Prevalence and risk factors for hepatitis E virus infection in blood donors: a nationwide survey in Italy, 2017 to 2019.

BackgroundIn high-income countries, hepatitis E virus (HEV) infection is mainly a zoonosis. However, it is also transfusion-transmissible and some countries, but not Italy, have introduced HEV screening for blood donations.AimWe assessed HEV infection prevalence and risk factors in a nationwide sample of Italian blood donors.MethodsWe selected 107 blood establishments (BE) distributed in the 20 Italian regions by a stratified two-stage design and invited them to participate in the study. Donors were tested for anti-HEV IgG and IgM and HEV RNA. Sociodemographic data and risk factors were collected through a questionnaire.ResultsOverall, 60 BE from 60 provinces in 19 Italian regions joined the study. We assessed HEV markers in 7,172 blood donors, of whom 6,235 completed the questionnaire. Overall crude and adjusted anti-HEV IgG prevalences were 8.3% and 5.5%, respectively. Overall anti-HEV IgM prevalence was 0.5%, while no blood donor was HEV RNA-positive. Anti-HEV IgG prevalence varied widely among regions (range: 1.3%-27.20%) and hyperendemic prevalences (> 40%) were detected in some provinces in two regions. Older age (AOR = 1.81; 95% CI: 1.36-2.41), foreign nationality (AOR = 2.77; 95% CI: 1.06-7.24), eating raw pork liver sausages (AOR = 2.23; 95% CI: 1.55-3.20) and raw homemade sausages (AOR = 3.63; 95% CI: 2.50-5.24) were independent infection predictors.ConclusionItalian blood donors showed a low to moderate HEV seroprevalence. High levels in some regions and/or provinces were mainly attributable to eating habits. Prevention should include avoiding consumption of raw or undercooked meat and safe production of commercial pork products.

High-dose ascorbate and arsenic trioxide selectively kill acute myeloid leukemia and acute promyelocytic leukemia blasts in vitro.

The use of high-dose ascorbate (ASC) for the treatment of human cancer has been attempted several decades ago and has been recently revived by several in vitro and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC, alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary blasts from AML and APL patients were treated with graded concentrations of ASC, alone or in association with standard concentration (1 µM) of ATO. The ASC/ATO combination killed myeloid blasts, including leukemic CD34+ cells, while sparing CD34+ progenitors obtained from normal cord blood and bone marrow. Actually, approximately one-third (11/36) of primary AML cases were highly sensitive to the ASC/ATO combination. The mechanism of cell killing appeared to be related to increased oxidative stress and overproduction of ROS in a non-quantitative fashion, which resulted in induction of apoptosis. These effects were reverted by the addition of the antioxidant N-Acetyl-Cysteine (NAC). In the APL NB4 model, ASC induced direct degradation of the PML and PML/RARA proteins via caspase activation, while the transcriptional repressor DAXX was recruited in re-constituted PML nuclear bodies. Our findings encourage the design of pilot studies to explore the potential clinical benefit of ASC alone or in combination with ATO in advanced AML and APL.

Conditioned medium from human umbilical vein endothelial cells markedly improves the proliferation and differentiation of circulating endothelial progenitors.

Circulating endothelial progenitor cells (EPCs) have been suggested as a precious source for generating functionally competent endothelial cells (ECs), candidate for various clinical applications. However, the paucity of these progenitor cells and the technical difficulties for their in vitro growth represent a main limitation to their use. In the present study we hypothesized that the paracrine effects of human umbilical vein endothelial cells (HUVECs) may improve endothelial cell generation from cord blood (CB) EPCs. In line with this hypothesis we showed that HUVEC conditioned medium (CM) or co-culture with HUVECs markedly improved the proliferation and differentiation and delayed the senescence of CB EPCs. The endothelial-promoting effect of CM seems to be related to smaller vesicles including exosomes (sEV/exo) contained in this medium and transferred to CB CD34(+) EPCs: in fact, purified preparations of sEV/exo isolated from CM mimicked the effect of CM to sustain endothelial formation. These observations provided the interesting indication that mature ECs exert a stimulatory effect on endothelial cell differentiation from CD34(+) cells.