Low prevalence of renal, cardiac, pulmonary, and neurological extra-articular clinical manifestations in spondyloarthritis: analysis of the Brazilian Registry of Spondyloarthritis

OBJECTIVE: To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients. MATERIALS AND METHODS: This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis). RESULTS: Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form. CONCLUSION: Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA.OBJETIVO: Descrever as manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas) geralmente não relacionadas às espondiloartrites (EpA) em uma grande coorte de pacientes brasileiros. MÉTODOS: Este estudo retrospectivo analisou 1.472 pacientes com o diagnóstico de EpA atendidos em 29 centros distribuídos pelas cinco principais regiões geográficas do Brasil, integrantes do Registro Brasileiro de Espondiloartrites. Todos os pacientes foram avaliados para a prevalência das principais manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas), divididas por diagnóstico [espondilite anquilosante (EA), artrite psoriásica (AP), artrite reativa (ARe), artrite associada a doença inflamatória intestinal (DII), EpA indiferenciada (EI) e EpA juvenil] e por forma clínica (axial, periférica, mista e entesítica). RESULTADOS: Dentre os pacientes avaliados com EpA, 963 apresentavam EA, 271 AP, 49 ARe, 48 artrite associada a DII, 98 EI e 43 EpA juvenil. Acometimento cardíaco foi observado em 44 pacientes (3,0%), seguido por acometimento pulmonar em 19 (1,3%), renal em 17 (1,2%) e neurológico em 13 pacientes (0,9%). A maioria dos casos de acometimento visceral ocorreu nos pacientes com EA ou AP e naqueles com forma clínica mista (axial e periférica) e/ou predominantemente axial. CONCLUSÃO: As manifestações extra-articulares cardíacas, renais, pulmonares e neurológicas são muito pouco frequentes nas EpA, variando de 0,9%-3% nesta grande coorte brasileira, estando mais associadas a EA e AP.37938

Quality of life in spondyloarthritis : analysis of a large Brazilian cohort

Objetivo: analisar as variáveis demográficas e clínicas associadas à diminuição da qualidade de vida em uma grande coorte brasileira de pacientes com espondiloartrite (EpA). Métodos: Foi aplicado um protocolo de pesquisa único a 1.465 pacientes brasileiros classificados como tendo EpA de acordo com os critérios do European Spondyloarthropaties Study Group (ESSG), atendidos em 29 centros de referência em reumatologia do Brasil. Foram registradas as variáveis clínicas e demográficas. A qualidade de vida foi analisada por meio do questionário Ankylosing Spondylitis Quality of Life (ASQoL). Resultados: A pontuação média do ASQoL foi de 7,74 (+ 5,39). Ao analisar doenças específicas no grupo de EpA, as pontuações do ASQoL não apresentaram diferença estatisticamente significativa. Os dados demográficos mostraram piores escores de ASQoL associados ao gênero feminino (p = 0,014) e etnia negra (p < 0,001). Quanto aos sintomas clínicos, a dor na região glútea (p = 0,032), a dor cervical (p < 0,001) e a dor no quadril (p = 0,001), estiveram estatisticamente associadas a piores escores no ASQoL. O uso contínuo de fármacos anti-inflamatórios não esteroides (p < 0,001) e agentes biológicos (p = 0,044) esteve associado a escores mais elevados de ASQoL, enquanto outros medicamentos não interferiram nos escores do ASQoL. Conclusão: Nesta grande série de pacientes com EpA, o sexo feminino e a etnia negra, bem como sintomas predominantemente axiais, estiveram associados a uma qualidade de vida reduzida.Objective: to analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (± 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African-Brazilian ethnicity (p < 0.001). Regarding clinical symptoms, buttock pain (p = 0.032), cervical pain (p < 0.001) and hip pain (p = 0.001), were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biologic agents (p = 0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores. Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021

Since the second version of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations were published in 2015, therapeutic options for psoriatic arthritis (PsA) have advanced considerably. This work reviews the literature since the previous recommendations (data published 2013–2020, including conference presentations between 2017 and 2020) and reports high-quality, evidence-based, domain-focused recommendations for medication selection in PsA developed by GRAPPA clinicians and patient research partners. The overarching principles for the management of adults with PsA were updated by consensus. Principles considering biosimilars and tapering of therapy were added, and the research agenda was revised. Literature searches covered treatments for the key domains of PsA: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis; additional searches were performed for PsA-related conditions (uveitis and inflammatory bowel disease) and comorbidities. Individual subcommittees used a GRADE-informed approach, taking into account the quality of evidence for therapies, to generate recommendations for each of these domains, which were incorporated into an overall schema. Choice of therapy for an individual should ideally address all disease domains active in that patient, supporting shared decision-making. As safety issues often affect potential therapeutic choices, additional consideration was given to relevant comorbidities. These GRAPPA treatment recommendations provide up-to-date, evidence-based guidance on PsA management for clinicians and people with PsA

