Graft Preservation Research Articles

THE TELL-TALE HEART. MACHINE PERFUSION IN HEART TRANSPLANTATION

Hear Transplantation (HTx) is the current best surgical treatment for patients affected by end-stage heart failure. However, the improvement of medical and interventional therapies has led to an increasingly old and high-risk population of HTx candidates. Moreover, the use of “extended” donor criteria to face the shortage of donors could increase the risk of worse outcomes after HTx. In this setting, donor organ preservation strategy could significantly affect HTx results. The cold storage (CS) represents the standard practice worldwide for donor graft preservation. However, prolonged ischemic time is known to be an independent risk factor for mortality after HTx. Machine perfusion (MP) systems continuously perfuse the donor heart, reducing ischemic time. Also, since MP permits to evaluate marginal donor organs, they could represent a safe and effective technique to expand the available donor pool. Despite the increasing number of donor hearts preserved with MP, whether MP could be considered superior to traditional CS still represents a matter of debate. The aim of this paper is to summarize and critically assess the available clinical data on MP employed for HTx.

A Comparative Study Using Fluorescent Confocal Microscopy and Flow Cytometry to Evaluate Chondrocyte Viability in Human Osteochondral Allografts.

The preservation conditions of fresh osteochondral allografts for clinical applications are critical due their objective: to transplant mature hyaline cartilage containing viable chondrocytes, maintaining their metabolic activity and also preserving the structural and functional characteristics of the extracellular matrix. The aim of the present study was to compare fluorescence confocal microscopy and flow cytometry techniques to evaluate the viability of the chondrocytes present in the osteochondral tissue, in order to determine their effectiveness and thus ensure reproducibility and robustness of the analysis. To this end, osteochondral allografts from human cadaveric donors were preserved at 4 °C for 3 weeks in a preservation medium supplemented with antibiotic and antifungal agents. Cell viability of chondrocytes was determined by monitoring the cartilage for 3 weeks of preservation by confocal fluorescence microscopy and flow cytometry, obtaining cell viabilities of 83.7 ± 2.6% and 55.8 ± 7.8% for week three, respectively. The confocal fluorescence microscopy approach is more advantageous and accurate, as it correlates better with actual cell viability values for monitoring osteochondral graft preservation, detecting only the cells that died a natural death associated with the preservation method.

Macrophage-mediated extracellular matrix remodeling after fat grafting in nude mice.

Clinical unpredictability and variability following fat grafting remain non-negligible problems due to the unknown mechanism of grafted fat retention. The role of the extracellular matrix (ECM), which renders cells with structural and biochemical support, has been ignored. This study aimed to clarify the ECM remodeling process, related cellular events, and the spatiotemporal relationship between ECM remodeling and adipocyte survival and adipogenesis after fat grafting. Labeled Coleman fat by the matrix-tracing technique was grafted in nude mice. The ECM remodeling process and cellular events were assessed in vivo. The related cytokines were evaluated by qRT-PCR. An in vitro cell migration assay was performed to verify the chemotactic effect of M2-like macrophages on fibroblasts. The results demonstrated that in the periphery, most of the adipocytes of the graft survived or regenerated, and the graft-derived ECM was gradually replaced by the newly-formed ECM. In the central parts, most adipocytes in the grafts died shortly after, and a small part of the graft-derived and newly-formed ECM was expressed with irregular morphology. Adipose ECM remodeling is associated with increased infiltration of macrophages and fibroblasts, as well as up-regulated expression of cytokines in the adipose tissue. To sum up, our results describe the various preservation mode of fat grafts after transplantation and underscore the importance of macrophage-mediated ECM remodeling in graft preservation after fat grafting. The appreciation and manipulation of underlying mechanisms that are operant in this setting stand to explore new therapeutic approaches and improve clinical outcomes of fat grafting.

Non-cryopreserved peripheral blood stem cells as a safe and effective alternative for autologous transplantation in multiple myeloma.

