefs" href="#bib0230">19–22</a> This suggests that it is important to perform a systematic approach to GI symptomatology in SSc patients at diagnosis irrespective of objective procedures of motility evaluation. This will identify early GI abnormalities, help alleviate symptoms and thereby lessen the impact on morbidity and mortality generated by this condition.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that they have followed the protocols of their work center on the publication of patient data.Right to privacy and informed consentThe authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.Funding sourcesNone.Authors’ contributionArana-Guajardo AC: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; obtained funding; administrative, technical, or material support.Barrera-Torres G: acquisition of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content.Villarreal-Alarcón MA: study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; study supervision.Vega-Morales D: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis; study supervision.Esquivel-Valerio JA: analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content.Conflict of interestNone declared." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1184369" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1104687" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1184368" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1104688" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Setting and population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Modified Rodnan skin score (mRSS)" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Carlsson–Dent questionnaire" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Dysphagia" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "High resolution manometry (HRM)" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0055" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding sources" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors’ contribution" ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-25" "fechaAceptado" => "2017-09-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1104687" "palabras" => array:4 [ 0 => "Systemic sclerosis" 1 => "Esophageal disease" 2 => "Comorbidity" 3 => "High resolution manometry" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1104688" "palabras" => array:4 [ 0 => "Esclerosis sistémica" 1 => "Enfermedad esofágica" 2 => "Comorbilidad" 3 => "Manometría de alta resolución" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundThe esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. MethodsWe carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson–Dent). ResultsWe included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. ConclusionWe observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesLa afectación esofágica en la esclerosis sistémica causa impacto en la morbimortalidad. La manometría de alta resolución evalúa la afectación esofágica. Nuestro objetivo fue categorizar el trastorno motor esofágico en pacientes con esclerosis sistémica por HRM. MétodosSe realizó un estudio observacional, descriptivo y transversal. Todos los pacientes se sometieron a HRM, así como a entrevistas semiestructuradas para evaluar la frecuencia y la gravedad de los síntomas gastrointestinales. Los pacientes también completaron el cuestionario de reflujo gastroesofágico (Carlsson-Dent). ResultadosSe incluyeron 19 pacientes con esclerosis sistémica, uno con morfea y uno con esclerodermia seno esclerodermia. La disfagia y la pirosis fueron los síntomas más frecuentes (un 61% cada uno). Encontramos una HRM anormal en 15 (71,4%) pacientes. No se halló ninguna asociación estadísticamente significativa entre las variables clínicas o demográficas y una HRM anormal, o entre cualquier síntoma GI superior y los hallazgos de HRM. ConclusiónSe observó una alta prevalencia de síntomas esofágicos y de anomalías de la HRM. Sin embargo, no hubo asociación clara entre la sintomatología y los hallazgos de HRM. La HRM no parece predecir con precisión la sintomatología gastrointestinal." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:2 [ 0 => 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:3 [ "leyenda" => "SSc, systemic sclerosis; SD, standard deviation; BMI, body mass index; mRSS, modified Rodnan skin score; NSAID, nonsteroidal anti-inflammatory drug; CCB, calcium channel blockers; PPI, proton pump inhibitors; HRM, high resolution manometry." "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">Variable \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=21 \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">HRM normal, n (%) n=6 \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">HRM abnormal, n (%) n=15 \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">p \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">Age, mean (SD) years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.2 (10.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44.6 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \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">Female gender, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (95.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (93.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \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="4" align="left" valign="top">BMI</td><td class="td" title="table-entry " align="char" valign="top">0.55 \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">Normal, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (23.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (26.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Overweight, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (23.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Obesity, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (13.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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="4" align="left" valign="top">SSc classification and variants</td><td class="td" title="table-entry " align="char" valign="top">0.94 \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">Limited, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (80.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (86.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Diffuse, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (9.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (13.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Scleroderma sine scleroderma, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Morphea, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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="4" align="left" valign="top">mRSS<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></td><td class="td" title="table-entry " align="char" valign="top">0.39 \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">Mild <20, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (83.