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1.
Med. intensiva (Madr., Ed. impr.) ; 44(3): 150-159, abr. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-190561

RESUMO

OBJECTIVE: Comparison of different diagnostic criteria for early liver allograft dysfunction (EAD) and their capability to predict mortality. DESIGN: Single-center, prospective, cohort study. SETTINGS: ICU in a Regional Hospital with a liver transplant program since 1997. PATIENTS: 253 consecutive patients admitted to our ICU immediately after liver transplantation between 2009 and 2015. Variables of interest: Differences in the incidence of EAD and its relation with ICU, Hospital and 2-year mortality depending on the definition applied using as comparator the UNOS (United Network for Organ Sharing) primary non-function criterion. RESULTS: The incidence of early liver allograft dysfunction according to UNOS was 13.8%, to Makowka 6.3%, to Ardite 10.7%, to Nanashima 20.6%, to Dhillon 30.8% and to MEAF 13.4%. Kappa test did not show a good correlation among these criteria. EAD was related with ICU mortality for all diagnostic criteria except Dhillon but only UNOS, Makowka and MEAF were associated with 2-year mortality. Hospital mortality was poorly predicted by all criteria except for the MEAF score. CONCLUSIÓN: We found a poor agreement between different criteria analyzed for the diagnosis of EAD. In our population, the MEAF score showed the best relationship with short- and long-term mortality


OBJETIVO: Comparar diferentes criterios diagnósticos de disfunción temprana del aloinjerto hepático y su capacidad para predecir mortalidad. DISEÑO: Estudio de cohortes prospectivo, unicéntrico. Ámbito: Unidad de Cuidados Intensivos de un Hospital Regional con programa de trasplante hepático desde 1997. PACIENTES: 253 pacientes consecutivos ingresados en nuestra UCI inmediatamente después del trasplante entre 2009-2015. Variables de interés: Incidencia de disfunción temprana del aloinjerto hepático según cada criterio diagnóstico, relación entre disfunción grave acorde a cada criterio y mortalidad en UCI, mortalidad hospitalaria y a los 2 años utilizando como comparador el criterio para fallo primario de la UNOS (United Network for Organ Sharing). RESULTADOS: La incidencia de disfunción temprana según UNOS fue 13.8%, Makowka 6.3%, Ardite 10.7%, Nanashima 20.6%, Dhillon 30.8% y MEAF 13.4%. El coeficiente kappa mostró una pobre correlación entre ellos. Todos los criterios, excepto el de Dhillon, mostraron relación con la mortalidad en la UCI, pero solo los criterios de UNOS, Makowka y MEAF se asociaron con la mortalidad a 2 años. Finalmente, la capacidad predictiva de la mortalidad hospitalaria fue baja para todos, excepto para MEAF. CONCLUSIÓN: Existe una pobre correlación entre diferentes criterios diagnósticos de disfunción temprana del injerto hepático. El MEAF muestra la mejor relación con el pronóstico a corto y largo plazo en nuestra población


Assuntos
Humanos , Transplante de Fígado , Sobrevivência de Enxerto/fisiologia , Disfunção Primária do Enxerto/diagnóstico , Estudos de Coortes , Disfunção Primária do Enxerto/fisiopatologia , Estudos Prospectivos , Aloenxertos/fisiopatologia , Disfunção Primária do Enxerto/epidemiologia
2.
BMC Cardiovasc Disord ; 19(1): 305, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856732

RESUMO

BACKGROUND: Coronary artery spasm (CAS) is an underdiagnosed disease especially in heart transplant patients, and in those patients the etiology and pathophysiology remain largely unknown, although it has been associated with cardiac allograft vasculopathy or graft rejection. CASE PRESENTATION: We report the case of a heart-transplant patient whose cardiac graft experienced two coronary vasospasms: the first before transplantation, and the other at one-month of a postoperative course complicated by primary graft failure. CONCLUSION: Our case illustrates that a transplanted heart predisposed with coronary vasospasm may suffer from early relapse in the recipient despite of complete post-surgical autonomic denervation. Exacerbated endothelial dysfunction of the donor heart after transplant, with the addition of systemic factors in the recipient may be involved in the genesis of this puzzling phenomenon.


Assuntos
Vasoespasmo Coronário/etiologia , Transplante de Coração/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Vasoespasmo Coronário/diagnóstico por imagem , Vasoespasmo Coronário/fisiopatologia , Vasoespasmo Coronário/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/diagnóstico por imagem , Disfunção Primária do Enxerto/fisiopatologia , Disfunção Primária do Enxerto/terapia , Recuperação de Função Fisiológica , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
4.
J Thorac Cardiovasc Surg ; 158(6): 1576-1584.e3, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30948318

RESUMO

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation is a useful treatment for severe primary graft dysfunction after heart transplant. The ideal timing of initiation is unknown. METHODS: We retrospectively reviewed 362 adult heart transplant recipients at our center between January 2011 and December 2017. Thirty-eight patients (10.5%) experienced severe primary graft dysfunction treated with venoarterial extracorporeal membrane oxygenation. As our institution adopted a prompt venoarterial extracorporeal membrane oxygenation policy in 2015, patients were stratified into pre-2015 (conservative extracorporeal membrane oxygenation: n = 18) and post-2015 (prompt extracorporeal membrane oxygenation: n = 20) cohorts. Clinical outcomes were compared. RESULTS: Baseline characteristics were similar (conservative vs prompt) except for age (51.82 vs 59.96 years, P = .036), aspartate transaminase (32 vs 21.5 U/L, P = .038), male donor (44.4 vs 80%, P = .042), and donor ejection fraction (60 vs 65%, P = .047). Median ischemic time was significantly longer in the conservative extracorporeal membrane oxygenation cohort (210 vs 148 minutes, P = .005). Median time to initiation of extracorporeal membrane oxygenation was significantly shorter in the prompt extracorporeal membrane oxygenation cohort (7.26 vs 1.95 hours, P < .0001). There was no difference in intensive care unit stay or major complications. In-hospital mortality improved from 28% (conservative) to 5% (prompt, P = .083). Post-transplant survival at 1 year was 67% in the conservative extracorporeal membrane oxygenation cohort and 90% in the prompt extracorporeal membrane oxygenation cohort (P = .117). There was no difference in the Kaplan-Meier survival curves (P = .071), although Cox regression suggested, but certainly did not prove, a 74.6% lower risk of mortality in the prompt extracorporeal membrane oxygenation group (P = .094). CONCLUSIONS: Prompt venoarterial extracorporeal membrane oxygenation use for primary graft dysfunction after heart transplant results in excellent myocardial recovery and a possible decrease in mortality without increased risk of complications.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Coração/efeitos adversos , Disfunção Primária do Enxerto/terapia , Adulto , Idoso , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Transplante de Coração/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/mortalidade , Disfunção Primária do Enxerto/fisiopatologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento
5.
Rev Col Bras Cir ; 46(1): e2039, 2019.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31017176

RESUMO

Avoiding deaths in the waiting list for an organ is no longer the only focus of the transplant teams attention. Research and care in clinical practice has been increasingly focused on post transplant graft survival and functioning. In the present work, we performed an integrative literature review to identify the terminology used about liver graft dysfunction and non-function, as well as to investigate the incidence and risk factors of these clinical events. We chosen articles written in Portuguese, English and Spanish between 2012 and 2016, based on CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE and Web of Science. We selected 14 studies, in which we identified the incidence of hepatic graft dysfunction ranging from 7% to 27%. The terminology used to describe this clinical event was initial malfunction, graft hypofunction, marginal function or delay in function. The primary non-function of the liver graft was found in 1.4% to 8.4% of the patients, and the terminology used to describe the event was early dysfunction or graft loss. The risk factors found are related to donor, recipient, graft and transplant logistics variables. We conclude that knowledge of the different terminologies employed in the literature, related to dysfunction and primary non- function incidence, and of their risk factors are fundamental to qualify the control of the events, aiming to improve patients' survival after liver transplantation.


Assuntos
Transplante de Fígado/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Humanos , Fígado/fisiopatologia , Transplante de Fígado/métodos , Disfunção Primária do Enxerto/fisiopatologia , Medição de Risco , Fatores de Risco , Doadores de Tecidos , Transplantados
6.
Ann Vasc Surg ; 59: 312.e7-312.e9, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31009723

RESUMO

Vascular complications such as renal artery or renal vein thrombosis and laceration and iliac artery dissection are rarely encountered after renal transplantation. Timely management of these vascular complications is important to prevent ischemic injury of a transplanted kidney. We hereby report a case of a 60-year-old male who had acute renal dysfunction due to iatrogenic left external iliac artery dissection after renal transplantation. An endovascular stenting of the dissected iliac artery resulted in a brisk flow across both iliac and transplanted renal arteries. The management issues related to this rare vascular complication is discussed in the article.


