RESUMEN
Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.
Asunto(s)
Adenosina , Alopurinol , Antioxidantes , Hígado Graso , Insulina , Hígado , Soluciones Preservantes de Órganos , Procaína , Rafinosa , Ratas Zucker , Daño por Reperfusión , Animales , Soluciones Preservantes de Órganos/farmacología , Ratas , Rafinosa/farmacología , Insulina/metabolismo , Adenosina/metabolismo , Adenosina/farmacología , Hígado Graso/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Antioxidantes/farmacología , Antioxidantes/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Alopurinol/farmacología , Masculino , Procaína/farmacología , Inflamación/metabolismo , Inflamación/patología , Inflamación/tratamiento farmacológico , Glucosa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Manitol/farmacología , Isquemia Fría/efectos adversos , Cloruro de Potasio/farmacología , Preservación de Órganos/métodos , Trasplante de Hígado/métodosRESUMEN
BACKGROUND: Pediatric liver transplantation for small recipients presents significant challenges, particularly in securing suitably sized donor organs. This case report illustrates the feasibility of performing an in situ split procurement in an 18.5-kg toddler, the smallest recorded case in the OPTN database to date, for a critically ill 8-week-old infant recipient. CASE PRESENTATION: An 8-week-old infant with severe hepatitis of unknown etiology was urgently listed as Status 1A. An organ offer from a 3.5-year-old donor, requiring a reduction procedure, became available 1939 nautical miles away. Instead of a back-table reduction procedure, we performed an in situ split to reduce cold ischemic time given the distance. The recipient surgery was started ahead of the organ's arrival, and the recipient was ready for graft implantation upon the organ's arrival, resulting in a total of 510 min of cold ischemic time. Post-operatively, the graft did not show signs of significant injury or dysfunction, which expedited recovery from her other medical conditions. CONCLUSIONS: In situ split liver procurement is an invaluable tool for pediatric centers as it effectively provides more graft options for pediatric patients on the waitlist. Additionally, in situ split can offer significant benefits in optimizing recipient surgery, especially when the donor is located at an extreme distance. Despite these benefits, in situ split is not currently widely utilized across transplant centers. Addressing the logistical challenges associated with this technique is crucial for broader implementation and improved patient outcomes.
Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Trasplante de Hígado/métodos , Lactante , Femenino , Obtención de Tejidos y Órganos/métodos , Donantes de Tejidos , Preescolar , Isquemia Fría , Tamaño de los ÓrganosRESUMEN
OBJECTIVE: It was aimed to examine the overall role of cold ischemia time and anhepatic phase durations in terms of peroperative blood transfusion needs, hospital stay conditions and postoperative charges, and survival in recipients. MATERIAL AND METHODS: One hundred forty-eight adult living donor liver transplant recipients (18 years and older) were included in the study. Whether the anhepatic phase and cold ischemia duration have an effect on the rates of surgery time, blood product transfusion, total hospital and intensive care unit stay, postoperative biliary complications, hepatic vein thrombosis, portal vein thrombosis, early postoperative bleeding, sepsis, and primary graft dysfunction. Was analyzed statistically. In addition, the effect of the anhepatic phase and cold ischemia time on graft survival was statistically examined by creating an average of the patient follow-up period. RESULTS: It was observed that the operation time increased statistically as the cold ischemia time increased (P = .000). No statistically significant relationship was found between other findings and cold ischemia time and anhepatic phase. CONCLUSION: Prolonged surgery time due to increased cold ischemia time may be an important finding in terms of peroperative and postoperative results of the graft.
Asunto(s)
Isquemia Fría , Trasplante de Hígado , Donadores Vivos , Tempo Operativo , Humanos , Trasplante de Hígado/efectos adversos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , Supervivencia de Injerto , Factores de Tiempo , Tiempo de Internación , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Transfusión Sanguínea/estadística & datos numéricosRESUMEN
PURPOSE: Protocol description for renal perfusion study using thermographic technology and description of the thermographic and clinical behavior of the transplanted kidneys before and after unclamping. METHODS: Infrared thermographic images of renal grafts are obtained before kidney reperfusion, 10 min after and just before closing the surgical wound. Thermographic data is evaluated together with the type of graft and donor, cold ischemia time, hypovascularized areas determined by the surgeon during surgical intervention, alterations in vascular flow in postoperative echo-Doppler, time at the beginning of graft function and serum creatinine monitoring during postoperative follow-up. RESULTS: 17 grafts were studied. The mean temperature of the grafts before reperfusion, 10 min after and at the end of the surgery were 18.7 °C (SD 6.27), 32.36 °C (SD1.47) and 32.07 °C (SD1.78) respectively. 4 grafts presented hypoperfused areas after reperfusion. These areas presented a lower temperature compared to the well perfused parenchyma surface using thermographic images. CONCLUSION: The study of the usefulness and applicability of thermography can allow the development of tools that provide additional objective information on organ perfusion in real time and non-invasive manner. Our protocol and initial results can contribute to provide new evidence. Further analyses should be developed to shed light on the role of this technology.
Asunto(s)
Trasplante de Riñón , Termografía , Termografía/métodos , Humanos , Masculino , Persona de Mediana Edad , Femenino , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Adulto , Rayos Infrarrojos , Protocolos Clínicos , Perfusión/métodos , Anciano , Isquemia Fría , Reperfusión/métodosRESUMEN
Optimizing graft preservation is key for ex-situ split grafts in pediatric liver transplantation (PSLT). Hypothermic Oxygenated Perfusion (HOPE) improves ischemia-reperfusion injury (IRI) and post-operative outcomes in adult LT. This study compares the use of HOPE in ex-situ partial grafts to static cold storage ex-situ partial grafts (SCS-Split) and to the gold standard living donor liver transplantation (LDLT). All consecutive HOPE-Split, SCS-Split and LDLT performed between 2018-2023 for pediatric recipients were included. Post-reperfusion syndrome (PRS, drop ≥30% in systolic arterial pressure) and reperfusion biopsies served as early indicators of IRI. We included 47 pediatric recipients (15 HOPE-Split, 17 SCS-Split, and 15 LDLT). In comparison to SCS-Split, HOPE-Split had a significantly shorter cold ischemia time (CIT) (470min vs. 538 min; p =0.02), lower PRS rates (13.3% vs. 47.1%; p = 0.04) and a lower IRI score (3 vs. 4; p = 0.03). The overall IRI score (3 vs. 3; p = 0.28) and PRS (13.3% vs. 13.3%; p = 1) after HOPE-Split were comparable to LDLT, despite a longer CIT (470 min vs. 117 min; p < 0.001). Surgical complications, one-year graft, and recipient survival did not differ among the groups. In conclusion, HOPE-Split mitigates early IRI in pediatric recipients in comparison to SCS-Split, approaching the gold standard of LDLT.
Asunto(s)
Trasplante de Hígado , Donadores Vivos , Preservación de Órganos , Perfusión , Daño por Reperfusión , Humanos , Trasplante de Hígado/métodos , Trasplante de Hígado/efectos adversos , Daño por Reperfusión/prevención & control , Daño por Reperfusión/etiología , Masculino , Femenino , Niño , Preescolar , Preservación de Órganos/métodos , Perfusión/métodos , Adolescente , Lactante , Isquemia Fría , Supervivencia de Injerto , Estudios Retrospectivos , Hígado/irrigación sanguíneaRESUMEN
BACKGROUND: Split liver transplantation is a valuable means of mitigating organ scarcity but requires significant surgical and logistical effort. Ex vivo splitting is associated with prolonged cold ischemia, with potentially negative effects on organ viability. Machine perfusion can mitigate the effects of ischemia-reperfusion injury by restoring cellular energy and improving outcomes. METHODS: We describe a novel technique of full-left/full-right liver splitting, with splitting and reconstruction of the vena cava and middle hepatic vein, with dual arterial and portal hypothermic oxygenated machine perfusion. The accompanying video depicts the main surgical passages, notably the splitting of the vena cava and middle hepatic vein, the parenchymal transection, and the venous reconstruction. RESULTS: The left graft was allocated to a pediatric patient having methylmalonic aciduria, whereas the right graft was allocated to an adult patient affected by hepatocellular carcinoma and cirrhosis. CONCLUSIONS: This technique allows ex situ splitting, counterbalancing prolonged ischemia with the positive effects of hypothermic oxygenated machine perfusion on graft viability. The venous outflow is preserved, safeguarding both grafts from venous congestion; all reconstructions can be performed ex situ, minimizing warm ischemia. Moreover, there is no need for highly skilled surgeons to reach the donor hospital, thereby simplifying logistical aspects.
