Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1+ DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1+ human DC. Assessment of the immunoactivation potential of XCR1+ human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1+ and XCR1− human DC in CD34+ progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1− CD34-DC are similar to canonical MoDC, whereas XCR1+ CD34-DC resemble XCR1+ blood DC (bDC). XCR1+ DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1+ DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1+ CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1+ bDC. Hence, it is feasible to generate high numbers of bona fide XCR1+ human DC in vitro as a model to decipher the functions of XCR1+ bDC and as a potential source of XCR1+ DC for clinical use.
Prolonged donor ischemic time is not a risk factor for decreased long-term survival. Procurement of hearts with prolonged donor ischemic time is justified in the setting of an increasing recipient pool with a fixed donor population.
Background: While potential benefits of robotic technology include decreased morbidity and improved recovery, some have suggested a prohibitively high cost. This study was undertaken to compare actual hospital costs of robotically assisted cardiac procedures with conventional techniques. Methods: We conducted a retrospective review of clinical and financial data of 20 patients who underwent atrial septal defect (ASD) closure and 20 patients who underwent mitral valve repair (MVr) using either robotic techniques or a conventional approach with a sternotomy. Total hospital cost (actual resource consumption) was subdivided into operative and postoperative costs. Results: Robotic technology did not significantly increase total hospital cost for ASD closure or MVr (p = 0.518 and p = 0.539). However, when including the initial capital investment for the robot through amortization of institutional costs, total hospital cost was increased by $3,773 for robotic ASD closure and $3,444 for robotic MVr (p = 0.021 and p = 0.004). The major driver of cost for robotic cases (operating room time) decreased over time. Conclusions: Robotic technology did not significantly increase hospital cost. While the absolute cost for robotic surgery was higher than conventional techniques after taking into account the institutional cost of the robot, the major driver of cost for robotic procedures will likely continue to decrease, as the surgical team becomes increasingly familiar with robotic technology. Furthermore, other benefits, such as improvement in postoperative quality of life and more expeditious return to work may make a robotic approach cost-effective. Thus, it is possible that the benefits of robotic surgery may justify investment in this technology.
Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing-remitting multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils. Teriflunomide also mitigated the disease-induced changes in immune cell populations in the blood and spleen suggesting an inhibitory effect on pathogenic immune responses.
Conventional and plasmacytoid dendritic cells (cDCs and pDCs) are the two populations of DCs that can be readily identified in human blood. Conventional DCs have been subdivided into CD1c+, or blood dendritic cells antigen (BDCA) 1 and CD141+, or BDCA-3, DCs, each having both unique gene expression profiles and functions. BDCA-3 DCs express high levels of toll-like receptor 3 and upon stimulation with Poly I:C secrete IFN-β, CXCL10, and IL-12p70. In this article, we show that activation of human BDCA-3 DCs with Poly I:C induces the expression of activation markers (CD40, CD80, and CD86) and immunoglobulin-like transcript (ILT) 3 and 4. This Poly I:C stimulation results in four populations identifiable by flow cytometry based on their expression of ILT3 and ILT4. We focused our efforts on profiling the ILT4− and ILT4+ DCs. These ILT-expressing BDCA-3 populations exhibit similar levels of activation as measured by CD40, CD80, and CD86; however, they exhibit differential cytokine secretion profiles, unique gene signatures, and vary in their ability to prime allogenic naïve T cells. Taken together, these data illustrate that within a pool of BDCA-3 DCs, there are cells poised to respond differently to a given input stimulus with unique output of immune functions.
These results demonstrate similar short-term and long-term survivals, as well as similar risks for infection and transplant coronary artery disease, in diabetic and nondiabetic patients undergoing cardiac transplantation. The trend toward worse survival in the diabetic cohort, however, raises the possibility that if a greater number of diabetic patients were evaluated, a significant difference in survival might be observed, suggesting the need for a multicenter analysis to validate these outcomes.
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