Artificial organs最新文献

Background: In patients with biventricular heart failure, a biventricular assist device (BVAD) may be necessary for hemodynamic support. BVAD inflows can be established through cannulation of the atrial (AC) and/or ventricular (VC) chambers, but no consensus exists on optimal cannulation techniques. This study aimed to characterize BVAD performance related to cannulation types (AC and VC) using a continuous-flow total artificial heart (CFTAH) as the BVAD.

Methods: Both methods of cannulation (AC and VC) were tested on a mock loop using dual pulsatile ventricles with valves (AB5000; Abiomed) paired as the native ventricles and a double-ended centrifugal pump with two volutes, CFTAH, as a BVAD. Pressures were collected at the inlet and outlets of the AB5000 (LAP, RAP, AoP, and PAP) and the CFTAH (Lin, Rin, Lout, and Rout). The left and right flows exiting the CFTAH (LPF and RPF) and total flow (TF), exiting systemic resistance, were monitored. Several heart failure conditions were simulated with adjustment of the pneumatic pressures (AB5000).

Results: Trends between the AC and VC are similar where RAP, Lin, and Lout decreased, and AoP, PAP, TF, LPF, and RPF increased with increased support. The trends differ in LAP with an increase during AC as opposed to a decrease during VC. As a result, with this setup, left-right balance is more easily achieved during VC. TF is higher with AC, even though LPF and RPF are lower. This signifies the flow going through the aortic valve (TF-LPF) and pulmonary valve (TF-RPF) is higher with AC.

Conclusions: The increased TF and valvular flow favored AC for introducing a CFTAH as BVAD to the native heart in these conditions.

The 2024 International Liver Transplantation Society (ILTS) Congress, held in Houston, Texas, brought together a dynamic, multidisciplinary community of global experts to explore and discuss cutting-edge innovations and unmet needs in liver transplantation. Key themes included liver machine perfusion and donation after circulatory death (DCD), reflecting the ongoing effort to expand the donor pool and improve transplantation outcomes. Machine perfusion technologies, including normothermic machine perfusion (NMP), hypothermic oxygenated perfusion (HOPE), and normothermic regional perfusion (NRP) have demonstrated great promise in optimizing graft quality, mitigating ischemia-reperfusion injury, and enhancing the use of marginal and DCD liver grafts. At this year's congress a total of 63 abstracts on liver machine perfusion were presented. For this report we selected all orally presented abstracts highlighting advances in organ preservation, artificial intelligence, treatments during ex-situ perfusion including cellular therapy as well as new the use of new biomarkers. Preclinical highlights included the potential of long-term NMP to sustain and regenerate grafts during extended ex-situ preservation, spontaneous defatting of steatotic grafts during LT-NMP, the delivery of regulatory T cells to enable organ-level immunomodulation and the removal of damage-associated molecular patterns from porcine DCD livers during NMP. On the clinical side, key points included the progression of HOPE to IDEAL-D Stage 4 evidence, increased transplant volumes through the application of NMP, the cost-effectiveness of NMP as well as the utilization of very old DCD donors through NRP. Collectively, these advancements mark a transition toward dynamic, data-driven, and personalized transplantation strategies. Machine perfusion remains central to optimizing grafts, expanding the pool of organs suitable for transplantation enhancing access to liver transplantation and improving outcomes for liver transplant recipients worldwide.

Background: Normothermic machine perfusion (NMP) represents an alternative to prolong liver preservation and reduce organ discard rates. We performed an updated systematic review and meta-analysis to compare NMP with static cold storage (SCS) in liver transplantation.

Methods: MEDLINE, Embase, and Cochrane were searched for randomized controlled trials (RCTs) or observational studies. Risk ratios (RR) and mean differences were calculated. p < 0.05 was considered significant. A random-effects model was applied for all outcomes.

Prospero id: CRD42023486184.

Results: We included 1295 patients from 5 RCTs and 6 observational studies from 2016 to 2023. 592 (45.7%) underwent NMP. A subgroup RCT analysis favored NMP for non-anastomotic strictures (RR 0.4; 95% CI 0.2, 0.9), postreperfusion syndrome (RR 0.4; 95% CI 0.27, 0.56), and early allograft dysfunction (RR 0.6; 95% CI 0.4, 0.9). NMP favored higher organ utilization rates (RR 1.1; 95% CI 1.02, 1.18). No significant differences between NMP and SCS were observed in graft survival or patient survival at 12 months, primary non-function, serious adverse events, overall biliary complications, AST, or bilirubin levels peak within the first 7 days, ICU or hospital length of stay.

Conclusion: Our findings suggest that NMP is associated with lower non-anastomotic biliary stricture rates, postreperfusion syndrome, early allograft dysfunction, and higher organ utilization in the RCT subgroup analysis, without increasing adverse events.

Background: Patients with end-stage renal disease often face prolonged waiting times for kidney transplants. Historically, the use of marginal kidneys was limited due to suboptimal preservation methods. Normothermic machine perfusion (NMP) preserves physiological activity during the preservation process, potentially improving graft function and viability, expanding the use of marginal kidneys. While preliminary results are promising, NMP has not yet undergone sufficient clinical trials to determine whether it offers advantages over more widely used techniques. The aim of this systematic review is to assess several outcomes between kidneys that underwent NMP compared to traditional preservation methods after kidney transplant.

Methods: A systematic review was conducted following PRISMA guidelines. Randomized controlled trials, case series, and studies comparing NMP with hypothermic machine perfusion (HMP) or static cold storage (SCS) were included. The primary outcome assessed was delayed graft function (DGF). Secondary outcomes included primary non-function (PNF), acute rejection, and 1-year graft survival.

Results: Eight NMP studies met the inclusion criteria. Meta-analysis showed significant differences in DGF between NMP and control (HMP or SCS) groups (OR: 0.47 [0.22, 0.99], p < 0.05). There were no significant differences between NMP and controls for PNF, acute rejection, or 1-year graft survival.

Conclusions: These findings suggest that NMP yields similar adverse outcome rates compared to traditional methods. Notably, NMP could be associated with reduced rates of DGF. While NMP is a promising technique for renal allograft preservation, further randomized controlled trials are necessary to definitively establish its benefits over conventional preservation methods.

Background: Membrane oxygenators facilitate extracorporeal gas exchange, necessitating the monitoring of blood gas. Recent advances in normothermic machine perfusion (NMP) for ex vivo liver offer solutions to the shortage of donor liver. However, maintaining physiological blood gas levels during prolonged NMP is complex and costly.

Methods: We introduce a noninvasive and economical approach for regulating the blood gas during NMP of ex vivo porcine livers. By monitoring gas fractions at the outlet of oxygenator, real-time adjustments of blood gas can be made without the online blood gas analyzer. The method involves constructing multivariate linear regression (MLR) models, aligning target setpoints of gas, and employing active disturbance rejection control (ADRC) to achieve closed-loop regulation.

Results: Ex vivo porcine liver perfusion experiments demonstrated the effectiveness of the method, maintaining blood gas within physiological levels over 24 h (oxygen partial pressure: 150.36 ± 3.33 mmHg, carbon dioxide partial pressure: 41.34 ± 0.91 mmHg).

Conclusion: ADRC-based continuous regulation of gas fraction at the outlet of oxygenator is a feasible and effective approach for managing blood gas during ex vivo porcine liver perfusion.

Introduction: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is increasingly used in the treatment of severe respiratory failure. Despite a significant increase in the worldwide use of extracorporeal lung assist devices recirculation remains a common complication and is associated with a reduced effectiveness of ECMO support and increased hemolysis. In this observational study we aimed to investigate the impact of cannula configuration and extracorporeal flow on recirculation.

Materials and methods: An observational retrospective study was performed, which included all patients, who received V-V ECMO and recirculation measurements at the University Medical Center Freiburg between August 2021 and June 2023. Recirculation and extracorporeal flow were determined using ultrasonic indicator dilution technology. Patients were divided into subgroups according to their type of cannulation (dual lumen single-site vs. bifemoral vs. femoro-jugular).

Results: A total of 215 recirculation measurements in 47 patients were performed. Dual lumen single-site cannulation was associated with significantly lower recirculation rates (8.7% [0.0; 12.0]) compared to single lumen dual-site cannulation (femoro-jugular: 17.6% [0.0; 25.8]; bifemoral: 27.9% ± 13.4%). In addition, a positive linear correlation was observed between extracorporeal flow and recirculation in all subgroups. Recirculation increased significantly with rising extracorporeal flow in all subgroups.

Conclusion: Recirculation is a common complication in V-V ECMO and can lead to a reduction of ECMO effectiveness. Particular attention should be paid to optimal positioning of the cannulas in patients with more than one cannula. The ultrasonic indicator dilution method is a simple and quick method for measuring recirculation in V-V ECMO and can be used at an early stage if effectiveness decreases.

