Transplantation Direct最新文献

Background: A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens.

Methods: Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling.

Results: Biopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5, CD8A, KLRK1, and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention.

Conclusions: The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.

Background: The concept of TO is expanding across various surgical disciplines to establish a standardized, comprehensive quality benchmark. Traditional metrics such as 1-y patient and graft survival have been key for evaluating transplant program performance but are now deemed inadequate because of significant field advancements. This systematic review aims to provide a comprehensive understanding of the applicability and validity of textbook outcome (TO) in the setting of solid organ transplantation.

Methods: A structured search, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, was conducted across PubMed, Embase, and Scopus databases on March 10, 2024.

Results: Fourteen articles were identified for inclusion in this review. Of these, 2 studies addressed TO in heart transplantation, 3 in lung transplantation, 2 in kidney transplantation, and 7 in liver transplantation. A subgroup analysis was conducted to categorize the different definitions of TOs and identify the most common reasons for TO failure.

Conclusions: Our systematic review highlights the ongoing efforts in the field of solid organ transplantation to define TO and emphasizes the importance of developing a universally recognized set of TO criteria for each type of transplant. TO provides a valuable framework for transplant centers to benchmark their performance against similar institutions on a risk-adjusted basis and to pinpoint specific areas for enhancing patient outcomes. Even the most successful programs may discover aspects within the composite outcome with scope for improvement.

Background: In the United States, universal screening for human T-lymphotropic virus (HTLV) in deceased organ donors was discontinued in 2009. Since then, the transplant guideline suggests considering targeted screening. However, the outcomes of this change in HTLV screening have not been evaluated.

Methods: Using the Organ Procurement and Transplantation Network database between 2010 and 2022, we analyzed the HTLV antibody screening frequency and seroprevalence in potential deceased organ donors and their correlations with HTLV infection risks, including race and high-risk behaviors for blood-borne pathogen infection. Although targeted screening has not been established for HTLV, we hypothesized that screening rates should correlate with the proportions of donors with infection risk if screening is targeted. We also evaluated the organ utilization of HTLV-seropositive donors.

Results: Of 130 284 potential organ donors, 22 032 (16.9%) were tested for HTLV antibody. The proportion of donors tested for HTLV varied between Organ Procurement Organizations (median [interquartile range], 3.8% [1.0%-23.2%]; range, 0.2%-99.4%) and was not correlated to HTLV infection risks. There were 48 seropositive donors (0.22%), and at least 1 organ from 42 of these donors (87.5%) was transplanted. The number of organs recovered and transplanted per donor was significantly lower in HTLV-seropositive than in HTLV-negative donors (recovered, 2 [2-3] versus 3 [3-5], P < 0.001; transplanted, 2 [1-3] versus 3 [2-4], P < 0.001). However, HTLV-1 infection was not attributed as the cause of nonrecovery except for only 1 HTLV-seropositive donor.

Conclusions: HTLV screening practices varied across the United States. Our findings suggest that targeted screening was not performed after the elimination of universal screening.

Background: Transplant centers have traditionally relied upon procurement teams from their own programs (transplant program procurement team [TPT]) to recover donation after circulatory death (DCD) livers and rarely use surgical procurement teams not affiliated with the recipient center (nontransplant program procurement team [NTPT]). However, in the era of wider geographic organ sharing, greater reliance on NTPTs is often necessary.

Methods: We used national data to study the association between the origin of the donor procurement team (NTPT versus TPT) and the risk of DCD liver allograft failure.

Results: Five hundred NTPT and 2257 TPT DCD transplants were identified: 1-y graft survival was 88.9 and 88.6%, respectively (P = 0.962). In a multivariable model, the origin of the procurement team was not associated with graft failure NTPT versus TPT (hazard ratio, 0.92; 95% confidence interval, 0.71-1.22; P = 0.57) but rather with known risks for DCD graft loss including donor age, degree of recipient illness, cold ischemic time, and retransplantation. The overall incidence of retransplantation and ischemic cholangiopathy as an indication for retransplantation were similar between NTPT and TPT.

Conclusions: This data suggests that transplant centers may be able to safely use DCD livers recovered by local surgical teams.

Background: Endomyocardial biopsy (EMB) is considered the gold-standard method to diagnose rejection after heart transplantation. However, the many disadvantages and potential complications of this test restrict its routine application, particularly in pediatric patients. Donor-derived cell-free DNA (dd-cfDNA), released by the transplanted heart as result of cellular injury, is emerging as a biomarker of tissue damage involved in ischemia/reperfusion injury and posttransplant rejection. In the present study, we systematically evaluated dd-cfDNA levels in pediatric heart transplant patients coming for follow-up visits to our clinic for 12 mo, with the aim of determining whether dd-cfDNA monitoring could be efficiently applied and integrated into the posttransplant management of rejection in pediatric recipients.

