Studio e validazione di una nuova metodica per la valutazione dello stato di forma

We observed 82 healthy subjects, from both sexes, aged between 19 and 77 years. All subjects performed two different tests: for being scientifically acknowledged, the first one was used as a reference and it was a stress test (CPX). During the entire test, heart rate and gas exchange were recorded continuously; the second, the actual object of this study, was a submaximal test (TOP). Only heart rate was recorded continuously. The main purpose was to determinate an index of physical fitness as result of TOP. CPX test allowed us to individuate anaerobic threshold. We used an incremental protocol of 10/20 Watt/min, different by age. For our TOP test we used an RHC400 UPRIGHT BIKE, by Air Machine. Each subject was monitored for heart frequency. After 2 minutes of resting period there was a first step: 3 minutes of pedalling at a constant rate of 60 RPM, (40 watts for elder subjects and 60 watts for the younger ones). Then, the subject was allowed to rest for a recovery phase of 5 minutes. Third and last step consisted of 3 minutes of pedalling again at 60 RPM but now set to 60 watts for elder subjects and 80 watts for the young subjects. Finally another five minutes of recovery. A good correlation was found between TOP and CPX results especially between punctua l heart rate reserve (HRR’) and anaerobic threshold parameters such as Watt, VO2, VCO2 . HRR’ was obtained by subtracting maximal heart rate during TOP from maximal theoretic heart rate (206,9-(0,67*age)). Data were analyzed through cluster analysis in order to obtain 3 homogeneous groups. The first group contains the least fit subjects (inactive, women, elderly). The other groups contain the “average fit” and the fittest subjects (active, men, younger). Concordance between test resulted in 83,23%. Afterwards, a linear combinations of the most relevant variables gave us a formula to classify people in the correct group. The most relevant result is that this submaximal test is able to discriminate subjects with different physical condition and to provide information (index) about physical fitness through HRR’. Compared to a traditional incremental stress test, the very low load of TOP, short duration and extended resting period, make this new method suitable to very different people. To better define the TOP index, it is necessary to enlarge our subject sample especially by diversifying the age range.

Effetti clinici e biologici della terapia epigenetica nelle sindromi mielodisplastiche a basso rischio

Background: Nucleoside 5-Azacitidine (5-Aza) in high risk MDS patients (pts) at a dose of 75mg/mq/day subcutaneously for 7 days, every 28 days, induces high hematologic response rates (hematologic improvement (HI) 50-60%, complete remission (CR) 10-30%) and prolongation of survival (at 2 years 50,8%). Aim: The role of 5-Aza in low-risk MDS patients is not well defined but its use in the earlier phases of disease could be more effective and useful to control the expansion of MDS clone and disease progression. In our phase II, prospective, multicentric trial a low-dose schedule of 5-Aza (75 mg/mq daily for 5 consecutive days every 28 days) was given to low-risk MDS pts in order to evaluate its efficacy and tolerability and to identify biological markers to predict the response. Methods: From September 2008 to February 2010, 34 patients were enrolled into the study. Fifteen patients had refractory anemia (RA), 5 patients refractory anemia with ringed sideroblasts (RARS), 7 patients refractory cytopenia with multilineage dysplasia (RCMD) and 7 patients refractory anemia with excess blasts-1 (RAEB-1). All patients failed previously EPO therapy and were in chronic red blood cell (RBC) supportive care with a median transfusions requirement of 4 units/monthly. The response treatment criteria was according to IWG 2006. Results: At present time 31 out of 34 pts are evaluable: 12/31 pts (39%) completed the treatment plan (8 courses), 7/31 pts (22%) performed the first 4 courses, 8/31 (26%) made 1 to 3 courses and 4/31 (13%) died during the treatment period. Out of 12 pts who completed the 8 courses of therapy 10 (83%) obtained an HI, 2/12 (17%) maintained a stable disease. Out of 10 pts who obtained HI, 4 pts (40%) achieved a CR. Generally the drug was very well tolerated. The most commonly reported hematologic toxicities were neutropenia (55%) and thrombocytopenia (19%) but they were transitory and usually no delay of treatment was necessary. 2/4 pts died early after the 1th cycle for septic shock and gastrointestinal hemorrage respectively whereas 2/4 pts died in a condition of stable disease after the 4th cycle for pneumonia and respiratory distress. Samples for biologic studies have been collected from the pts before starting the therapy and at the end of 4th and 8th course. Preliminary data on the lipid signalling pathways suggested a direct correlation between PI-PLC-β1 gene expression and 5-Aza responsiveness. Conclusion: Interim analysis of our study based on the small number of cases who completed the treatment program, shows that 83% of pts obtain an HI and 40% obtain a CR. 4 patients died during the treatment and even if the causes were reported as no related to the therapy it has been considered that caution has to be reserved in given 5-Aza in these pts who are elderly and frail. Preliminary data of PI-PLC-β1 gene expression suggest that this and probably other biological markers could help us to know a priori who are the patients who have more chances to respond.

