Perioperative management of face transplantation: A survey

Background: Since the first facial allograft transplantation was reported in France in 2005, 18 cases have been performed in 4 countries and the rate is increasing. Methods: We have devised a survey to assess anesthesia-related management and rationale of facial allograft transplantation. It was sent to the lead anesthesiologists of the first 14 face transplants performed worldwide. Results: Responses were received corresponding to 13 face transplants. The median duration of surgery and anesthesia was 19 hours (95% confidence interval 15-23 hours). The surgical preparation and dissection of multiple small anatomical structures of the recipient was time-consuming for 11 cases. Blood loss was considerable. All patients received packed red blood cells (median 20 U, 95% confidence interval 5-28 U). A median of 13 L of crystalloid was administered (95% confidence interval 10-18 L). Conclusions: During facial allograft transplantation, the anesthesiologist must be prepared for a long anesthetic with rapid blood loss after reperfusion of the graft. Comment in Out on a limb with composite tissue allografts: expanding the immunology toolbox. [Anesth Analg. 2012

mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis

Regulatory T cells (T-regs) have shown great promise as a means of cellular therapy in a multitude of allo- and auto-immune diseases-due in part to their immunosuppressive potency. Nevertheless, the clinical efficacy of human T-regs in patients has been limited by their poor in vivo homeostasis. To avert apoptosis, T-regs require stable antigenic (CD3 zeta/T-cell-receptor-mediated), co-stimulatory (CD28-driven), and cytokine (IL-2-dependent) signaling. Notably, this sequence of signals supports an activated T-reg phenotype that includes a high expression of granzymes, particularly granzyme B (GrB). Previously, we have shown that aside from the functional effects of GrB in lysing target cells to modulate allo-immunity, GrB can leak out of the intracellular lysosomal granules of host T-regs, initiating pro-apoptotic pathways. Here, we assessed the role of inhibiting mechanistic target of rapamycin complex 1 (mTORC1), a recently favored drug target in the transplant field, in regulating human T-reg apoptosis via GrB. Using ex vivo models of human T-reg culture and a humanized mouse model of human skin allotransplantation, we found that by inhibiting mTORC1 using rapamycin, intracytoplasmic expression and functionality of GrB diminished in host T-regs; lowering human T-reg apoptosis by in part decreasing the phosphorylation of S6K and c-Jun. These findings support the already clinically validated effects of mTORC1 inhibition in patients, most notably their stabilization of T-reg bioactivity and in vivo homeostasis