Machine perfusion is increasingly being tested in clinical transplantation. Despite this, the number of large prospective clinical trials remains limited. The aim of this study was to compare the ...impact of machine perfusion vs. static cold storage (SCS) on outcomes after liver transplantation.
A systematic search of MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted to identify randomized-controlled trials (RCTs) comparing “post-transplant” outcomes following machine perfusion vs. SCS. Data were pooled using random effect models. Risk ratios (RRs) were calculated for relevant outcomes. The quality of evidence was rated using the GRADE-framework.
Seven RCTs were identified (four on hypothermic oxygenated HOPE and three on normothermic machine perfusion NMP), including a total number of 1,017 patients. Both techniques were associated with significantly lower rates of early allograft dysfunction (NMP: n = 41/282, SCS: n = 74/253, RR 0.50, 95% CI 0.30-0.86, p = 0.01, I2 = 39%; HOPE: n = 45/241, SCS: n = 97/241, RR 0.48, 95% CI 0.35-0.65, p < 0.00001, I2 = 5%). The HOPE approach led to a significant reduction in major complications (Clavien Grade ≥IIIb; HOPE: n = 90/241; SCS: n = 117/241, RR 0.76, 95% CI 0.63-0.93, p = 0.006, I2 = 0%), “re-transplantation” (HOPE: n = 1/163; SCS: n = 11/163; RR 0.21, 95% CI 0.04-0.96, p = 0.04; I2 = 0%) and graft loss (HOPE: n = 7/163; SCS: n = 19/163; RR 0.40, 95% CI 0.17-0.95, p = 0.04; I2 = 0%). Both perfusion techniques were found to ‘likely’ reduce overall biliary complications and non-anastomotic strictures.
Although this study provides the highest current evidence on the role of machine perfusion, outcomes remain limited to a 1-year follow-up after liver transplantation. Comparative RCTs and large real-world cohort studies with longer follow-up are required to enhance the robustness of the data further, thereby supporting the introduction of perfusion technologies into routine clinical practice.
CRD42022355252.
For a decade, two dynamic perfusion concepts have increasingly been tested in several transplant centres worldwide. We undertook the first systematic review and meta-analysis and identified seven published RCTs, including 1,017 patients, evaluating the effect of machine perfusion (hypothermic and normothermic perfusion techniques) compared to static cold storage in liver transplantation. Both perfusion techniques were associated with lower rates of early allograft dysfunction in the first week after liver transplantation. Hypothermic oxygenated perfusion led to a reduction in major complications, lower “re-transplantation” rates and better graft survival. Both perfusion strategies were found to ‘likely’ reduce overall biliary complications and non-anastomotic biliary strictures. This study provides the highest current evidence on the role of machine perfusion. Outcomes remain limited to a 1-year post-transplant follow-up. Larger cohort studies with longer follow-up and clinical trials comparing the perfusion techniques are required. This is especially relevant to provide clarity and optimise implementation processes further to support the commissioning of this technology worldwide.
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•First systematic review and meta-analysis evaluating the effect of HOPE and NMP compared to SCS in liver transplantation.•HOPE and NMP were associated with lower rates of early allograft dysfunction in the first week after liver transplantation.•HOPE led to a significant reduction in major complications, lower “re-transplantation” rates and better graft survival.•Despite being the highest level of evidence, outcome data on machine perfusion remain limited to 1-year post-transplant follow-up.
Purpose
To develop and evaluate a high spatial resolution (1.25 × 1.25 mm2) spiral first‐pass myocardial perfusion imaging technique with whole‐heart coverage at 3T, to better assess transmural ...differences in perfusion between the endocardium and epicardium, to quantify the myocardial ischemic burden, and to improve the detection of obstructive coronary artery disease.
