Jordan S.,University of Zürich |
Distler J.H.W.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Maurer B.,University of Zürich |
Huscher D.,Charite University Hospital |
And 40 more authors.
Annals of the Rheumatic Diseases | Year: 2015
Objectives: To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods: Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. Results: 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs-7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs-7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. Conclusions: The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.
Amedei A.,University of Florence |
Niccolai E.,University of Florence |
Benagiano M.,University of Florence |
Della Bella C.,University of Florence |
And 14 more authors.
Cancer Immunology, Immunotherapy | Year: 2013
Pancreatic cancer (PC) is an aggressive disease with dismal prognosis. Surgical resection is the recommended treatment for long-term survival, but patients with resectable PC are in the minority (with a 5-year survival rate of 20 %). Therefore, development of novel therapeutic strategies, such as anti-PC immunotherapy, is crucial. α-Enolase (ENO1) is an enzyme expressed on the surface of pancreatic cancer cells and is able to promote cell migration and cancer metastasis. The capacity of ENO1 to induce an immune response in PC patients renders it a true tumor-associated antigen. In this study, we characterized the effector functions of ENO1-specific T cells isolated from PC patients, and we specifically evaluated the successful role of intra-tumoral T helper 17 (Th17) cells and the inhibitory role of regulatory T (Tregs) cells in respectively promoting or reducing the cancer-specific immune response. In this ex vivo study, we have demonstrated, for the first time, that ENO1-specific Th17 cells have a specific anti-cancer effector function in PC patients, and that there are decreased levels of these cells in cancer compared to healthy mucosa. Conversely, there are elevated levels of ENO1-specific Tregs in PC patients which lead to inhibition of the antigen-specific effector T cells, thus highlighting a possible role in promoting PC progression. These results may be relevant for the design of novel immunotherapeutic strategies in pancreatic cancer. © 2013 Springer-Verlag Berlin Heidelberg.
Rubin L.J.,University of California at San Diego |
Simonneau G.,University of Colorado at Denver |
Badesch D.,Boston University |
Galie N.,University of Washington |
And 7 more authors.
European Respiratory Review | Year: 2012
A growing body of published evidence exists on the risk factors for disease progression in pulmonary arterial hypertension (PAH). The Scientific Steering Committee for the Study of Risk in PAH was established to bring together leading clinical and statistical experts in PAH and risk modelling, for the purpose of advancing the understanding of the risk of development and progression of PAH. Herein, we discuss the impact of this information on three key areas: 1) clinical decision-making; 2) policy and reimbursement; and 3) future trials and research. © ERS 2012.
De Giorgi V.,University of Florence |
Gori A.,University of Florence |
Grazzini M.,University of Florence |
Rossari S.,University of Florence |
And 7 more authors.
Oncology | Year: 2010
One of the most significant advances in melanoma staging is sentinel lymph node biopsy (SLNB). It is a surgical technique to detect occult nonpalpable micrometastases in regional lymph nodes. Recently, contrast-enhanced ultrasound (CEUS) was introduced as a noninvasive procedure, in spite of SLNB, for the detection of SLNs in patients with cutaneous melanoma. The main purpose of this study was to evaluate the diagnostic accuracy of CEUS in the diagnostic workup of patients with melanoma in comparison with the final histology of SLNs detected through preoperative lymphoscintigraphy. Fifteen patients with cutaneous melanoma underwent prompt excisional biopsy with narrow margins in order to avoid impairment of the melanoma lymphatic basin and were referred for SLNB according to routine indications between January and February 2009. In our study CEUS showed, albeit based on a small patient sample, a negative predictive value of 100%, that means that all negative results were confirmed by negative SLN histopathological examination; all ultrasonographically negative lymph nodes corresponded to nonmetastatic sentinel nodes. Copyright © 2011 S. Karger AG, Basel.