Abstract Background: In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods: This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan's skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results: Median (range) age was 35.9 (19–59), with 57 (81.4%) female and median (range) non-Raynaud's disease duration of 2 (1–7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions: Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.

Abstract Background The reproducibility and reliability of the modified Rodnan's Skin Score (mRSS) are debated due to investigator-related subjectivity. Here, we evaluate if durometry correlates with mRSS in patients with diffuse systemic sclerosis (SSc). Methods This cross-sectional study was conducted from December 2018 to June 2019, including 58 diffuse SSc patients. Two certified researchers, blind to each other's scores, performed the mRSS, followed by durometry at 17 predefined skin sites. For durometry and mRSS, individual scores per skin site were registered. Durometry and mRSS results measured by each researcher, as well as scores from different researchers, were compared. Skin thickness measurements from forearm skin biopsies were available in a subset of the patients, for comparisons. Statistical analyses included Cohen's Kappa Coefficient, Intraclass Correlation Coefficient, Kendall's Coefficient and Spearman's test. Results Mean (standard deviation, SD) patient age was 44.8 (12.9) years, and 88% were female. Inter-rater agreement varied from 0.88 to 0.99 (Intraclass correlation coefficient) for durometry, and 0.54 to 0.79 (Cohen's Kappa coefficient) for mRSS, according to the specific evaluated sites. When data were compared with skin thickness assessed in forearm biopsies, durometry correlated better with skin thickness than mRSS. Conclusion Durometry may be considered as an alternative method to quantify skin involvement in patients with diffuse SSc. The strong inter-rater agreement suggests that the method may be useful for the assessment of patients by multiple researchers, as in clinical trials.

RESUMO Objetivo: descrever o desenvolvimento de um objeto virtual de aprendizagem para disponibilização de informações sobre transplante autólogo de células-tronco hematopoéticas para doenças autoimunes. Métodos: estudo metodológico de desenvolvimento de um website, empregando o modelo de design instrucional que envolve Análise, Design, Desenvolvimento e Implementação. Resultados: o objeto virtual, disponível no endereço eletrônico http://www.transplantardai.com.br, foi desenvolvido em plataforma web, na linguagem de marcação Hypertext Markup Language, utilizando-se o software WebAcappella - Responsive Website Creator (Intuisphere, França 2016). O conteúdo foi estruturado nos seguintes módulos: História, Transplante, Doenças Autoimunes, Links, Orientações, Fala Equipe e Dúvidas. Os ícones e menus foram criados de modo a atrair o usuário, facilitando a busca de informações e permitindo máximo uso dos recursos disponíveis no website. Conclusão: a metodologia empregada permitiu o desenvolvimento do objeto virtual de aprendizagem, que poderá ser utilizado como ferramenta para orientar e disseminar o conhecimento sobre esse tratamento.

ABSTRACT Objective: describe the development of a virtual learning object to provide information about autologous transplantation of hematopoietic stem cells to autoimmune diseases. Methods: methodological study of a website development, using the instructional design model that includes Analysis, Design, Development and Implementation. Results: the virtual object, available at http://www.transplantardai.com.br, was developed in a web platform, in the Hypertext Markup Language, using the software WebAcappella - Responsive Website Creator (Intuisphere, France 2016). The content was structured in the modules: History, Transplant, Autoimmune Diseases, Links, Guidelines, Speech Team and Doubts. The icons and menus were created in order to attract the user, facilitating the search for information and allowing maximum use of the resources available on the website. Conclusion: the methodology used allowed the development of the virtual learning object, which can be used as a tool to guide and disseminate knowledge about this treatment.