Methods
Whole‐heart high‐resolution spiral perfusion pulse sequences and corresponding motion‐compensated reconstruction techniques for both interleaved single‐slice (SS) and simultaneous multi‐slice (SMS) acquisition with or without outer‐volume suppression (OVS) were developed. The proposed techniques were evaluated in 34 healthy volunteers and 8 patients (55 data sets). SS and SMS images were reconstructed using motion‐compensated L1‐SPIRiT and SMS‐Slice‐L1‐SPIRiT, respectively. Images were blindly graded by 2 experienced cardiologists on a 5‐point scale (5, excellent; 1, poor).
Results
High‐quality perfusion imaging was achieved for both SS and SMS acquisitions with or without OVS. The SS technique without OVS had the highest scores (4.5 4, 5), which were greater than scores for SS with OVS (3.5 3.25, 3.75, P < .05), MB = 2 without OVS (3.75 3.25, 4, P < .05), and MB = 2 with OVS (3.75 2.75, 4, P < .05), but significantly higher than those for MB = 3 without OVS (4 4, 4, P = .95). SMS image quality was improved using SMS‐Slice‐L1‐SPIRiT as compared to SMS‐L1‐SPIRiT (P < .05 for both reviewers).
Conclusion
We demonstrated the successful implementation of whole‐heart spiral perfusion imaging with high resolution at 3T. Good image quality was achieved, and the SS without OVS showed the best image quality. Evaluation in patients with expected ischemic heart disease is warranted.
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.
To alleviate the persistent shortage of donor livers, high‐risk liver grafts are increasingly being considered for liver transplantation. Conventional preservation with static cold storage falls ...short in protecting these high‐risk livers from ischemia–reperfusion injury, as evident from higher rates of post‐transplant complications such as early allograft dysfunction and ischemic cholangiopathy. Moreover, static cold storage does not allow for a functional assessment of the liver prior to transplantation. To overcome these limitations, dynamic strategies of liver preservation have been proposed, designed to provide a protective effect while allowing pre‐transplant functional assessment. In this review, we discuss how different dynamic preservation strategies exert their effects, where we stand in assessing liver function and what challenges are lying ahead.
Using organ perfusion to optimize donor livers Lee-Riddle, Grace S; Panayotova, Guergana G; Guarrera, James V
Current opinion in organ transplantation,
04/2023, Volume:
28, Issue:
2
Journal Article
The shortage of donor organs has led to the use of marginal extended criteria donor (ECD) livers to increase access to liver transplant. Ex-vivo machine perfusion allows for treatment and assessment ...of organs during preservation, potentially facilitating safe use of ECD livers at risk for worse clinical outcomes. This article reviews the latest published literature on the application of ex-vivo machine perfusion technologies in liver transplantation.
Multiple randomized controlled trials on the use of hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) have been published in the past 5 years demonstrating improved graft function and decreased biliary complications after machine perfusion. Novel applications of machine perfusion include pretransplant organ viability testing, expansion to pediatric transplant, and prolonged preservation.
There is now a body of evidence that HMP and NMP treatment improves clinical outcomes in ECD livers. There is a wide horizon for future applications of these preservation techniques to further optimize donor livers and to facilitate more liver transplants for those on the waitlist.
Donation after circulatory death (DCD) could account for the largest expansion of the donor allograft pool in the contemporary era. However, the organ yield and associated costs of normothermic ...regional perfusion (NRP) compared to super-rapid recovery (SRR) with ex-situ normothermic machine perfusion, remain unreported. The Organ Procurement and Transplantation Network (December 2019 to June 2023) was analyzed to determine the number of organs recovered per donor. A cost analysis was performed based on our institution’s experience since 2022. Of 43 502 donors, 30 646 (70%) were donors after brain death (DBD), 12 536 (29%) DCD-SRR and 320 (0.7%) DCD-NRP. The mean number of organs recovered was 3.70 for DBD, 3.71 for DCD-NRP (P < .001), and 2.45 for DCD-SRR (P < .001). Following risk adjustment, DCD-NRP (adjusted odds ratio 1.34, confidence interval 1.04-1.75) and DCD-SRR (adjusted odds ratio 2.11, confidence interval 2.01-2.21; reference: DBD) remained associated with greater odds of allograft nonuse. Including incomplete and completed procurement runs, the total average cost of DCD-NRP was $9463.22 per donor. By conservative estimates, we found that approximately 31 donor allografts could be procured using DCD-NRP for the cost equivalent of 1 allograft procured via DCD-SRR with ex-situ normothermic machine perfusion. In conclusion, DCD-SRR procurements were associated with the lowest organ yield compared to other procurement methods. To facilitate broader adoption of DCD procurement, a comprehensive understanding of the trade-offs inherent in each technique is imperative.
Myocardial perfusion reflects the macro- and microvascular coronary circulation. Recent quantitation developments using cardiovascular magnetic resonance perfusion permit automated measurement ...clinically. We explored the prognostic significance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR, the ratio of stress to rest MBF).
A 2-center study of patients with both suspected and known coronary artery disease referred clinically for perfusion assessment. Image analysis was performed automatically using a novel artificial intelligence approach deriving global and regional stress and rest MBF and MPR. Cox proportional hazard models adjusting for comorbidities and cardiovascular magnetic resonance parameters sought associations of stress MBF and MPR with death and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, heart failure hospitalization, late (>90 day) revascularization, and death.
A total of 1049 patients were included with a median follow-up of 605 (interquartile range, 464-814) days. There were 42 (4.0%) deaths and 188 MACE in 174 (16.6%) patients. Stress MBF and MPR were independently associated with both death and MACE. For each 1 mL·g
·min
decrease in stress MBF, the adjusted hazard ratios for death and MACE were 1.93 (95% CI, 1.08-3.48,
=0.028) and 2.14 (95% CI, 1.58-2.90,
<0.0001), respectively, even after adjusting for age and comorbidity. For each 1 U decrease in MPR, the adjusted hazard ratios for death and MACE were 2.45 (95% CI, 1.42-4.24,
=0.001) and 1.74 (95% CI, 1.36-2.22,
<0.0001), respectively. In patients without regional perfusion defects on clinical read and no known macrovascular coronary artery disease (n=783), MPR remained independently associated with death and MACE, with stress MBF remaining associated with MACE only.
In patients with known or suspected coronary artery disease, reduced MBF and MPR measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcomes.
Abstract Objective Venoarterial extracorporeal membrane oxygenation (ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Owing to the large size of the cannulas inserted via ...the femoral vessels (≤24-F) required for adequate oxygenation, this procedure could result in significant limb ischemic complications (10%-70%). This study evaluates the results of a distal limb perfusion arterial protocol designed to reduce associated complications. Methods We conducted a retrospective institutional review board-approved review of consecutive patients requiring ECMO via femoral cannulation (July 2010-January 2015). To prevent arterial ischemia, a distal perfusion catheter (DPC) was placed antegrade into the superficial femoral artery and connected to the ECMO circuit. Limb perfusion was monitored via near-infrared spectroscopy (NIRS) placed on both calves. Decannulation involved open repair, patch angioplasty, and femoral thrombectomy as needed. Results A total of 91 patients were placed on ECMO via femoral arterial cannula (16-F to 24-F) for a mean duration of 9 days (range, 1-40 days). A percutaneous DPC was inserted prophylactically at the time of cannulation in 55 of 91 patients, without subsequent ischemia. Of the remaining 36 patients without initial DPC placement, 12 (33% without DPC) developed ipsilateral limb ischemia related to arterial insufficiency, as detected by NIRS and clinical findings. In these patients, the placement of a DPC (n = 7) with or without a fasciotomy, or with a fasciotomy alone (n = 4), resulted in limb salvage; only one patient required subsequent amputation. After decannulation (n = 7), no patients had further evidence of limb ischemia. Risk factors for the development of limb ischemia identified by categorical analysis included lack of DPC at time of cannulation and ECMO cannula size of less than 20-Fr. There was a trend toward younger patient age. Overall ECMO survival rate was 42%, whereas survival in patients with limb ischemia was only 25%. Conclusions Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy.
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