Autologous stem cell transplantation is the standard procedure for multiple myeloma and the grafts are usually cryopreserved. Previous studies reported advantages in the use of fresh peripheral blood stem cells (PBSC) autotransplantation compared to cryopreservation of the grafts. This study compared the transplant-related outcomes of two graft preservation methods: fresh storage (4°C/72 h) and cryopreservation (-80°C). We performed an analysis of 45 patients with multiple myeloma under autotransplantation (17 fresh and 28 cryopreserved) from 2017 to 2021. Fresh PBSC were maintained in the refrigerator for three days in a concentration up to 300 × 103 TNC/μL. Cryopreserved PBSC were concentrated by plasma reduction after centrifugation (950 g/10min/4°C) and an equal volume of cryoprotection solution was added for a final concentration of 300 × 103 TNC/μL, 5% DMSO, 6% hydroxyethyl starch, and 3% human albumin. Neutrophil engraftment was significantly faster with fresh PBSCs (10 vs. 11.5 days, p=0.045). Adverse effects were more common in cryopreserved PBSC transplantation (75% vs. 35.3% patients; p=0.013). Post transplantation hospital stay was 20 and 22 days for fresh and cryopreserved PBSCs respectively (p=0.091). There was no difference in platelet engraftment time (10.5 days for both; p=0.133), number of antibiotics used after transplantation (3 for fresh and 2.5 for cryopreserved; p=0.828), days of antibiotic use after transplantation (12.2 days for fresh and 13.3 days for cryopreserved, p=0.579), and overall survival (p=0.736). The infusion of fresh PBSC refrigerated for up to three days is effective and safe for autologous transplantation in patients with multiple myeloma, which is a useful alternative to cryopreserved PBSC.

Extra-Anatomic Bypass and Excision is Superior to Graft Salvage Attempts with Antibiotic Beads to Treat Vascular Graft Infections in the Groin

This study aimed to determine if conventional extra-anatomic bypass and graft removal versus aggressive attempts at graft preservation have better survival and limb salvage in patients with localized groin wound infections of vascular grafts. We conducted a retrospective review of 53 consecutive patients with vascular graft infections presenting in the groin. Treatment groups consisted of group 1 (extra-anatomic bypass and graft excision, n=22) and group 2 (initial graft preservation attempts with utilization of antibiotic beads, n=31). In group 2, patients underwent serial debridement and placement of antibiotic beads until culture-negative wounds were achieved. Significantly more patients underwent muscle flap coverage in group 2 (27/31) compared with group 1 (7/22; P<0.001). Data collected included demographics, comorbidities, intraoperative details, and outcomes, including patency, limb salvage, mortality, and number of procedures. Continuous variables were examined with Student's t-test, and dichotomous variables were examined with chi-squared test. Linear and logistic regressions were used to analyze factors associated with outcomes, in addition to Kaplan-Meier analysis with log rankfor actuarial analysis. Both groups were similar with respect to demographics. The overall Kaplan-Meier 1- and 3-year survival rates were 66.2% and 34.1%, with no statistically significant difference between groups. The Kaplan-Meier 1- and 3-year limb salvage rates were 68.8% and 36.6% for group 1 vs. 58.5% and 38.7% for group 2 (P=not significant [NS]). The 1- and 3-year primary patency rates were 71% and 71% in traditional group 1 vs. 72% and 56% in group 2 (P=NS). One-year and 3-year secondary patency rates in traditional group 1 were 83% and 71% vs. 85% and 61% in group 2 (P=NS). Patients in group 1 underwent fewer total procedures when compared with group 2 (2.3±0.2 vs. 5.1±0.7, P=0.03). The late reinfection rate was significantly less in group 1 (4.5%) compared with group 2 (26%; P=0.04). Freedom from reinfection at 1 and 3 years were 94% and 94% in traditional group 1 vs. 74% and 62% in group 2 (P=0.03). Multivariable analysis showed a higher incidence of amputation in patients who suffered reinfection (n=13, P=0.049). There was a higher mortality in patients with septic shock (n=10, P=0.007) and reinfection (n=13, P=0.036). Reinfection was associated with the highest mortality (P=0.03). Conventional graft excision with extra-anatomic bypass resulted in similar mortality when compared with aggressive attempts at graft preservation and trended toward improved limb salvage and patency. However, attempts at graft preservation with antibiotic beads resulted in a significantly higher reinfection rate and greater number of procedures, and therefore, this approach should be used very selectively.

