Brief Report
Acro-osteolysis as an Indicator of Severity in Systemic Sclerosis
La acrosteólisis como indicador de gravedad en los pacientes con esclerosis sistémica
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=> array:4 [ "autoresLista" => "Juan Carlos Arana-Ruiz, Luis Manuel Amezcua-Guerra" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Juan Carlos" "apellidos" => "Arana-Ruiz" "email" => array:1 [ 0 => "joannescarolus@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Luis Manuel" "apellidos" => "Amezcua-Guerra" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Residencia de Reumatología, Instituto Nacional de Cardiología, Mexico City, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Inmunología, Instituto Nacional de Cardiología, Mexico City, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La acrosteólisis como indicador de gravedad en los pacientes con esclerosis sistémica" ] ] "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 (SS) is an uncommon disease (the worldwide prevalence is 10–34.1 per 100,000 population), of unknown etiology, with a clear female predominance. The systemic forms are divided into 2 large groups, limited (LSS) and diffuse (DSS). The factors that interact in the pathogenesis are autoimmunity, inflammation and functional and structural changes in the small vessels, as well as interstitial and vascular fibrosis of the skin and internal organs, and collagen deposition in the extracellular matrix. The prognosis varies depending on the extent of the skin compromise, the degree of involvement of internal organs and the comorbidities.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">To date, it has been very difficult to build a consensus with regard to a practical and economical way to evaluate the extent of the damage in an individual in the outpatient setting. One of the tools most widely validated and employed in some clinical studies is the Medsger Disease Severity Scale (MDSS).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a> This scale does not take into consideration some of the complications of SS, such as acro-osteolysis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Acro-osteolysis is the erosion of the distal phalanges, affecting those of the hands in 22% of the patients.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a> It starts at the tip and, in the most severe cases, produces the destruction of a large portion of the distal phalanx, giving the finger a conical aspect.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Its clinical importance, according to some authors,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a> is its association with digital ulcers, severe Raynaud's phenomenon and calcinosis.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Main Objective</span><p id="par0020" class="elsevierStylePara elsevierViewall">We propose to determine whether acro-osteolysis is related to the severity of SS in accordance with the MDSS.</p></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Material and Methods</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study Design</span><p id="par0025" class="elsevierStylePara elsevierViewall">A cross-sectional, observational, quasi-experimental analysis was performed.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Description of the Study Population</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Inclusion Criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">We considered eligible any patient over 18 years of age who met the updated criteria of the American College of Rheumatology for SS, was being followed during the current year in the Department of Rheumatology of the Mexican National Institute of Cardiology, had a complete record for the determination of the MDSS, and had undergone capillaroscopy within the past year. This required:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0035" class="elsevierStylePara elsevierViewall">At least one indirect immunofluorescence assay, at the time of diagnosis, for antinuclear antibodies (ANA), as well as ANA specificities determined by enzyme-linked immunosorbent assay (ELISA): anti-centromere and anti-topoisomerase I.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0040" class="elsevierStylePara elsevierViewall">At least 2 clinical evaluations within the last year.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3.</span><p id="par0045" class="elsevierStylePara elsevierViewall">Examination within the preceding 2 years including: body weight and/or hematocrit; the presence of Raynaud's phenomenon and its severity; the presence of digital ulcers or digital gangrene; measurement of the finger-to-palm distance; evaluation of the presence or absence of muscle weakness and its degree, and the presence or absence of symptoms of esophageal or bowel dysfunction and the consequences; spirometry with determination of the diffusing capacity of the lungs for carbon monoxide (DLCO) and measurement of the forced vital capacity (FVC); evaluation of the presence or absence of pulmonary infiltrates on radiographs, and the presence or absence of pulmonary hypertension (PH) and, if present, its severity or whether or not continuous oxygen is required; electrocardiogram evaluated by an expert (cardiologist) to establish the presence or absence of arrhythmias, ventricular enlargement or heart failure; at least 1 transthoracic echocardiogram (TTE) to corroborate structural anomalies and left ventricular ejection fraction (LVEF), as well as calculated pulmonary artery systolic pressure (PASP); and creatinine determination and measurement of proteinuria, if detected.