L'associazione Tipifarnib-Bortezomib nel trattamento delle leucemie acute mieloidi: risultati di uno studio multicentrico di fase I/II e validazione di un profilo genico predittivo di risposta

Background. Outcome of elderly acute myeloid leukemia (AML) patients is dismal. Targeted-therapies might improve current results by overcoming drug-resistance and reducing toxicity. Aim. We conduced a phase II study aiming to assess efficacy and toxicity of Tipifarnib (Zarnestra®) and Bortezomib (Velcade®) association in AML patients >18 years, unfit for conventional therapy, or >60 years, in relapse. Furthermore, we aimed to evaluated the predictive value of the RASGRP1/APTX ratio, which was previously found to be associated to treatment sensitivity in patients receiving Zarnestra alone. Methods. Velcade (1.0 mg/m2) was administered as weekly infusion for 3 weeks (days 1, 8, 15). Zarnestra was administered at dose of 300-600 mg BID for 21 consecutive days. Real-time quantitative-PCR (q-PCR) was used for RASGRP1/APTX quantification. Results. 50 patients were enrolled. Median age was 71 years (56-89). 3 patients achieved complete remission (CR) and 1 partial response (PR). 2 patients obtained an hematological improvement (HI), and 3 died during marrow aplasia. 10 had progressive disease (PD) and the remaining showed stable disease (SD). RASGRP1/APTX was evaluated before treatment initiation on bone marrow (BM) and/or peripheral blood (PB). The median RASGRP/APTX value on BM was higher in responder (R) patients than in non responders (NR) ones, respectively (p=0.006). Interestingly, no marrow responses were recorded in patients with BM RASGRP1/APTX ratio <12, while the response rate was 50% in patients with ratio >12. Toxicity was overall mild, the most common being febrile neutropenia. Conclusion. We conclude that the clinical efficacy of the combination Zarnestra-Velcade was similar to what reported for Zarnestra alone. However we could confirm that the RASGPR1/APTX level is an effective predictor of response. Though higher RASGRP1/APTX is relatively rare (~10% of cases), Zarnestra (±Velcade) may represent an important option in a subset of high risk/frail AML patients.

Pervasive Sensing in Future Networks

Pervasive Sensing is a recent research trend that aims at providing widespread computing and sensing capabilities to enable the creation of smart environments that can sense, process, and act by considering input coming from both people and devices. The capabilities necessary for Pervasive Sensing are nowadays available on a plethora of devices, from embedded devices to PCs and smartphones. The wide availability of new devices and the large amount of data they can access enable a wide range of novel services in different areas, spanning from simple data collection systems to socially-aware collaborative filtering. However, the strong heterogeneity and unreliability of devices and sensors poses significant challenges. So far, existing works on Pervasive Sensing have focused only on limited portions of the whole stack of available devices and data that they can use, to propose and develop mainly vertical solutions. The push from academia and industry for this kind of services shows that time is mature for a more general support framework for Pervasive Sensing solutions able to enhance frail architectures, promote a well balanced usage of resources on different devices, and enable the widest possible access to sensed data, while ensuring a minimal energy consumption on battery-operated devices. This thesis focuses on pervasive sensing systems to extract design guidelines as foundation of a comprehensive reference model for multi-tier Pervasive Sensing applications. The validity of the proposed model is tested in five different scenarios that present peculiar and different requirements, and different hardware and sensors. The ease of mapping from the proposed logical model to the real implementations and the positive performance result campaigns prove the quality of the proposed approach and offer a reliable reference model, together with a direction for the design and deployment of future Pervasive Sensing applications.

