Transplantation最新文献

Background: Although lactate clearance provides important information regarding hepatocellular function during normothermic machine perfusion (NMP), the information inferred is adequate to exclude nonfunctioning grafts but is limited in evaluating comprehensive hepatocyte function. Liver maximum capacity (LiMAx), using C 13 -methacetin, has been adopted to assist in the functional assessment of the liver before major oncological resection. We evaluated the combined use of lactate clearance and LiMAx measurement to monitor liver function during extended-duration NMP.

Methods: Seven discarded donor livers underwent extended NMP for 87-184 h using a blood-based perfusate and a modified Liver Assist device incorporating hemofiltration. Hepatocellular function was assessed every 6 h using LiMAx: a fixed bolus of C 13 -methacetin was administered and the delta over baseline was measured. Lactate clearance capacity was tested every 24 h by administering 50% sodium lactate to achieve perfusate concentrations of 10-15 mmol/L.

Results: Initial lactate clearance to <2.5 mmol/L was achieved within 1.75-7.75 h post-NMP initiation. The median LiMAx value was 829 (range, 325-3130) µg/kg/h. Livers with efficient lactate clearance (<4 h) displayed stable LiMAx profiles with consistently low, flat delta over baseline curves, maintaining similar amplitude for 80 h of perfusion, indicative of preserved hepatocyte function. Conversely, livers with progressive reductions in LiMAx amplitude and curve flattening were associated with deteriorating function and eventual graft failure.

Conclusions: LiMAx enables real-time, longitudinal monitoring of hepatocyte metabolic activity during extended NMP. When combined with lactate clearance, it could offer a more comprehensive assessment of graft viability. Incorporating LiMAx into viability criteria could refine current decision-making frameworks for liver transplantation, particularly in marginal grafts.

Machine perfusion (MP) strategies have altered the landscape of deceased donor liver procurement and preservation in recent years. Upfront costs for MP are significantly higher than those of conventional procurement/preservation techniques. We performed a systematic review to evaluate the cost-effectiveness of various MP strategies as alternatives to conventional liver procurement and preservation before liver transplantation (LT). A systematic search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed for articles published up to February 2025, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Fourteen studies reported the cost-effectiveness of MP before LT, including hypothermic oxygenated liver perfusion (n = 4), normothermic machine perfusion (n = 8), and normothermic regional perfusion (n = 2). Inflation-adjusted costs per MP run varied: normothermic machine perfusion (US$11 455-35 766), hypothermic oxygenated liver perfusion (US$6489-12 686), and normothermic regional perfusion (US$9287; single study). Six studies analyzed cost-effectiveness using real-world cohorts. All but one study found MP to be cost-effective; 5 reported overall cost savings compared with conventional procurement and static cold storage. MP influenced costs across the entire LT pathway: pre-LT (lower waitlist healthcare costs, fewer procurement "dry runs," improved organ utilization) and post-LT (shorter intensive care unit/hospital stays, reduced allograft dysfunction, need for dialysis, cholangiopathy, and retransplantation). Three studies found cost-effective improvements in quality-adjusted life years with MP. Although direct and indirect MP costs varied and were inconsistently reported, all studies based on real-world data found MP to be at least cost-neutral. Initial MP costs were offset by savings in waitlist and postoperative costs. Real-world data on the cost-effectiveness of NRP remain limited. Future clinical studies should include cost-effectiveness analysis to support institutional and policy-level investment in MP technologies.

Background: Intestinal transplantation (ITx) is the definitive treatment for patients with intestinal failure who experience severe complications on total parenteral nutrition. However, ITx has the highest morbidity among solid organ transplants. Currently, there is little information to guide clinicians in choosing the timepoint at which the advantages of ITx outweigh the risks. We seek to predict post-ITx survival using a priori data to help patients determine whether to undergo ITx.

Methods: This study used data from the Organ Procurement and Transplantation Network database on all ITx procedure performed in the United States from 2016 to 2021 (n = 567), of whom 17.3% (n = 98) were censored as lost to follow-up and 33.3% (n = 189) died. The cohort included both pediatric and adult patients as well as multiorgan patients. The inclusion of such a diverse cohort was supported by sensitivity analyses. An adjusted Cox model was used to model 2-y posttransplant patient survival using data available before transplant.

Results: Repeat sepsis on total parenteral nutrition before transplant (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.07-1.97), older age (HR, 1.02; 95% CI, 1.02-1.03), and the need for a concomitant liver (HR, 1.43; 95% CI, 1.03-1.99) were associated with poorer posttransplant survival. Lower bilirubin levels were associated with higher posttransplant survival.

Conclusions: This research reinforces the conclusion that an ITx should be pursued before liver disease progresses to the point of requiring a concomitant liver.

Background: Advanced perfusion techniques have been shown to improve liver transplantation (LT) outcomes in donation after determination of death by both circulatory (DCD) and neurological (DBD) criteria, but allocation strategies are still controversial.

Methods: This study compared the outcomes of controlled DCD LT with normothermic regional perfusion and subsequent ex situ machine perfusion to those of DBD LT with static cold storage and extended criteria DBD (ECD) LT with dual hypothermic oxygenated perfusion (DHOPE), selected by propensity score matching.

