Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis

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"tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "123" "paginaFinal" => "127" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El uso de secukinumab tras la terapia anti-TNF es mayor de lo esperado por el riesgo de desarrollar enfermedad inflamatoria intestinal?" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 798 "Ancho" => 3434 "Tamanyo" => 171894 ] ] "descripcion" => array:1 [ "en" => "OR value for IBD in patients using secukinumab after anti-TNF was 8.71 (2.33–32.63) when compared to those using first-choice secukinumab." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Fatih Albayrak, Mustafa Gür, Ahmet Karataş, Süleyman Serdar Koca, Bünyamin Kısacık" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Fatih" "apellidos" => "Albayrak" ] 1 => array:2 [ "nombre" => "Mustafa" "apellidos" => "Gür" ] 2 => array:2 [ "nombre" => "Ahmet" "apellidos" => "Karataş" ] 3 => array:2 [ "nombre" => "Süleyman Serdar" "apellidos" => "Koca" ] 4 => array:2 [ "nombre" => "Bünyamin" "apellidos" => "Kısacık" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X23002541?idApp=UINPBA00004M" "url" => "/1699258X/0000002000000003/v1_202402290648/S1699258X23002541/v1_202402290648/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "117" "paginaFinal" => "122" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Juan Carlos Cortes-Quiroz, Jose Bernal, Jose Rosas, Javier Ena" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Juan Carlos" "apellidos" => "Cortes-Quiroz" "email" => array:1 [ 0 => "juancarloscortesq@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Jose" "apellidos" => "Bernal" ] 2 => array:2 [ "nombre" => "Jose" "apellidos" => "Rosas" ] 3 => array:2 [ "nombre" => "Javier" "apellidos" => "Ena" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor, 7, 03570 Villajoyosa, Alicante, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Rendimiento de la adenosina desaminasa en el líquido sinovial para el diagnóstico de la artritis tuberculosa: una revisión sistemática y metaanálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1692 "Ancho" => 2175 "Tamanyo" => 177751 ] ] "descripcion" => array:1 [ "en" => "Area under the receiver operating characteristic of synovial ADA for tuberculous arthritis detection compared with a composite reference standard." ] ] ] "textoCompleto" => "IntroductionBone and joint tuberculosis may account for up to 35 percent of cases of extrapulmonary tuberculosis. Skeletal tuberculosis most often involves the spine, followed by tuberculous arthritis in weight-bearing joints and extraspinal tuberculous osteomyelitis.<a class="elsevierStyleCrossRef" href="#bib0120">1</a> An early and correct diagnosis of tuberculosis is critical to reducing disability since a delay in the diagnosis can lead to joint destruction, joint deformity, and even paraplegia. In joint tuberculosis, conventional synovial fluid analysis and traditional protocols for diagnosis are time-consuming procedures with low sensitivity.<a class="elsevierStyleCrossRef" href="#bib0125">2</a> Recently, commercial automated molecular tests have been incorporated as rapid diagnostic tools. As an example, the Xpert MTB/RIF assay (Cepheid, CA, USA) is a nucleic acid amplification test targeting the IS6110 that simultaneously detects Mycobacterium tuberculosis complex and resistance to rifampin (RIF) in less than 2h.<a class="elsevierStyleCrossRef" href="#bib0130">3</a> However, nucleic acid amplification techniques require instrumentation and power requirements of polymerase chain reaction not always available in low-resource settings. Adenosine deaminase, referred to as ADA (EC 3.5.4.4), is a key enzyme in purine metabolism, which catalyzes the irreversible deamination of adenosine (deoxyadenosine) to inosine (deoxyinosine). A laboratory determination of ADA activity is simple, quick, and relatively cheap.<a class="elsevierStyleCrossRef" href="#bib0135">4</a> The activity of ADA is indirectly related to the subsets of T cell lymphocytes activated by the inflammatory response induced by tuberculosis. Several studies have confirmed the diagnostic potential of ADA for patients with suspected pleural, peritoneal o meningeal tuberculosis.<a class="elsevierStyleCrossRefs" href="#bib0140">5–7</a> The most commonly used cut-off values for ADA were ≥40IU/L for pleural and peritoneal tuberculosis, and ≥10IU/L for meningeal tuberculosis. However, the clinical performance of measuring the activity of ADA in the synovial fluid has received less attention. Considering the small number of studies analyzing the current role of ADA as a diagnostic tool for synovial tuberculosis, we conducted a systematic review of the literature and a meta-analysis to determine the usefulness of ADA levels in diagnosing tuberculous arthritis.MethodsThe present meta-analysis was performed according to the guidelines of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) (Supplementary file) statement and with methods recommended by the Cochrane Diagnostic Test Accuracy Working Group.<a class="elsevierStyleCrossRefs" href="#bib0155">8,9</a> The protocol for this meta-analysis is registered with PROSPERO (number CRD42021284472).Data sources and search strategyWe performed a systematic literature search using electronic datasets (i.e., PubMed, Embase, Cochrane Central, Web of Science, and MedRxiv databases) for adenosine deaminase as a tool for diagnosing synovial tuberculosis. We also screened for references from original articles, previous systematic reviews, and conference abstracts from the American College of Rheumatology and the European League Against Rheumatism to identify eligible trials until October 2021. The search strategy used was Adenosine Deaminase AND Tuberculosis AND Synovial fluid. No language restriction. Publication period: January 1986 to October 2021. References cited in the included articles and reviews were further explored for possible candidate studies.Inclusion criterialsWe included full-text original studies that assessed the diagnostic accuracy of adenosine deaminase activity for synovial tuberculosis. Reference standards were well-defined and appropriate to the studies. The articles directly provided true positive, false positive, false negative, and true negative values for the assay or included the data necessary to calculate these measures. We excluded case reports, articles written in languages other than English and Spanish, and studies with <10 samples.Reference standardThe reference standard was a composite of clinical symptoms, radiographic features, biochemical test results, smears, culture, histopathology, and response to antituberculosis drugs or a mycobacterial culture as it was defined in the original paper. Some or all of the factors with positive results were considered positive tuberculous arthritis. Cases were considered non-tuberculosis if all the results were negative. We used the composite reference standard as defined in the original paper.Literature screening and selectionTwo investigators (JCC-Q, JAB) independently assessed the candidate articles by reviewing their titles and abstracts, followed by the full text, for inclusion. Discrepancies between the two investigators were resolved by discussion with a third investigator (JR, JE).Data extractionWe extracted data including author name; year; country; patient selection method, adenosine deaminase assay, true positive, false positive, false negative, and true negative values. The same two investigators independently extracted the necessary information from each of the included articles; we crosschecked the information they obtained. Discrepancies in the two data sets were settled by a discussion with a third investigator, similar to that used during the literature selection phase.Assessment of study qualityTwo investigators independently used a revised tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) to assess study quality separately.