Transplantation最新文献

{"title":"Ischemia/Reperfusion Upregulates Genes Related to PANoptosis in Human Lung Transplants.","authors":"Yajin Zhao, Lubiao Liang, Jamie E Jeon, Shaf Keshavjee, Mingyao Liu","doi":"10.1097/TP.0000000000005268","DOIUrl":"https://doi.org/10.1097/TP.0000000000005268","url":null,"abstract":"<p><strong>Background: </strong>Activation of multiple programmed cell death (PCD) pathways has been reported in cellular and animal studies of ischemia/reperfusion injury in lung transplantation. However, the status of these pathways in human lung transplants remains unknown. This study investigates the involvement of PCD pathways and their relationship with inflammation and signaling pathways in human lung transplants.</p><p><strong>Methods: </strong>Transcriptomic analysis was conducted on 54 paired human lung tissue samples at the end of cold preservation time and 2 h after reperfusion, collected between 2008 and 2011. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA were used to examine the activation of genes in 6 PCD pathways. The relationships between PCD pathways and inflammation, as well as signaling pathways, were assessed via single-gene GSEA.</p><p><strong>Results: </strong>GSEA results indicated that apoptosis and necroptosis were significantly upregulated after reperfusion in human lung transplants, whereas the gene sets related to pyroptosis, ferroptosis, autophagy, and cuproptosis were not significantly upregulated. Notably, single-sample GSEA demonstrated an intricate interplay among pyroptosis, apoptosis, and necroptosis, collectively referred to as PANoptosis, which is further supported by enrichment of genes related to PANoptosome, inflammatory response, and nuclear factor-κB and interferon signaling pathways, via single-gene GSEA assays.</p><p><strong>Conclusions: </strong>This study demonstrated the genes of PANoptosis are upregulated in human lung grafts during reperfusion. The discovery of PANoptosis as an underlying mechanism of cell death in human lung grafts implies that effective therapeutics to prevent or reduce PANoptosis may alleviate ischemia/reperfusion injury and improve clinical lung transplant outcomes.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629016","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":"Advances in Understanding the Complexities of Recurrent HCC Following Liver Transplantation.","authors":"Parissa Tabrizian","doi":"10.1097/TP.0000000000005255","DOIUrl":"https://doi.org/10.1097/TP.0000000000005255","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629010","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":"Comparative Outcome Analysis of Lenvatinib Versus Sorafenib for Recurrence of Hepatocellular Carcinoma After Liver Transplantation.","authors":"Christian T J Magyar, Sheron Perera, Luckshi Rajendran, Zhihao Li, Fahad A Almugbel, Sophie Feng, Woo Jin Choi, Laia Aceituno, Arndt Vogel, Robert C Grant, Nazia Selzner, Elmar Jaeckel, Nazanin Falla-Rad, Jennifer J Knox, Eric X Chen, Gonzalo Sapisochin, Grainne M O'Kane","doi":"10.1097/TP.0000000000005240","DOIUrl":"https://doi.org/10.1097/TP.0000000000005240","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) recurs after liver transplantation (LT) in ~17% of patients. We aimed to retrospectively compare the outcomes of patients treated with different tyrosine kinase inhibitors (TKIs) for recurrent HCC post-LT.</p><p><strong>Methods: </strong>Patients with recurrent HCC post-LT between 2006 and 2019 were included. The impact of sorafenib and lenvatinib treatment for recurrent disease was assessed using survival analysis with an a priori multivariable Cox regression (alpha-fetoprotein [AFP] at recurrence, recurrence lesion diameter, single-site versus multisite metastases).