Ischemia–reperfusion injury (IRI) plays a pivotal role in liver transplantation by inducing oxidative stress and inflammation, thereby contributing to impaired graft function and postoperative complications. A key element of IRI is degradation of the endothelial glycocalyx, resulting in microcirculatory dysfunction. This study investigated the impact of normothermic machine perfusion (NMP) on glycocalyx integrity and its association with early postoperative outcomes. Thirty grafts undergoing NMP prior to transplantation were analyzed. Syndecan-1 and heparan sulfate were quantified in perfusate and recipient serum. Donor-related factors influencing glycocalyx injury during NMP were assessed, and correlations with outcomes established. Syndecan-1 levels increased during NMP and remained significantly elevated in grafts from circulatory-death (DCD) donors compared with brain-death (DBD) donors. Receiver operating characteristics revealed predictive potential for early allograft dysfunction (EAD) with a syndecan-1 cut-off of 4,796.13 ng/mL after 6 h of NMP. In contrast, heparan sulfate concentrations showed no relevant changes. Postoperatively, syndecan-1 levels in recipient serum were elevated immediately after transplantation but declined over subsequent days, while heparan sulfate remained stable. These findings indicate that glycocalyx injury develops during NMP, particularly in DCD livers, with elevated syndecan-1 reflecting endothelial vulnerability and a potentially modifiable aspect of graft physiology relevant to future protective strategies.Clinical Trial Registrationwww.Clinicaltrials.gov, identifier NCT: 04764266.

Objective: To report real-world data on hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP) in liver transplantation (LT). Summary Background Data: Real-world comparisons between HOPE and NMP are limited and methodologically challenging due to heterogeneity in donor and recipient risk profiles and regional differences in practice patterns. Methods: This international cohort study analyzed consecutive NMP-preserved LTs performed at 15 predominantly North American centers between 2021 and 2025. Outcomes were compared with the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Risk-adjusted analyses were performed, stratified by graft type and risk category. Imbalances in baseline characteristics were addressed using entropy balancing. Results: A total of 954 NMP-treated and 1202 HOPE-treated grafts were analyzed, revealing substantial differences in donor risk. Extended-criteria DBD grafts accounted for 30% versus 64%, and futile DCD grafts for 10% versus 30%, in the NMP and HOPE cohorts, respectively. In the NMP cohort, death-censored graft survival at 1, 2, and 3 years exceeded 96% for DBD grafts and 94% for DCD grafts. Comparable outcomes were observed in the HOPE cohort, with 93% survival in DBD and 87% in DCD grafts at up to 3 years, despite significantly higher donor risk in the HOPE-DCD cohort. After risk adjustment, death-censored graft survival remained similar between both modalities across graft types and risk categories. Conclusions: Real-world data on HOPE-treated and NMP-treated LT demonstrate excellent outcomes. Nevertheless, compared with HOPE, further high-quality evidence and longer preservation time is needed to substantiate the clinical benefits of NMP in high-risk grafts.

Background. Older patients undergoing kidney transplantation are at risk of perioperative complications, underscoring the need for optimized care. The number of kidney transplants in older adults has increased in the past decade, with greater reliance on transplants from deceased donors. Methods. The phase 3, randomized, double-blind, active-controlled P002 study evaluated 200 d of letermovir versus valganciclovir prophylaxis in cytomegalovirus-seronegative kidney transplant recipients who received kidneys from cytomegalovirus-seropositive donors. Outcomes among participants aged 65 y or older are reported. Results. Forty-eight and 55 participants aged 65 y or older received letermovir or valganciclovir, respectively. A lower percentage of participants receiving letermovir versus valganciclovir had committee-confirmed cytomegalovirus disease through week 52 posttransplant (9% versus 22%; stratum-adjusted difference, –12% [95% confidence interval [CI], –27% to 2%]), without significant differences in