P9.14: Massive Blood Transfusion: Risk Factors and Consequences

Introduction: Massive blood transfusion (MBT) is a common occurrence in liver transplant patients. Recipient-related risk factors include cirrhosis, history of multiple surgeries and suboptimal donors. And, while advances in surgical techniques, anaesthetic management and graft preservation have decreased the need for transfusions, this complication has not been completely eliminated. Materials and Methods: One thousand four hundred and sixty nine liver transplants were performed at our institution between May 1998 and December 2019, and data was available regarding transfusion for 1469 of them. We divided the patients into two groups, with regards to transfusion of 6 or more units of packed red blood cells in the first 24 hours post transplant, and we analyzed the differences between the groups. We analyzed the risk factors for massive transfusion, as well as factors that influence patient survival by using Cox regression. Results: Out of the 1198 patients, 607 (50.7%) met criteria for massive transfusion.Both groups were statistically different with regards to hepatocellular carcinoma, autoimmune cause, liver/kidney transplant, uDCD, retransplantation, albumin serum levels, creatinine, sodium, bilirubin, haemoglobin, platelets, INR, MELD, McCluskey and Child scores. Out of the variables from the McCluskey index, only the following were significant for massive bleeding: Haemoglobin <10, INR >2 and creatinine >1.2. We contrasted the efficiency of all of the previously mentioned scores for capacity to predict massive transfusion, but none reached an area below the curve above 0.7. Survival was statistically lower at 1, 3, and 5 years when comparing the groups that had MBT compared to those that did not (92,6%, 85,2% and 79,7% respectively in the non MBT group, vs. 78,1%, 71,6% y 66,8%, respectively, in the MBT group). Regarding survival analysis, MBT was associated with a 1.5 mortality risk as opposed to no MBT. Conclusion: Massive blood transfusion impacts patient survival in a statistically significant way. The most significant risk factors are preoperative haemoglobin, INR and creatinine.

Management of renal cell carcinoma in transplant kidney: a systematic review and meta-analysis.

After transplantation, approximately 10% of renal cell carcinomas are detected in graft kidneys. These tumors (gRCC) present surgeons with the difficulty of finding a treatment that guarantees both oncological clearance and maintenance of function. We conducted a systematic review and an individual patient data meta-analysis on the oncology, safety and functional outcomes of the available treatments for gRCC. A systematic search was performed across MEDLINE, EMBASE, and Web of Science including any study reporting perioperative, functional and survival outcomes for patients undergoing graft nephrectomy (GN), partial nephrectomy (PN) or thermal ablation (TA) for gRCC. Quade's ANCOVA, Spearman Rho and Pearson χ2, Kaplan-Meier, Log-rank and Standard Cox regression and other tests were used to compare treatments. Studies' quality was evaluated using a modified version of Newcastle Ottawa Scale. A number of 29 studies (357 patients) were included. No differences between TA and PN were found in terms of safety, functional and oncological outcomes for T1a gRCCs. When applied to pT1b gRCC, PN showed no difference in complications, progression or cancer-specific deaths compared to smaller lesions; PN validity for pT2 gRCCs should be considered unverified due to lack of sufficient evidence. The efficacy and safety of PN or TA for multiple gRCC remain controversial. In case of non-functioning, large (T≥2), complicated or metastatic gRCCs, GN appears to be the most reasonable choice. Quality of evidence ranged from very low to moderate. Studies with large cohorts and longer follow-up are still needed to clarify oncological and functional differences. PN and TA might be offered as a nephron-sparing treatment in patients with T1a gRCC. There is no significant difference between these options and GN in terms of oncological outcomes and complications. PN and TA offer similar functional outcomes and graft preservation. PN for T1b gRCC seems feasible and safe, but its validity should be considered unverified.