<a class="elsevierStyleCrossRef" href="#bib0165">10</a> We chose not to formally assess publication bias, as the available methods such as funnel plots are not considered valid for diagnostic accuracy reviews.<a class="elsevierStyleCrossRef" href="#bib0165">10</a>Data synthesis and statistical analysisWe first obtained the values corresponding to True Positive, False Positive, False Negative, and True Negative in each included study. We calculated the estimated pooled sensitivity and specificity of adenosine deaminase activity in synovial fluid associated with the 95% confidence interval (CI), against the composite reference standard or culture, using bivariate random effects models. Forest plots for sensitivity and specificity were generated for each study. The areas under the summary receiver operating characteristic (SROC) curves (AUC) were subsequently calculated. I2 statistics were used to assess heterogeneity across the studies. While 0% indicated no observed heterogeneity, values greater than 50% were considered to imply substantial heterogeneity.<a class="elsevierStyleCrossRef" href="#bib0170">11</a> We explored different patient selection methods, assay methods, and quality of study as potential sources of heterogeneity, using subgroup and metaregression analyses. MetaDisc 1.4 (HRC, Madrid, Spain) generated forest plots of sensitivity and specificity with 95% CI for each study and carried out meta-analyses and meta-regression analyses.<a class="elsevierStyleCrossRef" href="#bib0175">12</a>ResultsIdentification of studies and study characteristicsThrough our search strategy, we identified candidate articles from relevant databases, and seven articles with a total of 305 patients met the inclusion criteria (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0180">13–19</a> Four studies were conducted in India, and one study each was conducted in Korea, Thailand, and Spain (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The assay to measure the activity of ADA was carried out using the Galanti–Giusti method in five studies. There were three prospective studies, three retrospective studies, and one ambispective study. Six articles were written in English and one in Spanish.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Study qualityThe methodological quality of the included studies, using the QUADAS2 tools is summarized in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>. The risk of bias was below 50% and it was mainly due to patient selection and the reference standard; flow and timing from the index test were judged with low risk of bias. Overall, the applicability concern was low. Based on the risk of bias, prospective studies were classified as high-quality and retrospective–ambispective as low quality. Adenosine deaminase activity in tuberculous arthritis. The activity of ADA in synovial fluid was measured using the colorimetric method of Galanti–Giusti in 5 studies,<a class="elsevierStyleCrossRefs" href="#bib0180">13,19</a> one study used an enzymatic spectrophotometric method,<a class="elsevierStyleCrossRef" href="#bib0200">17</a> and one study used a commercial assay (ADA-N kit; Denka Seiken Co Ltd, Japan).<a class="elsevierStyleCrossRef" href="#bib0205">18</a> The values of ADA activity in patients with tuberculous joint infection varied across studies even in those publications using the same methodology. The cut-off values of ADA for diagnosing tuberculosis ranged from 15 to 60IU/L, being the median value between 40 and 50IU/L. Compared with other etiologies, patients with tuberculous joint infection had greater values of adenosine deaminase activity in every study, but there was some overlap in cases with septic arthritis (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Diagnostic accuracy of adenosine deaminase for tuberculous arthritisThe sensitivity of adenosine deaminase in synovial fluid ranged from 86% (95% CI, 64–97) to 100% (95% CI, 86–100). The pooled sensitivity was 94% (95% CI, 89–98; I2=23.2%) and the specificity ranged from 67% (95% CI, 30–93) to 100% (95% CI, 93–100) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>a). The pooled specificity of adenosine deaminase was 88% (95% CI, 83–92; I2=83%) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>b). There was substantial heterogeneity of specificity but not of sensitivity. The AUC of the SROC was 0.96 (95% CI, 0.92–0.99) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). We explored the heterogeneity among studies using subgroup and meta-regression analyses on predefined subgroups of quality of the study (High=1 vs Low=0), type of assay (Galanti–Giusti=1 vs. another type of assay=0), and country of study (India=1 vs. another country=0). We did not find heterogeneity among the studies according to the predefined subgroups.<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>DiscussionOur meta-analysis included 7 studies (305 patients) quantifying adenosine deaminase in synovial fluid with comparisons to the clinical reference standard for the diagnosis of tuberculous arthritis.<a class="elsevierStyleCrossRefs" href="#bib0180">13–19</a> The Galanti–Giusti method,<a class="elsevierStyleCrossRef" href="#bib0215">20</a> was used to assess adenosine deaminase activity in most studies. However, the cut-off point of adenosine deaminase activity for the diagnosis of tuberculosis varied across the publications, being 40–50IU/L the median value. The pooled sensitivity and specificity were 94% (95% CI, 89–98) and 88% (95% CI, 82–92), respectively. The meta-analysis showed homogeneity for pooled sensitivity but significant heterogeneity for the specificity of the test.Regarding specificity, the activity of adenosine deaminase in synovial fluids is also elevated in other conditions besides tuberculosis. We found a decreasing gradient in adenosine deaminase activity from arthritis caused by tuberculosis and bacterial infections through rheumatoid arthritis, crystal arthritis, and finally osteoarthritis. We found in some cases of overlap of adenosine deaminase activity between tuberculosis and septic arthritis<a class="elsevierStyleCrossRefs" href="#bib0180">13,19</a>; therefore it is necessary to routinely include biochemical analysis and culture as part of the diagnostic procedures.We analyzed the possible sources of heterogeneity in the analysis of the specificity of the adenosine deaminase test. Some of the studies were prospectively conducted and others were retrospective, which could have an impact on the selection of patients. Also, the reference standard could have varied among the articles included. Most studies used a composite of clinical, histological, microbiological, and response to therapy criteria, but the proportion of cases with a confirmed infection by microbiological methods was unknown. Publication bias was not assessed since at present there is no recognized and accepted statistical method for quantifying the potential publication bias in diagnostic studies.<a class="elsevierStyleCrossRef" href="#bib0220">21</a> The direction of the study, variations in the components of the clinical reference standard, and publication bias could explain some sources of heterogeneity. To assess the origin of heterogeneity we carried out subgroup and meta-regression analyses focused on the quality of the study, country, and type of assay. After carrying out metaregression analysis according to the aforementioned subgroups we could not identify the source of heterogeneity. The availability of data in the publications did not permit the analysis of other potential sources of heterogeneity.There are no direct comparisons between the diagnostic performances of adenosine deaminase and Xpert MTB/RIF in synovial fluid for the diagnosis of tuberculosis joint infection. In the meta-analysis carried out by Shen et al., the pooled sensitivity and specificity of Xpert MTB/RIF were 81% and 99%, respectively.