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Maggio M.,University of Parma | Cattabiani C.,University of Parma | Lauretani F.,University of Parma | Bandinelli S.,Azienda Sanitaria Firenze | And 7 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013

The aim of this study was to address the intriguing issue of the role of the insulin-like growth factor (IGF)-1 system in longevity looking at the role of different components of IGF system. Vital status was ascertained in 1,197 men and women aged greater than or equal to 65 years from the InCHIANTI study. Hormonal levels were categorized into quartiles, and ratio of IGF-1 to IGF-binding protein (IGFBP)-1 was calculated. The relationship between hormones and mortality was tested by Cox proportional hazard models adjusted for age, sex, and confounders. During the 8-year follow-up period, 240 died and 957 survived. Lowest quartiles of IGF-1 and IGFBP-1 were considered as reference. Compared with the lowest quartiles, IGF-1 in upper quartiles was a negative predictor of mortality independent of age and sex (p =. 01) but not independent of IGFBP-1 and other confounders. IGFBP-1 in second-third quartiles was negatively associated and that in the fourth quartiles was positively associated with risk of death. IGF-1/IGFBP-1 ratio in the lowest quartiles was a strong positive predictor of mortality, in age- and sex-adjusted model (p =. 005), and independent of additional confounders (p =. 037). High IGFBP-1 and low IGF-1/IGFBP-1 ratio are associated with all-cause mortality in older population. © 2013 The Author.


PubMed | UPMC San Pietro FBF, AUSL Piacenza, University of Turin, University of Rome Tor Vergata and 23 more.
Type: Journal Article | Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) | Year: 2016

A large-scale multi-institutional planning comparison on lung cancer SABR is presented with the aim of investigating possible criticism in carrying out retrospective multicentre data analysis from a dosimetric perspective.Five CT series were sent to the participants. The dose prescription to PTV was 54Gy in 3 fractions of 18Gy. The plans were compared in terms of PTV-gEUD2 (generalized Equivalent Uniform Dose equivalent to 2Gy), mean dose to PTV, Homogeneity Index (PTV-HI), Conformity Index (PTV-CI) and Gradient Index (PTV-GI). We calculated the maximum dose for each OAR (organ at risk) considered as well as the MLD2 (mean lung dose equivalent to 2Gy). The data were stratified according to expertise and technology.Twenty-six centers equipped with Linacs, 3DCRT (4% - 1 center), static IMRT (8% - 2 centers), VMAT (76% - 20 centers), CyberKnife (4% - 1 center), and Tomotherapy (8% - 2 centers) collaborated. Significant PTV-gEUD2 differences were observed (range: 105-161Gy); mean-PTV dose, PTV-HI, PTV-CI, and PTV-GI were, respectively, 56.83.4Gy, 14.210.1%, 0.700.15, and 4.91.9. Significant correlations for PTV-gEUD2 versus PTV-HI, and MLD2 versus PTV-GI, were observed.The differences in terms of PTV-gEUD2 may suggest the inclusion of PTV-gEUD2 calculation for retrospective data inter-comparison.


PubMed | Humanitas Clinical and Research Center, Casa di cura San Rossore Pisa, Malzoni Radiosurgery Center Salerno, Azienda Ospedaliera Santa Maria Terni and 10 more.
Type: Comparative Study | Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) | Year: 2016

To compare five liver metastasis stereotactic ablative radiotherapy (SABR) plans optimised in fourteen centres with 3D-Conformal-RT, IMRT, VMAT, CyberKnife and Tomotherapy and identify possible dosimetric differences.Dose prescription was 75Gy in 3 fractions, normalised at 67%-95% isodose.Excluding few cases, all institutions achieved the planning objectives. Differences up to 40% and 25% in mean dose to liver and PTV were found. No significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure.The human factor and the constraints imposed to the target volume have a greater dosimetric impact than treatment planning and radiation delivery technology in stereotactic treatment of liver metastases. Significant differences found both in terms of dosimetric target coverage and OAR sparing should be taken into consideration before starting a multi-institutional SARB clinical trial.


Buggiani G.,Private Practitioner of Dermatology and Venereology | Tsampau D.,Azienda Sanitaria Firenze | Krysenka A.,University of Florence | De Giorgi V.,Azienda Sanitaria Firenze | Hercogova J.,Charles University
Dermatologic Therapy | Year: 2012

Necrobiosis lipoidica diabeticorum is a granulomatous skin disease of uncertain pathogenesis. Many therapeutic approaches have been reported in the literature, but none of them can be considered the gold standard. Fractional CO2 laser treatment shows peculiar effects in the skin, mainly due to its ability of modulating cytokine pathways of tissue-repairing mechanisms. Thus, we propose fractional CO2 laser in the management of refractory necrobiosis lipoidica in selected recalcitrant patients. © 2012 Wiley Periodicals, Inc.