1035 Gender Equality in Heart Transplantation: A Single Centre Study

Abstract Background International Society for Heart and Lung Transplantation catergoirises female gender in donor/recipient, as a significant risk factor for mortality after heart transplantation. Further, donor-recipient gender mismatch is also reported to be a determinant of post-transplant morbidity/mortality. To examine the effect of gender in survival outcomes, we conducted a retrospective study. Method Population comprised of 298 patients undergoing heart transplantation from 2001 to 2021, divided into four groups on the basis of donor and recipient matching. Group A consisted of men who received male donor-hearts, group B of women who received female donor-hearts, group C of women who received male donor-hearts, and group D of men who received female donor-hearts. Standard heart transplantation protocols were applied to all patient groups for graft preservation, surgical technique, donor-recipient size matching, induction &amp; immunosuppressive therapy. Results The study groups were found to be homogeneous to the major preoperative- risk- factors (aetiology, transplantation status, donor-recipient-age, total ischemic time). Donor gender, recipient gender and donor-recipient gender mismatching did not significantly modify the short and mid-term survivals, functional recovery, and primary graft dysfunction post-surgery. Conclusions Even though previous reports suggest that gender negatively affects survival, this proved to have no influence on the outcomes in our study. These results can be explained by a correct donor-recipient size matching. The well-documented female recipients’ tendency to more frequent and fatal rejection was not confirmed in our experience. The patient's age at transplantation, the routine use of induction therapy and an aggressive immunosuppressive regimen may be the substrate of these findings.

1036 Gender Equality in Heart Transplantation: A Single Centre Study

Abstract Background International Society for Heart and Lung Transplantation categorises female gender in donor/recipient, as a significant risk factor for mortality after heart transplantation. Further, donor-recipient gender mismatch is also reported to be a determinant of post-transplant morbidity/mortality. To examine the effect of gender in survival outcomes, we conducted a retrospective study. Method Population comprised of 298 patients undergoing heart transplantation from 2001 to 2021, divided into four groups on the basis of donor and recipient matching. Group A consisted of men who received male donor-hearts, group B of women who received female donor-hearts, group C of women who received male donor-hearts, and group D of men who received female donor-hearts. Standard heart transplantation protocols were applied to all patient groups for graft preservation, surgical technique, donor-recipient size matching, induction &amp; immunosuppressive-therapy. Results The study groups were found to be homogeneous to the major preoperative- risk- factors (aetiology, transplantation status, donor-recipient-age, total ischemic time). Donor gender, recipient gender and donor-recipient gender mismatching did not significantly modify the short and mid-term survivals, functional recovery, and primary graft dysfunction post-surgery. Conclusions Even though previous reports suggest that gender negatively affects survival, this proved to have no influence on the outcomes in our study. These results can be explained by a correct donor-recipient size matching. The well-documented female recipients’ tendency to more frequent and fatal rejection was not confirmed in our experience. The patient's age at transplantation, the routine use of induction therapy and an aggressive immunosuppressive regimen may be the substrate of these findings.

Two decades of experience in explantation and graft preserving strategies following primary endovascular aneurysm repair and lessons learned.

We aim to scrutinize our evolving re-intervention strategies following primary endovascular aortic aneurysm repair (EVAR) - EVAR GORE SalvAge Fabric Technique (ARAFAT), aortic sac double breasting with endograft preservation, and stent-graft explantation. We performed 1,555 aortic interventions over the study period, including 910 EVARs. Factors associated with the need for reintervention and the likelihood of chronic fabric fatigue failure (CFFF) were investigated. Using conventional and innovative diagnostic modalities with Prone contrASt enHanced computed tomography Angiography (PASHA), 136 endoleaks (ELs) were identified (15 type I, 98 type II; 18 type III; 5 type IV). Forty-four (4.84%) patients underwent re-intervention post-primary EVAR; 18 ARAFATs, 12 double breastings, and 14 explantations. Choice of re-intervention was based on patient fitness and mode of failure. Mean EL detection duration following primary EVAR was 53.3 ± 6.82 months, while mean time to re-intervention was 70.20 ± 6.98 months. The mean sac size before the primary EVAR and re-intervention was 6.00 ± 1.75 cm and 7.51 ± 1.94 cm, respectively. Polyester (61.40%) was the most commonly employed stent-graft material. Use of more than three modular stent-graft components (3.42 ± 1.31, p = 0.846); with the proximal stent-graft diameter of 31.6 ± 3.80 cm (p = 0.651) and the use of iliac limbs more than 17 mm (p = 0.364), all added together are contributing factors. We had one peri-operative mortality following explantation due to sepsis-induced multiorgan failure. Our re-intervention strategies matured from stent graft explantation to graft preservation with endovascular relining of the stent-graft. Graft preservation with aortic sacotomy and double breasting were used to manage concealed ELs due to aortic hygroma.

