Publications by authors named "Barbas A"
Normothermic machine perfusion (NMP) facilitates utilization of marginal liver allografts. It remains unknown whether clinical benefits offset additional costs in the real-world setting. We performed a comparison of outcomes and hospitalization costs for donor livers preserved by NMP versus static cold storage (SCS) at a high-volume center.
View Article and Find Full Text PDFBackground: Invasive primary surgical site infections (IP-SSI) are a severe complication of liver transplant surgery. Identification of risk factors for IP-SSI is critical to IP-SSI prevention.
Methods: All adult single liver transplants performed at Duke University Hospital in the period 2015-2020 were reviewed for IP-SSI occurring within 90 d of transplant.
Article Synopsis
- This text talks about how the idea of "textbook outcome" (TO) is being used to create better standards for measuring how well organ transplants work.
- Traditionally, doctors looked at just one year of patient survival to judge their programs, but that's no longer enough.
- The review shows the need for clear TO guidelines that can help hospitals compare their results with others and find ways to improve patient care.
Background: The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function.
View Article and Find Full Text PDFGenetic modification of porcine donors, combined with optimized immunosuppression, has been shown to improve outcomes of experimental xenotransplant. However, little is known about outcomes in sensitized recipients, a population that could potentially benefit the most from the clinical implementation of xenotransplantation. Here, five highly allosensitized rhesus macaques received a porcine kidney from (α1,3-galactosyltransferase) knockout pigs expressing the human transgene (1KO.
View Article and Find Full Text PDFBackground: Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate.
View Article and Find Full Text PDFBackground: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA.
Methods: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT.
Sorafenib is a multikinase inhibitor indicated for first-line treatment of unresectable hepatocellular carcinoma. Despite its widespread use in the clinic, the existing knowledge of sorafenib mode-of-action remains incomplete. To build upon the current understanding, we used the Cellular Thermal Shift Assay (CETSA) coupled to Mass Spectrometry (CETSA-MS) to monitor compound binding to its target proteins in the cellular context on a proteome-wide scale.
View Article and Find Full Text PDFObjective: Adeno-associated virus is a clinically used gene therapy vector but has not been studied in lung transplantation. We sought to determine the efficacy of adeno-associated virus delivery during static cold storage via the airway versus the pulmonary artery before lung transplantation in a rodent model.
Methods: Lewis rat lung grafts were treated with a dose of 8e8 or 4e9 viral genome/μL recombinant adeno-associated virus subtype-9 vectors containing firefly luciferase genomes administered via the pulmonary artery or airway during cold storage.
Article Synopsis
- The 2023 Joint Annual Congress for liver transplantation was held in Rotterdam from May 3 to 6, marking the first time all speakers attended in person since the COVID-19 pandemic.
- The event gathered 1,159 delegates from 54 countries, showcasing 542 of the 647 submitted abstracts, with a significant portion coming from just 10 countries, mainly in North America, Europe, and Asia.
- Abstracts covered various topics including ischemia and reperfusion injury, machine perfusion, and artificial intelligence, while also evaluating scientific impact through publications resulting from prior presentations in the field.
Limitations of antifungal prophylaxis in preventing invasive surgical site infections after liver transplant surgery.
Antimicrob Agents Chemother
March 2024
Invasive primary surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of IP-SSI according to the peri-transplant antifungal prophylaxis received.
View Article and Find Full Text PDFArticle Synopsis
- Intestinal transplantation (IT) is considered the last resort for treating intestinal failure, with static cold storage (CS) being the traditional method for preserving donor organs, although it leads to harmful ischemia-reperfusion injury (IRI).
- A new method called normothermic machine perfusion (NMP) is hypothesized to cause less damage and better protect the intestines’ ability to regenerate when compared to CS.
- Experiments showed that intestines preserved using NMP had lower tissue damage, higher stem cell viability, and increased survivor rates after transplant, suggesting that NMP could enhance recovery and regeneration of transplanted intestines.
Objective: Ex vivo lung perfusion has emerged as a platform for organ preservation, evaluation, and restoration. Gene delivery using a clinically relevant adeno-associated vector during ex vivo lung perfusion may be useful in optimizing donor allografts while the graft is maintained physiologically active. We evaluated the feasibility of adeno-associated vector-mediated gene delivery during ex vivo lung perfusion in a rat transplant model.
View Article and Find Full Text PDFSterile inflammation is the immune response to damage-associated molecular patterns (DAMPs) released during cell death in the absence of foreign pathogens. In the setting of solid organ transplantation, ischemia-reperfusion injury results in mitochondria-mediated production of reactive oxygen and nitrogen species that are a major cause of uncontrolled cell death and release of various DAMPs from the graft tissue. When properly regulated, the immune response initiated by DAMP-sensing serves as means of damage control and is necessary for initiation of recovery pathways and re-establishment of homeostasis.
View Article and Find Full Text PDFArticle Synopsis
- This study compares two methods of preserving donor livers for transplantation: traditional static cold storage (SCS) and normothermic machine perfusion (NMP) which keeps the organs at body temperature.
- The research involved 383 donor livers from various US transplant centers, and while there was no significant difference in early allograft dysfunction rates overall, NMP showed better outcomes for higher-risk donors, particularly in cases of organ donation after circulatory death.
- The conclusion suggests that while NMP may not lower early liver injury rates universally, it is safe and potentially more beneficial for marginal donor livers.
Introduction: Recombinant adeno-associated virus (rAAV) is a novel strategy used clinically for gene delivery, but has not been characterized in the context of organ transplantation. We sought to determine the efficacy of rAAV-mediated gene delivery during static cold storage (SCS) prior to liver transplantation.
Methods: A triple-plasmid transfection protocol was used to produce rAAV subtype-9 vectors containing firefly luciferase genomes in HEK293 cells.
Article Synopsis
- - The study focuses on predicting the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) using data from over 4,900 patients, emphasizing the need for personalized assessment due to high recurrence rates.
- - Researchers developed the RELAPSE score, which utilizes clinicopathological and radiological factors, validated through advanced statistical and machine learning methods, to enhance the accuracy of recurrence predictions in HCC patients post-LT.
- - Key independent predictors of HCC recurrence identified include alpha-fetoprotein levels, tumor size, and vascular invasion, with a 5-year recurrence rate of 12.5% and a more robust predictive model achieved through machine learning techniques.
The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells.
View Article and Find Full Text PDFBackground: Hyperfibrinolysis is a possible complication during liver transplantation, particularly immediately after reperfusion.
Methods: We performed a retrospective study to examine the incidence, treatment, and resolution of postreperfusion hyperfibrinolysis in patients undergoing liver transplantation at Duke University Hospital from 2015 to 2020.
Results: Out of 535 patients undergoing liver transplantation, 21 or 3.
Article Synopsis
- - The American Society of Transplant Surgeons is advocating for increased organ donation, specifically focusing on organs from donation after circulatory death (DCD) donors due to growing demand for transplants in the U.S.
- - There are significant inconsistencies in DCD transplantation practices, which highlights the need for standardized best practices to optimize DCD organ recovery.
- - A work group identified key controversial areas such as prewithdrawal preparation and surgical techniques, providing evidence-based recommendations to assist transplant programs and organ procurement organizations.