TLR3 Signaling Promotes the Induction of Unique Human BDCA-3 Dendritic Cell Populations.

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-ß, 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.

Heart transplantation in diabetic recipients: a decade review of 161 patients at Columbia Presbyterian.

OBJECTIVE: Diabetes is considered by some transplant centers to be a relative contraindication for cardiac transplantation because of concerns regarding decreased survival, as well as increased incidence of infection and transplant coronary artery disease. We evaluated our experience with diabetic recipients over the last 10 years. METHODS: From January 1992 through June 2002, 881 patients underwent cardiac transplantation at New York Presbyterian Hospital. Of these, 161 (18.3%) were diabetic patients. Diabetic recipients were compared with a control group of 161 nondiabetic recipients matched for age, sex, cause of heart failure, United Network for Organ Sharing status, and immunosuppression era. Outcome measures included posttransplantation survival, incidence of infection, rejection, and transplant coronary artery disease. RESULTS: There was no statistically significant difference in survival between diabetic and nondiabetic recipients, with actuarial survival at 1, 5, and 10 years of 89.3%, 66.9%, and 45.6%, respectively, for diabetic patients and 87.4%, 78.8%, and 59.1%, respectively, for nondiabetic patients (P =.168). There was no significant difference in freedom from infection, rejection, or transplant coronary artery disease between the groups. By using Cox proportional hazard models, development of infection, rejection, and transplant coronary artery disease were independent predictors of decreased survival (P <.001, P =.004, and P =.004, respectively). CONCLUSIONS: 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.

Prolonged donor ischemic time does not adversely affect long-term survival in adult patients undergoing cardiac transplantation.

OBJECTIVE: With liberalization of donor eligibility criteria, organs are being harvested from remote locations, increasing donor ischemic times. Although several studies have evaluated the effects of prolonged donor ischemic times on short-term survival and graft function, few have addressed concerns regarding long-term survival. METHODS: Over the last 11 years, 819 consecutive adults underwent cardiac transplantation at Columbia Presbyterian Medical Center. Recipients were separated into the following 4 groups based on donor ischemic time: <150 minutes, 150 to 200 minutes, 200 to 250 minutes, and >250 minutes. Statistical analysis included Kaplan-Meier survival and Cox proportional hazard models to identify predictors of long-term survival. RESULTS: Donor ischemic time was 120.1 +/- 21.1 minutes for group 1 (n = 321), 174.1 +/- 14.7 minutes for group 2 (n = 264), 221.7 +/- 14.6 minutes for group 3 (n = 154), and 295.5 +/- 37.1 minutes for group 4 (n = 80) (P <.001). There were no significant differences in recipient age, donor age, etiology of heart failure, United Network for Organ Sharing status, or history of previous cardiac surgery among the groups (P = NS). Prolonged donor ischemic time did not adversely affect long-term survival, with actuarial survival at 1, 5, and 10 years of 86.9%, 75.2%, and 56.4% for group 1; 86.2%, 76.9%, and 50.9% for group 2; 86.4%, 71.0%, and 43.7% for group 3; and 86.7%, 70.1%, and 50.9% for group 4 (P =.867). There was no significant difference in freedom from transplant coronary artery disease among the 4 groups (P =.474). CONCLUSIONS: 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.

Off-pump right atrial thrombectomy for heparin-induced thrombocytopenia with thrombosis.

This report describes a 72-year-old woman with atrial fibrillation who presented with lower extremity ischemia secondary to thromboembolism. After lower extremity thrombectomy, the patient developed heparin-induced thrombocytopenia with thrombosis (HITT). Her postoperative course was complicated by recurrent supraventricular and ventricular tachycardia, secondary to a mobile thrombus in the right atrium extending into the right ventricle. Because administration of heparin was contraindicated, the patient underwent off-pump right atrial thrombectomy during a brief period of inflow occlusion. Postoperatively, she was placed on lepirudin. Her platelet count normalized without any further thrombotic episodes, and she was discharged on warfarin.