Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

Severe and Moderate Primary Graft Dysfunction in Adult Heart Recipients.

INTRODUCTION: The aims of this study were to determine the incidence of severe and moderate primary graft dysfunction (PGD) in our center, to identify, retrospectively, donors' and recipients' risk factors for PGD development, and to evaluate the impact of PGD within 30 days after heart transplantation. METHODS: Donors' and recipients' medical records of 64 consecutive adult cardiac transplantations performed between January 2016 and June 2017 were reviewed. The International Society for Heart and Lung Transplantation (ISHLT) criteria were used to diagnose moderate and severe PGD. Associations of risk factors for combined moderate/severe PGD were assessed with appropriate statistical analyses. RESULTS: Sixty-four patients underwent heart transplantation in this period. Twelve recipients (18.7%) developed severe or moderate PGD. Development of PGD was associated with previous donor cardiopulmonary resuscitation and a history of prior heart surgery in the recipient (P=0.01 and P=0.02, respectively). The 30-day in hospital mortality was similar in both PGD and non-PGD patients. CONCLUSION: The use of the ISHLT criteria for PGD is important to identify potential risk factor. The development of PGD did not affect short-term survival in our study. More studies should be done to better understand the pathophysiology of PGD.

Experiencia en trasplante pulmonar pediátrico en Chile / Experience with pediatric lung transplantation in Chile

El trasplante de pulmón (TP) es una opción para pacientes pediátricos con enfermedades pulmonares terminales. OBJETIVO: Evaluar resultados y sobrevida de pacientes pediátricos trasplantados de pulmón. MÉTODOS: Análisis retrospectivo de registros clínicos de pacientes TP ≤ 15 años de Clínica Las Condes. Se analizaron datos demográficos, tipo de trasplante, función pulmonar basal y post trasplante, complicaciones precoces y tardías y sobrevida. RESULTADOS: Nueve pacientes < 15 años de edad se han trasplantado. La edad promedio fue 12,7 años. La principal indicación fue fibrosis quística (7 pacientes). El IMC promedio fue de 17,6 y todos estaban con oxígeno domiciliario. El 77% utilizó soporte extracorpóreo intraoperatorio. Las principales complicaciones precoces fueron hemorragia y la disfunción primaria de injerto mientras que las tardías fueron principalmente las infecciones y la disfunción crónica de injerto. Cuatro pacientes han fallecido y la sobrevida a dos años fue de 85%. El trasplante les permitió una reinserción escolar y 3 lograron completar estudios universitarios. CONCLUSIÓN: El trasplante pulmonar es una alternativa para niños con enfermedades pulmonares avanzadas mejorando su sobrevida y calidad de vida.

Lung transplantation (TP) is a treatment option in children with terminal lung diseases. OBJECTIVE: To evaluate the results and survival of pediatrics lung transplant patients. METHODS: Retrospective analysis of clinical records of lung transplantation of patients ≤ 15 years from Clínica Las Condes, Santiago, Chile. Demographic data, type of transplant, baseline and post transplant lung function, early and late complications and survival rate were analyzed. RESULTS: Nine patients ≤ 15 years-old were transplanted. The average age at transplant was 12.7 years. The main indication was cystic fibrosis (7 patients). The average BMI was 17.6 and all the patients were with home oxygen therapy. 77% used extracorporeal intraoperative support. Average baseline FEV1 was 25.2% with progressive improvement in FEV1 of 77% in the first year. The main early complications were hemorrhage and primary graft dysfunction, while late complications were infections and chronic graft dysfunction. Four patients have died and the estimated 2 years survival was 85%. They achieved school reinsertion and three managed to complete university studies. CONCLUSION: Lung transplantation is an alternative for children with advanced lung diseases improving their survival and quality of life.

Early Graft Dysfunction Evaluation by Indocyanine Green Plasma Clearance Rate in the Immediate Postoperative Period After Liver Transplantation.