Buggiani G.,University of Florence | Tsampau D.,Azienda Sanitaria Firenze | Hercogova J.,Charles University | Rossi R.,Azienda Sanitaria Firenze | And 2 more authors.
Dermatologic Therapy | Year: 2012

Current vitiligo treatments are not always satisfactory for both patients and dermatologists. Recently, combination therapies have been introduced in order to obtain better results and reduce risks in the management of the disease. Novel efficacious products are needed to improve the therapeutic possibilities of dermatologists in the respect of safety for the patients. The objective of the present study was to evaluate the effects of a novel topical in a gel formulation containing phenylalanine, cucumis melo extract, and acetyl cysteine in vitiligo. The present study used an open observational study to evaluate the efficacy and safety of the investigated product, given alone or in combination with 311-nm narrow band microphototherapy. Results were compared with those obtained treating a matched patient population with microphototherapy alone and with clobetasol propionate 0.05% ointment alone. One hundred forty-nine patients suffering from symmetrical vitiligo affecting less than 10% of the skin surface were evaluated. Patients affected by acral vitiligo only were excluded from the analysis. Treatment duration was scheduled for 12 weeks. Excellent repigmentation (>75%) was achieved by 38-73% of patients, depending on the treatment regimen. Mild to moderate side effects were observed only in patients treated with clobetasol 0.05% ointment. The tested gel formulation showed a good efficacy in improving vitiligo repigmentation. No side effects were observed. © 2012 Wiley Periodicals, Inc.


Semba R.D.,Johns Hopkins University | Bandinelli S.,Azienda Sanitaria Firenze | Sun K.,Johns Hopkins University | Guralnik J.M.,U.S. National Institute on Aging | Ferrucci L.,U.S. National Institute on Aging
European Journal of Applied Physiology | Year: 2010

Advanced glycation end products (AGEs) are bioactive molecules found in foods and generated endogenously in the body. AGEs induce cross-linking of collagen and increase the stiffness of skeletal muscle and cartilage. We characterized the relationship between a plasma AGE, carboxymethyl-lysine (CML), and slow walking speed (lowest quintile of walking speed) in older adults. Walking speed over a 4 m course was assessed in 944 adults, aged ≥65 years, in the InCHIANTI study, a population-based study of aging and mobility disability conducted in two towns in Tuscany, Italy. Participants in the highest quartile of plasma CML were at higher risk of slow walking speed (Odds Ratio [O.R.] 1.56, 95% Confidence Interval [C.I.] 1.02-2.38, P = 0.04) compared to those in the lower three quartiles of plasma CML in a logistic regression models adjusting for age, education, cognitive function, smoking, and chronic diseases. After exclusion of participants with diabetes, participants in the highest quartile of plasma CML were at higher risk of slow walking speed (O.R. 1.87, 95% C.I. 1.15-3.04, P = 0.01) adjusting for the same covariates. In older community-dwelling adults, elevated plasma CML is independently associated with slow walking speed. © 2009 Springer-Verlag.


Crasto C.L.,Johns Hopkins University | Semba R.D.,Johns Hopkins University | Sun K.,Johns Hopkins University | Dalal M.,Johns Hopkins University | And 4 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2011

Background: Advanced glycation end products (AGEs) are thought to cause inflammation through interaction with the receptor for AGEs (RAGE), therefore contributing to adverse aging-related processes. The relationship between AGEs, RAGE, and inflammation has not been well characterized. Methods: We examined the relationship of plasma endogenous secretory RAGE (esRAGE); carboxymethyl-lysine (CML), a circulating AGE; and inflammatory mediators in 1,298 adults, 20-97 years, who participated in the InCHIANTI study in Tuscany, Italy. Blood levels of esRAGE, CML, interleukin-1 receptor antagonist (IL-1RA), IL-1β, tumor necrosis factor-α (TNF-α), IL-6, IL-6 receptor (IL-6R), IL-18, C-reactive protein (CRP), transforming growth factor-β (TGF-β), and fibrinogen were measured. Results. Log plasma esRAGE was associated with log IL-1RA (β = -0.069, SE = 0.036, p = .05) and log IL-6 (β = 0.077, SE = 0.035, p = .03), respectively, in separate multivariable linear regression models, adjusting for potential confounders. Log plasma esRAGE was also negatively associated with log TGF-β but did not reach statistical significance (β = -0.091, SE = 0.053, p = .09). Log plasma esRAGE was not significantly associated with log IL-1β, log TNF-α, IL-6R, log IL-18, or CRP. Log plasma CML was not associated with any of the inflammatory mediators except for IL-6R (β = -14.10, SE = 5.94, p = .02) and fibrinogen (β = 13.95, SE = 7.21, p = .05) in separate multivariable models, adjusting for potential confounders. Conclusions: Plasma esRAGE is correlated with higher IL-6 and lower IL-1RA. These findings suggest that plasma esRAGE plays a role in modulating inflammation, although the exact mechanisms remain to be elucidated. © The Author 2011. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.


PubMed | Instituto Europeo Oncologia, Ospedale Di Vicenza, Azienda Sanitaria Firenze, Centro Diagnostico Italiano and 6 more.
Type: Journal Article | Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) | Year: 2016

The aim of the present work was to evaluate small field size output factors (OFs) using the latest diamond detector commercially available, PTW-60019 microDiamond, over different CyberKnife systems. OFs were measured also by silicon detectors routinely used by each center, considered as reference.Five Italian CyberKnife centers performed OFs measurements for field sizes ranging from 5 to 60mm, defined by fixed circular collimators (5 centers) and by Iris() variable aperture collimator (4 centers). Setup conditions were: 80cm source to detector distance, and 1.5cm depth in water. To speed up measurements two diamond detectors were used and their equivalence was evaluated. MonteCarlo (MC) correction factors for silicon detectors were used for comparing the OF measurements.Considering OFs values averaged over all centers, diamond data resulted lower than uncorrected silicon diode ones. The agreement between diamond and MC corrected silicon values was within 0.6% for all fixed circular collimators. Relative differences between microDiamond and MC corrected silicon diodes data for Iris() collimator were lower than 1.0% for all apertures in the totality of centers. The two microDiamond detectors showed similar characteristics, in agreement with the technical specifications.Excellent agreement between microDiamond and MC corrected silicon diode detectors OFs was obtained for both collimation systems fixed cones and Iris(), demonstrating the microDiamond could be a suitable detector for CyberKnife commissioning and routine checks. These results obtained in five centers suggest that for CyberKnife systems microDiamond can be used without corrections even at the smallest field size.


PubMed | Instituto Europeo Oncologia, Ospedale di Vicenza, Azienda Sanitaria Firenze, Centro Diagnostico Italiano and 7 more.
Type: Journal Article | Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) | Year: 2016

New promising detectors are available for measuring small field size output factors (OFs). This study focused on a multicenter evaluation of two new generation detectors for OF measurements on CyberKnife systems.PTW-60019 microDiamond and W1 plastic scintillation detector (PSD) were used to measure OFs on eight CyberKnife units of various generations for 5-60mm fixed cones. MicroDiamond and PSD OF were compared to routinely used silicon diodes data corrected applying published Monte Carlo (MC) factors. PSD data were corrected for erenkov Light Ratio (CLR). The uncertainties related to CLR determination were estimated.Considering OF values averaged over all centers, the differences between MC corrected diode and the other two detectors were within 1.5%. MicroDiamond exhibited an over-response of 1.3% at 7.5mm and a trend inversion at 5mm with a difference of 0.2%. This behavior was consistent among the different units. OFs measured by PSD slightly under-responded compared to MC corrected diode for the smaller cones and the differences were within 1%. The observed CLR variability was 2.5% and the related variation in OF values was 1.9%.This study indicates that CyberKnife microDiamond OF require corrections below 2%. The results are enhanced by the consistency observed among different units. Scintillator shows a good agreement to MC corrected diode but CLR determination remains critical requiring further investigations. The results emphasized the value of a multi-center validation over a single center approach.


PubMed | Accuray, Azienda Sanitaria Firenze, General Hospital, San Bartlolo Hospital and 2 more.
Type: | Journal: Physics in medicine and biology | Year: 2016

Monte Carlo simulation was used to calculate correction factors for output factor (OF), percentage depth-dose (PDD), and off-axis ratio (OAR) measurements with the CyberKnife M6 system. These include the first such data for the InCise MLC. Simulated detectors include diodes, air-filled microchambers, a synthetic microdiamond detector, and point scintillator. Individual perturbation factors were also evaluated. OF corrections show similar trends to previous studies. With a 5mm fixed collimator the diode correction to convert a measured OF to the corresponding point dose ratio varies between -6.1% and -3.5% for the diode models evaluated, while in a 7.6mm x 7.7mm MLC field these are -4.5% to -1.8%. The corresponding microchamber corrections are +9.9% to +10.7% and +3.5% to +4.0%. The microdiamond corrections have a maximum of -1.4% for the 7.5mm and 10mm collimators. The scintillator corrections are <1% in all beams. Measured OF showed uncorrected inter-detector differences >15%, reducing to <3% after correction. PDD corrections at d>dmax were <2% for all detectors except IBA Razor where a maximum 4% correction was observed at 300mm depth. OAR corrections were smaller inside the field than outside. At the beam edge microchamber OAR corrections were up to 15%, mainly caused by density perturbations, which blurs the measured penumbra. With larger beams and depths, PTW and IBA diode corrections outside the beam were up to 20% while the Edge detector needed smaller corrections although these did vary with orientation. These effects are most noticeable for large field size and depth, where they are dominated by fluence and stopping power perturbations. The microdiamond OAR corrections were <3% outside the beam. This paper provides OF corrections that can be used for commissioning new CyberKnife M6 systems and retrospectively checking estimated corrections used previously. We recommend the PDD and OAR corrections are used to guide detector selection and inform the evaluation of results rather than to explicitly correct measurements.

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