Pub Date : 2024-08-06DOI: 10.1097/TP.0000000000005162
Amit I Bery, Natalia Belousova, Ramsey R Hachem, Antoine Roux, Daniel Kreisel
The term "chronic lung allograft dysfunction" has emerged to describe the clinical syndrome of progressive, largely irreversible dysfunction of pulmonary allografts. This umbrella term comprises 2 major clinical phenotypes: bronchiolitis obliterans syndrome and restrictive allograft syndrome. Here, we discuss the clinical manifestations, diagnostic challenges, and potential therapeutic avenues to address this major barrier to improved long-term outcomes. In addition, we review the immunologic mechanisms thought to propagate each phenotype of chronic lung allograft dysfunction, discuss the various models used to study this process, describe potential therapeutic targets, and identify key unknowns that must be evaluated by future research strategies.
{"title":"Chronic Lung Allograft Dysfunction: Clinical Manifestations and Immunologic Mechanisms.","authors":"Amit I Bery, Natalia Belousova, Ramsey R Hachem, Antoine Roux, Daniel Kreisel","doi":"10.1097/TP.0000000000005162","DOIUrl":"https://doi.org/10.1097/TP.0000000000005162","url":null,"abstract":"<p><p>The term \"chronic lung allograft dysfunction\" has emerged to describe the clinical syndrome of progressive, largely irreversible dysfunction of pulmonary allografts. This umbrella term comprises 2 major clinical phenotypes: bronchiolitis obliterans syndrome and restrictive allograft syndrome. Here, we discuss the clinical manifestations, diagnostic challenges, and potential therapeutic avenues to address this major barrier to improved long-term outcomes. In addition, we review the immunologic mechanisms thought to propagate each phenotype of chronic lung allograft dysfunction, discuss the various models used to study this process, describe potential therapeutic targets, and identify key unknowns that must be evaluated by future research strategies.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1097/TP.0000000000005170
Abhishek Jaiswal, David A Baran
{"title":"Moving Beyond the Ice Age in Heart Transplant Procurement.","authors":"Abhishek Jaiswal, David A Baran","doi":"10.1097/TP.0000000000005170","DOIUrl":"https://doi.org/10.1097/TP.0000000000005170","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-12-07DOI: 10.1097/TP.0000000000004876
Madhumitha Rabindranath, Maryam Naghibzadeh, Xun Zhao, Sandra Holdsworth, Michael Brudno, Aman Sidhu, Mamatha Bhat
Medical applications of machine learning (ML) have shown promise in analyzing patient data to support clinical decision-making and provide patient-specific outcomes. In transplantation, several applications of ML exist which include pretransplant: patient prioritization, donor-recipient matching, organ allocation, and posttransplant outcomes. Numerous studies have shown the development and utility of ML models, which have the potential to augment transplant medicine. Despite increasing efforts to develop robust ML models for clinical use, very few of these tools are deployed in the healthcare setting. Here, we summarize the current applications of ML in transplant and discuss a potential clinical deployment framework using examples in organ transplantation. We identified that creating an interdisciplinary team, curating a reliable dataset, addressing the barriers to implementation, and understanding current clinical evaluation models could help in deploying ML models into the transplant clinic setting.
机器学习(ML)的医疗应用在分析患者数据以支持临床决策和提供患者特定结果方面已显示出良好前景。在移植领域,机器学习有多种应用,包括移植前:患者优先排序、供体与受体匹配、器官分配和移植后结果。大量研究表明,ML 模型的开发和实用性具有增强移植医学的潜力。尽管越来越多的人努力开发用于临床的强大 ML 模型,但在医疗环境中部署这些工具的却寥寥无几。在此,我们总结了当前 ML 在移植中的应用,并以器官移植为例讨论了潜在的临床部署框架。我们发现,创建跨学科团队、策划可靠的数据集、解决实施障碍以及了解当前的临床评估模型有助于将 ML 模型部署到移植临床环境中。
{"title":"Clinical Deployment of Machine Learning Tools in Transplant Medicine: What Does the Future Hold?","authors":"Madhumitha Rabindranath, Maryam Naghibzadeh, Xun Zhao, Sandra Holdsworth, Michael Brudno, Aman Sidhu, Mamatha Bhat","doi":"10.1097/TP.0000000000004876","DOIUrl":"10.1097/TP.0000000000004876","url":null,"abstract":"<p><p>Medical applications of machine learning (ML) have shown promise in analyzing patient data to support clinical decision-making and provide patient-specific outcomes. In transplantation, several applications of ML exist which include pretransplant: patient prioritization, donor-recipient matching, organ allocation, and posttransplant outcomes. Numerous studies have shown the development and utility of ML models, which have the potential to augment transplant medicine. Despite increasing efforts to develop robust ML models for clinical use, very few of these tools are deployed in the healthcare setting. Here, we summarize the current applications of ML in transplant and discuss a potential clinical deployment framework using examples in organ transplantation. We identified that creating an interdisciplinary team, curating a reliable dataset, addressing the barriers to implementation, and understanding current clinical evaluation models could help in deploying ML models into the transplant clinic setting.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-12-07DOI: 10.1097/TP.0000000000004883
Mun Chae Choi, Eun-Ki Min, Seung Hyuk Yim, Deok-Gie Kim, Jae Geun Lee, Dong Jin Joo, Myoung Soo Kim
Background: Bacterial infections are major complications that cause significant mortality and morbidity in living donor liver transplantation (LDLT). The risk of bacterial infection has not been studied in ABO-incompatible (ABOi) recipients with a desensitization protocol in relation to the number of plasma exchanges (PEs). Therefore, we aimed to analyze the risk of bacterial infection in ABOi LDLT recipients with a high number of PEs compared with recipients with a low number of PEs.
