Outcomes with allogeneic stem cell transplant using cryopreserved versus fresh hematopoietic progenitor cell products.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (alloHSCT) is a mainstay of treatment for hematologic malignancies such as acute leukemias and aggressive lymphomas. Historically, fresh hematopoietic progenitor cell (HPC) products have been preferred to cryopreserved products (cryo-HPC) due to concerns of loss of stem cell viability and number with the cryopreservation procedure. OBJECTIVE: We aimed to analyze the outcomes of patients who received cryo-HPCs during the COVID-19 pandemic and compare this against historical cohorts that received fresh HPC. STUDY DESIGN: A retrospective chart review was conducted on all adult patients who received a peripheral blood alloHSCT in British Columbia, Canada between June 2017 and November 2021. Baseline characteristics, Kaplan-Meier (KM) overall survival (OS), engraftment, and incidences of acute and chronic graft versus host disease were compared between patients who received cryo-HPCs and fresh HPCs. Univariable analysis followed by multivariable analysis was performed using a backward stepwise selection procedure to generate predictors of OS, cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and primary and secondary graft failure. RESULTS: Three hundred eighty-three patients were included in the analysis, with cryo-HPC representing 40%. Median viability was higher in the fresh-HPC group at 99.2% (IQR 98.3-99.5) versus cryo-HPCs at 97.0% (96.0, 98.6) (P < 0.01). The 12-month actuarial survivals were 77% in the fresh HPC and 75% in the cryo-HPC groups (P = 0.21). There were no differences between cryo-HPCs and fresh HPCs on univariable analysis of OS, CIR, or NRM. There was a shorter median time to platelet engraftment in patients receiving fresh HPC at 17 days (IQR 16, 20) versus cryo-HPC at 21 days (IQR 18, 29), P < 0.001. There was a shorter median time to neutrophil engraftment in the fresh HPC group at 17 days (IQR 14, 20) versus 20 days (17, 23), P < 0.001. Cryo-HPC accounted for 5 out of 6 cases of primary graft failure (P = 0.04), and 3 out of five cases of secondary graft failure (P = 0.39). There were no significant differences in acute GVHD between the fresh HPC and cryo-HPC groups (P = 0.34). The incidence of moderate or severe chronic GVHD was 32% in the fresh-HPC group and 17% in the cryo-HPC group (P < 0.001). In multivariable analysis, cryopreservation did not emerge as an independent predictor of OS, CIR, NRM, primary GF or secondary GF. However, viability <90% on arrival at our center was a significant predictor of OS (HR 5.3, 2.3-12.3, P < 0.01), primary graft failure (OR 36.3, 5.4-210.2, P < 0.01), and secondary graft failure (OR 18.4, 1.7-121.1, P < 0.01). CONCLUSIONS: Patients who received cryo-HPCs had similar OS and relapse rates to those who received fresh-HPCs but typically took 2-3 days longer to achieve engraftment of platelets or neutrophils and were associated increased primary graft failure. However, after accounting for multiple variables, cryopreservation was no longer a significant predictor of survival or engraftment while viability <90% emerged as an important predictor of OS, primary graft failure, and secondary graft failure. If confirmed, this suggests that viability on arrival at the infusion center may be a good quality control indicator used to identify HPC products that may warrant recollection if the risk of graft failure is sufficiently increased.

Anion-Exchange Membrane Water Electrolyzers.

This Review provides an overview of the emerging concepts of catalysts, membranes, and membrane electrode assemblies (MEAs) for water electrolyzers with anion-exchange membranes (AEMs), also known as zero-gap alkaline water electrolyzers. Much of the recent progress is due to improvements in materials chemistry, MEA designs, and optimized operation conditions. Research on anion-exchange polymers (AEPs) has focused on the cationic head/backbone/side-chain structures and key properties such as ionic conductivity and alkaline stability. Several approaches, such as cross-linking, microphase, and organic/inorganic composites, have been proposed to improve the anion-exchange performance and the chemical and mechanical stability of AEMs. Numerous AEMs now exceed values of 0.1 S/cm (at 60-80 °C), although the stability specifically at temperatures exceeding 60 °C needs further enhancement. The oxygen evolution reaction (OER) is still a limiting factor. An analysis of thin-layer OER data suggests that NiFe-type catalysts have the highest activity. There is debate on the active-site mechanism of the NiFe catalysts, and their long-term stability needs to be understood. Addition of Co to NiFe increases the conductivity of these catalysts. The same analysis for the hydrogen evolution reaction (HER) shows carbon-supported Pt to be dominating, although PtNi alloys and clusters of Ni(OH)2 on Pt show competitive activities. Recent advances in forming and embedding well-dispersed Ru nanoparticles on functionalized high-surface-area carbon supports show promising HER activities. However, the stability of these catalysts under actual AEMWE operating conditions needs to be proven. The field is advancing rapidly but could benefit through the adaptation of new in situ techniques, standardized evaluation protocols for AEMWE conditions, and innovative catalyst-structure designs. Nevertheless, single AEM water electrolyzer cells have been operated for several thousand hours at temperatures and current densities as high as 60 °C and 1 A/cm2, respectively.

Incidence and socioeconomic factors in older adults with acute myeloid leukaemia: Real-world outcomes from a population-based cohort.