Methods: Twenty-nine patients were enrolled, and cfDNA was obtained from 158 blood samples collected during posttransplant follow-up. dd-cfDNA% was determined with a droplet-digital polymerase chain reaction assay. EMB scores, donor-specific antibody measurements, and distress marker quantification were correlated with dd-cfDNA, together with echocardiogram information.

Results: The percentage of dd-cfDNA increased when EMBs scored positive for rejection (P = 0.0002) and donor-specific antibodies were present (P = 0.0010). N-terminal pro-B-type natriuretic peptide and high-sensitive troponin I elevation were significantly associated with dd-cfDNA release (P = 0.02 and P < 0.0001, respectively), as were reduced isovolumetric relaxation time (P = 0.0031), signs of heart failure (P = 0.0018), and treatment for rejection (P = 0.0017). By determining a positive threshold for rejection at 0.55%, the test had a negative predictive value maximized at 100%.

Conclusions: Collectively, results indicate that dd-cfDNA monitoring has a high negative prognostic value, suggesting that in heart transplanted children with dd-cfDNA levels of <0.55% threshold, protocol EMBs may be postponed.

Background: Although COVID-19 is no longer a declared global health emergency, data remain limited on the impact of COVID-19 in lung transplant recipients.

Methods: We identified lung transplant recipients who were diagnosed with COVID-19 from March 2020 through August 2022 in our institutional database and investigated clinical outcomes. We then analyzed outcomes based on date of COVID-19 diagnosis (first wave March 2020-October 2020; second wave November 2020-2021; third wave December 2021-September 2022) and compared these results.

Results: Of the 210 lung transplant recipients (median age 67; 67% men) enrolled, 140 (67%) required hospital admission. Among admitted recipients, 35 (25%) were intubated and 7 (5%) were placed on extracorporeal membrane oxygenation. Overall survival was 67.1% at 1 y and 59.0% at 2 y post-COVID-19 diagnosis. COVID-19 led to mortality in all 5 patients diagnosed during their index admission for lung transplantation. Although overall survival was significantly better in recipients with COVID-19 during the third wave, in-hospital mortality remained high (first wave 28%, second wave 38%, and 28% third wave). Vaccination (partially vaccinated versus none and fully vaccinated versus none) was the only significant protective factor for hospital admission, and age 70 y and older and partially vaccinated (versus none or fully vaccinated) were independent risk factors for in-hospital mortality.

Conclusions: Overall survival after COVID-19 infection in lung transplant recipients continues to improve; however, in-hospital mortality remains remarkably high. Vaccination appears to have been impactful in preventing hospital admission, but its impact on in-hospital mortality is still unclear. Further research is needed to better identify lung transplant recipients at high risk for mortality from COVID-19.

Background: In HLA-incompatible kidney transplantation, the efficacy of desensitization in terms of anti-HLA antibody kinetics is not well characterized. We present an overview of the course of anti-HLA antibodies throughout plasma exchange (PE) desensitization in a series of crossmatch-positive patients.

Methods: All consecutive candidates in the Dutch HLA-incompatible kidney transplantation program between November 2012 and January 2022 were included. The eligibility criteria were a positive crossmatch with a living kidney donor and no options for compatible transplantation. Desensitization consisted of 5-10 PE with low-dose IVIg.

Results: A total of 16 patient-donor pairs were included. Patients had median virtual panel-reactive antibody of 99.58%. Cumulative donor-specific anti-HLA antibody (cumDSA) mean fluorescence intensity (MFI) was 31 399 median, and immunodominant DSA (iDSA) MFI was 18 677 for class I and 21 893 for class II. Median anti-HLA antibody MFI response to desensitization was worse in class II as compared with class I (P < 0.001), particularly for HLA-DQ. Class I cumDSA MFI decreased 68% after 4 PE versus 53% in class II. The decrease between the fifth and the 10th PE sessions was modest with 21% in class I versus 9% in class II. Antibody-mediated rejection occurred in 85% of patients, with the iDSA directed to the same mismatched HLA as before desensitization, except for 3 patients, of whom 2 had vigorous rebound of antibodies to repeated mismatches (RMMs). Rebound was highest (86%) in RMM-DSA with prior grafts removed (transplantectomy n = 7), lower (39%) in non-RMM-DSA (n = 30), and lowest (11%) for RMM-DSA with in situ grafts (n = 5; P = 0.018 for RMM-DSA transplantectomy versus RMM-DSA graft in situ). With a median follow-up of 59 mo, 1 patient had died resulting in a death-censored graft survival of 73%.

