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1.
Int J Mol Sci ; 22(5)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668105

RESUMO

We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 µM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related factor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage.


Assuntos
Isquemia Fria/efeitos adversos , Morte , Fígado/metabolismo , Preservação de Órgãos/métodos , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Traumatismo por Reperfusão/prevenção & controle , Isquemia Quente/efeitos adversos , Animais , Transplante de Fígado , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Doadores de Tecidos
2.
N Engl J Med ; 384(15): 1391-1401, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33626248

RESUMO

BACKGROUND: Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited. METHODS: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications. RESULTS: A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).


Assuntos
Sistema Biliar/patologia , Isquemia Fria , Transplante de Fígado , Preservação de Órgãos/métodos , Adulto , Temperatura Baixa , Constrição Patológica/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão , Traumatismo por Reperfusão/prevenção & controle
3.
Eur J Med Res ; 26(1): 15, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546770

RESUMO

BACKGROUND: Hypothermic machine perfusion (HMP) improves the quality of donor livers for transplantation, both in animal models and in clinical practice. Treatment with SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), can suppress the JNK signaling pathway to alleviate donor liver ischemia-reperfusion injury (IRI). We performed the present study with the objective of exploring the protective effects exerted by a combination of HMP and SP600125 on liver xenograft viability for donation after cardiac death (DCD) in a porcine model. METHODS: 54 adult BAMA mini-pigs were randomly assigned to 5 groups, including sham, cold storage for 4 h (CS 4 h), CS 4 h + SP600125, CS 2 h + HMP 2 h, and CS 2 h + HMP 2 h + SP600125 groups. Donor livers in the CS 4 h and CS 4 h + SP600125 groups were conventionally cold preserved for 4 h, whereas donor livers in the CS 2 h + HMP 2 h and CS 2 h + HMP 2 h + SP600125 groups were cold preserved for 2 h and then treated with HMP for 2 h. The preservation and perfusion solutions contained SP600125 (20 µM). Follow-up was conducted for 5 days after liver transplantation to compare the surgical outcomes by means of serological examination, pathological results, and survival rate. RESULTS: The most satisfactory outcome after liver transplantation was observed in the CS 2 h + HMP 2 h + SP600125 group, which presented with minimal damage of donor livers during 5 days' follow-up. Additionally, serological examination, pathological results, and survival rate concurred in showing better results in the CS 2 h + HMP 2 h ± SP600125 group than in the CS 4 h ± SP600125 group. CONCLUSION: HMP in combination with SP600125 has hepatoprotective properties and improves the quality and viability of porcine livers collected after DCD, thus improving prognosis after liver transplantation.


Assuntos
Aloenxertos/efeitos dos fármacos , Antracenos/farmacologia , Transplante de Fígado , Preservação de Órgãos/métodos , Perfusão/métodos , Animais , Temperatura Baixa , Morte , Modelos Animais de Doenças , Traumatismo por Reperfusão/prevenção & controle , Suínos , Porco Miniatura
4.
Anim Sci J ; 91(1): e13465, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33222358

RESUMO

The present study was conducted to investigate the effect of cold storage time on apoptosis of cumulus cells (CCs) from porcine ovaries, and to compare the sensitivity of four apoptosis-detection methods. Porcine ovaries were stored in physiological saline solution at 4°C for 0, 7, 24 and 48 hr, and then cumulus cells or granulosa cells (GCs) in antral follicles were retrieved to detect cell apoptosis. Cumulus cells isolated from stored ovaries for 24 hr presented obvious apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end-labeling (TUNEL) assay. A typical DNA ladder pattern of apoptosis was observed in GCs 24 hr post storage treatment. The mean Olive Tail Moment of CCs was significantly increased after 24 hr using comet assay; however, the mean tail migration and mean tail DNA increased gradually after 7 hr of storage. In addition, annexin V/PI staining assay showed an obvious increase in apoptotic CCs (Annexin V positive, PI negative) 7 hr after treatment, and the apoptotic rate reached to a peak at 24 hr followed by a decline after 48 hr of storage to the level at 7 hr. In conclusion, cold storage of porcine ovary in physiological saline solution induced a time-dependent increase in apoptosis of cumulus cells, and annexin V/PI staining combined with comet assay provided a sensitive and reliable method to detect early damages in cumulus cells induced by cold storage of ovary.


