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With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs . 31.7%, in SCS group ( p  =  0.05 ). Primary non-function was 3.3% for SCS-L vs . 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs .344 U/L, p  =  0.007 ). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT.

In September 2022, Belgium implemented a nationally reimbursed HMP service for all ECD and DCD kidneys procured and transplanted within the country. We retrospectively analyzed data from 242 kidney transplantations preserved with continuous HMP between October 2022 and September 2023. Active oxygenation (HMPO 2 ) was applied in DCD donors aged >50 years. One-year outcomes for all HMP kidneys included delayed graft function (DGF) in 14.4%, estimated glomerular filtration rate of 50 mL/min/1.73 m 2 , 10.1% acute rejection, 96.3% death-censored graft survival, and 98.3% patient survival. DGF rates were lower in ECD kidneys (9.1%) and in DCD ≤50 years (9.5%), while higher in DCD >50 years (19.6%). National transplantation rates of DCD kidneys significantly increased from 90 to 175 per year (p < 0.0001), but not for ECD kidneys (from 45 to 54 per year (p = 0.2965) post-HMP implementation without affecting kidney export. The annual cost savings from reduced dialysis requirements were estimated at €3.59 million. The national implementation of a centralized HMP service in Belgium led to excellent one-year transplant outcomes, increased utilization of ECD and DCD kidneys, and substantial healthcare cost savings. These findings support HMP, and where appropriate HMPO 2 , as the new standard of care for kidney preservation in Belgium, with potential implications for broader international collaboration.

IntroductionThe introduction of perfusion technologies in kidney transplantation has the potential to improve graft function and survival and increase utilisation. Our previous work demonstrated that kidneys with an enhanced inflammatory and immune response during normothermic machine perfusion (NMP) had significant graft dysfunction after transplantation. The addition of a cytokine filter (CytoSorb) to the NMP circuit dramatically reduces both circulating inflammatory mediators and inflammatory gene expression, but this has not been trialled in clinical practice.Methods and analysisThis is a randomised phase 1 pilot study to evaluate the safety and feasibility of using a CytoSorb filter in clinical NMP to remove inflammatory and immune mediators. Eligible kidney transplant recipients on the waiting list in the East of England will be approached for consent. A total of 20 patients will be recruited and randomised in a 1:1 ratio for the donor kidney to receive either NMP or NMP with a CytoSorb filter pre-transplantation. The kidney will be transplanted according to standard practice after NMP. The primary endpoint is inflammatory and immune gene expression measured in a cortical biopsy from the kidney 60 min post-transplant. Secondary endpoints include rates and duration of delayed graft function and graft function as assessed by change in creatinine clearance and estimated glomerular filtration rate 2 days, 5 days, 1 month and 3 months post-transplant. Additionally, inflammatory mediators and injury markers will be measured in peripheral blood and urine samples taken pre-operatively and on days 2 and 5 after transplant.Ethics and disseminationThis study has been approved by the Health Research Authority Health and Care Research Wales Committee (REC 23/WM/0141) and by National Health Service (NHS) Blood and Transplant (Ref: Study 148). Findings will be published in a peer-reviewed journal and disseminated at scientific conferences. The dataset will be made available on request.Trial registrationThe study is prospectively registered on the ISCRTN registry (ID: 13698207).

Hypothermic machine perfusion (HMP) is increasingly investigated as a means to assess liver quality, but data on viability markers is inconsistent and the effects of different perfusion routes and oxygenation on perfusion biomarkers are unclear. This is a single-centre, randomised, multi-arm, parallel study using discarded human livers for evaluation of HMP using arterial, oxygen-supplemented venous and non-oxygen-supplemented venous perfusion. The study included 2 stages: in the first stage, 25 livers were randomised into static cold storage (n = 7), hepatic artery HMP (n = 10), and non-oxygen-supplemented portal vein HMP (n = 8). In the second stage, 20 livers were randomised into oxygen-supplemented and non-oxygen-supplemented portal vein HMP (n = 11 and 9, respectively). Changes in dynamic, biochemical, and morphologic parameters during 4-hour preservation were compared between perfusion groups, and between potentially transplantable and non-transplantable livers. During arterial perfusion, resistance was higher and flow was lower than venous perfusion (p = 0.001 and 0.01, respectively); this was associated with higher perfusate markers during arterial perfusion (p>0.05). Supplementary oxygen did not cause a significant alteration in the studied parameters. Morphology was similar between static and dynamic preservation groups. Perfusate markers were 2 fold higher in non-transplantable livers (p>0.05). Arterial only perfusion might not be adequate for graft perfusion. Hepatocellular injury markers are accessible and easy to perform and could offer insight into graft quality, but large randomised trials are needed to identify reliable quality assessment biomarkers.