cytomegalovirus disease or viremia between groups. A significantly higher percentage of participants receiving letermovir had ≥90% prophylaxis adherence (96% [95% CI, 86%-100%] versus 49% [95% CI, 35%-63%]). The letermovir group showed numerically lower incidences of drug-related adverse events (25% versus 49%) and study medication discontinuations due to adverse events (10% versus 20%). A significantly lower percentage of participants receiving letermovir had leukopenia or neutropenia events through week 28 posttransplant (31% [95% CI, 19%-46%] versus 62% [95% CI, 48%-75%]). Participants receiving letermovir had numerically lower rates of opportunistic infections (11% versus 25%) and rehospitalizations (51% versus 69%) through week 52 posttransplant. Conclusions. Letermovir showed substantial advantages over valganciclovir in adherence, safety, and tolerability, supporting its use as an important option for cytomegalovirus disease prophylaxis for older patients undergoing kidney transplantation. Clinical trial registration number. ClinicalTrials.gov, NCT03443869

Introduction: Radical Antegrade Modular Pancreatosplenectomy (RAMPS) was developed to improve surgical radicality for left-sided pancreatic ductal adenocarcinoma (PDAC). Although widely accepted, the optimal surgical approach-open versus minimally invasive (MI)-is still being debated. Methods: We conducted a multicenter retrospective cohort study across three Austrian centers, including all patients undergoing RAMPS between 2016 and 2023 indicated for suspected (pre-)malignant pancreatic lesions. Patients were grouped based on the surgical approach (MI vs. open). The primary endpoints were resection margin status and lymph node yield following PDAC resection. Secondary outcomes included survival for PDAC patients and postoperative complications; non-PDAC resections were also taken into account. Results: A total of 57 patients were included, of whom 34 had PDAC. In PDAC patients, the rate of tumor-free margins and the median lymph node yield were equivalent between the MI and open approaches (R0 rate: MI 92.9% vs. open 85%, p = 0.484; median lymph node yield: MI 16 (IQR 10-23) vs. open 19 (IQR 15-25), p = 0.314). Two-year overall survival was also comparable (MI: 71.6% vs. open: 66.4%, p = 0.479). Postoperative outcomes at 90 days, like CR-POPF and major complications (Clavien-Dindo ≥ IIIa), did not differ between the two approaches. MI-RAMPS showed non-significant favorable trends in median length of stay (p = 0.093) and likelihood of receiving adjuvant chemotherapy (p = 0.075). Conclusions: In our experience, MI-RAMPS demonstrates oncologic equivalence and similar early postoperative outcomes to open RAMPS, with potential advantages such as shorter length of stay and likelihood of receiving adjuvant chemotherapy.

BACKGROUND:The adoption of technical variant grafts has expanded the donor pool for pediatric liver transplantation, but it also poses a risk of portal vein thrombosis (PVT). This study evaluated risk and prognostic factors of PVT in children undergoing liver transplantation with technical variant grafts. METHODS:A total of 3137 pediatric patients from 19 centers were included: 470 received split/reduced deceased donor grafts and 2667 received living donor grafts. Multivariable logistic regression was used to identify risk factors, whereas time-dependent Cox models were used to assess the impact on survival. RESULTS:PVT occurred in 102 patients (3.3%) and was associated with increased mortality (adjusted hazard ratio, 2.86; 95% confidence interval [CI], 1.13-7.25; P  = 0.027) and graft loss (adjusted hazard ratio, 9.97; 95% CI, 4.90-20.3; P  < 0.001). Risk factors included younger age, lower weight, higher Pediatric End-Stage Liver Disease score, longer cold ischemia and operation times, higher graft-to-recipient weight ratio, increased red blood cell transfusions, and biliary atresia. After adjusting for center, lower weight (odds ratio, 0.84 per kg; 95% CI, 0.71-1.00; P  = 0.047) and biliary atresia (odds ratio, 2.34; 95% CI, 1.10-5.00; P  = 0.027) remained predictors. Five-year patient (88.4% versus 93.1%) and graft survival (82.7% versus 96.3%) were significantly inferior in patients with PVT. CONCLUSIONS:Low-weight children with biliary atresia constituted a high-risk group, highlighting the necessity for early detection and management.