Assuntos
Apoptose , Temperatura Baixa/efeitos adversos , Células do Cúmulo/patologia , Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/métodos , Folículo Ovariano/citologia , Ovário , Animais , Separação Celular , Células Cultivadas , Células do Cúmulo/fisiologia , DNA , Feminino , Marcação In Situ das Extremidades Cortadas/métodos , Ovário/citologia , Suínos , Fatores de Tempo
5.
PLoS One ; 15(10): e0239604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044976

RESUMO

Demand for heart transplants far exceeds supply of donated organs. This is attributed to the high percentage of donor hearts that are discarded and to the narrow six-hour time window currently available for transplantation. Ex-vivo heart perfusion (EVHP) provides the opportunity for resuscitation of damaged organs and extended transplantation time window by enabling functional assessment of the hearts in a near-physiologic state. Present work investigates the fluid mechanics of the ex-vivo flow loop and corresponding impact on cardiac performance. A mechanical flow loop is developed that is analogous to the region of the EVHP system that mimics in-vivo systemic circulation, including the body's largest and most compliant artery, the aorta. This investigation is focused on determining the effect of mock aortic tubing compliance on pump performance. A custom-made silicone mock aorta was developed to simulate a range of in-vivo conditions and a physiological flow was generated using a commercial ventricular assist device (VAD). Monitored parameters, including pressure, tube distension and downstream velocity, acquired using time-resolved particle imaging velocimetry (PIV), were applied to an unsteady Bernoulli analysis of the flow in a novel way to evaluate pump performance as a proxy for cardiac workload. When compared to the rigid case, the compliant mock aorta case demonstrated healthier physiologic pressure waveforms, steadier downstream flow and reduced energetic demands on the pump. These results provide experimental verification of Windkessel theory and support the need for a compliant mock aorta in the EVHP system.


Assuntos
Aorta/fisiologia , Transplante de Coração/métodos , Modelos Cardiovasculares , Complacência (Medida de Distensibilidade) , Circulação Extracorpórea , Coração Auxiliar , Hemodinâmica , Humanos , Técnicas In Vitro , Preservação de Órgãos/instrumentação , Preservação de Órgãos/métodos , Perfusão/instrumentação , Perfusão/métodos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos
6.
J Vis Exp ; (162)2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32894268

RESUMO

In the present era of organ transplantation with critical organ shortage, various strategies are employed to expand the pool of available allografts for kidney transplantation (KT). Even though, the use of allografts from extended criteria donors (ECD) could partially ease the shortage of organ donors, ECD organs carry a potentially higher risk for inferior outcomes and postoperative complications. Dynamic organ preservation techniques, modulation of ischemia-reperfusion and preservation injury, and allograft therapies are in the spotlight of scientific interest in an effort to improve allograft utilization and patient outcomes in KT. Preclinical animal experiments are playing an essential role in translational research, especially in the medical device and drug development. The major advantage of the porcine orthotopic auto-transplantation model over ex vivo or small animal studies lies within the surgical-anatomical and physiological similarities to the clinical setting. This allows the investigation of new therapeutic methods and techniques and ensures a facilitated clinical translation of the findings. This protocol provides a comprehensive and problem-oriented description of the porcine orthotopic kidney auto-transplantation model, using a preservation time of 24 hours and telemetry monitoring. The combination of sophisticated surgical techniques with highly standardized and state-of-the-art methods of anesthesia, animal housing, perioperative follow up, and monitoring ensure the reproducibility and success of this model.


Assuntos
Transplante de Rim/métodos , Preservação de Órgãos/métodos , Telemetria , Aloenxertos , Animais , Rim , Modelos Animais , Traumatismo por Reperfusão/prevenção & controle , Reprodutibilidade dos Testes , Suínos , Doadores de Tecidos , Transplante Homólogo
7.
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
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
10.
Transplantation ; 104(9): 1890-1898, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32826843

RESUMO

BACKGROUND: Ex situ heart perfusion (ESHP) limits ischemic periods and enables continuous monitoring of donated hearts; however, a validated assessment method to predict cardiac performance has yet to be established. We compare biventricular contractile and metabolic parameters measured during ESHP to determine the best evaluation strategy to estimate cardiac function following transplantation. METHODS: Donor pigs were assigned to undergo beating-heart donation (n = 9) or donation after circulatory death (n = 8) induced by hypoxia. Hearts were preserved for 4 hours with ESHP while invasive and noninvasive (NI) biventricular contractile, and metabolic assessments were performed. Following transplantation, hearts were evaluated at 3 hours of reperfusion. Spearman correlation was used to determine the relationship between ESHP parameters and posttransplant function. RESULTS: We performed 17 transplants; 14 successfully weaned from bypass (beating-heart donation versus donation after circulatory death; P = 0.580). Left ventricular invasive preload recruitable stroke work (PRSW) (r = 0.770; P = 0.009), NI PRSW (r = 0.730; P = 0.001), and NI maximum elastance (r = 0.706; P = 0.002) strongly correlated with cardiac index (CI) following transplantation. Right ventricular NI PRSW moderately correlated to CI following transplantation (r = 0.688; P = 0.003). Lactate levels were weakly correlated with CI following transplantation (r = -0.495; P = 0.043). None of the echocardiography measurements correlated with cardiac function following transplantation. CONCLUSIONS: Left ventricular functional parameters, especially ventricular work and reserve, provided the best estimation of myocardial performance following transplantation. Furthermore, simple NI estimates of ventricular function proved useful in this setting. Right ventricular and metabolic measurements were limited in their ability to correlate with myocardial recovery. This emphasizes the need for an ESHP platform capable of assessing myocardial contractility and suggests that metabolic parameters alone do not provide a reliable evaluation.