Introduction: Minimized perfusion circuits (MPCs), although aiming at minimizing the adverse effects of cardiopulmonary bypass, have not yet gained popularity. This can be attributed to concerns regarding their safety, as well as lack of sufficient evidence of their benefit. Methods: Described is a randomized, multicentre study comparing the MPC - ROCsafeRX to standard cardiopulmonary bypass in patients undergoing elective coronary artery bypass grafting and/ or aortic valve replacement. Results: Five hundred patients were included in the study (252 randomized to the ROCsafeRX group and 248 to standard cardiopulmonary bypass). Both groups were well matched for demographic characteristics and type of surgery. No operative mortality and no device-related complications were encountered. Transfusion requirement (333 ± 603 vs. 587 ± 1010 ml; p=0.001), incidence of atrial fibrillation (16.3% vs. 24.2%; p=0.03) and the incidence of major adverse events (9.1% vs. 16.5%; p=0.02) were all in favour of the MPC group. Conclusion: These results confirm both the safety and efficacy of the ROCsafeRX MPC for a large variety of cardiac patients. Minimized perfusion circuits should, therefore, play a greater role in daily practice so that as many patients as possible can benefit from their advantages.

Background This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. Methods Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m 2 and docetaxel 60 mg/m 2 in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. Results One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245–820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3–23) days, to liquid food intake 6 (range, 4–24) days, and to abdominal suture removal 15 (range, 10–30) days. At the median follow-up of 19.7 (range, 7.5–89.2) months, the median OS was 24.2 (95 % CI, 15.0–33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. Conclusions CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. Trial registration ClinicalTrials.gov, NCT00454519

As engineered tissues progress toward therapeutically relevant length scales and cell densities, it is critical to deliver oxygen and nutrients throughout the tissue volume via perfusion through vascular networks. Furthermore, seeding of endothelial cells within these networks can recapitulate the barrier function and vascular physiology of native blood vessels. In this protocol, we describe how to fabricate and assemble customizable open-source tissue perfusion chambers and catheterize tissue constructs inside them. Human endothelial cells are seeded along the lumenal surfaces of the tissue constructs, which are subsequently connected to fluid pumping equipment. The protocol is agnostic with respect to biofabrication methodology as well as cell and material composition, and thus can enable a wide variety of experimental designs. It takes ~14 h over the course of 3 d to prepare perfusion chambers and begin a perfusion experiment. We envision that this protocol will facilitate the adoption and standardization of perfusion tissue culture methods across the fields of biomaterials and tissue engineering. Customizable tissue perfusion chambers facilitate seeding and perfusion culture of human endothelial cells within vascularized tissue constructs.

End stage kidney disease and dialysis are lifetime limiting and lifestyle-defining conditions with enormous costs to the health care system. Despite a severe organ shortage, thousands of organs that are retrieved for transplantation go to waste every year because of the presumed inadequacy of organ quality and/or the limited organ preservation time. Normothermic kidney machine perfusion (NMP) holds the potential to resolve this through improved preservation, prolonged preservation time, kidney quality assessment, reconditioning and treatment. We herein develop a perspective on the potential, but also the hurdles towards the breakthrough of this technology. Normothermic machine perfusion could prolong and/or improve preservation of kidneys in transplantation, but the technology has yet to reach clinical realization. Here, the authors show the hurdles, but also the solutions, for this technology to become a reality in transplantation and beyond.

Hypothermic oxygenated machine perfusion (HOPE) was introduced in liver transplantation (LT) to mitigate ischemia-reperfusion injury. Available clinical data mainly concern LT with donors after circulatory-determined death, whereas data on brain-dead donors (DBD) are scarce. To assess the impact of end-ischemic HOPE in DBD LT, data on primary adult LTs performed between March 2016 and June 2018 were analyzed. HOPE was used in selected cases of donor age >80 years, apparent severe graft steatosis, or ischemia time ≥10 hours. Outcomes of HOPE-treated cases were compared with those after static cold storage. Propensity score matching (1:2) and Bayesian model averaging were used to overcome selection bias. During the study period, 25 (8.5%) out of 294 grafts were treated with HOPE. After matching, HOPE was associated with a lower severe post-reperfusion syndrome (PRS) rate (4% versus 20%, p = 0.13) and stage 2–3 acute kidney injury (AKI) (16% versus 42%, p = 0.046). Furthermore, Bayesian model averaging showed lower transaminases peak and a lower early allograft dysfunction (EAD) rate after HOPE. A steeper decline in arterial graft resistance throughout perfusion was associated with lower EAD rate. HOPE determines a significant reduction of ischemia reperfusion injury in DBD LT.

Preservation of human organs at subzero temperatures has been an elusive goal for decades. The major complication hindering successful subzero preservation is the formation of ice at temperatures below freezing. Supercooling, or subzero non-freezing, preservation completely avoids ice formation at subzero temperatures. We previously showed that rat livers can be viably preserved three times longer by supercooling as compared to hypothermic preservation at +4 °C. Scalability of supercooling preservation to human organs was intrinsically limited because of volume-dependent stochastic ice formation at subzero temperatures. However, we recently adapted the rat preservation approach so it could be applied to larger organs. Here, we describe a supercooling protocol that averts freezing of human livers by minimizing air–liquid interfaces as favorable sites of ice nucleation and uses preconditioning with cryoprotective agents to depress the freezing point of the liver tissue. Human livers are homogeneously preconditioned during multiple machine perfusion stages at different temperatures. Including preparation, the protocol takes 31 h to complete. Using this protocol, human livers can be stored free of ice at –4 °C, which substantially extends the ex vivo life of the organ. To our knowledge, this is the first detailed protocol describing how to perform subzero preservation of human organs. Ice formation has hindered organ preservation below 0 °C. In this protocol, human livers are preconditioned with cryoprotective agents during machine perfusion and then supercooled to avoid ice formation.