Transplantation最新文献

{"title":"Metabolic Crosstalk in Steatotic Grafts: Pyruvate Kinase M2 as a Fibrogenic Switch in Allograft Fibrosis.","authors":"Frederik Schliephake, Deniz Uluk, Zoltan Czigany","doi":"10.1097/TP.0000000000005548","DOIUrl":"https://doi.org/10.1097/TP.0000000000005548","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309262","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":"Embracing Liver Transplantation From Donation After Circulatory Death in the United States in the Era of Perfusion Technology.","authors":"Yuki Bekki, Abigail Loszko, Yutaka Endo, Nicholas Lim, Toshihiro Nakayama, Kazunari Sasaki, Koji Tomiyama, Roberto Hernandez-Alejandro","doi":"10.1097/TP.0000000000005537","DOIUrl":"https://doi.org/10.1097/TP.0000000000005537","url":null,"abstract":"<p><strong>Background: </strong>Utilization rates of potential deceased donors for liver transplantation has declined following the implementation of the acuity circles system in 2020. Since then, ex situ machine perfusion (es-MP) and normothermic regional perfusion (NRP) have been introduced in the United States.</p><p><strong>Methods: </strong>Liver graft utilization rates were analyzed using the US national registry data from 2022 to 2024. The associations of es-MP and NRP practices with donation after circulatory death (DCD) utilization rates among organ procurement organizations (OPOs) and transplant center volume were evaluated.</p><p><strong>Results: </strong>DCD donor utilization significantly increased from 21.5% in 2022 to 42.5% in 2024 (P < 0.001). Utilization of extended criteria donors (ECDs), including DCD donors aged ≥60 y or with a body mass index ≥40 kg/m2, also rose substantially, from 7.1% in 2022 to 33.2% in 2024 (P < 0.001). At the transplant center level, a significant correlation was found between the increase in transplant volume and both the es-MP use (r = 0.29; P = 0.01) and ECD utilization (r = 0.26; P = 0.02). At the OPO level, a significant association was observed between the increase in DCD utilization rate and NRP use (r = 0.29; P = 0.03).</p><p><strong>Conclusions: </strong>DCD liver utilization has significantly increased, with a notable rise in the utilization of ECDs, which may be driven by new technologies such as es-MP and NRP. While es-MP at the center level use may increase transplant volume, NRP use at the OPO level appears to significantly improve DCD liver utilization.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293826","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":"Utilization and Transplantation of Unused Kidneys After Assessment Using Normothermic Machine Perfusion Technology.","authors":"Sarah A Hosgood, Chris J Callaghan, Colin H Wilson, Benedict L Phillips, Emily R Thompson, Lucy Bates, Maithili Mehta, Michael L Nicholson","doi":"10.1097/TP.0000000000005540","DOIUrl":"https://doi.org/10.1097/TP.0000000000005540","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293926","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":"Conventional and Contrast-enhanced Ultrasound Imaging in 2 Human Kidney Xenotransplant Recipients.","authors":"Sylvain Bodard, Amirkasra Mojtahed, Madeleine Sertic, Theodore T Pierce, Rory L Cochran, Reece J Goiffon, Leonardo V Riella","doi":"10.1097/TP.0000000000005538","DOIUrl":"https://doi.org/10.1097/TP.0000000000005538","url":null,"abstract":"<p><strong>Background: </strong>Kidney xenotransplantation offers a promising novel solution to the global organ shortage, although the expected postoperative imaging characteristics remain undefined.</p><p><strong>Methods: </strong>We report the first application of longitudinal grayscale, color, and spectral Doppler ultrasound in 2 human recipients of genetically engineered porcine kidney xenografts. One recipient additionally underwent serial contrast-enhanced ultrasound to assess parenchymal perfusion. Imaging findings were correlated with serum creatinine trajectories and biopsy-proven rejection.</p><p><strong>Results: </strong>In both recipients, spectral Doppler abnormalities-including elevation in resistive index-preceded biopsy-confirmed T-cell-mediated rejection. Contrast-enhanced ultrasound in 1 recipient revealed delayed contrast enhancement that paralleled rejection and normalized with treatment. Neither graft demonstrated significant posttransplant growth, with observed changes in graft length remaining within the expected range for Yucatan miniature swine-derived kidneys.