The New Year is a perfect opportunity, not only for resolutions (that are unlikely to last very long), but also to reflect on the events of the past year and how they are likely to impact the future. In this piece, the editorial board of Transplant International is presenting what we think are the original articles in clinical transplantation published in 2025 that are the most likely to be game changers in our field in the near or not-so-near future. As the saying goes, "it is diaicult to make predictions, especially about the future", but despite the (very limited) risk, we are hopeful that we have not succumbed to hype in our selection, which was based on insights from members of the editorial board, but also on how well cited these papers already were. So, here are the top 12 papers, listed in Table 1, grouped by the topic they address. Selection is obviously a tricky task and for this reason, we will also mention other significant 2025 papers to provide the readers with a somewhat broader picture of what has happened in each of the selected topics (Supplementary Table 1).Xenotransplantation (1,2) Xenotransplantation has repeatedly made the headlines in recent years since the nearsimultaneous transplantation in the fall of 2021of genetically modified porcine kidneys into human brain-dead recipients, or what is called the human decedent model (13). The availability of genome-edited pigs has been the game changer in the field, allowing to significantly lower the immune barriers met in xenotransplantation (14). The first clinical transplants using this resource were performed compassionately in 2022 in patients with no access to deceased donor organs and a compromised survival prognosis in the short term. Although the heart and the kidney xenotransplant recipients did not survive more than a few months, their causes of death not being fully clear, these first 2 cases provided evidence that the early phases of immune xenorejection had been harnessed (1,2) thanks to the gene modification strategy, in particular the knocking oa of 3 carbohydrate antigen genes known to cause hyperacute rejection (α 1-3 Gal, β 1-4 Gal, CMAH). The two featured articles provide a comprehensive narrative of the clinical course of the first heart recipient (1) and the first kidney recipient (2), from transplantation to death. While these cases cannot be considered successes from the patient perspective, they will provide invaluable information on the unforeseen hurdles met and how to overcome them (15). In this regard, and despite the limitations of the decedent model (16), the in-depth analysis of the physiology, immunology and pathology of the first pig-to-human decedent kidney xenotransplant (single gene modification), using multi-omics analysis techniques (17,18), and in particular the novel patterns of immune rejection unveiled and characterized, will also contribute to the better understanding of the physiological processes that will have to be tackled by the next generation of protocols and gene-edited animals. This paragraph would not be complete without mentioning the reports a case of geneedited pig-to-human auxiliary liver transplantation in a living recipient, as a bridge to transplant (19), and lung transplantation using the decedent model (20). Although the cell therapy procedure of islet transplantation would seem to have been an easier clinical model to explore in xenotransplantation, no attempt at transplanting genetically modified porcine islets has been reported to date (21).ABO-incompatible living-donor kidney transplantation has evolved into a standard option to expand the donor pool, but it usually requires desensitization to mitigate the risk posed by preformed anti-A/B antibodies. Protocols commonly include antibody removal (immunoadsorption/antibody adsorption and/or plasma exchange) alongside immunomodulatory therapy, adding complexity, cost, and potential morbidity despite outcomes approaching those of ABO-compatible living-donor transplantation. Kidney paired exchange is an alternative, although limited O-compatible availability may lead to extended waiting times for patients bearing the O blood group. This paper reports the successful conversion of an A blood group kidney into O blood group, using α-galactosidase from Bacteroides fragilis during hypothermic machine perfusion. Three hours of machine perfusion were suaicient to remove >95% of blood group A antigens and allowed successful transplantation of the kidney in a decedent model without experiencing hyperacute rejection (3). After A-antigen regeneration, antibody-mediated lesions and complement deposition were found starting 3 days post-transplant, but single-cell sequencing confirms the elevated expression of accommodation-related genes, suggesting the potential for longer-term tolerance (3). This paper was published a few months after a previous similar report in the less common B-to-O combination, with similar outcomes (22). These two papers provide compelling proof of concept that ex vivo antigen modification can safely expand the donor pool in ABO-incompatible living kidney donation and may therefore fundamentally reshape access in kidney transplantation. This strategy could also be employed in a deceased donor setting in the most urgent cases. While the validity of this method requires confirmation in the setting of clinical live donor kidney transplantation, it could also be explored in the more challenging model of liver transplantation, in which traditional techniques of pre-transplant ABO antibody clearance