Assuntos
Aneurisma Dissecante/cirurgia , Procedimentos Endovasculares , Doença Iatrogênica , Aneurisma Ilíaco/cirurgia , Transplante de Rim/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/fisiopatologia , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/instrumentação , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/etiologia , Aneurisma Ilíaco/fisiopatologia , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/fisiopatologia , Stents , Resultado do Tratamento , Ultrassonografia Doppler em Cores
7.
J Heart Lung Transplant ; 38(2): 184-193, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30466803

RESUMO

BACKGROUND: Chronic lung allograft dysfunction (CLAD), including the phenotypes of bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (R-CLAD), represents the leading cause of late death after lung transplantation. Little is known, however, regarding the natural history or prognostic significance of pulmonary function changes after the onset of these conditions. We examined changes in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) over the first 18 months after CLAD. We also sought to determine whether lung function changes occurring early after CLAD impact longer term outcomes. METHODS: We performed a retrospective analysis of 216 bilateral lung recipients with CLAD, which included those with R-CLAD (n = 65) or BOS (n = 151). The course of FEV1 and FVC after CLAD was described. Cox proportional hazards models were used to evaluate the impact of a ≥10% decline in FEV1 or FVC within the first 6 months of CLAD on graft loss after that time. RESULTS: Lung recipients with CLAD, whether BOS or R-CLAD, had the largest decreases in FEV1 and FVC within the first 6 months after onset. Moreover, a decline in FEV1 or FVC of ≥10% within the first 6 months after CLAD was associated with a significantly increased hazard for graft loss after that time (hazard ratio [HR] = 3.17, 95% confidence interval [CI] 1.56 to 6.42, p = 0.001, and HR = 2.80, 95% CI 1.66 to 4.70, p ≤ 0.001, respectively), an effect observed in both BOS and R-CLAD patients. CONCLUSIONS: Early physiologic changes after CLAD were independently associated with graft loss. This suggests lung function changes after CLAD, specifically a ≥10% decline in FEV1 or FVC, could be a surrogate measure of graft survival.


Assuntos
Bronquiolite Obliterante/complicações , Transplante de Pulmão/efeitos adversos , Pulmão/fisiopatologia , Disfunção Primária do Enxerto/fisiopatologia , Adulto , Aloenxertos , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/fisiopatologia , Doença Crônica , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Prognóstico , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Capacidade Vital
8.
Exp Clin Transplant ; 17(1): 6-10, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30084763

RESUMO

OBJECTIVES: Kidneys from expanded criteria donors with diagnosis of brain death have become a part of the organ transplant program, which have thus increased the number of transplants. MATERIALS AND METHODS: In this retrospective analysis, we identified the expanded criteria donors in a group of 156 kidney donors at our center. Basic parameters of the donors before kidney recovery were collected. Graft function, graft survival, and patient survival at 1, 3, and 5 years posttransplant were compared in expanded criteria versus standard criteria donors. RESULTS: Expanded criteria donors were significantly older than standard criteria donors (P < .001), had higher body mass index (P = .006), and had more frequent arterial hypertension (P < .001) and diabetes mellitus (P = .004) in their histories. When we considered the estimated glomerular filtration rate, graft function in the first 6 months after transplant was significantly worse in kidneys from expanded criteria donors (P = .011). In addition, recipients of grafts from expanded criteria donors had significantly worse survival in the first year posttransplant (P = .023); however, no differences in graft survival were observed. CONCLUSIONS: From the long-term aspect, graft function and graft and patient survival in cases of kidneys from expanded criteria donors were comparable to results with kidneys from standard criteria donors. Expanded use of organs available for transplant is important due to the constantly increasing demands versus limited offers of organs.


