Induction of monocyte-to-dendritic cell maturation by extracorporeal photochemotherapy: initiation via direct platelet signaling.

Extracorporeal Photochemotherapy (ECP) is a widely used therapy for cutaneous T cell lymphoma (CTCL). Although the mechanism of clinical action of ECP is not precisely established, previous studies have shown evidence of induction of dendritic cells (DCs). Here we show that, under flow conditions similar to those in post-capillary venules, ECP promotes platelet immobilization and activation, initiating stepwise receptor-ligand interactions with monocytes, which then differentiate into DC. These findings clarify how ECP directly stimulates DC maturation; suggest a new clinically applicable approach to the obtainment of DC; and identify a novel mechanism that may reflect physiological induction of DC.

Influence of race on the management of lower extremity ischemia: revascularization vs amputation.

IMPORTANCE: Among patients presenting with critical lower extremity ischemia, it has been previously documented that white individuals are more likely to undergo revascularization than nonwhite individuals, with the disparity largely attributed to differences in resources and access to care. OBJECTIVE: To investigate the amputation disparity between white and nonwhite patients with critical lower extremity ischemia in more detail using a larger data set than previous studies, with a focus on the role of confounding factors such as access and hospital resources. DESIGN, SETTING, AND PATIENTS: All hospital discharge records from the Nationwide Inpatient Sample of adult patients with the primary diagnosis of critical lower extremity ischemia from 2002-2008 were examined in detail using multiple logistic regression (n = 774,399). MAIN OUTCOMES AND MEASURES: Rates of amputation and revascularization for peripheral vascular disease across race/ethnicity. RESULTS: Controlling for confounding factors, black patients were found to have 1.77 times the odds of receiving an amputation compared with white patients (95% CI, 1.72-1.84; P < .001). Further analysis revealed the black to white odds ratio paradoxically increased with increasing revascularization capacity of the presenting hospital, from a low of 1.43 (95% CI, 1.23-1.65) to a high of 1.98 (95% CI, 1.83-2.24). The amputation disparity also paradoxically increased for patients living in wealthier zip codes. CONCLUSIONS AND RELEVANCE: Black patients have greater odds of undergoing amputation than white patients, even after correcting for an array of confounding parameters. Contrary to current beliefs that the disparity is mainly secondary to differences in access, this study found that the disparity was magnified in settings where resources were greatest. Whether the explanation lies primarily in patient-specific, physician-specific, or institutional-specific factors remains to be determined but is critical to better understanding our health care system and maintaining approaches that are consistently fair and equitable.