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Moderate ≥20, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Raynaud phenomenon, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (85.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (93.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.18 \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">Antibodies</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antinuclear antibodies, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (73.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.48 \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">Anti-Scl70, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (23.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (26.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.51 \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">Anti-centromere, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (23.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.15 \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">Drugs</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NSAID, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (9.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (6.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.50 \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">CCB, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (85.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (93.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.18 \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">PPI, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 (95.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (83.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2018993.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "20 patients." ] ] ] "descripcion" => array:1 [ "en" => "Clinical and demographic variables compared with HRM results." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "CDQ, Carlsson–Dent questionnaire; HRM, high resolution manometry." "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">Variable \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=21 \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">HRM normal, n (%) n=6 \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">HRM abnormal, n (%) n=15 \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">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Esophageal symptoms, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dysphagia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (61.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 \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">Heartburn \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (61.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.41 \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">Regurgitation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (42.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (83.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (26.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.02 \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">Cough \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (47.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (46.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \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">Chest pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (6.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.18 \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">Nausea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (13.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vomiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (6.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \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">CDQ, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.04 (4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 \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">0–3 score, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">4–15 score, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (61.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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="4" align="left" valign="top">Dysphagia classification, n (%)</td><td class="td" title="table-entry " align="char" valign="top">0.37 \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">No dysphagia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (42.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Dysphagia to normal solids<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (53.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">Dysphagia to soft solids<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (46.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">4–15 score, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2018994.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "20 patients." ] ] ] "descripcion" => array:1 [ "en" => "Association between upper GI symptoms and HRM results." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib0140" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic sclerosis: a world wide global analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Coral-Alvarado" 1 => "A.L. Pardo" 2 => "N. Castano-Rodriguez" 3 => "A. Rojas-Villarraga" 4 => "J.M. Anaya" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2009" "volumen" => "28" "paginaInicial" => "757" "paginaFinal" => "765" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0145" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gastrointestinal motility disorders in scleroderma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.W. Sjogren" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "1994" "volumen" => "37" "paginaInicial" => "1265" "paginaFinal" => "1282" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7945489" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0150" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictors of survival in systemic sclerosis (scleroderma)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.D. Altman" 1 => "T.A. Medsger Jr." 2 => "D.A. 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Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients

Falta de asociación de síntomas esofágicos con la manometría de alta resolución en pacientes con esclerosis sistémica

Ana Cecilia Arana-Guajardoa, Gustavo Barrera-Torresb, Miguel Ángel Villarreal-Alarcóna, David Vega-Moralesa,

