B-cell depletion extends the survival of GTKO.hCD46Tg pig heart xenografts in baboons for up to 8 months.

Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Rejection in Gal knockout (GTKO) pigs due to elicited non-Gal antibody response required further genetic modifications of donor pigs and better control of the B-cell response to xenoantigens. We report significant prolongation of heterotopic alpha Galactosyl transferase "knock-out" and human CD46 transgenic (GTKO.hCD46Tg) pig cardiac xenografts survival in specific pathogen free baboons. Peritransplant B-cell depletion using 4 weekly doses of anti-CD20 antibody in the context of an established ATG, anti-CD154 and MMF-based immunosuppressive regimen prolonged GTKO.hCD46Tg graft survival for up to 236 days (n = 9, median survival 71 days and mean survival 94 days). B-cell depletion persisted for over 2 months, and elicited anti-non-Gal antibody production remained suppressed for the duration of graft follow-up. This result identifies a critical role for B cells in the mechanisms of elicited anti-non-Gal antibody and delayed xenograft rejection. Model-related morbidity due to variety of causes was seen in these experiments, suggesting that further therapeutic interventions, including candidate genetic modifications of donor pigs, may be necessary to reduce late morbidity in this model to a clinically manageable level.

Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study.

Venous stasis ulcers (VSU) account for approximately 80-90% of lower extremity ulcerations. Given their prevalence and chronic nature, VSU are thought to impose a significant economic burden on Medicare (the USA's largest health insurance program) and other third party payers. However, comprehensive studies on the costs of VSU treatment are lacking. The objective of this study therefore was to examine comprehensively the direct medical costs of treating patients with a VSU in routine clinical practice. A cohort of 78 patients who presented with a VSU to the Cleveland Clinic Foundation (CCF), a large primary and tertiary referral center, was studied retrospectively. All inpatient and outpatient costs related to VSU treatment that were incurred during the year following VSU presentation or until the ulcer healed, whichever occurred first, were quantified. A total of 71 (91%) patients healed during the study. The average duration of follow-up was 119 days (median: 84 days). The average number of visits per patient was seven (range: 2 to 57). A total of 14 (18%) patients underwent 18 hospitalizations for VSU care. The average total medical cost per patient was $9685 (median: $3036). Home health care, hospitalizations and home dressing changes accounted for 48%, 25% and 21% of total costs, respectively. Total costs were related to duration of active therapy, ulcer size and the presence of at least one comorbidity (p<0.05). VSU are costly to manage, especially when time to healing is prolonged. The present findings reflect an underestimate of VSU costs since indirect costs were not examined. Time absent from work, forced early retirement, loss of functional independence and unquantifiable suffering may be additional factors that contribute to the overall burden of VSU.