Assuntos
Seleção do Doador/métodos , Transplante de Rim/métodos , Doadores de Tecidos/provisão & distribução , Adulto , Idoso , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Eslováquia , Fatores de Tempo , Resultado do Tratamento
9.
Semin Thorac Cardiovasc Surg ; 31(1): 1-6, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29935227
10.
Exp Clin Transplant ; 17(1): 64-73, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29363416

RESUMO

OBJECTIVES: An optimal initial graft function after living-donor liver transplant depends on optimal graft hemodynamics. Nonmechanical impediments to free hepatic venous outflow, due to elevated central venous pressure, may obstruct the "functional" hepatic venous outflow. Here, we evaluated whether central venous pressure affected early graft function and outcomes in adult living-donor liver transplant recipients. MATERIALS AND METHODS: This prospective observational study included 61 living-donor liver transplant recipients without technical complications who received transplants from August 2013 to November 2014. Hemodynamic variables were measured preoperatively, at anhepatic phase, 30 minutes postreperfusion, at end of surgery, and during postoperative days 1-5. RESULTS: Patients with high central venous pressure showed functional hepatic venous outflow obstruction, which caused delayed recovery of graft function. Although postoperative central venous pressure was the only identified independent risk factor for mortality, all 5 deaths in our study group occurred in those who had high central venous pressure at the anhepatic, postreperfusion, end of surgery, and postoperative phases. A postoperative central venous pressure value of ~11 mm Hg was determined to be the cutoff for high-risk mortality, with area under the curve of 0.859 (sensitivity of 80%, specificity of 68%). Increased central venous pressure was associated with increased portal venous pressure (increase of 45%, range, 28%-89%; P = .001). Central venous pressure at end of surgery (r = 0.45, P ≤ .001) and at posttransplant time points (r = 0.29, P = .02) correlated well with portal venous pressure at end of surgery. Other risk factors for early allograft dysfunction were Model for End-Stage Liver Disease and cardiac output posttransplant. CONCLUSIONS: High central venous pressure, modulating portal venous pressure, can result in functional hepatic venous outflow obstruction, causing delayed graft function recovery and increased risk of mortality. Maintaining a central venous pressure below 11 mm Hg is beneficial.


Assuntos
Pressão Venosa Central , Veias Hepáticas/fisiopatologia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Pressão na Veia Porta , Disfunção Primária do Enxerto/etiologia , Adulto , Feminino , Humanos , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/mortalidade , Disfunção Primária do Enxerto/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Pediatr Nephrol ; 34(6): 951-963, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29603016

RESUMO

The increasing use of extended criteria organs to meet the demand for kidney transplantation raises an important question of how the severity of early ischaemic injury influences long-term outcomes. Significant acute ischaemic kidney injury is associated with delayed graft function, increased immune-associated events and, ultimately, earlier deterioration of graft function. A comprehensive understanding of immediate molecular events that ensue post-ischaemia and their potential long-term consequences are key to the discovery of novel therapeutic targets. Acute ischaemic injury primarily affects tubular structure and function. Depending on the severity and persistence of the insult, this may resolve completely, leading to restoration of normal function, or be sustained, resulting in persistent renal impairment and progressive functional loss. Long-term effects of acute renal ischaemia are mediated by several mechanisms including hypoxia, HIF-1 activation, endothelial dysfunction leading to vascular rarefaction, sustained pro-inflammatory stimuli involving innate and adaptive immune responses, failure of tubular cells to recover and epigenetic changes. This review describes the biological relevance and interaction of these mechanisms based on currently available evidence.


Assuntos
Função Retardada do Enxerto/fisiopatologia , Transplante de Rim , Disfunção Primária do Enxerto/fisiopatologia , Animais , Progressão da Doença , Humanos , Traumatismo por Reperfusão/fisiopatologia
12.
J Heart Lung Transplant ; 38(2): 166-173, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30391199

RESUMO

BACKGROUND: Long-term survival after lung transplantation (LTx) is hampered by chronic lung allograft dysfunction (CLAD). Our study evaluated the prevalence and prognostic importance of obstructive and restrictive CLAD phenotypes, with or without an identifiable underlying cause, to validate the recently proposed classification system for CLAD. METHODS: Data for patients who underwent LTx between 2004 and 2015 with a minimal survival of 180 days post-LTx were retrospectively collected. Double LTx patients with CLAD (defined as a persistent forced expiratory volume in 1 second decline of ≥ 20% compared with baseline) were subsequently classified according to obstructive (forced expiratory volume in 1 second /forced vital capacity [FVC] < 70%, total lung capacity > 90%, and FVC > 80%) or restrictive (total lung capacity ≤ 90% or FVC ≤ 80%) pulmonary function and to the presence of an unknown (bronchiolitis obliterans syndrome [BOS]/restrictive allograft syndrome [RAS]) or known (non-BOS/non-RAS) underlying cause. RESULTS: After a median of 3.2 years, CLAD developed in 39% of double LTx patients (n = 219), of which 20% (n = 43) had an identifiable cause. Survival was worse in patients with restrictive CLAD (26%) compared with obstructive CLAD (64%; p < 0.0001). Non-BOS patients suffered from inferior survival compared with BOS patients (p = 0.0016), whereas there was no significant difference in survival between RAS and non-RAS (p = 0.17). Patients who evolved from an obstructive (BOS) to a restrictive (RAS) phenotype (10%) experienced better survival than RAS patients and a worse outcome compared with BOS patients (p < 0.0001). CONCLUSIONS: Given the differences in outcome, accurate diagnosis of CLAD phenotypes is important, because this helps to inform patients about their prognosis, to reveal underlying pathogenesis, to identify homogenous patient populations for clinical trials, and to guide future therapeutic approaches.