Asunto(s)
Venas Hepáticas , Trasplante de Hígado , Perfusión , Humanos , Venas Hepáticas/cirugía , Trasplante de Hígado/métodos , Perfusión/métodos , Perfusión/instrumentación , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Hígado/irrigación sanguínea , Hígado/cirugía , Preservación de Órganos/métodos , Preservación de Órganos/instrumentación , Carcinoma Hepatocelular/cirugía , Masculino , Resultado del Tratamiento , Isquemia Fría , Daño por Reperfusión/prevención & control , Daño por Reperfusión/etiología , Adulto , Cirrosis Hepática/cirugía , Hipotermia InducidaRESUMEN
BACKGROUND: Appropriate risk stratification for the difficulty of liver transplantation (LT) is essential to guide the selection and acceptance of grafts and avoid morbidity and mortality. METHODS: Based on 987 LTs collected from 5 centers, perioperative outcomes were analyzed across the 3 difficulty levels. Each LT was retrospectively scored from 0 to 10. Scores of 0-2, 3-5 and 6-10 were then translated into respective difficulty levels: low, moderate and high. Complications were reported according to the comprehensive complication index (CCI). RESULTS: The difficulty level of LT in 524 (53%), 323 (32%), and 140 (14%) patients was classified as low, moderate and high, respectively. The values of major intraoperative outcomes, such as cold ischemia time (p = 0.04) and operative time (p < 0.0001) increased gradually with statistically significant values among difficulty levels. There was a corresponding increase in CCI (p = 0.04), severe complication rates (p = 0.05) and length of ICU (p = 0.01) and hospital (p = 0.004) stays across the different difficulty levels. CONCLUSION: The LT difficulty classification has been validated.
Asunto(s)
Trasplante de Hígado , Complicaciones Posoperatorias , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Masculino , Medición de Riesgo , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Resultado del Tratamiento , Adulto , Reproducibilidad de los Resultados , Anciano , Factores de Tiempo , Tiempo de Internación , Europa (Continente) , Tempo Operativo , Isquemia Fría , Selección de Paciente , Valor Predictivo de las PruebasRESUMEN
INTRODUCTION: A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery community describes 12 hours of warm ischemia and 24 hours of cold ischemia as the upper limits for digit replantation; however, these limits are largely anecdotal and based on older studies. We aimed to compare survival data from the large body of literature to aid surgeons and all those involved in the replantation process in hopes of optimizing success rates. METHODS: The PubMed database was queried on April 4th, 2023, for articles that included data on digit replantation survival in terms of temperature of preservation and ischemia time. All primary outcomes were analyzed with the Mantel-Haenszel method within a random effects model. Secondary outcomes were pooled and analyzed using the chi-square statistic. Statistical analysis and forest plot generation were completed with RevMan 5.4 software with odds ratios calculated within a 95% confidence interval. RESULTS: Our meta-analysis identified that digits preserved in cold ischemia for over 12 hours had significantly higher odds of replantation success than the amputated digits replanted with 0-12 hours of warm ischemia time ( P ≤ 0.05). The odds of survival in the early (0-6 hours) replantation group were around 40% greater than the later (6-12 hours) replantation group ( P ≤ 0.05). Secondary outcomes that were associated with higher survival rates included a clean-cut amputation, increased venous and arterial anastomosis, a repair that did not require a vein graft, and replants performed in nonsmokers ( P ≤ 0.05). DISCUSSION: Overall, these findings suggest that when predicting digit replantation success, time is of the essence when the digit has yet to be preserved in a cold environment. This benefit, however, is almost completely diminished when the amputated digit is appropriately maintained in a cold environment soon after injury. In conclusion, our results suggest that there is potential for broadening the ischemia time limits for digit replant survival outlined in the literature, particularly for digits that have been stored correctly in cold ischemia.