can be associated with deleterious outcomes (23).The field of islet of Langerhans transplantation has seen 2 landmark clinical papers published last year. They represent a major step forward in beta-cell replacement therapies. The studies show that immune rejection and limited cell availability can be addressed. They set new benchmarks for safety, eaicacy, and translational feasibility. Importantly, they provide insights to guide the next generation of durable islet replacement strategies. They also provide strategies that have the potential to be applied in the bioengineering of other organs.The first is a proof-of-concept article in which the authors have applied their hypoimmune platform (HIP) approach to human primary islet cells. For the first time, they demonstrated the feasibility of gene-editing dissociated human islets using CRISPR-Cas12b and lentiviral transduction, to knock out HLA class I and II genes and overexpress the CD47 transmembrane molecule, which delivers a "don't eat me" signal to cells of the innate immune system. These modified islet cells were then re-aggregated and transplanted into the forearm muscle of a patient with long-standing type 1 diabetes. In this first-in-human study, HIP allogeneic islet cells transplanted without immunosuppression (IS) were not rejected, remained functional up to 12 weeks and achieved functional glucose-responsive insulin secretion. Meanwhile, this provides a landmark proof of concept that immune evasive cells can be generated by gene modification and could overcome one of the central barriers to curative cell therapy for type 1 diabetes. By design, the functional mass of endocrine cells implanted was insuaicient to reverse diabetes, and diaiculties in upscaling the technique to a suaicient islet mass can be anticipated. It should be mentioned that, before going to the clinical setting, the authors had reported successful reversal of diabetes, using the same islet modification methodology, in a humanized mouse model transplanted with human HIP stem cell islets (24) and remarkably in an allogeneic non-human primate model (25).The second landmark paper in the islet transplantation field reported the results of transplantation of stem cell-derived islets in 14 patients with type 1 diabetes (5). This trial was led by the Vertex company and utilized a cell product baptized zimislecel, obtained by an in vitro diaerentiation protocol able to obtain large quantities of fully diaerentiated and glucose-responsive islets (26). The trial was designed as phase 1-2 to determine safety and eaicacy of the product, and the paper is an unplanned interim analysis of the first 12 patients to have received a full dose of the product and completed a 12-month follow-up. The primary eaicacy endpoint was freedom from severe hypoglycemic events until day 365 after infusion, with a glycated hemoglobin level < 7%. Remarkably, all patients met the primary endpoint and 10/12 patients were insulin-independent at 1 year. All patients who came oa insulin did so after a period of several months, suggesting that further diaerentiation may have been taking place in vivo after transplantation (5). These data demonstrate a formidable technological and clinical achievement and advance and provide the first evidence that stem cell-derived tissues can be successfully used as an organ replacement therapy. However, zimislecel administration was done similarly to islet transplantation and used an identical IS protocol; accordingly, the clinical outcomes were similar to those achieved with the landmark "Edmonton protocol" (27). While zimislecel may become a solution in the USA, where allogeneic islet transplantation is essentially unavailable (29), several issues will have to be solved before it can become a real solution for bringing a cure to all type 1 diabetic patients (21). The application of the immune evasiveness strategy described above (4) to stem cell-derived islets may become a solution to that end.Ex vivo machine perfusion has rapidly developed in the last decade, driven by the everincreasing gap between the numbers of donor organs and patients on the waiting list concomitantly with the increase in the proportion of extended criteria and marginal donors (older age, DCD, fatty livers,…). Hypothermic (HMP), hypothermic oxygenated and later, normothermic machine perfusion (NMP) have become a standard-of-care solution for the reconditioning of marginal organs (29,30). Machine perfusion also oaers the possibility of assessing physical or biological parameters in the perfusate to provide information about organ quality, and thus transplantability (31).The seminal multicenter European randomized controlled trial (RCT), comparing hypothermic kidney perfusion, using the Organ Recovery Systems machine, to cold storage enrolled >800 patients and its results were published already in 2009. The primary endpoint of the trial, i.e. occurrence of delayed graft function, was verified, thus demonstrating a significantly lower rate of delayed graft function in the perfusion group. Superior 1-year graft survival was also reported (32). Better graft survival was still observed in a 3-year follow-up paper (33). The article selected presents the longawaited 10-year data (6). Remarkably, the graft survival advantage was still present, and the long term observation revealed that this advantage was only conferred to expanded criteria donors (6). This paper provides compelling evidence to recommend HMP for all kidneys procured from expanded criteria donors, notably DCDs.Advances