Assuntos
Transplante de Pulmão/efeitos adversos , Pulmão/fisiopatologia , Disfunção Primária do Enxerto/classificação , Adulto , Aloenxertos , Bélgica/epidemiologia , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/fisiopatologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Capacidade Pulmonar Total , Adulto Jovem
13.
Rev. Col. Bras. Cir ; 46(1): e2039, 2019. tab, graf
Artigo em Português | LILACS | ID: biblio-1003080

RESUMO

RESUMO Evitar mortes na fila de espera por um órgão não é mais o único foco de atenção das equipes de transplantação. As pesquisas e cuidados na prática clínica têm sido cada vez mais voltados para o funcionamento do enxerto pós-implante. O objetivo desse estudo foi identificar a nomenclatura utilizada na literatura para disfunção e não função de um enxerto hepático, bem como, investigar as incidências e fatores de risco. Trata-se de uma revisão integrativa da literatura de publicações na íntegra em português, inglês e espanhol, entre 2012 e 2016, nas bases: CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE e Web of Science. Foram selecionados 14 estudos em que se identificou incidências variando entre 7% e 27% e a nomenclatura utilizada para descrever o evento foi mau funcionamento inicial, hipofunção do enxerto, função marginal ou retardo na função. Foram encontradas incidências de não função primária do enxerto hepático entre 1,4% e 8,4% dos pacientes e a nomenclatura usada para descrever o evento foi disfunção precoce ou perda do enxerto. Os fatores de risco encontrados são relacionados às variáveis do doador, receptor, enxerto e logística do transplante. Conclui-se que o conhecimento das diferentes nomenclaturas empregadas na literatura, das incidências da disfunção e não função primária e seus fatores de risco são fundamentais para qualificar as intervenções de controle dos eventos na perspectiva de melhorar a sobrevida do paciente pós-transplante hepático.


ABSTRACT Avoiding deaths in the waiting list for an organ is no longer the only focus of the transplant teams attention. Research and care in clinical practice has been increasingly focused on post transplant graft survival and functioning. In the present work, we performed an integrative literature review to identify the terminology used about liver graft dysfunction and non-function, as well as to investigate the incidence and risk factors of these clinical events. We chosen articles written in Portuguese, English and Spanish between 2012 and 2016, based on CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE and Web of Science. We selected 14 studies, in which we identified the incidence of hepatic graft dysfunction ranging from 7% to 27%. The terminology used to describe this clinical event was initial malfunction, graft hypofunction, marginal function or delay in function. The primary non-function of the liver graft was found in 1.4% to 8.4% of the patients, and the terminology used to describe the event was early dysfunction or graft loss. The risk factors found are related to donor, recipient, graft and transplant logistics variables. We conclude that knowledge of the different terminologies employed in the literature, related to dysfunction and primary non- function incidence, and of their risk factors are fundamental to qualify the control of the events, aiming to improve patients' survival after liver transplantation.


Assuntos
Humanos , Transplante de Fígado/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Doadores de Tecidos , Fatores de Risco , Transplante de Fígado/métodos , Medição de Risco , Disfunção Primária do Enxerto/fisiopatologia , Transplantados , Fígado/fisiopatologia
14.
Transplant Proc ; 50(10): 3863-3872, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577279

