Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.340
Filtrar
2.
Transplantation ; 104(8): e224-e235, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732828

RESUMO

BACKGROUND: Lack of support for self-management may contribute to adverse health outcomes. eHealth has the potential to support self-management, but evidence in solid organ transplantation remains unclear. This review aims to evaluate the benefits and harms of eHealth interventions to support self-management in solid organ transplant recipients. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase databases for randomized trials of eHealth interventions in solid organ transplant recipients. We calculated the risk ratios or standardized mean difference of outcomes, and summary estimates were determined using random-effects models. The Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluations were used to assess trial quality. RESULTS: Twenty-one trials from 6 countries involving 2114 participants were included. Compared with standard care, eHealth interventions improved medication adherence (risk ratio, 1.34; CI, 1.12-2.56; I = 75%) and self-monitoring behavior (risk ratio, 2.58; CI, 1.56-4.27; I = 0%) up to 12 mo posttransplant. The treatment effects were largely consistent across different subgroups except for intervention functionality and mode of delivery. The effects on other outcomes were uncertain. Nine trials reported harms. The overall risk of bias was considered high or unclear, and the quality of evidence was low to very low for all outcomes. CONCLUSIONS: eHealth interventions may improve medication adherence and self-monitoring behavior in the short term, but high-quality intervention studies are needed to determine whether eHealth will improve long-term patient-relevant outcomes.


Assuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Órgãos/efeitos adversos , Autogestão/métodos , Telemedicina/métodos , Transplantados , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Educação de Pacientes como Assunto/métodos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistemas de Alerta , Resultado do Tratamento
3.
Transplantation ; 104(8): 1537-1541, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732829

RESUMO

This historical retrospective explores the study of the freemartin condition and its impact on the discovery of immunologic tolerance and the field of transplant surgery-from the ancient Romans, to early modern anatomists Valsalva, Scarpa, and Hunter, to contemporary immunologists Owen, Medawar, and Billingham, and to legendary transplant surgeon Joseph Murray. The legacy of freemartin cattle in the understanding of acquired tolerance and transplant immunology represents generations of scientific inquiry guided by careful observation and occasional serendipity, and the present-day immunologists and surgeons exploring immune transplant tolerance owe much to the history of the freemartin, several millennia in the making.


Assuntos
Rejeição de Enxerto/imunologia , Infertilidade Feminina/veterinária , Transplante de Órgãos/história , Transplante de Tecidos/história , Tolerância ao Transplante , Animais , Pesquisa Biomédica/história , Bovinos/imunologia , Feminino , Rejeição de Enxerto/prevenção & controle , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , Humanos , Infertilidade Feminina/imunologia , Transplante de Órgãos/efeitos adversos , Transplante de Tecidos/efeitos adversos
4.
Transplantation ; 104(8): 1542-1552, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732830

RESUMO

Uncontrolled donation after circulatory death (uDCD) refers to donation from persons who die following an unexpected and unsuccessfully resuscitated cardiac arrest. Despite the large potential for uDCD, programs of this kind only exist in a reduced number of countries with a limited activity. Barriers to uDCD are of a logistical and ethical-legal nature, as well as arising from the lack of confidence in the results of transplants from uDCD donors. The procedure needs to be designed to reduce and limit the impact of the prolonged warm ischemia inherent to the uDCD process, and to deal with the ethical issues that this practice poses: termination of advanced cardiopulmonary resuscitation, extension of advanced cardiopulmonary resuscitation beyond futility for organ preservation, moment to approach families to discuss donation opportunities, criteria for the determination of death, or the use of normothermic regional perfusion for the in situ preservation of organs. Although the incidence of primary nonfunction and delayed graft function is higher with organs obtained from uDCD donors, overall patient and graft survival is acceptable in kidney, liver, and lung transplantation, with a proper selection and management of both donors and recipients. Normothermic regional perfusion has shown to be critical to achieve optimal outcomes in uDCD kidney and liver transplantation. However, the role of ex situ preservation with machine perfusion is still to be elucidated. uDCD is a unique opportunity to improve patient access to transplantation therapies and to offer more patients the chance to donate organs after death, if this is consistent with their wishes and values.