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drdavidvega@yahoo.com.mx

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, Jorge Antonio Esquivel-Valerioa

a Universidad Autónoma de Nuevo León, Servicio de Reumatología, Departamento de Medicina Interna, Hospital Universitario “Dr. José Eleuterio González”, Monterrey, Mexico

b Universidad Autónoma de Nuevo León, Servicio de Gastroenterología, Departamento de Medicina Interna, Hospital Universitario “Dr. José Eleuterio González”, Monterrey, Mexico

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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">Systemic sclerosis &#40;SSc&#41; is an autoimmune disease of unknown cause characterized by microvasculopathy&#44; fibroblast activation&#44; and excessive production of collagen&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Involvement of the gastrointestinal &#40;GI&#41; tract in SSc is second in frequency only to the skin&#44; and it is characterized by esophageal dysmotility in 75&#8211;90&#37;&#44; stomach involvement in 50&#37;&#44; small bowel involvement in 40&#8211;70&#37;&#44; colon involvement in 20&#8211;50&#37;&#44; and anorectal involvement in 50&#8211;70&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">2</span></a> The mortality rate attributable to GI involvement is 6&#8211;12&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">3&#8211;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The great impact of esophageal involvement in the morbi-mortality of SSc is related to its association with interstitial lung disease&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">8</span></a> weight loss and malnutrition&#44; Barrett&#39;s esophagus<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">9&#44;10</span></a> and its progression to adenocarcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a> Around 18&#8211;40&#37; of patients are asymptomatic despite the objective documentation of esophageal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">10</span></a> Esophageal manometry is considered the method of choice for evaluation of esophageal motility in SSc patients&#44; even when they are asymptomatic&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">A new technique called high resolution manometry &#40;HRM&#41; in which catheters with 36 pressure sensors separated by 1<span class="elsevierStyleHsp" style=""></span>cm are used to measure intraesophageal pressure from the hypopharynx to the stomach&#44; was introduced recently&#46; The result is a color picture of the topography of esophageal pressure&#44; where the duration&#44; amplitude and velocity of esophageal contractions &#40;including the function of the upper and lower esophageal sphincter&#41; are plotted&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">12</span></a> Traditionally&#44; manometric findings were reported as rated by Spechler and Castell&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">13</span></a> From 2008 onwards &#40;and with the introduction of the HRM&#41; a new classification &#40;The Chicago classification&#41; was described&#44; and is currently the most widely used classification&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">14&#44;15</span></a> The aim of this study was to categorize esophageal motor disorder in patients with SSc by HRM and to describe its association with upper GI symptomatology&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Setting and population</span><p id="par0025" class="elsevierStylePara elsevierViewall">This is an observational&#44; descriptive and cross-sectional study&#44; carried out between May and August 2013 in a Tertiary-care University Hospital&#46; This study was approved by the ethics committee of our Institution&#46; We selected patients &#62;18 years old with SSc according to the American College Classification 1980 with or without esophageal symptoms who accepted to enter to the study with a signed informed consent&#46; Also&#44; we included only two patients other than SSc&#44; one with morphea and other with scleroderma <span class="elsevierStyleItalic">sine scleroderma</span>&#44; both of them with esophageal symptoms&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We evaluated clinical and demographics variables including&#58; age&#44; gender&#44; body mass index &#40;BMI&#41;&#44; SSc classification&#44; auto-antibodies&#44; previously use of nonsteroidal anti-inflammatory drug &#40;NSAID&#41;&#44; calcium channel blockers &#40;CCB&#41; and proton pump inhibitors &#40;PPIs&#41;&#46; We asked about esophageal symptoms using a semi-structured interview and recorded the frequency of&#58; dysphagia&#44; heartburn&#44; regurgitation&#44; cough&#44; chest pain&#44; nausea&#44; vomiting&#46; We also evaluated skin thickening&#44; gastro esophageal reflux symptoms&#44; and dysphagia symptoms&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Modified Rodnan skin score &#40;mRSS&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">The mRSS is a validated measure of skin thickening in SSc&#46; In the mRSS&#44; skin thickening is assessed at 17 body sites by palpation and rated on a scale with values of 0 &#40;normal&#41;&#44; 1 &#40;mild&#41;&#44; 2 &#40;moderate&#41; or 3 &#40;severe skin thickening&#41;&#46; The total skin score is the sum of the individual skin assessments in the 17 body areas&#44; with a possible range of 0&#8211;51&#59; higher scores indicate more severe skin thickening&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Carlsson&#8211;Dent questionnaire</span><p id="par0040" class="elsevierStylePara elsevierViewall">We applied a gastroesophageal reflux questionnaire &#40;Carlsson&#8211;Dent&#41; 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In addition&#44; chi-square or Fisher exact tests were used according to their distribution to assess whether there was an association between each variable and the HRM results&#46; A value of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46; All statistical analyses were performed using the SPSS version 20&#46;0 statistical software package&#46; This work has been assessed and approved by the local IRB with registration&#58; RE13-006&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">We included 21 patients&#44; 19 with SSc&#44; 1 with morphea&#44; and 1 with scleroderma <span class="elsevierStyleItalic">sine scleroderma</span>&#46; Seventeen patients &#40;80&#46;9&#37;&#41; had less than three years of being diagnosed&#46; Most patients were female &#40;95&#46;2&#37;&#41; with mean age of 44&#46;9 &#40;SD 14&#41; years&#44; a mean weight of 61&#46;9<span class="elsevierStyleHsp" style=""></span>kg &#40;SD 14&#46;4&#41; and height of 1&#46;57 &#40;SD 0&#46;8&#41; m&#59; the