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1.
PLoS One ; 15(10): e0239770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052974

RESUMO

Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r = - 0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.


Assuntos
Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/fisiopatologia , Microcirculação/fisiologia , Sepse/fisiopatologia , Lesão Renal Aguda/sangue , Estudos de Coortes , Creatinina/sangue , Feminino , Hidratação/métodos , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Perfusão/métodos , Prognóstico , Sepse/sangue , Sepse/mortalidade , Equilíbrio Hidroeletrolítico/fisiologia
2.
Ann Surg ; 272(5): 759-765, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889870

RESUMO

OBJECTIVE: The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation. PATIENTS AND METHODS: We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B). RESULTS: Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers. CONCLUSION: We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Isquemia Fria , Neoplasias Hepáticas/prevenção & controle , Transplante de Fígado , Recidiva Local de Neoplasia/prevenção & controle , Preservação de Órgãos/métodos , Sobrevivência de Enxerto , Humanos , Oxigênio , Perfusão/métodos
3.
J Vis Exp ; (162)2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32865531

RESUMO

Ex vivo perfusion is an important physiological tool to study the function of isolated organs (e.g. liver, kidneys). At the same time, due to the small size of mouse organs, ex vivo perfusion of bone, bladder, skin, prostate, and reproductive organs is challenging or not feasible. Here, we report for the first time an in situ lower body perfusion circuit in mice that includes the above tissues, but bypasses the main clearance organs (kidney, liver, and spleen). The circuit is established by cannulating the abdominal aorta and inferior vena cava above the iliac artery and vein and cauterizing peripheral blood vessels. Perfusion is performed via a peristaltic pump with perfusate flow maintained for up to 2 h. In situ staining with fluorescent lectin and Hoechst solution confirmed that the microvasculature was successfully perfused. This mouse model can be a very useful tool for studying pathological processes as well as mechanisms of drug delivery, migration/metastasis of circulating tumor cells into/from the tumor, and interactions of immune system with perfused organs and tissues.


Assuntos
Perfusão/métodos , Animais , Feminino , Fêmur , , Membro Posterior , Masculino , Camundongos , Músculos , Próstata , Pele , Testículo , Bexiga Urinária
4.
Transplantation ; 104(8): 1542-1552, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732830

RESUMO

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


Assuntos
Seleção do Doador/métodos , Rejeição de Enxerto/prevenção & controle , Parada Cardíaca/mortalidade , Preservação de Órgãos/métodos , Transplante de Órgãos/métodos , Aloenxertos/provisão & distribução , Seleção do Doador/ética , Seleção do Doador/legislação & jurisprudência , Rejeição de Enxerto/etiologia , Acesso aos Serviços de Saúde , Parada Cardíaca/terapia , Humanos , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/ética , Transplante de Órgãos/legislação & jurisprudência , Perfusão/instrumentação , Perfusão/métodos , Ressuscitação/ética , Resultado do Tratamento , Isquemia Quente/efeitos adversos
5.
Transplantation ; 104(8): 1560-1565, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732832

RESUMO

The 25th Annual Congress of the International Liver Transplantation Society was held in Toronto, Canada, from May 15 to 18, 2019. Surgeons, hepatologists, anesthesiologists, critical care intensivists, radiologists, pathologists, and research scientists from all over the world came together with the common aim of improving care and outcomes for liver transplant recipients and living donors. Some of the featured topics at this year's conference included multidisciplinary perioperative care in liver transplantation, worldwide approaches to organ allocation, donor steatosis, and updates in pediatrics, immunology, and radiology. This report presents excerpts and highlights from invited lectures and select abstracts, reviewed and compiled by the Vanguard Committee of International Liver Transplantation Society. This will hopefully contribute to further advances in clinical practice and research in liver transplantation.


Assuntos
Congressos como Assunto , Seleção do Doador/organização & administração , Transplante de Fígado , Assistência Perioperatória/métodos , Sociedades Médicas/organização & administração , Adulto , Fatores Etários , Canadá , Criança , Cuidados Críticos/métodos , Cuidados Críticos/organização & administração , Seleção do Doador/métodos , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Hepatectomia/efeitos adversos , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Cooperação Internacional , Doadores Vivos , Preservação de Órgãos/instrumentação , Preservação de Órgãos/métodos , Segurança do Paciente , Seleção de Pacientes , Perfusão/instrumentação , Perfusão/métodos , Melhoria de Qualidade , Alocação de Recursos/organização & administração , Resultado do Tratamento
6.
Transplantation ; 104(8): 1591-1603, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732836