Assuntos
Seleção do Doador/métodos , Rejeição de Enxerto/prevenção & controle , Parada Cardíaca/mortalidade , Preservação de Órgãos/métodos , Transplante de Órgãos/métodos , Aloenxertos/provisão & distribução , Seleção do Doador/ética , Seleção do Doador/legislação & jurisprudência , Rejeição de Enxerto/etiologia , Acesso aos Serviços de Saúde , Parada Cardíaca/terapia , Humanos , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/ética , Transplante de Órgãos/legislação & jurisprudência , Perfusão/instrumentação , Perfusão/métodos , Ressuscitação/ética , Resultado do Tratamento , Isquemia Quente/efeitos adversos
5.
Transplantation ; 104(8): 1566-1573, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732833

RESUMO

BACKGROUND: Xenogeneic organ transplantation has been proposed as a potential approach to fundamentally solve organ shortage problem. Xenogeneic immune responses across species is one of the major obstacles for clinic application of xeno-organ transplantation. The generation of glycoprotein galactosyltransferase α 1, 3 (GGTA1) knockout pigs has greatly contributed to the reduction of hyperacute xenograft rejection. However, severe xenograft rejection can still be induced by xenoimmune responses to the porcine major histocompatibility complex antigens swine leukocyte antigen class I and class II. METHODS: We simultaneously depleted GGTA1, ß2-microglobulin (ß2M), and major histocompatibility complex class II transactivator (CIITA) genes using clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins technology in Bamma pig fibroblast cells, which were further used to generate GGTA1ß2MCIITA triple knockout (GBC-3KO) pigs by nuclear transfer. RESULTS: The genotype of GBC-3KO pigs was confirmed by polymerase chain reaction and Sanger sequencing, and the loss of expression of α-1,3-galactose, SLA-I, and SLA-II was demonstrated by flow cytometric analysis using fluorescent-conjugated lectin from bandeiraea simplicifolia, anti-ß2-microglobulin, and swine leukocyte antigen class II DR antibodies. Furthermore, mixed lymphocyte reaction assay revealed that peripheral blood mononuclear cells from GBC-3KO pigs were significantly less effective than (WT) pig peripheral blood mononuclear cells in inducing human CD3CD4 and CD3CD8 T-cell activation and proliferation. In addition, GBC-3KO pig skin grafts showed a significantly prolonged survival in immunocompetent C57BL/6 mice, when compared with wild-type pig skin grafts. CONCLUSIONS: Taken together, these results demonstrate that elimination of GGTA1, ß2M, and CIITA genes in pigs can effectively alleviate xenogeneic immune responses and prolong pig organ survival in xenogenesis. We believe that this work will facilitate future research in xenotransplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Xenoenxertos/imunologia , Transplante de Órgãos/métodos , Transplante Heterólogo/métodos , Aloenxertos/provisão & distribução , Animais , Animais Geneticamente Modificados/imunologia , Sistemas CRISPR-Cas/genética , Modelos Animais de Doenças , Feminino , Galactosiltransferases/genética , Galactosiltransferases/imunologia , Técnicas de Inativação de Genes/métodos , Genes MHC da Classe II/genética , Genes MHC da Classe II/imunologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Xenoenxertos/transplante , Humanos , Masculino , Camundongos , Transplante de Órgãos/efeitos adversos , Suínos/genética , Suínos/imunologia , Transplante Heterólogo/efeitos adversos , Microglobulina beta-2/genética , Microglobulina beta-2/imunologia
6.
Transplantation ; 104(8): 1574-1579, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732834

