Transplantation Direct最新文献

{"title":"Patient-reported Opioid use and Pain Management After Living Kidney Donation.","authors":"Amanda Leonberg-Yoo, Kristin E Leonberg, Samir Abu Gazala, Sarah Hryzak, Robert R Redfield, Ronald F Parsons, Anish K Agarwal, M Kit Delgado, Daniel Lee, Jennifer Trofe","doi":"10.1097/TXD.0000000000001954","DOIUrl":"10.1097/TXD.0000000000001954","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated donor-reported opioid use and pain management outcomes after living donor nephrectomy at a single center. Prospective data were collected through an automated text-messaging platform to assess postdischarge pain intensity, perceived pain control, and use of prescribed opioids for acute postoperative pain.</p><p><strong>Methods: </strong>This prospective study was conducted at a large academic health system in Pennsylvania. Eligible participants were adult living kidney donors (aged 18 y and older) who underwent donor nephrectomy between July 2021 and March 2023. Data were collected using an automated text-messaging system from hospital discharge through postoperative day 28.</p><p><strong>Results: </strong>Of the eligible participants, 75 (71%) consented to participate. Donors who consented to follow-up did not differ significantly from those who did not consent in terms of demographic or perioperative characteristics. Inpatient opioid use and discharge prescribing practices were similar across groups. Of participants who responded at each follow-up, the median (interquartile range) self-reported pain intensity on day 4 was 4.0 (3.0-5.0) and decreased to 1.0 (0.0-2.0) by day 21. The median (interquartile range) perceived pain control increased to 10.0 (9.0-10.0) by day 14, with 3 (8.1%) of participants reporting opioid use by this time.</p><p><strong>Conclusions: </strong>From a systems perspective, these findings underscore the need to recalibrate default discharge prescribing practices. Implementing standardized order sets and feedback mechanisms may reduce excess opioid supply while maintaining living kidney donor comfort.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 6","pages":"e1954"},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869558","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":"Kidneys From Older Donors After Circulatory Death Plus Normothermic Regional Perfusion or Standard Rapid Retrieval Have Comparable Function in the Context of Ex Situ Oxygenated Hypothermic Machine Perfusion.","authors":"Emma F Van de Geijn, Martin B A Heemskerk, Madeleine C Van Dijk, Rutger M Van Rooden, Fenna J Van der Heijden, Femke H C De Goeij, Aiko P J De Vries, Ian P J Alwayn, Robert C Minnee, Dorottya K De Vries, Jeroen De Jonge, Volkert A L Huurman","doi":"10.1097/TXD.0000000000001953","DOIUrl":"10.1097/TXD.0000000000001953","url":null,"abstract":"<p><strong>Background: </strong>With growing transplant waiting lists, more extended criteria donor organs are being accepted, requiring optimization of the organs to increase utilization. Abdominal normothermic regional perfusion (aNRP) benefits the outcomes of transplanted livers and pancreatic islets, but its effects on donor kidneys subsequently preserved with (oxygenated) hypothermic machine perfusion (HMPO₂) remain to be determined. This study examines the function and survival of an aNRP-preserved controlled donation after circulatory death (cDCD) kidneys followed by HMPO₂.</p><p><strong>Methods: </strong>From October 2018 until June 2023, we evaluated all ≥50 y cDCD kidneys retrieved using aNRP during a pilot implementation project and compared posttransplant outcomes of these donor kidneys to those of cDCD kidneys retrieved by standard rapid retrieval during the same period. All kidneys received HMPO₂ as standard preservation. This study primarily compared estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration), 1 y graft and recipient survival.</p><p><strong>Results: </strong>Data of 70 aNRP-preserved kidneys were compared with a control group of 124 kidneys. One year estimated glomerular filtration rate was comparable between groups (40.4 mL/min/1.73 m² [29.3-52.3] versus 40.0 mL/min/1.73 m² [28.1-48.1]; <i>P</i> = 0.5) as well as graft and recipient survival at 1 y (81.4% versus 83.1%; hazard ratio, 1.1; 95% confidence interval [CI], 0.6-2.3; <i>P</i> = 0.63; 88.6% versus 88.7%, hazard ratio, 1.0; 95% CI, 0.4-2.4; <i>P</i> = 0.99, respectively). Primary nonfunction and delayed graft function were not significantly different (odds ratio, 1.3; 95% CI, 0.4-4.2; <i>P</i> = 0.68; odds ratio, 1.3; 95% CI, 0.7-2.5; <i>P</i> = 0.39).