Paul J Kim,Michael Olympios,Konstantinos Sideris,Eleni Tseliou,Taylor Y Tran,Spencer Carter,Alison Brann,Navchetan Kaur,Sandra A Carey,Sangeeta Bhorade,Yen-An Chen,David Barnes,Ebad Ahmed,Jing Xie,Adam Prewett,Matthew Rabinowitz,Bernhard G Zimmermann,Michelle S Bloom,Zachary Demko,Eric Adler,Josef Stehlik
{"title":"A Two-Threshold Algorithm using Donor-derived Cell-free DNA Fraction and Quantity to Detect Acute Rejection After Heart Transplantation.","authors":"Paul J Kim,Michael Olympios,Konstantinos Sideris,Eleni Tseliou,Taylor Y Tran,Spencer Carter,Alison Brann,Navchetan Kaur,Sandra A Carey,Sangeeta Bhorade,Yen-An Chen,David Barnes,Ebad Ahmed,Jing Xie,Adam Prewett,Matthew Rabinowitz,Bernhard G Zimmermann,Michelle S Bloom,Zachary Demko,Eric Adler,Josef Stehlik","doi":"10.1016/j.ajt.2025.04.021","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.021","url":null,"abstract":"Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker of acute rejection (AR) after heart transplantation (HTx). dd-cfDNA measured as a fraction of total cfDNA can be affected by changes in total cfDNA whereas dd-cfDNA quantity can mitigate this impact. This study investigates the performance of a two-threshold algorithm (2TA) that combines dd-cfDNA fraction (dd-cfDNA%) and donor-quantity score (DQS). A total of 808 plasma samples were prospectively collected for dd-cfDNA testing from 187 adult HTx patients with contemporaneous endomyocardial biopsies. cfDNA was analyzed by a single nucleotide polymorphism (SNP)-based next-generation sequencing workflow; dd-cfDNA% and DQS were measured using the sequencing reads and SNP genotypes. Both dd-cfDNA% and DQS were significantly higher in AR compared to non-AR samples (p<10-14). Considering samples exceeding either dd-cfDNA%=0.26% or DQS=18 cp/mL as positive, the 2TA demonstrated 86.5% sensitivity and 83.6% specificity for AR detection and an AUC of 0.881. Compared to dd-cfdNA% alone, performance improved with a mean net reclassification index (NRI) of 16.4% (SD: 4.0%; p=0.015) and a 37.3% reduction of the false positive rate compared to the previously established cutoff of 0.15%. Combining dd-cfDNA fraction and quantity estimate in a 2TA may improve AR detection accuracy in HTx recipients compared to dd-cfDNA% alone.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"37 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921085","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":"Active smokers should not be denied access to lung transplantation.","authors":"Andrew M Courtwright","doi":"10.1016/j.ajt.2025.04.022","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.022","url":null,"abstract":"International society consensus statements, health insurance policies, and individual transplant programs almost uniformly consider active cigarette smoking an absolute contraindication to lung transplant. This denial is typically supported on utilitarian grounds-active smokers are prohibitively high-risk because of anticipated poor long-term survival-or non-utilitarian grounds related to fairness in resource allocation to smokers. However, the available literature on lung transplant recipients who resume smoking post-transplant does not demonstrate increased mortality. At the same time, other conditions that carry significant short and long-term post-transplant mortality, such as retransplantation, are considered relative contraindications. I also suggest that arguments regarding responsibility and fairness do not support the exclusion of active smokers. Patients with lung disease from other ongoing inhalational exposures, including avian antigens in chronic hypersensitivity pneumonitis, are not automatically excluded from transplant. I argue that active smokers are stigmatized, leading smoking to be treated as an inappropriate proxy for non-adherence. I suggest that the lung transplant community should treat active smoking as a relative, not absolute, contraindication to transplant. Transplant program policy should be revised to improve access for active smokers, particularly those who are in urgent need of transplant and will not survive long enough to demonstrate smoking abstinence.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"35 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914807","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}
Vishnu S Potluri,Douglas E Schaubel,Emily A Blumberg,Harry Morford,Peter P Reese,Chethan M Puttarajappa
{"title":"High variability in the reported prevalence of EBV-seronegative status among US kidney transplant recipients.","authors":"Vishnu S Potluri,Douglas E Schaubel,Emily A Blumberg,Harry Morford,Peter P Reese,Chethan M Puttarajappa","doi":"10.1016/j.ajt.2025.04.019","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.019","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"23 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902876","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}
Kamal S Yadav,Nikhitha Shetty,Fysal Valappil,Akash Selvathangam,Suchet Chaudhary,Ankur Gupta,Prashant Bhangui,Arvinder S Soin
