Regione Toscana Research Articles

Well-being, Landscape and Sustainability of Communication

Abstract The paper deals with the concept of well-being and its relationship with landscape and agriculture. According to the literature, well-being is a multidimensional and subjective concept, it is related to happiness but it does not depend on mere economic welfare. In fact, the bond between material wealth and well-being is not causal: GDP is not the optimum way of assessing the level of well-being. On the contrary, there is a strict relationship between well-being, agriculture and rural development. The man/farmer, transforming the rural landscape, creates modifications that reverberate first on natural landscape, then on the whole territory, and finally back to the man itself. In this context, the generative communication arises as a model that best interprets the need to represent and promote the circular nature of the relationships between man and land. By doing this, it enhances and protects cultural diversity, social and natural environment of the territory itself. Hence, it strengthens the well-being of those who work and constantly transforms this landscape. The paper closes with the analysis of two case-studies, the “Comunicazione generativa per il Programma di Sviluppo Rurale 2014-2020 della Regione Toscana” project (in english: Generative Communication for the Tuscany Rural Development Programme, RDP, 2014-2020) and the “San Casciano Smart Place” project, both developed by the Communication Strategies Lab. The methodology used for the development of the projects is the generative communication ( Toschi, 2011 ), with its recent specification towards the concept of sustainable communication.

Quantification of CatSper1 expression in human spermatozoa and relation to functional parameters.

Is CatSper1 expression in human spermatozoa related to semen parameter values and sperm functions? CatSper1 expression is positively related to progressive and hyperactivated (HA) motility, [Ca(2+)]i responsiveness to progesterone but not the acrosome reaction (AR). The role of cationic channel of sperm (CatSper) in sperm functions is clear in animal models but less defined in human sperm cells. Current knowledge is mostly based on low specificity CatSper inhibitors showing agonistic and toxic effects on human spermatozoa and is thus of little help in clarifying the role of the CatSper channel in human sperm functions. CatSper1 protein expression was evaluated in 115 men undergoing semen analysis for couple infertility. CatSper1 expression was related to routine semen parameters, motility kinematic parameters and basal and progesterone-stimulated [Ca(2+)]i and the AR. CatSper1 expression was evaluated (n = 85 normozoospermic, n = 30 asthenozoospermic patients) by immunofluorescence coupled to flow cytometry leading to quantitative measurement of the percentage of ejaculated sperm cells expressing the protein. Semen analysis was evaluated according to World Health Organization guidelines. Kinematic parameters were evaluated by a computer-aided sperm analysis system. [Ca(2+)]i was measured by a spectrofluorimetric method in fura-2-loaded spermatozoa. The AR was evaluated in live sperm cells by fluorescent-labeled lectin. CatSper1 protein expression in spermatozoa was reduced in asthenozoospermic men (mean ± SD: 53.0 ± 15.5%, n = 30 versus 67.9 ± 17.1% in normozoospermic, n = 85, P < 0.01) and was significantly correlated with progressive (r = 0.36, P < 0.001), total (r = 0.35, P < 0.001) and HA (r = 0.41, P < 0.005) motility. In addition to a higher percentage of spermatozoa not expressing CatSper1, asthenozoospermic men showed a large number of spermatozoa with immunofluorescent signal localized outside the principal piece compared with those in normozoospermia. A significant positive correlation was found between CatSper1 protein expression and the increase of [Ca(2+)]i in response to progesterone (r = 0.36, P < 0.05, n = 40) but not with basal [Ca(2+)]i. No correlation was found with the AR, either basal or in response to progesterone. The study is partly descriptive. Furthermore, we cannot rule out the possibility that some round cells remain after a single round of 40% density gradient centrifugation or that this step may have removed some defective or slow swimming sperm, and therefore this preparation may not be representative of the entire sperm sample. Although our data suggest that CatSper1 may be a useful marker for infertility, and a possible contraceptive target, any clinical application is limited without further research. Our results demonstrate an association of CatSper1 expression with human sperm progressive and HA motility and provide preliminary evidence that lack of expression or mislocalization of CatSper1 in spermatozoa may be involved in the pathogenesis of asthenozoospermia. However, mechanistic studies are needed to confirm that the correlations between CatSper1 expression and sperm functions are causative. Supported by grants from Ministry of University and Scientific Research (PRIN project to E.B. and FIRB project to S.M.) and by Regione Toscana (to G.F.). L.T. was recipient of a grant from Accademia dei Lincei (Rome, Italy). The authors have no conflicts of interest to declare.

Groundwater Flow and Transport Model in Cecina Plain (Tuscany, Italy) using GIS processing

This work provides a groundwater flow and transport model of trichlorethylene and tetrachlorethylene contamination in the Cecina’s coastal aquifer. The contamination analysis, with source located in the Poggio Gagliardo area (Montescudaio, Pisa), was necessary to optimize the groundwater monitoring and remediation design. The work was carried out in two phases: • design of a conceptual model of the aquifer using GIS analysis of many stratigraphic, chemical and hydrogeological data, collected from 2004 to 2012 in six aqueduct wells; • implementation of a groundwater flow and transport numerical model using the MODFLOW 88/96 and MT3D code and the graphical user interface GroundWaterVistas 5. The conceptual model hypothesizes a multilayer aquifer in the coastal plain extended to the sandy-clay hills, recharged by rainfall and by the Cecina River. The aquifer shows important hydrodynamic features affecting both the contamination spreading, due to the presence of a perched and heavily polluted layer separate from the underlying productive aquifer, and the hydrological balance, due to a thick separation layer that limits exchanges between the river and the second groundwater aquifer. The numerical model, built using increasingly complex versions of the initial conceptual model, has been calibrated using monitoring surveys conducted by the Environmental Protection Agency of Regione Toscana (ARPAT), in order to obtain possible forecast scenarios based on the minimum and maximum flow periods, and it is currently used as a tool for decision support regarding the reclamation and/or protection of the aquifer. Future developments will regard the implementation of the multilayer transport model, based on a new survey, and the final coupling with the regional hydrological model named MOBIDIC.

The CatSper calcium channel in human sperm: relation with motility and involvement in progesterone-induced acrosome reaction

Does CatSper have a role in the achievement of human sperm motility and in the Progesterone (P)-induced acrosome reaction (AR)? CatSper1 expression is associated with human sperm progressive motility and the P-induced AR; it may have a role in the pathogenesis of asthenozoospermia. Knockout mice for any of the Catsper family genes fail to acquire hyperactivated motility and are infertile. CatSper channels mediate P-induced Ca(2+) influx in human sperm. The role of CatSper in human sperm hyperactivated/activated motility and in asthenospermia is less clear. A few men with CatSper mutations have been described but the phenotype regarding sperm motility has not been well established. The effects of two Catsper inhibitors, NNC55-0396 (NNC, 10 and 20 µM) and Mibefradil (Mib, 30 and 40 µM), were tested on human sperm motility parameters and the P-induced AR. Catsper1 protein expression was evaluated in unselected and swim-up selected sperm samples and in sperm from normo- and astheno-zoospermic subjects. Semen sample kinematic parameters were analysed by a CASA system. A fluorescent-labelled lectin was used to evaluate P-induced AR in live sperm by fluorescence microscopy. CatSper1 protein expression was determined by western blot analysis and by flow cytometry. Intracellular calcium concentrations ([Ca(2+)]i) were evaluated by a spectrofluorimetric method following sperm loading with the calcium-sensitive probe fura 2/AM. CatSper1 protein was localized in the tail of human sperm. CatSperI expression was higher in swim up selected than unselected sperm both when measured by western blot or by flow cytometry (52.7 ± 15.8% versus 27.2 ± 9.01%, n = 7, P < 0.01). Basal and P-stimulated [Ca(2+)]i were significantly higher in swim-up selected compared with unselected sperm. CatSper1 expression (western blot analysis) was found to be decreased in sperm from asthenozoospermic (n = 10) compared with those from normozoospermic (n = 9) men (intensity values relative to β-actin: 244.4 ± 69.3 versus 385.8 ± 139.5, P < 0.01). A positive correlation was found between CatSper1 protein expression and the percentage of sperm with progressive motility (n = 19, r = 0.59, P = 0.007). NNC (10 µM) and Mib (30 µM) significantly reduced the percentage of sperm with progressive motility and several kinematic parameters but did not affect the percentage of hyperactivated sperm. Their effects were the same whether they were added to swim-up selected and capacitated sperm or were added to the swim-up medium. Mib was found to have a slight but significant effect on sperm viability at both concentrations tested. P-stimulated AR was significantly reduced by both inhibitors (P < 0.05). Overall, our results indicate that, in human sperm, CatSper channel expression and function are associated with progressive motility and may be involved in the pathogenesis of asthenozoospermia. In general, studies evaluating the effect of inhibitors have the limitation of the specificity of the molecules. We show here that Mib may have toxic effect on human sperm. Although most of the parameters have been evaluated in live sperm, the toxic effect could have contributed to the observed decreases. More studies are necessary to evaluate further the role of CatSper1 in asthenozoospermia. In view of the involvement in P-induced AR and of the evidence of a role in the pathogenesis of astenozoospermia, CatSper channels may represent a promising target for the development of new drugs for the treatment of male infertility and for non-hormonal contraception. This work was supported by grants from Ministry of University and Scientific Research (Prin project to E.B. and FIRB project to S.M) and Regione Toscana (to G.F.). The authors have no conflicts of interest to declare.

Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials

Typhoid vaccination is a public health priority in developing countries where young children are greatly affected by typhoid fever. Because present vaccines are not recommended for children younger than 2 years, the Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant immunisation. We aimed to assess the immunogenicity and safety of Vi-CRM197 in participants of various ages in endemic countries in south and southeast Asia. We did two randomised, observer-blind, age de-escalation, phase 2 trials at two sites in Pakistan and India (study A), and at one site in the Philippines (study B), between March 2, 2011, and Aug 9, 2012. Adults aged 18-45 years, children aged 24-59 months, older infants aged 9-12 months, and infants aged 6-8 weeks were randomly assigned (1:1) with a computer-generated randomisation list (block size of four) to receive either 5 μg Vi-CRM197 or 25 μg Vi-polysaccharide vaccine (or 13-valent pneumococcal conjugate vaccine in children younger than 2 years). Both infant populations received Vi-CRM197 concomitantly with vaccines of the Expanded Programme on Immunization (EPI), according to WHO schedule. With the exception of designated study site personnel responsible for vaccine preparation, study investigators, those assessing outcomes, and data analysts were masked to treatment allocation. We specified no a-priori null hypothesis for the immunogenicity or safety objectives and all analyses were descriptive. Analyses were by modified intention-to-treat. These studies are registered with ClinicalTrials.gov, numbers NCT01229176 and NCT01437267. 320 participants were enrolled and vaccinated in the two trials: 200 in study A (all age groups) and 120 in study B (children and infants only), of whom 317 (99%) were included in the modified intention-to-treat analysis. One dose of Vi-CRM197 significantly increased concentrations of anti-Vi antibody in adults (from 113 U/mL [95% CI 67-190] to 208 U/mL [117-369]), children (201 U/mL [138-294] to 368 U/mL [234-580]), and older infants (179 U/mL [129-250] to 249 U/mL [130-477]). However, in children and older infants, a second dose of conjugate vaccine had no incremental effect on antibody titres and, at all ages, concentrations of antibodies increased substantially 6 months after vaccination (from 55 U/mL [33-94] to 63 U/mL [35-114] in adults, from 23 U/mL [15-34] to 51 U/mL [34-76] in children, and from 21 U/mL [14-31] to 22 U/mL [14-33] in older infants). Immune response in infants aged 6-8 weeks was lower than that in older participants and, 6 months after third vaccination, antibody concentrations were significantly higher than pre-vaccination concentrations in Filipino (21 U/mL [16-28] vs 2.88 U/mL [1.95-4.25]), but not Pakistani (3.76 U/mL [2.77-5.08] vs 2.77 U/mL [2.1-3.66]), infants. Vi-CRM197 was safe and well tolerated and did not induce any significant interference with EPI vaccines. No deaths or vaccine-related serious adverse events were reported throughout the studies. Vi-CRM197 is safe and immunogenic in endemic populations of all ages. Given at 9 months of age, concomitantly with measles vaccine, Vi-CRM197 shows a promise for potential inclusion in EPI schedules of countries endemic for typhoid. An apparent absence of booster response and a reduction in antibody titres 6 months after immunisation should be further investigated, but data show that an immunogenic typhoid vaccine can be safely delivered to infants during EPI visits recommended by WHO. Sclavo Vaccines Association and Regione Toscana.