Asunto(s)
Amputación Traumática , Traumatismos de los Dedos , Reimplantación , Humanos , Reimplantación/métodos , Amputación Traumática/cirugía , Traumatismos de los Dedos/cirugía , Factores de Tiempo , Dedos/irrigación sanguínea , Dedos/cirugía , Isquemia Tibia , Isquemia Fría , Isquemia/cirugía , TemperaturaRESUMEN
BACKGROUND: Cold ischemia time (CIT) influences short- and long-term outcomes in lung transplant recipients. Most studies proved that prolonged CIT causes increased mortality. This study aimed to investigate the impact of prolonged CIT on patient survival time after lung transplantation (LTx). METHODS: The retrospective study group consisted of 139 patients who underwent double LTx in a single center between January 2018 and August 2022. Prolonged ischemic time (PIT) was defined as total ischemic time >6 hours and divided into smaller time intervals according to increasing PIT (6-8, 8-10, 10-12, >12 hours). The assessed outcomes were 1- and 4-year survival. RESULTS: Among the study group, PIT was observed in 98% (n = 137), and its average value was 10.33 hours. The prolonged CIT of 6 to 8 hours occurred in 10% (n = 14), 8 to 10 hours in 34% (n = 47), 10 to 12 hours in 36% (n = 49), and >12 hours in 20% (n = 27). In a comparison of 1-year survival between the PIT 6- to 10-hour group and the >10-hour arm (88% vs 78%), the difference was not statistically significant (P > .05). CONCLUSION: PIT is a risk factor for reduced long-term survival in LTx recipients. Increasing PIT may be associated with higher mortality at 1 and 4 years. All efforts to reduce the duration of ischemic time can benefit patient survival after LTx.
Asunto(s)
Isquemia Fría , Trasplante de Pulmón , Humanos , Trasplante de Pulmón/mortalidad , Femenino , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Adulto , Factores de Tiempo , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: Machine perfusion has been adopted into clinical practice in Europe since the mid-2010s and, more recently, in the United States (US) following approval of normothermic machine perfusion (NMP). We aim to review recent advances, provide discussion of potential future directions, and summarize challenges currently facing the field. RECENT FINDINGS: Both NMP and hypothermic-oxygenated perfusion (HOPE) improve overall outcomes after liver transplantation versus traditional static cold storage (SCS) and offer improved logistical flexibility. HOPE offers additional protection to the biliary system stemming from its' protection of mitochondria and lessening of ischemia-reperfusion injury. Normothermic regional perfusion (NRP) is touted to offer similar protective effects on the biliary system, though this has not been studied prospectively.The most critical question remaining is the optimal use cases for each of the three techniques (NMP, HOPE, and NRP), particularly as HOPE and NRP become more available in the US. There are additional questions regarding the most effective criteria for viability assessment and the true economic impact of these techniques. Finally, with each technique purported to allow well tolerated use of riskier grafts, there is an urgent need to define terminology for graft risk, as baseline population differences make comparison of current data challenging. SUMMARY: Machine perfusion is now widely available in all western countries and has become an essential tool in liver transplantation. Identification of the ideal technique for each graft, optimization of viability assessment, cost-effectiveness analyses, and proper definition of graft risk are the next steps to maximizing the utility of these powerful tools.
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Supervivencia de Injerto , Trasplante de Hígado , Preservación de Órganos , Perfusión , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Trasplante de Hígado/tendencias , Perfusión/métodos , Perfusión/efectos adversos , Perfusión/tendencias , Perfusión/instrumentación , Preservación de Órganos/métodos , Preservación de Órganos/tendencias , Preservación de Órganos/efectos adversos , Daño por Reperfusión/prevención & control , Daño por Reperfusión/etiología , Resultado del Tratamiento , Factores de Riesgo , Isquemia Fría/efectos adversos , AnimalesRESUMEN
PURPOSE OF REVIEW: In an attempt to reduce waiting list mortality in liver transplantation, less-than-ideal quality donor livers from extended criteria donors are increasingly accepted. Predicting the outcome of these organs remains a challenge. Machine perfusion provides the unique possibility to assess donor liver viability pretransplantation and predict postreperfusion organ function. RECENT FINDINGS: Assessing liver viability during hypothermic machine perfusion remains challenging, as the liver is not metabolically active. Nevertheless, the levels of flavin mononucleotide, transaminases, lactate dehydrogenase, glucose and pH in the perfusate have proven to be predictors of liver viability. During normothermic machine perfusion, the liver is metabolically active and in addition to the perfusate levels of pH, transaminases, glucose and lactate, the production of bile is a crucial criterion for hepatocyte viability. Cholangiocyte viability can be determined by analyzing bile composition. The differences between perfusate and bile levels of pH, bicarbonate and glucose are good predictors of freedom from ischemic cholangiopathy. SUMMARY: Although consensus is lacking regarding precise cut-off values during machine perfusion, there is general consensus on the importance of evaluating both hepatocyte and cholangiocyte compartments. The challenge is to reach consensus for increased organ utilization, while at the same time pushing the boundaries by expanding the possibilities for viability testing.