and utilization of machine perfusion technology have largely been driven by the kidney and liver transplantation fields. The amount of evidence gathered for thoracic organs has been less extensive and has mostly addressed lung transplantation (34,35). The rapid development of DCD heart transplantation in the past decade has provided an incentive for maximizing utilization of DCD hearts using machine perfusion technology.In contrast to kidneys and livers, NMP has been the preferred, and indeed sole, approach employed in this setting (38). Unfortunately, and perhaps for understandable reasons, no prospective randomized trial is available to compare NMP to static cold storage (SCS) in DCD hearts.The OCS NMP machine (Transmedics, Andover, MA, USA) is the only one approved for clinical use in the USA. It allows normothermic pulsatile perfusion during transportation of the heart from recovery to implantation. The selected paper is a Transmedics-led study combining data from the OPTN and OCS Heart Perfusion (OHP) registries and providing real-world data on the largest cohort (854 patients in 56 US centers) of NMPpreserved heart transplants ever reported (7). The large numbers (> 3000 subjects, including OPTN data) and a rigorous methodology have allowed meaningful comparisons of DCD versus DBD cohorts, and NMP versus SCS strategies. The most striking result is the similar 1-year patient survival data in SCS-preserved DBD hearts and NMP-preserved DCD hearts (>90%), observed in spite of 2-3 times longer travelling distances and times. It is remarkable that >25% of hearts transplanted in the USA over the study period were preserved with NMP and <4% of procured NMP hearts were finally rejected (7). In summary the study convincingly shows that NMP allows the recovery of hearts with longer shipping distances and from extended-criteria donors. This is likely to lead to the rapid normalization, in the USA and beyond, of NMP for the preservation of DCD and other marginal donor hearts.Transplant oncology (8) Hepatocellular carcinoma (HCC) is the third most important indication for liver transplantation after alcohol-associated cirrhosis and metabolic dysfunctionassociated steatohepatitis (37). Recently, Immune checkpoint inhibitors (ICIs) have revolutionized the management of HCC and become standard-of-care as part of the treatment of advanced HCC (38). This has allowed not only prolonged patient survival, but also tumour downstaging, bringing patients within Milan or other liver transplantability criteria. Unfortunately, the mechanism of action of ICIs, which essentially boosts the adaptive immune system against the tumour, has resulted in the early experience in a high risk of acute rejection episodes in ICI-treated patients receiving a liver transplant (38,39). A consensus has evolved to suggest that ICIs were a powerful neoadjuvant therapy for downstaging or bridging purposes, but that the optimal "washout" period (free interval between end of ICI treatment and liver transplantation) was to be determined (40).The selected paper is a multi-center retrospective study of 119 liver transplant patients treated with ICIs before liver transplantation in 29 transplant centers worldwide (8). The authors analyzed the relationship between the washout period and several outcome measures, including occurrence and type of rejection, tumour recurrence and survival. They reported a 20% rejection rate, occurring early after transplantation, with a linear reverse relationship between rejection risk and washout period between 3 and 50 days. Beyond 50 days an increased rejection risk was no longer observed. Importantly, with a median follow-up of 18 months, patients with a longer washout period did not present a higher risk for HCC recurrence. There is a caveat with the fact that 9 diaerent ICIs were used in these 119 patients, making it diaicult to determine, due to low numbers, whether the 50-day cut-oa was applicable equally to each of these molecules. Nonetheless, this is the first study to provide convincing evidence about the optimal washout period to observe and the uselessness of waiting times >50 days before performing liver transplantation ICI-treated HCC patients.The field of liver transplantation oncology is not limited to HCC, as unresectable colorectal liver metastases are increasingly becoming a valid indication for liver transplantation in selected cases. The ARTx-Onc study (41) provides a US perspective and favourable outcome results that slightly diaer from those of the recent European Transmet RCT (42).BK polyomavirus nephropathy is a significant challenge for the transplant nephrologist that can have a serious impact on kidney graft function and compromise graft survival in the most serious cases. The standard IS regimen associating tacrolimus, mycophenolate (MMF) and steroids is the primary risk factor for BK viral replication, with a high risk of developing BK nephropathy. The primary strategy in the management of BK virus infection is reduction of the IS at the risk of triggering graft rejection. Due to their antireplicative properties, mTOR inhibitors, well established IS drugs, have demonstrated potent in vitro antiviral activity, including against BK polyomavirus. Accordingly, RCTs exploring the eaicacy of everolimus-based versus MMF-based IS regimens in kidney transplantation have also looked at the occurrence of BK infection and nephropathy. It was found that subjects receiving everolimus had experienced a lower rate of BK infection at 12 months, but none of these studies consistently