THU0011 MIR-223 expression in serum and CD3+ peripheral cells of rheumatoid arthritis

BackgroundWe have recently demonstrated that miR-223 is up-regulated in peripheral blood and synovial CD3+T lymphocytes (TL) from Rheumatoid Arthritis (RA) patients compared to healthy controls (1,2) suggesting that miR-223 could...

AB0012 Microrna-223 in synovial tissue of rheumatoid arthritis and osteoarthritis patients

BackgroundRheumatoid Arthritis (RA) is a systemic autoimmune disorder characterized by chronic synovitis and progressive joint destruction. MicroRNAs (miRNAs) are small non-coding RNA molecules able to modulate gene expression at post-transcriptional...

On the variability of concrete strength as a source of irregularity in elevation for existing RC buildings: a case study

A proper assumption of the concrete strength is essential to model existing RC structures; their seismic performance, in fact, can be affected by the poor quality of materials, both in terms of low strength and high variability. This paper considers the effects of the variability of concrete strength within buildings. Due to the high variability of concrete strength, in fact, buildings can experience irregular seismic responses, both in plan and in elevation. This research investigates the effects of irregularity in elevation due to the strength variability of concrete in a case study, namely a four-storey RC framed building, designed for vertical loads only. The variability of the concrete strength has been evaluated on the basis of an extensive survey carried out by the REGIONE TOSCANA (Tuscany Regional Government) on a large sample of RC framed buildings. Special attention has been paid to the adequacy of current codes provisions (Eurocodes, FEMA) on how to quantify concrete strength.

Hospitalizations performed in patients enrolled in assistance programs for not-self-sufficient individuals

The objective of this study was to verify if the enrollement of patients aged over sixty-five (over 65), in the territorial assistance programs of a mountain area, has reduced and optimized the volume of hospitalizations. During 2009, 422 patients over 65 who were non self-sufficient, with iso-severity level (IL) from 5 to 0 (Regione Toscana, Decreto n. 1354 del 25 Marzo 2010), were enrolled in home care programs. These data were processed despite the following analytical limitations: 1) inability to provide all tax codes (entered manually in database), the corrisponding personal data; 2) necessity to make cross-comparisons among numerous archives of data from different sources; and 3) lack to identify the outcome indicators for each patient. The assisted patients are characterized by a very high hospitalization rate. Among the main diseases, the following needed at least one hospitalization: dementia, stroke, cancer, osteoarticular diseases, cerebrovascular disease and Parkinson's disease. Therefore it is necessary to re-evaluate the current procedures adopted for the management of chronic diseases in the elderly in their own homes.

Effect of the variability in plan of concrete mechanical properties on the seismic response of existing RC framed structures

A proper characterization of concrete strength is essential to correctly model existing RC structures, whose seismic performance is affected by the poor quality of materials. The purpose of this work is to evaluate the effect of incorrect assumptions for concrete strength and the adequacy of current Codes provisions (Eurocodes, FEMA). Even the effects of the non homogeneity of concrete strength within the building is considered due to its high variability; in fact, buildings can experience an irregular seismic response, both in plan and in elevation. In this work the effects of irregularity in plan due to the strength variability of concrete is analyzed on a case study, a four storey RC framed building, designed for vertical loads only. The variability of concrete strength has been evaluated using the data of an extensive investigation developed by REGIONE TOSCANA on a large sample of RC framed buildings.

