Clofarabine and Treosulfan as Conditioning for Matched Related and Unrelated Hematopoietic Stem Cell Transplantation: Results from the Clo3o Phase II Trial

ABSTRACT Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for patients with hematologic malignancies. The ideal conditioning regimen before allo-HSCT has not been established. We conducted a Phase II study to evaluate the tolerability and efficacy of clofarabine and treosulfan as conditioning regimen before allo-HSCT. The primary objective was to evaluate the cumulative incidence of nonrelapse mortality (NRM) on day +100. Forty-four patients (36 with acute myelogenous leukemia, 5 with acute lymphoblastic leukemia, 3 with myelodysplastic syndromes) were enrolled. The median patient age was 47 years, and the median duration of follow-up was 27 months. The conditioning regimen was based on clofarabine 40 mg/m2 (days -6 to -2) and treosulfan 14 g/m2 (days -6 to -4). Allogeneic hematopoietic stem cells were derived from a sibling (n = 22) or a well-matched unrelated donor (n = 22). Graft-versus-host disease (GVHD) prophylaxis consisted of antithymocyte globulin, rituximab, cyclosporine, and a short-course of methotrexate. The regimen allowed for rapid engraftment and a 100-day NRM of 18%, due mainly to bacterial infections. The incidences of grade II-IV acute GVHD and chronic GVHD were 16% and 19%, respectively. The rates of overall survival (OS), progression-free survival, and relapse at 2 years were 51%, 31%, and 50%, respectively. Significantly different outcomes were observed between patients with low-intermediate and patients with high-very high Disease Risk Index (DRI) scores (1-year OS, 78% and 24%, respectively). Our findings show that the use of treosulfan and clofarabine as a conditioning regimen for allo-HSCT is feasible, with a 78% 1-year OS in patients with a low-intermediate DRI score. However, 1-year NRM was 18%, and despite the intensified conditioning regimen, relapse incidence remains a major issue in patients with poor prognostic risk factors

Progetto di Ricerca LARS (Laboratorio di Ricerca Infermieristica Agenzia Regionale alla Sanità, Friuli Venezia Giulia). Studio osservazionale sugli esiti dei modelli organizzativi assistenziali delle medicine, su infermieri, su pazienti ed organizzazione.

No large scale studies have been conducted in Italy to assess factors that influence hospital nurses’ satisfaction. Aims. To explore the relationship between participative organizative models and outcomes on nurses (work satisfaction, burnout, intention to stay), patients (satisfaction with quality of care) and organization (nurses turnover). Materials and methods. This multicentre regional study involves 20 acute medical wards and more than 500 nurses. Data on the organizative model adopted in the ward will be collected with an ad hoc questionnaire with scores from 7 (scarcelimited involvement of nurses in decision making) to 35 (nurses take decisions on the management of the ward). Nurses satisfaction with their work is measured with the Nursing Work Index Revised; burnout with the Maslack Burnout Inventory; patients satisfaction with the Experiences of Nursing Care Scale Newcastle Satisfaction with Nursing Scale. The outcomes considered for the organization will be turnover, absences from work, injuries. Resultats. The study is ongoing. The association of each outcome to the organizzative model will be explored. Multivariate regression model will be adjusted for casemix index of the previuos year. T test and chi square tests will be used and a p value of 0.05 will be considered significant

Genome-wide association study of the age of onset of childhood asthma

BACKGROUND: Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children. OBJECTIVE: To identify genetic variants associated with earlier onset of childhood asthma. METHODS: We conducted the first genome-wide association study (GWAS) of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP), and used three independent cohorts from North America, Costa Rica, and Sweden for replication. RESULTS: Two SNPs were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: : rs9815663 (Fisher’s P value=2.31 × 10−8) and rs7927044 (P=6.54 × 10−9). Of these two SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 × 10−7 < P < 8.22 ×10−6). Having ≥1 risk allele of the two SNPs of interest (rs9815663 and rs7927044) was associated with lower lung function and higher asthma medication use during 4 years of follow-up in CAMP. CONCLUSIONS: We have identified two SNPs associated with earlier onset of childhood asthma in four independent cohorts

Preliminary report of the First phase of the Bergamo 2.(035) Project

Il programma di ricerca Bergamo 2.(035) – "Un nuovo concetto urbano per un nuovo mondo " - è motivato dalla necessità di concepire una vision comparative, articolata, e di lungo termine dei più rilevanti sviluppi futuri degli ambienti urbani e dei loro territori. Questa visione costituirà l’innesco di una discussione volta a definire delle linee strategiche per gestire i cambiamenti futuri e identificare le leve decisionali per affrontare le criticità più importanti. Bergamo 2.(035) è un programma di ricerca che fornisce terreno comune per una serie di progetti che, pur orientati verso una specifica applicazione o un problema, possono trarre vantaggio dalla condivisione di una visione comune. La ricerca ha individuato quattro principali tendenze relative sviluppo della città nel lungo periodo: • La Comunità della Conoscenza. Un'idea di città dove una nuova società impara come usare al meglio le risorse disponibili per soddisfare le proprie esigenze e risolvere i propri problemi. • La Comunità dei “Prosumatori”. Due fenomeni hanno avuto luogo negli ultimi anni, e potrebbero diventare una tendenza importante in futuro. Da un lato , gli individui stanno diventando consapevoli che il loro ruolo non è semplicemente di agire come consumatori, ma anche di essere produttori attivi, generando non solo ciò di cui hanno bisogno per se stessi, ma anche di presidiare la distribuzione e la vendita verso la comunità. Dall'altro , le imprese non sono semplicemente dei produttori, ma anche utilizzano e acquistano beni per la gestione delle loro attività sia attraverso collaborazioni verticali e orizzontali. • La Comunità Mobile Multilivello. Mobilità multilivello si riferisce alla tendenza diffusa e crescente di individui / informazioni / prodotti / idee di muoversi in aree geografiche a vari livelli ( locale, regionale , internazionale , ...) e in spazi collegati, con un basso impatto ambientale, e concentrandosi su aspetti sociali. • Il Ruolo Sociale delle Imprese. Immaginiamo una città in cui le imprese operano con attenzione verso questioni sociali ampie e complesse, come il benessere della comunità, la giustizia sociale, la povertà ei diritti umani . Queste tendenze saranno contestualizzate con riferimento alle città del futuro e in particolare al futuro di Bergamo. L'approccio che cerchiamo si basa sulla creazione di "Living Labs" tematici in cui saranno attivati gruppi di stakeholder per definire la “visione Bergamo 2.(035)” all’interno di un vero contesto urbano, coinvolto in un processo di creazione strutturato e sistematico . Due principali risultati sono attesi : 1. la creazione di gruppi di discussione sarà un risultato in sé, dal momento che ci aspettiamo che questi gruppi diventino i semi del cambiamento e contribuiscono ad una crescente consapevolezza dei temi chiave per la città di domani. 2. questi gruppi definiranno nuove idee e concetti da considerare nelle fasi iniziali del processo di cambiamento.The Bergamo 2.(035) – “A new urban concept for a new world” – research program is motivated by the need to conceive an articulated, long-term and comparative vision of the most relevant future developments of an urban environment and its territory. This vision would trigger the discussion and the definition of the strategic lines for mastering their trajectories and identifying the decision-making leverages to tackle the most prominent critical issues. Bergamo 2.(035) is a research program providing the foundation and common ground of a number of projects which, though oriented on a specific application area or issue, would benefit from the sharing of a common vision. The research has identified four main relevant trends in the development of cities in the long term: • The Knowledge Intensive Community. An idea of city where a new society learns how to better use the available resources to satisfy its needs and solve its problems. • The Collaborative Prosumption Community. Two phenomena took place in the last years and might become a leading trend in the future. On one hand, people are becoming aware that their role is not simply to act as consumers, but also to be active producers, generating not only what they need for themselves, but also distributing and selling to the community. On the other, companies are not simply producers but they also use and purchase goods for managing their activities through both vertical and horizontal collaborations: these activities are more and more developing towards a sustainable perspective. • The Multiscale Mobile Community. Multiscale sustainable mobility refers to the widespread and growing behavioral tendency of individuals / information / goods / ideas to move in geographic areas at different levels (local, regional, international, …) and in connected spaces, with a low environmental impact, and focusing on a social point of view. • The Social role of Enterprises. We fancy of a city where companies operate with regard to broad and complex societal issues, such as community welfare, social justice, poverty and human rights. To design our specific roadmap, we will try contextualize these trends in the future of the city and specifically in the future of Bergamo. The approach we seek is based on the establishment of thematic “living labs” where target groups of stakeholders will be stimulated to deploy the Bergamo 2.(035) vision into the real urban context, involved in a structured and systematic creation process. Two main results are expected: 1. the creation of the discussion groups is going to be a result in itself, since we expect these groups to become the initiating seeds of change and growing awareness of key topics for the city of tomorrow. 2. these groups will establish new ideas and concepts to be considered the initial steps of the roadmap