Frontiers in transplantation最新文献

In a previous study, we showed an anti-inflammatory effect of propionic acid supplementation in dialysis patients. The present study intends to analyze the effect of propionic acid on the chronic inflammatory state and T-cell composition in kidney transplant patients compared to dialysis patients. A total of 10 dialysis patients and 16 kidney transplant patients under immunosuppressive standard triple immunosuppressive therapy received 2 × 500 mg propionic acid per day for 30 days. The cellular immune system was analyzed before and after the propionic acid supplementation and 30-90 days thereafter as a follow-up. We measured the main immune cell types and performed an in-depth characterization of T cells including regulatory T cells (Tregs), B cells, and dendritic cells. In addition, we assessed the functional activity and antigenic responsiveness by analysis of third-party antigen-specific T cells after their stimulation by recall (tetanus diphtheria vaccine) antigen. In dialysis patients, we observed an expansion of CD25^highCD127^- Tregs after propionic acid intake. In contrast, the same supplementation did not result in any expansion of Tregs in transplant patients under immunosuppressive therapy. We also did not observe any changes in the frequencies of the main immune cell subsets except for CD4⁺/CD8⁺ distribution with an increase of CD4⁺ T cells and decrease of CD8⁺ T cells in the transplant population. Our data suggest that dietary supplements containing propionate might have a beneficial effect decreasing systemic inflammation in dialysis patients through Treg expansion. However, this effect was not observed in transplant patients, which could be explained by counteracting effect of immunosuppressive drugs preventing Treg expansion.

Background: Donor liver transaminases (ALT and AST) have been used to decline livers for transplant, despite evidence that they do not influence transplant outcomes. This study assesses the effect that raised donor transaminases have on the unnecessary decline of livers.

Methods: This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019). Logistic regression models were built to assess the impact of donor transaminases on the utilisation of organs donated following brain stem death (DBD) and circulatory death (DCD). A further model was used to simulate the impact on liver decline if raised donor ALT was not used to make utilisation decisions.

Results: 5,424 adult livers were offered for transplant, of which 3,605 were utilised (2,841 DBD, 764 DCD). In multivariable analysis, adjusted for key factors, increasing peak donor ALT independently increased the odds of liver decline (DBD aOR = 1.396, 1.305-1.494, p < 0.001, DCD aOR = 1.162, 1.084-1.246, p < 0.001). AST was also a significant predictor of liver decline. 18.5% of livers from DBD donors with ALT > 40 U/L (n = 1,683) were declined for transplantation. In this group, our model predicted a 48% (38%-58%) decrease in decline if raised donor ALT was excluded from these decisions. This represents an additional 37 (30-45) liver transplants every year in the UK.

Conclusions: Raised donor ALT increased the likelihood of liver decline. As it does not influence transplant outcome, avoiding donor ALT-based organ decline is an immediate and effective way to expand the donor pool.

To date, little is known about the mechanisms of rejection in vascularized composite allotransplantation, particularly for antibody mediated rejection. Additionally, no clear guidelines exist for the diagnosis and management of antibody-mediated rejection in vascularized composite allotransplantation. A systematic review of electronic databases (Embase and PubMed) was conducted to evaluate the relationship of donor specific antibodies and C4d deposition in correlation with cellular rejection following hand and face transplantation reported by centers between 1998 and July 2023. We extracted data on serum donor specific antibodies at the time of biopsy proven rejection according to Banff classification and C4d staining of target tissues. Mann-Whitney U tests were performed to compare rejection grade between groups divided by status of C4d deposition and serum donor specific antibodies, and Fisher's Exact test was used to assess association between the two markers. This review adhered to PRISMA guidelines. A total of 26 patients (5 face, 21 hand) were identified and data on 90 acute rejection episodes with information on Banff grade, donor specific antibody status, and C4d deposition were available. Donor specific antibodies were found to be associated with higher rejection grade (p = 0.005). C4d was not found to be associated with higher rejection grade (p = 0.33). Finally, no significant association was found between concurrent status of the two markers (p = 0.23). These findings suggest that the presence of donor specifc antibodies may be associated with higher grades of acute cellular rejection following hand and face transplantation. More consistent reporting on rejection episodes is needed in order to better understand antibody-mediated rejection in vascularized composite allotransplantation.

With recent advancements in deep learning (DL) techniques, the use of artificial intelligence (AI) has become increasingly prevalent in all fields. Currently valued at 9.01 billion USD, it is a rapidly growing market, projected to increase by 40% per annum. There has been great interest in how AI could transform the practice of medicine, with the potential to improve all healthcare spheres from workflow management, accessibility, and cost efficiency to enhanced diagnostics with improved prognostic accuracy, allowing the practice of precision medicine. The applicability of AI is particularly promising for transplant medicine, in which it can help navigate the complex interplay of a myriad of variables and improve patient care. However, caution must be exercised when developing DL models, ensuring they are trained with large, reliable, and diverse datasets to minimize bias and increase generalizability. There must be transparency in the methodology and extensive validation of the model, including randomized controlled trials to demonstrate performance and cultivate trust among physicians and patients. Furthermore, there is a need to regulate this rapidly evolving field, with updated policies for the governance of AI-based technologies. Taking this in consideration, we summarize the latest transplant AI developments from the Ajmera Transplant Center's inaugural symposium.

Passenger lymphocyte syndrome (PLS) is most commonly observed after solid organ transplantation with minor ABO blood group incompatibility. It consists of a set of clinical symptoms brought on by the remaining lymphocytes of the donor organ developing antibodies against the recipient's antigens. Here, we describe a typical case of PLS in a type A⁺ recipient receiving a liver transplant from a type O⁺ donor. She suffered from jaundice, abnormally decreased hemoglobin level, and severe hemolytic anemia without bleeding. During hemolysis, we detected a positive direct antiglobulin test (DAT), and the thermal elution test revealed the presence of IgG anti-A antibodies in her serum. When immunosuppressive agents and blood transfusion were used together, cross-matched O⁺ washing red blood cells led to an expected outcome without side effects.

Introduction: Transplantation of kidneys from expanded criteria donors (ECD), including after circulatory death (DCD), is associated with a higher risk of adverse events compared to kidneys from standard criteria donors. In previous studies, improvements in renal transplant outcomes have been seen when kidneys were perfused with gaseous oxygen during preservation (persufflation, PSF). In the present study, we assessed ex-vivo renal function from a Diffusion Contrast Enhanced (DCE)-MRI estimation of glomerular filtration rate (eGFR); and metabolic sufficiency from whole-organ oxygen consumption (WOOCR) and lactate production rates.

Methods: Using a porcine model of DCD, we assigned one kidney to antegrade PSF, and the contralateral kidney to static cold storage (SCS), both maintained for 24 h at 4°C. Post-preservation organ quality assessments, including eGFR, WOOCR and lactate production, were measured under cold perfusion conditions, and biopsies were subsequently taken for histopathological analysis.

Results: A significantly higher eGFR (36.6 ± 12.1 vs. 11.8 ± 4.3 ml/min, p < 0.05), WOOCR (182 ± 33 vs. 132 ± 21 nmol/min*g, p < 0.05), and lower rates of lactate production were observed in persufflated kidneys. No overt morphological differences were observed between the two preservation methods.

Conclusion: These data suggest that antegrade PSF is more effective in preserving renal function than conventional SCS. Further studies in large animal models of transplantation are required to investigate whether integration with PSF of WOOCR, eGFR or lactate production measurements before transplantation are predictive of post-transplantation renal function and clinical outcomes.

Until relatively recently there has been a paucity of readily available information pertaining to the demographics of the medical and surgical workforces for the subspecialty of liver transplantation. This is relevant as it relates to whether gender equity is now being achieved across this particular workforce. This manuscript focuses on what eventually led to the recognition that more comprehensive data were required along with what is now actually known with respect to the gender ratios of the liver transplant workforce along with their related academic activities. Potential solutions to address any ongoing imbalances are also examined. The extent and range of gender disparities previously reported for other cohorts of physicians and surgeons, are also apparent amongst the liver transplant workforce in most regions of the world. This also pertains to the higher leadership positions within liver transplant centers as well as for the related editorial and scientific congress roles. Common themes/recommendations are now emerging as to how best to address the lack of progress towards gender equity. These include the development and implementation of policies, the removal of barriers to career progression, and proper governance. Ongoing actions are going to be required to achieve gender equity across the workforce in liver transplantation around the world.

Long-term outcome following lung transplantation remains one of the poorest of all solid organ transplants with a 1- and 5-year survival of 85% and 59% respectively for adult lung transplant recipients and with 50% of patients developing chronic lung allograft dysfunction (CLAD) in the first 5 years following transplant. Reducing the risk of inflammatory type primary graft dysfunction (PGD) is vital for improving both short-term survival following lung transplantation and long-term outcome due to the association of early inflammatory-mediated damage to the allograft and the risk of CLAD. PGD has a multifactorial aetiology and high-grade inflammatory-type PGD is the result of cumulative insults that may be incurred in one or more of the three variables of the transplantation continuum: the donor lungs, the recipient and intraoperative process. We set out a conceptual framework which uses a fully integrated approach to this transplant continuum to attempt to identify and, where possible, modify specific donor, recipient and intraoperative PGD risk with the goal of reducing inflammatory-type PGD risk for an individual recipient. We also consider the concept and risk-benefit of matching lung allografts and recipients on the basis of donor and recipient PGD-risk compatibility. The use of ex vivo lung perfusion (EVLP) and the extended preservation of lung allografts on EVLP will be explored as safe, non-injurious EVLP may enable extensive inflammatory testing of specific donor lungs and has the potential to provide a platform for targeted therapeutic interventions on lung allografts.

Introduction: Liver transplant recipients are at a heightened risk for oropharyngeal dysphagia; identification of those who are at high risk for postoperative dysphagia could reduce hospital costs and length of stay. We sought to identify predictors of dysphagia, in a large cohort of patients who underwent liver transplantation.

Methods: Electronic medical records were queried for patients undergoing liver transplantation, who underwent instrumental swallowing evaluations. Demographics, functional outcomes, and interventions were collected. Logistic regression analyses were performed to identify predictors of dysphagia.

Results: Seven hundred and ninety-five patients met inclusionary criteria. Multivariate analyses found ethnic group (p = .0191), MELD Score (p < 0001), cold ischemia time (p = .0123), and length of intubation (p < .0001) to be predictors of post-operative development of dysphagia. Pre-transplant dialysis (p < .0001), dysphagia related to end stage liver disease (p < .0001), Karnofsky Performance Status Scale (p < .0001), wait time to transplant (p = 0.0173), surgery time (p = 0.0095), tracheostomy (p < 0.0001), and transfusion of intraoperative RBC (p < .0001), intraoperative platelets (p = 0.0018), intraoperative FFP (p = 0.0495), perioperative FFP (p = 0.0002), perioperative platelets (p = 0.0151) and perioperative RBC (p = 0.0002) were variables of significance associated with the development of postoperative dysphagia from univariate analysis.

Conclusions: Our results propose a set of predictors that should be considered when identifying post-operative critically ill patients at risk for dysphagia.