Asunto(s)
Trasplante de Hígado , Hígado , Preservación de Órganos , Perfusión , Humanos , Perfusión/métodos , Perfusión/efectos adversos , Trasplante de Hígado/efectos adversos , Hígado/cirugía , Hígado/metabolismo , Preservación de Órganos/métodos , Preservación de Órganos/efectos adversos , Supervivencia Tisular , Donantes de Tejidos , Hepatocitos/metabolismo , Hepatocitos/trasplante , Animales , Selección de Donante , Bilis/metabolismo , Supervivencia Celular , Biomarcadores/metabolismo , Valor Predictivo de las Pruebas , Isquemia Fría/efectos adversosRESUMEN
BACKGROUND: We aimed to understand the association between cold ischemia time (CIT) and delayed graft function (DGF) after kidney transplantation and the impact of organ pumping on that association. METHODS: Retrospective cohort study using US registry data. We identified kidney pairs from the same donor where both kidneys were transplanted but had a CIT difference >0 and ≤20 h. We determined the frequency of concordant (both kidneys with/without DGF) or discordant (only 1 kidney DGF) DGF outcomes. Among discordant pairs, we computed unadjusted and adjusted relative risk of DGF associated with longer-CIT status, when then repeated this analysis restricted to pairs where only the longer-CIT kidney was pumped. RESULTS: Among 25 831 kidney pairs included, 71% had concordant DGF outcomes, 16% had only the longer-CIT kidney with DGF, and 13% had only the shorter-CIT kidney with DGF. Among discordant pairs, longer-CIT status was associated with a higher risk of DGF in unadjusted and adjusted models. Among pairs where only the longer-CIT kidney was pumped, longer-CIT kidneys that were pumped had a lower risk of DGF than their contralateral shorter-CIT kidneys that were not pumped regardless of the size of the CIT difference. CONCLUSIONS: Most kidney pairs have concordant DGF outcomes regardless of CIT difference, but even small increases in CIT raise the risk of DGF. Organ pumping may mitigate and even overcome the adverse consequences of prolonged CIT on the risk of DGF, but prospective studies are needed to better understand this relationship.
Asunto(s)
Isquemia Fría , Funcionamiento Retardado del Injerto , Trasplante de Riñón , Sistema de Registros , Humanos , Trasplante de Riñón/efectos adversos , Isquemia Fría/efectos adversos , Funcionamiento Retardado del Injerto/etiología , Funcionamiento Retardado del Injerto/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Riñón/fisiopatología , Supervivencia de Injerto , Anciano , Estados Unidos/epidemiología , Donantes de TejidosRESUMEN
BACKGROUND: Islet transplantation is a promising therapy for patients with type 1 diabetes. However, ischemic injury to the donor islets during cold preservation leads to reduced islet quality and compromises transplant outcome. Several studies imply that liraglutide, a glucagon-like peptide-1 receptor agonist, has a positive effect on promoting islet survival, but its impact on islet cold-ischemic injury remains unexplored. Therefore, the aim of this study was to investigate whether liraglutide can improve islet transplantation efficacy by inhibiting cold-ischemic injury and to explore the underlying mechanisms. METHODS: Liraglutide was applied in a mouse pancreas preservation model and a human islets cold-preservation model, and islet viability, function, oxidative stress levels were evaluated. Furthermore, islet transplantation was performed in a syngeneic mouse model and a human-to-nude mouse islet xenotransplantation model. RESULTS: The supplementation of liraglutide in preservation solution improved islet viability, function, and reduced cell apoptosis. Liraglutide inhibited the oxidative stress of cold-preserved pancreas or islets through upregulating the antioxidant enzyme glutathione levels, inhibiting reactive oxygen species accumulation, and maintaining the mitochondrial membrane integrity, which is associated with the activation of Akt signaling. Furthermore, the addition of liraglutide during cold preservation of donor pancreas or donor islets significantly improved the subsequent transplant outcomes in both syngeneic mouse islet transplantation model and human-to-nude mouse islet xenotransplantation model. CONCLUSIONS: Liraglutide protects islets from cold ischemia-related oxidative stress during preservation and hence improved islet transplantation outcomes, and this protective effect of liraglutide in islets is associated with the activation of Akt signaling.
