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1.
Nat Commun ; 15(1): 3818, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740760

RESUMEN

The growing disparity between the demand for transplants and the available donor supply, coupled with an aging donor population and increasing prevalence of chronic diseases, highlights the urgent need for the development of platforms enabling reconditioning, repair, and regeneration of deceased donor organs. This necessitates the ability to preserve metabolically active kidneys ex vivo for days. However, current kidney normothermic machine perfusion (NMP) approaches allow metabolic preservation only for hours. Here we show that human kidneys discarded for transplantation can be preserved in a metabolically active state up to 4 days when perfused with a cell-free perfusate supplemented with TCA cycle intermediates at subnormothermia (25 °C). Using spatially resolved isotope tracing we demonstrate preserved metabolic fluxes in the kidney microenvironment up to Day 4 of perfusion. Beyond Day 4, significant changes were observed in renal cell populations through spatial lipidomics, and increases in injury markers such as LDH, NGAL and oxidized lipids. Finally, we demonstrate that perfused kidneys maintain functional parameters up to Day 4. Collectively, these findings provide evidence that this approach enables metabolic and functional preservation of human kidneys over multiple days, establishing a solid foundation for future clinical investigations.


Asunto(s)
Riñón , Preservación de Órganos , Perfusión , Humanos , Riñón/metabolismo , Preservación de Órganos/métodos , Perfusión/métodos , Trasplante de Riñón , Masculino , Soluciones Preservantes de Órganos , Femenino , Persona de Mediana Edad , Sistema Libre de Células , Ciclo del Ácido Cítrico , Adulto , Nutrientes/metabolismo , Lipidómica/métodos , Anciano
2.
Front Mol Biosci ; 11: 1341108, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38784665

RESUMEN

Introduction: Normothermic ex vivo kidney perfusion (NEVKP) is designed to replicate physiological conditions to improve graft outcomes. A comparison of the impact of hypothermic and normothermic preservation techniques on graft quality was performed by lipidomic profiling using solid-phase microextraction (SPME) chemical biopsy as a minimally invasive sampling approach. Methods: Direct kidney sampling was conducted using SPME probes coated with a mixed-mode extraction phase in a porcine autotransplantation model of the renal donor after cardiac death, comparing three preservation methods: static cold storage (SCS), NEVKP, and hypothermic machine perfusion (HMP). The lipidomic analysis was done using ultra-high-performance liquid chromatography coupled with a Q-Exactive Focus Orbitrap mass spectrometer. Results: Chemometric analysis showed that the NEVLP group was separated from SCS and HMP groups. Further in-depth analyses indicated significantly (p < 0.05, VIP > 1) higher levels of acylcarnitines, phosphocholines, ether-linked and longer-chain phosphoethanolamines, triacylglycerols and most lysophosphocholines and lysophosphoethanolamines in the hypothermic preservation group. The results showed that the preservation temperature has a more significant impact on the lipidomic profile of the kidney than the preservation method's mechanical characteristics. Conclusion: Higher levels of lipids detected in the hypothermic preservation group may be related to ischemia-reperfusion injury, mitochondrial dysfunction, pro-inflammatory effect, and oxidative stress. Obtained results suggest the NEVKP method's beneficial effect on graft function and confirm that SPME chemical biopsy enables low-invasive and repeated sampling of the same tissue, allowing tracking alterations in the graft throughout the entire transplantation procedure.

3.
Transplant Direct ; 10(5): e1620, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38617463

RESUMEN

Background: Pancreas transplant volumes are limited because of poor utilization of "extended criteria grafts." Prolonged cold ischemia is a risk factor associated with poor allograft survival. We aimed to establish the feasibility of transplantation using grafts subjected to prolonged cold ischemia and determine whether these grafts could be optimized using normothermic ex vivo perfusion (NEVP) in a porcine model. Methods: The study population consisted of 35 to 40 kg male Yorkshire pigs in an allotransplantation model with a 3-d survival plan for recipients. Control grafts were subjected to cold storage (CS) in a University of Wisconsin solution for 21 to 24 h (n = 6), whereas the test group received an additional 3 h NEVP after CS of 21 h (n = 5). Results: The 3-d survival was 60% in the NEVP arm versus 0% in the control arm (P = 0.008; log rank). Graft parenchyma was 60% to 70% preserved in the NEVP arm at necropsy on gross appearance. In addition, the islet function was well preserved, and both the pancreas (including the islets) and the duodenal morphology were maintained histologically. The intravenous glucose tolerance test on the day of euthanasia was in the normoglycemic range for 80% of cases in the NEVP arm. Conclusions: Optimization of pancreas grafts exposed to extended CS with NEVP seems promising at rescuing and reanimating these grafts for transplantation, resulting in significantly improved survival in a porcine pancreas transplant model.

4.
Liver Transpl ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38619393

RESUMEN

Background Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with AILD; autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). We compared the survival of patients with a potential live donor (pLDLT) on the waitlist vs. no potential live donor (pDDLT), on an intention-to-treat (ITT) basis. Methods Our retrospective cohort study investigated adults with AILD listed for liver transplant at our program between 2000 and 2021. The pLDLT group comprised recipients with a potential live donor. Otherwise, they were included in the pDDLT group. ITT survival was assessed from the time of listing. Results Of the 533 patients included, 244(43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85[29.4%] vs. pLDLT 9[3.7], p<0.001). The 1-, 3- and 5-year ITT survival rates were higher for pLDLT vs. pDDLT among all AILDs (95.7%vs.78.1%, 89.0%vs.70.1%, and 87.1%vs.65.5%, p<0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR:0.62, 95%CI:0.42-0.93[p<0.05]), and 60% among the PSC cohort (HR:0.40, 95%CI:0.22-0.74[p<0.05]). There were no differences in the 1-, 3- and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6%vs.92.1%, 89.9%vs.89.4%, and 89.1%vs. 87.1%, p=0.41). This was consistent after adjusting for covariates (HR: 0.97, 95%CI:0.56-1.68[p>0.9]). Conclusion Our study suggests that having a potential live donor could decrease the risk of death in patients with PSC on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

6.
Transplantation ; 108(5): 1043-1052, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38494468

RESUMEN

The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registered delegates from 54 countries representing 5 continents, with the 10 countries comprising the bulk of the delegates. Of the 647 abstracts initially submitted, 542 were eventually presented at the meeting, coming from 38 countries (mainly North America, Europe, and Asia) and 85% of them (462 abstracts) came from only 10 countries. Fifty-three (9.8%) abstracts, originated from 17 countries, were submitted under the Basic/Translational Scientific Research category, a similar percentage as in 2022. Abstracts presented at the meeting were classified as (1) ischemia and reperfusion injury, (2) machine perfusion, (3) bioengineering and liver regeneration, (4) transplant oncology, (5) novel biomarkers in liver transplantation, (6) liver immunology (rejection and tolerance), and (7) artificial intelligence and machine learning. Finally, we evaluated the number of abstracts commented in the Basic and Translational Research Committee-International Liver Transplantation Society annual reports over the past 5 y that resulted in publications in peer-reviewed journals to measure their scientific impact in the field of liver transplantation.


Asunto(s)
Trasplante de Hígado , Investigación Biomédica Traslacional , Trasplante de Hígado/tendencias , Humanos , Investigación Biomédica Traslacional/organización & administración , Investigación Biomédica Traslacional/tendencias , COVID-19/epidemiología , SARS-CoV-2/inmunología , Sociedades Médicas , Congresos como Asunto
7.
Transplantation ; 108(1): 184-191, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37505906

