Raphael P H Meier, Moufida Ben Nasr, Brian T Fife, Erik B Finger, Paolo Fiorina, Xunrong Luo, Jonathan S Bromberg
{"title":"Best practices in islet transplantation in mice.","authors":"Raphael P H Meier, Moufida Ben Nasr, Brian T Fife, Erik B Finger, Paolo Fiorina, Xunrong Luo, Jonathan S Bromberg","doi":"10.1016/j.ajt.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.03.008","url":null,"abstract":"<p><p>Islet transplantation in mice serves as a crucial preclinical model for understanding alloimmune and autoimmune mechanisms, optimizing immunosuppressive strategies, and developing novel therapies for diabetes. This review provides a comprehensive overview of best practices in murine islet transplantation, including diabetes induction models, technical aspects of islet transplantation, and criteria for transplant graft and rejection. We discuss the immunological challenges posed by MHC disparities, the impact of various transplantation sites, and the limitations of murine models in translating findings to clinical settings. Special emphasis is placed on emerging strategies such as stem cell-derived insulin-producing cells, immune tolerance induction, and alternative transplantation sites. While mouse models have significantly advanced our understanding of diabetes and β-cell replacement, their inherent differences from human physiology necessitate careful interpretation of findings. The review also highlights novel imaging modalities, immunosuppressive protocols, and biomarkers for graft monitoring, underscoring the need for further refinement of these models to bridge the gap between experimental research and clinical application. By standardizing methodologies and addressing translational limitations, murine islet transplantation studies remains a key model in transplantation and can continue to shape the future of β-cell replacement therapies for insulin dependent diabetes.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633263","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}
{"title":"Cognitive impairment after liver and kidney transplant: an easy way to check.","authors":"Yvonne M Kelly, Sophoclis P Alexopoulos","doi":"10.1016/j.ajt.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.03.009","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629985","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}
{"title":"Living kidney donation from a death row inmate.","authors":"Michael J Moritz, John S Radomski, Cary E Moritz","doi":"10.1016/j.ajt.2025.03.007","DOIUrl":"10.1016/j.ajt.2025.03.007","url":null,"abstract":"<p><p>We report on living kidney donation from a prison inmate on death row. Thirty years ago, we were involved in an unusual set of circumstances that we assumed would never arise again. That assumption is incorrect as a current death row inmate wishes to be a living kidney donor and we speak now to describe the lessons learned and to help others. This report is focused on living donation, excluding posthumous donation, and discusses the ethical, legal, medical, and logistic considerations underpinning prisoner donation for both the general prison population and death row inmates. We believe inmates on death row can be considered as living organ donors and the ethical, logistic, and medical hurdles surmounted to enable donation. This experience with death row inmates should serve to encourage donations from the general prison population.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629986","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}
{"title":"Undiagnosed lymphoma detected during routine histocompatibility crossmatch: 3 case reports.","authors":"Taba Kheradmand, Sam Ho","doi":"10.1016/j.ajt.2025.02.018","DOIUrl":"10.1016/j.ajt.2025.02.018","url":null,"abstract":"<p><p>Unexpected transmission of donor-derived diseases, including infections and malignancies, through organ transplantation are occasionally observed and reported. Subclinical, or otherwise undiagnosed, hematological malignancies in potential donors are rare events and typically not identifiable via standard donor evaluation or laboratory testing. Flow cytometric crossmatching is a specialized assay routinely performed in clinical histocompatibility laboratories for the evaluation of immunological compatibility between recipients and organ donors through the detection of donor-specific antibodies. Here, we report 3 unusual cases of undiagnosed hematological malignancies in the organ donors that were identified during routine pretransplant flow cytometric crossmatching evaluation through abnormalities observed in the lymphocyte staining profile, size, and relative cell events that effectively prevented potential transmission of such donor-derived malignancies to the immunocompromised recipients.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612867","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}
