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Keywords = extended criteria donation

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18 pages, 1301 KiB  
Review
The Use of Residual Blood Specimens in Seroprevalence Studies for Vaccine-Preventable Diseases: A Scoping Review
by Monica Pilewskie, Christine Prosperi, Abigail Bernasconi, Ignacio Esteban, Lori Niehaus, Connor Ross, Andrea C. Carcelen, William J. Moss and Amy K. Winter
Vaccines 2025, 13(3), 321; https://doi.org/10.3390/vaccines13030321 - 18 Mar 2025
Cited by 2 | Viewed by 876
Abstract
Background: Residual blood specimens offer a cost- and time-efficient alternative for conducting serological surveys. However, their use is often criticized due to potential issues with the representativeness of the target population and/or limited availability of associated metadata. We conducted a scoping review [...] Read more.
Background: Residual blood specimens offer a cost- and time-efficient alternative for conducting serological surveys. However, their use is often criticized due to potential issues with the representativeness of the target population and/or limited availability of associated metadata. We conducted a scoping review to examine where, when, how, and why residual blood specimens have been used in serological surveys for vaccine-preventable diseases (VPDs) and how potential selection biases are addressed. Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and identified relevant papers published in 1990–2022. Results: A total of 601 articles met the inclusion criteria after title, abstract screening, and full-text review. The most studied VPDs using residual blood specimens were COVID-19 (27%), hepatitis E (16%), hepatitis B (10%), influenza (9%), HPV (7%), and measles (7%). Residual blood specimens were primarily sourced from diagnostic specimens (61%) or blood and plasma donations (37%). Almost all articles used specimens linked to basic demographic data (e.g., age and sex), with 47% having access to extended demographic data (e.g., geographic location). Common strategies to address potential biases included comparing results with published estimates (78%) and performing stratified analyses (71%). Conclusions: Residual blood specimens are widely used in seroprevalence studies, particularly during emerging disease outbreaks when rapid estimates are critical. However, this review highlighted inconsistencies in how researchers analyze and report the use of residual specimens. We propose a set of recommendations to improve the analysis, reporting, and ethical considerations of serological surveys using residual specimens. Full article
(This article belongs to the Section Vaccines and Public Health)
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7 pages, 165 KiB  
Review
Artificial Intelligence and Liver Transplantation; Literature Review
by Maria Serban, Irina Balescu, Sorin Petrea, Bodan Gaspar, Lucian Pop, Valentin Varlas, Marilena Stoian, Camelia Diaconu, Cristian Balalau and Nicolae Bacalbasa
J. Mind Med. Sci. 2024, 11(2), 374-380; https://doi.org/10.22543/2392-7674.1532 - 31 Oct 2024
Cited by 1 | Viewed by 544
Abstract
Liver transplantation is the last life-saving solution for patients with end stage liver disease. The discrepancy between waiting list and available organs has led to the appearance of extended donation criteria and the development of several scores (Child-Pugh score, MELD score, DRI score, [...] Read more.
Liver transplantation is the last life-saving solution for patients with end stage liver disease. The discrepancy between waiting list and available organs has led to the appearance of extended donation criteria and the development of several scores (Child-Pugh score, MELD score, DRI score, SOFT score), in order to find the most suitable donor-recipient match. But none of these scores can predict survival after transplantation. Artificial Intelligence (AI) has recently been shown as an excellent tool for the study of the liver and comes in this aid with its various methods (random forest, artificial neural networks, decision tree, Bayesian networks, and support vector machine). Materials and Methods. By reviewing the literature (mostly retrospective multicenter studies), we aimed to establish if the AI is a proper or even a more accurate method of predicting posttransplant survival, in comparison with the existing linear statistical models. Results. Machine learning showed better results than several current scoring systems that use either isolated donor/recipient scores or combined donor/recipient factors. The advantages of this model are its capacity for analyzing both linear and nonlinear relationships between features and outcomes, its robustness of overfitting by design, and built-in insights into feature importance aiding model explainability. Nevertheless, machine learning has its limitations because it requires large amounts of data, which can be difficult to obtain, it also requires high levels of technical skill, can be difficult to engineer and it’s expensive. Conclusion. AI may have significant potential in aiding clinical decision-making during liver transplantation, including donor-recipient matching. Full article
15 pages, 3356 KiB  
Review
Revolutionizing Donor Heart Procurement: Innovations and Future Directions for Enhanced Transplantation Outcomes
by Marc Leon
J. Cardiovasc. Dev. Dis. 2024, 11(8), 235; https://doi.org/10.3390/jcdd11080235 - 27 Jul 2024
Cited by 1 | Viewed by 2803
Abstract
Heart failure persists as a critical public health challenge, with heart transplantation esteemed as the optimal treatment for patients with end-stage heart failure. However, the limited availability of donor hearts presents a major obstacle to meeting patient needs. In recent years, the most [...] Read more.
Heart failure persists as a critical public health challenge, with heart transplantation esteemed as the optimal treatment for patients with end-stage heart failure. However, the limited availability of donor hearts presents a major obstacle to meeting patient needs. In recent years, the most groundbreaking progress in heart transplantation has been in donor heart procurement, significantly expanding the donor pool and enhancing clinical outcomes. This review comprehensively examines these advancements, including the resurgence of heart donation after circulatory death and innovative recovery and evaluation technologies such as normothermic machine perfusion and thoraco-abdominal normothermic regional perfusion. Additionally, novel preservation methods, including controlled hypothermic preservation and hypothermic oxygenated perfusion, are evaluated. The review also explores the use of extended-criteria donors, post-cardiopulmonary resuscitation donors, and high-risk donors, all contributing to increased donor availability without compromising outcomes. Future directions, such as xenotransplantation, biomarkers, and artificial intelligence in donor heart evaluation and procurement, are discussed. These innovations promise to address current limitations and optimize donor heart utilization, ultimately enhancing transplantation success. By identifying recent advancements and proposing future research directions, this review aims to provide insights into advancing heart transplantation and improving patient outcomes. Full article
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17 pages, 559 KiB  
Systematic Review
Post-Donation Evaluation: Emotional Needs for Social Connection and Social Support among Living Kidney Donors—A Systematic Review
by Valentina Colonnello, Gaetano La Manna, Gabriella Cangini and Paolo Maria Russo
Healthcare 2024, 12(12), 1216; https://doi.org/10.3390/healthcare12121216 - 18 Jun 2024
Cited by 2 | Viewed by 1494
Abstract
Introduction: Evaluation of post-nephrectomy social health in living kidney donors is essential. This systematic review examines their emotional need for social relatedness post-donation. Methods: Following the PRISMA guidelines, we systematically searched Scopus, CINAHL, and PsycINFO. Results: Among the screened records, 32 quantitative and [...] Read more.
Introduction: Evaluation of post-nephrectomy social health in living kidney donors is essential. This systematic review examines their emotional need for social relatedness post-donation. Methods: Following the PRISMA guidelines, we systematically searched Scopus, CINAHL, and PsycINFO. Results: Among the screened records, 32 quantitative and 16 qualitative papers met the inclusion criteria. Quantitative research predominantly utilized questionnaires featuring generic items on social functioning. However, a minority delved into emotional and social dimensions, aligning with qualitative studies emphasizing the importance of social connection and perceived social support post-donation. Specifically, post-donation changes in connecting with others encompass a sense of belongingness, heightened autonomy, shifts in concern for the recipient’s health, and continued care by shielding the recipient from personal health issues. Social acknowledgment and social support from both close and extended networks are reported as relevant for recovery after nephrectomy. Discussion: These findings underscore the necessity for targeted measures of emotional needs and social functioning to effectively assess post-donation adjustment. They also inform the identification of key health themes for kidney donor Patient-Reported Outcome Measures (PROMs) and Patient-Reported Experience Measures (PREMs) questions. Full article
(This article belongs to the Special Issue Emotions in Healthcare: Current and Emerging Directions)
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19 pages, 4913 KiB  
Article
Bioenergetic and Cytokine Profiling May Help to Rescue More DCD Livers for Transplantation
by Julia Hofmann, Andras T. Meszaros, Madita L. Buch, Florian Nardin, Verena Hackl, Carola J. Strolz, Bettina Zelger, Margot Fodor, Benno Cardini, Rupert Oberhuber, Thomas Resch, Annemarie Weissenbacher, Jakob Troppmair, Stefan Schneeberger and Theresa Hautz
Int. J. Mol. Sci. 2023, 24(11), 9536; https://doi.org/10.3390/ijms24119536 - 31 May 2023
Cited by 3 | Viewed by 1924
Abstract
The majority of organs used for liver transplantation come from brain-dead donors (DBD). In order to overcome the organ shortage, increasingly donation after circulatory death (DCD) organs are also considered. Since normothermic machine perfusion (NMP) restores metabolic activity and allows for in-depth assessment [...] Read more.
The majority of organs used for liver transplantation come from brain-dead donors (DBD). In order to overcome the organ shortage, increasingly donation after circulatory death (DCD) organs are also considered. Since normothermic machine perfusion (NMP) restores metabolic activity and allows for in-depth assessment of organ quality and function prior to transplantation, such organs may benefit from NMP. We herein compare the bioenergetic performance through a comprehensive evaluation of mitochondria by high-resolution respirometry in tissue biopsies and the inflammatory response in DBD and DCD livers during NMP. While livers were indistinguishable by perfusate biomarker assessment and histology, our findings revealed a greater impairment of mitochondrial function in DCD livers after static cold storage compared to DBD livers. During subsequent NMPs, DCD organs recovered and eventually showed a similar performance as DBD livers. Cytokine expression analysis showed no differences in the early phase of NMP, while towards the end of NMP, significantly elevated levels of IL-1β, IL-5 and IL-6 were found in the perfusate of DCD livers. Based on our results, we find it worthwhile to reconsider more DCD organs for transplantation to further extend the donor pool. Therefore, donor organ quality criteria must be developed, which may include an assessment of bioenergetic function and cytokine quantification. Full article
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20 pages, 1875 KiB  
Article
Impact of Hypothermic Oxygenated Machine Perfusion on Hepatocellular Carcinoma Recurrence after Liver Transplantation
by Federica Rigo, Nicola De Stefano, Damiano Patrono, Victor De Donato, Ludovico Campi, Diana Turturica, Teresa Doria, Veronica Sciannameo, Paola Berchialla, Francesco Tandoi and Renato Romagnoli
J. Pers. Med. 2023, 13(5), 703; https://doi.org/10.3390/jpm13050703 - 22 Apr 2023
Cited by 9 | Viewed by 2128
Abstract
Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective [...] Read more.
Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective study was conducted from 2016 to 2020. Pre- and postoperative data of HCC patients undergoing LT were analyzed. Recipients of a D-HOPE-treated graft were compared to those of livers preserved using static cold storage (SCS). The primary endpoint was recurrence-free survival (RFS). Results: Of 326 patients, 246 received an SCS-preserved liver and 80 received a D-HOPE-treated graft (donation after brain death (DBD), n = 66; donation after circulatory death (DCD), n = 14). Donors of D-HOPE-treated grafts were older and had higher BMI. All DCD donors were treated by normothermic regional perfusion and D-HOPE. The groups were comparable in terms of HCC features and estimated 5-year RFS according to the Metroticket 2.0 model. D-HOPE did not reduce HCC recurrence (D-HOPE 10%; SCS 8.9%; p = 0.95), which was confirmed using Bayesian model averaging and inverse probability of treatment weighting-adjusted RFS analysis. Postoperative outcomes were comparable between groups, except for lower AST and ALT peak in the D-HOPE group. Conclusions: In this single-center study, D-HOPE did not reduce HCC recurrence but allowed utilizing livers from extended criteria donors with comparable outcomes, improving access to LT for patients suffering from HCC. Full article
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9 pages, 5105 KiB  
Communication
Ex-Vivo Preservation of Heart Allografts—An Overview of the Current State
by Perin Kothari
J. Cardiovasc. Dev. Dis. 2023, 10(3), 105; https://doi.org/10.3390/jcdd10030105 - 2 Mar 2023
Cited by 18 | Viewed by 4966
Abstract
As heart transplantation continues to be the gold-standard therapy for end-stage heart failure, the supply-demand imbalance of available organs worsens. Until recently, there have been no advances in increasing the donor pool, as prolonged cold ischemic time excludes the use of certain donors. [...] Read more.
As heart transplantation continues to be the gold-standard therapy for end-stage heart failure, the supply-demand imbalance of available organs worsens. Until recently, there have been no advances in increasing the donor pool, as prolonged cold ischemic time excludes the use of certain donors. The TransMedics Organ Care System (OCS) allows for ex-vivo normothermic perfusion, which allows for a reduction of cold ischemic time and allows for long-distance procurements. Furthermore, the OCS allows for real-time monitoring and assessment of allograft quality, which can be crucial for extended-criteria donors or donation after cardiac death (DCD) donors. Conversely, the XVIVO device allows for hypothermic perfusion to preserve allografts. Despite their limitations, these devices have the potential to alleviate the supply-demand imbalance in donor availability. Full article
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32 pages, 2226 KiB  
Review
Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain?
by Jeannette Widmer, Janina Eden, Mauricio Flores Carvalho, Philipp Dutkowski and Andrea Schlegel
J. Clin. Med. 2022, 11(17), 5218; https://doi.org/10.3390/jcm11175218 - 3 Sep 2022
Cited by 27 | Viewed by 4147
Abstract
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, [...] Read more.
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques—dissimilar to SCS—mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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16 pages, 1859 KiB  
Article
Lung Biomolecular Profile and Function of Grafts from Donors after Cardiocirculatory Death with Prolonged Donor Warm Ischemia Time
by Francesca Gori, Jacopo Fumagalli, Caterina Lonati, Andrea Carlin, Patrizia Leonardi, Osvaldo Biancolilli, Antonello Rossetti, Ilaria Righi, Davide Tosi, Alessandro Palleschi, Lorenzo Rosso, Letizia Corinna Morlacchi, Francesco Blasi, Luigi Vivona, Gaetano Florio, Vittorio Scaravilli, Franco Valenza, Alberto Zanella and Giacomo Grasselli
J. Clin. Med. 2022, 11(11), 3066; https://doi.org/10.3390/jcm11113066 - 29 May 2022
Cited by 5 | Viewed by 2038
Abstract
The acceptable duration of donor warm ischemia time (DWIT) after cardiocirculatory death (DCD) is still debated. We analyzed the biomolecular profile and function during ex vivo lung perfusion (EVLP) of DCD lungs and their correlation with lung transplantation (LuTx) outcomes. Donor data, procurement [...] Read more.
The acceptable duration of donor warm ischemia time (DWIT) after cardiocirculatory death (DCD) is still debated. We analyzed the biomolecular profile and function during ex vivo lung perfusion (EVLP) of DCD lungs and their correlation with lung transplantation (LuTx) outcomes. Donor data, procurement times, recipient outcomes, and graft function up to 1 year after LuTx were collected. During EVLP, the parameters of graft function and metabolism, perfusate samples to quantify inflammation, glycocalyx breakdown products, coagulation, and endothelial activation markers were obtained. Data were compared to a cohort of extended-criteria donors after brain death (EC-DBD). Eight DBD and seven DCD grafts transplanted after EVLP were analyzed. DCD’s DWIT was 201 [188;247] minutes. Donors differed only regarding the duration of mechanical ventilation that was longer in the EC-DBD group. No difference was observed in lung graft function during EVLP. At reperfusion, “wash-out” of inflammatory cells and microthrombi was predominant in DCD grafts. Perfusate biomolecular profile demonstrated marked endothelial activation, characterized by the presence of inflammatory mediators and glycocalyx breakdown products both in DCD and EC-DBD grafts. Early graft function after LuTx was similar between DCD and EC-DBD. DCD lungs exposed to prolonged DWIT represent a potential resource for donation if properly preserved and evaluated. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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19 pages, 2003 KiB  
Review
Preservation of Organs to Be Transplanted: An Essential Step in the Transplant Process
by Maryne Lepoittevin, Sébastien Giraud, Thomas Kerforne, Benoit Barrou, Lionel Badet, Petru Bucur, Ephrem Salamé, Claire Goumard, Eric Savier, Julien Branchereau, Pascal Battistella, Olaf Mercier, Sacha Mussot, Thierry Hauet and Raphael Thuillier
Int. J. Mol. Sci. 2022, 23(9), 4989; https://doi.org/10.3390/ijms23094989 - 30 Apr 2022
Cited by 18 | Viewed by 5886
Abstract
Organ transplantation remains the treatment of last resort in case of failure of a vital organ (lung, liver, heart, intestine) or non-vital organ (essentially the kidney and pancreas) for which supplementary treatments exist. It remains the best alternative both in terms of quality-of-life [...] Read more.
Organ transplantation remains the treatment of last resort in case of failure of a vital organ (lung, liver, heart, intestine) or non-vital organ (essentially the kidney and pancreas) for which supplementary treatments exist. It remains the best alternative both in terms of quality-of-life and life expectancy for patients and of public health expenditure. Unfortunately, organ shortage remains a widespread issue, as on average only about 25% of patients waiting for an organ are transplanted each year. This situation has led to the consideration of recent donor populations (deceased by brain death with extended criteria or deceased after circulatory arrest). These organs are sensitive to the conditions of conservation during the ischemia phase, which have an impact on the graft’s short- and long-term fate. This evolution necessitates a more adapted management of organ donation and the optimization of preservation conditions. In this general review, the different aspects of preservation will be considered. Initially done by hypothermia with the help of specific solutions, preservation is evolving with oxygenated perfusion, in hypothermia or normothermia, aiming at maintaining tissue metabolism. Preservation time is also becoming a unique evaluation window to predict organ quality, allowing repair and/or optimization of recipient choice. Full article
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15 pages, 1065 KiB  
Review
Recent Methods of Kidney Storage and Therapeutic Possibilities of Transplant Kidney
by Anna Radajewska, Anna Krzywonos-Zawadzka and Iwona Bil-Lula
Biomedicines 2022, 10(5), 1013; https://doi.org/10.3390/biomedicines10051013 - 28 Apr 2022
Cited by 11 | Viewed by 3809
Abstract
Kidney transplantation is the standard procedure for the treatment of end-stage renal disease (ESRD). During kidney storage and before implantation, the organ is exposed to damaging factors which affect the decline in condition. The arrest of blood circulation results in oxygen and nutrient [...] Read more.
Kidney transplantation is the standard procedure for the treatment of end-stage renal disease (ESRD). During kidney storage and before implantation, the organ is exposed to damaging factors which affect the decline in condition. The arrest of blood circulation results in oxygen and nutrient deficiency that lead to changes in the cell metabolism from aerobic to anaerobic, damaging organelles and cell structures. Currently, most kidney grafts are kept in a cold preservation solution to preserve low metabolism. However, there are numerous reports that machine perfusion is a better solution for organ preservation before surgery. The superiority of machine perfusion was proved in the case of marginal donor grafts, such as extended criteria donors (ECD) and donation after circulatory death (DCD). Different variant of kidney machine perfusions are evaluated. Investigators look for optimal conditions to protect kidneys from ischemia-reperfusion damage consequences by examining the best temperature conditions and comparing systems with constant or pulsatile flow. Moreover, machine perfusion brings additional advantages in clinical practice. Unlike cold static storage, machine perfusion allows the monitoring of the parameters of organ function, which gives a real possibility to make a decision prior to transplantation concerning whether the kidney is suitable for implantation. Moreover, new pharmacological therapies are sought to minimize organ damage. New components or cellular therapies can be applied, since perfusion solution flows through the organ. This review outlines the pros and cons of each machine perfusion technique and summarizes the latest achievements in the context of kidney transplantation using machine perfusion systems. Full article
(This article belongs to the Special Issue Kidney Disease: From Pathophysiology to Novel Therapeutic Approaches)
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12 pages, 639 KiB  
Article
Effect of Aprotinin on Liver Injury after Transplantation of Extended Criteria Donor Grafts in Humans: A Retrospective Propensity Score Matched Cohort Analysis
by Anna B. Roehl, Anne Andert, Karsten Junge, Ulf P. Neumann, Marc Hein and Felix Kork
J. Clin. Med. 2021, 10(22), 5232; https://doi.org/10.3390/jcm10225232 - 10 Nov 2021
Cited by 2 | Viewed by 1848
Abstract
The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment [...] Read more.
The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. In this single center retrospective analysis of 84 propensity score matched patients out of 274 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR 1,6, AST/ALT > 2000 within 7–10 days) and recipient survival. The incidence of PRS (52.4% vs. 47.6%) and 30-day mortality did not differ (4.8 vs. 0%; p = 0.152) but patients treated with aprotinin suffered more often from EAD (64.3% vs. 40.5%, p = 0.029) compared to controls. Acceptable or poor (OR = 3.3, p = 0.035; OR = 9.5, p = 0.003) organ quality were independent predictors of EAD. Our data do not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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18 pages, 1618 KiB  
Article
Effluent Molecular Analysis Guides Liver Graft Allocation to Clinical Hypothermic Oxygenated Machine Perfusion
by Caterina Lonati, Andrea Schlegel, Michele Battistin, Riccardo Merighi, Margherita Carbonaro, Paola Dongiovanni, Patrizia Leonardi, Alberto Zanella and Daniele Dondossola
Biomedicines 2021, 9(10), 1444; https://doi.org/10.3390/biomedicines9101444 - 11 Oct 2021
Cited by 11 | Viewed by 2485
Abstract
Hypothermic-oxygenated-machine-perfusion (HOPE) allows assessment/reconditioning of livers procured from high-risk donors before transplantation. Graft referral to HOPE mostly depends on surgeons’ subjective judgment, as objective criteria are still insufficient. We investigated whether analysis of effluent fluids collected upon organ flush during static-cold-storage can improve [...] Read more.
Hypothermic-oxygenated-machine-perfusion (HOPE) allows assessment/reconditioning of livers procured from high-risk donors before transplantation. Graft referral to HOPE mostly depends on surgeons’ subjective judgment, as objective criteria are still insufficient. We investigated whether analysis of effluent fluids collected upon organ flush during static-cold-storage can improve selection criteria for HOPE utilization. Effluents were analyzed to determine cytolysis enzymes, metabolites, inflammation-related mediators, and damage-associated-molecular-patterns. Molecular profiles were assessed by unsupervised cluster analysis. Differences between “machine perfusion (MP)-yes” vs. “MP-no”; “brain-death (DBD) vs. donation-after-circulatory-death (DCD)”; “early-allograft-dysfunction (EAD)-yes” vs. “EAD-no” groups, as well as correlation between effluent variables and transplantation outcome, were investigated. Livers assigned to HOPE (n = 18) showed a different molecular profile relative to grafts transplanted without this procedure (n = 21, p = 0.021). Increases in the inflammatory mediators PTX3 (p = 0.048), CXCL8/IL-8 (p = 0.017), TNF-α (p = 0.038), and ANGPTL4 (p = 0.010) were observed, whereas the anti-inflammatory cytokine IL-10 was reduced (p = 0.007). Peculiar inflammation, cell death, and coagulation signatures were observed in fluids collected from DCD livers compared to those from DBD grafts. AST (p = 0.034), ALT (p = 0.047), and LDH (p = 0.047) were higher in the “EAD-yes” compared to the “EAD-no” group. Cytolysis markers and hyaluronan correlated with recipient creatinine, AST, and ICU stay. The study demonstrates that effluent molecular analysis can provide directions about the use of HOPE. Full article
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16 pages, 592 KiB  
Review
Assessing Kidney Graft Viability and Its Cells Metabolism during Machine Perfusion
by Maria Irene Bellini, Francesco Tortorici, Maria Ida Amabile and Vito D’Andrea
Int. J. Mol. Sci. 2021, 22(3), 1121; https://doi.org/10.3390/ijms22031121 - 23 Jan 2021
Cited by 25 | Viewed by 4846
Abstract
Kidney transplantation is the golden treatment for end-stage renal disease. Static cold storage is currently considered the standard method of preservation, but dynamic techniques, such as machine perfusion (MP), have been shown to improve graft function, especially in kidneys donated by extended criteria [...] Read more.
Kidney transplantation is the golden treatment for end-stage renal disease. Static cold storage is currently considered the standard method of preservation, but dynamic techniques, such as machine perfusion (MP), have been shown to improve graft function, especially in kidneys donated by extended criteria donors and donation after circulatory death. With poor organ quality being a major reason for kidneys not being transplanted, an accurate, objective and reliable quality assessment during preservation could add value and support to clinicians’ decisions. MPs are emerging technologies with the potential to assess kidney graft viability and quality, both in the hypothermic and normothermic scenarios. The aim of this review is to summarize current tools for graft viability assessment using MP prior to implantation in relation to the ischemic damage. Full article
(This article belongs to the Special Issue Protective Strategies against Organ Ischemic Injury)
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16 pages, 778 KiB  
Review
In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion
by Sebastien Giraud, Raphaël Thuillier, Jérome Cau and Thierry Hauet
Int. J. Mol. Sci. 2020, 21(21), 8156; https://doi.org/10.3390/ijms21218156 - 31 Oct 2020
Cited by 12 | Viewed by 4672
Abstract
Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly [...] Read more.
Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation. Full article
(This article belongs to the Special Issue Cellular Models of Oxidative Stress)
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