</p><p><strong>Conclusions: </strong>This study demonstrates that aNRP-preserved kidneys from cDCD donors aged 50 y and older had comparable outcomes to kidneys retrieved with standard rapid retrieval, in the context of HMPO₂ as a standard ex situ preservation technique. This differs from earlier studies showing improved results of aNRP in the context of cold storage without standard machine perfusion. With aNRP gaining interest because of its value for liver and pancreatic islet transplantation, a prospective randomized study should be performed to further analyze the benefit of continuous kidney HMP(O₂) after aNRP.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 6","pages":"e1953"},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869625","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":"Practical Guide to Address Common Myths in the Pre- and Post-kidney Transplant Management of the Elderly Patient with Cancer: An Opinion Paper.","authors":"Mary Ann Lim, Naoka Murakami, Christopher D Blosser, Salma Shaikhouni, Darshana M Dadhania, Evan T Hall, Krista Havlin, Arpita Basu","doi":"10.1097/TXD.0000000000001934","DOIUrl":"10.1097/TXD.0000000000001934","url":null,"abstract":"<p><p>Two areas of overlap between kidney transplantation and oncology that remain fraught with uncertainty and bias are (1) transplant candidacy for elderly patients with historic or active cancers or premalignant conditions, and (2) managing cancer in elderly kidney transplant recipients. These have led to inadvertent inequities in the care of elderly kidney transplant candidates with historic or active malignancies. Incorporating a patient's viewpoint and an oncologist's perspective, we present a nuanced, multidisciplinary approach to management that goes beyond mere consideration of chronological age and focuses on the individual patient and his/her goals.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 6","pages":"e1934"},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869611","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 Impact of Normothermic Machine Liver Perfusion on Early Renal Outcomes After Simultaneous Liver-kidney Transplantation: A Propensity Score-Matched Analysis.","authors":"Muhammad A Nadeem, Chase J Wehrle, Sangeeta Satish, Hafiz Umair Siddiqui, Sapana Verma, Valberto Sanha, Khaled Ali, Mazhar Khalil, Alejandro Pita, Jamak Modaresi Esfeh, David C H Kwon, Federico Aucejo, Jaekeun Kim, Antonio D Pinna, Mohamed Eltemamy, Charles Miller, Masato Fujiki, Robert L Fairchild, Richard A Fatica, Koji Hashimoto, Alvin Wee, Andrea Schlegel","doi":"10.1097/TXD.0000000000001955","DOIUrl":"10.1097/TXD.0000000000001955","url":null,"abstract":"<p><strong>Background: </strong>No study has assessed the effect of end-ischemic normothermic machine perfusion (NMP) on renal function in simultaneous liver-kidney (SLK) transplantation. We hypothesized that by mitigating liver ischemia/reperfusion injury, NMP exerts a renoprotective effect on kidney allografts. This study compares renal outcomes in SLK transplant recipients receiving NMP versus static cold storage (SCS) livers.</p><p><strong>Methods: </strong>We analyzed deceased-donor SLK transplant recipients (January 2019-July 2024) with at least 6 mo follow-up (n = 85). Primary outcomes included delayed graft function (DGF) and functional-DGF (f-DGF; failure of serum creatinine to decrease 10% daily for 3 d in the first week). Liver Core Outcome Sets were reported. NMP recipients (n = 17) were propensity score-matched 1:2 to SCS controls (n = 34). Kidneys underwent hypothermic machine perfusion in both groups.</p><p><strong>Results: </strong>Cohorts were well matched, although NMP had more donation after circulatory death donors (<i>P</i> = 0.006). f-DGF was significantly lower in NMP versus SCS (35% versus 68%, <i>P</i> = 0.025); this persisted in the hepatorenal syndrome subcohort (27% versus 65%, <i>P</i> = 0.03). Post-reperfusion syndrome was lower in NMP (<i>P</i> = 0.041). NMP demonstrated superior renal function: lower peak creatinine (2.58 versus 3.03 mg/dL, <i>P</i> = 0.031), higher lowest postoperative estimated glomerular filtration rate (25 versus 19 mL/min/1.73 m², <i>P</i> = 0.021), and reduced 6-mo dialysis requirement (6% versus 32%, <i>P</i> = 0.036).</p><p><strong>Conclusions: </strong>In this cohort, NMP was associated with improved early renal recovery in SLK transplant recipients, characterized by lower rates of f-DGF and higher estimated glomerular filtration rate. These findings suggest that mitigating liver ischemia via NMP may provide secondary benefits to the simultaneous kidney allograft.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 6","pages":"e1955"},"PeriodicalIF":2.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869618","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 SOFT Cluster Score as a Multifaceted Predictive Model for Postoperative Outcomes.","authors":"Gwendolyn B Henry, Spoorthi Kamepalli, Carter J Burns, Jeremy Birkmire, George Cholankeril, Avegail Flores, John A Goss, Abbas Rana","doi":"10.1097/TXD.0000000000001951","DOIUrl":"10.1097/TXD.0000000000001951","url":null,"abstract":"<p><strong>Background: </strong>Consideration of both donor and recipient factors at the time of an organ offer is crucial in achieving the most optimal outcome given the shortage of available donor organs and waitlist mortality risk. Our aim was to achieve a comprehensive risk assessment for liver transplant patients by creating a series of independent risk index equations for 6 distinct posttransplant endpoints in the transplant continuum of care.</p><p><strong>Methods: </strong>The Survival Outcomes Following Liver Transplantation (SOFT) Cluster score includes risk indices for patient mortality at 90 d, 1 y, 3 y, and 5 y posttransplant, graft failure at 1 y after transplantation, and prolonged length of stay (>30 d). Using a total sample of 61 231 patients, significant risk and protective factors were identified through univariable and multivariable analysis from a training set of 40 821 patients from the Organ Procurement and Transplantation Network database.</p><p><strong>Results: </strong>When applied to a validation set of 20 410 patients, the SOFT Cluster score has a <i>C</i>-statistic of 0.66 for 90-d mortality, 0.64 for 1-y mortality, 0.63 for 3-y mortality, 0.63 for 5-y mortality, 0.76 for prolonged length of stay, and 0.60 for 1-y graft failure.</p><p><strong>Conclusions: </strong>The SOFT Cluster score represents a novel proof-of-concept model for posttransplant risk assessment and provides physicians with a more holistic understanding of patient risk by examining a spectrum of outcomes after liver transplantation up to 5 y posttransplant using a modern cohort of recipients.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 6","pages":"e1951"},"PeriodicalIF":2.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869614","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":"Acellular Normothermic Machine Perfusion Does not Exacerbate Acute Rejection in Rodent Vascularized Composite Allografts.","authors":"Irina Filz von Reiterdank, Raphaela Bento, Eloi de Clermont-Tonnerre, Antonia T Dinicu, Hyshem H Lancia, Michelle E McCarthy, Alexandre G Lellouch, Basak E Uygun, Curtis L Cetrulo, J Henk Coert, Aebele B Mink van der Molen, Biju Parekkadan, Korkut Uygun","doi":"10.1097/TXD.0000000000001950","DOIUrl":"10.1097/TXD.0000000000001950","url":null,"abstract":"<p><strong>Background: </strong>Vascularized composite allotransplantation faces significant challenges, including limited preservation time and high rates of acute rejection because of the ischemia susceptibility of muscle and immunogenicity of skin. However, no studies have investigated whether normothermic machine perfusion (NMP) has an effect on acute rejection compared with static cold storage (SCS).</p><p><strong>Methods: </strong>Heterotopic hindlimb transplants were performed in a full-mismatch model after 6 h of SCS or NMP. Postoperative assessments included clinical scoring, histological examination, cytokine profiling, and flow cytometry of splenocytes and lymphocytes at the end of the study.</p><p><strong>Results: </strong>Clinical assessment revealed significantly lower rejection scores in the NMP group on postoperative day (POD) 2 (<i>P</i> = 0.03). Notably, histology indicated delayed rejection, with Banff scores showing severe rejection from POD2 in the SCS group and from POD6 in the NMP group. Cytokine profiling demonstrated early upregulation of anti-inflammatory interleukin-10 in the NMP group at POD1, and flow cytometry showed a reduction in B cell populations.</p><p><strong>Conclusions: </strong>While NMP is not a cure-all, it is associated with a delayed onset of acute rejection compared with SCS in a full-mismatch rodent vascularized composite allotransplantation model. Future studies should focus on analysis earlier in the rejection process and on long-term graft survival to further elucidate the mechanism of the effect of NMP on the immune response.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"12 6","pages":"e1950"},"PeriodicalIF":2.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869583","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":"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":"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":2.2,"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":"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":2.2,"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":"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":2.2,"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":"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":2.2,"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}