Application of a New Paradigm for Cytomegalovirus Disease Prevention in Mayo Clinic's First Face Transplant.

The optimal approach to preventing cytomegalovirus (CMV) disease after face transplant is unknown. We report an individualized hybrid approach, initially using valganciclovir prophylaxis followed by surveillance and preemptive therapy guided by viral and immunologic markers. A 31-year-old man received a near-total face allotransplant for gunshot injury-related severe facial deformities. He was CMV seronegative, and the donor was CMV seropositive (D+/R- mismatch), and he received intravenous ganciclovir followed by oral valganciclovir prophylaxis. Monthly CD8+ T-cell immune competence assay revealed no CMV-specific CD8+ T-cell immunity development during valganciclovir prophylaxis. Because of severe leukopenia, valganciclovir was discontinued at 7 months after transplant when the patient had recovered and sustained normal global CD8+ T-cell function. Weekly CMV polymerase chain reaction testing detected asymptomatic CMV replication (plasma CMV, 549 IU/mL) 3 months later. Short-course preemptive valganciclovir treatment resulted in sustained virologic clearance. The patient had development of CMV-specific CD8+ T cells (12 cells/µL) together with CMV IgM and IgG. No rejection or infection relapse was detected 20 months after transplant. In conclusion, viral and immunologic monitoring allowed for an individualized approach to effective CMV disease prevention after face transplant. This case highlights the importance of understanding the interplay between the host immunity and the pathogen in determining the clinical course and outcome of CMV and other infectious disease syndromes.

Effects of hyperbaric oxygen on the replanted extremity subjected to prolonged warm ischaemia.

In this investigation, the influence of hyperbaric oxygen (HBO) therapy on the survival of a replanted extremity subjected to prolonged warm ischaemia is evaluated. Among the relative contraindications to replantation are prolonged warm ischaemia time, since an obstruction to blood reflow ('no-reflow phenomenon') may occur in amputated parts that are subjected to more than 6h of warm ischaemia. Twenty-three rat hindlimbs were amputated and subjected to 4h of normothermic ischaemia. The average weight of the animals was 500 gm, and re-plantation of the hindlimb was performed by bone fixation followed by microvascular anastomosis of the femoral vessels. Limb re-vascularisation was confirmed at the end of all procedures by the milk test, clinical assessment and pulse oximetry recordings (>90%). Eleven animals served as a control group and no further therapy was instituted, whereas 12 animals served as the study (replantation) group and were subjected to HBO therapy for 3 days postoperatively. The therapy was conducted in a large animal chamber for 90 min at 2.5 ata. Limb survival was assessed by capillary refill upon compression, skin turgor assessment and colour. Confirmation of clinical findings was conducted with daily pulse oximetry readings of >90%. Animals were followed up for 7 days at which point all animals were euthanized or were euthanized earlier if a non-viable limb was present. Two of the 11 limbs in the control group survived following re-plantation, whereas eight of the 12 limbs in the experimental HBO group survived at least 7 days following replantation. This difference was statistically significant (p=0.0361) using chi-square analysis and Fisher's exact test. Although re-plantation of an amputated extremity after prolonged warm ischaemia is considered a relative contraindication due to the possibility of poor outcomes, our results indicate that the window for replantation may be increased if adjunctive HBO therapy is employed in the postoperative period.