Transplantation Direct最新文献

{"title":"In Vitro Evaluation of Necrostatin-1 Microparticles for Limiting Stress-induced Cell Death and Preserving Islet Function.","authors":"Nerea Cuesta-Gomez, Pulkit Kumar, Purushothaman Kuppan, Joy Paramor, Abdullah Saleh, Gregory S Korbutt, Andrew R Pepper","doi":"10.1097/TXD.0000000000001945","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001945","url":null,"abstract":"<p><strong>Background: </strong>Islet transplantation offers a promising therapy for type 1 diabetes, but early β-cell loss due to stress-induced cell death limits graft survival and function. Although apoptosis has been extensively studied, necroptosis, a regulated form of necrotic cell death, remains an underexplored contributor to β-cell dysfunction. Herein, we evaluated sustained necrostatin-1 (Nec-1) delivery via poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) to protect islets from stress-induced damage in vitro.</p><p><strong>Methods: </strong>Nec-1-loaded PLGA MPs were synthesized by single-emulsion solvent evaporation and characterized by scanning electron microscopy and high-performance liquid chromatography for size, morphology, and drug encapsulation. Mouse islets were coincubated with Nec-1 or empty MPs for 24 h, followed by induction of endoplasmic reticulum stress with thapsigargin. Glucose-stimulated insulin secretion and cytokine release were quantified to assess β-cell function and inflammatory response.</p><p><strong>Results: </strong>Nec-1 MPs were spherical with a median diameter of 10.34 μm (interquartile range [IQR], 6.55-15.17 μm) and an encapsulation efficiency of 36.2% (IQR, 31.1%-40.0%). Release studies demonstrated an initial burst of 24.8% (IQR, 21.8%-30.3%) by day 3, followed by sustained delivery up to 53.6% (IQR, 52.3%-57.4%) by day 14, with minimal impact on media pH. Under thapsigargin-induced stress, Nec-1 MP-treated mouse islets maintained glucose-stimulated insulin secretion, with insulin release increasing from 2.63% (IQR, 1.42%-5.74%) to 8.63% (IQR, 7.97%-14.42%, <i>P</i> = 0.0006) compared with 3.36% (IQR, 0.53%-9.08%) in stressed controls (<i>P = </i>0.0117). The Stimulation Index was similarly preserved (3.23; IQR, 2.51-4.77 versus 1.18; IQR, 0.65-1.62; <i>P = </i>0.0002). Nec-1 MPs partially attenuated IL-12p70 secretion (103.3 pg/mL; IQR, 67.7-162.4 versus 217.1 pg/mL; IQR, 86.2-367.6; <i>P</i> = 0.0381) while maintaining low levels of other proinflammatory cytokines.</p><p><strong>Conclusions: </strong>Nec-1-loaded PLGA MPs provide sustained, localized protection of β-cells from necroptotic and inflammatory stress in vitro. Given the sustained and targeted drug delivery, these findings provide a foundation for future in vivo translation to provide graft-localized therapeutic intervention and improve islet survival, engraftment, and long-term function.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 5","pages":"e1945"},"PeriodicalIF":1.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Simultaneous Liver-Kidney Transplant and Kidney After Liver Transplant Using the Safety Net Criteria-A Single-center Experience.","authors":"Srijan Tandukar, Vishnu S Potluri, Peter Abt, David E Kaplan, Therese Bittermann, Behdad Besharatian, Maarouf A Hoteit, Matthew Levine, Arwin Thomasson, Sarah Hryzak, Anjana Murali, Shreeya Thapaliya, Karthik Ranganna, Roy D Bloom, Ty B Dunn, Mary Ann Lim","doi":"10.1097/TXD.0000000000001940","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001940","url":null,"abstract":"<p><strong>Background: </strong>The impact of revised Organ Procurement and Transplantation Network policy defining eligibility for simultaneous liver-kidney (SLK) and the safety net criteria for kidney after liver (KAL) transplantation remains insufficiently characterized.</p><p><strong>Methods: </strong>We conducted a retrospective study of adults (>18 y) evaluated for liver transplant alone (LTA), SLK, or KAL at the University of Pennsylvania from August 10, 2017, to February 28, 2023. The primary outcome was mortality among SLK and KAL recipients and those patients waitlisted for KAL. Secondary outcomes included native kidney recovery in LTA recipients, estimated glomerular filtration rate (eGFR) at 1 y post-kidney transplant, and time between liver and kidney transplants.</p><p><strong>Results: </strong>Of 1655 patients evaluated, 57 (3.4%) met SLK criteria; 49 (86%) underwent SLK and 8 (14%) received LTA. Among 1598 LTA candidates, 1010 (63%) were waitlisted and 717 (71%) received LTA. After excluding 9 early deaths (1.3%) that were unrelated to KAL delay, 67 survivors (9.5%) met KAL safety net criteria. Thirty-four (50.8%) were waitlisted (15 transplanted over a median of 220 d), 30 (44.8%) declined, and 3 (4.8%) remained under evaluation. Mortality was 4.1% after SLK and no deaths occurred after KAL >3.7 and 3.1 y of follow-up, with 3 deaths (8.8%) among KAL waitlisted patients. Of the 16 KAL waitlisted patients alive without kidney transplant at last follow-up, 2 (12.5%) were delisted after documented renal recovery and an additional 9 (56.3%) had eGFR >20 ml/min/1.73 m² and were being considered for delisting; together, 11 (68.8%) met predefined criteria for substantial native kidney recovery. One-year median eGFR was similar (SLK 51 versus KAL 54 mL/min/1.73 m²; <i>P</i> = 0.6).</p><p><strong>Conclusions: </strong>Early post-LTA mortality was unrelated to delayed KAL transplantation. Recovery of native kidney function while waiting for KAL was frequent. KAL transplants occurred within a year of LTA with favorable survival and graft outcomes.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 5","pages":"e1940"},"PeriodicalIF":1.9,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147780881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Swine Leukocyte Antigen-12 Behaves Like a Swine Leukocyte Antigen Classical Class I Protein and is a Potential Xenoantigen in Humans.","authors":"Victor Novara Gennuso, Zheng Yu Wang, Luz M Reyes, Matt Tector, A Joseph Tector","doi":"10.1097/TXD.0000000000001948","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001948","url":null,"abstract":"<p><strong>Background: </strong>Using pigs as tissue donors may eliminate the shortage of replacement organs. As in allotransplantation, antidonor antibodies cause xenotransplant failure. Many antibodies target products of the major histocompatibility complex. Pigs contain a novel major histocompatibility complex gene, swine leukocyte antigen-12 (SLA-12), which has been proposed to behave as a classical class I SLA protein. Though predicted to bind B2m and short peptides, the functionality of the SLA-12 protein remains uncertain. In addition, its similarity to classical class I SLA molecules suggests that the SLA-12 could be a xenoantigen. Here we tested these predictions.</p><p><strong>Methods: </strong>Protein modeling was used to compare SLA-12 and classical class I proteins SLA-1, SLA-2, and SLA-3. cDNA encoding an isoform of SLA-12 was introduced into a cell line devoid of HLA proteins. B2m binding of SLA-12 at the surface of this cell line was evaluated. In addition, expression of SLA-12 molecules was examined in these cells after disrupting the genes encoding the transporters of antigenic peptides for class I proteins. Serum samples collected from transplant patients were also tested for the presence of SLA-12-specific IgG and IgM.</p><p><strong>Results: </strong>Predictive algorithms indicate SLA-12 and classical class I SLA proteins have very similar structures. We observed strong biochemical similarities as well in that SLA-12 binds to B2m and peptides to become a stable cell surface protein. Finally, we observed that SLA-12-expressing cells bind more serum IgG and IgM from some transplant patients, indicating that it can be a xenoantigen.</p><p><strong>Conclusions: </strong>SLA-12 has marked structural and biochemical similarities with classical class I SLA proteins and may be another target of human anti-pig antibodies. Similar approaches may be successful in mitigating the antigenic issues of SLA-12, SLA-1, SLA-2, and SLA-3.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 5","pages":"e1948"},"PeriodicalIF":1.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Cold Ischemic Time Before Normothermic Machine Perfusion Accentuates Postreperfusion Hepatocellular Injury.","authors":"Shaheed Merani, Kennedy Scheele, Lance Fristoe, Maddie Cloonan, Sarah Uhm, Marian Urban, Kurt W Fisher, Alan N Langnas, Matthew T Andrews","doi":"10.1097/TXD.0000000000001943","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001943","url":null,"abstract":"<p><strong>Background: </strong>Prolonged cold ischemic time (CIT) before liver transplantation with static cold storage preservation is associated with higher rates of ischemia-related complications. With the introduction of normothermic machine perfusion (NMP), the overall incidence of early allograft dysfunction and biliary complications is lower. NMP can be used as a device-to-donor approach (with short CIT) or back-to-base model which is typically associated with longer CIT. It is unknown if NMP can rehabilitate organs that have suffered from prolonged CIT.