monitored BK DNA levels (43,44). Therefore, the real role of a switch from MMF to everolimus remains undetermined and prompted the authors of this paper to launch a RCT comparing the eaicacy of reducing MMF dosage versus switching from MMF to everolimus, alongside in kidney transplant recipients with BK their the authors found that BK virus clearance was achieved significantly more and more rapidly in patients with MMF dosage reduction to those to of kidney function at the end of follow-up were identical in These data challenge the that a switch to mTOR inhibitors will lead to clearance of BK the it for BK in kidney transplant recipients and cannot be as a management strategy for BK of HLA has been utilized as an for years as a strategy to antibody and rejection for most organ A role for the innate immune system in the of graft rejection has been in recent years The to be are cell and the signal In the selected the authors have the impact of in the gene signal on the risk of rejection They first determined that only 2 were present in of the human In two of patients subjects, they found that were associated with an increased risk of rejection, graft and survival. in and graft were not only but also For the most acute survival was and graft survival was at years In a they were able to show that to CD47 in These results may impact on strategies and on the of innate and not only of with the of only 2 to and the high impact on kidney the of and could be an and strategy to as a of kidney pathology the has been the consensus system that the and of kidney graft rejection. It provides a for and that of lesions and their to guide patient and graft and to of outcomes the that the is a into of a that is a in the authors of this paper are to and for the of kidney transplant were developed from the analysis of from centers The for these can be found in the The first 2 and from were designed to the of the of kidney transplant rejection, and the last 2 and to the of rejection by more and The developed from a cohort of were in 2 of and of kidney transplant rejection of the and of rejection with the A significant of these is that it allows to better on a the and thus the for lesions as or rejection in the system. this paper oaers a replacement of rejection with the biological of kidney rejection. It provides a that can clinical and trial in transplant It has the potential of being a in the of kidney rejection in the very near lung is an term to the diaerent of lung its most common being in has been achieved in the and treatment of this and remains the cause for graft Recently, has as a treatment for the and management of rejection in heart and lung with evidence its use in kidney and liver transplants is an therapy, combining with It in the of the cells with a by before the cells into the was first developed for the treatment of cell and used in other including and organ rejection A recent multicenter study of lung transplant recipients on for a of reported a to treatment or in about of study subjects This article reports the outcomes of a RCT in which patients with were randomized to from day 2 to after lung in to or IS The primary outcome was the occurrence of acute rejection or within 2 of transplantation to IS resulted in a in the primary endpoint mostly driven by a lower of or Importantly, and of were similar in the treated and the group, that had not led to for the of an increase in This trial a potential game changer for the survival and of of lung transplant It could the standard IS protocol for lung transplantation these results are in patients transplanted for other and in

INTRODUCTION:Normothermic machine perfusion (NMP) has emerged as a promising tool for assessing kidney quality prior to transplantation; however, reliable biomarkers remain to be established. METHODS:In this study, thirteen porcine kidneys were perfused for 24 h using an autologous leukocyte-filtered whole blood-based perfusate applying urine recirculation. Functional, biochemical, and morphological parameters were assessed to comprehensively evaluate kidney quality. RESULTS:Stable hemodynamics, sustained urine output, and oxygen consumption rates indicated preserved kidney viability. Within two hours of perfusion, microperfusion in renal cortex and ureter improved significantly, as confirmed by near-infrared, tissue hemoglobin, and oxygen saturation metrics. Morphological assessment revealed progressive injury localized in proximal tubular cells, marked by increased vacuolization, reduced microvilli density, and swollen mitochondria with protruding membranes. In contrast, the architecture of distal tubules and glomeruli remained intact. Biomarker analysis corroborated these findings, with KIM-1 and IGFBP-7 levels, two biomarkers predominantly expressed in proximal tubular cells, rising. Notably, overall OXPHOS capacity declined with perfusion duration, while ATP production efficiency remained stable. Histological grading, in concordance with real-time confocal assessment, showed no significant alteration over time. CONCLUSION:This study provides a detailed phenotypical and bioenergetic profiling of kidney grafts over 24 h of NMP, demonstrating preserved kidney viability and function. The observed subcellular and molecular alterations, especially affecting the proximal tubules, were not reflected in frequently gathered metrics like hemodynamic flow, urine output, oxygen consumption, or lactate levels. Further studies are needed to confirm these findings and evaluate their clinical impact after transplantation.