Graft preservation confers myocardial protection during coronary artery bypass grafting.

BackgroundDuring on-pump coronary artery bypass grafting (ONCAB), graft flushing for distal anastomoses testing also perfuses the downstream myocardium. This single-center retrospective study evaluated the impact of specific preservation solutions on myocardial protection during ONCAB.Materials and methodsBetween July 2019 and March 2020 either DuraGraft (DG) or 0.9% Saline/Biseko (SB) was applied to 272 ONCAB. Overall, 166 patients were propensity-matched into two groups. Cardiac enzymes [high-sensitive Troponin I (hs-TnI) and creatine kinase (CK)] were evaluated 7 days post-surgery.ResultsPost-surgery, hs-TnI values were significantly lower from 3 to 6 h (h) up to 4 days in the DG group: 3–6 h: 4,034 ng/L [IQR 1,853–8,654] vs. 5,532 ng/L [IQR 3,633—8,862], p = 0.05; 12–24 h: 2,420 ng/L [IQR 1,408–5,782] vs. 4,166 [IQR 2,052–8,624], p < 0.01; 2 days: 1,095 ng/L [IQR 479–2,311] vs. 1,564 ng/L [IQR 659–5,057], p = 0.02 and at 4 days: 488 ng/L [IQR 232–1,061] vs. 745 ng/L [IQR 319–1,820], p = 0.03. The maximum value: 4,151 ng/L [IQR 2,056–8,621] vs. 6,349 ng/L [IQR 4,061–12,664], p < 0.01 and the median area under the curve (AUC): 6,146 ng/L/24 h [IQR 3,121–13,248] vs. 10,735 ng/L/24 h [IQR 4,859–21,484], p = 0.02 were lower in the DG group. CK values were not significantly different between groups: maximum value 690 [IQR 417–947] vs. 631 [464–979], p = 0.61 and AUC 1,986 [1,226–2,899] vs. 2,081 [1,311–3,063], p = 0.37.ConclusionRepeated graft flushing with DG resulted in lower Troponin values post-surgery suggesting enhanced myocardial protection compared to SB. Additional studies are warranted to further assess the myocardial protection properties of DG.

Normothermic machine perfusion of kidneys: current strategies and future perspectives.

This review aims to summarize the latest original preclinical and clinical articles in the setting of normothermic machine perfusion (NMP) of kidney grafts. Kidney NMP can be safely translated into the clinical routine and there is increasing evidence that NMP may be beneficial in graft preservation especially in marginal kidney grafts. Due to the near-physiological state during NMP, this technology may be used as an ex-vivo organ assessment and treatment platform. There are reports on the application of mesenchymal stromal/stem cells, multipotent adult progenitor cells and microRNA during kidney NMP, with first data indicating that these therapies indeed lead to a decrease in inflammatory response and kidney injury. Together with the demonstrated possibility of prolonged ex-vivo perfusion without significant graft damage, NMP could not only be used as a tool to perform preimplant graft assessment. Some evidence exists that it truly has the potential to be a platform to treat and repair injured kidney grafts, thereby significantly reducing the number of declined organs. Kidney NMP is feasible and can potentially increase the donor pool not only by preimplant graft assessment, but also by ex-vivo graft treatment.

Evaluation of new solution for cardiac graft preservation on cellular model

Evaluation of new solution for cardiac graft preservation on cellular model. Organ transplantation faces a growing shortage of grafts. To deal with this, surgeons have to consider organs from so-called “extended criteria” donors (elderly donors, smokers, donors with co-morbidities…) with increased sensitivity to ischemia-reperfusion injury. To improve preservation of these grafts, two approaches are possible: static preservation or dynamic preservation. Our laboratory has developed and patented a new solution, called LYPS (LYon Preservative Solution), intended for these two situations. The objective of the present study is to demonstrate the superiority of the LYPS compare to the other solutions currently used in clinical practice. In order to simultaneously study the effect of different solutions on cell conservation at different temperatures, we used a “Hypothermal Bioreactor”, specially developed for this work. We determined the impact of 6 different preservative solutions (LYPS, Celsior, UW, custodiol, Plegisol and IGL1) on H9C2 cells. We performed a 20 hours cold (5 °C) or mild hypothermic (20 °C) static preservation and 2 h of warm so-called “reoxygenation” (37 °C). Cell viability was assessed by MTT assay; and PI and Dilc1 staining determined cell necrosis and mitochondrial membrane potential by flow cytometry. We used a new automated cell imaging system (ImageXpress Pico) and metabolic biosensors to evaluate cytosolic NAD+ levels with SoNar and mitochondrial ATP levels modifications with ATeam-mito. It appears that, at the two temperatures studied (5 and 20 °C), the LYPS solution provides better viability at 5 and 20 °C (viability increased by 5.75 and 11.57 times compare to Plegisol). Necrosis after 20 h of preservation reached 17.3% and 13.54% at 5 and 20 °C with LYPS that is statically lower compared to the others solutions used. We also observed a smaller decrease of DYm with the use of LYPS solution. The levels of NAD and ATP were monitored and seem to be less impacted by the 20 hours of preservation in the presence of LYPS compared to the other solutions. All of these data show that the LYPS solution seems superior to the other solutions tested for the preservation of H9C2 cardiac cells, whether at 5 or at 20 °C. The following step is now to evaluate LYPS on heart preservation on porcine preclinical model.

Arterial graft preservation with an endothelial damage inhibitor reduces vascular dysfunction in a rat model of in vitro ischemia/reperfusion injury

Coronary artery bypass grafting (CABG) with autologous conduits is a common surgical operation to redirect blood flow to the ischemic myocardium. Vascular ischemia/reperfusion injury (IR) occurs during graft harvest and implantation, and can lead to endothelial dysfunction. DuraGraft®, a novel one-time intraoperative vascular graft treatment, has been shown to protect integrity and function in saphenous vein grafts against IRI. We compared the effect of DuraGraft® to saline solution on arterial grafts submitted to IRI. Rat thoracic aorta was harvested, prepared, and immediately mounted in organ bath chambers (control, n = 7 rats) or underwent 24-hour cold ischemic preservation (4 °C) either in physiological saline (IR, n = 9 rats) or DuraGraft® (IR + Dura, n = 9 rats). Reperfusion-associated endothelial injury was simulated by hypochlorite. Vascular function was measured ex vivo and immunohistochemistry was performed. Impaired maximal vasorelaxation (Rmax) to acetylcholine (ACh) in the IR-group compared to controls was ameliorated by DuraGraft®, indicating an improvement in endothelial function (Rmax to ACh (%): IR + Dura 73 ± 2 vs. IR 48 ± 3, P < 0.05). Additionally, decreased aortic ring sensitivity to ACh (pD2-value: -log 50% maximum response) seen after IR in the saline group was increased by DuraGraft® (pD2 to ACh: IR + Dura 7.1 ± 0.1 vs. IR 6.3 ± 0.2, P < 0.05). Impaired maximum contractile response to phenylephrine and high K+-induced depolarization in the IR-group compared to controls was improved by DuraGraft®. Immunohistochemical analysis for ICAM-1 showed positivity confined to the endothelial layer in the IR group compared to controls, which was decreased by the preservation of aortic rings with DuraGraft®. Furthermore, DuraGraft® decreased nitrotyrosine immunoreactivity in the IR + DuraGraft® compared to both control and IR groups. Also, endothelial PECAM-1 immunoreactivity was significantly reduced in the IR rings compared to controls, whereas a similar pattern was observed between control and IR + Duragraft® groups. DuraGraft® alleviates vascular dysfunction following in vitro IR injury, in part, by reducing nitro-oxidative stress and by lowering inflammatory response through ICAM-1.