other clinical and demographic variables are in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; We found 17 &#40;80&#46;9&#37;&#41; patients with limited SSc&#46; The mean mRSS for all patients was 9&#46;7 &#40;SD 7&#46;4&#41;&#46; Raynaud&#39;s phenomenon was reported in 18 &#40;85&#46;7&#37;&#41; patients&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">We found a normal HRM in 6 &#40;28&#46;5&#37;&#41; patients and an abnormal HRM in 15 &#40;71&#46;4&#37;&#41; patients&#46; Patients with an abnormal HRM were&#58; 1 &#40;6&#46;6&#37;&#41; patient with distal esophageal spasm&#44; 5 &#40;33&#46;3&#37;&#41; patients with absent peristalsis&#44; 4 &#40;26&#46;6&#37;&#41; patients with weak peristalsis with small peristaltic defects&#44; and 3 &#40;20&#37;&#41; patients with frequent failed peristalsis&#46; Only 2 &#40;13&#46;3&#37;&#41; patients in whom an abnormal HRM was found could not be classified&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The association between upper GI symptoms and HRM results is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Dysphagia and heartburn were the most frequent symptoms reported by the patients&#44; but in general&#44; symptom frequency did not vary between groups with or without HRM abnormalities&#46; Only regurgitation was found to be more frequent in patients with a normal HRM&#46; Additionally&#44; neither the Carlsson&#8211;Dent questionnaire nor dysphagia severity was different between groups&#46; Two patients with limited SSc who were asymptomatic &#40;one patient with absent peristalsis and the other with weak peristalsis with small peristaltic defects&#41; showed an abnormal HRM&#46; The two variant SSc patients &#40;scleroderma <span class="elsevierStyleItalic">sine scleroderma</span> and morphea&#41; had a normal HRM&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">In this cohort of SSc patients&#44; an abnormal HRM was found in 71&#46;4&#37;&#46; Dysphagia and heartburn were the most common esophageal symptoms reported&#44; which is similar to other published series&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">8&#8211;10</span></a> We did not find any association between clinical-demographic variables and the outcome of the HRM&#44; or between upper GI symptoms and HRM findings&#44; except for regurgitation&#44; which was found to be more frequent in patients with a <span class="elsevierStyleItalic">normal</span> HRM&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">There had been a previous study assessing the clinical features of Mexican scleroderma patients&#59; Santos-Navarro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">19</span></a> studied 60 patients and found hypotensive lower esophageal sphincter &#40;LES&#41; in 95&#37;&#46; Aperistalsis &#40;41&#37;&#41;&#44; slight hypomotility &#40;30&#37;&#41;&#44; and severe hypomotility &#40;27&#37;&#41; with different gastric manifestations as&#58; early satiety 45&#37;&#44; abdominal pain 35&#37;&#44; nausea 20&#37; and vomiting 10&#37;&#46; In contrast with our study they did not intent to correlate the clinical findings with manometry ones&#46; Also they performed standard manometry versus high resolution in our patients&#46; Even tough&#44; they found a high prevalence of manometry alterations&#44; maybe explained by age differences between cohorts&#44; and the established disease by ten years of more&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">This is not the first study to find a lack of an association between esophageal dysmotility evaluated by HRM and upper GI symptomatology in patients with SSc&#46; Roman et al&#46; studied HRM findings in 51 patients with SSc&#44; and found that 67&#46;3&#37; had HRM abnormalities &#40;most commonly hypotensive esophagogastric junction&#41;&#46; However&#44; up to 87&#37; of patients had esophageal symptoms that were not predictive of HRM alterations&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">20</span></a> Later&#44; Tang et al&#46; associated HRM findings with phenotypic and GI symptoms in 28 patients with SSc&#44; and could not find a clear association between dysphagia and HRM findings&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">21</span></a> Recently&#44; Raja et al&#46; reported the finding of a study on 31 patients with SSc who underwent HRM&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">22</span></a> They found that upper GI symptoms were absent in the majority of their patients&#44; even when they had severe esophageal involvement according to HRM findings&#46; The same basic results were reported in another recent study involving 79 patients with SSc&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">It has been known for some time that the severity of upper GI symptoms does not always correlate with objective measures of esophageal dysmotility&#44; and this may include HRM&#46; In a retrospective study of over 250 patients who underwent HRM due to upper GI symptoms&#44; these were not found to be related to abnormal motor function defined by HRM during liquid&#44; viscous or solid bolus swallows in the upright position&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">24</span></a> The discordance that we observed in our study might not be limited to patients with SSc&#46; Other studies on populations with systemic diseases that usually involve the esophagus&#44; such as Chagas disease&#44; have similarly found a lack of an association between HRM findings and upper GI symptomatology&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">25</span></a> Additionally&#44; in our study&#44; 95&#46;2&#37; of patients at the time of evaluation were treated with proton pump inhibitors &#40;PPIs&#41;&#46; The lack of association between the symptoms and the results of HRM may be also partly explained by the high percentage of patients using PPIs at the time of evaluation&#44; or even the use of other non-prescription medications for heartburn that could mask the symptoms evaluated&#46; This limitation was also seen in other study&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">21</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">On the other hand&#44; there are certain features of SSc that have been more consistently associated with HRM alterations&#46; Patients with SSc and Raynaud phenomenon have been found to have lower amplitude of distal esophageal contractions<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">21</span></a> as well as with more hypotensive lower esophageal sphincter<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">22</span></a> compared to those without&#46; Degree of skin involvement has also been positively correlated with esophageal dysmotility according to