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.

AIMTo establish a model to enrich and characterize stem-like cells from murine normal liver and hepatocellular carcinoma (HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition (EMT).METHODSIn this study, we utilized a stem cell conditioned serum-free medium to enrich stem-like cells from mouse HCC and normal liver cell lines, Hepa 1-6 and AML12, respectively. We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating the RNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR (qRT-PCR). Next, we examined the relationship between stem cells and EMT using qRT-PCR.RESULTSThree-dimensional spheres were enriched by culturing murine HCC and normal hepatocyte cell lines in stem cell conditioned serum-free medium supplemented with epidermal growth factor, basic fibroblast growth factor and heparin sulfate. The 3-dimensional spheres had enhanced stemness markers such as Klf4 and Bmi1 and hepatic cancer stem cell (CSC) marker Cd44 compared to parental cells grown as adherent cultures. We report that epithelial markers E-cadherin and ZO-1 were downregulated, while mesenchymal markers Vimentin and Fibronectin were upregulated in 3-dimensional spheres. The 3-dimensional spheres also exhibited changes in expression of Snai, Zeb and Twist family of EMT transcription factors.CONCLUSIONOur novel method successfully enriched stem-like cells which possessed an EMT phenotype. The isolation and characterization of murine hepatic CSCs could establish a precise target for the development of more effective therapies for HCC.

OBJETIVO: avaliar o programa de traçado cefalométrico Radiocef 2.0 quanto à confiabilidade e precisão, comparativamente ao método manual e ao programa Dentofacial Planner 7.02 (Gold Standard). METODOLOGIA: a amostra constou de 50 telerradiografias laterais de boa qualidade, de pacientes de ambos os gêneros, na faixa etária dos 11 aos 24 anos, pertencentes aos arquivos da disciplina de Ortodontia da Faculdade de Odontologia de Bauru, da Universidade de São Paulo. A partir das diferentes formas de medições executadas, 4 grupos experimentais foram obtidos: Grupo 1 (método manual); Grupo 2 (a partir da digitalização dos traçados no programa Radiocef 2.0); Grupo 3 (a partir da digitalização das radiografias no programa Radiocef 2.0); e Grupo 4 (a partir da digitalização dos pontos cefalométricos no programa Dentofacial Planner 7.02). Na composição do estudo, foram selecionadas medidas angulares e lineares. A comparação inter-grupos foi realizada por meio da análise de variância e do teste de Kruskal-Wallis. RESULTADOS E CONCLUSÕES: os programas mostraram-se comparáveis, sem diferenças estatisticamente significantes, ao nível de 5%, possibilitando as seguintes conclusões: 1) o programa de traçado cefalométrico computadorizado Radiocef 2.0 pode ser confiavelmente utilizado como recurso auxiliar no diagnóstico, plano de tratamento, acompanhamento e avaliação de tratamentos ortodônticos, nos âmbitos clínico e/ou de pesquisa; e 2) este programa também pode ser confiavelmente utilizado para efetuar medições a partir da digitalização dos traçados, além da forma proposta pelo fabricante.

OBJETIVO: avaliar a concordância entre a Análise Facial Subjetiva, proposta por Capelozza Filho, e a Análise Cefalométrica de Tecidos Moles, de Arnett e McLaughlin. MÉTODOS: fotografias de frente e de perfil e telerradiografias em norma lateral padronizadas de 50 indivíduos, com média de idade de 24 anos e 1 mês, foram utilizadas para essa avaliação. Verificou-se, também, nos indivíduos classificados como Padrão I, a correspondência dos valores médios e desvios-padrão das medidas obtidas com os valores normativos da Análise Cefalométrica de Tecidos Moles para os indivíduos com harmonia facial. RESULTADOS: constatou-se, em indivíduos do Padrão I, que os lábios sempre se encontram à frente da Linha Vertical Verdadeira e que, apesar de grandes variações do ponto pogônio, o equilíbrio facial ainda se mantinha. CONCLUSÃO: os resultados demonstraram que a Análise Facial Subjetiva é um método eficiente na classificação do padrão facial.