Methods: A retrospective study was performed with 681 adult LDLT recipients, of whom 171 ABOi LDLT recipients were categorized into the high (n = 52) or low (n = 119) PE groups based on a cutoff value of 6 PE sessions. We compared bacterial infections and postoperative bacteremia within 6 mo after liver transplantation with the ABO-compatible (ABOc) LDLT group (n = 510) as a control group.
Results: The high PE group showed a bacterial infection rate of 49.9% and a postoperative bacteremia rate of 28.8%, which were significantly higher than those of the low PE group (31.1%, 17.8%) and the ABOc group (26.7%, 18.0%). In multivariate analysis, the high PE group was found to have a 2.4-fold higher risk of bacterial infection ( P = 0.008). This group presented a lower 5-y survival rate of 58.6% compared with the other 2 groups (81.5% and 78.5%; P = 0.030 and 0.001).
Conclusions: A high number of preoperative PEs increases bacterial infection rate and postoperative bacteremia in ABOi LDLT.
{"title":"High Number of Plasma Exchanges Increases the Risk of Bacterial Infection in ABO-incompatible Living Donor Liver Transplantation.","authors":"Mun Chae Choi, Eun-Ki Min, Seung Hyuk Yim, Deok-Gie Kim, Jae Geun Lee, Dong Jin Joo, Myoung Soo Kim","doi":"10.1097/TP.0000000000004883","DOIUrl":"10.1097/TP.0000000000004883","url":null,"abstract":"<p><strong>Background: </strong>Bacterial infections are major complications that cause significant mortality and morbidity in living donor liver transplantation (LDLT). The risk of bacterial infection has not been studied in ABO-incompatible (ABOi) recipients with a desensitization protocol in relation to the number of plasma exchanges (PEs). Therefore, we aimed to analyze the risk of bacterial infection in ABOi LDLT recipients with a high number of PEs compared with recipients with a low number of PEs.</p><p><strong>Methods: </strong>A retrospective study was performed with 681 adult LDLT recipients, of whom 171 ABOi LDLT recipients were categorized into the high (n = 52) or low (n = 119) PE groups based on a cutoff value of 6 PE sessions. We compared bacterial infections and postoperative bacteremia within 6 mo after liver transplantation with the ABO-compatible (ABOc) LDLT group (n = 510) as a control group.</p><p><strong>Results: </strong>The high PE group showed a bacterial infection rate of 49.9% and a postoperative bacteremia rate of 28.8%, which were significantly higher than those of the low PE group (31.1%, 17.8%) and the ABOc group (26.7%, 18.0%). In multivariate analysis, the high PE group was found to have a 2.4-fold higher risk of bacterial infection ( P = 0.008). This group presented a lower 5-y survival rate of 58.6% compared with the other 2 groups (81.5% and 78.5%; P = 0.030 and 0.001).</p><p><strong>Conclusions: </strong>A high number of preoperative PEs increases bacterial infection rate and postoperative bacteremia in ABOi LDLT.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138499507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-20DOI: 10.1097/TP.0000000000004958
Yu Hisadome, Daniel L Eisenson, Michelle R Santillan, Hayato Iwase, Kazuhiko Yamada
Background: Xenotransplantation using pig organs is now a clinical reality. However, the process for xenograft recipient screening lacks clarity and scientific rigor: no established thresholds exist to determine which levels of preformed antipig natural antibodies (Nabs) will be safe for clinical xenograft transplantation, and hyperacute rejection (HAR) or acute humoral xenograft rejection (AHXR), which still impacts pig-to-primate kidney xenograft survivals, may impede broader application of pig-to-human clinical xenograft transplantation.