<a class="elsevierStyleCrossRef" href="#bib0225">22</a> In our study adenosine deaminase showed slightly better sensitivity of 94% with some poorer specificity of 88%. Compared with Xpert MTB/RIF, adenosine deaminase assessment has the disadvantage of not providing information on the susceptibility of Mycobacterium tuberculosis to rifampin in case of a positive result.Besides Xpert MTB/RIF, other nucleic acid amplification techniques are targeting the mpb64 and IS6110 genes. Combining the results of IS6110 RT PCR and mpb64 RT PCR improved the overall sensitivity and hence mpb64 can be used as an additional target for diagnosis of extrapulmonary tuberculosis.<a class="elsevierStyleCrossRef" href="#bib0230">23</a> However, due to the simplicity and availability of adenosine deaminase assays they can be used as complementary information to nucleic acid amplification techniques.In summary, measuring the activity of adenosine deaminase in synovial fluid is easy, cheap, and available in areas with poor resources. Adenosine deaminase activity values above the cut-off point add significant diagnostic information to start empirical treatment against tuberculosis while waiting for synovial fluid Lowenstein culture results. Adenosine deaminase activity in synovial fluid can be used as an additional tool for the diagnosis of tuberculosis joint infection in cases of negative results from nucleic acid amplification methods.Authors’ contributionsThis manuscript is co-authored by JCCQ, JB, JR, and JE (conception and design, analysis and interpretation of data, and writing of manuscript). All authors read and approved the final manuscript.Ethics approval and consent to participateEthics approval consent was waived. All the data presented in this review is from previously published studies.This study was presented as a POSTER/Abstract at the Annual European Congress of Rheumatology EULAR 2022.FundingThis study was not funded.Conflict of interestThey authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres2098011" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1787814" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2098010" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1787815" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Data sources and search strategy" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion criterials" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Reference standard" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Literature screening and selection" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Data extraction" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Assessment of study quality" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Data synthesis and statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0050" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Identification of studies and study characteristics" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Study quality" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Diagnostic accuracy of adenosine deaminase for tuberculous arthritis" ] ] ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Authors’ contributions" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Ethics approval and consent to participate" ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-02-15" "fechaAceptado" => "2023-11-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1787814" "palabras" => array:4 [ 0 => "Tuberculosis" 1 => "Adenosine deaminase" 2 => "Synovial fluid" 3 => "Sensitivity and specificity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1787815" "palabras" => array:4 [ 0 => "Tuberculosis" 1 => "Adenosina desaminasa" 2 => "Líquido sinovial" 3 => "Sensibilidad y especificidad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectivesAdenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. MethodsWe searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012–2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). ResultsSeven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89–98; I2=23%) and 88% (95% CI, 83–92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3–222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92–0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. ConclusionsMeasuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivosLa actividad de la adenosina desaminasa (ADA) ha mostrado un buen desempeño en el diagnóstico de la tuberculosis pleural, peritoneal y meníngea. Este metaanálisis tuvo como objetivo evaluar el rendimiento de la medición de la actividad de la ADA en el líquido sinovial para el diagnóstico precoz de la tuberculosis articular. MétodosSe realizaron búsquedas de resúmenes de congresos en la información publicada en las bases de datos MEDLINE, Embase, Cochrane Library, Web of Science y MedRxiv, así como en información no publicada en el American College of Rheumatology y la European League Against Rheumatism (2012-2021). También se escanearon las listas de referencias de los artículos. Dos revisores aplicaron de forma independiente los criterios de selección, evaluaron la calidad y extrajeron los datos (número PROSPERO CRD42021284472). ResultadosSe incluyeron siete estudios independientes (n=305 sujetos) que compararon la actividad de la ADA en el líquido sinovial con un método diagnóstico compuesto de referencia para la tuberculosis. En general, el riesgo de sesgo se consideró bajo. Los estudios se clasificaron como de alta calidad (n=3; 148 sujetos) y de baja calidad (n=4; 157 sujetos). La sensibilidad y la especificidad agrupadas de la actividad de la ADA fueron del 94% (intervalo de confianza [IC] del 95%: 0,89-98; I2=23%) y del 88% (IC95%: 83-92; I2=83%), respectivamente. El modelo de efectos aleatorios para el odds ratio diagnóstico agrupado fue de 67,1 (IC95%: 20,3-222,2; I2=30%). El área de la curva característica de operación del receptor fue de 0,96 (IC95%: 0,92-0,99). La metarregresión no identificó la calidad del estudio, el país de publicación o el tipo de ensayo como fuente de heterogeneidad. ConclusionesLa medición de la actividad de ADA en el líquido sinovial demuestra un buen rendimiento para el diagnóstico precoz de la tuberculosis articular." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2184 "Ancho" => 2508 "Tamanyo" => 353746 ] ] "descripcion" => array:1 [ "en" => "Process of selection of studies included in the meta-analysis. Revised abstracts after exclusion of duplicates (n=7)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 638 "Ancho" => 2508 "Tamanyo" => 140891 ] ] "descripcion" => array:1 [ "en" => "Risk of bias and applicability concerns graph: review authors’ judgements about each domain presented as percentages across included studies." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2137 "Ancho" => 2508 "Tamanyo" => 315159 ] ] "descripcion" => array:1 [ "en" => "(a) Pooled sensitivity. (b) Pooled specificity." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1692 "Ancho" => 2175 "Tamanyo" => 177751 ] ] "descripcion" => array:1 [ "en" => "Area under the receiver operating characteristic of synovial ADA for tuberculous arthritis detection compared with a composite reference standard." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ND: not described. TP: true positive. FP: false positive. FN: false negative. TN: true negative." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author [ref.] \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Year \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N° of subjects included \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N° of subjects analyzed \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ADA assay method \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ADA cut-off point \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TB cases (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TP \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FP \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FN \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TN \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Telenti<a class="elsevierStyleCrossRef" href="#bib0180">13</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1991 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Spain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Galanti–Giusti \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kumar<a class="elsevierStyleCrossRef" href="#bib0185">14</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1994 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">India \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Galanti–Giusti \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10μm/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gupta<a class="elsevierStyleCrossRef" href="#bib0190">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">India \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Galanti–Giusti \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Foocharoen<a class="elsevierStyleCrossRef" href="#bib0195">16</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thailand \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Galanti–Giusti \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sharma<a class="elsevierStyleCrossRef" href="#bib0200">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">India \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">122 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enzymatic method \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (64) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sohn<a class="elsevierStyleCrossRef" href="#bib0205">18</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2021 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">South Korea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADA N kit \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kawle<a class="elsevierStyleCrossRef" href="#bib0210">19</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2021 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">India \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ambispective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Galanti–Giusti \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3471842.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of studies included in the meta-analysis." ] ] 5 => 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" => "ND: not determined." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Studies included in meta-analysis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tuberculosis arthritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Septic arthritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rheumatoid arthritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Crystal-induced arthritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteoarthritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Post-traumatic arthritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Miscellaneous arthritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Telenti<a class="elsevierStyleCrossRef" href="#bib0180">13</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.5 [28–33] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 [17–37] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.2 [16–26] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kumar<a class="elsevierStyleCrossRef" href="#bib0185">14</a>,<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.0±2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.9±0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.9±0.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.5±0.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.9±0.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gupta<a class="elsevierStyleCrossRef" href="#bib0190">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88 [46–156] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.2 [25–32.6] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Foocharoen<a class="elsevierStyleCrossRef" href="#bib0195">16</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.7±10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.7±5.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.8±11.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.0±12.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sharma<a class="elsevierStyleCrossRef" href="#bib0200">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">146.5±116.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.0±48.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sohn<a class="elsevierStyleCrossRef" href="#bib0205">18</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">108 [76–150] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">119.8 [23–250] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31.5 [11–60] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kawle<a class="elsevierStyleCrossRef" href="#bib0210">19</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 [11–35] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 [3–12] \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3471843.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Adenosine deaminase activity in μm/L." ] ] ] "descripcion" => array:1 [ "en" => "Adenosine deaminase activity (U/L), mean±SD or median [range], in synovial fluid according etiology." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0120" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculosis of bones and joints" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.G. Watts" 1 => "R.M. Lifeso" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2106/00004623-199602000-00019" "Revista" => array:6 [ "tituloSerie" => "J Bone Joint Surg Am" "fecha" => "1996" "volumen" => "78" "paginaInicial" => "288" "paginaFinal" => "298" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8609123" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0125" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculosis of bones and joints: diagnostic approaches" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.A. Mousa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s002640050251" "Revista" => array:6 [ "tituloSerie" => "Int Orthop" "fecha" => "1998" "volumen" => "22" "paginaInicial" => "245" "paginaFinal" => "246" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9795812" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0130" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development, rollout and impact of Xpert MTB/RIF for tuberculosis: what lessons have we learnt and how can we do better?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Albert" 1 => "R.R. Nathavitharana" 2 => "C. Isaacs" 3 => "M. Pai" 4 => "C.M. Denkinger" 5 => "C.C. 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Original article

Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis

Rendimiento de la adenosina desaminasa en el líquido sinovial para el diagnóstico de la artritis tuberculosa: una revisión sistemática y metaanálisis

Juan Carlos Cortes-Quiroz

Autor para correspondencia

juancarloscortesq@gmail.com

Corresponding author.

