RESUMO
ABO incompatible living donor liver transplantation has the potential to expand the donor pool for patients with end stage liver diseases on the expense of challenges to overcome immunological barriers across blood type. There is a profound impact of age on incidence and severity of antibody mediated rejection (AMR). Even children older than 1 year have chances of AMR; children aged 8 years or older have risks of hepatic necrosis similar to adult liver recipients. The mechanism of AMR is based on circulatory disturbances secondary to inflammation and injury of the vascular endothelium caused by an antibody-antigen-complement reaction. The strategy to overcome ABO blood type barrier is based on both pre-transplant desensitization and adequate treatment of this phenomenon. Nowadays, rituximab is the standard means of desensitization but unfortunately an insufficient aid to treat AMR. Because of low incidence (less than 5% in the rituximab era), in practice of AMR only some case reports about the treatment of clinical AMR are available in the literature. Initial experiences revealed that the proteasome inhibitor, bortezomib might be a promising treatment based on its capacity to deplete plasma cell agents. Although ABO blood type barrier has been counteracted in 95% of patients by applying "rituximab-desensitization", many issues, such as prediction of high-risk patients of infection and AMR and secure treatment strategies for evoked AMR, remain to be resolved.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Sistema ABO de Grupos Sanguíneos/efeitos adversos , Complexo Antígeno-Anticorpo/imunologia , Reações Antígeno-Anticorpo/imunologia , Incompatibilidade de Grupos Sanguíneos/complicações , Incompatibilidade de Grupos Sanguíneos/fisiopatologia , Incompatibilidade de Grupos Sanguíneos/prevenção & controle , Protocolos Clínicos/normas , Proteínas do Sistema Complemento/imunologia , Rejeição de Enxerto/história , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/prevenção & controle , História do Século XX , História do Século XXI , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Transplante de Fígado/história , Transplante de Fígado/métodos , Rituximab/imunologia , Rituximab/uso terapêutico , Imunologia de Transplantes/imunologiaAssuntos
Alemtuzumab/história , Alergia e Imunologia/história , Pesquisa Biomédica/história , Rejeição de Enxerto/história , Imunidade Celular , Imunossupressores/história , Transplante de Rim/história , Alemtuzumab/uso terapêutico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , História do Século XX , História do Século XXI , Humanos , Imunidade Celular/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversosAssuntos
Pesquisa Biomédica/história , Rejeição de Enxerto/história , Cardiopatias/história , Transplante de Coração/história , Patologia/história , Distinções e Prêmios , Educação Médica/história , Rejeição de Enxerto/patologia , Cardiopatias/patologia , Transplante de Coração/efeitos adversos , História do Século XX , História do Século XXI , Humanos , Liderança , Patologia/educaçãoRESUMO
BACKGROUND: In 1964, faced with the challenge of traumatic amputation, a team of surgeons at Clinica Guayaquil was convinced that the transplantation of a hand could significantly improve function and quality of life for the recipient. With a current but basic understanding of immunosuppression, the surgeons identified a recipient and waited for the correct donor. A human hand transplant had never been performed to date. METHODS: The surgeons' criteria for the recipient included a young healthy individual who had sustained a traumatic amputation at the distal forearm level with full motion of the proximal joints. Communication with receiving hospitals and military facilities identified what they perceived to be a feasible donor for an allograft transplantation. Consent was obtained from the family in conjunction with the local military medical authorities and the clergy. Iced saline solution and Heparin irrigation were to be used to prepare the donor extremity. The immunosuppression regimen, limited at the time, consisted only of intravenous cortisone, Imuran, and a single dose of radiation. RESULTS: A member of the Ecuadorian marine sustained a limited blast injury that amputated his dominant hand but spared the forearm. He was transferred to the emergency department of Clinica Guayaquil. A donor who had recently died in a nearby hospital was identified not long after. A successful technical surgical transplantation was achieved. Consultants from major hospitals around the world (including Peter Bent Brigham Hospital) convened at the patient's bedside to observe the results. Despite all efforts, the patient suffered an irreversible rejection at 21 days post-transplant. CONCLUSION: This was the first allograft transplantation of a hand. The surgeons embarked on an intervention never tried before, firmly believing that better function and quality of life would result. The bravery of this surgical team was commendable. This early surgical endeavor opened the way for future successes in transplant surgery today.
Assuntos
Amputação Traumática/história , Antebraço/cirurgia , Rejeição de Enxerto/história , Transplante de Mão/história , Terapia de Imunossupressão/história , Procedimentos de Cirurgia Plástica/história , Adulto , Amputação Traumática/fisiopatologia , Amputação Traumática/cirurgia , Equador , Antebraço/fisiopatologia , Rejeição de Enxerto/fisiopatologia , Transplante de Mão/métodos , História do Século XX , Humanos , Masculino , Qualidade de Vida , Procedimentos de Cirurgia Plástica/métodos , Falha de TratamentoRESUMO
The first clinical use of the "Munich antilymphocyte globulin" (ALG) at the occasion of the first successful human heart transplantation is briefly described. The cardiac transplantation was carried out by Christiaan Barnard and his team in Cape Town, South Africa, in 1968. The patient developed an acute allograft rejection which could be successfully reversed within three weeks using the intravenous administration of ALG. This event can be regarded as the beginning of a success story of ALG in its use as a powerful immunosuppressive agent in all categories of clinical organ transplantation.
Assuntos
Rejeição de Enxerto/história , Rejeição de Enxerto/terapia , Transplante de Coração/história , Transplante Homólogo/história , História do Século XX , HumanosAssuntos
Falência Renal Crônica/história , Falência Renal Crônica/cirurgia , Transplante de Rim/história , Autopsia/história , Rejeição de Enxerto/história , Rejeição de Enxerto/patologia , História do Século XX , Humanos , Irlanda , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Transplante de Rim/efeitos adversos , Masculino , Fatores de Risco , Falha de Tratamento , Adulto JovemRESUMO
The Banff histopathology classification system is the gold standard for assessing the causes of kidney allograft dysfunction triggered by antibody-mediated and T-cell-mediated immune reactions, thereby providing mechanistic insight and guiding therapeutic decisions. The original Banff classification (1993) consisted of four histological categories representing cell-mediated rejection: interstitial inflammation (i), tubulitis (t), endoarteritis (v), and transplant glomerulitis (g). The revised Banff 2007 classification added total inflammation score (ti) from both scarred and unscarred areas based on evolving interpretations of interstitial infiltrates. Further reappraisal of cell-mediated interstitial inflammation led to the introduction of a new inflammation score specific for areas of interstitial fibrosis and tubular atrophy, termed i-IF/TA, in the Banff 2015 scheme, establishment of a new Banff working group on T-cell-mediated rejection (TCMR), and revised criteria of chronic active TCMR in Banff 2017 classification. These Banff scheme updates reflect the general recognition that chronic interstitial inflammation is a common denominator of poor kidney allograft outcome. However, revised theories on the pathogenic importance of interstitial infiltrates have created difficulties in interpretation of chronic tubulointerstitial inflammation, as there are currently no histological criteria to discriminate immune-mediated tissue injury from 'non-specific' injury. Evolving theories on vascular lesions, both active and chronic, have also complicated histological assessment by obscuring the distinction between antibody-mediated and T-cell-mediated tissue injury. This review provides an overview of recent ideas on interstitial inflammation and vascular lesions based on emerging concepts of T-cell-mediated rejection.
Assuntos
Rejeição de Enxerto/imunologia , Imunidade Celular , Transplante de Rim/efeitos adversos , Rim/imunologia , Linfócitos T/imunologia , Aloenxertos , Biópsia , Difusão de Inovações , Previsões , Rejeição de Enxerto/história , Rejeição de Enxerto/patologia , História do Século XX , História do Século XXI , Humanos , Rim/patologia , Transplante de Rim/história , Transplante de Rim/tendências , Valor Preditivo dos Testes , Fatores de Risco , Linfócitos T/patologia , Resultado do TratamentoRESUMO
Heart transplantation has become a standard therapy option for advanced heart failure. The translation of heart transplantation from innovative experiments to long-term clinical success has married prescient insights with discipline and organization in the domains of surgical techniques, organ preservation, immunosuppression, organ donation and transplantation logistics, infection control, and long-term graft surveillance. This review explores the key milestones of the past 50 years of heart transplantation and discusses current challenges and promising innovations on the clinical horizon.
Assuntos
Insuficiência Cardíaca/história , Transplante de Coração/história , Animais , Difusão de Inovações , Rejeição de Enxerto/história , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , História do Século XX , História do Século XXI , Humanos , Imunossupressores/história , Imunossupressores/uso terapêutico , Preservação de Órgãos/história , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores de Risco , Coleta de Tecidos e Órgãos/história , Resultado do TratamentoAssuntos
Pesquisa Biomédica/história , Transplante de Órgãos/história , Rejeição de Enxerto/história , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , História do Século XX , História do Século XXI , Humanos , Transplante de Órgãos/efeitos adversos , Imunologia de Transplantes , Transplante Heterólogo/históriaRESUMO
The British Journal of Hospital Medicine is 50 years old. This article takes a look back at articles published during the year of its inception from the British Medical Journal, the Lancet and the Journal of the American Medical Association.
