Frontiers in Transplantation最新文献

{"title":"Meta-analysis and systematic review of gout prevalence in the heart/lung transplantation population","authors":"Benedict Chui, Richard Day, Eshwar Umashankar, Christina Abdel Shaheed, Anne Keogh, Laila Girgis, Ross Penglase","doi":"10.3389/frtra.2024.1356058","DOIUrl":"https://doi.org/10.3389/frtra.2024.1356058","url":null,"abstract":"Gout may complicate solid organ transplantation with potentially serious consequences. An accurate prevalence of gout in this population is unknown.This study aimed to estimate the prevalence of gout in the heart and/or lung transplantation population through a systematic review and meta-analysis.MEDLINE, Embase, PsycINFO, CENTRAL and Cochrane Library (inception to February 2022) were searched for studies that reported the prevalence and/or incidence of gout in heart and/or lung transplant recipients. Two authors extracted outcomes data. Data were pooled using a random effects model. Overall quality of evidence was assessed using GRADE. Primary outcomes were the prevalence of pre- or post-transplant gout expressed as a prevalence rate (95% CI). Secondary outcomes included risk factors for gout, adverse events, and therapeutic complications of gout treatment.Ten studies were included. Gout prevalence (PR) was 8% pre-transplant (PR = 0.08; 95% CI: 0.05–0.12; 4 studies n = 651) and 6% post-transplant (PR = 0.06; 95% CI: 0.06–0.06; 10 studies n = 45,298). Post-transplant gout prevalence in heart transplant recipients was almost three times higher than lung transplant recipients (PR = 0.16; 95% CI: 0.13–0.20 vs. PR = 0.06; 95% CI: 0.05–0.06 respectively). Patients with a pre-transplant history of gout had a higher risk of developing post-transplant gout than patients without (RR = 3.61; 95% CI: 2.19–5.95). Factors associated with gout and outcomes for heart and/or lung transplant recipients with gout were comprehensively reviewed from the included studies.Gout is highly prevalent in heart and/or lung transplant patients. Pre-transplant gout is predictive of developing symptomatic post-transplant gout. This has significant implications for management of heart/lung transplant patients.https://www.crd.york.ac.uk/, PROSPERO (CRD42020190632).","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"5 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141119614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review: predicting liver transplant graft survival using artificial intelligence modeling","authors":"Aiste Gulla, I. Jakiūnaitė, I. Juchneviciute, G. Dzemyda","doi":"10.3389/frtra.2024.1378378","DOIUrl":"https://doi.org/10.3389/frtra.2024.1378378","url":null,"abstract":"Liver transplantation is the only treatment for patients with liver failure. As demand for liver transplantation grows, it remains a challenge to predict the short- and long-term survival of the liver graft. Recently, artificial intelligence models have been used to evaluate the short- and long-term survival of the liver transplant. To make the models more accurate, suitable liver transplantation characteristics must be used as input to train them. In this narrative review, we reviewed studies concerning liver transplantations published in the PubMed, Web of Science, and Cochrane databases between 2017 and 2022. We picked out 17 studies using our selection criteria and analyzed them, evaluating which medical characteristics were used as input for creation of artificial intelligence models. In eight studies, models estimating only short-term liver graft survival were created, while in five of the studies, models for the prediction of only long-term liver graft survival were built. In four of the studies, artificial intelligence algorithms evaluating both the short- and long-term liver graft survival were created. Medical characteristics that were used as input in reviewed studies and had the biggest impact on the accuracy of the model were the recipient's age, recipient's body mass index, creatinine levels in the recipient's serum, recipient's international normalized ratio, diabetes mellitus, and recipient's model of end-stage liver disease score. To conclude, in order to define important liver transplantation characteristics that could be used as an input for artificial intelligence algorithms when predicting liver graft survival, more models need to be created and analyzed, in order to fully support the results of this review.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":" 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141128556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Kidney transplant patients with COVID-19 infection","authors":"B. Özdemir","doi":"10.3389/frtra.2024.1407254","DOIUrl":"https://doi.org/10.3389/frtra.2024.1407254","url":null,"abstract":"","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Antibody-mediated rejection","authors":"R. Hachem, T. Mohanakumar","doi":"10.3389/frtra.2024.1408225","DOIUrl":"https://doi.org/10.3389/frtra.2024.1408225","url":null,"abstract":"","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"662 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140719239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pretransplant, Th17 dominant alloreactivity in highly sensitized kidney transplant candidates","authors":"Sarita Negi, Alissa K Rutman, C. Saw, S. Paraskevas, J. Tchervenkov","doi":"10.3389/frtra.2024.1336563","DOIUrl":"https://doi.org/10.3389/frtra.2024.1336563","url":null,"abstract":"Sensitization to donor human leukocyte antigen (HLA) molecules prior to transplantation is a significant risk factor for delayed access to transplantation and to long-term outcomes. Memory T cells and their cytokines play a pivotal role in shaping immune responses, thereby increasing the risk of allograft