OBJECTIVES: Acute myeloid leukaemia (AML) is a disease of older adults, who are vulnerable to socio-economic factors. We determined AML incidence in older adults and the impact of socio-economic factors on outcomes. METHODS: We included 3024 AML patients (1996-2016) identified from a population-based registry. RESULTS: AML incidence in patients ≥60 years increased from 11.01 (2001-2005) to 12.76 (2011-2016) per 100 000 population. Among 879 patients ≥60 years in recent eras (2010-2016), rural residents (<100 000 population) were less likely to be assessed by a leukaemia specialist (39% rural, 47% urban, p = .032); no difference was seen for lower (43%, quintile 1-3) vs. higher (47%, quintile 4-5) incomes (p = .235). Similar numbers received induction chemotherapy between residence (16% rural, 18% urban, p = .578) and incomes (17% lower, 17% high, p = 1.0). Differences between incomes were seen for hypomethylating agent treatment (14% low, 20% high, p = .041); this was not seen for residence (13% rural, 18% urban, p = .092). Among non-adverse karyotype patients ≥70 years, 2-year overall survival was worse for rural (5% rural, 12% urban, p = .006) and lower income (6% low, 15% high, p = .017) patients. CONCLUSIONS: AML incidence in older adults is increasing, and outcomes are worse for older rural and low-income residents; these patients face treatment barriers.

Acetaldehyde as an Intermediate in the Electroreduction of Carbon Monoxide to Ethanol on Oxide-Derived Copper.

Oxide-derived copper (OD-Cu) electrodes exhibit unprecedented CO reduction performance towards liquid fuels, producing ethanol and acetate with >50% Faradaic efficiency at -0.3 V (vs. RHE). By using static headspace-gas chromatography for liquid phase analysis, we identify acetaldehyde as a minor product and key intermediate in the electroreduction of CO to ethanol on OD-Cu electrodes. Acetaldehyde is produced with a Faradaic efficiency of ≈5% at -0.33 V (vs. RHE). We show that acetaldehyde forms at low steady-state concentrations, and that free acetaldehyde is difficult to detect in alkaline solutions using NMR spectroscopy, requiring alternative methods for detection and quantification. Our results represent an important step towards understanding the CO reduction mechanism on OD-Cu electrodes.

Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.

INTRODUCTION: Hypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute myeloid leukemia (AML) patients. MATERIALS AND METHODS: The Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases were independently searched by two investigators to identify relevant studies published inception to 18 November 2021. These trials compared HMA maintenance to observation following allo-SCT for AML or myelodysplastic syndrome. RESULTS: The meta-analysis eligibility criteria were fulfilled by 14 studies. The overall survival and relapse-free survival of the HMA maintenance group were superior to the observation group, with a pooled risk ratio (RR) of 1.38 and 1.46, respectively. Moreover, the cumulative incidence of relapse was significantly lower in those who received HMAs. The HMA group also had lower non-relapse mortality compared with the observation group. Overall, the incidences of grades III-IV acute graft-vs.-host disease (GVHD) and chronic GVHD did not differ in both groups. However, when looking specifically at those receiving decitabine maintenance, the rate of chronic GVHD seemed to be lower compared with observation alone. CONCLUSIONS: The current systematic review and meta-analysis illustrated that AML and MDS patients receiving HMA maintenance after allo-SCT had better outcomes in regards to OS, RFS, NRM, CIR as well as a reduced incidence of chronic GVHD.

Plasma B-esterase activities in European raptors.

B-esterases are serine hydrolases composed of cholinesterases, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and carboxylesterase (CbE). These esterases, found in blood plasma, are inhibited by organophosphorus (OP) and carbamate (CB) insecticides and can be used as nondestructive biomarkers of exposure to anticholinesterase insecticides. Furthermore, B-esterases are involved in detoxification of these insecticides. In order to establish the level of these enzymes and to have reference values for their normal activities, total plasma cholinesterase (ChE), AChE and BChE activities, and plasma CbE activity were determined in 729 European raptors representing 20 species, four families, and two orders. The diurnal families of the Falconiforme order were represented by Accipitridae and Falconidae and the nocturnal families of the Strigiforme order by Tytonidae and Strigidae. Intraspecies differences in cholinesterase activities according to sex and/or age were investigated in buzzards (Buteo buteo), sparrowhawks (Accipiter nisus), kestrels (Falco tinnunculus), barn owls (Tyto alba), and tawny owls (Strix aluco). Sex-related differences affecting ChE and AChE activities were observed in young kestrels (2-3-mo-old) and age-related differences in kestrels (ChE and AChE), sparrowhawks (AChE), and tawny owls (ChE, AChE, and BChE). The interspecies analysis yielded a negative correlation between ChE activity and body mass taking into account the relative contribution of AChE and BChE to ChE activity, with the exception of the honey buzzard (Pernis apivorus). The lowest ChE activities were found in the two largest species, Bonelli's eagle (Hieraaetus fasciatus) and Egyptian vulture (Neophron percnopterus) belonging to the Accipitridae family. The highest ChE activities were found in the relatively small species belonging to the Tytonidae and Strigidae families and in honey buzzard of the Accipitridae family. Species of the Accipitridae, Tytonidae, and Strigidae families were characterized by a BChE contribution that dominated the total ChE activity, while in the species of the Falconidae family, AChE activity dominated. With the exception of the barn owl, CbE activity (eserine-insensitive alpha-naphthyl acetate esterase [alpha-NAE] activity) in all species was almost absent or very low. The values obtained in this study for ChE, AChE, and BChE activities and the AChE:BChE ratios for buzzard, kestrel, barn owl, and tawny owl provide a good estimate of the normal values in free-living individuals of these European species. They can be used as a baseline to evaluate the effect of anticholinesterase insecticides in the field.