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1.
Liver Transpl ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38869990

RESUMEN

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.

2.
BMJ Open ; 14(6): e086777, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871657

RESUMEN

INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.


Asunto(s)
Inhibidores de la Calcineurina , Funcionamiento Retardado del Injerto , Trasplante de Riñón , Donantes de Tejidos , Humanos , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/uso terapéutico , Proyectos Piloto , Funcionamiento Retardado del Injerto/prevención & control , Tacrolimus/uso terapéutico , Tacrolimus/administración & dosificación , Muerte Encefálica , Supervivencia de Injerto/efectos de los fármacos , Quebec , Ensayos Clínicos Controlados Aleatorios como Asunto , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Estudios Multicéntricos como Asunto , Masculino , Ontario , Adulto , Femenino
3.
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.

4.
BMC Surg ; 24(1): 165, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802757

RESUMEN

BACKGROUND: Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30 days of transplantation on patient survival, graft function, and hospital readmissions. METHODS: We conducted a single-centre, observational cohort study examining adult patients (≥ 18 years) who received a kidney transplant from living and deceased donors between January 1st, 2005 and December 31st, 2015 with follow-up until December 31st, 2016 (n = 1,334). Univariable and multivariable analyses were performed with Cox proportional hazards models to analyze the outcomes of SC in the early post-operative period after KT. RESULTS: The cumulative probability of SC within 30 days of transplant was 25%, the most common SC being peri-graft collections (66.8%). Multivariable analyses showed significant relationships between Clavien Grade 1 SC and death with graft function (HR 1.78 [95% CI: 1.11, 2.86]), and between Clavien Grades 3 to 4 and hospital readmissions (HR 1.95 [95% CI: 1.37, 2.77]). CONCLUSIONS: Early SC following KT are common and have a significant influence on long-term patient outcomes.


Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Complicaciones Posoperatorias , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adulto , Fallo Renal Crónico/cirugía , Supervivencia de Injerto , Readmisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Factores de Tiempo
5.
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
6.
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.

8.
Liver Transpl ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38619393

RESUMEN

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. 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 intention-to-treat survival rates were higher for pLDLT versus 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 primary sclerosing cholangitis 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]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

9.
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
10.
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
11.
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
12.
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
13.
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
14.
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
15.
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.

17.
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
18.
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.

19.
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
20.
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
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