A magnetorheological clutch for efficient automotive auxiliary device actuation

In this paper the results of a project funded by Regione Toscana aimed at reducing the power absorption of auxiliary devices in vehicles are presented. In particular the design, testing and application of a magnetorheological clutch (MR) is proposed, aimed at disengaging the vacuum pump, which draws in air from the power-brake booster chamber, in order to reduce the device power absorption. Several clutch preliminary studies done to choose the clutch geometry and the magnetic field supply are illustrated. The final choice consisted in an MR clutch with permanent magnet, which satisfied size, torque and fail-safe specifications. The clutch characteristics, in terms of torque versus slip, were obtained experimentally for three different clutch prototypes on an ad-hoc developed test bench. As result of a preliminary simulation, a comparison between the power absorption of a current production vacuum pump, an innovative vacuum pump and both vacuum pumps coupled with the MR clutch is presented. The New European Driving Cycle is considered for simulating the vacuum pump operation both in urban and highway driving. Results show that the use of the innovative vacuum pump reduces the device consumption of about 35%, whereas the use of MR clutch coupled with the innovative vacuum pump reduces it up to about 44% in urban driving and 50% in highway driving.

Semen apoptotic M540 body levels correlate with testis abnormalities: a study in a cohort of infertile subjects

What are the associations between semen apoptotic M540 bodies and other parameters of semen quality and sonographic alterations of the male genital tract in a cohort of infertile subjects? In infertile subjects, semen M450 bodies are highly correlated with ultrasound and clinical signs of testis abnormalities but not with alterations of other parts of the male genital tract, suggesting a testicular origin of M540 bodies. We have reported the presence in semen of round anucleate elements, named 'M540 bodies', resembling apoptotic bodies as they contain several apoptotic markers. A consecutive series of 130 males with couple infertility were evaluated, during the same day session, for clinical, scrotal and transrectal color-Doppler ultrasound characteristics, and hormonal and semen parameters, including interleukin 8 (sIL-8) and M540 body levels. Semen parameters were analyzed by WHO recommended procedures. CDU was performed using the ultrasonographic console Hitachi H21. sIL-8 and serum hormones were evaluated by ELISA methods. The average percentage value of M540 bodies was 24.6 ± 18.3. After adjusting for possible confounders (age, waist, calculated free testosterone and smoking habit), M450 body levels negatively correlated with sperm number/ejaculate, progressive motility, normal morphology and sIL-8 levels (adj.r = -0.455, P < 0.0001; adj.r = -0.464, P < 0.0001; adj.r = -0.430, P < 0.001; adj.r = -0.236, P < 0.05, respectively). In a subset of patients with a history of cryptorchidism (n = 8), M540 bodies were higher than in non-cryptorchid men (40.5 ± 14.8 versus 23.6 ± 18.2%; P < 0.02). A negative correlation was found between M540 and ultrasound testis volume (adj.r = -0.241, P < 0.05), whereas a positive association was found with testis inhomogeneity [HR = 1.06 (1.02-1.09); P = 0.002], hypoechogenicity [HR = 1.05 (1.01-1.08); P < 0.02] and FSH levels (adj.r = 0.309, P < 0.01). No relationships were found with CDU characteristic of the prostate, seminal vesicles, epididymis and vas deferens. In a multivariate model, testis inhomogeneity and history of cryptorchidism were independently associated with M540 body levels (adj.r = 0.355, P < 0.01 and adj.r = 0.223, P < 0.05, respectively). Receiver operating characteristic analysis demonstrated that at the threshold of 27%, M540 bodies discriminate subjects with testis inhomogeneity with a sensitivity of 72% and specificity of 73%. The increased M540 body semen levels in men with a history of cryptorchidism should be confirmed in a larger number of patients. M540 bodies may be considered a semen marker of altered testis function and thus their evaluation may be helpful in the diagnosis of male infertility. This work was supported by grants from Ministry of University and Scientific Research (Prin project to E.B. and FIRB project to S.M.) and Regione Toscana (to G.F.).

TOUGH2Viewer: A post-processing tool for interactive 3D visualization of locally refined unstructured grids for TOUGH2

Within the MAC-GEO research project, funded by Regione Toscana and addressed to the exploitation of high enthalpy geothermal systems, the authors worked on the utilization and customization of the open source numerical simulator TOUGH2, as implemented in the code dedicated to model calibration iTOUGH2.TOUGH2 is one of the most used numerical simulation software for non-isothermal flow of multicomponent, multiphase fluids in one, two and three-dimensional porous and fractured media.Lacking an official Graphical User Interface tool for post-processing operations, several commercial and academic software have been developed to manage and display TOUGH2 input and output data files. Almost all of these tools seem to have limits to visualizing parameter values of the numerical model, work only with a predefined binary version of TOUGH2, and only a few of them can manage locally refined unstructured grids (i.e. Voronoi grids). To overcome these limitations, the authors have developed and tested a dedicated software application (called TOUGH2Viewer) for reading and managing TOUGH2 output files, written in Java and able to provide an interactive 3D view of the numerical model. Several functionalities have been implemented for block query and searching, contour mapping and 3D surface mapping of TOUGH2 primary variables (i.e. pressure, temperature, etc.).TOUGH2Viewer is also able to display 2D and 3D views of mass and heat flow between blocks, for each time step in which the simulation proceeds.The application described in this paper is under development to improve its functionalities; nevertheless the current software release is a valid support tool for post-processing that significantly improves the possibility to inspect the simulated data coming from TOUGH2.

Experimental study of hydrogen releases in the passenger compartment of a Piaggio Porter

Abstract There are currently projects and demonstration programs aiming at introducing Hydrogen powered Fuel Cell (HFC) vehicles into the market. Regione Toscana has been cofounder of the project “H2 Filiera Idrogeno”, whose goal is to achieve a clean and sustainable mobility through HFC vehicle studies covering their production, storage and use. Among the goals of the project was the substitution of the electric propulsion system with a hydrogen fuel cells propulsion system. This work presents a brief overview of the necessary modifications of the electric propulsion version of a Piaggio Porter to host a H 2 fuel cell and experimental studies of realistic H 2 releases from the vehicle. The scenarios covered H 2 unintended releases underneath the vehicle when at rest and focused on three types of releases, diffusive, major and minor, that might reach the interior of the vehicle and potentially pose a direct risk to the passengers.

Geographical Information System for the Cultural Heritage and Protected Landscape of Regione Toscana

LaMMA Consortium, with collaboration of Regione Toscana and Ministero per i Beni e le Attività Culturali (MiBAC), has created the web Geographical Information System for Cultural Heritage and Protected Landscape of Regione Toscana. This system now makes it possible to access the digital maps and the digital archives of archaeological, architectural and landscape related restrictions over the entire region. In order to continuously update the realized system for maintaining its utility and validity, Regione Toscana together with MiBAC signed a protocol agreement (2004), according to which every new restriction measure issued is sent as a copy also to the regional offices and then to LaMMA Consortium, that attends to update the digital archives and the digital maps. Thanks to this agreement, the system counts today over 18,000 measures, with an average yearly increase of almost 250 measures, that determine restrictions for 9.000 areas.

Minimally invasive aortic valve replacement via right anterior minithoracotomy: Early outcomes and midterm follow-up

FIGURE 1. A, Axial plane shows the right position of the aorta with respect t feasibility of cannulating the ascending aorta and replacing the aortic valve throu ment. AC, Aortic cannula; AT, aortic tourniquet; XC, crossclamp; LVV, left ven From the Department of Cardiothoracic Surgery, Fondazione G. Monasterio, CNR—Regione Toscana, Massa, Italy. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Jan 28, 2011; revisions received April 26, 2011; accepted for publication May 17, 2011; available ahead of print July 4, 2011. Address for reprints: Antonio Miceli, MD, Fondazione G. Monasterio, CNR-regione Toscana, 54100 Massa, Italy (E-mail: antoniomiceli79@alice.it). J Thorac Cardiovasc Surg 2011;142:1577-9 0022-5223/$36.00 Copyright 2011 by The American Association for Thoracic Surgery doi:10.1016/j.jtcvs.2011.05.011

Copper and Cashmere: A Winning Combination for the Textile Sector?

This paper summarizes the main results of the Italian project “Comfort Tecnologico”, that was granted a subvention by the HI TEX pilot Program 2007/2008 managed by Tuscany regional authority Regione Toscana. The “Comfort Tecnologico” Project goal is to combine fine natural fibers (such as cashmere, alpaca, mohair and wool, pure or mixed) with different types of metals yarns to create new category of fabrics and garments with high comfort characteristics. Different tests have been performed on several samples of different materials and results have been compared. Copper and cashmere turned out as the most promising combination in terms of improved characteristics of the newly created yarns and textiles. At the end, some remarks and perspectives regarding future development have been addressed.

Climate Change and the Contemporary Evolution of Foodways

Climate Change and the Contemporary Evolution of Foodways

Analisi di costo efficacia di trastuzumab nel trattamento adiuvante del carcinoma mammario precoce HER-2 positivo: l’esperienza della Regione Toscana

Trastuzumab, a humanized monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER-2), is an important cell proliferation regulator in HER2-overexpressing breast cancer. It has been implemented as a standard adjuvant treatment in combination with chemotherapy for early-stage breast cancer in many countries. The aim of this study was to analyse the cost-effectiveness of 1-year of trastuzumab given every three weeks compared with observation in patients with early-stage breast cancer (HER-2-positive) after excision and completion of chemotherapy, from the Health Service of Regione Toscana perspective. A Markov health-state transition model was constructed to simulate the natural development of breast cancer based on HERceptin Adjuvant (HERA) trial; outcomes included overall mean survival (Life Years, LYs), quality adjusted life years (QALYs) and direct costs (value year 2009). The model results showed that the utilization of adjuvant trastuzumab treatment increased life expectancy by 2.10 LYs (2.01 QALYs), compared with the observation group. The incremental cost-effectiveness ratio (ICER) of trastuzumab for an additional life-year gained (LYG) was €7,135.43. If measured by quality-adjusted life-years, the ICER was €7,461.91. Univariate and probabilistic sensitivity analyses confirmed robustness of results. Our findings seem to suggest that 1-year of treatment with trastuzumab after adjuvant chemotherapy among women with HER-2-positive breast cancer significantly improves overall survival with reasonable costs if compared to the internationally accepted threshold.

Tangier Disease in Severely Progressive Coronary and Peripheral Artery Disease

A 37-year-old man was first referred to our lipid clinic in December 2007 for plasma lipid alteration. He presented with large, orange tonsils (Figure 1) and hepatosplenomegaly. There was no evidence of corneal opacities nor of other ocular abnormalities, and there were no nervous system abnormalities as assessed by sensitive and motor electromyography. Figure 1. Orange large tonsils. Hematologic abnormalities included thrombocytopenia and erythrocytes with altered morphology (stomatocytes; Figure 2) and function (decreased osmotic resistance). Serum levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were 58, 184, and 4 mg/dL, respectively; plasma apolipoprotein A-I concentrations were very low (3.9 mg/dL); and apolipoprotein A-II plasma levels were 1.7 mg/dL. Figure 2. Peripheral blood erythrocytes with numerous stomatocytes. The patient’s father (58 years of age) had serum levels of total cholesterol, HDL cholesterol, and apolipoprotein A-I of 127, 25, and 99.5 mg/dL, respectively. Moreover, he had a …