{"title":"COMPLEX DONOR ANATOMY DOES NOT INFLUENCE EARLY DONOR OR RECIPIENT OUTCOMES AFTER ROBOTIC DONOR HEPATECTOMY AT A HIGH VOLUME CENTER.","authors":"Kamal S Yadav,Nikhitha Shetty,Fysal Valappil,Akash Selvathangam,Suchet Chaudhary,Ankur Gupta,Prashant Bhangui,Arvinder S Soin","doi":"10.1016/j.ajt.2025.04.017","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.017","url":null,"abstract":"INTRODUCTIONWith evolving expertise, criteria to select donors for robotic living donor hepatectomy (RDH) have expanded. We studied the comparative donor and recipient outcomes in RDH with standard grafts and complex grafts.METHODSWe have performed 360 right lobe RDH (RRDH) out of 4296 LDLT, with 280 having over 6 months follow-up. First 53 cases were excluded as we used a different (cut-suture) technique for hepatic duct division. Subsequent 227 RRDH were then divided into donors with standard (group S, n=76) and complex grafts (group C, n=151).RESULTSThree donors in each group were converted to open midline incision. In Groups S and C, 1(1.3%) and 3(1.9%) donors developed biliary complications (p=0.741). Both recipient groups had similar early and late post-operative complications. Group C recipients had non-significantly higher incidence of late biliary complications [3(3.9%) vs 17(11.2%); OR 3.09, 95% CI 0.88-10.88, p=0.067]. Early (< 30days) recipient mortality was similar with 4(6.6%) in group S, and 11(7.3%) in group C (p=0.755), all sepsis related.CONCLUSIONThe outcomes were similar among donors and recipients with both standard and complex grafts. With experience, RDH can be safely offered to \"all comer\" donors and has the potential to become standard of care.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"21 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897320","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":"A 46-year-old male with posttransplant lymphoproliferative disorder and massive hemoptysis following second bilateral lung transplantation","authors":"Biplab K. Saha","doi":"10.1016/j.ajt.2025.01.027","DOIUrl":"10.1016/j.ajt.2025.01.027","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 5","pages":"Pages 1127-1129"},"PeriodicalIF":8.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882662","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":"Rejection and Graft Vasculopathy Secondary to Effects of Crohn's Disease in a Heart-Transplanted Child.","authors":"Shannon Oliver,Jennifer Conway,Darren Freed,Anne Halpin,Hien Huynh,Michael Khoury,Cheryl Kluthe,Esme Dijke,Lori West,Simon Urschel","doi":"10.1016/j.ajt.2025.04.020","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.020","url":null,"abstract":"Patients require immunosuppression post heart transplantation. Conditions such as Crohn's disease can impact tacrolimus absorption and pharmacokinetics. Subtherapeutic tacrolimus levels can lead to rejection and development of donor-specific antibodies (DSA) resulting in development of cardiac allograft vasculopathy (CAV). We present a boy who underwent an ABO-incompatible heart transplant at 10-months of age, who developed diarrhea and subtherapeutic tacrolimus levels with subsequent development of de novo DSA, then acute cellular and antibody-mediated rejection. He was diagnosed with Crohn's disease, which required vedolizumab for control. Despite aggressive reduction of his DSA, he developed rapidly progressive CAV and required re-transplant, with a high prevalence of plasma cells in the explanted heart. Donor-directed blood group antibodies remained negative. This case demonstrates the importance of early consideration of inflammatory bowel disease for patients with diarrhea and subtherapeutic tacrolimus levels, as prompt diagnosis and treatment may prevent secondary graft injury.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"134 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897318","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}
Precil Diego Miranda de Menezes Neves,Juliana Mansur,Miguel Moyses-Neto,Roberta Weisheimer Rohde,Carlos Eduardo Poli-de-Figueiredo,Stanley Almeida Araújo,David Campos Wanderley,Henrique Machado Sousa Proença,Karla Lais Pêgas,Andréia Watanabe,Elieser Hitoshi Watanabe,Hélio Tedesco-Silva,Gianna Mastroianni Kirsztajn,Clotilde Druck Garcia,Gyl Eanes de Barros Silva,Osvaldo Merege Vieira-Neto,Márcio Dantas,Sergio Ricardo Antônio,Gilson Masahiro Murata,Irene Lourdes Noronha,Roberto Silva Costa,Luiz Fernando Onuchic
{"title":"Post-transplantation recurrence of lipoprotein glomerulopathy: report of 4 cases and literature review.","authors":"Precil Diego Miranda de Menezes Neves,Juliana Mansur,Miguel Moyses-Neto,Roberta Weisheimer Rohde,Carlos Eduardo Poli-de-Figueiredo,Stanley Almeida Araújo,David Campos Wanderley,Henrique Machado Sousa Proença,Karla Lais Pêgas,Andréia Watanabe,Elieser Hitoshi Watanabe,Hélio Tedesco-Silva,Gianna Mastroianni Kirsztajn,Clotilde Druck Garcia,Gyl Eanes de Barros Silva,Osvaldo Merege Vieira-Neto,Márcio Dantas,Sergio Ricardo Antônio,Gilson Masahiro Murata,Irene Lourdes Noronha,Roberto Silva Costa,Luiz Fernando Onuchic","doi":"10.1016/j.ajt.2025.04.018","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.018","url":null,"abstract":"Lipoprotein glomerulopathy (LPG) is an ultra-rare kidney disorder caused by pathogenic variants in the APOE gene. Although kidney biopsy presents typical findings, such as dilated capillary loops containing lipoprotein thrombi, definitive diagnosis requires molecular genetic analysis of APOE. There is no specific treatment for the disease and, in the scenario of a disorder with glomerular lipoprotein deposition, the disease may recur after kidney transplantation. Herein we report four cases of post-transplantation recurrence of LPG in Brazilian patients, including one case of early relapse (in the first year following transplantation) and three cases of late relapse. Two of the patients had the APOE Kyoto variant while two harbored the APOE Osaka/Kurashiki variant. As in previously described cases, the clinical response was heterogeneous despite the use of statins and antiproteinuric agents, including remission or persistence of proteinuria and progression to different stages of chronic kidney disease. Such cases strongly support molecular genetic investigation of cases with suspicion of LPG, even in a Latin American population, since a confirmed diagnosis raises the possibility of disease recurrence in the kidney graft and can provide valuable information for selecting a potential living kidney donor.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"114 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897319","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}
Thiago J Borges,Catherine A A Lee,Kyla Mucciarone,Karina Lima,Isadora T Lape,Mauricio Lima-Filho,Bruno Ayoama,Branislav Kollar,Rodrigo B Gassen,Cristina Bonorino,Simon G Talbot,Bohdan Pomahac,Christine G Lian,George F Murphy,Leonardo V Riella
{"title":"Human Type 1 Conventional Dendritic Cells Contribute to Skin Transplant Rejection.","authors":"Thiago J Borges,Catherine A A Lee,Kyla Mucciarone,Karina Lima,Isadora T Lape,Mauricio Lima-Filho,Bruno Ayoama,Branislav Kollar,Rodrigo B Gassen,Cristina Bonorino,Simon G Talbot,Bohdan Pomahac,Christine G Lian,George F Murphy,Leonardo V Riella","doi":"10.1016/j.ajt.2025.04.016","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.016","url":null,"abstract":"The skin is the most immunogenic tissue in transplantation and the hardest tissue to induce immune modulation. Batf3-dependent type 1 conventional dendritic cells (cDC1s) are important in initiating rejection in murine skin transplantation. In humans, the CD141+ cDC1 subset is the functional counterpart of the murine Batf3-dependent cDC1s. However, their contribution to the rejection of human skin allografts remains unknown. Using samples from human face and upper extremity transplant recipients, we demonstrated that CD141+ cDC1s are increased and more activated in human skin grafts than native skin tissue from the same individual. Moreover, circulating and tissue CD141+ cDC1s were elevated in rejection time points. Local modulation of graft CD141+ cDC1s decreased HLA-DR expression and increased regulatory T cells, which correlated with a decreased presence of skin allogeneic T cells in a humanized transplantation model. Thus, CD141+ cDC1s play an important role in rejecting human skin allografts, and their local modulation is a promising therapeutic approach.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"19 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885480","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":"Islet Autotransplantation in Focal Intraductal Papillary Mucinous Neoplasms: Evaluating Feasibility, Safety, and Metabolic Outcomes in Pancreatic Resection.","authors":"Francesca Aleotti,Gianpaolo Balzano,Raffella Melzi,Alessia Mercalli,Giovanni Capretti,Stefano Crippa,Davide Catarinella,Marco Schiavo Lena,Stefano Partelli,Francesco De Cobelli,Rossana Caldara,Massimo Falconi,Alessandro Zerbi,Lorenzo Piemonti","doi":"10.1016/j.ajt.2025.04.015","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.015","url":null,"abstract":"Islet auto transplantation (IAT) is a potential therapeutic option for patients undergoing pancreatectomy to preserve endocrine function, but its role in patients with intraductal papillary mucinous neoplasms (IPMN) remains controversial due to oncological concerns. This study evaluates the feasibility, safety, and metabolic outcomes of IAT in seven patients with focal IPMN who underwent pancreatectomy between 2008 and 2023, following the Milan protocol. Primary outcomes included the technical success of islet isolation and the absence of tumor dissemination. Secondary outcomes involved insulin independence and metabolic control post-transplantation. Islet isolation success was variable, with four patients meeting the criteria for transplantation. The average islet yield was 1,097 islet equivalents per kilogram of body weight (range: 219-1,833 IEQ/kg). No patients experienced complications related to islet infusion, and there was no evidence of tumor recurrence or metastasis during a mean follow-up of 7.9 years (range: 3.99-11.88 years). IAT recipients demonstrated preserved insulin secretion, while non-transplanted patients developed diabetes. These findings support the feasibility and safety of IAT in carefully selected patients with focal IPMN, providing promising metabolic outcomes. The results open the possibility to initiate larger cohort studies and explore the potential to expand the population of patients who could benefit from this approach.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"19 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885069","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}