RESUMO

Development of chronic lung allograft dysfunction involves various alloimmune-independent insults including those mediated by Toll-like receptor (TLR) signaling, which is known to activate alloimmune responses. We hypothesized that TLR signaling may also contribute to the activation of fibroblasts and promoting allograft airway fibrosis. Mouse orthotopic tracheal transplants were conducted between major histocompatibility complex (MHC)-mismatched Balb/c donor and wild-type C3H or C3H-derived TLR4 mutant recipients (nonfunctional TLR4). Immunohistochemistry on day 21 showed significantly smaller alpha-smooth muscle actin (α-SMA)-positive areas in TLR4 mutant recipients than wild-type recipients (P = .01). No difference was found for CD3+ T-cell infiltration. Proliferation of alloreactive T cells derived from the recipient spleen showed no difference between TLR4 mutant and wild-type recipients in a mixed lymphocyte reaction. The effect of TLR4 signaling was examined in primary pulmonary fibroblast cultures both with lipopolysaccharide (LPS) and transforming growth factor (TGF)-ß1. Stimulation with LPS significantly increased expression of α-SMA mRNA in wild-type fibroblasts cultured with TGF-ß1 compared with the control without LPS (P = .001). Taken together, these findings suggest disruption of TLR signaling leads to reduced activation of fibroblasts without affecting T-cell infiltration and proliferation in this model. TLR4-mediated activation of fibroblasts may be a potentially important mechanism of allograft remodeling.


Assuntos
Fibroblastos/metabolismo , Disfunção Primária do Enxerto/metabolismo , Disfunção Primária do Enxerto/patologia , Receptor 4 Toll-Like/metabolismo , Traqueia/transplante , Aloenxertos/metabolismo , Aloenxertos/patologia , Aloenxertos/fisiopatologia , Animais , Fibrose/metabolismo , Fibrose/patologia , Transplante de Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Disfunção Primária do Enxerto/fisiopatologia , Transplante Homólogo
15.
Ann Transplant ; 23: 481-490, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30013021

RESUMO

BACKGROUND Successful graft regeneration is important in living-donor liver transplantation (LDLT) because partial liver grafts are used. Early allograft dysfunction (EAD) is an intermediate outcome that affects the long-term postoperative course in liver transplantation. The aim of the present study was to investigate liver graft regeneration under EAD development in LDLT. MATERIAL AND METHODS The data of 226 patients who underwent LDLT from September 2010 to July 2014 were retrospectively analyzed. The patients were classified into 2 groups: one with and one without EAD. Graft regeneration, functional recovery, and long-term patient survival were compared between the 2 groups. RESULTS The grafts grew more vigorously in the EAD group than in the non-EAD group, as evidenced by the larger absolute (ALV) and relative liver volumes (RLV) of the former on postoperative days (POD) 7 and 21. The median (interquartile range) RLVs of the non-EAD group versus the EAD group were as follows: 55.2 (47.9-65.8) vs. 53.7 (46.6-64.5)% preoperatively, p>0.05; 76.1 (66.9-85.7) vs. 86.7 (73.9-96.8)% on POD 7, p<0.01; 79.6 (69.3-91.2) vs. 93.7 (79.6-101.6)%, p<0.01 on POD 21. In the early postoperative period, hepatic function, measured as total bilirubin and international normalized ratio, was higher in the EAD group; however, after EAD development, graft function recovered in these patients. In the follow-up period, overall patient survival was comparable between the 2 groups. CONCLUSIONS The liver grafts of EAD patients steadily regenerated, such that the development of EAD did not affect long-term patient survival after LDLT.


Assuntos
Sobrevivência de Enxerto/fisiologia , Regeneração Hepática/fisiologia , Transplante de Fígado , Fígado/fisiopatologia , Disfunção Primária do Enxerto/fisiopatologia , Feminino , Humanos , Fígado/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Heart Lung Transplant ; 37(7): 895-902, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29602706

RESUMO

BACKGROUND: The prognostic value of defining normal vs abnormal baseline post-transplant lung function (or baseline lung allograft dysfunction [BLAD]) has not been studied using standardized reference values of percent predicted of the population. Our aim was to assess the association between BLAD and survival in double-lung transplant recipients and assess for potential pre-transplant donor and recipient risk factors for BLAD. METHODS: We conducted a retrospective cohort study of double-lung transplant recipients in our program during the period 2004 to 2009. We defined normal baseline function as both forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) ≥80% predicted on at least 2 consecutive tests ≥3 weeks apart; we defined BLAD as failure to meet these criteria. We used a Cox regression model to assess the association between BLAD and survival. We used logistic regression to assess potential pre-transplant donor and recipient factors associated with BLAD. RESULTS: Of 178 patients double-lung transplant recipients eligible for study, 75 (42%) met the criteria for BLAD. BLAD was associated with impaired survival (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.41 to 3.54]) via Cox regression compared to patients with normal baseline, and lower baseline was associated with greater risk of death in a dose-dependent fashion. Pre-transplant factors associated with BLAD included interstitial lung disease (ILD) as an indication for transplant (odds ratio [OR] 2.66, 95% CI 1.17 to 6.15) and heavy donor smoking history (OR 3.07, 95% CI 1.17 to 8.43). CONCLUSIONS: BLAD is dynamic risk state associated with impaired survival after double-lung transplantation, and should be considered when physiologically phenotyping patients.


Assuntos
Transplante de Pulmão/métodos , Disfunção Primária do Enxerto/mortalidade , Adulto , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Capacidade Vital
17.
Exp Cell Res ; 369(1): 27-33, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29704468

RESUMO

Autophagy is upregulated under stress conditions to degrade superfluous proteins and recycle damaged organelles including damaged mitochondria. However, the occurrence of mitochondrial autophagy and its contribution remain to be elucidated during renal ischemia/reperfusion injury (IRI). In this study, mitophagosomes and engulfed mitochondria were frequently observed by electron microscopy after renal IRI vs. control. Meanwhile, the increase of lipidated microtubule associated protein light chain 3 (LC3-II) and decrease of mitochondrial proteins were detected by western blot, suggesting the presence of mitophagy. Drp1 translocated to mitochondria and was phosphorylated at S616 in response to IRI. Interestingly, we found that inhibiting drp1 phosphorylation with mdivi-1 significantly suppressed IRI-induced mitophagy without affecting general autophagy. Furthermore, our results showed that downregulation of mitophagy significantly exacerbated cell apoptosis and markedly aggravated kidney dysfunction induced by IRI. Taken together, these data indicate that mitophagy was activated via Drp1-dependent pathway and such mitophagic clearance of damaged mitochondria protects cells from IRI-induced apoptosis.


Assuntos
Lesão Renal Aguda/prevenção & controle , Dinaminas/fisiologia , Rim/irrigação sanguínea , Mitofagia/fisiologia , Traumatismo por Reperfusão/fisiopatologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/fisiopatologia , Animais , Apoptose/fisiologia , Autofagossomos/fisiologia , Citoproteção/fisiologia , Dinaminas/genética , Isquemia/complicações , Isquemia/genética , Isquemia/fisiopatologia , Rim/patologia , Transplante de Rim/efeitos adversos , Masculino , Disfunção Primária do Enxerto/genética , Disfunção Primária do Enxerto/fisiopatologia , Disfunção Primária do Enxerto/prevenção & controle , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/genética
18.
Transplant Proc ; 50(3): 815-818, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29661444

RESUMO

INTRODUCTION: The lung transplantation (LTx) program began in Ceará in 2011 and the first LTx was performed on June 11, 2011. The aim of this study was to present the initial results of the 6-year experience of our program. METHODS: We retrospectively reviewed our experience on LTx from June 2011 to August 2017. Data on recipients and transoperative and postoperative outcomes were recorded in a database. RESULTS: Twenty-two (56.4%) were single LTx, 15 (38.5%) were double, and 2 (5.1%) bilateral lobar. The mean age was 47.5 ± 15 years, and 26 (66.7%) were men. Twenty-eight (71.8%) had pulmonary fibrosis; 5 (12.8%) had pulmonary emphysema, 3 (7.7%) had bronchiectasis; 2 (5.1%) had pulmonary hypertension, and 1 (2.6%) had lymphangioleiomyomatosis. Complications occurred in 82% (32/39) and in-hospital mortality was 30.8% (single LTx = 27.8% and double LTx = 33.3%). The main complications were infection in 17 (43.5%) cases and primary graft dysfunction in 7 (17.9%). There was a significant improvement in pulmonary function in the first year of follow-up (forced expiratory volume pre-LTx = 37% ± 16% and 12 months post-LTx = 72% ± 22%, P = .001); and overall survival at 36 months was 59.0%, with no difference between single- and double-lung transplants. CONCLUSIONS: Idiopathic pulmonary fibrosis was the most common underlying disease and single LTx was the most commonly performed operation. There was a high incidence of postoperative complications and in-hospital mortality, but the 36-month follow-up showed a marked improvement in lung function and a global survival similar to the literature.


