Transplantation Direct最新文献

Background: Solid organ transplants are life-changing experiences that impact recipients, donors, care partners, medical teams, communities, and popular media. Social media is an influential part of modern life and provides a platform for healthcare experiences. This study assessed perspectives on solid organ transplantation by exploring the transplant community's utilization of the social media site Reddit.

Methods: The 1000 most recent and "Top" 100 posts from the r/transplant subreddit were extracted in April 2024. Posts underwent categorization to identify key themes and subthemes. The Python "Valence Aware Dictionary and sEntiment Reasoner" sentiment analysis tool was used to evaluate post sentiment.

Results: Posts most frequently discussed kidney (43.3%) and liver (18.3%) transplants. Most were authored by transplant recipients (66.5%) and centered on the posttransplant period (63.0%). Categorization of the 1000 most recent posts revealed 11 major themes: eligibility, pretransplant anticipation, logistics, early recovery, late recovery, medication, lifestyle, infection, seeking connection, sharing experience, and transplant in media. Over a third of posts sought Reddit user input on medical questions. Sentiment analysis demonstrated predominantly positive sentiment (0.25). The "Top" 100 posts had more positive sentiment (0.50) and focused on sharing experiences.

Conclusions: Reddit serves as a platform for information exchange and support for the transplant community, addressing a wide range of pre- and posttransplant topics. Future work should explore ways to incorporate the real-world solutions offered by social media into formal healthcare practices.

Background: Subnormal lung function after lung transplantation (LTx) has increasingly been recognized as an independent risk factor for mortality. Historically, baseline lung allograft dysfunction (BLAD) has been defined using the fixed "< 80% predicted" threshold from population-wide reference equations, which disregards age- and sex-related variability in spirometric values and can lead to systematic overdiagnosis, particularly in older and female recipients. While the lower limit of normal (LLN), derived from Global Lung Initiative reference equations, has been accepted as technical standard in spirometry, it has not yet been applied to define BLAD.

Methods: A retrospective multicenter study included LTx recipients transplanted between 2014 and 2018. Lung function trajectories and allograft survival were followed-up until August 2024. The association of BLAD defined by forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) < LNN as time-dependent variable with graft loss was studied using time-dependent Cox proportional hazard models.

Results: We analyzed 726 patients after LTx including 102 unilateral LTx recipients, of whom 470 (65%) of the cohort achieved normal baseline lung function defined as FEV1 and FVC ≥ LLN. Two hundred thirty-six patients experienced graft loss (n = 2 redo LTx) and 179 developed chronic lung allograft dysfunction. After adjusting for age, disease, transplant type, and chronic lung allograft dysfunction, baseline FEV1 or FVC < LLN was associated with graft loss (hazard ratio, 1.822; 95% confidence interval, 1.372-2.418; P < 0.001).

Conclusions: BLAD defined by concurrent baseline FEV1 or FVC below the LLN was strongly associated with increased risk of graft loss. These findings extend prior studies that used the fixed 80% threshold by demonstrating that an LLN-based, age- and sex-adjusted definition of BLAD identifies lung transplant recipients at risk, thereby avoiding fixed cutoff associated age- and sex-bias.

Background: Cytomegalovirus (CMV) antiviral drugs can cause side effects and promote the emergence of drug-resistance after transplantation. T cell-mediated immunity to CMV (CMI) can be used to limit and optimize the duration of antiviral therapy. However, interferon-gamma release assays show varying rates of CMI in CMV-seronegative recipients (R^-), who are at the highest risk of CMV infection with CMV-seropositive donors (D⁺). Here, we characterize CMI with CMV-specific T cells that express CD154 in R^- liver transplant and intestine transplant recipients.

Methods: Pretransplant blood leukocyte samples from 42 R^- recipients were stimulated with a 15-mer overlapping peptide mixture representing the pp65 CMV antigen. CMI was measured by flow cytometry with CMV-specific CD154⁺ T-cell frequencies.

Results: Recipients, median age (range) 3.3 (0.4-36.5 y), included 39 liver transplant and 3 intestine transplant. CMV serostatus was D⁺/R^- in 21, and D^-/R^- in 21. Protective CMI levels of >1.7% previously established in 142 liver or intestine recipients were observed in 25 of 42 total R^- recipients (60%), including 11 of 21 D⁺/R^- (52%) and 14 of 21 D^-/R^- (67%) participants. CMV DNAemia was observed in the first 60 d after transplantation in 10 of 42 (24%) R^- recipients, including 8 of 17 with CMI <1.7% and 2 of 25 with CMI >1.7%. Adjusted for D⁺/R^-, CMI<1.7% was independently associated with a higher risk of DNAemia (hazard ratio 6.04 [1.2-29.4], P = 0.026).

Conclusions: CMV-specific T cells that express CD154 demonstrate protective levels of CMI in half of all seronegative recipients and can be used to optimize antiviral prophylaxis across all risk categories.

Background: Protocol transbronchial biopsies (TBBx) are standard of practice (SOP) in most lung transplantation (LT) centers for surveillance of acute cellular rejection. In the context of higher LT center volumes, our program experienced increasing difficulty scheduling SOP protocol TBBx at months 1, 3, 6, 9, and 12 post-LT. As part of a Quality Assurance Performance Improvement initiative, we designed this prospective study to assess the efficacy and safety of adopting donor-derived cell-free DNA (dd-cfDNA) surveillance in lieu of protocol TBBx during the initial year after LT at our center.

Methods: Enrolled LT patients with "low-risk" dd-cfDNA (<1.0%) had their 9-mo (9M) protocol TBBx omitted, whereas the 9M protocol TBBx was performed when dd-cfDNA indicated a "high-risk" result (≥1.0%) or for clinical indications. All patients received a protocol TBBx at 12M to assure detection of subclinical acute cellular rejection. We also assessed clinical data from the first year, including change in forced expiratory volume-1 s, donor-specific antibodies, and performed a health economic analysis.

Results: Among 78 enrolled LT patients, 24 were "high risk" (8 with omitted 9M protocol TBBx because of clinical contraindications), and 54 "low risk" (41 with omitted 9M protocol TBBx) by dd-cfDNA. Of the patients with omitted 9M protocol TBBx, 10.2% (5/49) showed rejection at 12 mo compared with 20.7% (6/29), at either the 9M or 12M protocol TBBx. Median change in forced expiratory volume-1 s (baseline-12M) was similar between "high-risk" and "low-risk" cohorts (P = 0.592) and for "omitted" versus "performed" 9M protocol TBBx cohorts (P = 0.271).

Conclusions: Our Quality Assurance Performance Improvement study offered assurances for safety, efficacy, and reduction in healthcare costs when implementing SOP dd-cfDNA surveillance, with a >75% reduction in 9M protocol TBBx procedures among patients who were "low risk" by dd-cfDNA.

Background: Long-term outcomes in kidney transplantation remain suboptimal, with subclinical acute rejection (subAR) frequently going undetected by conventional methods. We hypothesized that subAR represents a molecular precursor to clinical acute rejection (cAR). Leveraging a large National Institutes of Health-funded cohort with matched kidney tissue and peripheral blood samples, our primary objective was to determine whether subAR and cAR share molecular patterns, establishing subAR as an early stage of cAR. As a secondary aim, we compared biopsy and blood gene expression profiles to identify unique and shared pathways and to assess their diagnostic utility.

Methods: This was a retrospective analysis of gene expression data from an observational clinical trial. We analyzed 578 blood and biopsy samples from 129 kidney transplant recipients enrolled in a multicenter observational study. Gene expression differences were analyzed using ANOVA with false discovery rate correction and molecular pathways analysis. Samples were matched and classified based on histologic findings and blood-based molecular diagnostics.

Results: Gene expression and pathway analyses revealed that subAR exhibits a molecular profile consistent with a milder form of clinical rejection in both tissue and blood. Molecular signatures distinguished immune-mediated injury from nonimmune injury. Notably, tissue gene expression profiling in cases that were misclassified by peripheral blood diagnostics were like correctly classified cases, suggesting that histology alone may not reliably define true clinical phenotypes.

Conclusions: Molecular profiling of tissue and blood reflects distinct but complementary aspects of transplant biology and confirms that subAR and cAR share overlapping molecular profiles, supporting the hypothesis that subAR represents an early stage in the progression toward clinical rejection. These findings highlight the limitations of relying solely on histological evaluation and support the use of molecular tissue profiling as an adjunct to histology, particularly in diagnostically ambiguous cases. Molecular profiling provides a supporting framework for identifying subclinical rejection and guiding personalized immunosuppression to improve long-term outcomes.

[This corrects the article DOI: 10.1097/TXD.0000000000001862.].

[This corrects the article DOI: 10.1097/TXD.0000000000001829.].

Background: Globally, deceased donor kidney allocation algorithms prioritize HLA matching, potentially disadvantaging transplant candidates with less common HLA alleles. This study developed an Australian Matchability score (M-score) to assess access to transplantation and posttransplant outcomes based on HLA match probability.

Methods: M-scores were calculated by comparing all recipients and donors with complete HLA-A, HLA-B, and HLA-DR data from the Australia and New Zealand Dialysis and Transplant Registry (July 1, 2006-December 31, 2023). Multivariable Cox regression was used to analyze associations between M-score quartiles and time to transplantation as well as transplantation outcomes.

Results: HLA data from 14 836 recipients and 7708 donors were used to generate M-scores. Of these, 10 760 recipients had available waitlist data and were included in the models. M-scores were normally distributed with a mean ± SD of 11.4 ± 0.9. The proportion of non-European Australians increased significantly with each quartile (ie, more difficult to HLA match), Q1: 16%, Q2: 26%, Q3: 40% Q4: 60% (P < 0.001). Compared with Q1, patients in Q4 were significantly less likely to receive a deceased donor kidney transplant (adjusted hazard ratio [aHR] 0.56; 95% confidence interval [CI], 0.52-0.60; P < 0.001) had the highest risk of death-censored graft loss (aHR 1.39; 95% CI, 1.01-1.91; P = 0.05) and acute rejection (aHR, 1.29; 95% CI, 1.09-1.52; P = 0.002).

Conclusions: The M-score identifies transplant recipients with difficult-to-match HLA profiles. Higher M-scores were associated with a lower likelihood of transplantation and an increased risk of death-censored graft loss and acute rejection. These findings highlight significant inequities in the current HLA-based algorithm for deceased donor allocation.

Background: Donation after circulatory death (DCD) is the major contributor to the growth in deceased organ donation in the United States. Normothermic regional perfusion (NRP) and ex situ machine perfusion (es-MP) have been vital for improving organ assessment and preservation in DCD donor organs. The procurement procedure and storage strategy for noncardiac donors were determined by liver transplant centers in the early era of machine perfusion in the United States. In this study, we analyzed the landscape of liver utilization from noncardiac DCD donors in the United States during the early era of machine perfusion.

Methods: All adult (18 y and older) DCD donors in the United States for which the heart was not used for transplantation from October 1, 2020, to December 31, 2023, were compared using procurement technique (NRP versus super rapid recovery [SRR]) and storage strategy (ex situ machine perfusion [es-MP] versus static cold storage).

Results: One hundred fifty-six livers were transplanted from 284 NRP donors (55% utilization) versus 2497 liver transplants from 9132 SRR donors (27% utilization). Es-MP was used in 19% (n = 30) of liver NRP cases versus 28% (n = 695) of liver SRR cases. Eight hundred fifty-one liver grafts (32%) were exposed to NRP, es-MP, or both.

Conclusions: Given the variation in liver graft management, further research needs to be conducted on the optimal strategies for using technologies such as NRP and es-MP in liver transplantation in the United States; better data collection is necessary to support this research and additional strategies are required to increase access to machine perfusion on a national level are needed.

One of the major hurdles in solid organ transplantation is graft rejection, which must be prevented with lifelong general immunosuppression. However, modern maintenance immunosuppression is accompanied by serious side effects, such as an increased risk of infection and malignancies. The search for alternative therapies specifically controlling allogeneic responses is fueling renewed interest in extracorporeal photopheresis (ECP). Despite guideline indications for ECP in cardiothoracic transplantation, potential applications in liver and kidney transplantation have not been adequately investigated. Presently, limited understanding of the pharmacodynamic effects of ECP and lack of consensus biomarkers are hindering the development of standardized multiparametric assays to assess patient responses. This review explores current knowledge about immune responses after ECP in transplant recipients and collates a set of biomarkers associated with favorable treatment responses.