Correction: Won et al. Ex Vivo Perfusion Using a Mathematical Modeled, Controlled Gas Exchange Self-Contained Bioreactor Can Maintain a Mouse Kidney for Seven Days. Cells 2022, 11, 1822.

In the original publication [...].

Combining Oxygenated Cold Perfusion With Normothermic Ex Vivo Perfusion Improves the Outcome of Donation After Circulatory Death Porcine Kidney Transplantation.

BACKGROUND: Ex vivo machine perfusion is a novel preservation technique for storing and assessing marginal kidney grafts. All ex vivo perfusion techniques have advantages and shortcomings. The current study analyzed whether a combination of oxygenated hypothermic machine perfusion (oxHMP) followed by a short period of normothermic ex vivo kidney perfusion (NEVKP) could combine the advantages of both techniques. METHODS: Porcine kidneys were exposed to 30 min of warm ischemia followed by perfusion. Kidneys underwent either 16-h NEVKP or 16-h oxHMP. The third group was exposed to 16-h oxHMP followed by 3-h NEVKP (oxHMP + NEVKP group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed up for 8 d. RESULTS: All animals survived the follow-up period. Grafts preserved by continuous NEVKP showed improved function with lower peak serum creatinine and more rapid recovery compared with the other 2 groups. Urine neutrophil gelatinase-associated lipocalin, a marker of kidney injury, was found to be significantly lowered on postoperative day 3 in the oxHMP + NEVKP group compared with the other 2 groups. CONCLUSIONS: A short period of NEVKP after oxHMP provides comparable short-term outcomes to prolonged NEVKP and is superior to oxHMP alone. A combination of oxHMP with end-ischemic NEVKP could be an attractive, practical strategy to combine the advantages of both preservation techniques.

Mixed reality combined with ALPPS for colorectal liver metastases, a case report.

INTRODUCTION: Improvement of treatments for patients suffering from colorectal carcinoma and extended liver metastases has increased the overall survival and enables more patients to undergo surgical therapy. If the future liver remnant (FLR) is expected to be low, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a potential treatment with high feasibility and an increase in overall survival. The evolving mixed reality technology could support hepatobiliary surgery. This case report demonstrates for the first time the combination of mixed reality technology and ALPPS procedure for a patient with low expected FLR. PRESENTATION OF CASE: A 49-year-old patient is presented with adenocarcinoma of the caecum with bilateral liver metastasis. After colon resection, a palliative chemotherapy was administered with good response and partial remission, so curative liver resection was intended. Based on the low expected FLR, calculated from the 3D-model of the liver, we decided to perform an in-situ split resection supported by mixed reality intraoperatively. The total operation time was 6 + 2 h. During both steps no blood transfusion was required and no major complication occurred. The patient was discharged 15 days after the second step. Final pathology revealed multiple predominantly necrotic metastases of the pre-existing colon carcinoma (ypM1, R0). DISCUSSION: After the first step of ALPPS, an increase of the FLR up to 57 % was achieved, so the second step was performed on postoperative day (POD)11. The 3D-model and the intraoperative use of mixed reality supported our decision making and intraoperative navigation. This technique could be implemented on a larger scale to support complex liver resections. CONCLUSION: The combination of mixed reality with ALPPS resulted in a good surgical outcome and should be considered as a potential alternative for liver resections.

Donor, Recipient and Surgeon Sex and Sex-Concordance and their Impact on Liver Transplant Outcome.

(1) Background: Patient sex is associated with differential outcome of many procedures although the exact mechanisms remain unknown. Especially in transplant surgery, surgeon-patient sex-concordance is rarely present for female patients and outcome may be negatively affected. (2) Methods: In this single-center retrospective cohort study, recipient, donor, and surgeon sex were evaluated and short- and long-term outcome was analyzed with regards to sex and sex-concordance of patients, donors, and surgeons. (3) Results: We included 425 recipients in our study; 50.1% of organ donors, 32.7% of recipients, and 13.9% of surgeons were female. Recipient-donor sex concordance was present in 82.7% of female recipients and in 65.7% of male recipients (p = 0.0002). Recipient-surgeon sex concordance was present in 11.5% of female recipients and in 85.0% of male recipients (p < 0.0001). Five-year patient survival was comparable between female and male recipients (70.0% vs. 73.3%, p = 0.3978). Five-year patient survival of female recipients treated by female surgeons was improved without reaching significance (81.3% vs. 68.4%, p = 0.3621). (4) Conclusions: Female recipients and female surgeons are underrepresented in liver transplant surgery. Societal factors influencing outcome of female patients suffering from end-stage organ failure need to be further examined and acted upon to possibly improve the outcome of female liver transplant recipients.

Ex Vivo Perfusion Using a Mathematical Modeled, Controlled Gas Exchange Self-Contained Bioreactor Can Maintain a Mouse Kidney for Seven Days.

Regenerative medicine requires better pre-clinical tools in order to increase the efficiency of novel therapies transitioning to the clinic. Current monolayer cell culture methods are suboptimal for effectively testing new therapies and live mouse models are expensive, time consuming and require invasive procedures. Fetal organ culture, organoids, microfluidics and culture of thick sections of adult organs all aim to fill the knowledge gap between monolayer culture and live mouse studies. Here we report on an ex vivo organ perfusion system that can support whole adult mouse organs. Ex vivo perfusion of healthy and diseased mouse organs allows for real-time analysis that provides immediate feedback and accurate data collection throughout the experiment. Having a suitable normothermic ex vivo perfusion system for mouse organs provides a tool that will help contribute to our understanding of kidney physiology and disease and can take advantage of the many mouse models of human disease that already exist. Furthermore, an ex vivo kidney perfusion system can be used for testing novel cell therapies, drug screening, drug validation and for the detection of nephrotoxic substances. Critical to the success of mouse ex vivo organ perfusion is having a suitable bioreactor to maintain the organ. Here we have focused on the mouse kidney and mathematically modeled, built and validated a bioreactor that can maintain a kidney for 7 days. The long duration of the ex vivo perfusion will help to advance studies on kidney disease and can rapidly test for new regenerative medicine therapies compared to whole animal studies.

Early Allograft Dysfunction After Liver Transplantation With Donation After Circulatory Death and Brain Death Grafts: Does the Donor Type Matter?

BACKGROUND: Early allograft dysfunction (EAD) after liver transplantation has been associated with long-term reduced graft and patient survival. METHODS: In this single-center cohort study, we aimed to compare incidence, risk factors, and outcomes in liver transplant recipients who developed EAD. Patients who received donation after circulatory death (DCD) or donation after brain death (DBD) grafts between January 2007 and December 2017 were included. EAD was defined as bilirubin of ≥10 mg/dL (171 µmol/L) or an international normalized ratio of ≥1.6 on postoperative day 7 or transaminases >2000 U\L in the first-week posttransplantation as previously described. RESULTS: In our cohort of 1068 patients, incidence of EAD was 44%. EAD occurred more frequently in the DCD versus DBD group (71% versus 41%, P < 0.01). Overall, recipients who developed EAD showed a significantly lower graft and patient survival at 1, 3, and 5 y after transplantation (all P < 0.05). This was also the case for recipients of DBD grafts. However, for recipients of DCD grafts, patient and graft survival were not affected by the presence of EAD. For recipients of DBD grafts, donor age, body mass index (BMI) and gender, recipient BMI and model for end-stage liver disease score and warm and cold ischemia time were associated with EAD. For DCD recipients, donor BMI and cold ischemia time were associated with EAD. CONCLUSIONS: In our cohort study, EAD resulted in reduced long-term patient and graft survival only for DBD recipients but not for DCD recipients. Predictive markers for EAD were dependent on the donor type.

Defatting strategies in the current era of liver steatosis.

Liver steatosis is emerging as a major cause of chronic liver disease worldwide, mainly due to the increasing rate of obesity, type 2 diabetes, and metabolic syndrome. Because of the increased incidence of liver steatosis, many organs are currently declined for transplantation despite high demand and waiting list mortality. Defatting strategies have recently emerged as a means of rapidly reducing liver steatosis to expand the pool of available organs. This review summarises advances in defatting strategies in experimental and human models of liver steatosis over the last 20 years.