Profile Of The Use Of Disease Modifying Drugs In The Brazilian Registry Of Spondyloarthritides [perfil Do Uso De Drogas Modificadoras De Doença No Registro Brasileiro De Espondiloartrites]

Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). Results: At least one DMD was used by 73.6 % of patients: MTX by 29.2 % and SSZ by 21.7%, while 22.7 % used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX, p = 0.014), inflammatory back pain (SSZ, p = 0.002), buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement. © 2014 Elsevier Editora Ltda.5413337Sieper, J., Rudwaleit, M., Baraliakos, X., Brandt, J., Braun, J., Burgos-Vargas, R., The Assessment of SpondyloArthritis international Society (ASAS) handbook: A guide to assess spondyloarthritis (2009) Ann Rheum Dis, 68 (SUPPL. II), pp. ii1-ii44Rudwaleit, M., van der Heijde, D., Landewé, R., Listing, J., Brandt, J., Braun, J., The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection (2009) Ann Rheum Dis, 68, pp. 770-776Rudwaleit, M., van der Heijde, D., Landewé, R., Akkoc, N., Brandt, J., Chou, C.T., The development of Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis (2011) Ann Rheum Dis, 70, pp. 25-31Sampaio-Barros, P.D., Gonçalves, C.R., Braga da Silva, J.A., Ximenes, A.C., Azevedo, V.C., Bianchi, W.A., Registro Iberoamericano de Espondiloartritis (RESPONDIA): Brasil (2008) Reumatol. Clin., 4 (SUPPL. 4), pp. 30-35Benegas, M., Muñoz-Gomariz, E., Font, P., Burgos-Vargas, R., Chaves, J., Palleiro, D., Comparison of the clinical expression of patients with ankylosing spondylitis from Europe and Latin America (2012) J Rheumatol, 39, pp. 2315-2320Braun, J., van den Berg, R., Baraliakos, X., Boehm, H., Burgos-Vargas, R., Collantes-Estevez, E., 2010 Update of the ASAS/EULAR recommendations for the management of ankylosing spondyltis (2011) Ann Rheum Dis, 70, pp. 896-904Sampaio-Barros, P.D., Pinheiro, M.M., Ximenes, A.C., Meirelles, E.S., Keiserman, M., Azevedo, V.F., Recomendações sobre o tratamento da espondilite anquilosante (2013) Rev Bras Reumatol, 53, pp. 242-257Gossec, L., Smolen, J.S., Gaujoux-Viala, C., Ash, Z., Marzo-Ortega, H., van der Heijde, D., European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies (2012) Ann Rheum Dis, 71, pp. 4-12Carneiro, S., Azevedo, V.F., Bonfiglioli, R., Ranza, R., Gonçalves, C.R., Keiserman, C.R., Recomendações sobre o tratamento da artrite psoriásica (2013) Rev Bras Reumatol, 53, pp. 227-241Dougados, M., van der Linden, S., Julin, R., Huitfeld, B., Amor, B., Calin, A., The European Spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy (1991) Arthritis Rheum, 34, pp. 1218-1227van der Linden, S., Valkenburg, H.A., Cats, A., Evaluation of diagnostic criteria for ankylosing spondylitis (1984) A proposal for modification of the New York criteria. Arthritis Rheum, 27, pp. 361-368Moll, J.M.H., Wright, V., Psoriatic arthritis (1973) Semin Arthritis Rheum, 3, pp. 55-78Kingsley, G., Sieper, J., Third International Workshop on Reactive Arthritis, 23-26 September 1995, Berlin, Germany (1996) Ann Rheum Dis, 55, pp. 564-584Bodur, H., Ataman, S., Akbulut, L., Evcik, D., Kavuncu, V., Kaya, T., Characteristics and medical management of patients with rheumatoid arthritis and ankylosing spondylitis (2008) Clin Rheumatol, 27, pp. 1119-1125Altan, L., Bingöl, U., Karakoç, Y., Aydiner, S., Yurtkuran, M., Yurtkuran, M., Clinical investigation of methotrexate in the treatment of ankylosing spondylitis (2001) Scand J Rheumatol, 30, pp. 255-259Marshall, R.W., Kirwan, J.R., Methotrexate in the treatment of ankylosing spondylitis (2001) Scand J Rheumatol, 