RESUMEN

We describe the incidence of early graft failure (EGF, defined as loss of function from any cause within 3 days after transplant) in a large cohort of GalTKO pig organs transplanted into baboons in three centers, and the effect of additional expression of a human complement pathway-regulatory protein, CD46 or CD55 (GalTKO.hCPRP). Baboon recipients of life-supporting GalTKO kidney (n = 7) or heterotopic heart (n = 14) grafts received either no immunosuppression (n = 4), or one of several partial or full immunosuppressive regimens (n = 17). Fourteen additional baboons received a GalTKO.hCPRP kidney (n = 5) or heart (n = 9) and similar treatment regimens. Immunologic, pathologic, and coagulation parameters were measured at frequent intervals. EGF of GalTKO organs occurred in 9/21 baboons (43%). hCPRP expression reduced the GalTKO EGF incidence to 7% (1/14; P < 0.01 vs. GalTKO alone). At 30 mins, complement deposits were more intense in organs in which EGF developed (P < 0.005). The intensity of peri-transplant platelet activation (as ß-thromboglobulin release) correlated with EGF, as did the cumulative coagulation score (P < 0.01). We conclude that (i) the transgenic expression of a hCPRP on the vascular endothelium of a GalTKO pig reduces the incidence of EGF and reduces complement deposition, (ii) complement deposition and platelet activation correlate with early GalTKO organ failure, and (iii) the expression of a hCPRP reduces EGF but does not prevent systemic coagulation activation. Additional strategies will be required to control coagulation activation.

Asunto(s)

Antígenos CD55/inmunología , Galactosiltransferasas/deficiencia , Rechazo de Injerto/prevención & control , Proteína Cofactora de Membrana/inmunología , Trasplante Heterólogo/métodos , Animales , Animales Modificados Genéticamente , Antígenos CD55/genética , Activación de Complemento , Disacáridos/inmunología , Galactosiltransferasas/genética , Galactosiltransferasas/inmunología , Técnicas de Inactivación de Genes , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/métodos , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Proteína Cofactora de Membrana/genética , Papio , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Porcinos , Trasplante Heterólogo/efectos adversos

RESUMEN

OBJECTIVE: Osteomyelitis of the skull is a rare condition that can lead to systemic illness, bone loss, intracranial complications, and mortality. Osteomyelitis of the skull typically presents as the boney invasion of an overlying infection of the scalp or sinuses, and it is typically treated with antibiotics and proper wound care. Surgical debridement of the affected bone in the form of a craniectomy may be initiated to stop the progression of the infection when antibiotics fail and the underlying bone becomes grossly eroded. METHOD: The authors present the case of a 54-year-old woman who required a total craniectomy after developing full-thickness osteomyelitis. A free omental flap along with dermal grafts and split-thickness skin grafts were utilized for soft tissue coverage. A semi-rigid helmet was used to provide durable protection to the brain. RESULTS: Omental free flap with skin graft coverage provided this patient with durable and long-term soft tissue coverage for a total craniectomy defect, as well as the ability to regain mental status. CONCLUSIONS: Many factors must be analyzed when approaching composite defects of the scalp. Modality of treatment must be customized to the individual, and the decisions should be based on whether the defect is composed of soft tissue, bone or both, its size, etiology, and presence of a cerebral spinal fluid leak. The goals of treatment are restoration of durable soft tissue coverage, protection of vital underlying structures and control of cerebral spinal fluid leaks.