Normothermic Machine Perfusion—Improving the Supply of Transplantable Livers for High-Risk Recipients

The effectiveness of liver transplantation to cure numerous diseases, alleviate suffering, and improve patient survival has led to an ever increasing demand. Improvements in preoperative management, surgical technique, and postoperative care have allowed increasingly complicated and high-risk patients to be safely transplanted. As a result, many patients are safely transplanted in the modern era that would have been considered untransplantable in times gone by. Despite this, more gains are possible as the science behind transplantation is increasingly understood. Normothermic machine perfusion of liver grafts builds on these gains further by increasing the safe use of grafts with suboptimal features, through objective assessment of both hepatocyte and cholangiocyte function. This technology can minimize cold ischemia, but prolong total preservation time, with particular benefits for suboptimal grafts and surgically challenging recipients. In addition to more physiological and favorable preservation conditions for grafts with risk factors for poor outcome, the extended preservation time benefits operative logistics by allowing a careful explant and complicated vascular reconstruction when presented with challenging surgical scenarios. This technology represents a significant advancement in graft preservation techniques and the transplant community must continue to incorporate this technology to ensure the benefits of liver transplant are maximized.

Human Thrombin–Gelatin Matrix With Rifampin: Novel Technique for Treating Vascular Graft Infections

Approximately 1% to 6% of prosthetic vascular grafts will be complicated by infections. However, the mortality rates range from 17% to 40%, and morbidity is also high, including reinfection rates reported at 18% and limb loss close to 11%. Early aggressive surgical management, including graft excision and wide wound debridement with extra-anatomic bypass creation is the reference standard. Graft preservation techniques have been increasingly used, with high cure rates. Muscle flap, coverage, and antibiotic-coated absorbable and nonabsorbable beads have been reported to provide high cure rates but, owing to the associated technical difficulties, with suboptimal graft salvage rates.

Human Thrombin–Gelatin Matrix With Rifampin: A Novel Technique for Treating Vascular Graft Infections

Approximately 1% to 6% of prosthetic vascular grafts will be complicated by infection. However, the mortality rates have ranged from 17% to 40%, and the morbidity is also high, including reinfection rates reported at 18% and limb loss close to 11%. Early aggressive surgical management, including graft excision and wide wound debridement with extra-anatomic bypass creation is the reference standard. Graft preservation techniques have been increasingly used, with high cure rates. Muscle flap, coverage, and antibiotic-coated absorbable and nonabsorbable beads have been reported to provide high cure rates but with associated technical difficulties and suboptimal graft salvage rates. We implemented a novel technique for localized antibiotic therapy using a human thrombin–gelatin matrix with rifampin (HTGM+R) at our institution for the past 5 years (Figs 1 and 2). We have described the rates of graft salvage, reintervention, limb salvage, and infection recurrence. We performed a retrospective cohort study of patients who had presented with prosthetic vascular graft infection from January 2016 through June 2021 and had been treated using our novel technique. Statistical analysis included descriptive frequencies of the demographic variables and outcomes of interest. A total number of 16 patients with a total of 32 interventions were included in the present study. Approximately 76.5% had required two or more interventions. HGTM+R was used for 15 interventions (46.9%) in 14 patients. Thrombectomy was the second most common intervention (n = 11; 34.4%). The mean age was 65.2 years, and the mean body mass index was 26.7 kg/m2. The common comorbidities are shown in the Table. The graft salvage rate was 80%, the limb salvage rate was 93.3%, and the freedom from infection rate was 86.7% for HGTM+R. However, the reintervention rate was 28.6%. Only four patients had required graft excision at an average follow-up of 12 months. Hypertension was the most common comorbidity, followed by diabetes and steroid use. Finally, no association with specific bacteria was seen. To date and to the best of our knowledge, the present study is the only study to describe this novel technique for treating prosthetic vascular graft infections. Moreover, it is the only study to describe the outcomes of HGTM+R in the treatment of prosthetic vascular graft infection.Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Normothermic Machine Perfusion as a Tool for Safe Transplantation of High-Risk Recipients

Normothermic machine perfusion (NMP) should no longer be considered a novel liver graft preservation strategy, but rather viewed as the standard of care for certain graft–recipient scenarios. The ability of NMP to improve the safe utilisation of liver grafts has been demonstrated in several publications, from numerous centres. This is partly mediated by its ability to limit the cold ischaemic time while also extending the total preservation period, facilitating the difficult logistics of a challenging transplant operation. Viability assessment of both the hepatocytes and cholangiocytes with NMP is much debated, with numerous different parameters and thresholds associated with a reduction in the incidence of primary non-function and biliary strictures. Maximising the utilisation of liver grafts is important as many patients require transplantation on an urgent basis, the waiting list is long, and significant morbidity and mortality is experienced by patients awaiting transplants. If applied in an appropriate manner, NMP has the ability to expand the pool of grafts available for even the sickest and most challenging of recipients. In addition, this is the group of patients that consume significant healthcare resources and, therefore, justify the additional expense of NMP. This review describes, with case examples, how NMP can be utilised to salvage suboptimal grafts, and our approach of transplanting them into high-risk recipients.

Biventricular Assist Devices for Acute Heart Failure After Orthotopic Liver Transplantation

Background: Medical comorbidities augment surgical risk of liver transplantation. This is a report of immediate post-operative biventricular failure following liver transplant requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO) and subsequent conversion to minimally invasive biventricular assist devices (BIVAD) for cardiac recovery and liver graft preservation. Case Report: 66-year-old male decompensated alcoholic cirrhotic with a pre-operative stress echocardiogram (ECHO) showing no significant valvular or coronary disease and a left ventricular ejection fraction (LVEF) of 65% underwent liver transplantation. Transesophageal echocardiogram at the conclusion of the case demonstrated a LVEF of 10% with biventricular dysfunction and severe mitral regurgitation requiring four pressors. VA-ECMO was initiated for temporary stabilization with subsequent transition to biventricular support using an Impella® 5.5 left ventricular device (VAD) via axillary artery graft and a Protek-Duo percutaneous right VAD via the right internal jugular vein, both placed peripherally through a minimally invasive approach. Serial echocardiograms showed recovery of myocardial function. BIVAD were removed on day 8 and day 13. Excellent liver function was maintained. Conclusion: This is the first report of minimally invasive BIVAD used for acute cardiogenic shock after liver transplantation. A multidisciplinary team approach to prompt mechanical support ensured preservation of liver graft while allowing for cardiac recovery.

Perfusate Metabolomics Content and Expression of Tubular Transporters During Human Kidney Graft Preservation by Hypothermic Machine Perfusion.

Ischemia-related injury during the preimplantation period impacts kidney graft outcome. Evaluating these lesions by a noninvasive approach before transplantation could help us to understand graft injury mechanisms and identify potential biomarkers predictive of graft outcomes. This study aims to determine the metabolomic content of graft perfusion fluids and its dependence on preservation time and to explore whether tubular transporters are possibly involved in metabolomics variations. Kidneys were stored on hypothermic perfusion machines. We evaluated the metabolomic profiles of perfusion fluids (n = 35) using liquid chromatography coupled with tandem mass spectrometry and studied the transcriptional expression of tubular transporters on preimplantation biopsies (n = 26), both collected at the end of graft perfusion. We used univariate and multivariate analyses to assess the impact of perfusion time on these parameters and their relationship with graft outcome. Seventy-two metabolites were found in preservation fluids at the end of perfusion, of which 40% were already present in the native conservation solution. We observed an increase of 23 metabolites with a longer perfusion time and a decrease of 8. The predictive model for time-dependent variation of metabolomics content showed good performance (R 2 = 76%, Q 2 = 54%, accuracy = 41%, and permutation test significant). Perfusion time did not affect the mRNA expression of transporters. We found no correlation between metabolomics and transporters expression. Neither the metabolomics content nor transporter expression was predictive of graft outcome. Our results call for further studies, focusing on both intra- and extratissue metabolome, to investigate whether transporter alterations can explain the variations observed in the preimplantation period.