Background/Objectives: The International Study Group for Pancreatic Surgery has recently defined post-pancreatectomy acute pancreatitis (PPAP), stating that sustained postoperative hyperamylasemia (POH) for at least 48 h is a pivotal criterion. However, the clinical relevance of POH and PPAP following distal pancreatectomy remains uncertain. This study compares two PPAP definitions differing in POH criteria. Methods: We retrospectively analyzed all patients who consecutively underwent distal pancreatectomy at our institution (2010-2023). PPAP diagnosis required clinical symptoms, characteristic CT findings, and either sustained POH ≥ 48 h (standard group) or transient POH less than 48 h (modified group). Outcomes were compared between definitions. Results: Among 207 patients included, in the standard group, PPAP was diagnosed in 12 (5.8%), and in the modified group in 27 (13.0%) patients. Independent of the applied POH criteria, PPAP was associated with the occurrence of clinically relevant postoperative pancreatic fistulas (standard: 66.7% vs. 23.7%; p < 0.001; modified: 44.4% vs. 23.7%; p = 0.027). Post-pancreatectomy hemorrhage and major complications (Clavien-Dindo grade ≥ III) were also significantly more frequent in patients with PPAP. This was mirrored by a significantly longer length of stay and higher costs. However, in the standard group, PPAP more often resulted in pancreas-specific and major complications compared to the modified group. Of note, in the standard group, only 50% of patients with POH progressed to PPAP, and one-third of patients suffering from PPAP did not develop harmful sequelae. Conclusions: PPAP is an uncommon, however clinically relevant complication following distal pancreatectomy that is better captured using the standard POH definition. Still, further stratification is needed to aid in the prediction of the clinical course.

Normothermic machine perfusion (NMP) enables liver preservation under close-to physiological conditions and thus, may serve as a platform to treat livers ex situ. Liver-directed adeno-associated virus (AAV) vectors are a promising candidate for the treatment of liver genetic diseases, but highly specific AAV vectors are lacking. We herein utilized the NMP platform for porcine livers to optimize AAV vector-based gene therapy protocols. Porcine livers (n = 4) were subjected to NMP (OrganOx® Metra) for 48 h and AAV3B encoding eYFP was applied to the perfusate. Serial perfusate samples were analysed for liver function and complement activation. Tissue biopsies were taken pre virus application, after 3 h, 24 h and 48 h for real-time confocal microscopy and immunofluorescent staining to assess eYFP protein or cryopreserved for quantification of AAV3B cDNA and gDNA levels. AAV3B vector administration in the perfusate did not disrupt stable liver NMP nor induce complement activation or an inflammatory response. At a dose of 1 × 1013 vg/kg AAV transduction was successfully detected by eYFP signals in immunofluorescence microscopy and confirmed by quantification of AAV3B vector genomes in tissue biopsies taken after 24 h and 48 h of NMP, but not as early as 3 h after vector application. Administration of a poloxamer (Pluronic®) enhanced transduction efficiency of AAV3B, while a dose reduction to 2 × 1012 vg/kg with Pluronic® resulted in comparable transduction efficiency to the high-dosage protocol without Pluronic®. AAV application during liver NMP is reasonable and does not induce adverse effects, which makes the pre-clinical porcine liver NMP model an excellent platform for the development of AAV-based gene therapies.

OBJECTIVE:To report real-world data on hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP) in liver transplantation (LT). SUMMARY BACKGROUND DATA:Real-world comparisons between HOPE and NMP are limited and methodologically challenging due to heterogeneity in donor and recipient risk profiles and regional differences in practice patterns. METHODS:This international cohort study analyzed consecutive NMP-preserved LTs performed at 15 predominantly North American centers between 2021 and 2025. Outcomes were compared with the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Risk-adjusted analyses were performed, stratified by graft type and risk category. Imbalances in baseline characteristics were addressed using entropy balancing. RESULTS:A total of 954 NMP-treated and 1202 HOPE-treated grafts were analyzed, revealing substantial differences in donor risk. Extended-criteria DBD grafts accounted for 30% versus 64%, and futile DCD grafts for 10% versus 30%, in the NMP and HOPE cohorts, respectively. In the NMP cohort, death-censored graft survival at 1, 2, and 3 years exceeded 96% for DBD grafts and 94% for DCD grafts. Comparable outcomes were observed in the HOPE cohort, with 93% survival in DBD and 87% in DCD grafts at up to 3 years, despite significantly higher donor risk in the HOPE-DCD cohort. After risk adjustment, death-censored graft survival remained similar between both modalities across graft types and risk categories. CONCLUSIONS:Real-world data on HOPE-treated and NMP-treated LT demonstrate excellent outcomes. Nevertheless, compared with HOPE, further high-quality evidence and longer preservation time is needed to substantiate the clinical benefits of NMP in high-risk grafts.

[This corrects the article DOI: 10.3389/ti.2026.15502.].

