From soil remediation to biofuel. Process simulation of bioethanol production from Arundo donax

A range of energy crops can be grown on marginal land (i.e. land that is not suitable for food crop production or contaminated site) to provide feedstocks for bioenergy, non-food products and biofuels. The food versus fuel debate had a significant negative impact in Europe on first generation biofuels production from food crops (i.e. wheat, rapeseed, etc). A new approach involving the use of marginal land for the production of lignocellulosic species for the production of bioethanol is now pursued in Italy and in many other countries, where the demand for high quality water resources, arable land, food and fossil fuels is rapidly growing. With an emerging “feed versus fuel debate” there is a pressing need to find options for the use of marginal lands and wastewaters or saline ground waters to produce second generation biofuel or bio paper crops. Arundo donax was selected as a potential crop for use in these areas, since it produces more cellulosic biomass and sequesters more contaminants, using less land and pesticides than any other alternative crops reported in the literature. The objective of this paper is to evaluate economically a simplified process for the production of second generation bioethanol from A. donax. Process calculations and economic analyses are performed using the software SuperPro Designer®

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved a superior clinical benefit over Pd with a manageable toxicity profile, leading to its approval in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI). We report here a real-world experience of 200 RRMMs treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was 2, with 51% of cases undergoing autologous stem cell transplant (ASCT) and 73% exposed to daratumumab. After a median follow-up of 9 months, 126 patients stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate (ORR) was 55.4%, in line with the pivotal trial results. Regarding adverse events, our cohort experienced a toxicity profile similar to the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival (PFS) was 7 months, shorter than that observed in the ELOQUENT-3, probably due to the different clinical characteristics of the two cohorts. Interestingly, the ISS stage III (HR:2.55) was associated with worse PFS. Finally, our series's median overall survival (OS) was shorter than that observed in the ELOQUENT-3 trial (17.5 versus 29.8 months). In conclusion, our real-world study confirms EloPd as a safe and possible therapeutic choice for RRMM who received at least two prior therapies, including lenalidomide and a PI

Environmental and safety aspects of integrated biorefineries (IBR) in Italy

Among the major new technologies that have appeared since the 1970s, biotechnology has perhaps attracted the most attention. Biotechnology has proved capable of generating enormous wealth and of influencing every significant sector of the economy. Biotechnology has already substantially affected healthcare, production and processing of food, environmental protection and production of materials and chemicals. The achievements and future prospects are in sustainable production of goods and services, especially those that are derived at present mostly from the traditional chemical industry. In fact, the international scientific community, under the pressing demand for a green chemistry, is launching the input about the creation of a new industrial concept based on innovative industrial biotechnological approaches. To this aim, the concept of Integrated BioRefinery (IBR), defined as a scientific and technical platform through which the biomass, designed as waste products, are turned into fuels, energy and chemicals, such as basic chemicals, fine chemicals and specialties of biopolymers and bioplastics, through technologies and processes that produce minimal waste and have limited impact on the environment are becoming increasingly popular also in the Italian territory. An IBR is a structure (or a network of systems) that integrates both biomass conversion processes and equipment to produce biofuels, energy and/or chemicals. In this perspective it is desirable the creation of an industrial concept ''bio-cluster", in which the exchange of material (flows) between different companies are promoted to transform a residue downstream of a plant in an up-stream of raw material for another industry. Although the environmental and health risks posed by these new realities are expected to be lower than with traditional chemical and petrochemical plants, there is still a lack of information about safety aspects of these new generation plants. Existing lessons suggest that the development of effective, responsive and responsible safety standard can improve the trust of the public and affected industries in biotechnologies. The fist step should be replacing the current retrospective risk-based paradigm for governing biotechnology with a proactive safety paradigm. Safety principles, applied early in the design process, can benefit multiple stakeholders concerned with safety. The aim of the present work is providing a tool for transparent development of proactive safety standards and it is a part of the project funded by the National Centre for Disease Prevention and Control (CCM) of the Italian Ministry of Health. This paper presents an analysis of the unit operations and equipment of the main industrial biorefineries and some of process and occupational hazards are preliminarly discussed. Basing on a preliminary analysis of IBR installations, a substantial reduction of the environmental impact and an increase of both occupational and process safety is expected with respect to the most common chemical plants. The use of biological agents has been identified as the main hazardous aspect involved in those processes. Copyright © 2013, AIDIC Servizi S.r.l

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials

: In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved a superior clinical benefit over Pd with a manageable toxicity profile, leading to its approval in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI). We report here a real-world experience of 200 RRMMs treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was 2, with 51% of cases undergoing autologous stem cell transplant (ASCT) and 73% exposed to daratumumab. After a median follow-up of 9 months, 126 patients stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate (ORR) was 55.4%, in line with the pivotal trial results. Regarding adverse events, our cohort experienced a toxicity profile similar to the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival (PFS) was 7 months, shorter than that observed in the ELOQUENT-3, probably due to the different clinical characteristics of the two cohorts. Interestingly, the ISS stage III (HR:2.55) was associated with worse PFS. Finally, our series's median overall survival (OS) was shorter than that observed in the ELOQUENT-3 trial (17.5 versus 29.8 months). In conclusion, our real-world study confirms EloPd as a safe and possible therapeutic choice for RRMM who received at least two prior therapies, including lenalidomide and a PI

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended follow‐up of a multicenter, retrospective real‐world experience with 321 cases outside of controlled clinical trials

The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab