Louise Barbier

Background: Donor organ scarcity and increasing use of extended‐criteria donors have driven the development of dynamic preservation methods to improve outcomes following liver transplantation. Hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP), controlled oxygenated rewarming (COR), and ischemia‐free liver transplantation (IFLT) are dynamic preservation methods that have been compared with traditional static cold storage (SCS). However, no randomized clinical trials (RCTs) have directly compared HMP with NMP. The aim of the present study is to conduct a network meta‐analysis (NMA) of RCTs to compare the effects of available dynamic preservation strategies on clinical outcomes. Methods: Electronic databases were systematically searched for RCTs evaluating dynamic preservation methods in human liver transplantation. Eligibility criteria included reporting of at least one of the following primary outcome measures: early allograft dysfunction (EAD), biliary complications, and graft survival. A random‐effects Bayesian NMA with a non‐informative prior was conducted. Results: Thirteen RCTs were included with a total of 1888 recipients and assessed 5 interventions. IFLT had the highest probability of being the best‐ranked treatment for EAD and biliary complications, but these findings were based on a single RCT. HMP (7 RCTs) ranked higher than NMP (4 RCTs) across all primary outcomes, whereas NMP ranked higher than SCS for EAD and biliary complications. Subgroup analysis of extended criteria brain‐dead donors was consistent with overall findings. Conclusions: Dynamic preservation modalities were associated with improved outcomes compared with SCS. HMP ranked higher than NMP across the primary outcomes. However, these comparisons were predominantly indirect and do not establish superiority of HMP over NMP.

Hypothermic oxygenated machine perfusion (HOPE) is a simple ex‐situ treatment for liver grafts. However, it lacks viability assessment capabilities. Flavin mononucleotide (FMN) and D‐dimer may be useful biomarkers of graft quality during HOPE. This exploratory study aimed to determine whether effluent FMN and D‐dimer concentrations were associated with outcomes in liver transplants treated with HOPE. This is a retrospective, single‐center study of all grafts treated with HOPE in New Zealand from 2022‐2025. Fifty‐four grafts were treated with HOPE. Effluent concentrations of FMN ( n = 30) and D‐dimer ( n = 24) were analyzed. Post‐transplant cholangiopathy (PTxC) with graft loss occurred in five recipients of donation after circulatory death grafts. The median summation of FMN concentrations taken over the first two hours of perfusion was higher in the PTxC group (four PTxC events among the 30 grafts with FMN measurements; p = 0.034). Decision curve analysis suggested that summated FMN models may add net benefit over default strategies, particularly in DCD grafts, although with only five outcome events these analyses do not define implantation thresholds. D‐dimer concentrations were not significantly different in PTxC grafts ( p > 0.05). Whilst perfusate FMN has promise as a predictor of PTxC in HOPE grafts, especially if summated over several time points, prospective external validation is required before it could contribute to transplantation decision‐making.

Introduction: Self‐directed learning (SDL) and reflection are critically important for clinicians. There is limited evidence describing the utilization of artificial intelligence (AI) to support medical SDL. AI simulated patients (AISP) may allow for high‐fidelity, reflective educational interactions. We aimed to determine how SDL with AISP interaction compared to standard SDL in the development of clinical reasoning skills. Methods: This was a single‐institution randomized controlled study in early clinical years' undergraduate students, learning about gallstone disease. For 90% power and a 20% noninferiority margin, 36 participants were randomized either to an intervention group using an AISP or to a control group using current educational resources. Both groups underwent a standardized clinical skills assessment. Quantitative and qualitative data were collected. Results: Twenty‐seven participants completed the study. The intervention group demonstrated statistical noninferiority compared with the control group (assessment scores of 13.1 vs. 12.1, respectively, p = 0.11). In addition, there were fewer borderline grades, and significantly more distinction grades in the intervention group than control (6 vs. 1, respectively, p = 0.037), suggesting the AISP may have improved performance in clinical management. The qualitative data suggested widespread satisfaction and enthusiasm for AISPs. Conclusion: Our results suggest that AISPs are comparable to traditional resources in developing undergraduate clinical skills, and may contribute to improved academic performance in undergraduate surgery. Globally, there is an appetite for their introduction into the clinical curriculum. Real patient interaction is the standard. However, AISPs may have a supplementary role and are likely to become increasingly prominent in medical curricula.

Introduction L’IL-33 joue un rôle d’alarmine dans l’initiation de la réponse inflammatoire aux lésions d’ischémie-reperfusion (I/R) rénale, impliquant les lymphocytes “invariant natural killer” (iNKT). ObjectifsDéterminer si l’IL-33 agit également comme une alarmine en I/R hépatique et évaluer la contribution de l’IL-33 et des cellules iNKT dans le recrutement des granulocytes neutrophiles et des monocytes/macrophages après IR.MéthodesNous avons choisi un modèle d’ischémie chaude hépatique par clampage à 70% du foie de souris C57BL/6 sauvages, déficientes en IL-33 (IL-33 KO) ou déficientes en cellules iNKT (Jalpha18 KO). La sévérité des lésions d’I/R a été évaluée par dosage plasmatique des ALAT et analyse histologique des lobes de foie clampés. L’IL-33 a été déterminée dans le sang et le foie, respectivement par ELISA et western blot et sa néo-synthèse par RT-PCRq. Le recrutement des cellules immuno-inflammatoires dans le foie après IR a été analysé par cytométrie en flux.Résultats Chez les souris sauvages, l’IL-33 était constitutivement exprimée dans les cellules endothéliales des sinusoïdes et des veinules portes du foie et était immédiatement libérée pendant la phase d’ischémie dans la circulation sanguine sans néo-synthèse. Quatre heures après la reperfusion, les lésions d’I/R étaient diminuées chez les souris déficientes en IL-33, comparativement aux souris sauvages. Ainsi, dès les premières heures après l’ischémie, l’IL-33 agit comme une alarmine et est en partie responsable des lésions d’I/R.Les lésions d’I/R étaient également diminuées chez les souris déficientes en cellules iNKT, tandis que chez les souris sauvages, les cellules iNKT étaient activées en périphérie (dans la rate) et recrutées localement. Les granulocytes neutrophiles et les monocytes/macrophages étaient recrutés dans le foie après une heure de reperfusion chez les souris sauvages, alors que ce recrutement était significativement réduit chez les souris déficientes en IL-33 et chez les souris déficientes en iNKT, suggérant qu’à la fois l’IL-33 et les iNKT contribuent au recrutement de cellules immuno-inflammatoires. Cet ensemble de résultat est conciliable avec l’existence d’un axe IL-33/iNKT intervenant dans les phases précoces de l’inflammation lors de l’I/R hépatique.Conclusion L’IL-33, en tant qu’alarmine, contribue précocement aux lésions d’I/R hépatique. L’IL-33 pourrait agir en mobilisant les cellules iNKT, lesquelles avec l’IL-33, amplifieraient le recrutement des cellules immuno-inflammatoires. L’IL-33 représente donc une cible thérapeutique essentielle pour réduire les lésions d’I/R en transplantation hépatique.

Introduction: Previous guidelines considered body mass index (BMI) over 40 kg/m² a relative contra‐indication to liver transplantation (LT). The aims were to examine the selection process and study outcomes of patients with Class I–III obesity.Methods: Retrospective analysis of outcomes of obese patients assessed for LT at our center between 2010 and 2023, divided into three groups: Class I (BMI30‐34.9 kg/m²), Class II (BMI35‐39.9 kg/m²), and Class III (BMI>40 kg/m²). Survival of non‐obese adult patients was used for comparison.Results: Three hundred fifteen patients with BMI ≥30 kg/m² were assessed for LT. Seventeen (5.4%) were not wait‐listed due to comorbidities. One hundred sixty‐eight patients were transplanted: 100 Class I, 43 Class II, and 25 Class III. There were no differences in postoperative complications (Clavien‐Dindo Grade 3 or more; 41%, 42%, 48% for Class I–III obesity respectively) or patient and graft survival (5‐y rates 84.4% and 82.7%, respectively, for the whole cohort) according to the different classes of obesity. Furthermore, patient and graft survival was not different between non‐obese and obese patients (p = 0.932).Conclusion: With a rigorous selection process, short‐term outcomes after LT for patients with Class III obesity were comparable to patients with Class I–II obesity. Long‐term survival was identical for obese and non‐obese patients.

Background: The aim of the present study was to compare the outcomes of pediatric LT with left liver grafts, obtained either from a living donor (LD) or a split deceased donor (sDD).Methods: Retrospective single‐center study from 2002 to 2022. All pediatric LT with left liver grafts (not including middle hepatic vein) from LD or sDD were included. Reduced grafts were not included.Results: A total of 112 pediatric LT were performed: 58 with LD grafts and 54 with sDD grafts (17 split ex situ and 37 in situ). Donor characteristics were similar, apart from donor age (33 years in LD vs. 30 years in sDD, p = 0.03). Indications were similar with 55% biliary atresia in each group. Retransplantation was more frequently performed in the sDD group (2% vs. 15%, p = 0.01). Recipient age, weight, and PELD score at transplant were not significantly different between groups. Cold ischemia time was longer for sDD (158 min in LD vs. 390 min in sDD; p < 0.0001). Posttransplant peak ALT was higher with sDD grafts (1470 vs. 1063, p = 0.018), and hospital stay was longer with sDD grafts (27 vs. 21 days, p = 0.005). However, there was no difference between groups in terms of major morbidity (Dindo‐Clavien grade ≥3), vascular and biliary complications, and 90‐day mortality. Patient survival at 10 years was 93.1% for LD and 92.8% for sDD (p = 0.807). Graft survival at 10 years was 89.7% for LD and 83.1% for sDD (p = 0.813).Conclusions: Technically similar LD and sDD grafts achieve very similar postoperative and long‐term outcomes with excellent patient and graft survival.