Background: Pancreatoduodenectomy with venous resection (PDVR) may be performed to achieve tumour clearance in patients with a pancreatic ductal adenocarcinoma (PDAC) with venous involvement. This study aimed to evaluate the impact of PDVR on PDAC outcomes. Methods: In total, 435 PDAC patients with either R0 status (n = 322) or R1 status within the superior mesenteric vein groove (n = 113) were extracted from the Recurrence After Whipple’s (RAW) study dataset. PDVR patients were matched in a 1:2 ratio with standard PD patients. Comparisons were then made between the two groups (surgical radicality and survival). Results: A total of 81 PDVRs were matched with 162 PDs. Neoadjuvant chemotherapy (5.7% vs. 13.6%, p = 0.032) and R1 resection rates (17.9% vs. 42%, p < 0.001) were higher in the PDVR group. Risk factors for R1 resection included venous resection (p < 0.001 for sleeve and p = 0.034 for segmental resection), pT3 (p = 0.007), and pN1 stage (p = 0.045). PDVR patients had lower median overall survival (OS, 21 vs. 30 months (m), p = 0.023) and disease-free survival (DFS, 17 m vs. 24 m, p = 0.043). Among PDVR patients, R status did not impact on OS (R0: 23 m, R1: 21 m, p = 0.928) or DFS (R0: 18 m, R1: 17 m, p = 0.558). Irrespective of R status, systemic recurrence was higher in the PDVR group (p = 0.034). Conclusions: Independent of R status, the PDVR group had lower overall survival and higher systemic recurrence rates.

INTRODUCTION:Delayed graft function after pancreas transplantation (pDGF) is still lacking of a homogenous definition. So, its incidence and clinical impact are poorly understood. METHODS:151 consecutive pancreas transplants (PTx) performed at the Medical University of Innsbruck between January 2011 and December 2021. 142 were finally evaluated analyzed after excluding those with early graft loss due to surgical or infectious problems. RESULTS:pDGF was defined as a total mean insulin requirement of 2.5 UI or greater within postoperative day 10. Of the 142 recipients, 52 (36.6 %) developed pDGF. By multivariate analysis, pDGF was found to be associated with a donor age (odds ratio, 1.05; 95 % CI: 1.01-1.09; p = 0.010) and the continuous postoperative administration of unfractioned heparin (odds ratio, 2.52; 95 % CI: 1.12-5.64; p = 0.025). The occurrence of pDGF lead to longer hospital stay (23 vs 20 days, p = 0.049), intensive care unit stay (5 vs 3 days, p < 0.003) and impaired glycemia at day 10 postoperative (146.0 vs 126.4 mg/dl, p < 0.001). Also, pDGF was found to be associated with a greater risk of pancreas graft failure at 5 years (p = 0.047) in the univariable analysis, while in the multivariable this trend was not statistically significant (p = 0.076). Of note, in the multivariable analysis pDGF showed a strong trend towards worse graft survival without reaching statistical significance (HR:2.33, 95 % CI: 0.95-5.82; p = 0.069) CONCLUSION: pDGF represents a common condition, depending both from donor and recipient conditions. Its clinical impact concerns the early postoperative stay and the long-term graft survival as well.

Kidneys from brain-death small pediatric donors ≤2 years are still classified as marginal organs. Herein, we analyse the outcomes following en-bloc kidney transplantation (EBKT) from pediatric donors ≤2 years into adult recipients compared to standard criteria donor kidney transplant recipients (SKTs). A retrospective single center analysis of a prospectively collected and auditable database identified six EBKTs and 75 SKTs between January 2015 and June 2017. Propensity score matching minimized selection bias. After a median follow-up of 74 months, five-year patient and graft survival were 100%, each in the EBKTs group. Following SKTs, the five-year patient survival rate was 94.7%, likewise death-censored graft survival reached 94.7%. Two EBKT cases experienced unilateral arterial graft thrombosis requiring unilateral nephrectomy, with full recovery and good kidney function. At hospital discharge, recipients of EBKTs showed decreased eGFR compared to SKTs, however, from 3 months onward this reversed and following a median follow-up of 74 months the median eGFR was twice as high after EBKT compared to SKT (107 ml/min/1.73m2 vs. 52 ml/min/1.73m2, p < 0.001). These favourable results persist in the PSM analysis. EBKTs from very small pediatric donors show excellent long-term kidney function. The higher incidence of postoperative complications does not translate into poorer mid-term patient and graft survival.