RESUMEN

BACKGROUND: Ex vivo machine perfusion is a novel preservation technique for storing and assessing marginal kidney grafts. All ex vivo perfusion techniques have advantages and shortcomings. The current study analyzed whether a combination of oxygenated hypothermic machine perfusion (oxHMP) followed by a short period of normothermic ex vivo kidney perfusion (NEVKP) could combine the advantages of both techniques. METHODS: Porcine kidneys were exposed to 30 min of warm ischemia followed by perfusion. Kidneys underwent either 16-h NEVKP or 16-h oxHMP. The third group was exposed to 16-h oxHMP followed by 3-h NEVKP (oxHMP + NEVKP group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed up for 8 d. RESULTS: All animals survived the follow-up period. Grafts preserved by continuous NEVKP showed improved function with lower peak serum creatinine and more rapid recovery compared with the other 2 groups. Urine neutrophil gelatinase-associated lipocalin, a marker of kidney injury, was found to be significantly lowered on postoperative day 3 in the oxHMP + NEVKP group compared with the other 2 groups. CONCLUSIONS: A short period of NEVKP after oxHMP provides comparable short-term outcomes to prolonged NEVKP and is superior to oxHMP alone. A combination of oxHMP with end-ischemic NEVKP could be an attractive, practical strategy to combine the advantages of both preservation techniques.


Asunto(s)
Trasplante de Riñón , Porcinos , Animales , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Preservación de Órganos/métodos , Modelos Animales , Riñón/cirugía , Perfusión/efectos adversos , Perfusión/métodos
8.
Transl Res ; 267: 79-90, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38052298

RESUMEN

Transplant centers are currently facing a lack of tools to ensure adequate evaluation of the quality of the available organs, as well as a significant shortage of kidney donors. Therefore, efforts are being made to facilitate the effective use of available organs and expand the donor pool, particularly with expanded criteria donors. Fulfilling a need, we aim to present an innovative analytical method based on solid-phase microextraction (SPME) - chemical biopsy. In order to track changes affecting the organ throughout the entire transplant procedure, porcine kidneys were subjected to multiple samplings at various time points. The application of small-diameter SPME probes assured the minimal invasiveness of the procedure. Porcine model kidney autotransplantation was executed for the purpose of simulating two types of donor scenarios: donors with a beating heart (HBD) and donors after cardiac death (DCD). All renal grafts were exposed to continuous normothermic ex vivo perfusion. Following metabolomic and lipidomic profiling using high-performance liquid chromatography coupled to a mass spectrometer, we observed differences in the profiles of HBD and DCD kidneys. The alterations were predominantly related to energy and glucose metabolism, and differences in the levels of essential amino acids, purine nucleosides, lysophosphocholines, phosphoethanolamines, and triacylglycerols were noticed. Our results indicate the potential of implementing chemical biopsy in the evaluation of graft quality and monitoring of renal function during perfusion.


Asunto(s)
Riñón , Lipidómica , Porcinos , Animales , Humanos , Donantes de Tejidos , Muerte , Perfusión/métodos , Supervivencia de Injerto
9.
Ann Hepatol ; 29(1): 101168, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37858675

RESUMEN

INTRODUCTION AND OBJECTIVES: Recurrent cirrhosis complicates 10-30% of Liver transplants (LT) and can lead to consideration for re-transplantation. We evaluated the trajectories of relisted versus primary listed patients on the waitlist using a competing risk framework. MATERIALS AND METHODS: We retrospectively examined 1,912 patients listed for LT at our centre between from 2012 to 2020. Cox proportional hazard models were used to assess overall survival (OS) by listing type and competing risk analysis Fine-Gray models were used to assess cumulative incidence of transplant by listing type. RESULTS: 1,731 patients were included (104 relisted). 44.2% of relisted patients received exception points vs. 19.8% of primary listed patients (p<0.001). Patients relisted without exceptions, representing those with graft cirrhosis, had the worst OS (HR: 4.17, 95%CI 2.63 - 6.67, p=<0.0001) and lowest instantaneous rate of transplant (HR: 0.56, 95%CI 0.38 - 0.83, p=0.006) than primary listed with exception points. On multivariate analysis listing type, height, bilirubin and INR were associated with cumulative incidence of transplant, while listing type, bilirubin, INR, sodium, creatinine were associated with OS. Within relisted patients, there was a trend towards higher mortality (HR: 1.79, 95%CI 0.91 - 3.52, p=0.08) and low transplant incidence (HR: 0.51, 95%CI 0.22 - 1.15, p=0.07) for graft cirrhosis vs other relisting indications. CONCLUSIONS: Patients relisted for LT are carefully curated and comprise a minority of the waitlist population. Despite their younger age, they have worse liver/kidney function, poor waitlist survival, and decreased transplant incidence suggesting the need for early relisting, while considering standardized exception points.


Asunto(s)
Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/cirugía , Modelos de Riesgos Proporcionales , Listas de Espera , Bilirrubina
10.
Can J Surg ; 66(6): E561-E571, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38016726

RESUMEN

BACKGROUND: Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors. METHODS: Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study. Short-and long-term outcomes were analyzed for 4 groups of patients: those who received DCD and DBD grafts from younger (< 50 yr) and older (≥ 50 yr) donors. RESULTS: Of the 807 patients included in the analysis, 44.7% (n = 361) of grafts were received from older donors, with grafts for older DCD donors comprising 4.7% of the total cohort (n = 38). Patients who received grafts from older donors had a lower incidence of biliary strictures than those who received grafts from younger donors (7.9% v. 20.0% for DCD donation, p = 0.14, and 4.9% v. 6.8% for DBD donation, p = 0.34), with a significantly lower incidence of ischemic-type biliary strictures in patients who received grafts from older versus younger DCD donors (2.6% v. 18.0%, p = 0.04). There was no difference in 1- and 3-year graft survival rates among patients who received grafts from older and younger DCD donors (92.1% v. 90.8% and 80.2% v. 80.9%, respectively) and those who received grafts from older and younger DBD donors (90.1% v. 93.2% and 85.3% v. 84.4%, respectively) (p = 0.85). Pretransplantation admission to the intensive care unit (hazard ratio [HR] 9.041, p < 0.001) and nonalcoholic steatohepatitis (HR 2.197, p = 0.02) were found to significantly affect survival of grafts from older donors. CONCLUSION: Donor age alone should not be the criterion to determine the acceptability of grafts in liver transplantation. With careful selection criteria, older DCD donors could make a valuable contribution to expanding the liver donor pool, with grafts that produce comparable results to those obtained with standard-criteria grafts.


Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Constricción Patológica , Estudios Retrospectivos , Donadores Vivos , Donantes de Tejidos , Muerte , Muerte Encefálica
11.
Transplantation ; 107(10): 2238-2246, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37749813

RESUMEN

Small-for-size syndrome (SFSS) following living donor liver transplantation is a complication that can lead to devastating outcomes such as prolonged poor graft function and possibly graft loss. Because of the concern about the syndrome, some transplants of mismatched grafts may not be performed. Portal hyperperfusion of a small graft and hyperdynamic splanchnic circulation are recognized as main pathogenic factors for the syndrome. Management of established SFSS is guided by the severity of the presentation with the initial focus on pharmacological therapy to modulate portal flow and provide supportive care to the patient with the goal of facilitating graft regeneration and recovery. When medical management fails or condition progresses with impending dysfunction or even liver failure, interventional radiology (IR) and/or surgical interventions to reduce portal overperfusion should be considered. Although most patients have good outcomes with medical, IR, and/or surgical management that allow graft regeneration, the risk of graft loss increases dramatically in the setting of bilirubin >10 mg/dL and INR>1.6 on postoperative day 7 or isolated bilirubin >20 mg/dL on postoperative day 14. Retransplantation should be considered based on the overall clinical situation and the above postoperative laboratory parameters. The following recommendations focus on medical and IR/surgical management of SFSS as well as considerations and timing of retransplantation when other therapies fail.


