Graft Perfusion Research Articles

Color Doppler Ultrasonographic Examination of Ovarian Grafts in Goats.

The aim of this study was to evaluate the effectiveness of color Doppler ultrasonography for examination of the blood flow areas in superficial grafts after 7 or 15 days of heterotopic allotransplantation, comparing an in-ear subcutaneous area (IE) with an in-neck cervical intramuscular area (IN) in goats. To monitor the local blood flow in the graft areas, color Doppler signals were assessed daily until days seven and fifteen, when the left and right implants, respectively, were removed. The areas of blood flow around the transplanted ovarian fragments were significantly larger (p < 0.05) in the IE area compared to the IN area after 7 (IE: 4.70 ± 0.33A vs. IN: 3.67 ± 0.33B) and 15 (IE: 5.27 ± 0.21A vs. IN: 4.66 ± 0.22B) days of transplantation. A positive and significant correlation was observed between the area of blood flow and the day of assessment after 7 (IE: r = 0.43; p < 0.05) and 15 (IE: r = 0.52; p = 0.001; IN: r = 0.42; p = 0.001) days of transplantation. In conclusion, color Doppler ultrasonography can be used for real-time assessment of local blood perfusion in ovarian grafts, making it possible to identify alterations in the blood flow area in the period following a transplant procedure.

Perfusion Computed Tomography for Assessing Pancreas Graft Volumetric Perfusion After Simultaneous Pancreas and Kidney Transplantation.

Background: There is paucity of data in the available medical literature regarding the parameters of the volumetric perfusion of pancreas grafts. Methods: From 5 February 2016 to 23 December 2021, we performed perfusion computed tomography in 41 patients at different times after simultaneous pancreas and kidney transplantation. The study group consisted of 18 men (44%) and 23 women (56%) with a long history of type 1 diabetes mellitus complicated by terminal chronic renal failure. The results of the perfusion computed tomography of the pancreas graft were studied, and the effects of post-transplantation timing and graft revascularization peculiarities on volumetric perfusion parameters were evaluated. Results: The median arterial blood flow, arterial blood volume, and permeability of the pancreas graft were 115.1 [99.7;130.3] mL/100 mL/min, 46.7 [37.4;56.9] mL/min, and 8.6 [4.1;11.4] mL/100 mL/min, respectively. No statistically significant differences in the averaged perfusion values were found in the head, body, and tail of the pancreas graft. The post-transplantation timing and the number of arteries involved in graft revascularization did not have a significant effect on the volumetric perfusion of the graft. Conclusion: The volumetric perfusion results of the pancreas graft correspond to those obtained in the study of pancreatic perfusion in healthy participants.

Expression of sPD-L1 levels in an ex vivo liver perfusion model.

The programmed cell death protein 1 (PD-1) acts as a central inhibitory immune checkpoint receptor. The soluble form of its primary ligand, sPD-L1, was found to be elevated in serum of patients with cancer, infectious diseases and chronic inflammation. So far, the hepatic origin of sPD-L1 has received relatively little attention and is therefore subject of this study in the context of normothermic machine perfusion (NMP) of liver grafts. sPD-L1 concentrations as well as several well-established clinically relevant laboratory parameters were determined in the perfusate of 16 donor liver grafts undergoing normothermic machine perfusion (NMP) up to 30 hours (h). sPD-L1 levels continuously increased during NMP and significantly correlated with markers of hepatic synthesis (cholinesterase), acute-phase proteins (von Willebrand factor, procalcitonin, antithrombin, interleukin-6, fibrinogen) and liver decay markers (gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase). Perfusate leukocytes were in the lower reference range, and decreased after 12h. Mean sPD-L1 levels in the perfusate correlated with donor levels of gamma-glutamyltransferase, alanine aminotransferase, creatinine and blood urea nitrogen. Our study reveals a significant increase of concentration of sPD-L1 following ischemia-reperfusion injury in a hepatic ex vivo model. sPD-L1 concentrations during NMP correlate with established acute-phase proteins and liver cell decay markers suggesting that hepatic sPD-L1 synthesis or shedding increases during the acute phase and cell decay. Furthermore, sPD-L1 correlates with established liver function and synthesis parameters as well as with donor laboratory values and might therefore be a potential biomarker for hepatic function of liver grafts.

Targeted immune cell therapy for hepatocellular carcinoma using expanded liver mononuclear cell-derived natural killer cells

Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells in vitro, and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69+ in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions.

261.10: Prolonged static cold storage results in significant pelvic hematomas during normothermic machine perfusion of porcine kidney grafts.

261.10: Prolonged static cold storage results in significant pelvic hematomas during normothermic machine perfusion of porcine kidney grafts.

Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis.

Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway. Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl4)-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity. The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n=385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence. Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis.

Revolutionizing Liver Transplantation: Transitioning to an Elective Procedure Through Ex Situ Normothermic Machine Perfusion - A Benefit Analysis.

To assess the impact of normothermic machine perfusion (NMP) on patients, medical teams, and costs by gathering global insights and exploring current limitations. NMP for ex situ liver graft perfusion is gaining increasing attention for its capability to extend graft preservation. It has the potential to transform liver transplantation (LT) from an urgent to a purely elective procedure, which could revolutionize LT logistics, reduce burden on patients and health care providers, and decrease costs. A 31-item survey was sent to international transplant directors to gather their NMP experiences and vision. In addition, we performed a systematic review on cost-analysis in LT and assessed studies on cost-benefit in converting urgent-to-elective procedures. We compared the costs of available NMPs and conducted a sensitivity analysis of NMP's cost benefits. Of 120 transplant programs contacted, 64 (53%) responded, spanning North America (31%), Europe (42%), Asia (22%), and South America (5%). Of the total, 60% had adopted NMP, with larger centers (>100 transplants/year) in North America and Europe more likely to use it. The main NMP systems were OrganOx-metra (39%), XVIVO (36%), and TransMedics-OCS (15%). Despite NMP adoption, 41% of centers still perform >50% of LTs at nights/weekends. Centers recognized NMP's benefits, including improved work satisfaction and patient outcomes, but faced challenges like high costs and machine complexity. 16% would invest $100,000 to 500'000, 33% would invest $50,000 to 100'000, 38% would invest $10,000 to 50'000, and 14% would invest <$10,000 in NMP. These results were strengthened by a cost analysis for NMP in emergency-to-elective LT transition. Accordingly, while liver perfusions with disposables up to $10,000 resulted in overall positive net balances, this effect was lost when disposables' cost amounted to >$40,000/organ. The adoption of NMP is hindered by high costs and operational complexity. Making LT elective through NMP could reduce costs and improve outcomes, but overcoming barriers requires national reimbursements and simplified, automated NMP systems for multiday preservation.

Serum Lactate Clearance as a Predictive Biomarker for Optimal Graft Perfusion in Living Donor Liver Transplantation

BackgroundThe optimal balance between the graft volume (GV) and portal venous flow (PVF) in living donor liver transplantation (LDLT) is unclear. As lactate is mainly metabolized in the liver, perioperative lactate levels are reportedly a useful biomarker for early graft dysfunction (EGD). The present study analyzed perioperative lactate levels according to the PVF. MethodsThe PVF/GV (mL/min per 100 g GV) of 97 recipients from 1996 to 2022 was retrospectively classified as low (LPVF; PVF/GV ≤ 100, N = 29), moderate (MPVF; PVF/GV 100–250, N = 40), or high (HPVF; PVF/GV > 250, N = 28). Lactate levels were obtained preoperatively (L0), immediately after graft reperfusion (L1), 4 h after reperfusion (L2), and on postoperative day 3 (L3). The lactate clearances were then calculated. ResultsThe lower the PVF/GV ratio, the younger the age at LDLT and the higher the graft-to-recipient weight ratio. The median L2 and L3 in the HPVF group were significantly higher than those in the other groups (p = 0.019 and p = 0.003, respectively). The median ΔL1 in the HPVF group was lower than that in the LPVF and MPVF groups (0.23 vs. 0.50, p < 0.0001 and 0.23 vs. 0.41, p = 0.011, respectively). ΔL1 was negatively correlated with the PVF/GV. Although no patient had EGD, three patients with HPVF with low ΔL1 developed small-for-size syndrome. ConclusionsGraft hyperperfusion may delay the recovery of the graft function and result in poor lactate clearance. The combination of the PVF/GV and lactate clearance may be useful as a prognostic marker for optimal graft perfusion in LDLT. Level of evidenceIV.

Protocol description and initial experience in kidney graft perfusion using infrared thermography.

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. Infrared thermographic images of renal grafts are obtained before kidney reperfusion, 10min 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. 17 grafts were studied. The mean temperature of the grafts before reperfusion, 10min 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. 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.

Portal vein arterialization in 25 liver transplant recipients: A Latin American single-center experience.

Portal vein arterialization (PVA) has been used in liver transplantation (LT) to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis (PVT). The effect of PVA on portal perfusion and primary graft dysfunction (PGD) has not been assessed. To examine the outcomes of patients who required PVA in correlation with their LT procedure. All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed. To account for the time-sensitive effects of graft perfusion, patients were classified into two groups: prereperfusion (pre-PVA), if the arterioportal anastomosis was performed before graft revascularization, and postreperfusion (post-PVA), if PVA was performed afterward. The pre-PVA rationale contemplated poor portal hemodynamics, severe vascular steal, or PVT. Post-PVA was considered if graft hypoperfusion became evident. Conservative interventions were attempted before PVA. A total of 25 cases were identified: 15 before and 10 after graft reperfusion. Pre-PVA patients were more affected by diabetes, decompensated cirrhosis, impaired portal vein (PV) hemodynamics, and PVT. PGD was less common after pre-PVA (20.0% vs 60.0%) (P = 0.041). Those who developed PGD had a smaller increase in PV velocity (25.00 cm/s vs 73.42 cm/s) (P = 0.036) and flow (1.31 L/min vs 3.34 L/min) (P = 0.136) after arterialization. Nine patients required PVA closure (median time: 62 d). Pre-PVA and non-PGD cases had better survival rates than their counterparts (56.09 months vs 22.77 months and 54.15 months vs 31.91 months, respectively). This is the largest report presenting PVA in LT. Results suggest that pre-PVA provides better graft perfusion than post-PVA. Graft hyperperfusion could play a protective role against PGD.

Postoperative Time and Anatomic Location Influence Skin Graft Reperfusion Assessed With Laser Speckle Contrast Imaging.

Under optimal conditions, afferent and efferent human skin graft microcirculation can be restored 8-12 days postgrafting. Still, the evidence about the reperfusion dynamics beyond this period in a dermato-oncologic setting is scant. We aimed to characterise the reperfusion of human skin grafts over 4 weeks according to the necrosis extension (less than 20%, or 20%-50%) and anatomic location using laser speckle contrast imaging (LSCI). Over 16 months, all eligible adults undergoing skin grafts following skin cancer removal on the scalp, face and lower limb were enroled. Perfusion was assessed with LSCI on the wound margin (control skin) on day 0 and on the graft surface on days 7, 14, 21 and 28. Graft necrosis extension was determined on day 28. Forty-seven grafts of 47 participants were analysed. Regardless of necrosis extension, graft perfusion equalled the control skin by day 7, surpassed it by day 21, and stabilised onwards. Grafts with less than 20% necrosis on the scalp and lower limb shared this reperfusion pattern and had a consistently better-perfused centre than the periphery for the first 21 days. On the face, the graft perfusion did not differ from the control skin from day 7 onwards, and there were no differences in reperfusion within the graft during the study. Skin graft reperfusion is a protracted process that evolves differently in the graft centre and periphery, influenced by postoperative time and anatomic location. A better knowledge of this process can potentially enhance the development of strategies to induce vessel ingrowth into tissue-engineered skin substitutes.

The Use of Titanium Pins for the Management and Fixation of Free Gingival Grafts and Apically Repositioned Flaps During Vestibuloplasty. A Technique Report.

The presence of adequate keratinized mucosa (KM) around dental implants and natural dentition is pivotal for the long-term success of dental restorations. Despite various techniques to augment KM, challenges persist in achieving stable, keratinized, and adherent mucosa, especially in the context of significant muscle pull or compromised tissue conditions. This study introduces a novel application of titanium pins for the fixation of free gingival grafts (FGG) and apically repositioned flaps (APF) during vestibuloplasty, aiming to overcome important limitations associated with traditional suturing methods and shorten the treatment time and patient morbidity. Three patients with insufficient KM width, presenting discomfort during oral hygiene and inflammation around implant restorations and natural teeth, underwent soft tissue augmentation using titanium pins traditionally used in guided bone regeneration (GBR) for the stabilization of FGGs and APFs. This method ensures intimate contact between the graft and the periosteum, facilitating proper graft perfusion and revascularization, minimizing shrinkage and the risk for necrosis of the graft. Postoperative follow-up revealed successful integration of the grafts, with minimal shrinkage and increased width and depth of KM. The use of titanium pins allowed for reliable fixation in challenging surgical sites, where traditional suturing methods were impractical due to the presence of extensive muscle pull and an unstable recipient bed. The application of titanium pins for the fixation of FGGs and APFs during vestibuloplasty provides a promising alternative to traditional suturing techniques, particularly in complex cases where the recipient bed is suboptimal for suturing. This method simplifies and shortens the procedure, offering a predictable outcome with increased mechanical stability and minimal shrinkage of the graft. Randomized clinical trials are recommended to further evaluate the efficacy of this technique.

Normothermic Liver Machine Perfusion and Successful Transplantation of Split Liver Grafts: From Proof of Concept to Clinical Implementation.

Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day. We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity. Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7). NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.

#573 Development of a model for simultaneous normothermic perfusion in porcine kidney grafts

Abstract Background and Aims In recent years, DCD or ECD deceased donors have been increasingly used in kidney transplantation as a partial response to the deceased donor shortage, leading to a suboptimal quality of kidney grafts. There is a need for developing better kidney graft preservation methods, such as hypo- or normo- thermic machine perfusion. Machine perfusion might provide the unique opportunity to directly treat the perfused kidney grafts to improve their quality and to decrease ischemia/reperfusion injury during transplantation. Our aim was to develop a pig model of simultaneous normothermic perfusion of both kidneys procured from the same donor and to compare the assessment of renal function through the injection of creatinine and iohexol. Method Under general anaesthesia, the donor pigs (n = 5) were euthanized by exsanguination and the blood was recovered using a cell-saving system. Both kidneys (n = 10) were submitted to 30 min of warm and a 2-hour cold ischemia period, before being perfused for 6 hrs at 37°C. Kidney perfusion started and run in parallel using 2 independents, modified extracorporeal machines. Urine production, arterial blood gas exchange, and perfusion parameters (flow, pressure, resistance) were monitored and compared. Creatinine and iohexol were added to the perfusate of both machines to assess renal function. Results A parallel evolution of blood parameters in both perfusions was observed. By maintaining a constant perfusion pressure of 70 mmHg, flow rates increased to 100 mL/min. Despite variations in urinary excretion, creatinine and iohexol clearances remained comparable, demonstrating a parallel kidney function. Conclusion In conclusion, we established a model of parallel and simultaneous normothermic perfusion of pig kidneys, and for the first time, we demonstrated the utility of iohexol measurements for improved functional assessment in an isolated perfusion model. After randomization of the grafts, this model will be used for testing innovative therapies as MSC during perfusion, both in swine kidneys and human discarded grafts, using the contralateral kidney as a paired control.

#621 The effect of intra-operative mean arterial pressure on early graft function in deceased donor kidney transplantation

Abstract Background and Aims The adequate perfusion pressure to the graft is essential for proper graft function in kidney transplantation, especially in deceased donor kidney transplantation. In particular, Mean arterial pressure (MAP) during operation can affect early graft function because MAP is associated with renal blood flow and glomerular filtration rate. Therefore, the analysis of intra-operative parameters are necessary to evaluate adequate graft perfusion. The aim of this study is to investigate the relationship between intra-operative parameters including MAP and early graft function in deceased donor kidney transplantation. Method We retrospectively analyzed 363 recipients who underwent deceased donor kidney transplantation from March 2010 to December 2020. Anesthetic monitoring data during intraoperative period was analyzed and basic clinical parameters were evaluated. Results In total 363 recipients, the mean recipient age was 48.9 ± 10.3 and mean donor age was 48.2 ± 15.2. Anesthetic time was mean 285.9 ± 63.8 (min) and operation time was 226.4 ± 48.7 (min). Median value of baseline MAP and MAP at reperfusion were 124 mmHg and 88 mmHg. After initial analysis, the recipients were divided into two groups, high MAP group (n = 185) and low MAP group (n = 178), according to median value of baseline MAP (124 mmHg) and these two groups were analyzed. High MAP group showed higher estimated glomerular filtration rate (eGFR) and urine output compared to low MAP group during immediate postoperative 1 week. At postoperative day 5, eGFRs were 43.4 ± 26.7 and 37.3 ± 24.2 mL/min/1.73 m2 respectively (p = 0.022) and urine outputs were 2942.6 ± 1368.6 and 2474.3 ± 1199.1 mL respectively (p = 0.001). The incidences of delayed graft function showed no significant difference between two groups (2.2% vs 6.2%, p = 0.066). We additionally analyzed the effect of MAP at reperfusion, and the result showed that there was no significant relationship between MAP at reperfusion and early graft function. Conclusion In this retrospective study, MAP at reperfusion was not significantly related to early graft function and incidence of delayed graft function. In baseline MAP analysis, high baseline MAP group showed early recovery of eGFR and more urine output than low baseline MAP group. As a result, the recipients with high baseline MAP were related to early recovery of graft function in deceased donor kidney transplantation.

Normothermic Machine Perfusion Reduces Transfusion Requirements Even After Static Cold Storage: A 1 y Retrospective Single-center Analysis.

Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements. Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared. After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P < 0.001 and P = 0.018, respectively). In addition, patients in the NMP after SCS group received less fibrinogen concentrate (NMP after SCS group 0 [0-1.5] g versus SCS group 2 [0-4] g; P = 0.0163). No differences in postreperfusion hemodynamics could be detected between groups. This retrospective analysis shows that NMP reduces postreperfusion requirements of red blood cells, platelet concentrates, and fibrinogen concentrate even if installed after a phase of organ SCS, because it may be practiced on most centers where NMP is available.

Effects of extraoral storage time on autologous gingival graft early healing: A split-mouth randomized study.

Despite the established use of palatal tissue grafts for mucogingival procedures, there are no studies on the effect of extraoral storage time on graft outcomes. This prospective split-mouth randomized experimental clinical trial aimed to assess whether gingival graft extraoral storage time affects graft healing. Standardized grafts were harvested from the palate and stored extraorally for 2 (Control) or 40 (Test) minutes before being placed at recipient beds. Intraoral scans, clinical photographs, and tissue blood perfusion were obtained preoperatively, postoperatively, and at follow-up visits (Days 2 (PO2), 3 (PO3), 7 (PO7), and 14 (PO14)). Healing Score Index (HSI) and wound fluid (WF) biomarkers (angiogenin, IL-6, IL-8 (CXCL8), IL-33, VEGF-A, and ENA-78 (CXCL5)) were also assessed. Twenty-three participants completed all study visits. Extraoral storage time was 2.3 ± 1.1 min and 42.8 ± 3.4 min for C and T grafts, respectively (p < .0001). Recipient beds remained open for 21.4 ± 1.7 min. No graft underwent necrosis or failed to heal by PO14. Minimal volumetric changes were observed, without significant intergroup differences (p ≥ .11). Graft perfusion initially decreased post-harvesting before peaking on PO7 for both C and T grafts, with no significant intergroup differences (p ≥ .14). HSI values progressively increased, with no significant intergroup differences (p ≥ .22). WF analysis revealed detectable levels for all biomarkers tested, without significant intergroup differences (p ≥ .23). Extraoral storage time of 40 min has neither statistically significant nor clinically discernible effects on autologous graft revascularization, early healing, or survival, as determined by physiological, wound healing, and molecular parameters.

Untargeted NMR-based metabolomics analysis of kidney allograft perfusates identifies a signature of delayed graft function.

Kidney transplantation (KTx) necessarily conveys an ischemia/reperfusion (I/R) process, which impacts on allograft outcomes. Delayed graft function (DGF) is defined as a non-decrease of serum creatinine by at least 10% daily on 3 consecutive days during the first 7days post-KTx. DGF significantly conditions both short- and long-term graft outcomes. Still there is a lack of DGF predictive biomarkers. This study aimed to explore the potential of kidney graft perfusate metabolomics to predict DGF occurrence. 49 human perfusates from grafts categorized upon donor type [donation after brain death (DBD)/donation after circulatory death (DCD)] and DGF occurrence and 19 perfusates from a murine model classified upon death type (DBD/DCD) were collected and analyzed by NMR-based metabolomics. The multivariate analysis of the murine data highlighted significant differences between perfusate metabolomes of DBD versus DCD. These differences were similarly observed in the human perfusates. After correcting for the type of donor, multivariate analysis of human data demonstrated a metabolomics signature that could be correlated with DGF occurrence. The metabolome of kidney grafts is influenced by the donor's type in both human and pre-clinical studies and could be correlated with DGF in the human DBD cohort. Thus, metabolomic analysis of perfusate applied prior to KTx may represent a new predictive tool for clinicians in a more personalized management of DGF. Moreover, our data paves the way to better understand the impact of donor's types on the biochemical events occurring between death and the hypothermic storage.

Endovascular Treatment of a Multi-visceral Aortic Conduit Blowout With Parallel Stent Grafts and Coils.

Multi-visceral transplantation (MVT) is a complex surgical procedure involving the transplantation of multiple abdominal organs as a single unit, typically used as bailout treatment of patients with devastating abdominal pathologies. Due to the complexity of the procedure, major and even life-threatening complications can happen. Vascular complications, including anastomotic breakdowns or pseudoaneurysms due to infections, can be universally lethal. Open surgical repair is often not an option due to the hostile operative field. We report a case of endovascular salvage of multi-visceral aortic conduit blowout utilizing parallel stent grafts and coils without sacrifice of the transplanted viscera. This combination can successfully control bleeding and maintain graft perfusion in this rare but devastating complication.

The role of cold ischemia time and hypothermic perfusion in predicting early hepatocellular carcinoma recurrences after liver transplantation.

The aim of the study was to identify predictors of early tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). 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. 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). Reducing cold ischemia time and graft perfusion with HOPE can lead to lower rates of early HCC recurrences and higher recurrence-free survival.