HRM as well as with more severe dysphagia&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">21&#44;23</span></a> The latter were not found in our cohort&#46; The presence of pulmonary fibrosis in SSc patients was also found to be associated with more absent contractility in HRM as well as with more symptoms of gastroesophageal reflux&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">22&#44;23</span></a> At least one study found that alterations in HRM were correlated to presence of Scl70 and absence of anti-centromere antibodies&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">20</span></a> but these findings were not replicated in another recent study&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a> In our study we did not assess lung function&#44; and neither the severity of skin involvement or presence of Raynaud phenomenon was significantly associated with HRM abnormalities&#44; although there was a trend toward more alterations in patients with Raynaud phenomenon&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The patients with morphea and scleroderma sine scleroderma we included both had a normal HRM&#46; Recently&#44; Arif et al&#46; evaluated SSc and morphea patients with upper gastrointestinal endoscopy&#44; esophageal manometry and 24-h pH monitoring&#44; and found that of the 31 patients with morphea&#44; none had manometric findings&#44; although only four patients had symptoms&#46; The authors concluded that in morphea&#44; an assessment of GI manifestations is not necessary&#44; unlike SSc&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">26</span></a> We also observed two patients with SSc without esophageal symptoms but with an abnormal HRM&#46; Previously&#44; Thonhofer et al&#46; conducted a retrospective study&#44; where they evaluated patients with SSc and Mixed Connective Tissue Disease &#40;MCTD&#41; without GI symptoms&#46; The patients underwent a baseline evaluation and follow-up at three to six months&#46; In all thirteen SSc patients&#44; significant pathology of the upper GI-tract was found&#46; In patients with esophageal abnormalities&#44; starting treatment led to favorable results&#44; which was confirmed in the follow-up study&#46; The authors suggest that the GI evaluation must be performed early in patients diagnosed with SSc&#44; even if they do not report typical symptoms&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">27</span></a> an opinion that we share considering our results&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">We consider that the strengths of the study are&#58; a population with a relatively early diagnosis of SSc&#44; the use of HRM and the Chicago classification&#46; The limitations include&#58; cross-sectional study design&#44; small cohort of patients&#44; heterogeneity in the treatment of patients&#44; lack of description of other comorbidities that could affect the outcome of the HRM&#44; as well as lack of further studies to complement the manometry result&#44; such as pH monitoring or endoscopy&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In conclusion&#44; we found a high prevalence of esophageal symptoms but a lack of association between these and the presence of an abnormal HRM&#44; which is in accordance to other published&#44; studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">19&#8211;22</span></a> This suggests that it is important to perform a systematic approach to GI symptomatology in SSc patients at diagnosis irrespective of objective procedures of motility evaluation&#46; This will identify early GI abnormalities&#44; help alleviate symptoms and thereby lessen the impact on morbidity and mortality generated by this condition&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethical disclosures</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Protection of human and animal subjects</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Confidentiality of data</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Right to privacy and informed consent</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding sources</span><p id="par0130" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authors&#8217; contribution</span><p id="par0135" class="elsevierStylePara elsevierViewall">Arana-Guajardo AC&#58; study concept and design&#59; acquisition of data&#59; analysis and interpretation of data&#59; drafting of the manuscript&#59; critical revision of the manuscript for important intellectual content&#59; obtained funding&#59; administrative&#44; technical&#44; or material support&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Barrera-Torres G&#58; acquisition of data&#59; drafting of the manuscript&#59; critical revision of the manuscript for important intellectual content&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Villarreal-Alarc&#243;n MA&#58; study concept and design&#59; analysis and interpretation of data&#59; drafting of the manuscript&#59; critical revision of the manuscript for important intellectual content&#59; study supervision&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Vega-Morales D&#58; study concept and design&#59; acquisition of data&#59; analysis and interpretation of data&#59; drafting of the manuscript&#59; critical revision of the manuscript for important intellectual content&#59; statistical analysis&#59; study supervision&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Esquivel-Valerio JA&#58; analysis and interpretation of data&#59; drafting of the manuscript&#59; critical revision of the manuscript for important intellectual content&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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              "titulo" => "Modified Rodnan skin score &#40;mRSS&#41;"
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              "titulo" => "Carlsson&#8211;Dent questionnaire"
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              "titulo" => "Dysphagia"
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              "titulo" => "High resolution manometry &#40;HRM&#41;"
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    "fechaRecibido" => "2017-06-25"
    "fechaAceptado" => "2017-09-15"
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            0 => "Systemic sclerosis"
            1 => "Esophageal disease"
            2 => "Comorbidity"
            3 => "High resolution manometry"
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            0 => "Esclerosis sist&#233;mica"
            1 => "Enfermedad esof&#225;gica"
            2 => "Comorbilidad"