RESUMEN Objetivo: describir el desarrollo de un objeto de aprendizaje virtual para proporcionar información sobre el trasplante autólogo de células madre hematopoyéticas en las enfermedades autoinmunes. Métodos: estudio metodológico del desarrollo del sitio web, utilizando el modelo de diseño instruccional (Análisis, Diseño, Desarrollo e Implementación). Resultados: el objeto virtual, disponible en http://www.transplantardai.com.br, fue desarrollado en una plataforma web, en el lenguaje de marcación Hypertext Markup Language, utilizando el software WebAcappella - Responsive Website Creator (Intuisphere, Francia 2016). El contenido se estructuró en los módulos: Historia, Trasplante, Enfermedades Autoinmunes, Links, Guías, Habla Equipo y Dudas. Los iconos y menús fueron creados para atraer al usuario, facilitando la búsqueda de información y permitiendo el máximo aprovechamiento de los recursos disponibles en el sitio web. Conclusión: la metodología utilizada permitió el desarrollo del objeto de aprendizaje virtual, que puede ser utilizado como una herramienta para guiar y difundir el conocimiento sobre este tratamiento.

ABSTRACT Objective: describe the development of a virtual learning object to provide information about autologous transplantation of hematopoietic stem cells to autoimmune diseases. Methods: methodological study of a website development, using the instructional design model that includes Analysis, Design, Development and Implementation. Results: the virtual object, available at http://www.transplantardai.com.br, was developed in a web platform, in the Hypertext Markup Language, using the software WebAcappella - Responsive Website Creator (Intuisphere, France 2016). The content was structured in the modules: History, Transplant, Autoimmune Diseases, Links, Guidelines, Speech Team and Doubts. The icons and menus were created in order to attract the user, facilitating the search for information and allowing maximum use of the resources available on the website. Conclusion: the methodology used allowed the development of the virtual learning object, which can be used as a tool to guide and disseminate knowledge about this treatment.

RESUMEN Objetivo: describir el desarrollo de un objeto de aprendizaje virtual para proporcionar información sobre el trasplante autólogo de células madre hematopoyéticas en las enfermedades autoinmunes. Métodos: estudio metodológico del desarrollo del sitio web, utilizando el modelo de diseño instruccional (Análisis, Diseño, Desarrollo e Implementación). Resultados: el objeto virtual, disponible en http://www.transplantardai.com.br, fue desarrollado en una plataforma web, en el lenguaje de marcación Hypertext Markup Language, utilizando el software WebAcappella - Responsive Website Creator (Intuisphere, Francia 2016). El contenido se estructuró en los módulos: Historia, Trasplante, Enfermedades Autoinmunes, Links, Guías, Habla Equipo y Dudas. Los iconos y menús fueron creados para atraer al usuario, facilitando la búsqueda de información y permitiendo el máximo aprovechamiento de los recursos disponibles en el sitio web. Conclusión: la metodología utilizada permitió el desarrollo del objeto de aprendizaje virtual, que puede ser utilizado como una herramienta para guiar y difundir el conocimiento sobre este tratamiento.

RESUMO Objetivo: descrever o desenvolvimento de um objeto virtual de aprendizagem para disponibilização de informações sobre transplante autólogo de células-tronco hematopoéticas para doenças autoimunes. Métodos: estudo metodológico de desenvolvimento de um website, empregando o modelo de design instrucional que envolve Análise, Design, Desenvolvimento e Implementação. Resultados: o objeto virtual, disponível no endereço eletrônico http://www.transplantardai.com.br, foi desenvolvido em plataforma web, na linguagem de marcação Hypertext Markup Language, utilizando-se o software WebAcappella - Responsive Website Creator (Intuisphere, França 2016). O conteúdo foi estruturado nos seguintes módulos: História, Transplante, Doenças Autoimunes, Links, Orientações, Fala Equipe e Dúvidas. Os ícones e menus foram criados de modo a atrair o usuário, facilitando a busca de informações e permitindo máximo uso dos recursos disponíveis no website. Conclusão: a metodologia empregada permitiu o desenvolvimento do objeto virtual de aprendizagem, que poderá ser utilizado como ferramenta para orientar e disseminar o conhecimento sobre esse tratamento.