Asunto(s)
Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Bilirrubina , Consenso , Laboratorios , Síndrome
12.
Transplant Direct ; 9(9): e1519, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37649790

RESUMEN

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes. Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results: Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions: Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

14.
Transpl Int ; 36: 10936, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37252614

RESUMEN

Pancreas transplantation is the only curative treatment for patients with complicated diabetes, and organ shortage is a common and increasing problem. Strategies to expand the donor pool are needed, and normothermic ex vivo perfusion of the pancreas has the potential to test and repair grafts before implantation. Between January 2021 and April 2022, six human pancreases, declined for transplantation or islet isolation, were perfused using a previously established method by our group. All 6 cases were successfully perfused for 4 h, with minimal edema. The mean age of the donors was 44.16 ± 13.8 years. Five grafts were obtained from neurological death donors, and one was obtained from a donation after cardiac death. The mean glucose and lactate levels decreased throughout perfusion and insulin levels increased. All 6 grafts were metabolically active during perfusion and histopathology showed minimal tissue injury and no edema. Human normothermic ex vivo perfusion of the pancreas is feasible and safe and has the potential to expand the donor pool. Future studies will focus on tests and biomarkers for the assessment of grafts.


Asunto(s)
Preservación de Órganos , Donantes de Tejidos , Humanos , Adulto , Persona de Mediana Edad , Preservación de Órganos/métodos , Estudios de Factibilidad , Perfusión/métodos , Páncreas , Aloinjertos
15.
Ann Med Surg (Lond) ; 85(4): 732-737, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37113957

RESUMEN

Despite having emerged as a definitive treatment for diabetes mellitus (DM), pancreas transplantation remains a formidable surgical task owing to complications like graft pancreatitis, enteric leaks, and rejection. This becomes more challenging in the setting of underlying bowel pathology, such as inflammatory bowel disease (IBD), which has a strong immune-genomic association of co-existence with DM. Risk of anastomotic leaks, dose adjustments of immunosuppressants and biologicals, and management of IBD flares constitute some of the major perioperative challenges calling for a protocol-based, systematic, multidisciplinary approach. Patients and methods: This was a retrospective case series of patients between January 1996 and July 2021, with all patients being followed up until December 2021. All consecutive patients with end-stage DM who underwent pancreas transplantation (alone, simultaneous with kidney transplantation or after kidney transplantation) and had pre-existing IBD were included in the study. A Comparison of 1-, 5-, 10-year survival was done with pancreas transplant recipients without underlying IBD using Kaplan-Meir curves. Results: Of the total 630 pancreas transplants performed between 1996 and 2021, eight patients had IBD, mostly Crohn's disease. Following pancreas transplantation, two of the eight patients had duodenal leaks, with one a requiring graft pancreatectomy. The 5-year graft survival rate for the cohort was 75% compared to 81.6% for the overall cohort of patients undergoing pancreas transplantation (P=0.48) with a median graft survival of 48.4 months compared to 68.1 months in the latter (P=0.56). Conclusion: The findings of the series provide a snapshot of the outcome of pancreas transplantation in the background of IBD, suggesting a graft and overall patient survival rates comparable with pancreas transplantation in patients without underlying IBD, with further validation of the findings required in a larger cohort of patients in the future.