</p><p><strong>Conclusions: </strong>These findings provide the first preliminary ultrasound-based insights into kidney xenograft vascular dynamics and growth patterns, underscoring the potential of ultrasound as an essential tool for noninvasive monitoring of kidney xenotransplants.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293866","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":"The Nitroalkene SANA Dampens Alloreactivity Through Heme Oxygenase-1 and Regulatory T Cells.","authors":"Alain Le Moine","doi":"10.1097/TP.0000000000005535","DOIUrl":"https://doi.org/10.1097/TP.0000000000005535","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281085","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":"Predicting Post-intestinal Transplant Patient Survival Based on A Priori Data.","authors":"Samantha A Weiss, Erin Schnellinger, Julia Foutz, Simran Shah, Syed-Mohammed Jafri, Simon Horslen, Joshua Weiner","doi":"10.1097/TP.0000000000005532","DOIUrl":"https://doi.org/10.1097/TP.0000000000005532","url":null,"abstract":"<p><strong>Background: </strong>Intestinal transplantation (ITx) is the definitive treatment for patients with intestinal failure who experience severe complications on total parenteral nutrition. However, ITx has the highest morbidity among solid organ transplants. Currently, there is little information to guide clinicians in choosing the timepoint at which the advantages of ITx outweigh the risks. We seek to predict post-ITx survival using a priori data to help patients determine whether to undergo ITx.</p><p><strong>Methods: </strong>This study used data from the Organ Procurement and Transplantation Network database on all ITx procedure performed in the United States from 2016 to 2021 (n = 567), of whom 17.3% (n = 98) were censored as lost to follow-up and 33.3% (n = 189) died. The cohort included both pediatric and adult patients as well as multiorgan patients. The inclusion of such a diverse cohort was supported by sensitivity analyses. An adjusted Cox model was used to model 2-y posttransplant patient survival using data available before transplant.</p><p><strong>Results: </strong>Repeat sepsis on total parenteral nutrition before transplant (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.07-1.97), older age (HR, 1.02; 95% CI, 1.02-1.03), and the need for a concomitant liver (HR, 1.43; 95% CI, 1.03-1.99) were associated with poorer posttransplant survival. Lower bilirubin levels were associated with higher posttransplant survival.</p><p><strong>Conclusions: </strong>This research reinforces the conclusion that an ITx should be pursued before liver disease progresses to the point of requiring a concomitant liver.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281024","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":"Impact of the 6-mo Wait Policy on Transplantation, Resection, and Ablation Outcomes for Patients With Hepatocellular Carcinoma: A National Cancer Database Analysis.","authors":"Bima J Hasjim, Mitchell Paukner, Allison J Kwong, Mamatha Bhat, Hirohito Ichii, Robert R Redfield, Oliver S Eng, Zeljka Jutric, David K Imagawa, Reed I Ayabe","doi":"10.1097/TP.0000000000005536","DOIUrl":"https://doi.org/10.1097/TP.0000000000005536","url":null,"abstract":"<p><strong>Background: </strong>The mandatory 6-mo waiting period implemented in 2015 for accruing model for end-stage liver disease exception points in patients with early-stage hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) has been associated with improved outcomes. However, most of these findings are dependent on cohorts who have had access to the OLT waitlist, and the policy's impact on non-OLT treatment strategies (eg, liver resection, ablation) remains poorly understood.</p><p><strong>Methods: </strong>This was a retrospective analysis of patients with early-stage HCC (T2N0M0) from the National Cancer Database from 2010 to 2021. The pre-/post-policy era was defined by HCC diagnosis before or after 2015, respectively. The Kaplan-Meier survival method and multivariable Cox proportional hazard regression were used to estimate survival.</p><p><strong>Results: </strong>Among 53 928 patients, rates of OLT decreased (13.1%-7.4%), ablation increased (19.1%-25.3%), and resection remained constant (9.2% versus 9.2%) from the pre- to post-policy era (P < 0.001 for all). OLT was associated with the highest 5-y postoperative survival (79.7%), followed by resection (63.5%) and ablation (42.9%; P < 0.001, all pairwise comparisons). Overall survival improved in the post-policy era (hazard ratio, 0.89; 95% confidence interval, 0.87-0.92), with resection having the greatest improvement in survival (hazard ratio, 0.69; 95% confidence interval, 0.62-0.77). Among all treatment modalities, time-to-intervention was not a predictor of mortality (P > 0.05).</p><p><strong>Conclusions: </strong>Overall, the post-policy era was associated with improved outcomes in early-stage HCC. While survival outcomes between policy eras were similar for OLT or ablation, liver resection was shown to have the highest improvement in survival and remains a durable treatment option in early-stage HCC.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281077","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":"Enhanced Diagnosis of Chronic Antibody-mediated Rejection Using Peritubular Capillary Multilayering.","authors":"Brian J Nankivell, Meena Shingde, Chow Heok P'Ng, Thomas Tran","doi":"10.1097/TP.0000000000005534","DOIUrl":"https://doi.org/10.1097/TP.0000000000005534","url":null,"abstract":"<p><strong>Background: </strong>Peritubular capillary multilayering (PTCML) of basement membranes is an ultrastructural feature of chronic antibody-mediated rejection (AMR) with uncertain diagnostic thresholds.</p><p><strong>Methods: </strong>This single-center, prospective cohort study evaluated the relationships of PTCML with chronic AMR in 2541 kidney samples from 1195 recipients.</p><p><strong>Results: </strong>Epidemiological modeling found that younger recipients, living donation, early AMR, pulse corticosteroid rejection treatment, later presentation, and higher donor-specific antibody strength were clinical risk factors for an abnormal PTCML score of ≥3. The total number of PTC layers was correlated with posttransplant time, AMR histology, donor-specific antibody positivity, renal dysfunction, proteinuria, and graft failure. Histological Banff cg, ptc, C4dptc, and C4dglom independently predicted PTCML ≥3. Mild PTCML of 3-4 layers with circumferential remodeling in multiple PTC showed 82.9% sensitivity and 72.7% specificity against the Banff cg≥1a reference test, verified using Banff 2022 AMR criteria, and considered \"suspicious\" for chronic AMR. PTCML ≥5 correlated with late graft failure. Normal PTC (n = 322) in early protocol samples showed 1 basement membrane layer, except for 12.5% with mild segmental reduplication involving 13.7 ± 10.2% capillary circumference. Circumferential scoring efficiently separated mild segmental PTCML from normal variability against pathological AMR multilayering. The poor 30.0% sensitivity and 91.1% specificity (n = 374 late indication biopsies, 2029 PTCs) of the Banff 2013 AMR criteria improved to 55.0% and 89.7% using modified PTCML ≥7 or 2×PTCML ≥5 criteria, which allowed for a diagnostic disease \"rule-in.\"</p><p><strong>Conclusions: </strong>Circumferential multilayering from PTCML ≥3 replicated across multiple capillaries optimally recognized mild chronic AMR as a superior histological marker of chronic tissue injury with high sensitivity. These ultrastructural diagnostic criteria for the detection of early chronic AMR phenotypes require multicenter validation.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252862","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":"Proteinuria Remains a Significant Hurdle to Successful Pig Kidney Xenotransplantation Despite an Effective Immunosuppressive Regimen.","authors":"Kohei Kinoshita, Akihiro Maenaka, Maho Terashita, Ivy A Rosales, Yuji Hidaka, Gweneth Eliza Lavalla, Madelyn Ma, Zahra Habibabady, David Ayares, Seth Lederman, Robert B Colvin, Richard N Pierson, Tatsuo Kawai, David K C Cooper","doi":"10.1097/TP.0000000000005508","DOIUrl":"https://doi.org/10.1097/TP.0000000000005508","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated the efficacy of an optimized immunosuppressive regimen, including a higher dose of anti-CD154 monoclonal antibody (TNX-1500), in prolonging graft survival in pig-to-baboon kidney xenotransplantation. Despite advances in genetic engineering of organ-source pigs and immunosuppressive regimens, we report that the development of nephrotic-range proteinuria remains a significant problem.</p><p><strong>Methods: </strong>We assessed the TNX-1500-based immunosuppressive regimen in 9 baboon recipients of gene-edited pig kidney transplants. The regimen included induction with antithymocyte globulin, anti-CD20 monoclonal antibody (rituximab), and C1 esterase inhibitor, and maintenance with TNX-1500, rapamycin, methylprednisolone, and anti-interleukin-6 receptor blockade (tocilizumab).</p><p><strong>Results: </strong>Although an increased dose of TNX-1500 of 30 mg/kg (higher dose, n = 6) versus 20 mg/kg (lower dose, n = 3) improved overall survival (median 214 versus 86 d; P < 0.05), 4 of 9 baboons (including 3 with higher dose) developed persistent nephrotic-range proteinuria. The histopathology of these 4 grafts revealed focal glomerular thrombotic microangiopathy (4/4), transplant glomerulopathy (3/4), focal segmental glomerulosclerosis (2/4), and/or membranous nephropathy (1/4) but no definitive features of rejection. Proteinuria was associated with decreased serum albumin and, very importantly, with loss of TNX-1500 in the urine.</p><p><strong>Conclusions: </strong>Despite the efficacy of the immunosuppressive regimen, we suggest that proteinuria may lead to inadequate immunosuppressive therapy through loss of the therapeutic antibody, thus increasing the risk of rejection. Further research is needed to develop strategies to prevent this complication.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239626","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":"Direct Procurement and Perfusion Using Hypothermic Oxygenated Perfusion for DCD Cardiac Allografts in North America.","authors":"John M Trahanas, Nathan J Smith, Swaroop Bommareddi, Stephen A Devries, Juglans Alvarez, Brian Lima, Aaron M Williams, Duc Nguyen, Eric Quintana, Susan Sacks, Sandip Zalawadiya, Amy Friedman, Andreas Wallinder, Shelley Scholl, Kelly Schlendorf, JoAnn Lindenfeld, Ashish S Shah","doi":"10.1097/TP.0000000000005415","DOIUrl":"10.1097/TP.0000000000005415","url":null,"abstract":"<p><strong>Background: </strong>Donation after circulatory death (DCD) is a viable avenue for recovery of cardiac allografts for transplantation. Previous methods have utilized direct procurement and perfusion (DPP) using commercially available normothermic perfusion systems or in situ normothermic regional perfusion. A novel portable hypothermic oxygenated perfusion device (HOPE) (XVIVO Perfusion) has been developed and is in clinical trials for preservation of cardiac allografts. Here, we report the first North American experience using a HOPE preservation device for DPP recovery of DCD cardiac allografts and detail our experience and early patient outcomes.</p><p><strong>Methods: </strong>DCD cardiac allografts were procured and preserved using the HOPE platform and transported to our medical center for transplantation into awaiting recipients. Patient clinical course and outcomes are reported. Permission for this report was granted by the study sponsor and by our institutional review board.</p><p><strong>Results: </strong>Five end-stage heart failure patients underwent orthotopic heart transplantation at our institution using DCD allografts preserved with the HOPE platform. Average preservation time was 298 min with no observed cases of severe primary graft dysfunction. One patient died because of multiple extracardiac complications, but with preserved allograft function, and 1 patient required mechanical circulatory support for secondary graft dysfunction. All patients surviving to discharge were alive at last follow-up.</p><p><strong>Conclusions: </strong>This early, limited, single-institution experience of DPP preservation of DCD cardiac allografts using a HOPE platform demonstrates early success in transplanting adequately functioning allografts with acceptable patient outcomes. Further study and experience with HOPE for DCD allografts is needed.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1639-1645"},"PeriodicalIF":5.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047953","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}