Christopher D Blosser, Lianna J Marks, Vikas R Dharnidharka
{"title":"Posttransplant lymphoproliferative disorder - it's best to face this growing challenge at the start.","authors":"Christopher D Blosser, Lianna J Marks, Vikas R Dharnidharka","doi":"10.1016/j.ajt.2025.03.006","DOIUrl":"10.1016/j.ajt.2025.03.006","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595851","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}
{"title":"Recipient toll-like receptor 4 determines the outcome of ischemia-reperfusion injury in steatotic liver transplantation in mice.","authors":"Kosuke Tanaka, Yoichiro Uchida, Kentaro Kadono, Shoichi Kageyama, Hiroshi Kawamoto, Masaaki Ito, Yuki Kidoguchi, Kenichi Saga, Hidenobu Kojima, Hirofumi Hirao, Kojiro Nakamura, Kojiro Taura, Hiroaki Terajima, Takeshi Watanabe, Etsuro Hatano","doi":"10.1016/j.ajt.2025.03.005","DOIUrl":"10.1016/j.ajt.2025.03.005","url":null,"abstract":"<p><p>Toll-like receptor 4 (TLR4) plays a crucial role in ischemia-reperfusion injury (IRI) after liver transplantation (LT). However, the role of TLR4 in the context of steatotic grafts remains unclear. In this study, we developed a mouse model to explore IRI mechanisms in steatotic LT using TLR4 knockout mice as recipients. We successfully transplanted steatotic grafts with approximately 35% macrosteatosis and 5 hours of cold storage. Compared to normal LT, steatotic LT resulted in significantly higher serum level of alanine aminotransferase and high mobility group box 1 (HMGB1), higher transcriptional expression of inflammatory markers (C-X-C motif chemokine ligand 2, caspase-1, and caspase-11), and increased infiltration of CD11b-positive cells, correlating with lower survival. Serum HMGB1 and cleaved caspase-3 activation peaked earlier than serum alanine aminotransferase, with cold-stored steatotic grafts releasing more HMGB1. Notably, TLR4 knockout recipients demonstrated improved survival, attenuated inflammatory response, and reduced apoptosis. These findings suggest that TLR4 deficiency in recipients ameliorates IRI in steatotic LT, highlighting the importance of recipient immune modulation in mitigating steatotic graft injury.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595856","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}
Shyfuddin Ahmed, Ruth M Pfeiffer, Karena Volesky-Avellaneda, Christopher D Blosser, Jon J Snyder, Ajay K Israni, Charles F Lynch, Baozhen Qiao, Judy R Rees, Fiona Zwald, Kelly J Yu, Eric A Engels
{"title":"Real-world evidence regarding cancer, mortality, and graft failure risk with de novo belatacept use among kidney transplant recipients in the United States.","authors":"Shyfuddin Ahmed, Ruth M Pfeiffer, Karena Volesky-Avellaneda, Christopher D Blosser, Jon J Snyder, Ajay K Israni, Charles F Lynch, Baozhen Qiao, Judy R Rees, Fiona Zwald, Kelly J Yu, Eric A Engels","doi":"10.1016/j.ajt.2025.03.004","DOIUrl":"10.1016/j.ajt.2025.03.004","url":null,"abstract":"<p><p>Belatacept is a selective T cell costimulation blocker used in maintenance immunosuppression for kidney transplant recipients (KTRs), but evidence on cancer risk and other outcomes is limited. This retrospective cohort study used linked US transplant and cancer registry data on KTRs treated with belatacept (N = 1514) or tacrolimus (N = 7570) as initial maintenance therapy. We used multivariable Cox regression models to compare the incidence of invasive cancer, cutaneous squamous cell carcinoma, posttransplant lymphoproliferative disorder (PTLD), death, and graft failure/retransplantation (GF/RT) between belatacept and tacrolimus users. Overall, cancer incidence was 10.1 and 12.6 per 1000 person-years in belatacept and tacrolimus users, respectively. We did not find increased risk with belatacept for cancer overall (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.53-1.30), individual cancer types, or cutaneous squamous cell carcinoma. Belatacept was associated with increased risk of death (adjusted HR, 1.22; 95% CI, 1.04-1.43) but lower risk of GF/RT >4 years after transplantation (adjusted HR, 0.54; 95% CI, 0.35-0.83). PTLD risk was increased among Epstein-Barr virus-seropositive KTRs (adjusted HR, 1.96; 95% CI, 1.03-3.73). This study provides reassurance that belatacept does not increase cancer risk among KTRs, and there was a long-term protective association for GF/RT. However, we found evidence suggesting a potentially increased risk of PTLD and death with belatacept use.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595854","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}
Yasar Caliskan, Deana Mikhalkova, Baris Afsar, Rengin Elsurer Afsar, Fadee Abu Al Rub, Krista L Lentine
{"title":"Approach to kidney transplant candidates with hereditary transthyretin (TTR) amyloidosis and TTR variants: case reports and mini-review.","authors":"Yasar Caliskan, Deana Mikhalkova, Baris Afsar, Rengin Elsurer Afsar, Fadee Abu Al Rub, Krista L Lentine","doi":"10.1016/j.ajt.2025.03.002","DOIUrl":"10.1016/j.ajt.2025.03.002","url":null,"abstract":"<p><p>Evaluating kidney transplant candidates with transthyretin (TTR) variants requires a multidisciplinary approach, considering clinical, genetic, and psychosocial factors. Hereditary transthyretin amyloidosis, an autosomal dominant disorder, can affect cardiovascular and renal allograft health, complicating transplant candidacy. We present 2 cases of Black women with end-stage kidney disease of unknown etiology, identified with the pathogenic Val142Ile TTR variant during transplant evaluation. Cardiac assessments, including technetium-99m pyrophosphate scintigraphy and biopsy, ruled out cardiac amyloidosis, enabling transplant eligibility. This highlights the growing role of genetic testing in kidney transplant clinics and the need for collaboration among nephrologists, cardiologists, and genetic counselors for optimal patient management.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583997","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}
Roberta Angelico, Silvia Trapani, Tommaso Maria Manzia, Ilaria Lenci, Paolo Grossi, Andrea Ricci, Patrizia Burra, Enzo Andorno, Salvatore Agnes, Sherrie Bhoori, Umberto Baccarani, Luca S Belli, Paola Carrai, Lucio Caccamo, Amedeo Carraro, Matteo Cescon, Michele Colledan, Umberto Cillo, Luciano De Carlis, Nicola De Maria, Paolo De Simone, Fabrizio di Benedetto, Maria Francesca Donato, Giuseppe Maria Ettorre, Flaminia Ferri, Alfonso Galeota Lanza, Davide Ghinolfi, Antonio Grieco, Salvatore Gruttadauria, Simona Marenco, Silvia Martini, Vincenzo Mazzaferro, Adriano Pellicelli, Domenico Pinelli, Maria Rendina, Mario Rizzetto, Renato Romagnoli, Massimo Rossi, Francesco Paolo Russo, Laura Schiadà, Francesco Tandoi, Pierluigi Toniutto, Laura Turco, Giovanni Vennarecci, Mauro Viganò, Marco Vivarelli, Giuseppe Tisone, Giuseppe Feltrin, Alessandra Nardi, Mario Angelico
{"title":"Liver Transplantation For HDV/HBV Coinfection In Italy: An Intention-To-Treat Analysis Of Long-Term Outcomes.","authors":"Roberta Angelico, Silvia Trapani, Tommaso Maria Manzia, Ilaria Lenci, Paolo Grossi, Andrea Ricci, Patrizia Burra, Enzo Andorno, Salvatore Agnes, Sherrie Bhoori, Umberto Baccarani, Luca S Belli, Paola Carrai, Lucio Caccamo, Amedeo Carraro, Matteo Cescon, Michele Colledan, Umberto Cillo, Luciano De Carlis, Nicola De Maria, Paolo De Simone, Fabrizio di Benedetto, Maria Francesca Donato, Giuseppe Maria Ettorre, Flaminia Ferri, Alfonso Galeota Lanza, Davide Ghinolfi, Antonio Grieco, Salvatore Gruttadauria, Simona Marenco, Silvia Martini, Vincenzo Mazzaferro, Adriano Pellicelli, Domenico Pinelli, Maria Rendina, Mario Rizzetto, Renato Romagnoli, Massimo Rossi, Francesco Paolo Russo, Laura Schiadà, Francesco Tandoi, Pierluigi Toniutto, Laura Turco, Giovanni Vennarecci, Mauro Viganò, Marco Vivarelli, Giuseppe Tisone, Giuseppe Feltrin, Alessandra Nardi, Mario Angelico","doi":"10.1016/j.ajt.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.03.003","url":null,"abstract":"<p><p>Patients with HDV/HBV-related end-stage liver disease candidates for liver transplantation(LT) have traditionally been regarded as a special population, although their outcomes are controversial. A intention-to-treat(ITT) analysis of long-term outcomes of HDV/HBV-coinfected patients waitlisted for LT in Italy, between 2011-2020, was performed and compared to HBV-monoinfected LT candidates. Out of 1,731 HBV-infected LT candidates, 1,237(71.5%) had HBV-monoinfection and 494(28.5%) HDV/HBV-coinfection. At listing, HDV/HBV-coinfected patients were significantly younger, listed mainly for decompensated cirrhosis, and with less hepatocellular carcinoma (HCC:26% vs 65.8%,P<0.0001) compared to HBV-monoinfected patients. HDV/HBV-coinfected patients showed better 5-year ITT-survival (83.2%,95%CI:79.4-83.4% vs 71.6%,95%CI:68.8-74.2%;P<0.0001). ITT-multivariable analysis identified the presence of HCC, advanced recipient age, and high-MELD-Na scores as mortality risk factors. Five-years after LT, 99.1% of HDV/HBV-coinfected patients received oral nucleos(t)ide analogues, with immunoglobulins against HBsAg(HBIg) in 91.8% of cases. HBV and HDV viral recurrences were 1.1% and 0.2%, respectively, whereas recurrent or de novo HCC were 8.9% and 0.3%, respectively. In Italy, HDV/HBV-coinfected patients waitlisted for LT showed more favourable outcomes compared to HBV-monoinfected patients, both before and after LT. These excellent results, from the largest cohort reported so far, suggest that HDV/HBV-coinfected LT recipients don't represent a risky population and may be considered for simpler long-term antiviral prophylactic strategies.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583999","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}