</p><p><strong>Results: </strong>Seven hundred fifty-four patients underwent LT for HCC, of whom 120 (15.9%) developed recurrence. Of these patients, 56 received TKIs: sorafenib (n = 42) or lenvatinib (n = 14). The median age at LT was 60.8 y (interquartile range, 54.0-66.2); 52 (93%) were men and 26 (46%) were within Milan criteria at listing. Baseline characteristics at recurrence were comparable between the 2 groups, including largest tumor diameter (P = 0.15), receipt of local therapies before TKI (P = 0.33), and single-site recurrence (P = 0.75), and time from interventional treatment to start of TKI (P = 0.44). The AFP at recurrence was higher in the sorafenib group (95.0 versus 3.0 µg/L, P < 0.001). The median overall survival (OS) after initiation of TKI treatment was longer in the lenvatinib group (15.0 mo [95% confidence interval [CI], 11.5-31.5] versus 7.8 mo [95% CI, 4.0-15.4]; P = 0.02) with a 2.3-fold a priori adjusted effect on OS (adjusted hazard ratio 2.32 [95% CI, 1.03-5.20], P = 0.04).</p><p><strong>Conclusions: </strong>Our findings suggest lenvatinib is a valuable treatment option for patients with HCC recurrence after LT.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629014","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":"Another Viral Infection Linked to Posttransplant Diabetes Mellitus?","authors":"Adam G Stewart, Camille N Kotton","doi":"10.1097/TP.0000000000005254","DOIUrl":"https://doi.org/10.1097/TP.0000000000005254","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629011","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":"Association of COVID-19 With Risk of Posttransplant Diabetes Mellitus.","authors":"Amanda J Vinson, A Jerrod Anzalone, Makayla Schissel, Ran Dai, Amy L Olex, Roslyn B Mannon","doi":"10.1097/TP.0000000000005227","DOIUrl":"https://doi.org/10.1097/TP.0000000000005227","url":null,"abstract":"<p><strong>Background: </strong>Posttransplant diabetes mellitus (PTDM) is an important complication for solid organ transplant recipients (SOTRs). COVID-19 has been associated with an increased risk of incident diabetes in the general population. However, the association between COVID-19 and new-onset PTDM has not been explored.</p><p><strong>Methods: </strong>Using the National COVID Cohort Collaborative Enclave, we conducted a cohort study of adults without diabetes receiving a solid organ transplant (heart, lung, kidney, or liver) in the United States between April 1, 2020, and March 31, 2023, with and without a first diagnosis of COVID-19 (COVID+ versus COVID-) within 180 d of SOT. We propensity score matched a single COVID+ SOTR with a COVID- SOTR who was diabetes free at the same point posttransplant. Within this matched cohort, we used multivariable Cox proportional hazards models to examine the adjusted risk of PTDM associated with COVID+.</p><p><strong>Results: </strong>Among 1342 COVID+ SOTRs matched to 1342 COVID- SOTRs, the crude rate of newly diagnosed PTDM in the 2 y post-COVID was 17% in those with versus 13% in those without COVID-19 (P = 0.007). COVID-19 was significantly associated with new PTDM (adjusted hazard ratio, 1.37; 95% confidence interval, 1.12-1.68 at 2 y).</p><p><strong>Conclusions: </strong>Similar to other viral infections, COVID-19 is associated with an increased risk of PTDM in SOTRs.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629013","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":"Open AI in Transplantation: A Friend or a Foe?","authors":"Germaine Wong, Jennifer Li","doi":"10.1097/TP.0000000000005275","DOIUrl":"https://doi.org/10.1097/TP.0000000000005275","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576659","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":"Successful Implementation of a Multidisciplinary Weight Loss Program Including GLP1 Receptor Agonists for Liver Transplant Candidates With High Body Mass Index.","authors":"Humberto C Gonzalez, Daniel T Myers, Deepak Venkat","doi":"10.1097/TP.0000000000005070","DOIUrl":"https://doi.org/10.1097/TP.0000000000005070","url":null,"abstract":"<p><strong>Background: </strong>Body mass index (BMI) >40 is considered a relative contraindication to liver transplant. However, there is little research regarding best practices for weight loss in this population. We hypothesized that providing multidisciplinary support, including the use of glucagon-like protein 1 receptor agonists would facilitate patients' achievement of weight loss necessary for transplant eligibility.</p><p><strong>Methods: </strong>Patients 18 y or older were referred to the Henry Ford Health Liver Metabolic Clinic from August 2019 to September 2023, with either BMI >40 or >35 with abdominal adiposity that would complicate surgery. Patients were provided individualized support from hepatologists, dieticians, and counselors, as well as prescribed antiobesity medication and monitored closely for weight loss progress.</p><p><strong>Results: </strong>Among 19 patients referred to the Liver Metabolic Clinic, median baseline BMI was 42 (range, 34.6-48.8) with median goal weight loss of 14.1 kg (range, 4.1-31.4). Sixteen patients (84%) had metabolic dysfunction-associated steatohepatitis and 3 patients had alcohol-associated liver disease. Seven had comorbid hepatocellular carcinoma. Median Model for End-stage Liver Disease score was 14 (range, 7-22). Fifteen patients were treated with a glucagon-like peptide 1 receptor agonist (6 patients received liraglutide, 8 received semaglutide, and 1 received tirzepatide) and 4 received phentermine. Median weight loss was 11.7 kg for all 19 patients (range, 0-33). Eight patients received a transplant and 4 more patients were waitlisted. Time from baseline to waitlisting was ~5.5 mo (median 166 d; range, 68-840). Three patients remained on treatment, whereas 4 were deceased due to progressive liver disease or infection.</p><p><strong>Conclusions: </strong>Providing high BMI patients with individualized dietary and medical support can facilitate weight loss necessary to achieve liver transplant eligibility.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":"108 11","pages":"2233-2237"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508787","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 Effects of Sustained Immunosuppression Withdrawal After Liver Transplantation on Metabolic Syndrome.","authors":"Roberta Angelico, Bruno Sensi, Luca Toti, Elisa Campanella, Ilaria Lenci, Leonardo Baiocchi, Giuseppe Tisone, Tommaso Maria Manzia","doi":"10.1097/TP.0000000000005026","DOIUrl":"10.1097/TP.0000000000005026","url":null,"abstract":"<p><strong>Background: </strong>Liver transplant (LT) recipients often experience adverse effects of immunosuppressive (IS) drugs, especially on metabolic profiles. Selected LT recipients can achieve successful IS withdrawal; however, its effects on metabolic syndrome (MS) are unknown.</p><p><strong>Methods: </strong>This is a retrospective single-center study investigating the incidence and/or regression of MS in 75 selected LT recipients who were previously enrolled in prospective IS withdrawal trials between 1999 and 2017. Patients who were transplanted due to nonalcoholic steatohepatitis/metabolic-associated fatty liver disease were excluded, as well as those with a follow-up <3 y after IS weaning.</p><p><strong>Results: </strong>Forty-four patients (58.7%) achieved sustained withdrawal or minimization of immunosuppression (WMIS) and 31 patients (41.3%) required reintroduction of immunosuppression (no-WMIS). Among LT recipients who were metabolically healthy (n = 52, 69.3%) before the start of IS weaning, there was a significantly lower rate of de novo MS in WMIS patients compared with no-WMIS patients after 5 y (8.3% and 47.8%, respectively, P  = 0.034). Of 23 LT recipients (30.7%) who had MS at the time of commencing IS withdrawal, complete regression of MS was observed in 47.1% of WMIS patients and in none (0%) of the no-WMIS patients after 5 y ( P  = 0.054). Furthermore, individual components of MS were better controlled in IS-weaned patients, such as arterial hypertension and abnormal serum lipids.</p><p><strong>Conclusions: </strong>Achievement of sustained IS withdrawal reduces the incidence of de novo MS development in metabolically healthy patients and increases the likelihood of MS regression in patients with established MS. The foreseeable long-term beneficial effects of these favorable metabolic changes on morbidity and mortality of LT recipients require further investigation.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"2247-2259"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071913","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":"Effects of the March 2021 Allocation Policy Change on Key Deceased-donor Kidney Transplant Metrics.","authors":"Alissa M Cutrone, Scott A Rega, Irene D Feurer, Seth J Karp","doi":"10.1097/TP.0000000000005044","DOIUrl":"10.1097/TP.0000000000005044","url":null,"abstract":"<p><strong>Background: </strong>A major change to deceased-donor kidney allocation in the United States, Kidney Allocation System 250 (KAS250), was implemented on March 15, 2021. Evaluating the consequences of this policy on critical system performance metrics is critical to determining its success.</p><p><strong>Methods: </strong>We performed a retrospective analysis of critical performance measures of the kidney transplant system by reviewing all organs procured during a 4-y period in the United States. To mitigate against possible effects of the COVID-19 pandemic, Scientific Registry of Transplant Recipients records were stratified into 2 pre- and 2 post-KAS250 eras: (1) 2019; (2) January 1, 2020-March14, 2021; (3) March 15, 2021-December 31, 2021; and (4) 2022. Between-era differences in rates of key metrics were analyzed using chi-square tests with pairwise z -tests. Multivariable logistic regression and analysis of variations methods were used to evaluate the effects of the policy on rural and urban centers.</p><p><strong>Results: </strong>Over the period examined, among kidneys recovered for transplant, nonuse increased from 19.7% to 26.4% (all between-era P < 0.05) and among all Kidney Donor Profile Index strata. Cold ischemia times increased ( P < 0.001); however, the distance between donor and recipient hospitals decreased ( P < 0.05). Kidneys from small-metropolitan or nonmetropolitan hospitals were more likely to not be used over all times ( P < 0.05).</p><p><strong>Conclusions: </strong>Implementation of KAS250 was associated with increased nonuse rates across all Kidney Donor Profile Index strata, increased cold ischemic times, and shorter distance traveled.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e376-e381"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237741","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 Potential Utilization of Machine Perfusion to Increase Transplantation of Macrosteatotic Livers.","authors":"Claire Cywes, Amay Banker, Nicolas Muñoz, Matthew Levine, Samir Abu-Gazala, Therese Bittermann, Peter Abt","doi":"10.1097/TP.0000000000005057","DOIUrl":"10.1097/TP.0000000000005057","url":null,"abstract":"<p><strong>Background: </strong>The demand for liver transplantation has led to the utilization of marginal grafts including moderately macrosteatotic livers (macrosteatosis ≥30% [Mas30]), which are associated with an elevated risk of graft failure. Machine perfusion (MP) has emerged as a technique for organ preservation and viability testing; however, little is known about MP in Mas30 livers. This study evaluates the utilization and outcomes of Mas30 livers in the era of MP.</p><p><strong>Methods: </strong>The Organ Procurement and Transplantation Network database was queried to identify biopsy-proven Mas30 deceased donor liver grafts between June 1, 2016, and June 23, 2023. Univariable and multivariable models were constructed to study the association between MP and graft utilization and survival.</p><p><strong>Results: </strong>The final cohort with 3317 Mas30 livers was identified, of which 72 underwent MP and were compared with 3245 non-MP livers. Among Mas30 livers, 62 (MP) and 1832 (non-MP) were transplanted (utilization of 86.1% versus 56.4%, P  < 0.001). Donor and recipient characteristics were comparable between MP and non-MP groups. In adjusted analyses, MP was associated with significantly increased Mas30 graft utilization (odds ratio, 7.89; 95% confidence interval [CI], 3.76-16.58; P  < 0.001). In log-rank tests, MP was not associated with 1- and 3-y graft failure (hazard ratio, 0.49; 95% CI, 0.12-1.99; P  = 0.319 and hazard ratio 0.43; 95% CI, 0.11-1.73; P  = 0.235, respectively).</p><p><strong>Conclusions: </strong>The utilization rate of Mas30 grafts increases with MP without detriment to graft survival. This early experience may have implications for increasing the available donor pool of Mas30 livers.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e370-e375"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076874","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}