Frontiers in transplantation最新文献

{"title":"Variability in pediatric and neonatal organ offering, acceptance and utilization: a survey of Canadian pediatric transplant programs and organ donation organizations.","authors":"Laurie A Lee, Augustina Okpere, Dori-Ann Martin, Meagan Mahoney, Lee James, Yaron Avitzur, Bailey Piggott, Christopher Tomlinson, Simon Urschel, Lorraine Hamiwka","doi":"10.3389/frtra.2024.1458563","DOIUrl":"https://doi.org/10.3389/frtra.2024.1458563","url":null,"abstract":"<p><strong>Introduction: </strong>Solid organ transplantation in children is a lifesaving therapy, however, pediatric organ donation rates remain suboptimal.</p><p><strong>Methods: </strong>We conducted a cross-sectional survey of Canadian organ donation organizations (ODOs) and pediatric transplant programs (TPs), aiming to describe policies and practices for pediatric organ allocation, acceptance, and utilization in Canada.</p><p><strong>Results: </strong>Response rates were 82% and 83% respectively for ODOs and transplant programs comprising 7 kidney, 3 heart, 2 lung, 2 liver and 1 intestine programs. All 9 ODOs reported offering pediatric organs following death by neurological criteria (DNC), while 8 reported offering organs following death by circulatory criteria (DCC) for some organs. Variability was found across ODOs and TPs. There was little agreement on both absolute and organ-specific donor exclusion criteria between ODOs. There was further disagreement in organ specific acceptance criteria between ODOs and TPs and between TPs themselves. Notably, despite the development of pediatric donation after DCC guidelines, organs from DCC donors are excluded by many ODOs and TPs.</p><p><strong>Discussion: </strong>Further variability in pediatric specific training, policies, and allocation guidelines are also documented. Significant areas for improvement in standardization in organ acceptance, offering, and allocation in pediatric donation and transplantation across Canada were identified.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1458563"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of switching from twice-daily tacrolimus to once-daily extended-release meltdose tacrolimus on cellular immune response.","authors":"Moritz Anft, Panagiota Zgoura, Sarah Skrzypczyk, Michael Dürr, Richard Viebahn, Timm H Westhoff, Ulrik Stervbo, Nina Babel","doi":"10.3389/frtra.2024.1405070","DOIUrl":"10.3389/frtra.2024.1405070","url":null,"abstract":"<p><strong>Background: </strong>LCP-Tacro [LCPT], a novel once-daily, extended-release formulation of tacrolimus, has a reduced C_max with comparable AUC exposure, requiring a ∼30% dose reduction in contrast to immediate-release tacrolimus (IR-Tac). Once-daily LCPT in <i>de novo</i> kidney transplantation has a comparable efficacy and safety profile to that of IR-Tac with advantages in bioavailability and absorption. The present investigation intends to analyze the effects of conversion from IR-Tac to LCPT on phenotype and function of T-cells and B-cells.</p><p><strong>Methods: </strong>16 kidney transplant patients treated by triple standard immunosuppression with a stable graft function undergoing a switch from IR-Tac to LCPT were included in this observational prospective study. We measured the main immune cell types and performed an in-depth characterization of B cell, dendritic cells and T cells including regulatory T cells of the patients before, 4 and 8 weeks after IR-Tac to LCPT conversion using multi-parameter fl ow cytometry. Additionally, we analyzed T cells by assessing third-party antigens (Tetanus Diphtheria, TD)-reactive T cells, which could be analyzed by restimulation with tetanus vaccine.</p><p><strong>Results: </strong>Overall, we found no significant alterations following LCPT conversion for the most immune cell populations with a few cell populations showing transient quantitative increase. Thus, 4 weeks after conversion, more regulatory T cells could be measured in the patients with a significant shift from memory to naïve Tregs. Furthermore, we found a transient B cell expansion 4 weeks after conversion from IR-Tac to LCPT. There were no changes in the percentage of other basic immune cell types and the antigen-reactive T cells were also not altered after changing the medication to LCP-tacrolimus.</p><p><strong>Conclusion: </strong>Here, we demonstrate first insights into the immune system changes occurred under IR-Tac to LCPT conversion therapy in kidney transplant patients. While phenotypic and functional characteristics of the most immune cell populations did not change, we could observe an a transient expansion of regulatory T cells in peripheral blood following IR-Tac to LCTP conversion, which might additionally contribute to the overall immunosuppressive effect.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1405070"},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic subclasses differentially perturb the gut microbiota in kidney transplant recipients.","authors":"Hanbo Dong, Runzhe Li, Ni Zhao, Darshana M Dadhania, Manikkam Suthanthiran, John R Lee, Wodan Ling","doi":"10.3389/frtra.2024.1400067","DOIUrl":"10.3389/frtra.2024.1400067","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of antibiotics on the gut microbiota in kidney transplant recipients is not well characterized. In this study, we determine the impact of different subclasses of antibiotics on the gut microbiota in a cohort of 168 kidney transplant recipients.</p><p><strong>Methods: </strong>Gut microbiome profiling was performed on 510 fecal specimens using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified fecal specimens by antibiotic exposure into 5 categories: Beta-lactam, Fluoroquinolone (FQ), Beta-lactam & FQ Group, Other Antibiotics, and No Antibiotic (No Abx). Mixed-effects regression models were utilized to identify changes in microbial diversity and in the centered log-ratio (CLR) transformed abundance of genera while adjusting for important covariates.</p><p><strong>Results: </strong>Antibiotic administration was associated with a significant decrease in the Shannon alpha diversity index, a decreased abundance of 11 taxa including <i>Eubacterium</i> and <i>Ruminococcus</i>, and an increased abundance of 16 taxa including <i>Enterococcus</i> and <i>Staphylococcus.</i> Exposure to Beta-lactam antibiotics was associated with an increased abundance of 10 taxa including <i>Enterococcus</i> and a decreased abundance of 5 taxa including <i>Eubacterium</i> while exposure to FQ antibiotics was associated with an increased abundance of 3 taxa and a decreased abundance of 4 taxa including <i>Ruminococcus</i>.</p><p><strong>Conclusions: </strong>Beta-lactam antibiotics and FQ antibiotics have a profound impact on the gut microbiota in kidney transplant recipients. Given the link of the gut microbiota to infectious complications, antibiotic associated changes in the microbiota may lead to an increased risk for further infections.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1400067"},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Walter Brendel and the dawn of transplantation research in Germany.","authors":"Walter G Land","doi":"10.3389/frtra.2024.1461399","DOIUrl":"10.3389/frtra.2024.1461399","url":null,"abstract":"<p><p>Walter Brendel was a physiologist who headed the Institut of Experimental Surgery at the University of Munich (LMU) from 1961 until 1989. His legendary career began with the development of an anti-human lymphocyte globulin (ALG) at his Institute during the late 1960s. The initial successful treatment of a small number of patients culminated in the co-treatment of the first successfully heart-transplanted patient in Capetown, South Africa (successful reversal with ALG of an acute allograft rejection). Walter Brendel was a pioneering personality whose work has laid a wide platform for the promotion of interdisciplinarily conducted innovative research programs in various domains of translational science and medicine. Among the many innovative achievements, the most notable are: discovery of involvement of the alternative pathway of complement activation in hyperacute xenograft rejection; induction of immunological tolerance to horse IgG as a means to prevent anaphylactic reactions during ALG therapy; development and clinical implementation of the extracorporeal shock wave lithotripsy for extracorporeal destruction of renal and ureteral calculi. The legacy of Brendel continues with the foundation of the <i>Walter-Brendel Kolleg für Transplantationsmedizin</i> (i.e., the German Transplant School for Transplantation Medicine), which has been held annually since 1994.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1461399"},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propionic acid supplementation promotes the expansion of regulatory T cells in patients with end-stage renal disease but not in renal transplant patients.","authors":"Moritz Anft, Fabian Meyer, Sirin Czygan, Felix S Seibert, Benjamin J Rohn, Fotios Tsimas, Richard Viebahn, Timm H Westhoff, Ulrik Stervbo, Nina Babel, Panagiota Zgoura","doi":"10.3389/frtra.2024.1404740","DOIUrl":"10.3389/frtra.2024.1404740","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1404740"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of donor transaminases on liver transplant utilisation and unnecessary organ discard: national registry cohort study.","authors":"Joseph J Dobbins, Samuel J Tingle, Jennifer Mehew, Emily R Thompson, Georgios Kourounis, Stuart McPherson, Steve A White, Colin H Wilson","doi":"10.3389/frtra.2024.1458996","DOIUrl":"https://doi.org/10.3389/frtra.2024.1458996","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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, <i>p</i> < 0.001, DCD aOR = 1.162, 1.084-1.246, <i>p</i> < 0.001). AST was also a significant predictor of liver decline. 18.5% of livers from DBD donors with ALT > 40 U/L (<i>n</i> = 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1458996"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of C4d and donor specific antibodies in face and hand transplantation-a systematic review.","authors":"Lioba Huelsboemer, Jake Moscarelli, Alna Dony, Sam Boroumand, Alejandro Kochen, Leonard Knoedler, Catherine T Yu, Sacha C Hauc, Viola A Stögner, Richard N Formica, Christiane G Lian, Georg F Murphy, Bohdan Pomahac, Martin Kauke-Navarro","doi":"10.3389/frtra.2024.1442006","DOIUrl":"https://doi.org/10.3389/frtra.2024.1442006","url":null,"abstract":"<p><p>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 (<i>p </i>= 0.005). C4d was not found to be associated with higher rejection grade (<i>p </i>= 0.33). Finally, no significant association was found between concurrent status of the two markers (<i>p </i>= 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.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1442006"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the 2024 Transplant AI Symposium.","authors":"Sara Naimimohasses, Shaf Keshavjee, Bo Wang, Mike Brudno, Aman Sidhu, Mamatha Bhat","doi":"10.3389/frtra.2024.1399324","DOIUrl":"https://doi.org/10.3389/frtra.2024.1399324","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1399324"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R. Randal Bollinger, M.D., Ph.D., Master Surgeon.","authors":"Stuart J Knechtle, Allan D Kirk","doi":"10.3389/frtra.2024.1469916","DOIUrl":"https://doi.org/10.3389/frtra.2024.1469916","url":null,"abstract":"","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1469916"},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: A case of immune hemolytic anemia after liver transplantation: passenger lymphocyte syndrome is the culprit.","authors":"Qianzhe Zhao","doi":"10.3389/frtra.2024.1463325","DOIUrl":"https://doi.org/10.3389/frtra.2024.1463325","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"3 ","pages":"1463325"},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}