Assuntos
Transplante de Coração/métodos , Preservação de Órgãos/métodos , Perfusão , Doadores de Tecidos , Função Ventricular Esquerda/fisiologia , Animais , Ecocardiografia , Masculino , Contração Miocárdica , Miocárdio/metabolismo , Suínos
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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
Medicine (Baltimore) ; 99(28): e20934, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664090

RESUMO

This study aimed to investigate the myocardial protective effect of liquid sodium phosphocreatine cardiac arrest in extracorporeal circulation surgery treating infants with atrial septal defects.Eighty-four infants with atrial septal defects who required extracorporeal circulation surgery treatment at our hospital from January 2016 to June 2018 were divided into an observation group and a control group through a digitally randomized method, with 42 cases in each group. The control group adopted the conventional modified St Thomas II high potassium cold liquid crystal cardiac arrest, while the observation group adopted the liquid sodium phosphocreatine cardiac arrest.The myocardial enzyme indexes of the 2 groups 3, 6, 12, and 24 hours postoperatively were higher than before establishing the cardiopulmonary bypass and the enzyme indexes of the control group at the same time were higher than that of the observation group; adenosine triphosphate, adenosine diphosphate, and other energy levels and the postoperative recovery rate energy levels of the observation group were higher than those in the control group, the difference was statistically significant (P < .05).Liquid sodium phosphocreatine cardiac arrest used in extracorporeal circulation surgery treating infants with atrial septal defects can reduce myocardial ischemia-reperfusion injury, maintain energy supply during ischemia, strengthen the St Thomas II effect, and aid postoperative cardiac function recovery of high potassium cold liquid crystal cardiac arrest used in infants with atrial septal defects and treated with extracorporeal circulation surgery.


Assuntos
Ponte Cardiopulmonar/métodos , Cardiotônicos/farmacologia , Parada Cardíaca Induzida/métodos , Comunicação Interatrial/cirurgia , Fosfocreatina/farmacologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Cardiotônicos/administração & dosagem , Estudos de Casos e Controles , Pré-Escolar , Circulação Extracorpórea/métodos , Feminino , Parada Cardíaca/induzido quimicamente , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/tratamento farmacológico , Humanos , Lactente , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/química , Miocárdio/enzimologia , Preservação de Órgãos/métodos , Fosfocreatina/administração & dosagem , Período Pós-Operatório , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/farmacologia , Substâncias Protetoras/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos
19.
PLoS One ; 15(7): e0235635, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614897

RESUMO

BACKGROUND: Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP). METHODS: Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion. RESULTS: Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend. CONCLUSION: Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.


Assuntos
Dipirona/farmacologia , Transplante de Fígado , Preservação de Órgãos/métodos , Vasodilatação/efeitos dos fármacos , Animais , Pressão Arterial/efeitos dos fármacos , Bile/metabolismo , Ductos Biliares/patologia , Artéria Hepática/patologia , Fígado/irrigação sanguínea , Fígado/patologia , Testes de Função Hepática , Masculino , Ratos , Ratos Wistar
20.
PLoS One ; 15(7): e0236183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697805

RESUMO

BACKGROUND: Herpetic keratitis (HK) models using whole human corneas are essential for studying virus-host relationships, because of high species specificity and the role of interactions between corneal cell populations that cell culture cannot reproduce. Nevertheless, the two current corneal storage methods (hypothermia and organ culture (OC)) do not preserve corneas in good physiological condition, as they are characterized by epithelial abrasion, stromal oedema, and excessive endothelial mortality. METHODS: To rehabilitate human corneas intended for scientific use, we used an active storage machine (ASM) that restores two physiological parameters that are essential for corneal homeostasis: intraocular pressure and storage medium renewal (21mmHg and 2.6 µL/min, respectively). ASM storage regenerates a normal multilayer epithelium in 2 weeks. We infected six pairs of corneas unsuitable for graft by inoculating the epithelium with herpes simplex virus type 1 (HSV-1), and compared each ASM-stored cornea with the other cornea stored in the same medium using the conventional OC method. RESULTS: Only corneas in the ASM developed a dendritic (n = 3) or geographic (n = 2) epithelial ulcer reproducing typical HSV-1-induced clinical lesions. Corneas in OC showed only extensive desquamations. None of the uninfected controls showed epithelial damage. Histology, immunohistochemistry, transmission electron microscopy and polymerase chain reaction on corneal tissue confirmed infection in all cases (excluding negative controls). CONCLUSIONS: The ASM provides an innovative ex vivo model of HK in whole human cornea that reproduces typical epithelial lesions.


Assuntos
Córnea/patologia , Herpesvirus Humano 1/patogenicidade , Ceratite Herpética/patologia , Técnicas de Cultura de Órgãos/instrumentação , Preservação de Órgãos/instrumentação , Idoso , Idoso de 80 Anos ou mais , Córnea/diagnóstico por imagem , Córnea/ultraestrutura , Córnea/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Ceratite Herpética/diagnóstico , Ceratite Herpética/tratamento farmacológico , Ceratite Herpética/virologia , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos/métodos , Preservação de Órgãos/métodos , Microscopia com Lâmpada de Fenda
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