Asunto(s)
Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Liraglutida , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Liraglutida/farmacología , Animales , Estrés Oxidativo/efectos de los fármacos , Trasplante de Islotes Pancreáticos/métodos , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Transducción de Señal/efectos de los fármacos , Isquemia Fría/efectos adversos , Masculino , Ratones , Ratones Desnudos , Supervivencia de Injerto/efectos de los fármacos , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos , Trasplante Heterólogo , Criopreservación , Preservación de Órganos/métodos , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Daño por Reperfusión/metabolismoRESUMEN
INTRODUCTION: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. METHODS: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. PRIMARY ENDPOINT: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. RESULTS: Thirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23-13:29); 2nd: 14:24 (12:00-16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18-6:40); 2nd: 7:15 (6:33-7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). CONCLUSIONS: Preservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.
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Trasplante de Pulmón , Preservación de Órganos , Disfunción Primaria del Injerto , Humanos , Preservación de Órganos/métodos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Disfunción Primaria del Injerto/prevención & control , Adulto , Donantes de Tejidos , Isquemia Fría , Interleucina-8/análisis , Interleucina-8/sangre , Pulmón , Factores de Tiempo , Interleucina-10/sangre , Tiempo de Internación/estadística & datos numéricos , Respiración Artificial , Citocinas/sangreRESUMEN
BACKGROUND: Uterus transplantation (UTx) is an emerging treatment for uterine factor infertility. Determining the maximum tolerable cold ischemia time is crucial for successful UTx. However, the limit for cold ischemia in the uterus is unclear. This study aimed to examine cold ischemia's effects on mouse uteri and identify the maximum cold ischemia duration that uteri can endure. METHODS: We systematically assessed the tolerance of mouse uteri to extended cold ischemia, 24 h, 36 h, and 48 h, using the cervical heterotopic UTx model. Multiple indicators were used to evaluate ischemia-reperfusion injury, including reperfusion duration, macroscopic examination, oxidative stress, inflammation, and histopathology. The function of transplants was evaluated through estrous cycle monitoring and embryo transfer. RESULTS: Mouse uteri subjected to 48 h of cold ischemia exhibited significant delays and insufficiencies in reperfusion, substantial tissue necrosis, and loss of the estrous cycle. Conversely, uteri that underwent cold ischemia within 36 h showed long survival, regular estrous cycles, and fertility. CONCLUSIONS: Our study demonstrated that mouse uteri can endure at least 36 h of cold ischemia, extending the known limits for cold ischemia and providing a pivotal reference for research on the prevention and treatment of cold ischemic injury in UTx.
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Isquemia Fría , Daño por Reperfusión , Trasplante Heterotópico , Útero , Animales , Femenino , Isquemia Fría/efectos adversos , Útero/trasplante , Útero/irrigación sanguínea , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Factores de Tiempo , Ratones , Ciclo Estral , Infertilidad Femenina/etiología , Infertilidad Femenina/cirugía , Estrés Oxidativo , Embarazo , Fertilidad , Transferencia de EmbriónRESUMEN
Static ice storage has long been the standard-of-care for lung preservation, although freezing injury limits ischemic time (IT). Controlled hypothermic storage (CHS) at elevated temperature could safely extend IT. This retrospective analysis assesses feasibility and safety of CHS with IT > 15 hours. Three lung transplant (LuTx) centers (April-October 2023) included demographics, storage details, IT, and short-term outcome from 13 LuTx recipients (8 male, 59 years old). Donor lungs were preserved in a portable CHS device at 7 (5-9.3)°C. Indication was overnight bridging and/or long-distance transport. IT of second-implanted lung was 17.3 (15.1-22) hours. LuTx were successful, 4/13 exhibited primary graft dysfunction grade 3 within 72 hours and 0/13 at 72 hours. Post-LuTx mechanical ventilation was 29 (7-442) hours. Intensive care unit stay was 9 (5-28) and hospital stay 30 (16-90) days. Four patients needed postoperative extracorporeal membrane oxygenation (ECMO). One patient died (day 7) following malpositioning of an ECMO cannula. This multicenter experience demonstrates the possibility of safely extending IT > 15 hours by CHS.