RESUMO

BACKGROUND: Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important pathway responsible for antibody-mediated rejection (AMR). Imlifidase (IdeS) cleaves human IgG into F(ab')2 and Fc fragments, potentially inhibiting ADCC. Here we examined the effect of IdeS on allo-antibody-mediated NK cell activation (Allo-CFC) and ADCC in vitro. METHODS: For Allo-CFC, normal whole blood was incubated with third-party peripheral blood mononuclear cells (PBMCs) pretreated with anti-HLA antibody positive (HS) or negative (NC) sera to measure IFNγ+ NK cell%. For ADCC, normal PBMCs were incubated with Farage B (FB) cells with HS or NC sera to measure 7-AAD+ lysed FB cell%. To assess the effect of IdeS on these assays, serum-treated PBMCs (Allo-CFC-1) and serum used for PBMC pretreatment (Allo-CFC-2) in Allo-CFC, and serum used for ADCC were preincubated with IdeS. Sera from IdeS-treated patients were also tested for Allo-CFC (Allo-CFC-3). RESULTS: IFNγ+ NK cell% were significantly elevated in HS versus NC sera in Allo-CFC-1 (10 ± 3% versus 2 ± 1%, P = 0.001), Allo-CFC-2 (20 ± 10% versus 4 ± 2%, P = 0.01) and 7AAD+ FB cell% (11 ± 3% versus 4 ± 2%, P = 0.02) in ADCC. These were significantly reduced by IdeS treatment. Patient sera with significantly reduced anti-HLA antibody levels at 1 day postimlifidase lost the capacity to activate NK cells in Allo-CFC-3, but those at 1-3 months postimlifidase regained the capacity. CONCLUSIONS: IdeS inhibited NK cell activation and ADCC in vitro and in treated patients. These results and reported inhibition of complement activating anti-HLA antibodies by IdeS suggest its possible role in treatment of AMR.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Proteínas de Bactérias/uso terapêutico , Imunossupressores/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Transplante de Órgãos/efeitos adversos , Adulto , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Proteínas de Bactérias/farmacologia , Bioensaio , Células Cultivadas , Ativação do Complemento/efeitos dos fármacos , Dessensibilização Imunológica/métodos , Antígenos HLA/imunologia , Humanos , Imunossupressores/uso terapêutico , Interferon gama/imunologia , Interferon gama/metabolismo , Isoanticorpos/imunologia , Isoanticorpos/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares , Cultura Primária de Células , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Transplante Homólogo/efeitos adversos
7.
Nat Commun ; 11(1): 4289, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855397

RESUMO

Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses to injury and increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates with aging and augments immunogenicity. Ischemia reperfusion injury induces a systemic increase of cf-mt-DNA that promotes dendritic cell-mediated, age-specific inflammatory responses. Comparable events are observed clinically, with the levels of cf-mt-DNA elevated in older deceased organ donors, and with the isolated cf-mt-DNA capable of activating human dendritic cells. In experimental models, treatment of old donor animals with senolytics clear senescent cells and diminish cf-mt-DNA release, thereby dampening age-specific immune responses and prolonging the survival of old cardiac allografts comparable to young donor organs. Collectively, we identify accumulating cf-mt-DNA as a key factor in inflamm-aging and present senolytics as a potential approach to improve transplant outcomes and availability.


Assuntos
DNA Mitocondrial/efeitos adversos , Dasatinibe/farmacologia , Inflamação/prevenção & controle , Transplante de Órgãos/métodos , Quercetina/farmacologia , Adulto , Envelhecimento/fisiologia , Animais , Diferenciação Celular , Ácidos Nucleicos Livres , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Citocinas/metabolismo , DNA Mitocondrial/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/fisiologia , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Humanos , Inflamação/etiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Doadores de Tecidos
8.
Transplantation ; 104(8): 1644-1653, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732843

RESUMO

BACKGROUND: Obesity is a significant public health concern; however, the incidence post solid-organ transplantation is not well reported. METHODS: This study determined the incidence and risk factors of obesity among pediatric solid-organ transplant recipients (heart, lung, liver, kidney, multiorgan) at The Hospital for Sick Children (2002-2011), excluding prevalent obesity. Follow-up occurred from transplantation until development of obesity, last follow-up, or end of study. Incidence of obesity was determined overall, by baseline body mass index, and organ group. Risk factors were assessed using Cox proportional-hazards regression. RESULTS: Among 410 (55% male) children, median transplant age was 8.9 (interquartile range [IQR]: 1.0-14.5) years. Median follow-up time was 3.6 (IQR: 1.5-6.4) years. Incidence of obesity was 65.2 (95% confidence interval [CI]: 52.7-80.4) per 1000 person-years. Overweight recipients had a higher incidence, 190.4 (95% CI: 114.8-315.8) per 1000 person-years, than nonoverweight recipients, 56.1 (95% CI: 44.3-71.1). Cumulative incidence of obesity 5-years posttransplant was 24.1%. Kidney relative to heart recipients had the highest risk (3.13 adjusted hazard ratio [aHR]; 95% CI: 1.53-6.40) for obesity. Lung and liver recipients had similar rates to heart recipients. Those with higher baseline body mass index (z-score; 1.72 aHR; 95% CI: 1.39-2.14), overweight status (2.63 HR; 95% CI: 1.71-4.04), and younger transplant age (y; 1.18 aHR; 95% CI: 1.12-1.25) were at highest risk of obesity. Higher cumulative steroid dosage (per 10 mg/kg) was associated with increased risk of obesity after adjustment. CONCLUSIONS: Among all transplanted children at The Hospital for Sick Children, 25% developed obesity within 5-years posttransplant. Kidney recipients, younger children, those overweight at transplant, and those with higher cumulative steroid use (per 10 mg/kg) were at greatest risk. Early screening and intervention for obesity are important preventative strategies.


