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Bracarda S.,Azienda USL8 | Porta C.,University of Pavia | Boni C.,Azienda Ospedaliera di Reggio Emilia | Santoro A.,Instituto Clinico Humanitas | And 11 more authors.
European Urology | Year: 2013

Background: Sorafenib has proven efficacy in metastatic renal cell carcinoma (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both dose- and administration-schedule dependent. Objective: To compare two different schedules of IFN combined with sorafenib. Design, setting, and participants: Single-stage, prospective, noncomparative, randomized, open-label, multicenter, phase 2 study on previously untreated patients with mRCC and Eastern Cooperative Oncology Group performance status 0-2. Intervention: Sorafenib 400 mg twice daily plus subcutaneous IFN, 9 million units (MU) three times a week (Arm A) or 3 MU five times a week (Arm B). Outcome measurements and statistical analysis: Primary end points were progression-free survival (PFS) for each arm and safety. Data were evaluated according to an intent-to-treat analysis. Results and limitations: A total of 101 patients were evaluated. Median PFS was 7.9 mo in Arm A and 8.6 mo in Arm B (p = 0.049) and the median duration of response was 8.5 and 19.2 mo, respectively (p = 0.0013). Nine partial responses were observed in Arm A, and three complete and 14 partial responses were observed in Arm B (17.6% vs 34.0%; p = 0.058); 24 and 21 patients (47% and 42%), respectively, achieved stable disease. The most common grade 3-4 toxicities were fatigue plus asthenia (28% vs 16%; p = 0.32) and hand-foot skin reactions (20% vs 18%). Conclusions: Sorafenib plus frequent low-dose IFN showed good efficacy and tolerability. Further investigations should be warranted to identify a possible positioning of this intriguing regimen (6% complete response rate) in the treatment scenario of mRCC. © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Punzi L.,University of Padua | Matucci Cerinic M.,Azienda Ospedaliero Universitaria di Careggi | Cantini F.,Servizio di Reumatologia | Bagnato G.,Policlinico Universitario rtino | And 2 more authors.
Reumatismo | Year: 2011

Objective: This study aims to provide a description of real life treatment patterns of biologic anti-TNF in 23 Italian Rheumatology centers.Methods: This was an observational, multicenter, retrospective study. Patients above 18 years of age, diagnosed with rheumatoid arthritis and treated with the first biologic anti-TNF agent between the 1st July 2002 to the 31st March 2004 were included. Total follow-up was 36 months. Results: In total, 248 patients were first treated with inftiximab, 259 with etanercept and 196 with adalimumab. First course of therapy with inftiximab was associated with lower cumulative drug survival than the other two agents. At 36 months, 74.7% of patients on etanercept, 72.0% of those on dalimumab and 57.7% of subjects receiving inftiximab were still on therapy. In total, 149 patients switched to a second anti-TNF agent. At 24 months of the second line treatment, 75%, 22%, and 54% of inftiximab, etanercept and adalimumab recipients, respectively, had discontinued their second anti-TNF. Conclusions: Anti-TNF agents may be associated to a rather high incidence of discontinuation and dose adjustments over a 36-month period, with a possible effect on healthcare expense. In particular, inftiximab was associated with a higher incidence of discontinuations compared with etanercept and adalimumab.


Filippi M.,Vita-Salute San Raffaele University | Agosta F.,Vita-Salute San Raffaele University | Barkhof F.,VU University Amsterdam | Dubois B.,University Pierre and Marie Curie | And 11 more authors.
European Journal of Neurology | Year: 2012

