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.

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 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.

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.

Factors Associated with Lung Function Recovery at the First Year after Lung Transplantation

PURPOSE: Post-operative pulmonary function is an important prognostic factor for lung transplantation. The purpose of this study was to identify factors affecting recovery of forced expiratory volume in 1 second (FEV1) at the first year after lung transplantation. MATERIALS AND METHODS: We retrospectively reviewed the medical records of lung transplantation patients between October 2012 and June 2016. Patients who survived for longer than one year and who underwent pulmonary function test at the first year of lung transplantation were enrolled. Patients were divided into two groups according to whether they recovered to a normal range of FEV1 (FEV1 ≥80% of predicted value vs. < 80%). We compared the two groups and analyzed factors associated with lung function recovery. RESULTS: Fifty-eight patients were enrolled in this study: 28 patients (48%) recovered to a FEV1 ≥80% of the predicted value, whereas 30 patients (52%) did not. Younger recipients [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.87–0.98; p=0.010], longer duration of mechanical ventilator use after surgery (OR, 1.14; 95% CI, 1.03–1.26; p=0.015), and high-grade primary graft dysfunction (OR, 8.08; 95% CI, 1.67–39.18; p=0.009) were identified as independent risk factors associated with a lack of full recovery of lung function at 1 year after lung transplantation. CONCLUSION: Immediate postoperative status may be associated with recovery of lung function after lung transplantation.

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.

The role of bradykinin in lung ischemia-reperfusion injury in a rat lung transplantation model

ABSTRACT PURPOSE: To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4. METHODS: Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192). LTx was performed after 18 h cold ischemia time and harvested two days post-LTx. Blood gas analysis (PO2), wet/dry weight ratio (W/D), myeloperoxidase activity (MPO), and lipid peroxidation (MDA) were analyzed at 48 hr after transplantation. Immunohistochemical (IHC) analysis was performed in the same sample and validated by Western-Blot. RESULTS: Compared to the LPD group, the AB192 group showed higher PO2, lower W/D ratio, and decreased MPO and MDA. IHC studies showed strong bradykinin β2 receptor (B2R) staining in the LPD group, especially in inflammatory cells, alveolar macrophages, and respiratory epithelial cells. Expression of B2R by Western-Blot was significantly different between the AB192 and LPD groups. CONCLUSION: Bradykinin may be a competitive substrate of DPP-4, and decreased bradykinin levels may enhance protective effects against ischemia/reperfusion injury during LTx.

Tres casos de mieloma múltiple de novo después de trasplante renal / Three cases of de novo multiple myeloma after kidney transplantation

RESUMEN La enfermedad renal asociada a cadenas ligeras es frecuente en el contexto de las gammapatías monoclonales, afecta los glomérulos o los túbulos renales, y su causa más común es el mieloma múltiple. Puede desarrollarse después de un trasplante renal por recurrencia de un mieloma múltiple ya existente, o puede ser de diagnóstico nuevo y presentarse con deterioro de la función renal y proteinuria. Siempre se requiere una biopsia renal para confirmar el diagnóstico.

ABSTRACT Light chain-associated kidney compromise is frequent in patients with monoclonal gammopathies; it affects the glomeruli or the tubules, and its most common cause is multiple myeloma. It may develop after a kidney transplant due to recurrence of a preexisting multiple myeloma or it can be a de novo disease manifesting as graft dysfunction and proteinuria. A kidney biopsy is always necessary to confirm the diagnosis.

Primary graft dysfunction of the liver: definitions, diagnostic criteria and risk factors / Disfunção primária do enxerto hepático: definições, critérios diagnósticos e fatores de risco

ABSTRACT Primary graft dysfunction is a multifactorial syndrome with great impact on liver transplantation outcomes. This review article was based on studies published between January 1980 and June 2015 and retrieved from PubMed database using the following search terms: “primary graft dysfunction”, “early allograft dysfunction”, “primary non-function” and “liver transplantation”. Graft dysfunction describes different grades of graft ischemia-reperfusion injury and can manifest as early allograft dysfunction or primary graft non-function, its most severe form. Donor-, surgery- and recipient-related factors have been associated with this syndrome. Primary graft dysfunction definition, diagnostic criteria and risk factors differ between studies.

RESUMO A disfunção primária do enxerto hepático é uma síndrome multifatorial com grande impacto no resultado do transplante de fígado. Foi realizada uma ampla revisão da literatura, consultando a base de dados PubMed, em busca de estudos publicados entre janeiro de 1980 e junho de 2015. Os termos descritivos utilizados foram: “primary graft dysfunction”, “early allograft dysfunction”, “primary non-function” e “liver transplantation”. A disfunção traduz graus diferentes da lesão de isquemia e reperfusão do órgão, e pode se manifestar como disfunção precoce ou, na forma mais grave, pelo não funcionamento primário do enxerto. Fatores relacionados ao doador, ao transplante e ao receptor contribuem para essa síndrome. Existem definições diferentes na literatura quanto ao diagnóstico e aos fatores de risco associados à disfunção primária.

Post-reperfusion liver biopsy and its value in predicting mortality and graft dysfunction after liver transplantation / Biópsia hepática pós-reperfusão e sua utilização na predição da mortalidade e da disfunção hepática pós-transplante

ABSTRACT Background: The outcome of the patients after liver transplant is complex and to characterize the risk for complications is not always easy. In this context, the hepatic post-reperfusion biopsy is capable of portraying alterations of prognostic importance. Aim: To compare the results of liver transplantation, correlating the different histologic features of the hepatic post-reperfusion biopsy with graft dysfunction, primary non-function and patient survival in the first year after transplantation. Method: From the 377 transplants performed from 1996 to 2008, 164 patients were selected. Medical records were reviewed and the following clinical outcomes were registered: mortality in 1, 3, 6 and 12 months, graft dysfunction in varied degrees and primary graft non-function. The post-reperfusion biopsies had been examined by a blinded pathologist for the outcomes. The following histological variables had been evaluated: ischemic alterations, congestion, steatosis, neutrophilic exudate, monomorphonuclear infiltrate and necrosis. Results: The variables associated with increased mortality were: steatosis (p=0.02209), monomorphonuclear infiltrate (p=0.03935) and necrosis (p<0.00001). The neutrophilic exudate reduced mortality in this study (p=0.00659). The primary non-function showed significant association (p<0.05) with the necrosis, steatosis and the monomorphonuclear infiltrate. Conclusion: Post-reperfusion biopsy is useful tool to foresee complications after liver transplant.

RESUMO Racional: A evolução dos pacientes após transplante hepático é complexa e caracterizar o risco para complicações nem sempre é fácil. Nesse contexto, a biópsia hepática pós-reperfusão é capaz de retratar alterações de importância prognóstica. Objetivo: Avaliar os resultados no primeiro ano após transplante hepático, correlacionando as alterações histológicas à biópsia hepática pós-reperfusão com a sobrevida, a disfunção e o não-funcionamento primário do enxerto. Método: Dos 377 transplantes ocorridos de 1996 a 2008, 164 pacientes foram selecionados para estudo. Os seguintes desfechos clínicos foram registrados: mortalidade em 1, 3, 6 e 12 meses, disfunção do enxerto em graus variados e o não-funcionamento primário do enxerto. As biópsias pós-reperfusão foram examinadas por um patologista sem conhecimento dos resultados. As seguintes variáveis histológicas foram avaliadas: alterações isquêmicas, congestão, esteatose, exsudato neutrofílico, infiltrado monomorfonuclear e necrose. Resultados: As variáveis associadas com aumento da mortalidade foram: esteatose (p=0.02209), infiltrado monomorfonuclear (p=0.03935) e necrose (p<0.00001). O infiltrado neutrofílico reduziu a mortalidade neste estudo (p=0.00659). O não-funcionamento primário do enxerto mostrou associação significativa (p<0.05) com a necrose, a esteatose e com o infiltrado monomorfonuclear. Conclusão: A biópsia hepática pós-reperfusão é ferramenta útil em prever complicações após o transplante hepático.

Biopsia hepática en la patología del trasplante, período postrasplante temprano, enfoque dirigido al diagnóstico histopatológico y su correlación clínico-patológica: Histopathological Diagnosis and Clinicopathological Correlation in the Early Post-Transplant Period / Liver Biopsies in Transplant Pathology

La biopsia hepática de los aloinjertos sigue siendo considerada el estándar de oro y juega un papel importante e integral en la interpretación y explicación de los cambios que puedan ocurrir en respuesta a alteraciones en las pruebas de la función o bioquímica hepática, anomalías funcionales o alteración en las imágenes diagnósticas, las cuales pueden, o no, ir acompañadas de síntomas. También es útil en el seguimiento o biopsias por protocolo (1-3). La evaluación de biopsias, después del trasplante, puede ser difícil debido a que es muy amplio el espectro de las complicaciones que pueden presentarse en el período postrasplante; más aún, cuando muchas de ellas necesitan un diagnóstico y tratamiento inmediato. La patología más frecuente es el rechazo agudo. Sin embargo, también pueden observarse cambios de perfusión/reperfusión, alteraciones funcionales, recidiva de enfermedad de base, lesión de la vía biliar, lesiones vasculares, infecciones oportunistas, patologías de novo, como la hepatitis autoinmune, hepatitis crónica idiopática postrasplante, toxicidad farmacológica o tumores, entre otras patologías (4). En este artículo relacionado con la patología del trasplante hepático se tratarán las patologías más frecuentes, no quirúrgicas, en el período postrasplante temprano, con un enfoque histopatológico dirigido a las dificultades y controversias para una adecuada correlación clínico-patológica.

Biopsies of liver allografts are still considered to be the gold standard. They play an important and integral role in the interpretation and explanation of changes that may occur in response to alterations in function tests, in the interpretation and explanation of liver biochemistry, in the interpretation and explanation of functional abnormalities, and in the interpretation and explanation of diagnostic images (whether or not accompanied by symptoms). Biopsies are also useful for monitoring and are often part of the protocol (1-3). The evaluation of biopsy samples after transplantation can be difficult especially because of the very broad spectrum of complications that may arise in the post-transplant period. Many of them require immediate diagnosis and treatment despite this difficulty. Although the most common condition is acute rejection, many other conditions and disorders can be observed. They include perfusion/reperfusion alterations, functional impairment, recurrence of underlying diseases, injury to the bile duct, vascular lesions, opportunistic infections, de novo pathologies such as autoimmune hepatitis, post-transplant idiopathic chronic hepatitis, drug toxicity, and tumors (4). This is the second article about the pathology of liver transplantation. It discusses the most common pathologies in the early post-transplant period and provides a histopathological approach towards difficulties and controversies for adequate clinicopathological correlation.

Associated clinical and laboratory markers of donor on allograft function after heart transplant

Abstract Introduction: Primary graft dysfunction is a major cause of mortality after heart transplantation. Objective: To evaluate correlations between donor-related clinical/biochemical markers and the occurrence of primary graft dysfunction/clinical outcomes of recipients within 30 days of transplant. Methods: The prospective study involved 43 donor/recipient pairs. Data collected from donors included demographic and echocardiographic information, noradrenaline administration rates and concentrations of soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2), interleukins (IL-6 and IL-10), monocyte chemoattractant protein-1, C-reactive protein and cardiac troponin I. Data collected from recipients included operating, cardiopulmonary bypass, intensive care unit and hospitalization times, inotrope administration and left/right ventricular function through echocardiography. Results: Recipients who developed moderate/severe left ventricular dysfunction had received organs from significantly older donors (P =0.020). Recipients from donors who required moderate/high doses of noradrenaline (>0.23 µg/kg/min) around harvesting time exhibited lower post-transplant ventricular ejection fractions (P =0.002) and required longer CPB times (P =0.039). Significantly higher concentrations of sTNFR1 (P =0.014) and sTNFR2 (P =0.030) in donors were associated with reduced intensive care unit times (≤5 days) in recipients, while higher donor IL-6 (P =0.029) and IL-10 (P =0.037) levels were correlated with reduced hospitalization times (≤25 days) in recipients. Recipients who required moderate/high levels of noradrenaline for weaning off cardiopulmonary bypass were associated with lower donor concentrations of sTNFR2 (P =0.028) and IL-6 (P =0.001). Conclusion: High levels of sTNFR1, sTNFR2, IL-6 and IL-10 in donors were associated with enhanced evolution in recipients. Allografts from older donors, or from those treated with noradrenaline doses >0.23 µg/kg/min, were more frequently affected by primary graft dysfunction within 30 days of surgery.

Experience of ECMO in Primary Graft Dysfunction after Orthotopic Heart Transplantation / Experiência na Utilização de ECMO na Disfunção Primária de Enxerto Pós-Transplante Cardíaco Ortotópico

Background:Primary graft dysfunction is the main cause of early mortality after heart transplantation. Mechanical circulatory support has been used to treat this syndrome.Objective:Describe the experience with extracorporeal membrane oxygenation to treat post-transplant primary cardiac graft dysfunction.Methods:Between January 2007 and December 2013, a total of 71 orthotopic heart transplantations were performed in patients with advanced heart failure. Eleven (15.5%) of these patients who presented primary graft dysfunction constituted the population of this study. Primary graft dysfunction manifested in our population as failure to wean from cardiopulmonary bypass in six (54.5%) patients, severe hemodynamic instability in the immediate postoperative period with severe cardiac dysfunction in three (27.3%), and cardiac arrest (18.2%). The average ischemia time was 151 ± 82 minutes. Once the diagnosis of primary graft dysfunction was established, we installed a mechanical circulatory support to stabilize the severe hemodynamic condition of the patients and followed their progression longitudinally.Results:The average duration of extracorporeal membrane oxygenation support was 76 ± 47.4 hours (range 32 to 144 hours). Weaning with cardiac recovery was successful in nine (81.8%) patients. However, two patients who presented cardiac recovery did not survive to hospital discharge.Conclusion:Mechanical circulatory support with central extracorporeal membrane oxygenation promoted cardiac recovery within a few days in most patients.

Fundamento:A disfunção primária de enxerto é a principal causa de mortalidade precoce após o transplante cardíaco. O uso de assistência circulatória mecânica tem sido empregado no tratamento dessa síndrome.Objetivo:Descrever a experiência com o uso de oxigenação por membrana extracorpórea para tratamento de disfunção primária de enxerto pós-transplante cardíaco.Métodos:Entre janeiro de 2007 e dezembro de 2013, foram realizados 71 transplantes cardíacos ortotópicos em pacientes com insuficiência cardíaca avançada. Destes, 11 (15,5%) pacientes apresentaram disfunção primária de enxerto, os quais constituíram a população deste estudo. As manifestações da disfunção primária de enxerto na nossa população foram falência no desmame da circulação extracorpórea em seis (54,5%) pacientes, instabilidade hemodinâmica grave no pós-operatório imediato com disfunção cardíaca acentuada em três (27,3%) e pós-parada cardíaca em dois (18,2%). O tempo de isquemia médio foi 151 ± 82 minutos. Assim que o diagnóstico de disfunção primária de enxerto foi estabelecido, procedeu-se à instalação de suporte circulatório mecânico para estabilização de quadro hemodinâmico grave, e a evolução dos pacientes foi estudada temporalmente.Resultados:A duração média de assistência em oxigenação por membrana extracorpórea foi 76 ± 47,4 horas (variação de 32 a 144 horas). O desmame com recuperação cardíaca obteve sucesso em nove (81,8%) pacientes. No entanto, dois pacientes, que tiveram recuperação cardíaca, não sobreviveram à alta hospitalar.Conclusão:O uso de assistência circulatória mecânica por meio de oxigenação por membrana extracorpórea central promoveu recuperação cardíaca em poucos dias na maioria dos pacientes.

Heart transplantation: review / Transplante cardíaco: revisão

ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.

RESUMO O transplante cardíaco é atualmente a abordagem cirúrgica definitiva padrão-ouro no tratamento da insuficiência cardíaca refratária. No entanto, a escassez de doadores limita a realização de um número maior de transplantes cardíacos, situação em que vem aumentando a utilização de dispositivos de assistência circulatória mecânica. Com indicações e contraindicações bem estabelecidas, além de diagnóstico e tratamento de rejeição, por meio de protocolos definidos de imunossupressão, os resultados do transplante cardíaco são muito favoráveis. Dentre as complicações precoces que podem impactar a sobrevida, destacamos a disfunção primária do enxerto, a disfunção do ventrículo direito, rejeição e infecções; já as complicações tardias incluem a doença vascular do enxerto e as neoplasias. Apesar das dificuldades para realização do transplante cardíaco, em especial pela escassez de doadores e pela elevada mortalidade em fila de espera, no Brasil, existe um grande potencial, tanto no aumento de doadores efetivos, quanto na utilização de dispositivos de assistência circulatória, o que pode vir a impactar positivamente no número e nos resultados do transplante cardíaco.

Pediatric lung transplantation: 10 years of experience

Lung transplantation is a well-established treatment for advanced lung diseases. In children, the diseases that most commonly lead to the need for a transplantation are cystic fibrosis, pulmonary hypertension, and bronchiolitis. However, the number of pediatric lung transplantations being performed is low compared with the number of transplants performed in the adult age group. The objective of this study was to demonstrate our experience with pediatric lung transplants over a 10-year period in a program initially designed for adults.

Percutaneous Extracorporeal Membrane Oxygenation for Graft Dysfunction after Heart Transplantation

BACKGROUND: We evaluated the safety and efficacy of percutaneous extracorporeal membrane oxygenation (ECMO) in patients with primary graft dysfunction after heart transplantation. METHODS: Of 65 patients (44 males and 21 females) who underwent heart transplantation from January 2006 to December 2012, 13 patients (group I) needed peripheral ECMO support due to difficulty in weaning from cardiopulmonary bypass (CPB) and 52 patients (group II) were weaned from CPB without mechanical support. The mean age of the patients at the time of operation was 54.4+/-13.6 years. There were no differences in the preoperative characteristics of the two groups. Multivariable analysis was performed to identify the risk factors for ECMO therapy. RESULTS: All group I patients were successfully weaned from ECMO after 53+/-9 hours of circulatory support. Early mortality occurred in four patients (1 [7.7%] in group I and 3 [5.8%] in group II, p>0.999). There were no differences in the postoperative complications between the two groups, with the exception of reoperation for bleeding. A greater number of group I patients underwent reoperation for bleeding (5 [38.5%] in group I vs. 6 [11.5%] in group II, p=0.035). In multivariable analysis, preoperative mechanical support (ECMO and intra-aortic balloon pump) and longer CPB time were the risk factors of ECMO therapy for graft dysfunction (odds ratio, 6.377; 95% confidence interval, 1.519 to 26.77; p=0.011 and odds ratio, 1.010; 95% confidence interval, 1.001 to 1.019; p=0.033). CONCLUSION: Percutaneous ECMO support could be a viable option for rescuing patients when graft dysfunction refractory to medical management develops after heart transplantation.

Prolonged post-reperfusion syndrome during multivisceral organ transplantation in a pediatric patient: a case report / 대한마취과학회지

Multivisceral organ transplantation involves the transplantation of three or more abdominal organs, including small bowel, duodenum, stomach, liver, pancreas, colon, and so on. The large amounts of cold and acidic loading into systemic circulation from the graft during multivisceral organ transplantation may result in severe post-reperfusion syndrome (PRS). We describe here a 6-year-old pediatric patient with chronic intestinal pseudo-obstruction who experienced prolonged PRS and severe metabolic acidosis during seven abdominal organ transplantation including the liver, spleen, stomach, duodenum, small bowel, colon and pancreas. The hypotensive period lasted approximately 10 minutes after graft reperfusion and was accompanied by severe metabolic acidosis and hypothermia. Since PRS can be easily associated with adverse outcomes, such as poor early graft function and primary non-function, not only meticulous surveillance for aggravating factors for PRS but also their immediate correction were necessary in managing a pediatric patient undergoing multivisceral organ transplantation.

Frecuencia y factores de riesgo de la hipertrofia ventricular izquierda como marcador de daño cardiovascular en el trasplante renal / Frequency and risk factors of the left ventricular hypertrophy like scoreboard of cardiovascular damage in renal transplant

Introducción: las complicaciones cardiovasculares son frecuentes y constituyen la principal causa de muerte en los pacientes con trasplantes renales, su alta incidencia está dada por múltiples factores de riesgo. Objetivos: determinar la frecuencia de la hipertrofia del ventrículo izquierdo como marcador de daño cardiovascular, y los factores de riesgo que facilitarían su aparición. Métodos: se hizo un estudio prospectivo, de corte transversal y de tipo casos y controles, a 70 enfermos con trasplantes renales a los cuales se les realizó un ecocardiograma convencional para determinar la presencia o no de hipertrofia del ventrículo izquierdo y se relacionó, mediante un estudio univariado y multivariado (regresión logística), con factores de riesgo cardiovascular. Resultados: las afecciones cardiovasculares constituyeron la segunda causa de pérdida de los pacientes en este estudio (33,1 porciento), La hipertrofia del ventrículo izquierdo se encontró en 45 (64 porciento) de los enfermos pesquisados. La dislipemia, el uso de la ciclosporina A y la disfunción del injerto, fueron las complicaciones que constituyeron, tanto en el estudio univariado como multivariado (factor independiente), p < 0,05, condicionales que favorecieron la existencia de hipertrofia del ventrículo izquierdo, aseveraciones estas que constituyen las conclusiones de la investigación...

Introduction: the cardiovascular complications are frequent and are the leading cause of death in patients underwent renal transplantation and its high incidence is due to multiple risk factors. Objectives: to determine the frequency of the left ventricle hypertrophy as a marker of cardiovascular damage and the risk factors leading to its appearance. Methods: a case-control, cross-sectional and prospective study was conducted in 70 patients with renal transplantations and underwent a conventional echocardiogram to determine the presence or not of left ventricle hypertrophy and it was related to cardiovascular risk factors by means of a univariate and multivariate study (logistic regression) with cardiovascular risk factors. Results: the cardiovascular affections were the second cause of loss of patients in present study (33,1 porciento). The left ventricle hypertrophy was found in the 45 (64 porceinto) of screened patients. The dyslipidemia, the use of A cyclosporine and the graft dysfunction, were the complications in the univariate and the multivariate study (independent factor) , p < 0,05, the conditional favoring the existence of left ventricle hypertrophy, assertions that are the research conclusions...