A subpopulation of tissue remodeling monocytes stimulates revascularization of the ischemic limb.

Despite decades of effort aimed at developing clinically effective cell therapies, including mixed population mononuclear cells, to revascularize the ischemic limb, there remains a paucity of patient-based studies that inform the function and fate of candidate cell types. In this study, we showed that circulating proangiogenic/arteriogenic monocytes (PAMs) expressing the FcγIIIA receptor CD16 were elevated in patients with chronic limb-threatening ischemia (CLTI), and these amounts decreased after revascularization. Unlike CD16-negative monocytes, PAMs showed large vessel remodeling properties in vitro when cultured with endothelial cells and smooth muscle cells and promoted salvage of the ischemic limb in vivo in a mouse model of hindlimb ischemia. PAMs showed a propensity to migrate toward and bind to ischemic muscle and to secrete angiogenic/arteriogenic factors, vascular endothelial growth factor A (VEGF-A) and heparin-binding epidermal growth factor. We instigated a first-in-human single-arm cohort study in which autologous PAMs were injected into the ischemic limbs of five patients with CLTI. Greater than 25% of injected cells were retained in the leg for at least 72 hours, of which greater than 80% were viable, with evidence of enhanced large vessel remodeling in the injected muscle area. In summary, we identified up-regulation of a circulatory PAM subpopulation as an endogenous response to limb ischemia in CLTI and tested a potentially clinically relevant therapeutic strategy.

A survey on perceived medication guide reading and comprehension ease among US adults.

Medication guides (MGs) provide patients with important information about certain prescription drugs to help them take these drugs safely. We surveyed US residents about their perceptions of MG readability and understandability. We randomly sampled 5204 US residents (age 18+) from Ipsos's KnowledgePanel to complete a two-part survey. Only respondents who reported receiving an MG with their prescription drugs (n = 3852) completed part 2, which included two key items: How easy to [(1)read/(2)understand] are the MGs that you have received from a pharmacy along with your prescription medicines? (1 = Very easy, 5 = Very difficult; reverse-coded). Health literacy (HL) and demographic data were also collected. After weighting our data, we found that 85% of respondents who reported receiving an MG perceived this information as 'very easy' (27.3%), 'somewhat easy' (28.3%) or 'about average' (29.3%) to read. Eighty-seven percent of respondents who reported receiving an MG perceived it as 'very easy' (27.6%), 'somewhat easy' (30.2%) or 'about average' (29.5%) to understand. ANOVAs revealed higher average perceived MG reading and comprehension ease scores among respondents presumed to have adequate versus inadequate HL (ps ≤ 0.0006). Younger or less-educated respondents and non-Hispanic Blacks perceived MGs as easier to read and understand, on average, than their counterparts (ps ≤ 0.0001). Many of these relationships remained intact in models predicting perceived MG reading and comprehension ease (ps ≤ 0.001). Adjusted R2 values across models were small, however (≤0.06). Our findings suggest most US residents (18+) who received MGs perceived them to be 'about average' to 'very easy' to read and understand.