16.
Can J Surg ; 66(2): E162-E169, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37001976

RESUMEN

BACKGROUND: Because kidney transplant recipients may be at increased risk for deep vein thrombosis (DVT) following transplantation, we investigated the incidence, risk factors, treatments and outcomes of early DVT among kidney transplant recipients. METHODS: An observational, single-centre cohort study was conducted among adult kidney transplant recipients from Jan. 1, 2005, to Dec. 31, 2016 with 1-year followup. Time to DVT was assessed using the Kaplan-Meier method. Cox proportional hazards and linear regression models were used to analyze risk factors for and outcomes of DVT. RESULTS: The cumulative incidence of DVT was 4.25% at 3 months after transplant. In multivariable analysis, the use of depleting induction agents (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.05-4.35]), white recipient race (HR 1.84. 95% CI 1.08-3.12), the use of kidneys from expanded criteria donors (HR 2.13, 95% CI 1.05-4.32) and lower recipient body mass index (HR 0.95, 95% CI 0.91-1.00) increased the risk for early DVT. Peritransplant DVT prophylaxis was not associated with early DVT. Early DVT was not associated with reduced graft function, death, graft failure or first hospital readmission. CONCLUSION: Risk factors for early DVT in our cohort of kidney transplant recipients included white recipient race, use of depleting agents, lower recipient body mass index and use of expanded criteria donors. As practice patterns of donor and recipient selection in kidney transplantation evolve, the results of this study may aid in perioperative risk assessments and decision-making about the use of DVT prophylaxis.


Asunto(s)
Trasplante de Riñón , Trombosis de la Vena , Adulto , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Estudios de Cohortes , Riñón , Donantes de Tejidos , Factores de Riesgo , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Resultado del Tratamiento
17.
Int J Mol Sci ; 24(3)2023 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-36768452

RESUMEN

The development of surgical techniques, immunosuppressive strategies and new organ preservation methods have meant that transplant centers have to face the problem of an insufficient number of organs for transplantation concerning the constantly growing demand. Therefore, using organs from expanded criteria donors and developing new analytical solutions to find parameters or compounds that would allow a more efficient assessment of organ quality before transplantation are options for meeting this challenge. This study proposed bile metabolomic analysis to evaluate liver metabolism and biliary tract function depending on the organ preservation method and degree of warm ischemia time. The analyses were performed on solid-phase microextraction-prepared bile samples from porcine model donors with mild (heart beating donor [HBD]) and moderate warm ischemia (donation after circulatory death [DCD]) grafts subjected to static cold storage (SCS) or normothermic ex vivo liver perfusion (NEVLP) before transplantation. Bile produced in the SCS-preserved livers was characterized by increased levels of metabolites such as chenodeoxycholic acid, arachidonic acid and 5S-hydroxyeicosatetraeonic acid, as well as saturated and monounsaturated lysophosphatidylcholines (LPC). Such changes may be associated with differences in the bile acid synthesis pathways and organ inflammation. Moreover, it has been shown that NEVLP reduced the negative effect of ischemia on organ function. A linear relationship was observed between levels of lipids from the LPC group and the time of organ ischemia. This study identified metabolites worth considering as potential markers of changes occurring in preserved grafts.


Asunto(s)
Sistema Biliar , Trasplante de Hígado , Daño por Reperfusión , Porcinos , Animales , Preservación de Órganos/métodos , Trasplante de Hígado/métodos , Daño por Reperfusión/metabolismo , Perfusión/métodos , Sistema Biliar/metabolismo , Hígado/metabolismo , Isquemia/metabolismo , Isquemia Tibia , Metaboloma
18.
J Vis Exp ; (192)2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36807320

RESUMEN

Translational surgical research models in swine are crucial for developing safe preclinical protocols. However, the success of the experimental surgeries does not solely rely on the research team's surgical skills; perioperative care and management procedures, like intubation, central venous line, and arterial line placement, are necessary and of the utmost importance for favorable experiment results. As it is uncommon for research teams to have anesthesiologists or any other staff other than the surgical team, the surgical team involved in translational research must acquire and/or develop the skills to perform the perioperative care. The purpose of this paper is to show the techniques of intubation, central venous catheter, and arterial line placement used and perfected at the Toronto Organ Preservation Laboratory over the last 10 years, to be used as a reference for future researchers joining either this team or any other lab performing translational research protocols in swine and/or abdominal transplantation.