            3 => "Manometr&#237;a de alta resoluci&#243;n"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The esophageal involvement in systemic sclerosis &#40;SSc&#41; causes impact in the morbidity and mortality&#46; High resolution manometry assesses esophageal involvement&#46; Our aim was to categorize esophageal motor disorder in patients with SSc by HRM&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We carried out an observational&#44; descriptive and cross-sectional study&#46; All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms&#46; Patients also completed the gastroesophageal reflux questionnaire &#40;Carlsson&#8211;Dent&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We included 19 patients with SSc&#44; 1 with morphea&#44; and 1 with scleroderma sine scleroderma&#46; Dysphagia and heartburn were the most frequent symptoms &#40;61&#37; each&#41;&#46; We found an abnormal HRM in 15 &#40;71&#46;4&#37;&#41; patients&#46; We found no statistically significant association between clinical or demographic variables and an abnormal HRM&#44; or between any upper GI symptom and HRM findings&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We observed a high prevalence of esophageal symptoms and of HRM abnormalities&#46; However&#44; there was no clear association between symptomatology and HRM findings&#46; HRM does not seem to accurately predict upper GI symptomatology&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La afectaci&#243;n esof&#225;gica en la esclerosis sist&#233;mica causa impacto en la morbimortalidad&#46; La manometr&#237;a de alta resoluci&#243;n eval&#250;a la afectaci&#243;n esof&#225;gica&#46; Nuestro objetivo fue categorizar el trastorno motor esof&#225;gico en pacientes con esclerosis sist&#233;mica por HRM&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio observacional&#44; descriptivo y transversal&#46; Todos los pacientes se sometieron a HRM&#44; as&#237; como a entrevistas semiestructuradas para evaluar la frecuencia y la gravedad de los s&#237;ntomas gastrointestinales&#46; Los pacientes tambi&#233;n completaron el cuestionario de reflujo gastroesof&#225;gico &#40;Carlsson-Dent&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 19 pacientes con esclerosis sist&#233;mica&#44; uno con morfea y uno con esclerodermia seno esclerodermia&#46; La disfagia y la pirosis fueron los s&#237;ntomas m&#225;s frecuentes &#40;un 61&#37; cada uno&#41;&#46; Encontramos una HRM anormal en 15 &#40;71&#44;4&#37;&#41; pacientes&#46; No se hall&#243; ninguna asociaci&#243;n estad&#237;sticamente significativa entre las variables cl&#237;nicas o demogr&#225;ficas y una HRM anormal&#44; o entre cualquier s&#237;ntoma GI superior y los hallazgos de HRM&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se observ&#243; una alta prevalencia de s&#237;ntomas esof&#225;gicos y de anomal&#237;as de la HRM&#46; Sin embargo&#44; no hubo asociaci&#243;n clara entre la sintomatolog&#237;a y los hallazgos de HRM&#46; La HRM no parece predecir con precisi&#243;n la sintomatolog&#237;a gastrointestinal&#46;</p></span>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">SSc&#44; systemic sclerosis&#59; SD&#44; standard deviation&#59; BMI&#44; body mass index&#59; mRSS&#44; modified Rodnan skin score&#59; NSAID&#44; nonsteroidal anti-inflammatory drug&#59; CCB&#44; calcium channel blockers&#59; PPI&#44; proton pump inhibitors&#59; HRM&#44; high resolution manometry&#46;</p>"
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                  \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">Variable&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;&#37;&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&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">HRM normal&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&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">HRM abnormal&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&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"><span class="elsevierStyleItalic">p</span>&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="elsevierStyleItalic">Age&#44; mean &#40;SD&#41; years</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&#46;2 &#40;10&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;6 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;63&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="elsevierStyleItalic">Female gender&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20 &#40;95&#46;2&#41;&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;100&#41;&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;93&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;71&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="4" align="left" valign="top"><span class="elsevierStyleItalic">BMI</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#46;55&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>Normal&#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="char" valign="top">7 &#40;33&#46;3&#41;&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;16&#46;6&#41;&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;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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&#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="char" valign="top">5 &#40;23&#46;8&#41;&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;16&#46;6&#41;&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;26&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Overweight&#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="char" valign="top">5 &#40;23&#46;8&#41;&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;33&#46;3&#41;&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;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Obesity&#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="char" valign="top">4 &#40;19&#41;&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;33&#46;3&#41;&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;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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="4" align="left" valign="top"><span class="elsevierStyleItalic">SSc classification and variants</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#46;94&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>Limited&#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="char" valign="top">17 &#40;80&#46;9&#41;&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;66&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;86&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Diffuse&#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="char" valign="top">2 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&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;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Scleroderma sine