Background: Kidney transplantation (KT) is the most effective treatment for end-stage renal disease. End-ischemic hypothermic machine perfusion (EI-HMP) has emerged as a promising method for preserving grafts before transplantation. This study aimed to compare graft function recovery in KT recipients of deceased brain-death (DBD) grafts preserved with EI-HMP versus static cold storage (SCS). The primary outcome was the rate of delayed graft function (DGF). Secondary outcomes included urine output, intensive care unit (ICU) stay, hospital stay duration, and survival rates.

Methods: A retrospective, single-center observational study was conducted at Sapienza University of Rome, analyzing 313 KT patients between January 2014 and September 2021. Patients were stratified into two groups based on graft preservation methods (EI-HMP, n = 95; SCS, n = 218). A stabilized inverse probability treatment weighting (IPTW) method was employed to adjust for potential confounders.

Results: There were no significant differences in DGF rates between the two groups (17.9% vs. 15.6% in SCS and EI-HMP cases, respectively; p = 0.75). EI-HMP group demonstrated a higher urine output on day 2 (p = 0.046), a shorter ICU stay (p < 0.0001), and a trend toward a shorter overall hospital stay (p = 0.07). No statistically significant differences were found between EI-HMP and SCS cases in 1- and 3-year overall survival rates (3.2% and 6.7% vs. 5.6% and 6.6%, respectively; log-rank p = 0.53) or in death-censored graft loss rates (5.4% and 8.9% vs. 5.7% and 7.3%, respectively; log-rank p = 0.88). In a sub-analysis of expanded criteria donors (ECD), EI-HMP demonstrated a protective effect by reducing the risk of DGF (OR = 0.31, 95% CI = 0.09-0.95; p = 0.047).

Conclusion: EI-HMP was associated with certain short-term benefits, including increased urine output and reduced ICU stays, but showed no significant impact on long-term survival outcomes. A reduction in DGF rates was observed only in the ECD subgroup. Randomized controlled trials are necessary to further investigate the long-term clinical benefits of EI-HMP.

Background: Contrast-associated acute kidney injury (CA-AKI) is frequent in patients with chronic kidney disease who are submitted to cardiac endovascular procedures using iodinated contrast. In hemoadsorption, cartridges containing styrene-divinylbenzene sorbent resin are applied to remove substances from the blood through an extracorporeal circuit. Importantly, iodinated contrast is also removed via adsorption. We aimed to determine the adsorptive kinetics of the iodinated contrast medium iohexol using a 1:3 scale model of the HA380 cartridge.

Methods: An experimental in vitro study utilizing a closed-loop extracorporeal circuit with an interposed sorbent cartridge. A solution spiked with iohexol was recirculated for 60 min. Samples for the measurement of iohexol were drawn at 0, 5, 10, 15, 20, 30, 40, and 60 min. The experiment was carried out twice.

Results: In experiments 1 and 2, the reduction ratio after 60 min was 53.0% and 53.1%, respectively. In experiment 1, iohexol clearance was 46.79 mL/min during the first 5 min and decayed to 3.57 mL/min during the last 20 min. In experiment 2, iohexol clearance was 46.72 mL/min and decayed to 3.87 mL/min during the last 20 min. The ratio of adsorbate/sorbent was 155 mg/g.

Conclusion: A 1:3 scale model of the HA380 cartridge efficiently removes iodinated contrast in a clinical-scale in vitro circuit. These findings provide a rationale for hemoadsorption as an intervention in clinical trials to prevent or attenuate CA-AKI.

Intrahepatic islet transplantation is a promising strategy for β-cell replacement therapy in the treatment of Type 1 Diabetes. However, several obstacles hinder the long-term efficacy of this therapy. A major challenge is the scarcity of donor organs. During the isolation process, islets are disconnected from their extracellular matrix (ECM) and vasculature, leading to significant loss due to anoikis and hypoxia. Additionally, inflammatory and rejection reactions further compromise islet survival and engraftment success. Extensive efforts are being made to improve the efficacy of islet transplantation. These strategies include promoting revascularization and ECM support through bioengineering techniques, exploring alternative sources of insulin-secreting cells, and providing immunomodulation for the graft. Despite these advancements, a significant gap remains in integrating these strategies into a cohesive approach that effectively replicates the native endocrine environment. Specifically, the lack of comprehensive methods to address both the structural and functional aspects of the endocrine niche limits reproducibility and clinical translation. Therefore, bioengineering an endocrine pancreas must aim to recreate the endocrine niche to achieve lifelong efficacy and insulin independence. This review discusses various strategies developed to produce the building blocks for generating a vascularized, immune-protected insulin-secreting construct, emphasizing the importance of the endocrine niche's composition and function.