Dal repertorio al database: il progetto Monete al femminile. L'iconografia monetale dell'Augusta nella prima età imperiale

Il presente lavoro si pone l'obiettivo di fornire una rilettura filologica delle fonti numismatiche sui membri femminili della domus imperiale romana da Livia a Matidia Maggiore, supportata da una schedatura informatizzata del documento monetale. La compilazione è stata condotta tramite lo spoglio dei repertori di maggiore consultazione (RIC, BMCRE, BNCMER, HCC) e ha posto l'attenzione sia sugli elementi iconografici che su quelli epigrafici che vanno a comporre l'aspetto estrinseco della moneta. La scelta di tali elementi nelle emissioni imperiali è l'espressione di un vero e proprio linguaggio dotato di una logica comunicativa ben precisa e finalizzata a garantire la comprensibilità del messaggio. La sua decodifica consente di individuare possibili linee di definizione del ruolo pubblico e politico delle Auguste nel quadro dell'ideologia imperiale. A veicolare questo significato contribuiscono ugualmente gli elementi iconografici, con valore connotativo rispetto al soggetto raffigurato, e quelli epigrafici, con valore esplicativo ai fini della comprensione del dato visivo. La moneta rappresenta dunque un documento complesso, che necessita di una specifica metodologia di indagine volta a interpretarne tutti gli elementi.

La cerchia di Giulio Clovio: gli incontri, i viaggi, le amicizie di un artista europeo

La tesi riguarda il miniatore Giulio Clovio (Grižane, Croazia, 1498 – Roma, 1578), considerandolo come il fulcro di una rete di relazioni tra committenti, artisti e letterati. È divisa in tre parti, seguendo la vita dell’artista: giovinezza (1498-1534), maturità (1534-1561) e vecchiaia (1561-1578). Tra i committenti più significativi: Domenico e Marino Grimani e il cardinale Alessandro Farnese. Tra gli artisti italiani: Giulio Romano, Girolamo dai Libri, Valerio Belli, Sofonisba Anguissola. Tra gli artisti europei: Francisco de Hollanda, Pieter Brueghel il Vecchio, Bartholomeus Sprangher, El Greco e Lampsonio.

Valutazione preoperatoria del rischio chirurgico in pazienti onco-geriatrici (studio PREOP)

La maggior parte dei pazienti che vengono sottoposti a interventi chirurgici per tumori solidi hanno un’età superiore a 70 anni1. Circa il 30% di questi pazienti vengono considerati “fragili”. Questi infatti presentano numerose comorbidità ed hanno un più elevato rischio di sviluppare complicanze postoperatorie con perdita della riserva funzionale residua. Per questo non esistono sistemi semplici di screening che permettano ai medici responsabili del trattamento di identificare questi pazienti con aumentato rischio postoperatorio. Identificare i pazienti a rischio è infatti il primo passo nel processo attraverso il quale è possibile prevenire in necessarie complicanze postoperatorie come delirio, eventi cardiovascolari e perdita della funzionalità complessiva con conseguente perdita di autonomia. Scopo di questo studio è quello di confrontare l’accuratezza nella previsione di mortalità e morbidità a 30 giorni dei tre test preditivi “Groningen Frailty Index” (GFI); “Vulnerable Elders Survey” (VES-13); “timed up and go test” con alcune componenti del Preoperative Assessment of Cancer in the Elderly (PACE). Lo studio verrà effettuato sui pazienti con età maggiore di 70 anni che dovranno essere sottoposti a intervento chirurgico in anestesia generale per la presenza di una neoplasia solida.

La violenza sull'anziano: Aspetti medico-legali di una problematica sommersa

L’abuso dell’anziano è una condizione estremamente diffusa e ha un grande costo umano e finanziario. La dimensione reale del problema del maltrattamento dell’anziano non è stata correttamente definita, in particolare i casi segnalati ufficialmente di abuso sono solo la "punta dell'iceberg". In questi anni il problema è stato riconosciuto a livello internazionale come un fenomeno comune, che viene sottostimato e degno di attenzione da parte della comunità scientifica. In Italia non ci sono molti dati, la prevalenza degli abusi e maltrattamenti può essere circa il 5% e il problema è ampiamente sottovalutato, perché sono scarse le segnalazioni di abusi. Le evidenze disponibili dimostrano che l'abuso sugli anziani in Italia costituisce una questione pubblica, tuttavia, la legislazione e le politiche per affrontare il fenomeno sono scarse, riflettendo la mancanza di una strategia nazionale coerente e globale. Il codice civile italiano non contiene alcun riferimento esplicito a persone anziane, e pochi sono anche gli articoli del codice penale che riguardano le persone anziane. Gli articoli più rilevanti interessate sono le seguenti: art. 572: "Maltrattamenti contro familiari e conviventi" e art. 643: "circonvenzione di persone incapaci". Il presente studio ha lo scopo di analizzare la situazione attuale del fenomeno nel nostro Paese, al fine di valutare la dimensione del problema e le relazioni di abuso e maltrattamenti tra vittime, caregiver e operatori sanitari alle autorità.

Balloon Aortic Valvuloplasty as Bridge-to-Decision in High Risk Patients with Severe Aortic Valve Stenosis

Background. A sizable group of patients with symptomatic aortic stenosis (AS) can undergo neither surgical aortic valve replacement (AVR) nor transcatheter aortic valve implantation (TAVI) because of clinical contraindications. The aim of this study was to assess the potential role of balloon aortic valvuloplasty (BAV) as a “bridge-to-decision” in selected patients with severe AS and potentially reversible contraindications to definitive treatment. Methods. We retrospectively enrolled 645 patients who underwent first BAV at our Institution between July 2007 and December 2012. Of these, the 202 patients (31.2%) who underwent BAV as bridge-to-decision (BTD) requiring clinical re-evaluation represented our study population. BTD patients were further subdivided in 5 groups: low left ventricular ejection fraction; mitral regurgitation grade ≥3; frailty; hemodynamic instability; comorbidity. The main objective of the study was to evaluate how BAV influenced the final treatment strategy in the whole BTD group and in its single specific subgroups. Results. Mean logistic EuroSCORE was 23.5±15.3%, mean age was 81±7 years. Mean transaortic gradient decreased from 47±17 mmHg to 33±14 mmHg. Of the 193 patients with BTD-BAV who received a second heart team evaluation, 72.5% were finally deemed eligible for definitive treatment (25.4%for AVR; 47.2% for TAVI): respectively, 96.7% of patients with left ventricular ejection fraction recovery; 70.5% of patients with mitral regurgitation reduction; 75.7% of patients who underwent BAV in clinical hemodynamic instability; 69.2% of frail patients and 68% of patients who presented relevant comorbidities. 27.5% of the study population was deemed ineligible for definitive treatment and treated with standard therapy/repeated BAV. In-hospital mortality was 4.5%, cerebrovascular accident occurred in 1% and overall vascular complications were 4% (0.5% major; 3.5% minor). Conclusions. Balloon aortic valvuloplasty should be considered as bridge-to-decision in high-risk patients with severe aortic stenosis who cannot be immediate candidates for definitive percutaneous or surgical treatment.