</p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">In addition to the analysis of these data, a radiological examination was performed to determine the presence or absence of acro-osteolysis.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Exclusion Criteria</span><p id="par0055" class="elsevierStylePara elsevierViewall">We excluded patients in whom the diagnosis was not clearly established, who had any syndromes that overlapped or mixed connective tissue disease that had the features of SS, who had been lost to follow-up in the past year, or for whom the data (referring to any of the abovementioned variables) were not complete.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Definition of the Variables</span><p id="par0060" class="elsevierStylePara elsevierViewall">All of the patients who had been diagnosed with PH had at least 2 of 3 studies that, while not confirmatory, created a high degree of suspicion as they indicated the presence of the disease: (a) a radiograph with thickening of the pulmonary artery associated with “pruning” of peripheral blood vessels (present in 90% of those affected, according to the literature) and/or (b) a TTE performed within the preceding 2 years showing tricuspid regurgitation with a pressure gradient >40<span class="elsevierStyleHsp" style=""></span>mmHg (tricuspid regurgitation velocity >3.2<span class="elsevierStyleHsp" style=""></span>m/s), with an assumed right atrial pressure of 10<span class="elsevierStyleHsp" style=""></span>mmHg (thus equivalent to a pulmonary artery systolic pressure > 50<span class="elsevierStyleHsp" style=""></span>mmHg),<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> and/or complete spirometry that included FVC and DLCO; the latter is usually between 40% and 80% of the predicted value in affected patients.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">We took into account all the variables proposed by Medsger for the evaluation of severity, in accordance with the definitions he and his collaborators had previously established, which were revised by the same group in 2003.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> However, we wish to make the following points.</p><p id="par0070" class="elsevierStylePara elsevierViewall">To determine the distance from pulp to palm in flexion, we took into account the worst score obtained in the most severely affected hand, in the absence of burns, Dupuytren's contracture or any other condition of the palm that could jeopardize this parameter.</p><p id="par0075" class="elsevierStylePara elsevierViewall">With respect to the gastrointestinal evaluation, a change was considered to be present only if there was an imaging study that supported the clinical suspicion (upper gastrointestinal series in the case of esophageal or duodenal disease and/or endoscopy, tomography in the case of intestinal involvement or evidence of blind loop syndrome observed in special coprological examinations).</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the section on lung, to achieve the final score, we considered the worse parameter evaluated, given that DLCO, FVC, PASP and radiographic changes are grouped together in each section. The identification of interstitial lung disease (ILD) was based not only on changes in those parameters, but on the presence of characteristic pulmonary infiltrates on high-resolution tomography with or without the presence of fine crepitant rales on auscultation. The same was carried out in the section on the heart, in which the final score was defined by the worst parameter (changes on the electrocardiogram or TTE showing an abnormal LVEF).</p><p id="par0085" class="elsevierStylePara elsevierViewall">Any change in the pericardium reported in TTE was considered to be a pericardial disease, once it had been evaluated by an expert in echocardiography. Pericardial effusion was classified according to Maisch et al.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Although the MDSS was not designed to sum up the points in the section corresponding to each organ, we performed this addition to facilitate the statistical analysis.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical Study</span><p id="par0095" class="elsevierStylePara elsevierViewall">The dichotomous variables were expressed as percentages, whereas the dimensional variables were expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation (SD).</p><p id="par0100" class="elsevierStylePara elsevierViewall">Statistical inference was based on chi-square tests, with adjustment for trends when possible, or the Kruskal–Wallis test with Dunn's post hoc test, as appropriate.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The results were divided into tertiles to improve the statistical calculation.</p><p id="par0110" class="elsevierStylePara elsevierViewall">All of the analyses were two-tailed and significance was set at <span class="elsevierStyleItalic">P</span><.05.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The statistical software package used was GraphPad Prism (version 4.02) (GraphPad Inc., San Diego, United States).</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0120" class="elsevierStylePara elsevierViewall">We studied a total of 40 patients who met the inclusion criteria. The mean age of the study population was 52 years, with a range of 13–77 years.