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BACKGROUND. Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive. METHODS. We conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population. RESULTS. Between April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087). CONCLUSION. CP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant. TRIAL REGISTRATION. Clinicaltrials.gov, NCT04345523. FUNDING. Government of Spain, Instituto de Salud Carlos III., Introduction The pressing need for treatments for the COVID-19 pandemic obliged the medical community and authorities to embrace the use of convalescent plasma (CP) as a potentially effective and easily [...]

Ethanol to n‐butanol conversion is a process that can increase the carbon number of alcohols by coupling. There is increasing interest in the mechanisms for n‐butanol production in a simple step through the effective use of bifunctional acid–base catalysts. In this context, commercial hydroxyapatite (HAP) and two synthetized model supported catalysts, Ca/Al2O3 and Ca‐P/Al2O3, were used in bioethanol condensation. Characterization and acid–base sites were considered, and Fourier‐transform infrared (FTIR) spectroscopy and diffuse reflectance infrared Fourier‐transform spectroscopy–mass spectrometry (DRIFT‐MS) reactivity tests were performed in situ, as a first approximation to design a sustainable catalytic process rationally, and with the aim of understanding the process at the catalytic surface. The results indicated that the reactions occur at a large range of temperatures (200–450 °C). Hydroxyapatite and Ca/Al2O3 have similar basic sites (low and medium) and Ca‐P/Al2O3 presented the strongest Brönsted and Lewis combined acid sites. Three major reactions were identified: non‐oxidative dehydrogenation, aldol condensation, and intermolecular reduction, associated with the basic‐acid sites Ca‐O‐Ca/Ca‐O‐P/Ca‐O‐Al. Side reactions also occur involving different acid sites related to Lewis alumina centers favoring ethylene or diethyl‐ether production. © 2020 Society of Industrial Chemistry and John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

The use of daratumumab in combination with established regimens for the treatment of newly diagnosed multiple myeloma has recently been authorized by the European Medicines Agency based on results from three separate phase III randomized, active controlled, open‐label studies that have confirmed enhanced efficacy and tolerability in both transplant‐ineligible (MMY3008 and MMY3007) and transplant‐eligible (MMY3006) patients, without compromising transplant ability. Trial MMY3008 showed an improvement in progression‐free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone; the median PFS had not been reached in the daratumumab arm and was 31.9 months in the control arm (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43–0.73; p <.0001). Trial MMY3007 showed an improvement in PFS when daratumumab was added to bortezomib, melphalan, and prednisone compared with bortezomib, melphalan, and prednisone; PFS had not been reached in the daratumumab arm and was 18.1 months in the control arm (HR, 0.5; 95% CI, 0.38–0.65; p <.0001). In trial MMY3006, daratumumab added to bortezomib, thalidomide, and dexamethasone was compared with bortezomib, thalidomide, and dexamethasone as induction and consolidation treatment prior to autologous stem cell transplant. The stringent complete response rate at day 100 after transplant in the daratumumab group was 29% compared with 20% in the control group (odds ratio, 1.60; 1.21–2.12 95% CI; p =.0010). Overall adverse events were manageable, with an increased rate of neutropenia and infections in the daratumumab arms. Regulatory assessment of efficacy and safety results from trials MMY3006, MMY3007, and MMY3008 confirmed a positive benefit‐risk ratio leading to an approval of the extensions of indication. Implications for Practice: A set of extensions of indication was recently approved for daratumumab (Darzalex) in the setting of newly diagnosed multiple myeloma in combination with established regimens. Results of the MMY3006, MMY3007, and MMY3008 trials have shown enhanced efficacy and a favorable side effect profile of several daratumumab‐based combinations in patients both ineligible and eligible for transplant, without compromising transplant ability. The combinations of daratumumab with either lenalidomide and low‐dose dexamethasone or bortezomib, melphalan, and prednisone were approved for transplant‐ineligible patients. The combination of daratumumab with bortezomib, thalidomide, and dexamethasone was approved for transplant‐eligible patients. These combinations are expected to improve the survival outlook for patients with multiple myeloma, without an unacceptable risk of increase in adverse events, and updated information on progression‐free survival and overall survival is expected from the above trials. This report outlines the regulatory steps taken for the approval of extensions of indication of daratumumab for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. The pivotal clinical data submitted and EMA review of the benefit‐risk assessment are summarized. [ABSTRACT FROM AUTHOR]

The long-term repopulating capacity of mobilized peripheral blood (MPB) CD34+ cells can be abrogated during ex vivo expansion due to cell-cycle related changes. In this study, we traced cell cycle kinetic and quiescent status of CD34+ cells during ex vivo expansion with exogenous cytokines. The addition of interleukin-3 (IL-3) and interleukin-6 (IL-6) to early acting cytokines resulted in a significantly lower percentage of cells remaining undivided or in quiescent G0 phase when compared to the use of early acting cytokines alone. We conclude that ex vivo expansion of MPB CD34+ cells with a cocktail of five cytokines yields a highly cycling offspring, which could impair long-term repopulating capacity.