, Jose Bernal, Jose Rosas, Javier Ena

Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor, 7, 03570 Villajoyosa, Alicante, Spain

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        "titulo" => "Rendimiento de la adenosina desaminasa en el l&#237;quido sinovial para el diagn&#243;stico de la artritis tuberculosa&#58; una revisi&#243;n sistem&#225;tica y metaan&#225;lisis"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Area under the receiver operating characteristic of synovial ADA for tuberculous arthritis detection compared with a composite reference standard&#46;</p>"
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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">Bone and joint tuberculosis may account for up to 35 percent of cases of extrapulmonary tuberculosis&#46; Skeletal tuberculosis most often involves the spine&#44; followed by tuberculous arthritis in weight-bearing joints and extraspinal tuberculous osteomyelitis&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> An early and correct diagnosis of tuberculosis is critical to reducing disability since a delay in the diagnosis can lead to joint destruction&#44; joint deformity&#44; and even paraplegia&#46; In joint tuberculosis&#44; conventional synovial fluid analysis and traditional protocols for diagnosis are time-consuming procedures with low sensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> Recently&#44; commercial automated molecular tests have been incorporated as rapid diagnostic tools&#46; As an example&#44; the Xpert MTB&#47;RIF assay &#40;Cepheid&#44; CA&#44; USA&#41; is a nucleic acid amplification test targeting the IS6110 that simultaneously detects Mycobacterium tuberculosis complex and resistance to rifampin &#40;RIF&#41; in less than 2<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">3</span></a> However&#44; nucleic acid amplification techniques require instrumentation and power requirements of polymerase chain reaction not always available in low-resource settings&#46; Adenosine deaminase&#44; referred to as ADA &#40;EC 3&#46;5&#46;4&#46;4&#41;&#44; is a key enzyme in purine metabolism&#44; which catalyzes the irreversible deamination of adenosine &#40;deoxyadenosine&#41; to inosine &#40;deoxyinosine&#41;&#46; A laboratory determination of ADA activity is simple&#44; quick&#44; and relatively cheap&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">4</span></a> The activity of ADA is indirectly related to the subsets of T cell lymphocytes activated by the inflammatory response induced by tuberculosis&#46; Several studies have confirmed the diagnostic potential of ADA for patients with suspected pleural&#44; peritoneal o meningeal tuberculosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">5&#8211;7</span></a> The most commonly used cut-off values for ADA were &#8805;40<span class="elsevierStyleHsp" style=""></span>IU&#47;L for pleural and peritoneal tuberculosis&#44; and &#8805;10<span class="elsevierStyleHsp" style=""></span>IU&#47;L for meningeal tuberculosis&#46; However&#44; the clinical performance of measuring the activity of ADA in the synovial fluid has received less attention&#46; Considering the small number of studies analyzing the current role of ADA as a diagnostic tool for synovial tuberculosis&#44; we conducted a systematic review of the literature and a meta-analysis to determine the usefulness of ADA levels in diagnosing tuberculous arthritis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">The present meta-analysis was performed according to the guidelines of the preferred reporting items for systematic reviews and meta-analysis &#40;PRISMA&#41; &#40;Supplementary file&#41; statement and with methods recommended by the Cochrane Diagnostic Test Accuracy Working Group&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">8&#44;9</span></a> The protocol for this meta-analysis is registered with PROSPERO &#40;number CRD42021284472&#41;&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Data sources and search strategy</span><p id="par0015" class="elsevierStylePara elsevierViewall">We performed a systematic literature search using electronic datasets &#40;i&#46;e&#46;&#44; PubMed&#44; Embase&#44; Cochrane Central&#44; Web of Science&#44; and MedRxiv databases&#41; for adenosine deaminase as a tool for diagnosing synovial tuberculosis&#46; We also screened for references from original articles&#44; previous systematic reviews&#44; and conference abstracts from the American College of Rheumatology and the European League Against Rheumatism to identify eligible trials until October 2021&#46; The search strategy used was Adenosine Deaminase AND Tuberculosis AND Synovial fluid&#46; No language restriction&#46; Publication period&#58; January 1986 to October 2021&#46; References cited in the included articles and reviews were further explored for possible candidate studies&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion criterials</span><p id="par0020" class="elsevierStylePara elsevierViewall">We included full-text original studies that assessed the diagnostic accuracy of adenosine deaminase activity for synovial tuberculosis&#46; Reference standards were well-defined and appropriate to the studies&#46; The articles directly provided true positive&#44; false positive&#44; false negative&#44; and true negative values for the assay or included the data necessary to calculate these measures&#46; We excluded case reports&#44; articles written in languages other than English and Spanish&#44; and studies with &#60;10 samples&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Reference standard</span><p id="par0025" class="elsevierStylePara elsevierViewall">The reference standard was a composite of clinical symptoms&#44; radiographic features&#44; biochemical test results&#44; smears&#44; culture&#44; histopathology&#44; and response to antituberculosis drugs or a mycobacterial culture as it was defined in the original paper&#46; Some or all of the factors with positive results were considered positive tuberculous arthritis&#46; Cases were considered non-tuberculosis if all the results were negative&#46; We used the composite reference standard as defined in the original paper&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Literature screening and selection</span><p id="par0030" class="elsevierStylePara elsevierViewall">Two investigators &#40;JCC-Q&#44; JAB&#41; independently assessed the candidate articles by reviewing their titles and abstracts&#44; followed by the full text&#44; for inclusion&#46; Discrepancies between the two investigators were resolved by discussion with a third investigator &#40;JR&#44; JE&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Data extraction</span><p id="par0035" class="elsevierStylePara elsevierViewall">We extracted data including author name&#59; year&#59; country&#59; patient selection method&#44; adenosine deaminase assay&#44; true positive&#44; false positive&#44; false negative&#44; and true negative values&#46; The same two investigators independently extracted the necessary information from each of the included articles&#59; we crosschecked the information they obtained&#46; Discrepancies in the two data sets were settled by a discussion with a third investigator&#44; similar to that used during the literature selection phase&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Assessment of study quality</span><p id="par0040" class="elsevierStylePara elsevierViewall">Two investigators independently used a revised tool for Quality Assessment of Diagnostic Accuracy Studies &#40;QUADAS-2&#41; to assess study quality separately&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a> We chose not to formally assess publication bias&#44; as the available methods such as funnel plots are not considered valid for diagnostic accuracy reviews&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Data synthesis and statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">We first obtained the values corresponding to True Positive&#44; False Positive&#44; False Negative&#44; and True Negative in each included study&#46; We calculated the estimated pooled sensitivity and specificity of adenosine deaminase activity in synovial fluid associated with the 95&#37; confidence interval &#40;CI&#41;&#44; against the composite reference standard or culture&#44; using bivariate random effects models&#46; Forest plots for sensitivity and specificity were generated for each study&#46; The areas under the summary receiver operating characteristic &#40;SROC&#41; curves &#40;AUC&#41; were subsequently calculated&#46; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> statistics were used to assess heterogeneity across the studies&#46; While 0&#37; indicated no observed heterogeneity&#44; values greater than 50&#37; were considered to imply substantial heterogeneity&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">11</span></a> We explored different patient selection methods&#44; assay methods&#44; and quality of study as potential sources of heterogeneity&#44; using subgroup and metaregression analyses&#46; MetaDisc 1&#46;4 &#40;HRC&#44; Madrid&#44; Spain&#41; generated forest plots of sensitivity and specificity with 95&#37; CI for each study and carried out meta-analyses and meta-regression analyses&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">12</span></a></p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Identification of studies and study characteristics</span><p id="par0050" class="elsevierStylePara elsevierViewall">Through our search strategy&#44; we identified candidate articles from relevant databases&#44; and seven articles with a total of 305 patients met the inclusion criteria &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">13&#8211;19</span></a> Four studies were conducted in India&#44; and one study each was conducted in Korea&#44; Thailand&#44; and Spain &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The assay to measure the activity of ADA was carried out using the Galanti&#8211;Giusti method in five studies&#46; There were three prospective studies&#44; three retrospective studies&#44; and one ambispective study&#46; Six articles were written in English and one in Spanish&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Study quality</span><p id="par0055" class="elsevierStylePara elsevierViewall">The methodological quality of the included studies&#44; using the QUADAS2 tools is summarized in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; The risk of bias was below 50&#37; and it was mainly due to patient selection and the reference standard&#59; flow and timing from the index test were judged with low risk of bias&#46; Overall&#44; the applicability concern was low&#46; Based on the risk of bias&#44; prospective studies were classified as high-quality and retrospective&#8211;ambispective as low quality&#46; Adenosine deaminase activity in tuberculous arthritis&#46; The activity of ADA in synovial fluid was measured using the colorimetric method of Galanti&#8211;Giusti in 5 studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">13&#44;19</span></a> one study used an enzymatic spectrophotometric method&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">17</span></a> and one study used a commercial assay &#40;ADA-N kit&#59; Denka Seiken Co Ltd&#44; Japan&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">18</span></a> The values of ADA activity in patients with tuberculous joint infection varied across studies even in those publications using the same methodology&#46; The cut-off values of ADA for diagnosing tuberculosis ranged from 15 to 60<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#44; being the median value between 40 and 50<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#46; Compared with other etiologies&#44; patients with tuberculous joint infection had greater values of adenosine deaminase activity in every study&#44; but there was some overlap in cases with septic arthritis &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Diagnostic accuracy of adenosine deaminase for tuberculous arthritis</span><p id="par0060" class="elsevierStylePara elsevierViewall">The sensitivity of adenosine deaminase in synovial fluid ranged from 86&#37; &#40;95&#37; CI&#44; 64&#8211;97&#41; to 100&#37; &#40;95&#37; CI&#44; 86&#8211;100&#41;&#46; The pooled sensitivity was 94&#37; &#40;95&#37; CI&#44; 89&#8211;98&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#46;2&#37;&#41; and the specificity ranged from 67&#37; &#40;95&#37; CI&#44; 30&#8211;93&#41; to 100&#37; &#40;95&#37; CI&#44; 93&#8211;100&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>a&#41;&#46; The pooled specificity of adenosine deaminase was 88&#37; &#40;95&#37; CI&#44; 83&#8211;92&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>83&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>b&#41;&#46; There was substantial heterogeneity of specificity but not of sensitivity&#46; The AUC of the SROC was 0&#46;96 &#40;95&#37; CI&#44; 0&#46;92&#8211;0&#46;99&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; We explored the heterogeneity among studies using subgroup and meta-regression analyses on predefined subgroups of quality of the study &#40;High<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1 vs Low<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;&#44; type of assay &#40;Galanti&#8211;Giusti<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1 vs&#46; another type of assay<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;&#44; and country of study &#40;India<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1 vs&#46; another country<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;&#46; We did not find heterogeneity among the studies according to the predefined subgroups&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Our meta-analysis included 7 studies &#40;305 patients&#41; quantifying adenosine deaminase in synovial fluid with comparisons to the clinical reference standard for the diagnosis of tuberculous arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">13&#8211;19</span></a> The Galanti&#8211;Giusti method&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">20</span></a> was used to assess adenosine deaminase activity in most studies&#46; However&#44; the cut-off point of adenosine deaminase activity for the diagnosis of tuberculosis varied across the publications&#44; being 40&#8211;50<span class="elsevierStyleHsp" style=""></span>IU&#47;L the median value&#46; The pooled sensitivity and specificity were 94&#37; &#40;95&#37; CI&#44; 89&#8211;98&#41; and 88&#37; &#40;95&#37; CI&#44; 82&#8211;92&#41;&#44; respectively&#46; The meta-analysis showed homogeneity for pooled