30, pp. 313-314Roychowdhury, B., Bintley-Bagot, S., Bulgen, D.Y., Thompson, R.N., Tunn, E.J., Moots, R.J., Is methotrexate effective in ankylosing spondylitis? (2002) Rheumatology (Oxford), 41, pp. 1330-1332Sampaio-Barros, P.D., Costallat, L.T., Bertolo, M.B., Marques-Neto, J.F., Samara, A.M., Methotrexate in the treatment of ankylosing spondylitis (2000) Scand J Rheumatol, 29, pp. 160-162Gonzalez-Lopez, L., Garcia-Gonzalez, A., Vazquez-Del-Mercado, M., Muñoz-Valle, J.F., Gomez-Nava, J.I., Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial (2004) J Rheumatol, 31, pp. 1568-1574Haibel, H., Brandt, H.C., Song, I.H., Brandt, A., Listing, J., Rudwaleit, M., Sieper, J., No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial (2007) Ann Rheum Dis., 66, pp. 419-421Abu-Shakra, M., Gladman, D.D., Thorne, J.C., Long, J., Gough, J., Farewell, V.T., Long-term methotrexate therapy in psoriatic arthritis: clinical and radiological outcome (1995) J Rheumatol, 22, pp. 241-245Scarpa, R., Peluso, R., Atteno, M., Manguso, F., Spanò, A., Iervolino, S., The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: Results of a pilot randomised 6-month trial with methotrexate (2008) Clin Rheumatol, 27, pp. 823-826Lie, E., van der Heijde, D., Uhlig, T., Heiberg, M.S., Koldingsnes, W., Rødevand, E., Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis (2010) Ann Rheum Dis, 69, pp. 671-676Chandran, V., Raychaudhuri, S.P., Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis (2010) J Autoimm, 34, pp. 314-321Skare, T.L., Bortoluzzo, A.B., Gonçalves, C.R., Braga da Silva, J.A., Ximenes, A.C., Bértolo, M.B., Ethnic influence in clinical and functional measures of Brazilian patients with spondyloarthritis (2012) J. Rheumatol, 39, pp. 141-147Clegg, D.O., Reda, D.J., Weisman, M.H., Blackburn, W.D., Cush, J.J., Cannon, G.W., Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis (1996) A Department of Veterans Affairs Cooperative Study. Arthritis Rheum, 39, pp. 2004-2012Chen, J., Liu, C., Is sulfasalazine effective in ankylosing spondylitis? (2006) A systematic review of randomized controlled trials. J Rheumatol, 33, pp. 722-731Gupta, A.K., Grober, J.S., Hamilton, T.A., Ellis, C.N., Siegel, M.T., Voorhees, J.J., Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial (1995) J Rheumatol, 22, pp. 894-898Combe, B., Goupille, P., Kuntz, J.L., Tebib, J., Lioté, F., Bregeon, C., Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study (1996) Br J Rheumatol, 35, pp. 664-668Clegg, D.O., Reda, D.J., Mejias, E., Cannon, G.W., Weisman, M.H., Taylor, T., Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis (1996) A Department of Veterans Affairs Cooperative Study. Arthritis Rheum, 39, pp. 2004-2012Clegg, D.O., Reda, D.J., Weisman, M.H., Cush, J.J., Vasey, F.B., Schumacher Jr., H.R., Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome) (1996) A Department of Veterans Affairs Cooperative Study. Arthritis Rheum, 39, pp. 2021-2027Consensus guidelines for the management of inflammatory bowel disease (2010) Arq Gastroenterol, 47, pp. 313-325. , Brazilian Study Group of Inflammatory Bowel DiseasesD'Haens, G.R., Panaccione, R., Higgins, P.D., Vermeire, S., Gassull, M., Chowers, Y., The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: When to start, when to stop, which drug to choose, and how to predict response? (2011) Am J Gastroenterol, 106, pp. 199-212Carneiro, S., Bortoluzzo, A.B., Gonçalves, C.R., Braga da Silva, J.A., Ximenes, A.C., Bértolo, M.B., Impact of enthesitis in 1505 Brazilian patients with spondyloarthritis (2013) J Rheumatol, 40, pp. 1719-172