Asunto(s)
Cateterismo Venoso Central , Catéteres Venosos Centrales , Porcinos , Animales , Investigación Biomédica Traslacional , Cateterismo , Arterias , Intubación Intratraqueal , Cateterismo Venoso Central/métodos
19.
Ann Surg ; 277(5): 713-718, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36515405

RESUMEN

OBJECTIVE: To report the clinical outcomes of liver transplants from donors after medical assistance in dying (MAiD) versus donors after cardiac death (DCD) and deceased brain death (DBD). SUMMARY BACKGROUND DATA: In North America, the number of patients needing liver transplants exceeds the number of available donors. In 2016, MAiD was legalized in Canada. METHODS: All patients undergoing deceased donor liver transplantation at Toronto General Hospital between 2016 and 2021 were included in the study. Recipient perioperative and postoperative variables and donor physiological variables were compared among 3 groups. RESULTS: Eight hundred seven patients underwent deceased donor liver transplantation during the study period, including DBD (n=719; 89%), DCD (n=77; 9.5%), and MAiD (n=11; 1.4%). The overall incidence of biliary complications was 6.9% (n=56), the most common being strictures (n=55;6.8%), highest among the MAiD recipients [5.8% (DBD) vs. 14.2% (DCD) vs. 18.2% (MAiD); P =0.008]. There was no significant difference in 1 year (98.4% vs. 96.4% vs. 100%) and 3-year (89.3% vs. 88.7% vs. 100%) ( P =0.56) patient survival among the 3 groups. The 1- and 3- year graft survival rates were comparable (96.2% vs. 95.2% vs. 100% and 92.5% vs. 91% vs. 100%; P =0.37). CONCLUSION: With expected physiological hemodynamic challenges among MAiD and DCD compared with DBD donors, a higher rate of biliary complications was observed in MAiD donors, with no significant difference noted in short-and long-term graft outcomes among the 3 groups. While ethical challenges persist, good initial results suggest that MAiD donors can be safely used in liver transplantation, with results comparable with other established forms of donation.


Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Trasplante de Hígado/métodos , Donadores Vivos , Supervivencia de Injerto , Estudios Retrospectivos , Donantes de Tejidos , Muerte , Muerte Encefálica , Hígado
20.
Surgery ; 173(2): 529-536, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36334982

RESUMEN

BACKGROUND: Despite most liver transplants in North America being from deceased donors, the number of living donor liver transplants has increased over the last decade. Although outcomes of liver retransplantation after deceased donor liver transplantation have been widely published, outcomes of retransplant after living donor liver transplant need to be further elucidated. METHOD: We aimed to compare waitlist outcomes and survival post-retransplant in recipients of initial living or deceased donor grafts. Adult liver recipients relisted at University Health Network between April 2000 and October 2020 were retrospectively identified and grouped according to their initial graft: living donor liver transplants or deceased donor liver transplant. A competing risk multivariable model evaluated the association between graft type at first transplant and outcomes after relisting. Survival after retransplant waitlisting (intention-to-treat) and after retransplant (per protocol) were also assessed. Multivariable Cox regression evaluated the effect of initial graft type on survival after retransplant. RESULTS: A total of 201 recipients were relisted (living donor liver transplants, n = 67; donor liver transplants, n = 134) and 114 underwent retransplant (living donor liver transplants, n = 48; deceased donor liver transplants, n = 66). The waitlist mortality with an initial living donor liver transplant was not significantly different (hazard ratio = 0.51; 95% confidence interval, 0.23-1.10; P = .08). Both unadjusted and adjusted graft loss risks were similar post-retransplant. The risk-adjusted overall intention-to-treat survival after relisting (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32; P = .30) and per protocol survival after retransplant (hazard ratio:1.51; 95% confidence interval, 0.54-4.19; P = .40) were equivalent in those who initially received a living donor liver transplant. CONCLUSION: Patients requiring relisting and retransplant after either living donor liver transplants or deceased donor liver transplantation experience similar waitlist and survival outcomes.


Asunto(s)
Trasplante de Hígado , Donadores Vivos , Adulto , Humanos , Trasplante de Hígado/métodos , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Supervivencia de Injerto
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