Assuntos
Fibrose Pulmonar Idiopática/cirurgia , Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Complicações Pós-Operatórias/mortalidade , Disfunção Primária do Enxerto/mortalidade , Adulto , Brasil , Feminino , Volume Expiratório Forçado , Mortalidade Hospitalar , Humanos , Incidência , Pulmão/fisiopatologia , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Período Pós-Operatório , Disfunção Primária do Enxerto/fisiopatologia , Testes de Função Respiratória , Estudos Retrospectivos , Resultado do Tratamento
19.
J Thorac Cardiovasc Surg ; 155(5): 2193-2206.e3, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29653665

RESUMO

OBJECTIVES: The value of intraoperative extracorporeal membrane oxygenation (ECMO) in lung transplantation remains controversial. In our department, ECMO has been used routinely for intraoperatively unstable patients for more than 15 years. Recently, we have extended its indication to a preemptive application in almost all cases. In addition, we prolong ECMO into the early postoperative period whenever graft function does not meet certain quality criteria or in patients with primary pulmonary hypertension. The objective of this study was to review the results of this strategy. METHODS: All standard bilateral lung transplantations performed between January 2010 and June 2016 were included in this single-center, retrospective analysis. Patients were divided into 3 groups: group I-no ECMO (n = 116), group II-intraoperative ECMO (n = 343), and group III-intraoperative and prolonged postoperative ECMO (n = 123). The impact of different ECMO strategies on primary graft function, short-term outcomes, and patient survival were analyzed. RESULTS: The use of intraoperative ECMO was associated with improved 1-, 3-, and 5-year survival compared with non-ECMO patients (91% vs 82%, 85% vs 76%, and 80% vs 74%; log-rank P = .041). This effect was still evident after propensity score matching of both cohorts. Despite the high number of complex patients in group III, outcome was excellent with higher survival rates than in the non-ECMO group at all time points. CONCLUSIONS: Intraoperative ECMO results in superior survival when compared with transplantation without any extracorporeal support. The concept of prophylactic postoperative ECMO prolongation is associated with excellent outcomes in recipients with pulmonary hypertension and in patients with questionable graft function at the end of implantation.


Assuntos
Oxigenação por Membrana Extracorpórea , Cuidados Intraoperatórios/métodos , Pneumopatias/cirurgia , Transplante de Pulmão , Adulto , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Sobrevivência de Enxerto , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Cuidados Intraoperatórios/efeitos adversos , Cuidados Intraoperatórios/mortalidade , Pneumopatias/diagnóstico , Pneumopatias/mortalidade , Pneumopatias/fisiopatologia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/fisiopatologia , Disfunção Primária do Enxerto/prevenção & controle , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Transplant Proc ; 50(2): 605-609, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29579865

RESUMO

INTRODUCTION: The current imbalance between available donors and potential recipients for orthotopic liver transplantation (OLT) has led to a liberalization of organ acceptance criteria, increasing the risk of post-transplant complications such as early allograft dysfunction (EAD). Consequently, we need accurate criteria to detect patients with early poor graft function to guide the strategies of management. We evaluated the usefulness of two frequently used criteria: the definition from Olthoff et al and the Model for Early Allograft Function (MEAF) scoring. PATIENTS AND METHODS: Unicentric cohort study of patients undergoing OLT between January 1, 2010, and November 20, 2016. We performed a univariate study to detect donor, recipient, and transplant factors favoring EAD, defined both by Olthoff criteria and a MEAF score higher than 7. Finally, we developed a comparative survival analysis for cases having or not EAD. RESULTS: In all, 201 transplants met inclusion criteria. According to the stated cutoff for MEAF score, the frequency of EAD was 9.3%, with a significant association to low recipient body mass index and prolonged total graft ischemia time, resulting in lower patient 3-month postoperative survival. According to Olthoff criteria, EAD incidence was 22.1% and was associated with younger donor and recipient ages and higher Model for End-stage Liver Disease and Child-Pugh recipient scores. Its development resulted in lower graft and recipient survival at 3 months after OLT. CONCLUSION: MEAF score and Olthoff criteria are useful tools for detection of EAD. The latter could select more appropriately patients at risk, but its calculation cannot be done until the seventh day after OLT, unlike MEAF score, available on third day.


Assuntos
Sobrevivência de Enxerto/fisiologia , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/epidemiologia , Índice de Gravidade de Doença , Adulto , Aloenxertos/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/fisiopatologia , Fatores de Risco , Fatores de Tempo , Doadores de Tecidos , Transplante Homólogo/efeitos adversos
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