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021

Since the second version of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations were published in 2015, therapeutic options for psoriatic arthritis (PsA) have advanced considerably. This work reviews the literature since the previous recommendations (data published 2013–2020, including conference presentations between 2017 and 2020) and reports high-quality, evidence-based, domain-focused recommendations for medication selection in PsA developed by GRAPPA clinicians and patient research partners. The overarching principles for the management of adults with PsA were updated by consensus. Principles considering biosimilars and tapering of therapy were added, and the research agenda was revised. Literature searches covered treatments for the key domains of PsA: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis; additional searches were performed for PsA-related conditions (uveitis and inflammatory bowel disease) and comorbidities. Individual subcommittees used a GRADE-informed approach, taking into account the quality of evidence for therapies, to generate recommendations for each of these domains, which were incorporated into an overall schema. Choice of therapy for an individual should ideally address all disease domains active in that patient, supporting shared decision-making. As safety issues often affect potential therapeutic choices, additional consideration was given to relevant comorbidities. These GRAPPA treatment recommendations provide up-to-date, evidence-based guidance on PsA management for clinicians and people with PsA

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021.

Since the second version of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations were published in 2015, therapeutic options for psoriatic arthritis (PsA) have advanced considerably. This work reviews the literature since the previous recommendations (data published 2013-2020, including conference presentations between 2017 and 2020) and reports high-quality, evidence-based, domain-focused recommendations for medication selection in PsA developed by GRAPPA clinicians and patient research partners. The overarching principles for the management of adults with PsA were updated by consensus. Principles considering biosimilars and tapering of therapy were added, and the research agenda was revised. Literature searches covered treatments for the key domains of PsA: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis; additional searches were performed for PsA-related conditions (uveitis and inflammatory bowel disease) and comorbidities. Individual subcommittees used a GRADE-informed approach, taking into account the quality of evidence for therapies, to generate recommendations for each of these domains, which were incorporated into an overall schema. Choice of therapy for an individual should ideally address all disease domains active in that patient, supporting shared decision-making. As safety issues often affect potential therapeutic choices, additional consideration was given to relevant comorbidities. These GRAPPA treatment recommendations provide up-to-date, evidence-based guidance on PsA management for clinicians and people with PsA

Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients

Objectives To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. Methods A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 +/- 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 15.1 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). Results Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low hack pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. Conclusion There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset <= 40 years and another favouring the peripheral manifestations in those with later disease onset.303351357Wyeth/Pfizer BrazilFederico Foundation, Switzerlan

Effect of Enthesitis on 1505 Brazilian Patients with Spondyloarthritis

Objective. To analyze the clinical effect of enthesitis in a large Brazilian cohort of patients with spondyloarthritis (SpA).Methods. A common protocol of investigation was prospectively applied to 1505 patients with SpA in 29 centers in Brazil. Clinical and demographic variables and disease indexes were investigated. the Maastricht Ankylosing Spondylitis Enthesitis Score was used to investigate the enthesitis component. Ankylosing spondylitis was the most frequent disease in the group (65.4%). Others were psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), and enteropathic arthritis (3.2%).Results. At least 1 affected enthesis was observed in 54% of the patients with SpA, with a mean of 2.12 +/- 2.98 entheses affected. According to the clinical presentation, enthesitis was significantly more frequent in patients with axial + peripheral joint involvement compared to isolated axial or peripheral involvement (p < 0.001). There was a statistical association between the presence of enthesites and axial symptoms (buttock pain, cervical pain, and hip pain), and peripheral symptoms (lower limb arthritis, number of painful and swollen joints; p < 0.05). Patients with enthesitis also presented higher mean scores of Bath Ankylosing Spondylitis Functional Index (BASFI; p < 0.001), Bath Ankylosing Spondylitis Disease Activity Index (p < 0.001), and Ankylosing Spondylitis Quality of Life (ASQoL; p < 0.001). Multivariate logistic regression showed that BASFI (p < 0.0001; OR 74.839), ASQoL (p = 0.0001; OR 14.645), and Achilles tendonitis (p = 0.0059; OR 7.593) were associated with work incapacity.Conclusion. the clinical presence of enthesitis in this large cohort of patients with SpA was frequent and was associated with a significant increase in disease activity and decline in functional capacity and quality of life.Wyeth/Pfizer BrazilFederico FoundationUniv Fed Rio de Janeiro, BR-21941 Rio de Janeiro, BrazilUniv Estado Rio de Janeiro, Rio de Janeiro, BrazilUniv São Paulo, Div Rheumatol, BR-05508 São Paulo, BrazilUniv Brasilia, BR-70910900 Brasilia, DF, BrazilHosp Geral Goiania, Goiania, Go, BrazilUniv Estadual Campinas, Campinas, BrazilUniv Fed Amazonas, Porto Alegre, RS, BrazilPontificia Univ Catolica, Porto Alegre, RS, BrazilFac Med Sao Jose Rio Preto, Sao Jose Dos Campos, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilHosp Geral Fortaleza, Fortaleza, Ceara, BrazilSanta Casa Rio de Janeiro, Rio de Janeiro, BrazilSanta Casa São Paulo, São Paulo, BrazilUniv Fed Pernambuco, Recife, PE, BrazilUniv Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, BrazilUniv São Paulo, Inst Ortoped & Traumatol, BR-05508 São Paulo, BrazilUniv Fed Santa Catarina, BR-88040900 Florianopolis, SC, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilSanta Casa Belo Horizonte, Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilFed Univ Para, BR-66059 Belem, Para, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc