Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

The impact of digital supply chain on operational a case study on cruise sector

In the last decade, the cruise sector operates in a dynamic and highly competitive environment requiring more flexible and resilient organizations. With the Fourth Industrial Revolution, many companies in the cruise sector recognize the importance of innovative digital technologies for their business. Digital Supply Chain describes an organizational change process leading to the application and implementation of digital technology in order to achieve effective and efficient flows of products, services and information, to provide maximum value to the customer. This study explores the potential of cloud-based B2B integration brokerage solution in order to improve efficiency and collaboration in extended enterprise processes, by enabling a multiformat and multi-protocol data exchange management. The paper uses primary data obtained through in-depth semi-structured interview with an executive staff from a cruise company operating in the Mediterranean region. Research findings unveil the strategy of a cruise company’s supply chain and the operational performance with the use of digital technologies

GenOA week 2021

La GenOA week è una settimana di iniziative per riflettere sulla comunicazione scientifica e sulle sfide lanciate dalla Scienza aperta (Open Science) per rendere l'accesso alla Conoscenza aperta (Open Knowledge) equo per tutti. Si svolge nell'ambito della International Open Access week. +info Qui sono raccolti gli interventi* di tutte le sessioni della GenOA week 2021, organizzata da Università di Genova, IIT (Istituto Italiano di Tecnologia), INFN (Istituto Nazionale di Fisica Nucleare), CNR (Consiglio Nazionale delle Ricerche) e Consortium GARR sul tema: It matters how we Open Knowledge: building structural equity: * solo degli autori che hanno concesso l'autorizzazione. Per l'intervento di Stefano Bianco: openaccessrepository.it lunedì 25 ottobre 2021 Open Science e Horizon Europe: La Scienza Aperta, una sfida per l'Europa... L'Open Science nei progetti europei Open Science e open data 1.: Rendere open i dati della ricerca: dalla teoria alla pratica del repository UniGe Open Science e open access 1.: Introduzione ai temi Open Access e Open Data: la loro importanza dal punto di vista del ricercatore Open Science e biblioteche accademiche: Biblioteche accademiche e Open Science: nuove competenze o nuovi servizi? martedì 26 ottobre 2021 Open Science e open access 2.: Implementazione pratica dell'Open Access: dal rapporto con la valutazione alle politiche e ai progetti in corso Open Science e open data 2.: Il Geoportale SiT del Comune di Genova: quando gli open data generano nuova conoscenza Open Science e comunicazione scientifica: Le sfide dell'Open Access hanno modificato la comunicazione scientifica? Editori e Accademia a confronto mercoledì 27 ottobre 2021 Open Science e valutazione della ricerca: Nuove prospettive di valutazione della qualità della ricerca grazie alla Scienza Aperta: esperienza locale, nazionale ed europea Open Science e infrastrutture per la ricerca: Panoramica di infrastrutture e strategie IT locali, nazionali ed europee giovedì 28 ottobre 2021 Open Science e proprietà intellettuale: Open Science e Proprietà Intellettuale: una nuova opportunità per l'accademia e il mondo dell'impresa. Open Science e terza missione: Dalla citizen science alle licenze aperte per la digitalizzazione dei beni culturali: l'Open Science è terza missione? Open Science e didattica: Le Open Educational Resources e la didattica aperta: si può fare! Dal progetto EDUOpen ad un esempio di MooC venerdì 29 ottobre 2021 Open Science e capacity building: Servono strumenti per l'Open Science. Una riflessione sulla data stewardship e sulle nuove strutture di supporto GenOA week 2021: tavola rotonda conclusiva: Open Science è condivisione e collaborazione. La GenOA week 2021 termina con una conversazione sui temi emersi durante la settimana Per il programma completo della GenOA week 2021: +agenda Per conoscere tutti i relatori della GenOA week 2021: +persone Per rivedere l'intera GenOA week 2021: +playlis

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| &lt; 0.8) in the transverse momentum range 1 &lt; pt &lt; 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Combination of bendamustine and rituximab as front-line therapy for patients with chronic lymphocytic leukaemia: Multicenter, retrospective clinical practice experience with 279 cases outside of controlled clinical trials

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008-2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43-86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region (IGHV) unmutated status, del17p and BR dose intensity <80% were independently associated with shorter PFS. Grade III or IV neutropenia, thrombocytopenia, and anaemia were observed in 25.9%, 15.4%, and 15.1% of patients, respectively. Twenty-four patients (8.6%) had severe infections. BR is also an effective and safe regimen for untreated CLL patients, outside of controlled clinical trials