RESUMO

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Preservação de Órgãos/métodos , Idoso , Aloenxertos/imunologia , Aloenxertos/provisão & distribução , Isquemia Fria/instrumentação , Isquemia Fria/métodos , Isquemia Fria/estatística & dados numéricos , Doença Hepática Terminal/complicações , Estudos de Viabilidade , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Rim/imunologia , Transplante de Rim/ética , Transplante de Rim/métodos , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/ética , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Futilidade Médica/ética , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Preservação de Órgãos/estatística & dados numéricos , Perfusão/instrumentação , Perfusão/métodos , Perfusão/estatística & dados numéricos , Insuficiência Renal/etiologia , Insuficiência Renal/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/ética , Transplante Homólogo/métodos , Resultado do Tratamento
7.
J Card Surg ; 35(10): 2469-2476, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32789962

RESUMO

BACKGROUND: Pulmonary artery perfusion during cardiopulmonary bypass (CPB) is a known but rarely used technique in adult cardiac surgery. In this study, we aimed to investigate biochemical and histopathological effects of pulmonary artery perfusion during CPB on lung functions. METHODS: Between May 2014 and August 2014, all patients (n = 24) who gave informed consent for participating this study with inclusion criteria were included. Patients undergoing isolated coronary artery bypass grafting were sequentially randomized to conventional CPB (control group, n = 12) and conventional CPB with selective pulmonary artery perfusion (study group, n = 12). Lung functions were monitored using PF ratio, alveolar-arterial oxygen gradient, and lactate levels. A small sample tissue from the left lung was excised for histopathologic examination. Immunocytochemistry analysis was performed using anti-rabbit polyclonal vascular endothelial growth factor (VEGF), rabbit polyclonal inducible nitric oxide synthase (i-NOS), and BCL-2 antibodies. RESULTS: Postoperative course of the patients were uneventful without any clinical outcome differences in terms of cardiopulmonary complications, ventilation time and hospital stay. Pulmonary perfusion group had significantly better oxygenation values after extubation and at postoperative 24-hour. Electron microscopy examinations revealed better preservation of the alveolar wall integrity with pulmonary perfusion. The intensity of VEGF, i-NOS, and BCL-2 antibody expressions in bronchial epithelial cells were more prominent in the pulmonary perfusion group. CONCLUSIONS: Pulmonary artery perfusion during aortic cross-clamping provides better oxygenation and preservation of the wall alveolar integrity after coronary artery bypass grafting surgery. This technique can be used as a protective strategy to minimize CPB-induced lung injury in adult cardiac surgery.


Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Ponte Cardiopulmonar/efeitos adversos , Perfusão/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Artéria Pulmonar , Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/patologia , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Contagem de Células Sanguíneas , Proteína C-Reativa , Ponte de Artéria Coronária/métodos , Feminino , Hemoglobinas , Humanos , Inflamação , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/análise , Recuperação de Função Fisiológica , Esternotomia , Fator A de Crescimento do Endotélio Vascular/análise
8.
Ann Surg ; 272(5): 751-758, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833758

RESUMO

OBJECTIVE: To compare HOPE and NRP in liver transplantation from cDCD. SUMMARY OF BACKGROUND DATA: Liver transplantation after cDCD is associated with higher rates of graft loss. Dynamic preservation strategies such as NRP and HOPE may offer safer use of cDCD grafts. METHODS: Retrospective comparative cohort study assessing outcomes after cDCD liver transplantation in 1 Swiss (HOPE) and 6 French (NRP) centers. The primary endpoint was 1-year tumor-death censored graft and patient survival. RESULTS: A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients CONCLUSION:: NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations.


Assuntos
Isquemia Fria , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado , Preservação de Órgãos/métodos , Isquemia Quente , Criopreservação , Função Retardada do Enxerto , França , Sobrevivência de Enxerto , Humanos , Oxigênio , Perfusão/métodos , Estudos Retrospectivos , Doadores de Tecidos
9.
Transplantation ; 104(9): 1929-1942, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32769628

RESUMO

BACKGROUND: Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome. METHODS: In the period October 2018-February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney injury, and comprehensive complication index were analyzed using Pearson coefficient, receiver-operating characteristics analysis and by univariable and multivariable regression. RESULTS: Median D-HOPE time was 122 minutes. All parameters were normalized to liver weight. Only macrovesicular steatosis (MaS) significantly impacted PP levels and slope. Grafts with ≥30% MaS exhibited significantly different PP values and slope. Graft loss and EAD rate were 2% (n = 1) and 26% (n = 13). All PP except lactate correlated with EAD, 90-minute alanine aminotransferase showing the highest area under the receiver-operating characteristics curve (0.84). However, at multivariable analysis, the only factor independently associated with EAD was MaS (odds ratio, 5.44; confidence interval, 1.05-28.21; P = 0.04). Ninety minutes lactate dehydrogenase had the strongest correlation with L-GrAFT (R = 0.70; P < 0.001). PP correlated poorly with comprehensive complication index and grades 2-3 acute kidney injury rate. CONCLUSIONS: PP were predictive of graft function after transplant, but their association with graft survival and clinical outcomes requires further evaluation. MaS influenced levels of PP and was the only independent predictor of EAD.


Assuntos
Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Temperatura Baixa , Feminino , Sobrevivência de Enxerto , Humanos , Concentração de Íons de Hidrogênio , L-Lactato Desidrogenase/análise , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Transplant Proc ; 52(9): 2707-2710, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32800515

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has changed life on a global scale. The numbers of transplantations have plummeted as a result of fear of disease transmission, recipient coronavirus disease 2019 infection, priority shift, and resource limitations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates transplantation because donor testing, (re)allocation of limited resources, and recipient testing may exceed permissible ischemia times. Normothermic machine perfusion (NMP) helps safely prolong liver preservation up to 38 hours. Additional time is essential under the current circumstances. Here we present the case of a 29-year-old liver transplant recipient in whom prolonged liver preservation required for SARS-CoV-2 screening was accomplished through NMP. Donor and recipient test results for SARS-CoV-2 were negative, and intensive care unit capacity was eventually available. The surgical procedure and postoperative course were uneventful. NMP can extend preservation times in liver transplantation while awaiting SARS-CoV-2 test results and available intensive care unit capacity.


Assuntos
Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Pneumonia Viral/diagnóstico , Adulto , Betacoronavirus , Feminino , Humanos , Pandemias , Perfusão/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Doadores de Tecidos
14.
Z Gastroenterol ; 58(10): 945-954, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32838433

RESUMO

BACKGROUND: The lack of suitable allografts limits the availability of liver transplantation in Germany. The quality of potentially available German donor livers has to date not been analyzed. METHODS: Analysis of all donors for potential liver transplantations reported to the Eurotransplant by the German Organ Transplantation Foundation from 2010 to 2018. Categorization of transplanted and discarded organs utilizing available histopathological reports and predefined extended criteria for organ donation. RESULTS: A total of 8594 livers were offered for transplantation, of which 15.2 % were discarded. During the analysis period the proportion of donor livers from extended criteria donors increased from 65 % to 70 % (p = 0.005). In 2018, 21.3 % of offered donor livers were discarded, more than half (56.4 %) of these organs came from donors meeting multiple extended criteria. Livers were significantly more likely to be not transplanted, when from donors of older age (> 65 years; 41 vs. 28 %), BMI > 30 kg/m2 (29 vs. 14 %) or elevated transaminase levels (all p < 0,001). CONCLUSION: Despite the consistent organ scarcity in Germany, a relevant amount of livers cannot be transplanted due to a multitude of organ quality limitations. This should stimulate the search for concepts such as normothermic ex vivo machine perfusion to evaluate, protect and potentially improve organ quality.


Assuntos
Rejeição de Enxerto , Hepatopatias/cirurgia , Transplante de Fígado , Fígado/fisiopatologia , Perfusão/métodos , Doadores de Tecidos/estatística & dados numéricos , Alemanha , Humanos , Fígado/cirurgia , Preservação de Órgãos
15.
Transplantation ; 104(9): 1943-1951, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32639402

RESUMO

BACKGROUND: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT. METHODS: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT. RESULTS: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68). CONCLUSIONS: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.


Assuntos
Morte Encefálica , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Adulto , Doenças Biliares/epidemiologia , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
16.
Nat Med ; 26(7): 1102-1113, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32661401

RESUMO

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.


Assuntos
Lesão Pulmonar Aguda/terapia , Transplante de Pulmão/métodos , Pulmão/irrigação sanguínea , Preservação de Órgãos/métodos , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/fisiopatologia , Animais , Circulação Extracorpórea/métodos , Humanos , Pulmão/fisiopatologia , Perfusão/métodos , Suínos , Doadores de Tecidos
17.
J Card Surg ; 35(8): 1927-1932, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32667074

RESUMO

BACKGROUND AND AIM: There is no report on silent brain infarction (SBI) after minimally invasive cardiac surgery (MICS) with retrograde perfusion. Thus, the current study aimed to investigate the incidence of SBI after MICS using magnetic resonance imaging (MRI). METHODS: This study included 174 patients who underwent MICS with retrograde perfusion between July 2014 and July 2018. Preoperative computed tomography (CT) angiography was routinely performed and vascular pathology was evaluated for patient selection. Postoperative MRI was performed to investigate the occurrence of SBI. RESULTS: Out of the total 174 patients, 26 (14.9%) presented with SBI. A total of 61 SBI lesions were found in the 26 patients; of these, 34 (56%) SBI lesions were in the right hemisphere and 27 (44%) in the left hemisphere. SBIs were primarily observed in the posterior cerebral artery territory. Multivariate analysis revealed aortic stenosis to be the only risk factor of SBI. CONCLUSIONS: Retrograde perfusion via femoral cannulation may not increase the incidence of SBI in selected MICS patients based on preoperative CT findings.


Assuntos
Infarto Encefálico/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Perfusão/efeitos adversos , Perfusão/métodos , Complicações Pós-Operatórias/etiologia , Idoso , Estenose da Valva Aórtica , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/epidemiologia , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Incidência , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco
18.
Nephrol Dial Transplant ; 35(6): 1043-1070, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32516809

RESUMO

BACKGROUND: Most studies comparing the efficacy of hypothermic machine perfusion (HMP) versus static cold storage (SCS) are based on short-term outcomes. We aimed to better evaluate the mid-term impact of HMP in patients receiving expanded criteria donor (ECD) kidneys. METHODS: The analyses were based on the French Données Informatisées et VAlidées en Transplantation (DIVAT) observational cohort. Patients aged ≥45 years transplanted for the first or second times from an ECD donor since 2010 were studied. Our study reported the graft and/or patient survivals and the incidence of acute rejection episode. The Cox models and the Kaplan-Meier estimators, weighted on the propensity score, were used to study the times-to-events. RESULTS: Among the 2019 included patients, 1073 were in the SCS group versus 946 in the HMP group. The mean life expectancy with functioning graft was 5.7 years [95% confidence interval (CI) 5.4-6.1] for the HMP cohort followed-up for 8 years post-transplantation versus 6.0 years (95% CI 5.7-6.2) for the SCS group. These mid-term results were comparable in the patients receiving grafts from donors aged ≥70 years and in the transplantations with cold ischaemia time ≥18 h. CONCLUSIONS: Our study challenges the utility of using HMP to improve mid-term patient and graft survival. Nevertheless, the improvement of the short-term outcomes is indisputable. It is necessary to continue technological innovations to obtain long-term results.


Assuntos
Criopreservação/métodos , Função Retardada do Enxerto/prevenção & controle , Hipotermia Induzida/métodos , Transplante de Rim/métodos , Perfusão/instrumentação , Perfusão/métodos , Doadores de Tecidos/provisão & distribução , Idoso , Estudos de Coortes , Seleção do Doador , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade
19.
Nat Commun ; 11(1): 2939, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546694

RESUMO

There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria. Thirty-one livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring re-transplantation. This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia.


Assuntos
Sobrevivência de Enxerto/fisiologia , Testes de Função Hepática/métodos , Transplante de Fígado/métodos , Fígado/fisiologia , Preservação de Órgãos/métodos , Doadores de Tecidos/estatística & dados numéricos , Idoso , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Preservação de Órgãos/estatística & dados numéricos , Perfusão/métodos , Estudos Prospectivos , Análise de Sobrevida , Temperatura , Fatores de Tempo , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/estatística & dados numéricos
20.
Transplantation ; 104(9): 1899-1905, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32502131

RESUMO

BACKGROUND: Primary graft dysfunction and allograft rejection represent major caveats to successful lung transplantation. Reducing inflammation in donor lungs before transplantation may improve outcomes. Evidence exists that ex vivo lung perfusion (EVLP) can alter the donor lung environment, although the mechanisms remain unclear. This study aimed to characterize the inflammatory signaling profile of the lung following standard and EVLP transplant and delineate the immediate impact on the recipient circulation. METHODS: Female recipient pigs (n = 12) were randomized to undergo left lung transplantation from male donors either using the gold standard protocol (static cold storage) or following 3 hours of EVLP. The relative phosphorylation of 44 phosphokinases and the relative expression of 35 apoptosis-related molecules were profiled within the donor lung 24 hours posttransplantation. RESULTS: A global profile of mitochondrial salvage and cell survival was observed in the EVLP lung tissue compared with lungs undergoing standard transplantation. This included increased phosphorylation of downstream prosignaling kinases, including ERK1/2 and FAK. In addition, there was upregulated expression of the antiapoptotic proteins Bcl-2, HSP-70, LIVIN, and PON2 with downregulation of apoptosis inducing mitochondrial associated molecules, including clusterin, cytochrome C, and HTRA2/OMI. In the early postoperative period, there were significantly lower levels of circulating mitochondrial DNA in recipients receiving EVLP lungs compared with a standard transplant (P = 0.016). Genomic DNA did not differ between groups, with donor DNA undetectable at all time points. CONCLUSIONS: EVLP alters the inflammatory signaling profile of the donor lung before transplantation, with a global cell survival and antiapoptotic signature.


Assuntos
Inflamação/prevenção & controle , Transplante de Pulmão/métodos , Pulmão/metabolismo , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Animais , DNA Mitocondrial/sangue , Feminino , Masculino , Proteoma , Transdução de Sinais/fisiologia , Suínos
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