Methods: We retrospectively examined 28 cases of pig-to-baboon kidney xenotransplantation using GalTKO±human complement regulatory protein (hCRP)-transgenic (Tg) pig donors, as well as 6 cases of triple-KO multi-Tg (10GE) pig donors, and developed screening algorithms to predict risk of HAR/AHXR based on recipient antipig Nab levels. Preformed Nabs were evaluated using both complement-dependent cytotoxicity and antibody (IgM and IgG) binding flow-cytometry assays.
Results: High complement-dependent cytotoxicity was associated with HAR/AHXR as expected. However, we also found that high levels of IgG were independently associated with HAR/AHXR, and we developed 2 indices to interpret and predict the risk of IgG-mediated HAR/AHXR.
Conclusions: Based on the data in this study, we have established a new 2-step screening, which will be used for future clinical kidney xenotransplantation trials.
{"title":"Pretransplant Screening for Prevention of Hyperacute Graft Loss in Pig-to-primate Kidney Xenotransplantation.","authors":"Yu Hisadome, Daniel L Eisenson, Michelle R Santillan, Hayato Iwase, Kazuhiko Yamada","doi":"10.1097/TP.0000000000004958","DOIUrl":"10.1097/TP.0000000000004958","url":null,"abstract":"<p><strong>Background: </strong>Xenotransplantation using pig organs is now a clinical reality. However, the process for xenograft recipient screening lacks clarity and scientific rigor: no established thresholds exist to determine which levels of preformed antipig natural antibodies (Nabs) will be safe for clinical xenograft transplantation, and hyperacute rejection (HAR) or acute humoral xenograft rejection (AHXR), which still impacts pig-to-primate kidney xenograft survivals, may impede broader application of pig-to-human clinical xenograft transplantation.</p><p><strong>Methods: </strong>We retrospectively examined 28 cases of pig-to-baboon kidney xenotransplantation using GalTKO±human complement regulatory protein (hCRP)-transgenic (Tg) pig donors, as well as 6 cases of triple-KO multi-Tg (10GE) pig donors, and developed screening algorithms to predict risk of HAR/AHXR based on recipient antipig Nab levels. Preformed Nabs were evaluated using both complement-dependent cytotoxicity and antibody (IgM and IgG) binding flow-cytometry assays.</p><p><strong>Results: </strong>High complement-dependent cytotoxicity was associated with HAR/AHXR as expected. However, we also found that high levels of IgG were independently associated with HAR/AHXR, and we developed 2 indices to interpret and predict the risk of IgG-mediated HAR/AHXR.</p><p><strong>Conclusions: </strong>Based on the data in this study, we have established a new 2-step screening, which will be used for future clinical kidney xenotransplantation trials.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-03-29DOI: 10.1097/TP.0000000000004994
Luana Cristina Lins de Medeiros Oliveira, Rand Randall Martins, Renata Borges de Oliveira, Ítala Morgânia Farias da Nóbrega, Lorena de Medeiros Batista, Francisca Sueli Monte Moreira, Cinthya Cavalcante de Andrade, Raquel Padilha Martins Tavares, Alan Lucena de Vasconcelos, Antonio Gouveia Oliveira
Background: The self-administered Kidney AlloTransplant Immunosuppressive Therapy Adherence (KATITA-25) questionnaire is a multidimensional scale for use in the pretransplant setting that evaluates the predisposition to nonadherence of patients who are candidates to kidney transplant. The scale has shown adequate internal consistency and test-retest reliability. This study presents the results of an external validation study of the KATITA-25 scale.
Methods: Patients >18 y old scheduled for kidney transplant were included in this multicenter study. The KATITA-25 scale was administered before surgery and then at 3-mo posttransplantation for evaluation of scale sensitivity to change. At this time, 2 validated medication adherence scales were applied for assessment of concurrent validity. For evaluation of predictive validity, nonadherence to immunosuppressive medication was assessed at 6 and 12 mo after transplantation by 3 independent methods: patient self-report of nonadherence using the Morisky-Green-Levine Medication Assessment Questionnaire scale, serum trough levels of immunosuppressants, and pharmacy refills.
Results: Three twenty-two patients were available for evaluation of concurrent validity and 311 patients of predictive validity. After kidney transplant, the median KATITA-25 score decreased from 20 to 8 ( P < 0.001), demonstrating scale sensitivity to change, and the KATITA-25 score showed correlation with the Basel Assessment of Adherence to Immunosuppressive Medication Scale score (Spearman's ρ 0.18, P = 0.002) and the Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral scores (ρ -0.17, P = 0.002), confirming concurrent validity. The nonadherence rate was 57.6%. The scale predictive validity was demonstrated by the area under the receiver operating characteristics curve (0.68), sensitivity (59.8%), specificity (68.2%), and positive predictive value (71.8%).
Conclusions: This external validation study of KATITA-25 scale provided evidence of sensitivity to change, and structural, criterion, and predictive validity.
{"title":"Nonadherence to Immunosuppressant Therapy of Kidney Transplant Candidate Patients: External Validation of the KATITA-25 Scale.","authors":"Luana Cristina Lins de Medeiros Oliveira, Rand Randall Martins, Renata Borges de Oliveira, Ítala Morgânia Farias da Nóbrega, Lorena de Medeiros Batista, Francisca Sueli Monte Moreira, Cinthya Cavalcante de Andrade, Raquel Padilha Martins Tavares, Alan Lucena de Vasconcelos, Antonio Gouveia Oliveira","doi":"10.1097/TP.0000000000004994","DOIUrl":"10.1097/TP.0000000000004994","url":null,"abstract":"<p><strong>Background: </strong>The self-administered Kidney AlloTransplant Immunosuppressive Therapy Adherence (KATITA-25) questionnaire is a multidimensional scale for use in the pretransplant setting that evaluates the predisposition to nonadherence of patients who are candidates to kidney transplant. The scale has shown adequate internal consistency and test-retest reliability. This study presents the results of an external validation study of the KATITA-25 scale.</p><p><strong>Methods: </strong>Patients >18 y old scheduled for kidney transplant were included in this multicenter study. The KATITA-25 scale was administered before surgery and then at 3-mo posttransplantation for evaluation of scale sensitivity to change. At this time, 2 validated medication adherence scales were applied for assessment of concurrent validity. For evaluation of predictive validity, nonadherence to immunosuppressive medication was assessed at 6 and 12 mo after transplantation by 3 independent methods: patient self-report of nonadherence using the Morisky-Green-Levine Medication Assessment Questionnaire scale, serum trough levels of immunosuppressants, and pharmacy refills.</p><p><strong>Results: </strong>Three twenty-two patients were available for evaluation of concurrent validity and 311 patients of predictive validity. After kidney transplant, the median KATITA-25 score decreased from 20 to 8 ( P < 0.001), demonstrating scale sensitivity to change, and the KATITA-25 score showed correlation with the Basel Assessment of Adherence to Immunosuppressive Medication Scale score (Spearman's ρ 0.18, P = 0.002) and the Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral scores (ρ -0.17, P = 0.002), confirming concurrent validity. The nonadherence rate was 57.6%. The scale predictive validity was demonstrated by the area under the receiver operating characteristics curve (0.68), sensitivity (59.8%), specificity (68.2%), and positive predictive value (71.8%).</p><p><strong>Conclusions: </strong>This external validation study of KATITA-25 scale provided evidence of sensitivity to change, and structural, criterion, and predictive validity.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-20DOI: 10.1097/TP.0000000000004985
Jun Shoji, William C Goggins, Jason R Wellen, Patrick N Cunningham, Olwyn Johnston, Shirley S Chang, Kim Solez, Vicki Santos, Tami J Larson, Masahiro Takeuchi, Xuegong Wang
Background: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS.
Methods: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant.
Results: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study.
Conclusions: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.
{"title":"Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study.","authors":"Jun Shoji, William C Goggins, Jason R Wellen, Patrick N Cunningham, Olwyn Johnston, Shirley S Chang, Kim Solez, Vicki Santos, Tami J Larson, Masahiro Takeuchi, Xuegong Wang","doi":"10.1097/TP.0000000000004985","DOIUrl":"10.1097/TP.0000000000004985","url":null,"abstract":"<p><strong>Background: </strong>Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS.</p><p><strong>Methods: </strong>A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant.</p><p><strong>Results: </strong>Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study.</p><p><strong>Conclusions: </strong>In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-02-05DOI: 10.1097/TP.0000000000004913
Ruiqi Sun, Ning Wang, Shusen Zheng, Hangxiang Wang, Haiyang Xie
Organ transplantation is the preferred paradigm for patients with end-stage organ failures. Despite unprecedented successes, complications such as immune rejection, ischemia-reperfusion injury, and graft dysfunction remain significant barriers to long-term recipient survival after transplantation. Conventional immunosuppressive drugs have limited efficacy because of significant drug toxicities, high systemic immune burden, and emergence of transplant infectious disease, leading to poor quality of life for patients. Nanoparticle-based drug delivery has emerged as a promising medical technology and offers several advantages by enhancing the delivery of drug payloads to their target sites, reducing systemic toxicity, and facilitating patient compliance over free drug administration. In addition, nanotechnology-based imaging approaches provide exciting diagnostic methods for monitoring molecular and cellular changes in transplanted organs, visualizing immune responses, and assessing the severity of rejection. These noninvasive technologies are expected to help enhance the posttransplantation patient survival through real time and early diagnosis of disease progression. Here, we present a comprehensive review of nanotechnology-assisted strategies in various aspects of organ transplantation, including organ protection before transplantation, mitigation of ischemia-reperfusion injury, counteraction of immune rejection, early detection of organ dysfunction posttransplantation, and molecular imaging and diagnosis of immune rejection.
{"title":"Nanotechnology-based Strategies for Molecular Imaging, Diagnosis, and Therapy of Organ Transplantation.","authors":"Ruiqi Sun, Ning Wang, Shusen Zheng, Hangxiang Wang, Haiyang Xie","doi":"10.1097/TP.0000000000004913","DOIUrl":"https://doi.org/10.1097/TP.0000000000004913","url":null,"abstract":"<p><p>Organ transplantation is the preferred paradigm for patients with end-stage organ failures. Despite unprecedented successes, complications such as immune rejection, ischemia-reperfusion injury, and graft dysfunction remain significant barriers to long-term recipient survival after transplantation. Conventional immunosuppressive drugs have limited efficacy because of significant drug toxicities, high systemic immune burden, and emergence of transplant infectious disease, leading to poor quality of life for patients. Nanoparticle-based drug delivery has emerged as a promising medical technology and offers several advantages by enhancing the delivery of drug payloads to their target sites, reducing systemic toxicity, and facilitating patient compliance over free drug administration. In addition, nanotechnology-based imaging approaches provide exciting diagnostic methods for monitoring molecular and cellular changes in transplanted organs, visualizing immune responses, and assessing the severity of rejection. These noninvasive technologies are expected to help enhance the posttransplantation patient survival through real time and early diagnosis of disease progression. Here, we present a comprehensive review of nanotechnology-assisted strategies in various aspects of organ transplantation, including organ protection before transplantation, mitigation of ischemia-reperfusion injury, counteraction of immune rejection, early detection of organ dysfunction posttransplantation, and molecular imaging and diagnosis of immune rejection.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-03-29DOI: 10.1097/TP.0000000000004996
Sean P Martin, Juliet Emamaullee
{"title":"Equitable Access to Deceased Donor Livers in the United States: Are We There Yet?","authors":"Sean P Martin, Juliet Emamaullee","doi":"10.1097/TP.0000000000004996","DOIUrl":"10.1097/TP.0000000000004996","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-20DOI: 10.1097/TP.0000000000004995
Hui Zhang, Jin-Quan Luo, Guo-Dong Zhao, Yang Huang, Shi-Cong Yang, Pei-Song Chen, Jun Li, Cheng-Lin Wu, Jiang Qiu, Xu-Tao Chen, Gang Huang
Background: Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN).
Methods: A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated.
Results: The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group ( P = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P = 0.031). Kaplan-Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group ( P = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival.
Conclusions: Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN.
{"title":"Concurrent JCPyV-DNAemia Is Correlated With Poor Graft Outcome in Kidney Transplant Recipients With Polyomavirus-associated Nephropathy.","authors":"Hui Zhang, Jin-Quan Luo, Guo-Dong Zhao, Yang Huang, Shi-Cong Yang, Pei-Song Chen, Jun Li, Cheng-Lin Wu, Jiang Qiu, Xu-Tao Chen, Gang Huang","doi":"10.1097/TP.0000000000004995","DOIUrl":"10.1097/TP.0000000000004995","url":null,"abstract":"<p><strong>Background: </strong>Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN).</p><p><strong>Methods: </strong>A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated.</p><p><strong>Results: </strong>The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group ( P = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P = 0.031). Kaplan-Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group ( P = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival.</p><p><strong>Conclusions: </strong>Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}