Assuntos
Transplante de Órgãos/efeitos adversos , Obesidade Pediátrica/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Transplantados/estatística & dados numéricos , Adolescente , Fatores Etários , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Seguimentos , Glucocorticoides/efeitos adversos , Humanos , Incidência , Lactente , Masculino , Programas de Rastreamento/organização & administração , Ontário/epidemiologia , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/etiologia , Obesidade Pediátrica/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
11.
Am J Surg Pathol ; 44(10): 1340-1352, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32554995

RESUMO

Monomorphic posttransplant lymphoproliferative disorders have been defined as lymphoid or plasmacytic proliferations that fulfill criteria for one of the B-cell or T/NK-cell neoplasms recognized in immunocompetent hosts in the current WHO Classification. Low-grade B-cell neoplasms have historically been excluded from this category, although rare reports of marginal zone lymphoma (MZL) have been described. We report 9 cases of posttransplant Epstein-Barr virus-negative MZL, all arising in solid organ transplant recipients (4 renal, 3 liver, 1 cardiac, and 1 liver, pancreas, and small bowel). Seven were extranodal MZL of mucosa-associated lymphoid tissue type, all of which had gastrointestinal involvement (4 colon, 1 duodenum, 1 stomach, and 1 oropharynx/base of tongue). Notably, the preferential involvement of intestine distinguishes posttransplant extranodal MZL from sporadic cases. Immunoglobulin light-chain restriction was seen in all cases, with polymerase chain reaction showing a monoclonal pattern in 7 of 8 cases with successful amplification of polymerase chain reaction products. A clonally unrelated recurrence was seen in one case. Next-generation sequencing identified recurrent mutations previously reported in MZL in 3/5 cases. MZL was diagnosed at least 1 year after solid organ transplant (median time to presentation, 84 mo; range, 13 to 108 mo). The median age was 44 (range, 9 to 73 y); the male: female ratio was 5:4. The mean follow-up was 33.4 months, with an indolent clinical course observed. A subset responded to reduction in immunosuppression and anti-CD20 therapy alone. These data support the designation of Epstein-Barr virus-negative MZL as an uncommon form of monomorphic posttransplant lymphoproliferative disorders.


Assuntos
Hospedeiro Imunocomprometido , Linfoma de Zona Marginal Tipo Células B/imunologia , Transplante de Órgãos/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Infecções por Vírus Epstein-Barr , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade
12.
Transplant Proc ; 52(9): 2626-2630, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32553507

RESUMO

BACKGROUND: One of the peculiar aspects of the transplant patient's life is that, in the post-surgery phase, the patient lives in an "isolation" condition, having to pay particular attention to the living environment and preferring a limited social life given that the immunosuppressive treatment entails immunodepression in the patient. With coronavirus disease 2019 (COVID)-19, as in a post-surgery situation, social isolation is being implemented. MATERIALS AND METHODS: The study started on March 17, 2020, and ended on April 24, 2020. Consulting/phone interviews were made. The phone questionnaire, submitted to 71 patients, consisted of a set of 15 questions that investigated structure and psychological resistance. Eight patients have been monitored exclusively for the psychological aspect through a more articulate supporting path. RESULTS: In essence, from the overall analysis of the data derived from the study of the positioning of patients based on the stage of renal function, the bands related to the development of psychopathological aspects, and the use of positive personal resources, it emerges that patients in stage V kidney failure are in the first bracket as regards the development of psychopathological aspects (absence of these experiences) and in the third bracket as regards the good use of positive resources to deal with isolation. Therefore, it can be deduced that, although with data that can be expanded, a serious or medium-serious situation from an organic point of view in this socio-health emergency situation is well addressed by the transplanted patient. CONCLUSION: Transplant patients have faced the measure of social distancing adequately and in adherence to the treatment thanks to the phone assistance of all the medical-surgical and psychological team.


