medRxiv - Transplantation最新文献

{"title":"Rethinking the Impact of Pretransplant Malignancy (Pre-TM) on Double Lung Transplantation (DLT) Eligibility: An Analysis of 23,291 DLT Recipients","authors":"Wongi Woo, Hye Sung Kim, Ankit Bharat, Young Kwang Chae","doi":"10.1101/2024.03.14.24304302","DOIUrl":"https://doi.org/10.1101/2024.03.14.24304302","url":null,"abstract":"Background: Given the increasing need for lung transplants among older patients with a history of cancer, this study analyzed database registry to assess outcomes for DLT recipients with Pre-TM.\u0000Methods: This study evaluated the United Network for Organ Sharing (UNOS) registry for adult DLT performed between 2005 and 2023. Patients with a history of previous or multi-organ transplants, and those with donors who had cancer history, were excluded. Propensity-score matching was used to compare patients with or without Pre-TM. Overall and Post-TM-free survival were analyzed.\u0000Results: Among the 23,291 recipients of DLT, 8.0%(1,870) had Pre-TM. Compared to those without Pre-TM, patients with Pre-TM had worse overall (hazard ratio[HR] 1.20, 95% confidence interval[CI] 1.12-1.29, p<0.001) and Post-TM-free survival (HR 1.32, 95% CI 1.24-1.41, p<0.001). However, after adjusting for age, sex, and race through propensity-score matching, the survival difference between the groups became non-significant (HR 1.05, 95% CI 0.97-1.13, p=0.229). While the Pre-TM group still had worse Post-TM-free survival, this difference diminished after excluding cutaneous Post-TM (HR 1.06, 95% CI 0.99-1.15, p=0.116). Additionally, the recurrence rate of Pre-TM after transplant wasn't higher than de novo cancers in patients without Pre-TM.\u0000Conclusion: Patients with Pre-TM had similar overall survival rates after DLT as those without Pre-TM. Importantly, there is no increased risk of the primary Pre-TM type recurring post-transplant compared to patients without Pre-TM. These findings highlight the necessity for a more nuanced evaluation of transplant candidacy to prevent premature exclusion of Pre-TM patients from life-saving surgeries.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140154261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Mismatching in Isolated Heart Transplant Confers No Postoperative Risk","authors":"Reid Dale, Matthew Leipzig, Nataliya Bahatyrevich, Katharine Casselman Pines, Quidong Chen, Jeffrey Teuteberg, Joseph Woo, Maria Currie","doi":"10.1101/2024.02.23.24303301","DOIUrl":"https://doi.org/10.1101/2024.02.23.24303301","url":null,"abstract":"Background: For heart transplantation, optimal donor-recipient matching is an important factor in the ongoing development of the United Network for Organ Sharing (UNOS) continuous distribution framework. Donor-recipient sex-mismatch has decreased since the 1990s, but this may be related to the risk posed by size mismatching, particularly when donor hearts are undersized. Thus, the impact of sex-mismatching, controlling for other factors including size mismatch, is uncertain. Methods: Adult first-time, isolated heart transplant patients from the UNOS database between October 1, 1987 and December 31, 2022 were analyzed. Cohorts were separated into male and female recipients. Propensity score matching on known preoperative risk factors was performed. Equivalence testing via Two One-Sided Testing (TOST) was performed to assess between-arm equivalence in postoperative outcomes. Survival differences were measured by the between-arm ratio of Restricted Mean Survival Time and binary outcome differences by the Odds Ratio (OR). Results: In the propensity matched cohort, we found significant equivalence between arms in both male (TOST P<0.001) and female (TOST P<0.001) recipients for overall survival at all temporal endpoints, postoperative treatment for rejection within one year, and pre-discharge dialysis. Conclusions: Sex-mismatch in isolated heart transplantation confers no additional risk to postoperative outcomes when controlling for other factors, including size mismatch. Consequently, sex-mismatch should not factor into individual assessments of organ acceptance or be incorporated into any national organ allocation policy. Increasing the acceptance of sex-mismatched donors has the potential to expand the donor pool and increase female donor utilization.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140003963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular signatures of chronic antibody-mediated rejection in human liver transplants","authors":"Bastian Engel, Ahmed Alaswad, Alejandro Campos-Murguia, Martijn Zoodsma, Anne Klingbeil, Kinan Chihab, Emily A. Bosselmann, Sophia Heinrich, Björn Hartleben, Danny D. Jonigk, Murielle Verboom, Michael Hallensleben, Robert Geffers, Heiner Wedemeyer, Cheng-Jian Xu, Elmar Jaeckel, Yang Li, Richard Taubert","doi":"10.1101/2024.02.08.24302515","DOIUrl":"https://doi.org/10.1101/2024.02.08.24302515","url":null,"abstract":"<strong>Background&amp;Aims</strong> The role of antibody-mediated rejection (ABMR) after liver transplantation (LT) remains controversial. Chronic ABMR (cABMR) is often subclinical and potentially missed without surveillance biopsies (svLbx) which are not established in most LT centers. Transcriptome analysis previously characterized molecular changes in T cell-mediated rejection (TCMR) after solid organ transplantation. We aimed to identify molecular cABMR signatures after LT for a more comprehensive understanding of cABMR.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Urinary tract infection on the outcome of the Allograft in patients with Renal transplantation","authors":"Rahul Sai Gangula, Mahesh Eswarappa, Rajashekar Reddy, Gireesh Mathihally Siddaiah, Gurudev Konana, Hamsa Reddy, Pooja Prakash Prabhu, Yousuff Mohammad, Lia Sara Anish","doi":"10.1101/2024.02.06.24302324","DOIUrl":"https://doi.org/10.1101/2024.02.06.24302324","url":null,"abstract":"<strong>Background</strong> Urinary Tract Infections (UTIs) are the second most common cause of graft dysfunction, accounting for significant morbidity, and are associated with poor graft and patient survival. This study aimed to determine the association between post-renal transplant UTI and graft outcomes.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary Cell Gene Signature of Acute Rejection in Kidney Allografts","authors":"Thalia Salinas, Carol Li, Catherine Snopkowski, Vijay K Sharma, Darshana M Dadhania, Karsten Suhre, Thangamani Muthukumar, Manikkam Suthanthiran","doi":"10.1101/2023.12.18.23300165","DOIUrl":"https://doi.org/10.1101/2023.12.18.23300165","url":null,"abstract":"Introduction. A kidney allograft biopsy may display acute T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), or concurrent TCMR + ABMR (MR). Development of noninvasive biomarkers diagnostic of all three types of acute rejection is a useful addition to the diagnostic armamentarium.\u0000Methods. We developed customized RT-qPCR assays and measured urinary cell mRNA copy number in 145 biopsy-matched urine samples from 126 kidney allograft recipients and calculated urinary cell three-gene signature score from log10-transformed values for the 18S-normalized CD3E mRNA, 18S-normalized CXCL10 mRNA and 18S rRNA. We determined whether the signature score in biopsy-matched urine specimens discriminates biopsies without rejection (NR, n=50) from biopsies displaying TCMR (n=47), ABMR (n=28) or MR (n=20).\u0000Results. Urinary cell three-gene signature discriminated TCMR, ABMR or MR biopsies from NR biopsies (P &lt;0.0001, One-way ANOVA). Dunnett's multiple comparisons test yielded P&lt;0.0001 for NR vs. TCMR; P &lt;0.001 for NR vs. ABMR; and P &lt;0.0001 for NR vs. MR. By bootstrap resampling, optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.749 (bias-corrected 95% confidence interval [CI], 0.638 to 0.840) for NR vs. TCMR (P&lt;0.0001); 0.780 (95% CI, 0.656 to 0.878) for NR vs. ABMR (P&lt;0.0001); and 0.857 (95% CI, 0.727 to 0.947) for NR vs. MR (P&lt;0.0001). All three rejection biopsy categories were distinguished from NR biopsies with similar accuracy (all AUC comparisons P&gt;0.05).\u0000Conclusion. Urinary cell three-gene signature score may serve as a universal diagnostic signature of acute rejection due to TCMR, ABMR or MR in human kidney allografts with similar performance characteristics.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138819044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Donor Inhibitory KIR Are Associated with Reduced GVHD and Improved Survival Following HLA Matched Unrelated Donor HCT in Pediatric Acute Leukemia","authors":"Elizabeth Krieger, Rehan Qayyum, Amir Toor","doi":"10.1101/2023.12.14.23299955","DOIUrl":"https://doi.org/10.1101/2023.12.14.23299955","url":null,"abstract":"Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after hematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138741389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selection bias in reporting of median waiting times in organ transplantation","authors":"Simon Schwab, Andreas Elmer, Daniel Sidler, Lisa Straumann, Ueli Stürzinger, Franz Immer","doi":"10.1101/2023.12.13.23299859","DOIUrl":"https://doi.org/10.1101/2023.12.13.23299859","url":null,"abstract":"Median waiting times published by transplant organizations around the world may be biased when death or censoring is disregarded. This leads to too optimistic waiting times, particularly in kidney transplantation, and as a consequence can deceive patients on the waiting list, transplant physicians, and healthcare policy maker. Competing risk multistate models are suited for the analysis of time-to-event data of the organ waiting list. Resulting cumulative incidences are probabilities for transplantation or death by a given time, and are a more accurate description of the events occurring on the waiting list. In accordance with the concept of median survival time in survival analysis in clinical trials, we suggest the median time to transplantation (MTT), the waiting time duration at which the transplant probability is 0.50, as a measure of average waiting time.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"109 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138717315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deceased donor kidney function is determined by branch chained amino acid metabolism during ex vivo normothermic perfusion","authors":"Armin Ahmadi, Jacquelyn Min-Ung Yu, Jennifer E. Loza, Brian Christopher Howard, Ivonne Palma, Peter Adam Than, Naeem Makarm G Goussous, Junichiro Sageshima, Baback Roshanravan, Richard V. Perez","doi":"10.1101/2023.11.15.23298543","DOIUrl":"https://doi.org/10.1101/2023.11.15.23298543","url":null,"abstract":"Current kidney perfusion protocols are not optimized for addressing the ex vivo physiological and metabolic needs of the kidney. Ex vivo normothermic perfusion (EVNP) may be utilized to distinguish high-risk kidneys to determine suitability for transplantation. We assessed the association of tissue metabolic changes with changes in kidney injury biomarkers and functional parameters in eight deceased donor kidneys deemed unsuitable for transplantation during a 12-hour ex vivo normothermic perfusion (EVNP). The kidneys were grouped into good and poor performers based on blood flow and urine output. The mean (SD) age of the deceased kidney donors was 43 (16) years with an average cold ischemia time of 37 (12) hours. Urine output and creatinine clearance progressively increased and peaked at 6 hours post-perfusion among good performers. Poor performers had 71 ng/ml greater (95% CI 1.5, 140) urinary neutrophil gelatinase-associated lipocalin (NGAL) at 6 hours compared to good performers corresponding to peak functional differences. Organ performance was distinguished by tissue metabolic differences in branch-chained amino acid (BCAA) metabolism. Tissue BCAA levels negatively correlated with urine output among all kidneys at 6 hours. Tissue lipid profiling showed poor performers were highlighted by the accumulation of membrane structure components including glycerolipids and sphingolipids at early perfusion time points. Overall, we showed that 6 hours is needed for kidney functional recovery during ENVP and that BCAA metabolism may be a major determinant of organ function and resilience.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchoalveolar lavage metabolome dynamics reflect underlying disease and chronic lung allograft dysfunction","authors":"Christian Martin, Kathleen S Mahan, Talia D Wiggen, Adam J Gilbertsen, Marshall I Hertz, Ryan C Hunter, Robert A Quinn","doi":"10.1101/2022.11.16.22281980","DOIUrl":"https://doi.org/10.1101/2022.11.16.22281980","url":null,"abstract":"Background Progression of chronic lung disease often leads to the requirement for a lung transplant (LTX). Despite improvements in short-term survival after LTX, chronic lung allograft dysfunction (CLAD) remains a critical challenge for long-term survival. This study investigates the relationship between the metabolome of bronchoalveolar lavage fluid (BALF) collected longitudinally from subjects post-LTX with underlying chronic lung diseases and its association with CLAD severity. Methods Untargeted LC-MS/MS metabolomics was performed on 960 BALF samples collected over 10 years from LTX recipients with alpha-1-antitrypsin disease (AATD, n = 22), cystic fibrosis (CF, n = 46), chronic obstructive pulmonary disease (COPD, n = 79) or pulmonary fibrosis (PF, n = 47). Datasets were analyzed using machine learning and multivariate statistics for associations with underlying disease and final CLAD severity.\u0000Results. BALF metabolomes varied by underlying disease state, with AATD LT recipients being particularly distinctive (PERMANOVA, p = 0.001). We also found significant associations of the metabolome with a subjects final CLAD severity score (PERMANOVA, p = 0.001), especially those with underlying CF. Association with CLAD severity was driven by changes in phosphoethanolamine (PE) and phosphocholine lipids that increased and decreased, respectively, and metabolites from the bacterial pathogen Pseudomonas aeruginosa. P. aeruginosa siderophores, quorum-sensing quinolones, and phenazines were detected in BALF, and 4-hydroxy-2-heptylquinoline (HHQ) was predictive of the final CLAD stage in samples from CF patients (R = 0.34; p ≤ 0.01). Relationships between CLAD stage and P. aeruginosa metabolites were especially marked in those with CF, where 61% of subjects had at least one of these metabolites in their first BALF sample after transplant. These molecules also correlated with the relative abundance of P. aeruginosa from microbiome sequence data. Conclusions: BALF metabolomes after LTX are distinctive based on the underlying disease. Metabolomic data also reflected measures of the final CLAD stage, which was driven by a lipid transition from mostly PC to predominantly PE phospholipids, and metabolites from P. aeruginosa. The association of P. aeruginosa metabolites with CLAD stages in LTX recipients indicates this bacterium and its associated metabolites may be drivers of allograft dysfunction.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"198 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients","authors":"Ilies Benotmane, Jérôme Olagne, Gabriela Gautier-Vargas, Noëlle Cognard, Francoise Heibel, Laura Braun-Parvez, Nicolas Keller, Jonas Martzloff, Peggy Perrin, Romain Pszczolinski, Bruno Moulin, Samira Fafi-Kremer, Sophie Caillard","doi":"10.1101/2022.09.30.22280568","DOIUrl":"https://doi.org/10.1101/2022.09.30.22280568","url":null,"abstract":"Objective: This single-center retrospective study evaluated the use of tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients (KTRs) during the omicron wave. Methods: KTRs were deemed at high risk for moderate-to-severe COVID-19 in presence of at least one comorbidity (age &gt;60 years, diabetes, obesity, or cardiovascular disease) associated with a weak humoral response (&lt;264 BAU/mL). All other KTRs were considered at low risk. The two groups were stratified according to the administration of tixagevimab-cilgavimab and compared in terms of COVID-19-related hospitalization, oxygen need, ICU admission, and mortality.\u0000Results: Of the 61 KTRs at high risk, 26 received tixagevimab-cilgavimab. COVID-19-related hospitalizations (3.8% versus 34%, p=0.006) and oxygen need (3.8% versus 23%, p=0.04) were significantly less frequent in patients who received tixagevimab-cilgavimab. In addition, non-significant trends towards a lower number of ICU admissions (3.8% versus 14.3% p=0.17) and deaths (0 versus 3, p=0.13) were observed after administration of tixagevimab-cilgavimab. Ten of the 73 low-risk KTRs received tixagevimab-cilgavimab, and no significant clinical benefit was observed in this subgroup. Conclusion: Early administration of tixagevimab-cilgavimab may be clinically useful in high-risk KTRs with COVID-19; however, no major benefit was observed for low-risk patients.","PeriodicalId":501561,"journal":{"name":"medRxiv - Transplantation","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}