Pub Date : 2024-05-20DOI: 10.3389/frtra.2024.1356058
Benedict Chui, Richard Day, Eshwar Umashankar, Christina Abdel Shaheed, Anne Keogh, Laila Girgis, Ross Penglase
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).
{"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}
Pub Date : 2024-05-13DOI: 10.3389/frtra.2024.1378378
Aiste Gulla, I. Jakiūnaitė, I. Juchneviciute, G. Dzemyda
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.
{"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}
Pub Date : 2024-04-10DOI: 10.3389/frtra.2024.1408225
R. Hachem, T. Mohanakumar
{"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}
Pub Date : 2024-04-08DOI: 10.3389/frtra.2024.1336563
Sarita Negi, Alissa K Rutman, C. Saw, S. Paraskevas, J. Tchervenkov
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.
移植前对供体人类白细胞抗原（HLA）分子致敏是导致移植手术延迟和长期预后的一个重要风险因素。记忆 T 细胞及其细胞因子在形成免疫反应方面起着关键作用，从而增加了高度致敏患者发生异体移植排斥反应的风险。用各种多克隆刺激剂刺激外周血单核细胞（PBMC）以评估非特异性免疫反应，结果显示，与非致敏（NS）患者相比，HS 患者甚至在肾移植前就表现出较高的免疫反应性。HS 患者的 PBMC 中表达 IFNγ、IL4、IL6、IL17A 和 TNFα 的 CD4+ T 细胞频率较高，在 PMA/ionomycin 刺激下分泌的 IL17A 和 IL21 水平也相对较高。此外，用刺激 T 细胞的植物血凝素（PHA）刺激 HS 患者的 PBMC，其 IFNγ、IL4 和 IL21 的表达水平也会升高。另一方面，用瑞喹莫德（R848）和 IL2 联合刺激以激活记忆 B 细胞时，经实时定量 PCR 检测，IL17A、TNFα 和 IL21 的表达较高。采用第三方供体抗原递呈细胞（APCs）进行混合白细胞反应（MLR）测定，以评估直接异体反应。HS患者表达IL4、IL6和IL17A的CD4+T细胞频率明显更高。有趣的是，在致敏患者中，与缺乏回顾性HLA抗原的APC相比，表达回顾性HLA抗原的APC能引发更强的Th17反应。这些结果提供了对高度致敏患者移植前异体反应T细胞亚群的评估，并强调了Th17细胞在异体免疫反应中的重要性。这些发现为开发针对致敏肾移植受者的治疗策略带来了希望，并具有潜在的临床意义。
{"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}
Pub Date : 2024-04-04DOI: 10.3389/frtra.2024.1370945
K. Ahopelto, Juulia Grasberger, Fernanda Ortiz, A. Ekstrand, Arno Nordin, Marko Lempinen, I. Helanterä
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.
{"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}
Pub Date : 2024-04-03DOI: 10.3389/frtra.2024.1305468
Ka Ho Tam, Maria F. Soares, Jesper Kers, Edward J. Sharples, Rutger Ploeg, M. Kaisar, Jens Rittscher
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.
在数字组织病理学分类任务中，限制数据驱动算法性能的两个常见障碍是缺乏专家注释和数据集的多样性狭窄。多实例学习（Multi-instance Learning，MIL）可以解决前者在分析整张切片图像（WSI）时所面临的挑战，但其性能往往不如全面监督。我们的研究表明，加入弱注释可以显著提高 MIL 的效果，同时保持该方法的可扩展性。我们开发了一个分析框架来处理肾活检的周期性酸-希夫（PAS）和天狼星红（SR）玻片。工作流程将组织划分为粗略的组织类别。从这些组织中提取手工和深度特征，并使用软注意力模型进行组合，以预测多个幻灯片级标签：延迟移植物功能（DGF）、急性肾小管损伤（ATI）和雷穆齐分级成分。此外，还开发了一种组织分割质量指标，以减少分割不佳实例的不利影响。在混合数据集上使用 5 倍交叉验证对软注意力模型进行了训练，并在 QUOD 数据集上进行了测试，该数据集包含 n=373 个 PAS 和 n=195 个 SR 活检样本。结果发现，不同预测任务的平均 ROC-AUC 为 0.598±0.011，明显高于仅使用 ResNet50（0.545±0.012）、仅使用手工特征（0.542±0.011）和最先进性能基线（0.532±0.012）。与软关注相结合，根据分割质量对组织进行加权可进一步提高性能（AUC=0.618±0.010）。通过直观的可视化方案，我们展示了我们的方法也可用于支持临床决策，因为它可以精确定位与预测相关的单个组织。
{"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}
Pub Date : 2024-03-07DOI: 10.3389/frtra.2024.1371701
S. Nadig, Joseph P. Leventhal, Lorenzo Gallon, Carl Atkinson
{"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}
Pub Date : 2024-01-26DOI: 10.3389/frtra.2024.1352777
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
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.
{"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}
Pub Date : 2024-01-24DOI: 10.3389/frtra.2024.1309927
Sandesh Parajuli, Fahad Aziz, Weixiong Zhong, A. Djamali
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.
BK 多瘤病毒（BKPyV）是一种无处不在的人类多瘤病毒，也是肾移植后的一种主要感染，这主要是由于免疫抑制造成的。30%-40% 的受者会出现 BKPyV 再激活，10%-20% 的受者会出现病毒血症，1%-10% 的受者会出现 BK 多瘤病毒相关性肾病（BKPyVAN）。BKPyVAN 是导致肾移植失败的一个重要原因。虽然第一例 BKPyV 病例是在 1971 年发现的，但其治疗进展有限。具体来说，目前还没有安全有效的抗病毒药物或疫苗来治疗或预防感染。即使在当今时代，治疗 BKPyV 的主要方法也是减少免疫抑制，但这也受到安全性（产生新的供体特异性抗体和排斥反应的风险）和有效性（移植物失败）的限制。不过，最近 BKPyV 在该领域受到越来越多的关注，一些新的治疗策略正在出现，包括利用病毒特异性 T 细胞疗法。鉴于所有这些挑战，本文的主要重点是与 BKPyV 相关的并发症以及减轻不良后果的策略。
{"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}
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