Assuntos
Infecções por Coronavirus/prevenção & controle , Transplante de Órgãos/psicologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Quarentena/psicologia , Isolamento Social/psicologia , Betacoronavirus , Infecções por Coronavirus/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Pneumonia Viral/psicologia , Complicações Pós-Operatórias/psicologia , Complicações Pós-Operatórias/virologia , Período Pós-Operatório , Distância Social , Inquéritos e Questionários
14.
Acta Haematol ; 143(4): 352-364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32535598

RESUMO

Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding intermediaries, which are deposited in target tissues causing progressive organ damage. In all forms of amyloidosis, vital organs may fail; depending on the specific amyloidosis type, this may occur rapidly or progress slowly. Beyond therapies to reduce the precursor protein (chemotherapy for light chain [AL] amyloidosis, anti-inflammatory therapy in serum A amyloid-osis [AA], and antisense RNA therapy in transthyretin amyloidosis [ATTR]), organ transplantation may also be a means to reduce amyloidogenic protein, e.g., in types of amyloid-osis in which the variant precursor is produced by the liver. Heart transplantation is a life-saving approach to the treatment of patients with advanced cardiac amyloidosis; however, amyloidosis may still be considered a contraindication to the procedure despite data supporting improved outcomes, similar to patients with other indications. Kidney transplantation is associated with particularly favorable outcomes in patients with amyloidosis, especially if the precursor protein has been eliminated. Overall, outcomes of solid organ transplantation are improving, but more data are needed to refine the selection criteria and the timing for organ transplantation, which should be performed in highly experienced centers involving multidisciplinary teams with close patient follow-up to detect amyloid recurrence.


Assuntos
Amiloidose/terapia , Transplante de Órgãos , Amiloidose/diagnóstico , Amiloidose/etiologia , Amiloidose/mortalidade , Gerenciamento Clínico , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/etiologia , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos , Resultado do Tratamento
16.
Am J Transplant ; 20(7): 1795-1799, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32368850

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained health care resources, and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplant continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of coronavirus disease 2019 (COVID-19)-positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID-19-positive donors. The factors we consider include (1) the risk of blood transmission of SARS-CoV-2, (2) involvement of donor organs, (3) lack of effective therapies, (4) exposure of health care and recovery teams, (5) disease transmission and propagation, and (6) hospital resource utilization. While we acknowledge that transplant fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients but also to the community and to health care workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID-19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplant societies.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/tendências , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/tendências , Ética Médica , Humanos , Unidades de Terapia Intensiva , Exposição Ocupacional , Equipamento de Proteção Individual , Alocação de Recursos , Risco , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Estados Unidos
17.
Am J Transplant ; 20(7): 1800-1808, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32330343

RESUMO

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Transplante de Órgãos/efeitos adversos , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Transplantados , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Cuidados Críticos , Feminino , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressão , Imunossupressores/uso terapêutico , Unidades de Terapia Intensiva , Intubação , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Pneumonia Viral/mortalidade , Respiração Artificial , Esteroides/uso terapêutico , Resultado do Tratamento , Estados Unidos
18.
PLoS One ; 15(4): e0232323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348371

RESUMO

Uterine transplantation (UTx) associated with IVF restores fertility in women affected by absolute uterine factor infertility (AUFI). Pregnancies achieved both in women undergoing any solid organ transplantation and following IVF are associated with an increased risk of maternal and neonatal complications. This systematic review evaluated this risk in UTx-IVF treated women focusing on the safety and efficacy features of the treatment. Twenty-two studies and three press releases reporting on 52 UTx-IVF treatments were identified. Regarding the safety of treatment, 38/52 (73,1%) of surgical procedures led to the restoration of uterine function in recipients, 12/52 (23,1%) of recipients experienced post-operative complications requiring hysterectomy, and 2/52 (3,8%) of procedures failed before uterine recipients' surgery due to intra-operative complications. Regarding the efficacy of treatment, results focused on transplanted patients showing full recovery of organ functioning: 16/38 (42,1%) of patients achieved a pregnancy, including two women who gave births twice. UTx-IVF pregnancies led to 16 deliveries and all new-borns were healthy. Six out of 16 (37,5%) UTx pregnancies faced major complications during gestation. Preterm births occurred in 10/16 (62,5%) UTx deliveries. Our data indicates that the risk of gestational and delivery complications deserves important consideration in AUFI women receiving UTx-IVF treatments. However, these observations are preliminary and need to be revised after larger series of data are published.