scleroderma&#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="char" valign="top">1 &#40;4&#46;8&#41;&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;16&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Morphea&#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="char" valign="top">1 &#40;4&#46;8&#41;&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;16&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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="4" align="left" valign="top"><span class="elsevierStyleItalic">mRSS</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td><td class="td" title="table-entry  " align="char" valign="top">0&#46;39&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>Mild &#60;20&#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="" valign="top">&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;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Moderate &#8805;20&#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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&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;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Raynaud phenomenon&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18 &#40;85&#46;7&#41;&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;66&#46;6&#41;&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;93&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;18&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">Antibodies</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>Antinuclear antibodies&#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="char" valign="top">15 &#40;75&#41;&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;66&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;73&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;48&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>Anti-Scl70&#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="char" valign="top">5 &#40;23&#46;8&#41;&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;16&#46;6&#41;&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;26&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;51&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>Anti-centromere&#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="char" valign="top">5 &#40;23&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&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;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;15&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">Drugs</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>NSAID&#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="char" valign="top">2 &#40;9&#46;5&#41;&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;16&#46;6&#41;&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;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;50&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>CCB&#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="char" valign="top">18 &#40;85&#46;7&#41;&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;66&#46;6&#41;&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;93&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;18&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>PPI&#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="char" valign="top">20 &#40;95&#46;2&#41;&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;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">CDQ&#44; Carlsson&#8211;Dent questionnaire&#59; HRM&#44; high resolution manometry&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&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;&#37;&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&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">HRM normal&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&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">HRM abnormal&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&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"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Esophageal symptoms&#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>Dysphagia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;61&#46;9&#41;&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;66&#46;6&#41;&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;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;59&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>Heartburn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;61&#46;9&#41;&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;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;66&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;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>Regurgitation&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;42&#46;9&#41;&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;83&#46;3&#41;&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;26&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;02&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>Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;47&#46;6&#41;&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;50&#41;&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;46&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;63&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>Chest pain&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;14&#46;3&#41;&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;33&#46;3&#41;&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;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;18&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>Nausea&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;19&#41;&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;33&#46;3&#41;&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;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;31&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>Vomiting&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;4&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&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;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;71&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">CDQ&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;04 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;59&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>0&#8211;3 score&#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="char" valign="top">8 &#40;38&#41;&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;50&#41;&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;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>4&#8211;15 score&#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="char" valign="top">13 &#40;61&#46;9&#41;&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;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;66&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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="4" align="left" valign="top"><span class="elsevierStyleItalic">Dysphagia classification&#44; n &#40;&#37;&#41;</span></td><td class="td" title="table-entry  " align="char" valign="top">0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No dysphagia&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;42&#46;8&#41;&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;66&#46;6&#41;&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;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Dysphagia to normal solids<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&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;53&#46;8&#41;&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;16&#46;6&#41;&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;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>Dysphagia to soft solids<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&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;46&#46;1&#41;&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;16&#46;6&#41;&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;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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>4&#8211;15 score&#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="char" valign="top">7 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Association between upper GI symptoms and HRM results&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:27 [
            0 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Systemic sclerosis&#58; a world wide global analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "P&#46; Coral-Alvarado"
                            1 => "A&#46;L&#46; Pardo"
                            2 => "N&#46; Castano-Rodriguez"
                            3 => "A&#46; Rojas-Villarraga"
                            4 => "J&#46;M&#46; Anaya"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Rheumatol"
                        "fecha" => "2009"
                        "volumen" => "28"
                        "paginaInicial" => "757"
                        "paginaFinal" => "765"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                          ]
                        ]
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                  "host" => array:1 [
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                      "Revista" => array:6 [
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                        "link" => array:1 [
                          0 => array:2 [
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                            "web" => "Medline"
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                        ]
                      ]
                    ]
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                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictors of survival in systemic sclerosis &#40;scleroderma&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "R&#46;D&#46; Altman"
                            1 => "T&#46;A&#46; Medsger Jr&#46;"
                            2 => "D&#46;A&#46; Bloch"
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
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                        "volumen" => "34"
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                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1901491"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality in systemic sclerosis &#40;scleroderma&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Lee"
                            1 => "P&#46; Langevitz"
                            2 => "C&#46;A&#46; Alderdice"
                            3 => "M&#46; Aubrey"
                            4 => "P&#46;A&#46; Baer"
                            5 => "M&#46; Baron"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Q J Med"
                        "fecha" => "1992"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1620814"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
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            4 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mortality and causes of death in a Swedish series of systemic sclerosis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Hesselstrand"
                            1 => "A&#46; Scheja"
                            2 => "A&#46; Akesson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "1998"
                        "volumen" => "57"
                        "paginaInicial" => "682"
                        "paginaFinal" => "686"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9924211"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence of clinical features&#44; serum antinuclear antibodies&#44; and lung function on survival of patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Jacobsen"
                            1 => "S&#46; Ullman"
                            2 => "G&#46;Q&#46; Shen"
                            3 => "A&#46; Wiik"
                            4 => "P&#46; Halberg"
                          ]
                        ]
                      ]
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2017.09.005

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	13	13	26
2024 October	28	13	41
2024 September	28	11	39
2024 August	62	29	91
2024 July	41	24	65
2024 June	39	29	68
2024 May	50	27	77
2024 April	39	24	63
2024 March	34	33	67
2024 February	36	15	51
2024 January	32	18	50
2023 December	21	24	45
2023 November	34	25	59
2023 October	20	26	46
2023 September	110	38	148
2023 August	26	13	39
2023 July	24	18	42
2023 June	29	25	54
2023 May	31	20	51
2023 April	13	7	20
2023 March	59	29	88
2023 February	39	20	59
2023 January	21	11	32
2022 December	61	21	82
2022 November	38	33	71
2022 October	63	22	85
2022 September	25	18	43
2022 August	28	37	65
2022 July	25	38	63
2022 June	29	25	54
2022 May	28	36	64
2022 April	34	33	67
2022 March	40	42	82
2022 February	47	40	87
2022 January	38	33	71
2021 December	25	34	59
2021 November	26	31	57
2021 October	48	52	100
2021 September	30	40	70
2021 August	24	32	56
2021 July	18	24	42
2021 June	28	27	55
2021 May	39	48	87
2021 April	81	91	172
2021 March	47	24	71
2021 February	20	13	33
2021 January	25	18	43
2020 December	17	12	29
2020 November	15	13	28
2020 October	11	12	23
2020 September	18	14	32
2020 August	26	17	43
2020 July	15	9	24
2020 June	12	9	21
2020 May	11	9	20
2020 April	14	12	26
2020 March	3	1	4

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