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Regarding the duration of the disease course, the count began from the first year of diagnosis, even if this had not taken place in the institute, and continued once the patient had been enrolled in the study, in the department of rheumatology. As was to be expected, the patients with the longest history of disease had LSS, although there was not much difference with respect to DSS.</p><p id="par0130" class="elsevierStylePara elsevierViewall">The immense majority of the patients (39) were women and of the total group, 27 (70%) had LSS.</p><p id="par0135" class="elsevierStylePara elsevierViewall">In all, 18.6% of the patients with LSS had been diagnosed with PH (without specifying the group), the same incidence as pericardial effusion. Less common was ILD, with a prevalence of 3.7%. In DSS, the most common comorbidity was PH (29%), followed by ILD. Of all these conditions, only ILD had a statistically significant influence on the disease severity (see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Acro-osteolysis also showed a statistically significant difference in relation to severity (see <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0145" class="elsevierStylePara elsevierViewall">By far, a large part of the literature on SS is based on the observations of physicians from other countries in which Caucasians usually predominate and, to a lesser degree, Afro-Americans. The most widely known groups studying this disease are from the United Kingdom, The Netherlands, Italy and, to a lesser extent, North America. In contrast, it has been studied very little in Latin American countries, where there is a predominance of mestizos and, to a lesser extent, indigenous populations. A recent study published in <span class="elsevierStyleItalic">Science</span> shows how important the differences in the Mexican population can be with respect to the behavior of different diseases.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">With regard to the prevalence of ILD in SS, most of the literature reports a rate of 8%–12%, although it is usually milder in the diffuse forms, especially if it is associated with anti-centromere B.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">10,11</span></a> In the present study, we found it in only 3.7% of the patients. It was not very different in the patients with DSS, in whom a prevalence of 50%–80% has been reported in referral centers,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> whereas in this analysis, the prevalence scarcely reached 20% in that group of patients. However, these results should be taken with caution, given that many patients without respiratory symptoms may have been overlooked because they had not undergone high-resolution tomography.</p><p id="par0155" class="elsevierStylePara elsevierViewall">In a cohort of patients studied for ILD, with the usual type of interstitial pneumonia, Fischer et al.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> found that SS was the underlying disease in 8.7% of the overall cohort. In an observational study of the treatment of ILD in SS, the most extensive published to date, Iudici et al.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> found it to be much more common in DSS, and especially those patients who were positive for Scl were less likely to respond to treatment with cyclophosphamide and more likely to have more severe pulmonary compromise.</p><p id="par0160" class="elsevierStylePara elsevierViewall">With respect to PH, there are many discrepancies in the literature, having to do with the year of publication and the changes that have taken place in the diagnostic criteria. It is known that, in general, it is more widespread among patients with LSS, in whom it can come to be highly aggressive, and it usually belongs to group 1 of the Dana Point 2008 classification (true pulmonary arterial hypertension). The literature mentions an estimated prevalence in asymptomatic patients of 8%–14%,<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">12,15,16</span></a> whereas in the population of the Mexican National Institute of Cardiology, it was slightly more common (18.5%) in the limited forms, being even more frequent in the diffuse forms (29%). In these patients, a lower prevalence has characteristically been reported, and they usually develop this complication as a consequence of left heart disease (group 2) or secondary to restrictive lung disease (group 3).<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">17,18</span></a> In this respect, it is important to take into consideration the fact that several patients had not undergone right cardiac catheterization to confirm the diagnosis, which was based only on the TTE findings and clinical signs.</p><p id="par0165" class="elsevierStylePara elsevierViewall">While the literature indicates that acro-osteolysis is associated with a greater number of vascular complications, its association with disease severity is not clearly established. In our study, we confirm that there is a difference between the patients with mild and severe forms in terms of its frequency.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0170" class="elsevierStylePara elsevierViewall">Systemic sclerosis is an uncommon disease, of unknown etiology, about which we still have much to learn. It is still necessary to devise methods of evaluation much more widely available in clinical practice, that enable us to establish the severity of the disease with much simpler resources and, thus, to perform a proper stratification for patient follow-up. Acro-osteolysis is a clinical complication that is not considered in the MDSS, but is directly related to the severity. Should this be corroborated in future studies, this parameter could replace other complications that require complex and expensive measures for their evaluation.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical Disclosures</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Protection of human and animal subjects</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Confidentiality of data</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Right to privacy and informed consent</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of Interest</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors declare they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres823640" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec820303" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres823639" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec820302" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Main Objective" ] ] ] 5 => array:3 [ "identificador" => "sec0015" "titulo" => "Material and Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Study Design" ] 1 => array:3 [ "identificador" => "sec0025" "titulo" => "Description of the Study Population" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Inclusion Criteria" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Exclusion Criteria" ] ] ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Definition of the Variables" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Statistical Study" ] ] ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conclusions" ] 9 => array:3 [ "identificador" => "sec0065" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-03-02" "fechaAceptado" => "2015-11-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec820303" "palabras" => array:3 [ 0 => "Systemic sclerosis" 1 => "Medsger severity scale" 2 => "Acrosteolysis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec820302" "palabras" => array:3 [ 0 => "Esclerosis sistémica" 1 => "Escala de severidad de Medsger" 2 => "Acrosteólisis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic sclerosis is a rare disease that predominantly affects women. The Medsger severity scale has been used to assess the severity, but it requires expensive and poorly accessible studies and it does not include complications such acrosteolysis, calcinosis, pericardial disease or hypothyroidism that occur on a relatively frequent basis in this disease. There is no study that considers if comorbidities, such as primary biliary cirrhosis, are related to gravity.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the correlation between severity and the presence of such complications.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">40 patients with systemic sclerosis, dividing them into tertiles according to severity were studied. Dichotomous variables were described using percentages, while dimensional by averages<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>SD. Statistical inference was performed using chi square test or Kruskal–Wallis test with Dunn post-test, as appropriate. A significance at <span class="elsevierStyleItalic">P</span><.05 was set.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Of all the complications studied there were only differences in severity with acrosteolysis. Within comorbidities, primary biliary cirrhosis is not associated with gravity.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La esclerosis sistémica es una patología rara que afecta predominantemente a las mujeres. Se utiliza la escala de Medsger para evaluar la severidad, pero precisa de estudios caros y de difícil acceso y no incluye complicaciones tales como acrosteólisis, calcinosis, enfermedades pericárdicas o hipotiroidismo, que se presentan con relativa frecuencia en esta enfermedad. No existen estudios que tengan en cuenta si las comorbilidades, como la cirrosis biliar primaria, se asocian a la gravedad.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Establecer la correlación entre la gravedad y la presencia de complicaciones asociadas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se estudió a 40 pacientes con esclerosis sistémica, divididos entre terciles conforme a su gravedad. Se describen las variables dicotómicas con porcentajes, mientras que las variables dimensionales se describen con medias<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>DE. La interferencia estadística se llevó a cabo con la prueba de la χ<span class="elsevierStyleSup">2</span> y de Kruskal–Wallis con la prueba de Dunn después del test, según procediera. Se estableció la significación estadística en p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,05.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">De todas las complicaciones analizadas, solo había diferencias en el caso de la acrosteólisis. Entre las comorbilidades, la cirrosis biliar primaria no se asocia a la gravedad.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as: Arana-Ruiz JC, Amezcua-Guerra LM. La acrosteólisis como indicador de gravedad en los pacientes con esclerosis sistémica. Reumatol Clin. 2016;12:263–266.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">ILD, interstitial lung disease; PBC, primary biliary cirrhosis; PH, pulmonary hypertension.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">All patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Tertiles according to severity</th><th class="td" title="table-head " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">P</span> value<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Lowest (n=13) \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">Middle (n=13) \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">Highest (n=14) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Age in years</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Women</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Duration of the disease (years)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Limited SS</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 (70%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">.002</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Diffuse SS</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (30%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">.002</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" 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="6" align="left" valign="top"><span class="elsevierStyleItalic">Comorbidities</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PH \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">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ILD \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">.01</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PBC \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">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" 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="6" align="left" valign="top"><span class="elsevierStyleItalic">Therapeutic agents</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vasodilators \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">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Immunosuppressive agents \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">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">.004</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Glucocorticoids \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">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1384896.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Chi square test for two-tailed analysis.</p> <p class="elsevierStyleNotepara" id="npar0010">The <span class="elsevierStyleItalic">P</span> values for the statistically significant findings are in boldface.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Demographic and Clinical Data Related to the Medsger Disease Severity Scale.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Severity in the MDSS in tertiles</th><th class="td" title="table-head " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">P</span> value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Lowest (n=13) \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">Middle (n=13) \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">Highest (n=14) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Acro-osteolysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">.02</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Calcinosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pericardial disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 13 | 22 |
| 2024 October | 50 | 35 | 85 |
| 2024 September | 64 | 32 | 96 |
| 2024 August | 73 | 41 | 114 |
| 2024 July | 52 | 31 | 83 |
| 2024 June | 75 | 38 | 113 |
| 2024 May | 70 | 32 | 102 |
| 2024 April | 56 | 28 | 84 |
| 2024 March | 65 | 24 | 89 |
| 2024 February | 70 | 29 | 99 |
| 2024 January | 43 | 21 | 64 |
| 2023 December | 41 | 25 | 66 |
| 2023 November | 57 | 31 | 88 |
| 2023 October | 61 | 36 | 97 |
| 2023 September | 92 | 31 | 123 |
| 2023 August | 44 | 11 | 55 |
| 2023 July | 54 | 32 | 86 |
| 2023 June | 56 | 27 | 83 |
| 2023 May | 62 | 24 | 86 |
| 2023 April | 40 | 6 | 46 |
| 2023 March | 67 | 21 | 88 |
| 2023 February | 34 | 26 | 60 |
| 2023 January | 50 | 7 | 57 |
| 2022 December | 70 | 27 | 97 |
| 2022 November | 59 | 28 | 87 |
| 2022 October | 40 | 30 | 70 |
| 2022 September | 54 | 29 | 83 |
| 2022 August | 44 | 40 | 84 |
| 2022 July | 42 | 31 | 73 |
| 2022 June | 40 | 30 | 70 |
| 2022 May | 73 | 40 | 113 |
| 2022 April | 94 | 35 | 129 |
| 2022 March | 57 | 46 | 103 |
| 2022 February | 45 | 25 | 70 |
| 2022 January | 63 | 32 | 95 |
| 2021 December | 59 | 43 | 102 |
| 2021 November | 69 | 39 | 108 |
| 2021 October | 63 | 52 | 115 |
| 2021 September | 45 | 40 | 85 |
| 2021 August | 45 | 40 | 85 |
| 2021 July | 34 | 33 | 67 |
| 2021 June | 48 | 48 | 96 |
| 2021 May | 58 | 50 | 108 |
| 2021 April | 155 | 100 | 255 |
| 2021 March | 74 | 27 | 101 |
| 2021 February | 34 | 26 | 60 |
| 2021 January | 36 | 26 | 62 |
| 2020 December | 44 | 18 | 62 |
| 2020 November | 31 | 21 | 52 |
| 2020 October | 26 | 13 | 39 |
| 2020 September | 65 | 21 | 86 |
| 2020 August | 25 | 24 | 49 |
| 2020 July | 26 | 16 | 42 |
| 2020 June | 34 | 23 | 57 |
| 2020 May | 37 | 20 | 57 |
| 2020 April | 32 | 13 | 45 |
| 2020 March | 17 | 12 | 29 |
| 2020 February | 2 | 0 | 2 |
| 2018 May | 3 | 0 | 3 |
| 2018 April | 87 | 14 | 101 |
| 2018 March | 34 | 11 | 45 |
| 2018 February | 20 | 8 | 28 |
| 2018 January | 16 | 5 | 21 |
| 2017 December | 20 | 13 | 33 |
| 2017 November | 20 | 9 | 29 |
| 2017 October | 29 | 9 | 38 |
| 2017 September | 21 | 15 | 36 |
| 2017 August | 24 | 7 | 31 |
| 2017 July | 32 | 10 | 42 |
| 2017 June | 39 | 11 | 50 |
| 2017 May | 42 | 19 | 61 |
| 2017 April | 35 | 11 | 46 |
| 2017 March | 21 | 4 | 25 |
| 2017 February | 13 | 13 | 26 |
| 2017 January | 17 | 7 | 24 |
| 2016 December | 48 | 21 | 69 |
| 2016 November | 37 | 31 | 68 |
| 2016 October | 85 | 39 | 124 |
| 2016 September | 82 | 28 | 110 |
| 2016 August | 27 | 4 | 31 |
| 2016 July | 2 | 0 | 2 |
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