Assuntos
Fertilização In Vitro/métodos , Infertilidade Feminina/terapia , Útero/transplante , Feminino , Fertilização In Vitro/efeitos adversos , Humanos , Histerectomia , Infertilidade Feminina/etiologia , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , Resultado do Tratamento
19.
Transplant Proc ; 52(5): 1522-1524, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32299708

RESUMO

BACKGROUND: Rare diseases (RDs) are a heterogeneous group of pathologies, which, when present in a donor, with their anatomic or functional deficiencies, may put the recipient at risk. The aim of our work is to analyze the incidence of RDs in our donors to support transplant experts in the evaluation of these organs. METHODS: We retrospectively assessed the incidence of RDs in donors from July 2017 to June 2019, along with the risk attributed, the number of transplanted organs, and the follow-up results of the recipients. RESULTS: Over a 24-month period, we had 19 donors with RDs. Of those, the organs of 4 donors were rejected before the risk assessment, the organs of 4 other donors were deemed an unacceptable risk, the organs of 4 more donors were rejected by transplant centers, and the organs of 7 donors were accepted with 16 organs ultimately transplanted (2 hearts, 3 livers, and 11 kidneys). Three of the recipients died of causes not related to the RDs. Thirteen of the recipients are still alive with a functioning organ with an average follow-up of 9 months. CONCLUSIONS: Although the evaluation of the results is influenced by the limited follow-up period, the use of donors with RDs has proved safe. One of the critical issues encountered in the evaluation process was the impossibility of carrying out genetic and histologic investigations for each organ in urgency. Moreover, the heterogeneity of RDs and the lack of solid literature data require, for the purpose of assessing the level of risk, a specific assessment of individual cases. To overcome these limitations, a group of experts was set up at the Superior Health Council, who drafted a reference document, which allowed for the assessment of the suitability and risk level of donors with the most frequent RDs.


Assuntos
Seleção do Doador/estatística & dados numéricos , Transplante de Órgãos/estatística & dados numéricos , Doenças Raras/fisiopatologia , Doadores de Tecidos/provisão & distribução , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Transplantes/fisiopatologia
20.
PLoS Pathog ; 16(4): e1008477, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32251475

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication after organ transplantation frequently associated with the Epstein-Barr virus (EBV). Immunosuppressive treatment is thought to allow the expansion of EBV-infected B cells, which often express all eight oncogenic EBV latent proteins. Here, we assessed whether HLA-A2 transgenic humanized NSG mice treated with the immunosuppressant FK506 could be used to model EBV-PTLD. We found that FK506 treatment of EBV-infected mice led to an elevated viral burden, more frequent tumor formation and diminished EBV-induced T cell responses, indicative of reduced EBV-specific immune control. EBV latency III and lymphoproliferation-associated cellular transcripts were up-regulated in B cells from immunosuppressed animals, akin to the viral and host gene expression pattern found in EBV-PTLD. Utilizing an unbiased gene expression profiling approach, we identified genes differentially expressed in B cells of EBV-infected animals with and without FK506 treatment. Upon investigating the most promising candidates, we validated sCD30 as a marker of uncontrolled EBV proliferation in both humanized mice and in pediatric patients with EBV-PTLD. High levels of sCD30 have been previously associated with EBV-PTLD in patients. As such, we believe that humanized mice can indeed model aspects of EBV-PTLD development and may prove useful for the safety assessment of immunomodulatory therapies.


Assuntos
Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Tacrolimo/farmacologia , Animais , Linfócitos B/metabolismo , DNA Viral , Modelos Animais de Doenças , Infecções por Vírus Epstein-Barr/virologia , Feminino , Perfilação da Expressão Gênica/métodos , Antígeno HLA-A2 , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Herpesvirus Humano 4/patogenicidade , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Transplante de Órgãos/efeitos adversos , Transcriptoma/genética , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA