The effectiveness of United Network of Organ Sharing status 2 transplantation in the modern era.

BACKGROUND: The continued benefit of United Network of Organ Sharing (UNOS) status 2 transplantation in the modern era has been questioned. METHODS: We measured deterioration to higher status designations, improvement allowing delisting, and risk of death or delisting as too ill, regardless of subsequent status, from the Scientific Registry of Transplant Recipients database. Extended Cox models were used to assess the relative hazard of status 2 transplantation vs waiting after status 2 listing. The likelihood of transplantation was measured with logistic regression. RESULTS: We analyzed 14,153 candidates listed from 2003 to 2008. Within 1 year of initial listing, deterioration to status 1B occurred frequently (63%), while delisting as too well occurred rarely (2%-7%). Death or delisting as too ill occurred among 27% at 2 years after initial status 2 listing. Mortality at 2 years after status 2 transplantation was 13%. The hazard ratio (HR) after 180 days of status 2 transplantation vs waiting during or after initial status 2 listing was 0.41 (95% confidence interval, 0.31-0.55). The likelihood of transplantation was markedly diminished for women (odds ratio, 0.71; p < 0.001) and congenital heart disease (odds ratio, 0.24; p < 0.001). Death or delisting as too ill for women (HR, 1.7; p < 0.001) and congenital heart disease (HR, 3.2; p < 0.001) were substantially higher than in other groups. CONCLUSIONS: Escalation of UNOS status is common and delisting as too well is uncommon after initial status 2 listing. Despite the decreasing number of transplants provided to status 2 registrants, sub-groups of patients may be at high risk of waiting at status 1A, justifying the continued use of the status 2 designation.

Avaliação da interferência da tolerância oral na rejeição do transplante de coração alogênico avascular na orelha de camundongo / Evaluation of the interference of oral tolerance in the rejection of avascular allogeneic heart grafts to mouse ears

OBJETIVO: Apesar da evolução das técnicas cirúrgicas que permitiram a padronização do transplante cardíaco e da descoberta dos imunossupressores, ainda hoje, a rejeição, os efeitos colaterais dos medicamentos e o processo de vasculopatia crônica são os principais problemas nos pós-transplantados. A procura por alternativas para superar estes impedimentos é o objetivo principal deste trabalho. Assim, foram realizados experimentos para determinar se a tolerância oral pode interferir no transplante cardíaco. MÉTODO: Camundongos C57BI/6J e C3H/HEJ, machos adultos foram divididos em dois grupos. O grupo denominado tolerante recebeu amendoim ad libitum na dieta por sete dias, enquanto o grupo imune foi mantido com uma dieta convencional para murinos. Ambos foram imunizados com 100 mg de extrato protéico derivado do amendoim por via sc. O transplante de coração de BAL/C recém-nato, de 24h, foi depositado no tecido subcutâneo das orelhas dos animais de ambos os grupos, com ou sem imunização concomitante do antígeno alimentar. RESULTADOS: Confirmamos que a administração de proteínas por via oral é capaz de induzir tolerância sistêmica, uma vez que os grupos tolerantes apresentam títulos de anticorpos específicos ao amendoim mais baixos que os grupos imunes. O coração transplantado apresentou-se mais preservado no grupo de animais C3H/HEJ tolerantes que foram desafiados concomitantemente com o antígeno da dieta do que os demais grupos. CONCLUSAO: Foi determinado que os mecanismos de tolerância oral interferem no processo de rejeição de transplantes cardíacos alogênicos avasculares para a orelha de camundongos adultos, no entanto, de maneira não homogênea. Como os mecanismos de tolerância oral que alteram o sistema imunológico de modo a reduzir a rejeição ainda não foram esclarecidos, são precisos mais trabalhos nesta linha de pesquisa.

Pediatric heart and lung transplantation.

During the last two decades, several advances have resulted in marked improvement in medium-term survival with excellent quality of life in pediatric heart transplant recipients. These were possible due to better donor and recipient selection, increased surgical experience in transplantation for complex congenital heart disease, development of effective rejection surveillance, and wider choice of immunosuppressive medications. Despite all of these advances, recipients suffer from the adverse effects of non-specific immunosuppression including infections, post-transplant lymphoproliferative disorders and other malignancies, renal dysfunction and other important end-organ toxicities. Furthermore, newer immunosuppressive regimens appear (so far) to have had relatively little impact on the incidence of allograft coronary vasculopathy (chronic rejection). Progress in our understanding of the immunologic mechanisms of rejection and graft acceptance should lead to more targeted immunosuppressive therapy and avoidance of non-specific immunosuppression. The ultimate goal is to induce a state of tolerance, wherein the recipient will accept the allograft indefinitely without the need for long-term immunosuppression and yet remain immunocompetent to other antigens. This quest is currently being realized in many animal models of solid organ transplantation and offers great hope for the future.