Although red blood cell (RBC) transfusions can be lifesaving, they are not without risk. In critically ill patients, RBC transfusions are associated with increased morbidity and mortality, which may increase with prolonged RBC storage before transfusion. The mechanisms responsible remain unknown. We hypothesized that acute clearance of a subset of damaged, stored RBCs delivers large amounts of iron to the monocyte/macrophage system, inducing inflammation. To test this in a well-controlled setting, we used a murine RBC storage and transfusion model to show that the transfusion of stored RBCs, or washed stored RBCs, increases plasma nontransferrin bound iron (NTBI), produces acute tissue iron deposition, and initiates inflammation. In contrast, the transfusion of fresh RBCs, or the infusion of stored RBC-derived supernatant, ghosts, or stroma-free lysate, does not produce these effects. Furthermore, the insult induced by transfusion of stored RBC synergizes with subclinical endotoxinemia producing clinically overt signs and symptoms. The increased plasma NTBI also enhances bacterial growth in vitro. Taken together, these results suggest that, in a mouse model, the cellular component of leukoreduced, stored RBC units contributes to the harmful effects of RBC transfusion that occur after prolonged storage. Nonetheless, these findings must be confirmed by prospective human studies.

We conducted an open-label crossover trial to test whether proton pump inhibitors (PPIs) affect the gastrointestinal microbiome to facilitate Clostridium difficile infection (CDI). Twelve healthy volunteers each donated 2 baseline fecal samples, 4 weeks apart (at weeks 0 and 4). They then took PPIs for 4 weeks (40 mg omeprazole, twice daily) and fecal samples were collected at week 8. Six individuals took the PPIs for an additional 4 weeks (from week 8 to 12) and fecal samples were collected from all subjects at week 12. Samples were analyzed by 16S rRNA gene sequencing. We found no significant within-individual difference in microbiome diversity when we compared changes during baseline vs changes on PPIs. There were, however, significant changes during PPI use in taxa associated with CDI (increased Enterococcaceae and Streptococcaceae, decreased Clostridiales) and taxa associated with gastrointestinal bacterial overgrowth (increased Micrococcaceae and Staphylococcaceae). In a functional analysis, there were no changes in bile acids on PPIs, but there was an increase in genes involved in bacterial invasion. These alterations could provide a mechanism by which PPIs predispose to CDI. ClinicalTrials.gov:NCT01901276.

Patients with cancer may be at increased risk of severe coronavirus disease 2019 (COVID-19), but the role of viral load on this risk is unknown. We measured SARS-CoV-2 viral load using cycle threshold (C T ) values from reverse transcription-polymerase chain reaction assays applied to nasopharyngeal swab specimens in 100 patients with cancer and 2914 without cancer who were admitted to three New York City hospitals. Overall, the in-hospital mortality rate was 38.8% among patients with a high viral load, 24.1% among patients with a medium viral load, and 15.3% among patients with a low viral load ( P <0.001). Similar findings were observed in patients with cancer (high, 45.2% mortality; medium, 28.0%; low, 12.1%; P =0.008). Patients with hematologic malignancies had higher median viral loads (C T =25.0) than patients without cancer (C T =29.2; P =0.0039). SARS-CoV-2 viral load results may offer vital prognostic information for patients with and without cancer who are hospitalized with COVID-19.