Circular economy in the water and wastewater sector: Tariff impact and financial performance of SMARTechs

This paper proposes a financial evaluation of the investment in SMARTechs in wastewater companies. SMAR Techs are innovative technologies that enable companies to work toward the circular economy approach, thanks to allowing the development of by-products from wastewater. A simulation of the financial impact of the SMARTech introduction was conducted based on the Italian tariff system. It is performed assuming two different scenarios. These relate to a market’s presence (or absence) for the by-products resulting from the application of SMARTechs. The results show that investing in these technologies provides both financial and environmental benefits

Biorefinery Gets Hot: Thermophilic Enzymes and Microorganisms for Second-Generation Bioethanol Production

To mitigate the current global energy and the environmental crisis, biofuels such as bioethanol have progressively gained attention from both scientific and industrial perspectives. However, at present, commercialized bioethanol is mainly derived from edible crops, thus raising serious concerns given its competition with feed production. For this reason, lignocellulosic biomasses (LCBs) have been recognized as important alternatives for bioethanol production. Because LCBs supply is sustainable, abundant, widespread, and cheap, LCBs-derived bioethanol currently represents one of the most viable solutions to meet the global demand for liquid fuel. However, the cost-effective conversion of LCBs into ethanol remains a challenge and its implementation has been hampered by several bottlenecks that must still be tackled. Among other factors related to the challenging and variable nature of LCBs, we highlight: (i) energy-demanding pretreatments, (ii) expensive hydrolytic enzyme blends, and (iii) the need for microorganisms that can ferment mixed sugars. In this regard, thermophiles represent valuable tools to overcome some of these limitations. Thus, the aim of this review is to provide an overview of the state-of-the-art technologies involved, such as the use of thermophilic enzymes and microorganisms in industrial-relevant conditions, and to propose possible means to implement thermophiles into second-generation ethanol biorefineries that are already in operation

Microalgae Cultivation on Anaerobic Digestate of Municipal Wastewater, Sewage Sludge and Agro-Waste

Microalgae are fast-growing photosynthetic organisms which have the potential to be exploited as an alternative source of liquid fuels to meet growing global energy demand. The cultivation of microalgae, however, still needs to be improved in order to reduce the cost of the biomass produced. Among the major costs encountered for algal cultivation are the costs for nutrients such as CO2, nitrogen and phosphorous. In this work, therefore, different microalgal strains were cultivated using as nutrient sources three different anaerobic digestates deriving from municipal wastewater, sewage sludge or agro-waste treatment plants. In particular, anaerobic digestates deriving from agro-waste or sewage sludge treatment induced a more than 300% increase in lipid production per volume in Chlorella vulgaris cultures grown in a closed photobioreactor, and a strong increase in carotenoid accumulation in different microalgae species. Conversely, a digestate originating from a pilot scale anaerobic upflow sludge blanket (UASB) was used to increase biomass production when added to an artificial nutrient-supplemented medium. The results herein demonstrate the possibility of improving biomass accumulation or lipid production using different anaerobic digestates. \ua9 2016 by the authors; licensee MDPI, Basel, Switzerland

Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n= 95) or nilotinib (n= 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation

INCB84344-201: Ponatinib and steroids in frontline therapy for unfit patients with Ph+ acute lymphoblastic leukemia

Tyrosine kinase inhibitors have improved survival for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, prognosis for old or unfit patients remains poor. In the INCB84344-201 (formerly GIMEMA LAL 1811) prospective, multicenter, phase 2 trial, we tested the efficacy and safety of ponatinib plus prednisone in newly diagnosed patients with Ph+ ALL 6560 years, or unfit for intensive chemotherapy and stem cell transplantation. Forty-four patients received oral ponatinib 45 mg/d for 48 weeks (core phase), with prednisone tapered to 60 mg/m2/d from days-14-29. Prophylactic intrathecal chemotherapy was administered monthly. Median age was 66.5 years (range, 26-85). The primary endpoint (complete hematologic response [CHR] at 24 weeks) was reached in 38/44 patients (86.4%); complete molecular response (CMR) in 18/44 patients (40.9%) at 24 weeks. 61.4% of patients completed the core phase. As of 24 April 2020, median event-free survival was 14.31 months (95% CI 9.30-22.31). Median overall survival and duration of CHR were not reached; median duration of CMR was 11.6 months. Most common treatment-emergent adverse events (TEAEs) were rash (36.4%), asthenia (22.7%), alanine transaminase increase (15.9%), erythema (15.9%), and \u3b3-glutamyltransferase increase (15.9%). Cardiac and vascular TEAEs occurred in 29.5% (grade 653, 18.2%) and 27.3% (grade 653, 15.9%), respectively. Dose reductions, interruptions, and discontinuations due to TEAEs occurred in 43.2%, 43.2%, and 27.3% of patients, respectively; 5 patients had fatal TEAEs. Ponatinib and prednisone showed efficacy in unfit patients with Ph+ ALL; however, a lower ponatinib dose may be more appropriate in this population. This trial was registered at www.clinicaltrials.gov as #NCT01641107

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Relevance of antiphospholipid antibody profile in the clinical outcome of ITP: a single-centre study

OBJECTIVES: The relevance of detecting antibodies against anticardiolipin, \u3b22-glycoprotein I (\u3b22gpI) or lupus anticoagulant (LA), collectively called antiphospholipid autoantibodies (APA), in subjects with immune thrombocytopenia (ITP) is still a debated issue. In particular, whether APA profile may affect the clinical course of ITP is unknown. METHODS: In this study, we report our experience in a cohort of ITP patients with APA with specific interest to the relevance of different antiphospholipid antibody profiles in clinical outcome and response to treatment. RESULTS: Thirty-seven out of 159 patients (23.2%) fulfilling ITP criteria had a platelet count 6450\u2009 7\u2009109/L and tested positive at APA at ITP onset. Twenty-three (62.1%) patients received at least one line of treatment for ITP. Fourteen subjects (37.8%) showing triple positivity for APA showed a significantly lower median platelet count compared to other APA patients (p\u2009=\u2009.006). Among these ITP subjects with triple positivity, 85.7% needed a treatment because of low platelet count compared to 47.8% ITP patients with non-triple-positive APA (p\u2009=\u2009.0094). ITP/APA subjects who received immunosuppressors had a higher rate of thrombosis (p\u2009=\u2009.024) as well as thrombosis developed in subjects who were on steroid therapy at a significantly higher dosage than subjects who did not develop thrombotic episodes (p\u2009<\u2009.001). When considering treatment, CR and SR rate were significantly higher in ITP/triple-positive patients compared to non-triple-positive subjects (p\u2009=\u2009.021 and p\u2009=\u2009.005). CONCLUSIONS: The profile of APA may affect the outcome of patients with ITP