Assuntos
Publicações Periódicas como Assunto/história , Aborto Induzido/história , Acetaminofen/história , Acetaminofen/toxicidade , Adenoma Adrenocortical/história , Alopurinol/história , Alopurinol/uso terapêutico , Analgésicos/história , Analgésicos/toxicidade , Antineoplásicos/história , Antineoplásicos/uso terapêutico , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Pulmão do Criador de Aves/história , Doença Celíaca/complicações , Doença Celíaca/história , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/história , Dermatite Herpetiforme/complicações , Dermatite Herpetiforme/história , Descoberta de Drogas/história , Gota/tratamento farmacológico , Gota/história , Supressores da Gota/história , Supressores da Gota/uso terapêutico , Rejeição de Enxerto/história , Rejeição de Enxerto/imunologia , Doença Granulomatosa Crônica/história , História do Século XX , Humanos , Medicare/história , Editoração/história , Reino Unido , Estados UnidosAssuntos
Rejeição de Enxerto , Terapia de Imunossupressão , Transplante de Rim , Congressos como Assunto , Rejeição de Enxerto/história , Rejeição de Enxerto/prevenção & controle , História do Século XX , História do Século XXI , Humanos , Hungria , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/história , Transplante de Rim/história , Transplante de Rim/tendências , Doadores Vivos , Transplante de Órgãos/história , Transplante de Órgãos/tendências , ReoperaçãoAssuntos
Aloenxertos/história , Transplante de Medula Óssea/história , Rejeição de Enxerto/história , Aloenxertos/diagnóstico por imagem , Aloenxertos/imunologia , Animais , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/imunologia , História do Século XX , Terapia de Imunossupressão/história , Camundongos , Camundongos Endogâmicos C57BL , RadiografiaAssuntos
Aloenxertos/história , Transplante de Medula Óssea/história , Rejeição de Enxerto/história , Aloenxertos/diagnóstico por imagem , Aloenxertos/imunologia , Animais , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/imunologia , Antígenos H-2/história , Antígenos H-2/imunologia , História do Século XX , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Radiografia , Transplante Homólogo/históriaRESUMO
Developments in transplantation have progressed dramatically over the past century. Current research is underway to optimize immune modulation, genetically engineering animals for xenografting, and breakthroughs are occurring in regenerative medicine. However, pioneering live-donor transplantation has transformed transplantation in the organ shortage, and these contribute an increased proportion of transplanted organs. Live-donor transplantation is associated with better long-term outcomes, and techniques to recover organs have become less invasive. We set out to examine the evolution of transplantation from its historic beginnings to the developments that make it successful today.
Assuntos
Doadores Vivos/história , Transplante/história , Animais , Rejeição de Enxerto/história , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , História do Século XX , História do Século XXI , Humanos , Imunossupressores/história , Imunossupressores/uso terapêutico , Doadores Vivos/provisão & distribuição , Transplante/efeitos adversos , Resultado do TratamentoRESUMO
I am very grateful to the Council and members of the International Xenotransplantation Association for this Honorary Membership. In accepting this prestigious award, I pay tribute to my mentors Antonio Oriol i Anguera, Carlos Martinez, Robert A. Good, and Hans Müller-Eberhard for their guidance and friendship as I was beginning my travels in biomedical research. I also thank the many gifted collaborators, students, and technical personnel, as well as the agencies and taxpayers, who funded our research and made our scientific contributions possible. Here I briefly mention some of these contributions, including early work on the immunobiology of the thymus, my short incursion in the immunology of Chagas disease, and what have been the dominant themes of my career: the mechanisms of complement injury, the role of complement in pathophysiology, and induction of cytoprotection in the vascular endothelium. I emphasize our contributions on the role of complement as related to understanding and overcoming xenograft injury, a work that has been personally very rewarding. Now it is exciting to see that the field of xenotransplantation research is moving forward vigorously, a time of great optimism suggesting that many potential clinical applications of xenotransplantation will come to fruition in the near future.
Assuntos
Distinções e Prêmios , Doença de Chagas/história , Rejeição de Enxerto/história , Pesquisa Translacional Biomédica/história , Transplante Heterólogo/história , Animais , História do Século XX , História do Século XXI , HumanosRESUMO
Every liver transplant (LT) center has had patients who either self-discontinue immunosuppressive (IS) therapy or are deliberately withdrawn due to a research protocol or clinical concern (ie, lymphoproliferative disorder [LPD], overwhelming infection). This is understandable because maintenance IS therapy, particularly calcineurin inhibitors (CNI), is associated with significant cost, side effects, and considerable long-term morbidity and mortality. Detrimental effects of IS therapy include increased risk of cardiovascular disease, metabolic syndrome, bone loss, opportunistic and community-acquired infections, and malignancy. In fact, LT recipients have among the highest rates of chronic kidney disease and associated mortality among all nonkidney solid organ recipients. This mortality is only ameliorated by undergoing a curative kidney transplant, usurping costs and valuable organ resources. The search for improved treatment algorithms includes trial and error CNI dose minimization, the use of alternative IS agents (antimetabolites, mammalian target of rapamycin [mTOR] inhibitors), or even complete CNI withdrawal. Yet those who are successful in achieving such operational tolerance (no immunosuppression and normal allograft function) are considered lucky. The vast majority of recipients will fail this approach, develop acute rejection or immune-mediated hepatitis, and require resumption of IS therapy. As such, withdrawal of IS following LT is not standard-of-care, leaving clinicians to currently maintain transplant patients on IS therapy for life. Nonetheless, the long-term complications of all IS therapies highlight the need for strategies to promote immunologic or operational tolerance. Clinically applicable biomarker assays signifying the potential for tolerance as well as tolerogenic IS conditioning are invariably needed if systematic, controlled rather than "hit or miss" approaches to withdrawal are considered. This review will provide an overview of the basic mechanisms of tolerance, particularly in relation to LT, data from previous IS withdrawal protocols and biomarker studies in tolerant recipients, and a discussion on the prospect of increasing the clinical feasibility and success of withdrawal.