Background and purpose: The European Federation of the Neurological Societies (EFNS) guidelines on the use of neuroimaging in the diagnosis and management of dementia are designed to revise and expand previous EFNS recommendations for the diagnosis and management of patients with Alzheimer's disease (AD) and to provide an overview of the evidence for the use of neuroimaging techniques in non-AD dementias, as well as general recommendations that apply to all types of dementia in clinical practice. Methods: The task force working group reviewed evidence from original research articles, meta-analyses and systematic reviews, published before April 2012. The evidence was classified, and consensus recommendations were given and graded according to the EFNS guidance regulations. Results: Structural imaging, which should be performed at least once in the diagnostic work-up of patients with cognitive impairment, serves to exclude other potentially treatable diseases, to recognize vascular lesions and to identify specific findings to help distinguish different forms of neurodegenerative types of dementia. Although typical cases of dementia may not benefit from routine functional imaging, these tools are recommended in those cases where diagnosis remains in doubt after clinical and structural imaging work-up and in particular clinical settings. Amyloid imaging is likely to find clinical utility in several fields, including the stratification of patients with mild cognitive impairment into those with and without underlying AD and the evaluation of atypical AD presentations. Conclusions: A number of recommendations and good practice points are made to improve the diagnosis of AD and other dementias. © 2012 The Author(s). European Journal of Neurology © 2012 EFNS.


Filippi M.,Vita-Salute San Raffaele University | Agosta F.,Vita-Salute San Raffaele University | Frisoni G.B.,Irccs Centro San Giovanni Of Dio Fatebenefratelli | de Stefano N.,University of Siena | And 8 more authors.
Current Alzheimer Research | Year: 2012

Quantitative outcome variables in Alzheimer's disease (AD) are of interest because of their low longitudinal variability compared with that of repeated clinical and cognitive measurements. Conventional MR-based volumetry of structures within and beyond the medial temporal lobe has proven to be useful in the diagnostic work up of early AD patients, and measures of atrophy have the potential to monitor the efficacy of disease-modifying agents. The extensive application of new non-conventional MR-based techniques to the study of AD, such as proton magnetic resonance spectroscopy, diffusion tensor MRI, and functional MRI, has undoubtedly improved our understanding of the pathophysiology of the disease, and might lead to the identification of additional useful markers of disease progression. This review summarizes the main results obtained from the application of conventional and non-conventional MRI in AD patients, and supports their more extensive use in studies of disease evolution and clinical trials. © 2012 Bentham Science Publishers.


Mata S.,Azienda Ospedaliero Universitaria di Careggi | Mata S.,Neuroimmunology Laboratory | Lolli F.,Azienda Ospedaliero Universitaria di Careggi
Journal of the Neurological Sciences | Year: 2011

Neuromyelitis optica (NMO) is an inflammatory condition characterized by the selective involvement of the optic nerves and spinal cord, and by a frequent relapsing course. Many clinical, laboratory and neuroimaging studies have provided useful means to distinguish NMO from multiple sclerosis (MS). The detection of aquaporin-4 (AQP4) antibodies has broadened the spectrum of the disorder, which now includes limited variants (either recurrent myelitis or optic neuritis), Asian opticospinal MS, and "atypical" forms with brain involvement. Many in vitro and in vivo evidence have recently demonstrated that AQP4 antibody plays a relevant pathogenetic role in NMO by inducing an increase of BBB permeability, complement cascade activation and astrocytic cytotoxicity. While corticosteroids and plasma exchange are better therapeutic options during NMO attacks, other treatments should be aimed at the prevention of recurrence, possibly by targeting autoantibody production and/or effector mechanisms. Rituximab and Mofetil Mycophenolate appear at the moment the most promising drugs. Since even the most sensitive AQP4 antibody tests fail to mark about 20-30% of the NMO cases, while 20-30% of positive patients have "atypical" or MS-like variants, it remains to be clarified if NMO, as a clinical entity, can still be considered a disease rather than a syndrome, with more possible pathogenetic mechanisms. © 2011 Elsevier B.V.


Detti B.,Azienda Ospedaliero Universitaria di Careggi | Scoccianti S.,Azienda Ospedaliero Universitaria di Careggi | Cassani S.,Azienda Ospedaliero Universitaria di Careggi | Cipressi S.,Azienda Ospedaliero Universitaria di Careggi | And 11 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Aim: In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART). Materials and methods: Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy. Results: In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively. Conclusion: Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs. © 2012 Springer-Verlag.