</p><p><strong>Methods: </strong>Livers from a Yorkshire cross-bred pig donation after circulatory death model were recovered using conventional in situ flush with University of Wisconsin solution after systemic heparinization, followed by static cold storage in University of Wisconsin solution at 4 °C for short (2 h), long (24 h), or extended (48 h) periods of CIT before ex situ NMP. Visual appearance of the liver, perfusion hemodynamics including pressure and flow, as well as perfusate concentration of lactate, aspartate aminotransferase, and alanine aminotransferase, bile production, and histological evaluation of liver biopsies stained with hematoxylin and eosin and caspase-3 were compared between groups during NMP.</p><p><strong>Results: </strong>In addition to gross visual differences in the heterogeneity of livers with long or extended CIT compared with short CIT, the NMP perfusate from livers with extended CIT demonstrated an elevation in lactate that did not decrease with time. Although livers with long CIT showed a temporal reduction in NMP perfusate lactate concentration similar to those with short CIT, there was associated hepatocellular injury in the long CIT group manifested in the form of higher aspartate aminotransferase and alanine aminotransferase in perfusate, and increased frequency of caspase-3 positive cells indicating increased apoptosis.</p><p><strong>Conclusions: </strong>While NMP offers improved clinical outcomes post-liver transplantation, the application of NMP in back-to-base format with prolonged CIT before NMP requires further evaluation to understand the impact of ischemia-reperfusion injury.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 5","pages":"e1943"},"PeriodicalIF":1.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147780921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Laparoscopic and Hand-assisted Live Donor Nephrectomy: An Analysis of NSQIP Transplant.","authors":"Dominic Amara, Arielle Grieco, Karina Covarrubias, Yaoming Liu, Peter G Stock, David Foley, Stuart Greenstein, Ryutaro Hirose, Justin R Parekh","doi":"10.1097/TXD.0000000000001946","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001946","url":null,"abstract":"<p><strong>Background: </strong>Pure laparoscopic and hand-assisted approaches are the predominant techniques for living donor nephrectomy, yet high-quality multicenter comparisons remain limited.</p><p><strong>Methods: </strong>Using prospectively collected data from the American College of Surgeons National Surgical Quality Improvement Program Transplant pilot (from March 2017 to July 2020), we compared outcomes between pure laparoscopic and hand-assisted donor nephrectomy. Outcomes included operative duration, postoperative length of stay (LOS), and 30-d unplanned readmission. Mixed-effects linear, Poisson, and logistic regression models with hospital-level random intercepts quantified center variation and the independent association of surgical approach with outcomes.</p><p><strong>Results: </strong>Among 1542 donors, 890 (57.7%) underwent pure laparoscopic and 652 (42.3%) hand-assisted nephrectomies. Donors were predominantly female (63%), mean age 43.4 y, and 61.8% were overweight or obese. Pure laparoscopic procedures had longer operative times (180 versus 150 min; <i>P</i> < 0.001). Median LOS was similar (2 d for both), although pure laparoscopy had more extended-stay cases (<i>P</i> < 0.001). Readmission was rare and comparable (2.4% versus 2.9%; pure laparoscopic versus hand-assisted; <i>P</i> = 0.50). Center-level variation was substantial for operative duration (intraclass correlation coefficient = 0.51), and notable for LOS (median rate ratio [RR] = 1.25) and readmission (median odds ratio = 1.60). In unadjusted and adjusted models, pure laparoscopy was not associated with differences in operative duration relative to hand-assisted (β = 5.05 min; 95% confidence interval [CI], -4.56 to 14.66 and adjusted β = 5.59; 95% CI, -3.71 to 14.88), LOS (RR = 0.99; 95% CI, 0.87-1.13 and adjusted RR = 0.98; 95% CI, 0.86-1.12), or readmission (odds ratio = 0.63; 95% CI, 0.28-1.44).</p><p><strong>Conclusions: </strong>In this national, multicenter analysis using prospectively collected data, pure laparoscopic and hand-assisted donor nephrectomy demonstrated similar perioperative outcomes and very low complication rates. Surgical approach did not independently influence operative duration or LOS. Readmission was rare. Substantial center-level variation suggests institutional practice patterns may play a larger role than technique selection.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 5","pages":"e1946"},"PeriodicalIF":1.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of Standardized Genetic Testing in Kidney Transplant Candidate Evaluation.","authors":"Yasar Caliskan, Rengin Elsurer Afsar, Fadee Abu Al Rub, Kate Rabideau, Ava DeLonais-Parker, Dzuy Truong, Bahar Bastani, Mustafa Nazzal, Henry Randall, Chintalapati Varma, Baris Afsar, Krista L Lentine","doi":"10.1097/TXD.0000000000001933","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001933","url":null,"abstract":"<p><strong>Background: </strong>Genetic testing is increasingly used in the evaluation of kidney transplant (KT) candidates, yet its direct association with transplant-related outcomes remains unclear. This study assessed whether genetic test results are associated with key steps in the KT process.</p><p><strong>Methods: </strong>In this observational cohort study, 270 KT candidates underwent standardized genetic testing between January 2021 and November 2024. The outcomes, including waitlisting and transplantation, were compared between candidates with and without positive results. Primary outcomes assessed clinical utility during transplant evaluation, including diagnostic reclassification of end-stage kidney disease (ESKD), effects on living donor evaluation, and genetic counseling. Secondary outcomes included waitlisting, transplantation, and post-transplant allograft function (estimated glomerular filtration rate).</p><p><strong>Results: </strong>Among 270 KT candidates, indications for testing included family history (45.9%), hypertension-attributed ESKD without biopsy (30%), and ESKD of unknown etiology (24.4%). Positive genetic results were identified in 104 candidates (38.5%), who were younger and more frequently Black. Family history independently predicted a positive result (adjusted odds ratio = 1.91 and 95% confidence interval, 1.13-3.27; <i>P</i> = 0.02). Genetic kidney disease was identified in 36.4% of candidates with ESKD of unknown etiology and 43.2% of those with hypertension-attributed ESKD, most commonly <i>APOL1</i>-mediated disease. <i>APOL1</i> high-risk genotypes were present in 50% of focal segmental glomerulosclerosis cases. Overall, 75.9% received pretest counseling and positive results (n = 104) prompted post-test counseling (n = 85) and guided living donor risk assessment and evaluation for extrarenal manifestations. During follow-up, waitlisting, transplantation rates, and post-transplant estimated glomerular filtration rate did not differ between candidates with and without positive results (<i>P</i> = 0.72, <i>P</i> = 0.35, and <i>P</i> = 0.06, respectively).</p><p><strong>Conclusions: </strong>Genetic testing demonstrated a high diagnostic rate among KT candidates, particularly in identifying <i>APOL1</i>-associated risk. Testing clarified disease etiology, informed recipient and family counseling, and supported safe living donor selection without affecting waitlisting. Integrating genetic testing into transplant evaluation may enhance precision medicine and transplant care.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 5","pages":"e1933"},"PeriodicalIF":1.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Donor-recipient Size on Graft Growth in Pediatric Donor-to-pediatric Recipient Kidney Transplantation.","authors":"Jing Wang, Chunyan Wang, Zhiqing Zhang, Meijie Hao, Yubo Sun, Rui Chen, Feng Liu, Yihui Zhai, Hong Xu, Qian Shen","doi":"10.1097/TXD.0000000000001938","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001938","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation is the optimal treatment for pediatric end-stage kidney disease, yet donor shortages have driven the use of pediatric donor kidneys through pediatric donor-to-pediatric recipient (PTP) kidney transplantation. This study aimed to investigate the effect of donor-recipient size on graft growth in PTP kidney transplantation.</p><p><strong>Methods: </strong>This retrospective cohort study included kidney transplant recipients who underwent regular follow-ups between January 2016 and December 2023 at the Children's Hospital of Fudan University. All donors were deceased and aged <18 y. Dynamic clinical data were obtained from medical records spanning the pretransplant to posttransplant period.</p><p><strong>Results: </strong>A total of 136 patients were enrolled, 93 of whom had an initial transplant kidney length. Cumulative average growth of kidney length was 5.5 mm at 1 mo, 9.9 mm at 3 mo, 15.3 mm at 6 mo, 22.3 mm at 1 y, 31.5 mm at 3 y, and 39.5 mm at 5 y posttransplant. The corresponding growth rates were 8.3%, 15.1%, 22.3%, 30.6%, 41.3%, and 53.4%. Kidney growth rates were negatively correlated with the donor-recipient body weight ratio at 3 mo, 6 mo, and 1 y posttransplant (<i>P</i> < 0.01). The mean estimated glomerular filtration rate at the last follow-up was 84.1 ± 31.8 mL/min/1.73 m². Posttransplant estimated glomerular filtration rate showed a significant positive correlation with donor-recipient body weight ratio during the early posttransplant period (1, 3, and 6 mo; <i>P</i> < 0.01). Smaller grafts required approximately 6 mo to reach a normative size consistent with the recipients' age.</p><p><strong>Conclusions: </strong>Grafts showed stable growth patterns and favorable short-term follow-up outcomes. Additionally, PTP kidney transplantation demonstrated both clinical value and practical utility.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 5","pages":"e1938"},"PeriodicalIF":1.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evolution of Molecular Phenotypes Through Time in Kidney Transplant Recipients.","authors":"Brigitte Baragar, Benjamin A Adam, Michael Mengel, Robert Balshaw, Ian W Gibson, Julie Ho, James Shaw, Martin Karpinski, Aaron Trachtenberg, Denise Pochinco, Aviva Goldberg, Patricia Birk, Maury Pinsk, David Rush, Peter W Nickerson, Chris Wiebe","doi":"10.1097/TXD.0000000000001919","DOIUrl":"10.1097/TXD.0000000000001919","url":null,"abstract":"<p><strong>Background: </strong>The correlation between histologic lesions and allograft gene expression data is a subject of significant interest. Most analyses include a single for-cause biopsy from each recipient, precluding serial assessment of gene scores.</p><p><strong>Methods: </strong>Using the nCounter system, we evaluated the Banff Human Organ Transplant gene panel in a unique cohort of 8 renal transplant recipients, each with 3 distinct histologic phenotypes (no rejection, T cell-mediated rejection [TCMR], and antibody-mediated rejection [AMR]), to explore the serial evolution of molecular phenotypes.</p><p><strong>Results: </strong>No rejection biopsies showed large interindividual differences in TCMR and AMR gene scores. Compared with biopsies with No Rejection, TCMR gene scores were greater in those with TCMR (mean fold change 1.95 ± 0.87, <i>P</i> = 0.0174). Similarly, compared with biopsies with No rejection, gene scores for AMR (mean fold change 1.43 ± 0.24, <i>P</i> = 0.0002), donor-specific antibody selective transcripts (mean fold change 1.33 ± 0.22, <i>P</i> = 0.002), and endothelial cell-associated transcripts (mean fold change 1.17 ± 0.06, <i>P</i> = 0.04) were greater at the time of AMR.</p><p><strong>Conclusions: </strong>In most cases, deviations in gene scores occurred in the expected direction as recipients transitioned through histologic phenotypes. The unexpected deviations in gene scores and the significant variability among individuals within histologic phenotypes warrant further investigation.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 4","pages":"e1919"},"PeriodicalIF":1.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13012213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like Peptide-1 Receptor Agonists in Liver Transplant Recipients: A Retrospective Cohort Study.","authors":"Hesham Sheashaa, Ramzi Ibrahim, Amani Elshaer, Hoang Nhat Pham, Rama Mouhaffel, Eiad Habib, Mahmoud Abdelnabi, Juan M Farina, Steven J Lester, David Simper, Said Alsidawi, Eric D Steidley, Bashar A Aqel, Michele Barnhill, W Ray Kim, Chadi Ayoub, Reza Arsanjani","doi":"10.1097/TXD.0000000000001932","DOIUrl":"10.1097/TXD.0000000000001932","url":null,"abstract":"<p><strong>Background: </strong>Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied.</p><p><strong>Methods: </strong>This retrospective cohort study used TriNetX data (January 2010-December 2023) to compare outcomes in liver transplant recipients prescribed GLP1RAs (semaglutide, dulaglutide, liraglutide) within 1-mo posttransplant (n = 546) versus nonusers (n = 37 153). Propensity score matching (1:1) balanced demographics, comorbidities, and medications (n = 541 per group). Outcomes included mortality, hospitalizations, cardiovascular/renal/respiratory events, and graft outcomes.</p><p><strong>Results: </strong>Over a mean follow-up 838.5 d (SD 291.9) in the GLP1RA cohort and 884.3 d (SD 313.7) in the non-GLP1RA group, GLP1RA use was associated with a 43% lower all-cause mortality (7.0% versus 12.9%; hazard ratio [HR], 0.566; 95% confidence interval [CI], 0.381-0.841) and 39% fewer hospitalizations (60.4% versus 74.5%; HR, 0.613; 95% CI, 0.530-0.710). Acute heart failure (HR, 0.386; 95% CI, 0.285-0.524), renal failure/dialysis (HR, 0.489; 95% CI, 0.413-0.579), and respiratory failure (HR, 0.484; 95% CI, 354-0.662) risks were significantly reduced. No differences were observed in graft failure/rejection, myocardial infarction, stroke, atrial fibrillation/flutter, ventricular tachycardia, or ischemic optic neuropathy.</p><p><strong>Conclusions: </strong>Early GLP1RA initiation in liver transplant recipients was associated with reduced mortality, hospitalizations, respiratory, and cardiorenal complications without compromising graft safety. These findings support GLP1RAs as a promising adjunct therapy, warranting prospective trials to confirm benefits in this high-risk population.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 4","pages":"e1932"},"PeriodicalIF":1.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13012210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Varying Perfusate Hemoglobin During Normothermic Ex Situ Heart Perfusion: Elevated Hemoglobin Exacerbates Functional Decline Through Hemolysis.","authors":"Mitchell J Wagner, Guilherme Mainardi Aguiar da Silva, Parham Hassanzadeh, Sanaz Hatami, Xiuhua Wang, Jayan Nagendran, Darren H Freed","doi":"10.1097/TXD.0000000000001926","DOIUrl":"10.1097/TXD.0000000000001926","url":null,"abstract":"<p><strong>Background: </strong>Ex-situ heart perfusion (ESHP) enables improved donor heart preservation, yet still suffers functional decline. The perfusate is 1 area that requires optimization, especially with regard to hemoglobin (Hb) content. We sought to compare performance of concentrated, physiologic, and dilute perfusates in minimally damaged hearts.</p><p><strong>Methods: </strong>Hearts of juvenile Yorkshire pigs (45-55 kg) were procured and subject to 11 h of working-mode ESHP in 1 of 4 groups varying in Hb: concentrated blood (CB, ~12 g/dL Hb, n = 4), whole blood (WB, ~8g/dL Hb, n = 6), plasma (~4g/dL Hb, n = 6, diluted with donor plasma), and control (~4g/dL Hb, n = 5, diluted with modified Krebs-Heinseleit). Functional, metabolic, and hemolytic markers were recorded and compared between groups statistically using appropriate statistical tests.</p><p><strong>Results: </strong>CB hearts exhibited worsened decline from baseline in cardiac index, dP/dT max/min, and stroke work (<i>P</i> < 0.05) and had greater elevations in hemolytic markers by end perfusion. Preservation of baseline cardiac index did not differ significantly between controls, WB, or plasma groups over time (<i>P</i> > 0.05). The CB group displayed elevated early oxygen consumption compared with controls (<i>P</i> < 0.05), with WB and plasma groups trending toward increased oxygen consumption. Lactate elevated over time in all groups, however, was not comparatively elevated within the CB group; it was reduced in the plasma group during early perfusion compared with control.</p><p><strong>Conclusions: </strong>Hb dilution appears to lower absolute output but preserves baseline function. Supraphysiologic Hb elevation or sublethal blood cell damage exacerbates hemolysis, which contributes to functional decline during ESHP. Lactate evolution did not appear to associate with the degree of functional loss.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 4","pages":"e1926"},"PeriodicalIF":1.9,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}