Results: Three comparable cohorts were selected from transplants performed between January 2016 and June 2024: 61 DCD (DHOPE, n = 50; normothermic machine perfusion, n = 11), 122 DBD-static cold storage, and 122 ECD-DHOPE. Median functional warm ischemia time in DCD donors was 44 (39-48) min. Livers were assessed and accepted for LT based on normothermic regional perfusion parameters. All considered outcomes were comparable between groups and in line with benchmark values. One-year graft and patient survival exceeded 90% in all groups, whereas 3-y graft survival was 91.8%, 93.4%, and 88% in the DCD, DBD-static cold storage, and ECD-DHOPE groups, respectively. In the same groups, incidence of ischemic cholangiopathy was 3.3%, 4.9%, and 3.3%.

Conclusions: Tailored application of advanced perfusion techniques allows achieving optimal outcomes in both DCD with prolonged warm ischemia time and ECD-DBD LT.

Background: The spirometric response to standard-of-care (SOC) immunosuppressive therapy for the management of bronchiolitis obliterans syndrome (BOS) has been sparsely reported in the literature. Data from a Medicare-approved Registry were analyzed to characterize the effectiveness/durability of a wide range of SOC interventions to manage the decline of lung function and to validate the study spirometric criteria for initiation of rescue therapy.

Methods: Lung transplant recipients with refractory BOS at 21 US collaborating centers were enrolled in the Registry. Data included both nonspirometric (eg, demographic, Immunosuppressive Regimens for management of BOS) and spirometric parameters (ie, forced expiratory volume in 1 s [FEV 1 ] measurements and derived indices). The utility of study FEV 1 criteria for treatment (ie, statistically significant rate of FEV 1 decline >30 mL/mo) was evaluated by comparing the spirometric course between participants who met or did not meet this criterion.

Results: Only 21% of participants treated with SOC therapy had >50% decrease (76 ± 25% decrease) in the rate of FEV 1 decline. Although 51% of participants had a partial response (rate of FEV 1 decline decreased on average 71%), 49% of participants had a substantial increase (mean increase 224%). The FEV 1 criterion for treatment was able to identify 19% of participants (48/258) who achieved durable stabilization (ie, nonsignificant rate of FEV 1 <30 mL/mo) with SOC therapy.

Conclusions: Patients with BOS have a widely variable response to SOC therapy. Our findings support the use of FEV 1 rate of decline to assess response to SOC therapy and to ensure appropriate assignment of participants with refractory BOS to rescue therapy treatment cohorts.

Background: The critical shortage of transplantable organs and suboptimal preservation efficacy of static cold storage (SCS)-limited to 24-h kidney preservation at 4 °C-necessitate transformative technological solutions. This study pioneers the application of deep-supercooling (DSC) for ice-free rat kidney preservation at -10 °C, aiming to systematically compare DSC's efficacy against conventional SCS and establish its maximum viable preservation window.

Methods: Rat kidneys underwent preservation via SCS (4 °C) or DSC (-10 °C) for 24, 96, or 168 h, with subset groups subjected to normothermic reperfusion. Comprehensive biomarker profiling was performed on preservation solutions, perfusate, urine, and renal tissues to assess functional, metabolic, and structural integrity.

Results: DSC reliably maintained stable supercooled preservation at -10 °C. After 24-h DSC storage, kidneys exhibited superior functional recovery versus SCS controls, demonstrating enhanced glomerular filtration (2.1-fold elevated creatinine clearance), optimized energy homeostasis (57% higher ATP level), and attenuated ischemic injury (39% lower injury score). Remarkably, 96-h DSC preservation achieved outcomes at least comparable to 24-h SCS, effectively quadrupling the functional preservation window.

Conclusions: DSC represents a paradigm-shifting advancement in renal preservation, extending viable storage duration by 4-fold while improving graft quality compared with SCS. This technique's operational simplicity position it as a clinically translatable solution to expand donor organ utilization.

Technological innovations have improved many barriers in lung transplantation, but high rates of acute and chronic rejection still limit lung allograft survival. This may be explained by the unique environment of the lung. As a mucosal barrier organ, the lung is constantly exposed to the external environment, leading to unique immunological features that are not seen in other transplantable solid organ allografts such as hearts, kidneys, and livers. Thus, the higher rates of rejection and poor long-term survival of lung transplant recipients may stem from the global immunosuppression strategies that are indiscriminately used for all solid organ grafts. Data from our laboratory, and others, have demonstrated that the unique immunoregulatory pathways of the lung may require different strategies for long-term graft survival. For example, depletion of CD8 + T cells typically contributes to the acceptance of transplanted organs. However, these cells facilitate lung allograft acceptance through interferon gamma mediated nitric oxide production. Interestingly CD8 + T cells modify and polarize eosinophils to produce nitric oxide as a means of tolerance induction. Such eosinophils also function to maintain long-term lung allograft acceptance by interfering with humoral alloimmunity. For most other organs eosinophils are suspected to contribute to graft rejection. In this review, we aim to describe the cytokine pathways involved in lung allograft rejection or tolerance, contrast such pathways to those evident in other solid organs, and discuss the need for further studies that can be used to design rational methods for altering the cytokine environment to improve lung allograft survival.