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Trasplante de Pulmón , Preservación de Órganos , Humanos , Trasplante de Pulmón/métodos , Persona de Mediana Edad , Masculino , Femenino , Preservación de Órganos/métodos , Estudios Retrospectivos , Factores de Tiempo , Adulto , Isquemia Fría , Anciano , Estudios de FactibilidadRESUMEN
We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.
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Isquemia Fría , Funcionamiento Retardado del Injerto , Tasa de Filtración Glomerular , Supervivencia de Injerto , Trasplante de Riñón , Donantes de Tejidos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Donantes de Tejidos/provisión & distribución , Factores de Riesgo , Adulto , Estudios de Seguimiento , Funcionamiento Retardado del Injerto/etiología , Pronóstico , Tasa de Supervivencia , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Rechazo de Injerto/etiología , Pruebas de Función Renal , Obtención de Tejidos y Órganos , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. METHODS: Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. RESULTS: OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells. CONCLUSION: Our study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.
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Ferroptosis , Daño por Reperfusión , Ratas , Animales , 3-O-Metilglucosa/farmacología , Isquemia Fría/efectos adversos , Preservación de Órganos/métodos , Riñón , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Isquemia/patología , HierroRESUMEN
INTRODUCTION: Biliary complications (BCs) are a well-documented post-liver transplantation concern with potential implications for patient survival. This study aims at identifying risk factors associated with the development of BCs in recipients after liver transplantation (LT) and exploring strategies for their management. METHODS: We conducted a retrospective analysis of 1595 adult patients (age > 18 years) who underwent LT surgery between 2019 and 2021. The study assessed the incidence of BCs in this cohort. RESULTS: Of 1595 patients, 178 (11.1%) experienced BCs, while 1417 (88.8%) did not exhibit any signs of such complications. Patients who developed BCs were found to have a significantly lower average age (p < 0.001) and longer cold ischemic times (p < 0.001) compared to those without BCs. Variables such as sex, body mass index (BMI), model for end-stage liver disease (MELD) score, primary diagnosis, type of anastomosis, hepatectomy technique, type of transplanted liver and mortality did not demonstrate statistically significant differences between the two groups (p > 0.05). Univariate logistic regression analysis revealed that a cold ischemic time exceeding 12 hours and duct-to-duct anastomosis were positive predictors for BC development (odds ratios of 6.23 [CI 4.29-9.02] and 1.47 [CI 0.94-2.30], respectively). Conversely, increasing age was associated with a protective effect against BC development, with an odds ratio of 0.64 (CI 0.46-0.89). CONCLUSION: Our multi-variate analysis identified cold ischemia time (CIT) as the sole significant predictor of post-liver transplantation biliary complications. Additionally, this study observed that advancing patient age had a protective influence in this context. Notably, no significant disparities were detected between hepatectomy techniques and the etiology of liver disease types in the two study groups.
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Enfermedades de las Vías Biliares , Trasplante de Hígado , Complicaciones Posoperatorias , Humanos , Trasplante de Hígado/efectos adversos , Factores de Riesgo , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Adulto , Enfermedades de las Vías Biliares/etiología , Enfermedades de las Vías Biliares/epidemiología , Isquemia Fría/efectos adversos , Estudios de Cohortes , Factores de Edad , IncidenciaRESUMEN
AIM: The aim of the study was to identify predictors of early tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: Retrospective cohort study in 237 consecutive liver recipients with HCC between 2016 and 2021. Multivariate logistic analysis was performed to identify predictors of early HCC recurrences. The impact of hypothermic-oxygenated perfusion (HOPE) on outcome was analyzed after propensity score weighting. RESULTS: Early recurrences were observed in 15 cases. Microvascular invasion (OR 3.737, 95% CI 1.246-11.206, p = 0.019) and cold ischemia time (OR 1.155, 95% CI 1.001-1.333, p = 0.049) were independently associated with a lower risk of HCC recurrences. After balancing for relevant variables, patients in the HOPE group had lower rates of tumor recurrence (weighted OR 0.126, 95% CI 0.016-0.989, p = 0.049) and higher recurrence free survival (weighted HR 0.132, 95% CI 0.017-0.999, p = 0.050). CONCLUSION: Reducing cold ischemia time and graft perfusion with HOPE can lead to lower rates of early HCC recurrences and higher recurrence-free survival.