BACKGROUND: Liver transplantation (LT) has evolved to improve graft and patient survival. Early graft dysfunction (EGD) and primary nonfunction are an important cause of morbi-mortality. We had formulated the scientific hypothesis that the liver function can be evaluated by the indocyanine green (IG) after LT. The aim was to evaluate the EGD by plasma disappearance rate (PDR) of IG after LT. METHOD: Prospective and observational clinical study, from July 2014 to June 2015. IG evaluation by pulse densitometry, Limon system. Degree analysis of ischemia and reperfusion injury in groups as follows: 1 (G0/G1/G2) and 2 (G3/G4). Donor risk index (DRI), Wagener and Olthoff criteria, and prognostic predictors were evaluated. All tests were performed with bidirectional α of 0.05 and a confidence interval of 95% and support by IBM SPSS 25. RESULTS: A total of 40 patients, mean age 53.3 ± 14.0 years and a majority of men and hepatitis C virus. PDR were more relevant with high degrees of ischemia and reperfusion injury grades G3/G4 (P = .030). The PDR related to the donor risk index showed positive significance at DRI >1.5 (P = .066). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death (P = .063). CONCLUSION: EGD can be assessed by PDR with high degrees of ischemia and reperfusion injury (G3/G4) and with marginal donors (DRI >1.5). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death of the patient.

Fatores de risco para disfunção e para não função primária do fígado transplantado em um contexto brasileiro / Risk factors for dysfunction and primary non-function of the transplanted liver in a Brazilian context

A disfunção precoce do enxerto é descrita como mau funcionamento inicial, função marginal ou retardo na função e incide entre 7% e 27% dos pacientes transplantados de fígado. A não função primária é a perda do enxerto e incide entre 1,4% e 8,4% nessa população. O presente estudo foi conduzido para analisar fatores de risco para disfunção e para não função primária de fígados transplantados. Foram pesquisados fatores do doador, do enxerto, do paciente e da logística do transplante. Trata-se de um estudo epidemiológico, tipo coorte histórica conduzido com 180 prontuários de pacientes transplantados e admitidos na Unidade de Terapia Intensiva, cujos doadores estavam em morte encefálica. Todos os transplantes foram realizados no Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil, entre 2012 e 2018. Análises estatísticas descritiva, bivariada e multivariada foram realizadas usando o método de Kaplan-Meier e o teste Log-rank. Associação entre os fatores de risco e os desfechos foi estabelecida aplicando a regressão de Cox e o processo de seleção Backward, ajustada pelo Hazard ratio. Verificou-se que os receptores de fígado tinham idade média de 52,1 anos; em sua maioria homens brancos. As indicações do transplante foram: doença alcoólica, 31,7%; doença metabólica e Hepatite viral, 26,1%; tumor, 22,2%; doença colestática, 17,8% e doença vascular, 2,8%. Índice de Massa Corporal igual ou superior a 30 kg/m² foi encontrado em 3,9%. O escore médio do Model for End-Stage Liver Disease foi de 23 e a creatinina sérica média foi de 1,35mg/dl. Em relação aos doadores, a idade média foi de 37,6 anos, sendo 39,4% do sexo feminino. As causas da morte encefálica foram acidente vascular cerebral em 86 (47,8%), traumatismo craniano em 77 (42,8%) e por outras causas 17 (9,4%). A aspartato aminotransferase foi, em média, 77,20 UI/L, a alanina aminotransferase foi, em média, 60,42 UI/L. Sódio sérico >160 mmol/l ocorreu em 18,6% e a Gamaglutamiltransferase média foi de 77 UI/L. O Índice de Risco do Doador médio foi de 1,476. Quanto ao enxerto verificou-se que sua origem foi local em 37,8%; regional, em 56,7% e nacional, em 5,5% dos casos. O tempo de isquemia fria (>10 horas) ocorreu em 58 (32,2%). O tempo de isquemia quente (> 60 minutos) ocorreu em 14 (9,9%) % dos transplantes e o tempo médio da cirurgia do receptor foi de 6,1 horas. Estes receberam, em média, 4 U de plaquetas e 5 (2.8%) receberam Plasma Fresco Congelado > 30U. O Equilíbrio do Risco médio foi de 10. A evolução clínica9 normal ocorreu em 66 (36,7%) dos pacientes. A disfunção precoce do enxerto foi identificada em 104 (57,8%) e a não função primária em 10 (5,5%). Encontrou-se que o doador do sexo feminino, o tempo de isquemia quente do enxerto superior a 60 minutos e o consumo de Plasma Fresco Congelado > 30 U pelo receptor, constituem risco aumentado para disfunção precoce do enxerto nesta amostra. O fator de risco para a não função primária foi o volume de plaquetas consumido pelo receptor. O controle desses fatores de risco contribui para a função adequada do fígado após o transplante e melhora da sobrevida dos enxertos e dos pacientes.

Early graft dysfunction is described as initial malfunction, marginal function or delayed function, and it affects between 7% and 27% of liver transplant patients. The primary nonfunction is graft loss, and it affects between 1.4% and 8.4% of this population. The present study was conducted to analyze risk factors for dysfunction and non-primary function of transplanted livers. Donor, graft, patient, and transplant logistics factors were researched. This is an epidemiological study, with a historical cohort conducted with 180 medical records of transplanted patients admitted to the Intensive Care Unit, whose donors were brain dead. All transplants were performed at the Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Brazil, between 2012 and 2018. Descriptive, bivariate, and multivariate statistical analyzes were performed using the Kaplan-Meier method and the Log-rank test. Association between risk factors and outcomes was assessed by Cox regression and the Backward selection process, adjusted by the Hazard ratio. The liver receptors were mostly white males with an average age of 52.1 years. Transplant indications were: alcoholic disease, 31.7%; metabolic disease and viral hepatitis, 26.1%; tumor, 22.2%; cholestatic disease, 17.8% and vascular disease, 2.8%. Body Mass Index equal to or greater than 30 kg / m² occurred 3.9%. The average score for the Model for End-Stage Liver Disease was 23, and the mean serum creatinine was 1.35mg / dl. Regarding donors, the average age was 37.6 years, with 39.4% being female. The causes of brain death were stroke in 86 (47.8%), head injury in 77 (42.8%), and for other causes in 17 (9.4%). Aspartate aminotransferase was, on average, 77.20 UI/L. Alanine aminotransferase was, on average, 60.42 UI/L. Serum sodium > 160 mmol/l occurred in 18.6%, and the mean Gamaglutamiltransferase was 77 IU / L. The average Donor Risk Index was 1.476. As for the graft, it was found that its origin was local in 37.8%; regional, in 56.7%; and national, in 5.5% of cases. The cold ischemia time (> 10 hours) occurred in 58 (32.2%), the warm ischemia time (> 60 minutes) occurred in 14 (9.9%) of the transplants. The average time of the recipient's surgery was 6.1 hours, who received 4 U of platelets on average. 5 (2.8%) received fresh frozen plasma > 30 U. The average Balance of risk was 10. The normal clinical evolution occurred in 66 (36.7%) of the patients. Early graft dysfunction occurred in 104 (57.8%), and primary non-function in 10 (5.5%). The risk factors for early graft dysfunction were the female donor, the graft warm ischemia time greater than 60 minutes, and the11 consumption of fresh frozen plasma > 30 U by the recipient. The risk factor for primary nonfunction was the volume of platelets consumed by the recipient. The control of these risk factors contributes to the adequate function of the liver after transplantation and to improve grafts and patient's survival

A simple scoring model for predicting early graft failure and postoperative mortality after liver transplantation.

INTRODUCTION AND OBJECTIVES: Graft failure and postoperative mortality are the most serious complications after liver transplantation. The aim of this study is to establish a prognostic scoring system to predict graft and patient survival based on serum transaminases levels that are routinely used during the postoperative period in human cadaveric liver transplants. PATIENTS AND METHODS: Postoperative graft failure and patient mortality after liver transplant were analyzed from a consecutive series of 1299 patients undergoing cadaveric liver transplantation. This was correlated with serum liver function tests and the rate of reduction in transaminase levels over the first postoperative week. A cut-off transaminase level correlating with graft and patient survival was calculated and incorporated into a scoring system. RESULTS: Aspartate-aminotransferase (AST) on postoperative day one showed significant correlation with early graft failure for levels above 723U/dl and early postoperative mortality for levels above 750U/dl. AST reduction rate (day 1 to 3) greater than 1.8 correlated with reduced graft failure and greater than 2 with mortality. Alanine-aminotransferase (ALT) reduction in the first 48h post transplantation also correlated with outcomes. CONCLUSION: A scoring system with these three variables allowed us to classify our patients into three groups of risk for early graft failure and mortality.

Primary liver graft dysfunction and non-function: integrative literature review. / Disfunção e não função primária do enxerto hepático: revisão integrativa.

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.

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.

Brain death-induced cytokine release is not associated with primary graft dysfunction: a cohort study. / A liberação de citocinas induzida pela morte cerebral não está associada à disfunção primária do enxerto: um estudo de coorte.

OBJECTIVE: To examine the association between donor plasma cytokine levels and the development of primary graft dysfunction of organs transplanted from deceased donors. METHODS: Seventeen deceased donors and the respective 47 transplant recipients were prospectively included in the study. Recipients were divided into two groups: group 1, patients who developed primary graft dysfunction; and group 2, patients who did not develop primary graft dysfunction. Donor plasma levels of TNF, IL-6, IL-1ß, and IFN-γ assessed by ELISA were compared between groups. RESULTS: Sixty-nine organs were retrieved, and 48 transplants were performed. Donor plasma cytokine levels did not differ between groups (in pg/mL): TNF, group 1: 10.8 (4.3 - 30.8) versus group 2: 8.7 (4.1 - 33.1), p = 0.63; IL-6, group 1: 1617.8 (106.7 - 5361.7) versus group 2: 922.9 (161.7 - 5361.7), p = 0.56; IL-1ß, group 1: 0.1 (0.1 - 126.1) versus group 2: 0.1 (0.1 - 243.6), p = 0.60; and IFN-γ, group 1: 0.03 (0.02 - 0.2) versus group 2: 0.03 (0.02 - 0.1), p = 0.93). Similar findings were obtained when kidney transplants were analyzed separately. CONCLUSION: In this sample of transplant recipients, deceased donor plasma cytokines TNF, IL-6, IL-1ß, and IFN-γ were not associated with the development of primary graft dysfunction.

OBJETIVO: Examinar a associação entre os níveis de citocinas no plasma do doador e o desenvolvimento de disfunção primária do enxerto de órgãos transplantados a partir de doadores falecidos. MÉTODOS: Foram incluídos no estudo de forma prospectiva 17 doadores falecidos e os respectivos 47 pacientes receptores de transplante. Os receptores foram divididos em dois grupos: grupo 1, de pacientes que desenvolveram disfunção primária do enxerto, e grupo 2, de pacientes que não desenvolveram disfunção primária do enxerto. Os níveis de TNF, IL-6, IL-1ß, e IFN-γ, avaliados por meio de ELISA, foram comparados entre os grupos. RESULTADOS: Obtiveram-se 69 órgãos, sendo realizados 48 transplantes. Os níveis plasmáticos de citocinas nos doadores não diferiram entre os grupos (em pg/mL): TNF no grupo 1, com 10,8 (4,3 - 30,8) versus no grupo 2, com 8,7 (4,1 - 33,1), com valor de p = 0,63; IL-6 no grupo 1: 1.617,8 (106,7 - 5.361,7) versus no grupo 2: 922,9 (161,7 - 5.361,7), com p = 0,56; IL-1ß, no grupo 1: 0,1 (0,1 - 126,1) versus no grupo 2: 0,1 (0,1 - 243,6), com p = 0,60; e IFN-γ, no grupo 1: 0,03 (0,02 - 0,2) versus no grupo 2: 0,03 (0,02 - 0,1), p = 0,93). Obtivemos resultados similares ao examinar separadamente os casos de transplante renal. CONCLUSÃO: Nesta amostra de receptores de transplante, os níveis plasmáticos das citocinas TNF, IL-6, IL-1ß e IFN-γ nos doadores não se associaram com o desenvolvimento de disfunção primária do enxerto.

A liberação de citocinas induzida pela morte cerebral não está associada à disfunção primária do enxerto: um estudo de coorte / Brain death-induced cytokine release is not associated with primary graft dysfunction: a cohort study

RESUMO Objetivo: Examinar a associação entre os níveis de citocinas no plasma do doador e o desenvolvimento de disfunção primária do enxerto de órgãos transplantados a partir de doadores falecidos. Métodos: Foram incluídos no estudo de forma prospectiva 17 doadores falecidos e os respectivos 47 pacientes receptores de transplante. Os receptores foram divididos em dois grupos: grupo 1, de pacientes que desenvolveram disfunção primária do enxerto, e grupo 2, de pacientes que não desenvolveram disfunção primária do enxerto. Os níveis de TNF, IL-6, IL-1β, e IFN-γ, avaliados por meio de ELISA, foram comparados entre os grupos. Resultados: Obtiveram-se 69 órgãos, sendo realizados 48 transplantes. Os níveis plasmáticos de citocinas nos doadores não diferiram entre os grupos (em pg/mL): TNF no grupo 1, com 10,8 (4,3 - 30,8) versus no grupo 2, com 8,7 (4,1 - 33,1), com valor de p = 0,63; IL-6 no grupo 1: 1.617,8 (106,7 - 5.361,7) versus no grupo 2: 922,9 (161,7 - 5.361,7), com p = 0,56; IL-1β, no grupo 1: 0,1 (0,1 - 126,1) versus no grupo 2: 0,1 (0,1 - 243,6), com p = 0,60; e IFN-γ, no grupo 1: 0,03 (0,02 - 0,2) versus no grupo 2: 0,03 (0,02 - 0,1), p = 0,93). Obtivemos resultados similares ao examinar separadamente os casos de transplante renal. Conclusão: Nesta amostra de receptores de transplante, os níveis plasmáticos das citocinas TNF, IL-6, IL-1β e IFN-γ nos doadores não se associaram com o desenvolvimento de disfunção primária do enxerto.

ABSTRACT Objective: To examine the association between donor plasma cytokine levels and the development of primary graft dysfunction of organs transplanted from deceased donors. Methods: Seventeen deceased donors and the respective 47 transplant recipients were prospectively included in the study. Recipients were divided into two groups: group 1, patients who developed primary graft dysfunction; and group 2, patients who did not develop primary graft dysfunction. Donor plasma levels of TNF, IL-6, IL-1β, and IFN-γ assessed by ELISA were compared between groups. Results: Sixty-nine organs were retrieved, and 48 transplants were performed. Donor plasma cytokine levels did not differ between groups (in pg/mL): TNF, group 1: 10.8 (4.3 - 30.8) versus group 2: 8.7 (4.1 - 33.1), p = 0.63; IL-6, group 1: 1617.8 (106.7 - 5361.7) versus group 2: 922.9 (161.7 - 5361.7), p = 0.56; IL-1β, group 1: 0.1 (0.1 - 126.1) versus group 2: 0.1 (0.1 - 243.6), p = 0.60; and IFN-γ, group 1: 0.03 (0.02 - 0.2) versus group 2: 0.03 (0.02 - 0.1), p = 0.93). Similar findings were obtained when kidney transplants were analyzed separately. Conclusion: In this sample of transplant recipients, deceased donor plasma cytokines TNF, IL-6, IL-1β, and IFN-γ were not associated with the development of primary graft dysfunction.

Serum Factor V Is a Continuous Biomarker of Graft Dysfunction and a Predictor of Graft Loss After Liver Transplantation.

BACKGROUND: Factor V has never been compared to a validated early allograft dysfunction (EAD) definition. We aimed to assess factor V as a biomarker of EAD and a predictor of graft loss after liver transplantation (LT). METHODS: We retrospectively assessed the serum factor V levels on postoperative day 1 after LT. Patients were divided according to their factor V levels into the ≤36.1 U/mL and > 36.1 U/mL groups. The primary outcome was graft loss within 1, 3, and 6 months. The secondary outcome was EAD, as defined by Olthoff et al. Predictors of outcomes were identified by multivariable logistic regression. RESULTS: Two hundred twenty-seven patients were included in the study: 74 with factor V of 36.1 U/mL or less and 153 with factor V >36.1 U/mL. EAD was diagnosed in 41 (55.4%) of 74 patients with factor V of 36.1 U/mL or less and in 20/153 (13.1%) patients with factor V >36.1 U/mL (P < 0.001). According to the multivariable regression model, factor V was a continuous marker of EAD (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94-0.98 per U/mL). Among the study groups, the 1-, 3-, and 6-month graft survival rates were 82%, 74%, and 74%, respectively, for patients with factor V of 36.1 U/mL or less and 98%, 95%, and 95%, respectively, for patients with factor V >36.1 U/mL (P = 0.001). Factor V was a continuous predictor for 3- and 6-month graft losses (OR, 0.96; 95% CI, 0.94-0.99 and OR, 0.97; 95% CI, 0.94-0.99 per U/mL), whereas EAD was not significant when adjusted for factor V. CONCLUSION: Factor V is an early marker for EAD and is a continuous predictor of short-term graft loss after LT.

Disfunção e não função primária do enxerto hepático: revisão integrativa / Primary liver graft dysfunction and non-function: integrative literature review

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.

Evolución clínica, funcional y radiológica de pacientes trasplantados pulmonares con síndrome de bronquiolitis obliterante y disfunción de injerto pulmonar restrictivo / Clinical, functional and radiological evolution of pulmonary transplant patients with bronchiolitis obliterans syndrome and restrictive graft dysfunction

Resumen La principal complicación a largo plazo en trasplantados de pulmón es la disfunción crónica de injerto identificado como bronquiolitis obliterante, existiendo un nuevo patrón denominado Disfunción de Injerto Restrictivo. Objetivo: Evaluar seguimiento espirométrico, radiológico y clínico entre pacientes con síndrome de bronquiolitis obliterante (SBO) y Disfunción de Injerto Restrictivo (DIR) post trasplante pulmonar. Metodología: Se revisaron registros clínicos de trasplantados pulmonares desde 1999 hasta 2017. Se efectuó seguimiento espirométrico e imágenes por tomografía de tórax y factores asociados: infección por Citomegalovirus(CMV), reflujo gastro-esofágico (RGE) y episodios de rechazo agudo. Se analizó sobrevida por Kaplan Meier. Resultados: De 88 pacientes trasplantados de pulmón, 40 desarrollaron disfunción crónica de injerto: 31 (80%) presentaron SBO y 9 (20%) tuvieron DIR. Edad promedio: 47 años en SBO y 46 años en DIR. Siendo fibrosis pulmonar la patología basal predominante en ambos. En SBO se consignaron 14 episodios de rechazo agudo (50%), infección por CMV en 18% y RGE activo en 26%. En la serie DIR hubo 5 episodios de rechazo agudo (62%), 13% de infección por CMV y 67% de RGE activo 6 (p = 0,02). En el seguimiento a 1-2-4-5 años el promedio del VEF1 en SBO fue: 67,3,65, 60 y 48% del valor predicho y en DIR fue 61, 65, 62 y 45% respectivamente. Las imágenes tomográficas en SBO mostraron: hiperinflación y en DIR: fibrosis pleuropulmonar superior. La sobrevida fue de 96,9 meses en SBO y 65,6 meses en DIR (p = 0,06). Conclusions: La disfunción restrictiva presentó menor sobrevida que SBO. RGE se asoció a rechazo restrictivo. La tomografía de tórax difiere en ambos tipos de rechazo crónico.

The main long-term complication in lung transplant patients is chronic graft dysfunction identified as bronchiolitis obliterans, and there is a new pattern called Restrictive Graft Dysfunction. Objective: To evaluate spirometric, radiological and clinical follow-up among patients with bronchiolitis obliterans syndrome (BOS) and Restrictive Allograft Syndrome (RAS) after lung transplantation. Methodology: Lung transplant recipients ' clinical records were reviewed from 1999 to 2017. We carried out a follow up of spirometry, chest tomography imaging and associated factors: cytomegalovirus (CMV) infection, gastroesophageal reflux (GER) and episodes of acute rejection. Survival was analyzed by Kaplan Meier. Results: Out of 88 lung transplant patients, 40 developed chronic graft dysfunction: 31 (80%) presented BOS and 9 (20%) had RAS. Mean age: 47 yr.o. in BOS and 46 yr. o. in RAS. Lung fibrosis was the primary pathology predominant in both conditions. In BOS were reported 14 episodes of acute rejection (50%), CMV infection in 18% and active GER in 26%. In RAS there were 5 episodes of acute rejection (62%), CMV infection in 13% and active GER in 67% (p = 0.02). VEF1 follow-up at 1-2-4-5 years averaged 67, 65, 60 and 8% of reference value in BOS and 61, 65, 62 and 45% in RAS respectively. CT scans showed hyperinflation in BOS and upper pleuropulmonary fibrosis in RAS. BOS survival time was 96.9 months versus 65.6 months in RAS (p = 0.06). Conclusiones: Restrictive dysfunction presented a lower survival rate than BOS. GER was associated with restrictive rejection. Chest tomography differs in both types of chronic rejection.

Single- and Double-Lung Transplantation: Results of an Initial Experience of 39 Cases in Ceará (Northeast Brazil).

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.

Transvenous dual-chamber pacemaker after paediatric heart transplantation using left ventricle pacing through the coronary sinus.

A 12-year-old child with end-stage heart failure due to restrictive cardiomyopathy was submitted to orthotopic heart transplantation. Primary graft dysfunction required venous arterial extra-corporeal membrane oxygenation. Heart function normalized, but complete atrioventricular block remained after 3 weeks. A dual-chamber pacing with transvenous left ventricle pacing through the coronary sinus was performed. At 5-year follow-up, the patient is stable with the same pacing system and with preserved ventricular function.

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction.

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Massive donor transfusion potentially increases recipient mortality after lung transplantation.

OBJECTIVE: Donor blood transfusion has been identified as a potential risk factor for primary graft dysfunction and by extension early mortality. We sought to define the contributing risk of donor transfusion on early mortality for lung transplant. METHODS: Donor and recipient data were abstracted from the Organ Procurement and Transplantation Network database updated through June 30, 2014, which included 86,398 potential donors and 16,255 transplants. Using the United Network for Organ Sharing 4-level designation of transfusion (no blood, 1-5 units, 6-10 units, and >10 units, massive), we analyzed all-cause mortality at 30-days with the use of logistic regression adjusted for confounders (ischemic time, donor age, recipient diagnosis, lung allocation score and recipient age, and recipient body mass index). Secondary analyses assessed 90-day and 1-year mortality and hospital length of stay. RESULTS: Of the 16,255 recipients transplanted, 8835 (54.35%) donors received at least one transfusion. Among those transfused, 1016 (6.25%) received a massive transfusion, defined as >10 units. Those donors with massive transfusion were most commonly young trauma patients. After adjustment for confounding variables, donor massive transfusion was associated significantly with an increased risk in 30-day (P = .03) and 90-day recipient mortality (P = .01) but not 1-year mortality (P = .09). There was no significant difference in recipient length of stay or hospital-free days with respect to donor transfusion. CONCLUSIONS: Massive donor blood transfusion (>10 units) was associated with early recipient mortality after lung transplantation. Conversely, submassive donor transfusion was not associated with increased recipient mortality. The mechanism of increased early mortality in recipients of lungs from massively transfused donors is unclear and needs further study but is consistent with excess mortality seen with primary graft dysfunction in the first 90 days posttransplant.

Peripheral Blood Gene Expression Changes Associated With Primary Graft Dysfunction After Lung Transplantation.

Recipient responses to primary graft dysfunction (PGD) after lung transplantation may have important implications to the fate of the allograft. We therefore evaluated longitudinal differences in peripheral blood gene expression in subjects with PGD. RNA expression was measured throughout the first transplant year in 106 subjects enrolled in the Clinical Trials in Organ Transplantation-03 study using a panel of 100 hypothesis-driven genes. PGD was defined as grade 3 in the first 72 posttransplant hours. Eighteen genes were differentially expressed over the first year based on PGD development, with significant representation from innate and adaptive immunity genes, with most differences identified very early after transplant. Sixteen genes were overexpressed in the blood of patients with PGD compared to those without PGD within 7 days of allograft reperfusion, with most transcripts encoding innate immune/inflammasome-related proteins, including genes previously associated with PGD. Thirteen genes were underexpressed in patients with PGD compared to those without PGD within 7 days of transplant, highlighted by T cell and adaptive immune regulation genes. Differences in gene expression present within 2 h of reperfusion and persist for days after transplant. Future investigation will focus on the long-term implications of these gene expression differences on the outcome of the allograft.

The Perioperative Lung Transplant Virome: Torque Teno Viruses Are Elevated in Donor Lungs and Show Divergent Dynamics in Primary Graft Dysfunction.

Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. To date, studies using standard clinical assays have not linked microbial factors to PGD. We previously used comprehensive metagenomic methods to characterize viruses in lung allografts >1 mo after transplant and found that levels of Anellovirus, mainly torque teno viruses (TTVs), were significantly higher than in nontransplanted healthy controls. We used quantitative polymerase chain reaction to analyze TTV and shotgun metagenomics to characterize full viral communities in acellular bronchoalveolar lavage from donor organs and postreperfusion allografts in PGD and non-PGD lung transplant recipient pairs. Unexpectedly, TTV DNA levels were elevated 100-fold in donor lungs compared with healthy adults (p = 0.0026). Although absolute TTV levels did not differ by PGD status, PGD cases showed a smaller increase in TTV levels from before to after transplant than did control recipients (p = 0.041). Metagenomic sequencing revealed mainly TTV and bacteriophages of respiratory tract bacteria, but no viral taxa distinguished PGD cases from controls. These findings suggest that conditions associated with brain death promote TTV replication and that greater immune activation or tissue injury associated with PGD may restrict TTV abundance in the lung.

Adipose Gene Expression Profile Changes With Lung Allograft Reperfusion.

Obesity is a risk factor for primary graft dysfunction (PGD), a form of lung injury resulting from ischemia-reperfusion after lung transplantation, but the impact of ischemia-reperfusion on adipose tissue is unknown. We evaluated differential gene expression in thoracic visceral adipose tissue (VAT) before and after lung reperfusion. Total RNA was isolated from thoracic VAT sampled from six subjects enrolled in the Lung Transplant Body Composition study before and after allograft reperfusion and quantified using the Human Gene 2.0 ST array. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment for genes involved in complement and coagulation cascades and Jak-STAT signaling pathways. Overall, 72 genes were upregulated and 56 genes were downregulated in the postreperfusion time compared with baseline. Long pentraxin-3, a gene and plasma protein previously associated with PGD, was the most upregulated gene (19.5-fold increase, p = 0.04). Fibronectin leucine-rich transmembrane protein-3, a gene associated with cell adhesion and receptor signaling, was the most downregulated gene (4.3-fold decrease, p = 0.04). Ischemia-reperfusion has a demonstrable impact on gene expression in visceral adipose tissue in our pilot study of nonobese, non-PGD lung transplant recipients. Future evaluation will focus on differential adipose tissue gene expression and the development of PGD after transplant.