sensitivity but significant heterogeneity for the specificity of the test&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Regarding specificity&#44; the activity of adenosine deaminase in synovial fluids is also elevated in other conditions besides tuberculosis&#46; We found a decreasing gradient in adenosine deaminase activity from arthritis caused by tuberculosis and bacterial infections through rheumatoid arthritis&#44; crystal arthritis&#44; and finally osteoarthritis&#46; We found in some cases of overlap of adenosine deaminase activity between tuberculosis and septic arthritis<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">13&#44;19</span></a>&#59; therefore it is necessary to routinely include biochemical analysis and culture as part of the diagnostic procedures&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We analyzed the possible sources of heterogeneity in the analysis of the specificity of the adenosine deaminase test&#46; Some of the studies were prospectively conducted and others were retrospective&#44; which could have an impact on the selection of patients&#46; Also&#44; the reference standard could have varied among the articles included&#46; Most studies used a composite of clinical&#44; histological&#44; microbiological&#44; and response to therapy criteria&#44; but the proportion of cases with a confirmed infection by microbiological methods was unknown&#46; Publication bias was not assessed since at present there is no recognized and accepted statistical method for quantifying the potential publication bias in diagnostic studies&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">21</span></a> The direction of the study&#44; variations in the components of the clinical reference standard&#44; and publication bias could explain some sources of heterogeneity&#46; To assess the origin of heterogeneity we carried out subgroup and meta-regression analyses focused on the quality of the study&#44; country&#44; and type of assay&#46; After carrying out metaregression analysis according to the aforementioned subgroups we could not identify the source of heterogeneity&#46; The availability of data in the publications did not permit the analysis of other potential sources of heterogeneity&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">There are no direct comparisons between the diagnostic performances of adenosine deaminase and Xpert MTB&#47;RIF in synovial fluid for the diagnosis of tuberculosis joint infection&#46; In the meta-analysis carried out by Shen et al&#46;&#44; the pooled sensitivity and specificity of Xpert MTB&#47;RIF were 81&#37; and 99&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">22</span></a> In our study adenosine deaminase showed slightly better sensitivity of 94&#37; with some poorer specificity of 88&#37;&#46; Compared with Xpert MTB&#47;RIF&#44; adenosine deaminase assessment has the disadvantage of not providing information on the susceptibility of Mycobacterium tuberculosis to rifampin in case of a positive result&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Besides Xpert MTB&#47;RIF&#44; other nucleic acid amplification techniques are targeting the mpb64 and IS6110 genes&#46; Combining the results of IS6110 RT PCR and mpb64 RT PCR improved the overall sensitivity and hence mpb64 can be used as an additional target for diagnosis of extrapulmonary tuberculosis&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">23</span></a> However&#44; due to the simplicity and availability of adenosine deaminase assays they can be used as complementary information to nucleic acid amplification techniques&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In summary&#44; measuring the activity of adenosine deaminase in synovial fluid is easy&#44; cheap&#44; and available in areas with poor resources&#46; Adenosine deaminase activity values above the cut-off point add significant diagnostic information to start empirical treatment against tuberculosis while waiting for synovial fluid Lowenstein culture results&#46; Adenosine deaminase activity in synovial fluid can be used as an additional tool for the diagnosis of tuberculosis joint infection in cases of negative results from nucleic acid amplification methods&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Authors&#8217; contributions</span><p id="par0095" class="elsevierStylePara elsevierViewall">This manuscript is co-authored by JCCQ&#44; JB&#44; JR&#44; and JE &#40;conception and design&#44; analysis and interpretation of data&#44; and writing of manuscript&#41;&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Ethics approval and consent to participate</span><p id="par0100" class="elsevierStylePara elsevierViewall">Ethics approval consent was waived&#46; All the data presented in this review is from previously published studies&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">This study was presented as a POSTER&#47;Abstract at the Annual European Congress of Rheumatology EULAR 2022&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study was not funded&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">They authors declare that they have no conflict of interest&#46;</p></span></span>"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1787815"
          "palabras" => array:4 [
            0 => "Tuberculosis"
            1 => "Adenosina desaminasa"
            2 => "L&#237;quido sinovial"
            3 => "Sensibilidad y especificidad"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Adenosine deaminase &#40;ADA&#41; activity has shown good performance in diagnosing pleural&#44; peritoneal&#44; and meningeal tuberculosis&#46; This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We searched published information in MEDLINE&#44; Embase&#44; Cochrane Library&#44; Web of Science&#44; and MedRxiv databases&#44; as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts &#40;2012&#8211;2021&#41;&#46; We also scanned the reference lists of articles&#46; Two reviewers independently applied the criteria for selection&#44; assessed quality&#44; and extracted data &#40;PROSPERO number CRD42021284472&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Seven independent studies &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>305 subjects&#41; that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included&#46; Overall&#44; the risk of bias was judged low&#46; Studies were classified as high quality &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#59; 148 subjects&#41; and low quality &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#59; 157 subjects&#41;&#46; Pooled sensitivity and specificity of ADA activity was 94&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#44; 0&#46;89&#8211;98&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#37;&#41; and 88&#37; &#40;95&#37; CI&#44; 83&#8211;92&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>83&#37;&#41;&#44; respectively&#46; The random-effects model for pooled diagnostic Odds ratio was 67&#46;1 &#40;95&#37;CI&#44; 20&#46;3&#8211;222&#46;2&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#37;&#41;&#46; The receiver operating characteristic curve area was 0&#46;96 &#40;95&#37; CI&#44; 0&#46;92&#8211;0&#46;99&#41;&#46; Meta-regression did not identify the quality of the study&#44; country of publication&#44; or the type of assay as a source of heterogeneity&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La actividad de la adenosina desaminasa &#40;ADA&#41; ha mostrado un buen desempe&#241;o en el diagn&#243;stico de la tuberculosis pleural&#44; peritoneal y men&#237;ngea&#46; Este metaan&#225;lisis tuvo como objetivo evaluar el rendimiento de la medici&#243;n de la actividad de la ADA en el l&#237;quido sinovial para el diagn&#243;stico precoz de la tuberculosis articular&#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 realizaron b&#250;squedas de res&#250;menes de congresos en la informaci&#243;n publicada en las bases de datos MEDLINE&#44; Embase&#44; Cochrane Library&#44; Web of Science y MedRxiv&#44; as&#237; como en informaci&#243;n no publicada en el <span class="elsevierStyleItalic">American College of Rheumatology</span> y la <span class="elsevierStyleItalic">European League Against Rheumatism</span> &#40;2012-2021&#41;&#46; Tambi&#233;n se escanearon las listas de referencias de los art&#237;culos&#46; Dos revisores aplicaron de forma independiente los criterios de selecci&#243;n&#44; evaluaron la calidad y extrajeron los datos &#40;n&#250;mero PROSPERO CRD42021284472&#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 siete estudios independientes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>305 sujetos&#41; que compararon la actividad de la ADA en el l&#237;quido sinovial con un m&#233;todo diagn&#243;stico compuesto de referencia para la tuberculosis&#46; En general&#44; el riesgo de sesgo se consider&#243; bajo&#46; Los estudios se clasificaron como de alta calidad &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#59; 148 sujetos&#41; y de baja calidad &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#59; 157 sujetos&#41;&#46; La sensibilidad y la especificidad agrupadas de la actividad de la ADA fueron del 94&#37; &#40;intervalo de confianza &#91;IC&#93; del 95&#37;&#58; 0&#44;89-98&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#37;&#41; y del 88&#37; &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 83-92&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>83&#37;&#41;&#44; respectivamente&#46; El modelo de efectos aleatorios para el odds ratio diagn&#243;stico agrupado fue de 67&#44;1 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 20&#44;3-222&#44;2&#59; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#37;&#41;&#46; El &#225;rea de la curva caracter&#237;stica de operaci&#243;n del receptor fue de 0&#44;96 &#40;IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 0&#44;92-0&#44;99&#41;&#46; La metarregresi&#243;n no identific&#243; la calidad del estudio&#44; el pa&#237;s de publicaci&#243;n o el tipo de ensayo como fuente de heterogeneidad&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La medici&#243;n de la actividad de ADA en el l&#237;quido sinovial demuestra un buen rendimiento para el diagn&#243;stico precoz de la tuberculosis articular&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Objetivos"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Process of selection of studies included in the meta-analysis&#46; Revised abstracts after exclusion of duplicates &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#46;</p>"
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        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Risk of bias and applicability concerns graph&#58; review authors&#8217; judgements about each domain presented as percentages across included studies&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Pooled sensitivity&#46; &#40;b&#41; Pooled specificity&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Area under the receiver operating characteristic of synovial ADA for tuberculous arthritis detection compared with a composite reference standard&#46;</p>"
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      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at1"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">ND&#58; not described&#46; TP&#58; true positive&#46; FP&#58; false positive&#46; FN&#58; false negative&#46; TN&#58; true negative&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author &#91;ref&#46;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#176; of subjects included&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#176; of subjects analyzed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ADA assay method&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ADA cut-off point&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TB cases &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Telenti<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1991&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Spain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Galanti&#8211;Giusti&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kumar<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1994&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Galanti&#8211;Giusti&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gupta<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Galanti&#8211;Giusti&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Foocharoen<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thailand&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Galanti&#8211;Giusti&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">31<span class="elsevierStyleHsp" style=""></span>U&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sharma<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Enzymatic method&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">South Korea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ADA N kit&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kawle<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ambispective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Galanti&#8211;Giusti&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">8 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  """
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        "tabla" => array:3 [
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            0 => array:2 [
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                0 => """
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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="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Studies included in meta-analysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tuberculosis arthritis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Septic arthritis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Crystal-induced arthritis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Post-traumatic arthritis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Miscellaneous arthritis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25 &#91;17&#8211;37&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21&#46;2 &#91;16&#8211;26&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Kumar<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gupta<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">88 &#91;46&#8211;156&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8 &#91;3&#8211;12&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Información del artículo

ISSN: 1699258X
Idioma original: Inglés

DOI:10.1016/j.reuma.2023.11.003

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