Gori F.,University of Florence | Mulinacci B.,University of Florence | Massai L.,University of Florence | Avolio C.,University of Foggia | And 7 more authors.
Journal of Neuroimmunology | Year: 2011

Antibodies to MOG in serum have a dubious prognostic value in multiple sclerosis. The MOG recombinant protein conformational properties relevant to the antigenic activity are unknown. We employed a solid-phase ELISA based on a product (rMOGED(His)6) expressed in E. coli after subcloning the cDNA of the extracellular domain of rat MOG, performing a refolding procedure on column and affinity purification. The far-UV Circular Dichroism (CD) spectra of rMOGED(His)6 showed a β-sheet, a characteristic feature of the Ig-fold. However, in MS sera and controls we failed to detected IgM or IgG antibodies. © 2010 Elsevier B.V.


Mata S.,Azienda Ospedaliero Universitaria di Careggi | Muscas G.C.,Azienda Ospedaliero Universitaria di Careggi | Cincotta M.,Piero Plagi Hospital | Bartolozzi M.L.,San Giuseppe Hospital | And 2 more authors.
Journal of Neuroimmunology | Year: 2010

We investigated the prevalence and the clinical association of high titer of antibodies against glutamic acid decarboxylase (hGADAb) among unselected patients with inflammatory/autoimmune disorders of the nervous system. By indirect immunofluorescence examination of samples from 1435 patients, we identified 7 cases (0.48%) with hGADAb. Although stiff-person plus syndrome was the commonest clinical accompaniment, most of the patients presented with a combination of different symptoms, including psychiatric disturbances and intestinal motility disorders. Diagnosis delay and chronic evolution were common findings. In two cases persistently high values of hGADAb over the years were observed. The rarity and the phenotype heterogeneity of hGADAb clinical association should not discourage clinicians from antibody screening, at least in selected cases, as an early immunotherapy can change the otherwise chronic progression of this complex disorder spectrum. © 2010 Elsevier B.V.


PubMed | Azienda Ospedaliero Universitaria di Careggi
Type: Journal Article | Journal: Journal of the neurological sciences | Year: 2011

Neuromyelitis optica (NMO) is an inflammatory condition characterized by the selective involvement of the optic nerves and spinal cord, and by a frequent relapsing course. Many clinical, laboratory and neuroimaging studies have provided useful means to distinguish NMO from multiple sclerosis (MS). The detection of aquaporin-4 (AQP4) antibodies has broadened the spectrum of the disorder, which now includes limited variants (either recurrent myelitis or optic neuritis), Asian opticospinal MS, and atypical forms with brain involvement. Many in vitro and in vivo evidence have recently demonstrated that AQP4 antibody plays a relevant pathogenetic role in NMO by inducing an increase of BBB permeability, complement cascade activation and astrocytic cytotoxicity. While corticosteroids and plasma exchange are better therapeutic options during NMO attacks, other treatments should be aimed at the prevention of recurrence, possibly by targeting autoantibody production and/or effector mechanisms. Rituximab and Mofetil Mycophenolate appear at the moment the most promising drugs. Since even the most sensitive AQP4 antibody tests fail to mark about 20-30% of the NMO cases, while 20-30% of positive patients have atypical or MS-like variants, it remains to be clarified if NMO, as a clinical entity, can still be considered a disease rather than a syndrome, with more possible pathogenetic mechanisms.


PubMed | Azienda Ospedaliero Universitaria di Careggi
Type: Comparative Study | Journal: Journal of neuroimmunology | Year: 2010

We investigated the prevalence and the clinical association of high titer of antibodies against glutamic acid decarboxylase (hGADAb) among unselected patients with inflammatory/autoimmune disorders of the nervous system. By indirect immunofluorescence examination of samples from 1435 patients, we identified 7 cases (0.48%) with hGADAb. Although stiff-person plus syndrome was the commonest clinical accompaniment, most of the patients presented with a combination of different symptoms, including psychiatric disturbances and intestinal motility disorders. Diagnosis delay and chronic evolution were common findings. In two cases persistently high values of hGADAb over the years were observed. The rarity and the phenotype heterogeneity of hGADAb clinical association should not discourage clinicians from antibody screening, at least in selected cases, as an early immunotherapy can change the otherwise chronic progression of this complex disorder spectrum.

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