rejection among highly sensitized patients. This study aims to elucidate the precise contribution of different CD4+ memory T cell subsets to alloreactivity in highly sensitized (HS) kidney transplant recipients.Stimulation of peripheral blood mononuclear cells (PBMC) with various polyclonal stimulating agents to assess non-specific immune responses revealed that HS patients exhibit elevated immune reactivity even before kidney transplantation, compared to non-sensitized (NS) patients. HS patients' PBMC displayed higher frequencies of CD4+ T cells expressing IFNγ, IL4, IL6, IL17A, and TNFα and secreted relatively higher levels of IL17A and IL21 upon stimulation with PMA/ionomycin. Additionally, PBMC from HS patients stimulated with T cell stimulating agent phytohemagglutinin (PHA) exhibited elevated expression levels of IFNγ, IL4 and, IL21. On the other hand, stimulation with a combination of resiquimod (R848) and IL2 for the activation of memory B cells demonstrated higher expression of IL17A, TNFα and IL21, as determined by quantitative real-time PCR. A mixed leukocyte reaction (MLR) assay, employing third-party donor antigen presenting cells (APCs), was implemented to evaluate the direct alloreactive response. HS patients demonstrated notably higher frequencies of CD4+ T cells expressing IL4, IL6 and IL17A. Interestingly, APCs expressing recall HLA antigens triggered a stronger Th17 response compared to APCs lacking recall HLA antigens in sensitized patients. Furthermore, donor APCs induced higher activation of effector memory T cells in HS patients as compared to NS patients.These results provide an assessment of pretransplant alloreactive T cell subsets in highly sensitized patients and emphasize the significance of Th17 cells in alloimmune responses. These findings hold promise for the development of treatment strategies tailored to sensitized kidney transplant recipients, with potential clinical implications.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"54 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140730016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High burden of CMV infections after simultaneous pancreas-kidney transplantation—a nationwide cohort study","authors":"K. Ahopelto, Juulia Grasberger, Fernanda Ortiz, A. Ekstrand, Arno Nordin, Marko Lempinen, I. Helanterä","doi":"10.3389/frtra.2024.1370945","DOIUrl":"https://doi.org/10.3389/frtra.2024.1370945","url":null,"abstract":"Cytomegalovirus (CMV) infections remain a common problem after solid-organ transplantation. We characterized the burden of CMV infections, and adverse events of CMV prophylaxis after simultaneous pancreas-kidney transplantation (SPK). We included all SPK patients (n = 236) since 2010 in our country. Immunosuppression was ATG, tacrolimus, mycophenolate, and steroids. Valganciclovir prophylaxis was given to all CMV D+/R− patients for six months, and to seropositive SPK patients for three months since February 2019. CMV DNAemia was monitored with quantitative PCR from plasma. Among D+/R− SPK recipients, post prophylaxis CMV infection was detected in 41/60 (68%) during follow-up. In seropositive SPK recipients with no prophylaxis, CMV infection was detected in 53/95 (56%), vs. 28/78 (36%) in those who received 3 months of prophylaxis (P = 0.01). CMV was symptomatic in 35 (15%) patients, of which 10 required hospitalization. Mean duration of viremia was 28 days (IQR 21–41). Leukopenia was detected in 63 (46%) of the 138 patients with valganciclovir prophylaxis. 7/122 (6%) of the CMV infections detected were defined as refractory to treatment, and three patients had confirmed ganciclovir resistance. SPK recipients experience a high burden of CMV infections despite CMV prophylaxis. Leukopenia is common during valganciclovir prophylaxis.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"5 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140745617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting clinical endpoints and visual changes with quality-weighted tissue-based renal histological features","authors":"Ka Ho Tam, Maria F. Soares, Jesper Kers, Edward J. Sharples, Rutger Ploeg, M. Kaisar, Jens Rittscher","doi":"10.3389/frtra.2024.1305468","DOIUrl":"https://doi.org/10.3389/frtra.2024.1305468","url":null,"abstract":"Two common obstacles limiting the performance of data-driven algorithms in digital histopathology classification tasks are the lack of expert annotations and the narrow diversity of datasets. Multi-instance learning (MIL) can address the former challenge for the analysis of whole slide images (WSI), but performance is often inferior to full supervision. We show that the inclusion of weak annotations can significantly enhance the effectiveness of MIL while keeping the approach scalable. An analysis framework was developed to process periodic acid-Schiff (PAS) and Sirius Red (SR) slides of renal biopsies. The workflow segments tissues into coarse tissue classes. Handcrafted and deep features were extracted from these tissues and combined using a soft attention model to predict several slide-level labels: delayed graft function (DGF), acute tubular injury (ATI), and Remuzzi grade components. A tissue segmentation quality metric was also developed to reduce the adverse impact of poorly segmented instances. The soft attention model was trained using 5-fold cross-validation on a mixed dataset and tested on the QUOD dataset containing n=373 PAS and n=195 SR biopsies. The average ROC-AUC over different prediction tasks was found to be 0.598±0.011, significantly higher than using only ResNet50 (0.545±0.012), only handcrafted features (0.542±0.011), and the baseline (0.532±0.012) of state-of-the-art performance. In conjunction with soft attention, weighting tissues by segmentation quality has led to further improvement (AUC=0.618±0.010). Using an intuitive visualisation scheme, we show that our approach may also be used to support clinical decision making as it allows pinpointing individual tissues relevant to the predictions.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"83 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140751039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Precision therapeutics using next generation technologies in transplantation","authors":"S. Nadig, Joseph P. Leventhal, Lorenzo Gallon, Carl Atkinson","doi":"10.3389/frtra.2024.1371701","DOIUrl":"https://doi.org/10.3389/frtra.2024.1371701","url":null,"abstract":"","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"40 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140077053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted mapping and utilization of the perihepatic surface for therapeutic beta cell replacement and retrieval in diabetic non-human primates","authors":"David J. Leishman, S. Oppler, L. Stone, Timothy D O'Brien, Sabarinathan Ramachandran, Bradley J Willenberg, Andrew B. Adams, Bernhard J. Hering, Melanie L. Graham","doi":"10.3389/frtra.2024.1352777","DOIUrl":"https://doi.org/10.3389/frtra.2024.1352777","url":null,"abstract":"Successful diabetes reversal using pancreatic islet transplantation by various groups illustrates the significant achievements made in cell-based diabetes therapy. While clinically, intraportal islet delivery is almost exclusively used, it is not without obstacles, including instant blood-mediated inflammatory reaction (IBMIR), relative hypoxia, and loss of function over time, therefore hindering long-term success. Here we demonstrate the perihepatic surface of non-human primates (NHPs) as a potential islet delivery site maximizing favorable characteristics, including proximity to a dense vascular network for adequate oxygenation while avoiding IBMIR exposure, maintenance of portal insulin delivery, and relative ease of accessibility through minimally invasive surgery or percutaneous means. In addition, we demonstrate a targeted mapping technique of the perihepatic surface, allowing for the testing of multiple experimental conditions, including a semi-synthetic hydrogel as a possible three-dimensional framework to improve islet viability.Perihepatic allo-islet cell transplants were performed in immunosuppressed cynomolgus macaques using a targeted mapping technique to test multiple conditions for biocompatibility. Transplant conditions included islets or carriers (including hydrogel, autologous plasma, and media) alone or in various combinations. Necropsy was performed at day 30, and histopathology was performed to assess biocompatibility, immune response, and islet viability. Subsequently, single-injection perihepatic allo-islet transplant was performed in immunosuppressed diabetic cynomolgus macaques. Metabolic assessments were measured frequently (i.e., blood glucose, insulin, C-peptide) until final graft retrieval for histopathology.Targeted mapping biocompatibility studies demonstrated mild inflammatory changes with islet-plasma constructs; however, significant inflammatory cell infiltration and fibrosis were seen surrounding sites with the hydrogel carrier affecting islet viability. In diabetic NHPs, perihepatic islet transplant using an autologous plasma carrier demonstrated prolonged function up to 6 months with improvements in blood glucose, exogenous insulin requirements, and HbA1c. Histopathology of these islets was associated with mild peri-islet mononuclear cell infiltration without evidence of rejection.The perihepatic surface serves as a viable site for islet cell transplantation demonstrating sustained islet function through 6 months. The targeted mapping approach allows for the testing of multiple conditions simultaneously to evaluate immune response to biomaterials at this site. Compared to traditional intraportal injection, the perihepatic site is a minimally invasive approach that allows the possibility for graft recovery and avoids IBMIR.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"29 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139595634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BK polyomavirus infection: more than 50 years and still a threat to kidney transplant recipients","authors":"Sandesh Parajuli, Fahad Aziz, Weixiong Zhong, A. Djamali","doi":"10.3389/frtra.2024.1309927","DOIUrl":"https://doi.org/10.3389/frtra.2024.1309927","url":null,"abstract":"BK polyomavirus (BKPyV) is a ubiquitous human polyomavirus and a major infection after kidney transplantation, primarily due to immunosuppression. BKPyV reactivation can manifest as viruria in 30%–40%, viremia in 10%–20%, and BK polyomavirus-associated nephropathy (BKPyVAN) in 1%–10% of recipients. BKPyVAN is an important cause of kidney graft failure. Although the first case of BKPyV was identified in 1971, progress in its management has been limited. Specifically, there is no safe and effective antiviral agent or vaccine to treat or prevent the infection. Even in the current era, the mainstay approach to BKPyV is a reduction in immunosuppression, which is also limited by safety (risk of de novo donor specific antibody and rejection) and efficacy (graft failure). However, recently BKPyV has been getting more attention in the field, and some new treatment strategies including the utilization of viral-specific T-cell therapy are emerging. Given all these challenges, the primary focus of this article is complications associated with BKPyV, as well as strategies to mitigate negative outcomes.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"29 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139599951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}