Conclusions: Patients with class II DSA, and particularly those directed against HLA-DQ locus, were difficult to desensitize.

Background: Organ transplantation is a well-established intervention but is reliant on the donation of organs and tissues, mostly from deceased donors. The proportion of Australians proceeding to organ donation (OD) has increased, but the proportion of Indigenous Australians proceeding remains two-thirds that of non-Indigenous Australians. We sought to explore perceived barriers and enablers for the involvement of Indigenous peoples in the OD process.

Methods: Qualitative methodology centered around focus groups was used to capture the experiences and perspectives of Indigenous people regarding OD. A purposively sampled group of Aboriginal Liaison Officers working within the Alice Springs Hospital Intensive Care Unit (ASH ICU) participated in up to 6 focus groups during 2021 with subsequent thematic analysis of the enablers and barriers to Indigenous participation in the OD process. The ASH ICU is the only ICU servicing Central Australia, and 70% of admissions are Indigenous patients.

Results: Four primary themes emerged: OD is a new and culturally taboo topic; conversations related to OD are confronting; education is needed (both about OD and cultural education for clinicians); and lack of trust in the healthcare system.

Conclusions: There are cultural barriers to engaging in the OD process and clinicians need more training on the delivery of culturally safe communication is needed. Despite this, there was a recognition that OD is important. Education about OD needs to be place based, culturally and linguistically appropriate, informed by local knowledge, delivered in community, and occur before a family member is admitted to ICU.

Background: The number of patients waiting for heart transplant far exceeds the number of hearts available. Donation after circulatory death (DCD) combined with machine perfusion can increase the number of transplantable hearts by as much as 48%. Emerging studies also suggest machine perfusion could enable allograft "reconditioning" to optimize outcomes. However, a detailed understanding of the energetic substrates and metabolic changes during perfusion is lacking.

Methods: Metabolites were analyzed using 1-dimensional ¹H and 2-dimensional ¹³C-¹H heteronuclear spectrum quantum correlation nuclear magnetic resonance spectroscopy on serial perfusate samples (N = 98) from 32 DCD hearts that were successfully transplanted. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test for significant differences in metabolite resonances during perfusion and network analysis was used to uncover altered metabolic pathways.

Results: Metabolite differences were observed comparing baseline perfusate to samples from hearts at time points 1-2, 3-4, and 5-6 h of perfusion and all pairwise combinations. Among the most significant changes observed were a steady decrease in fatty acids and succinate and an increase in amino acids, especially alanine, glutamine, and glycine. This core set of metabolites was also altered in a DCD porcine model perfused with a nonblood-based perfusate.

Conclusions: Temporal metabolic changes were identified during ex vivo perfusion of DCD hearts. Fatty acids, which are normally the predominant myocardial energy source, are rapidly depleted, while amino acids such as alanine, glutamine, and glycine increase. We also noted depletion of ketone, β-hydroxybutyric acid, which is known to have cardioprotective properties. Collectively, these results suggest a shift in energy substrates and provide a basis to design optimal preservation techniques during perfusion.

Background: The effect of donor body mass index (BMI) on liver transplantation (LT) outcomes remains unclear.

Methods: A systematic search of the MEDLINE, CENTRAL, Web of Science, and bibliographic reference lists was conducted. All comparative studies evaluating the outcomes of LT in obese (BMI > 30 kg/m²) and nonobese donors (BMI < 30 kg/m²) were included, and their risk of bias was assessed using the ROBINS-I assessment tool. Patient and graft survival, acute rejection, and graft failure requiring retransplantation were evaluated as outcome parameters. A random-effects model was used for outcome synthesis.

Results: We included 6 comparative studies reporting a total of 5071 liver transplant recipients from 708 obese and 4363 nonobese donors. There was no significant difference in 1-y (89.1% versus 84.0%, odds ratio [OR] 1.58; 95% CI 0.63-3.94, P = 0.33), 5-y (74.2%% versus 73.5%, OR 1.12; 95% CI 0.45-2.80, P = 0.81) graft survival, and 1-y (87.1% versus 90.3%, OR 0.71; 95% CI 0.43-1.15, P = 0.17) and 5-y (64.5% versus 71.6%, OR 0.71; 95% CI 0.49-1.05, P = 0.08) patient survival between 2 groups. Furthermore, recipients from obese and nonobese donors had a comparable risk of graft failure requiring retransplantation (OR 0.92; 95% CI 0.33-2.60, P = 0.88) or acute graft rejection (OR 0.70; 95% CI 0.45-1.11, P = 0.13).

Conclusions: A meta-analysis of the best available evidence (level 2a) demonstrates that donor obesity does not seem to have a negative impact on graft or patient outcomes. The available studies might be subject to selection bias as the grafts from obese donors are usually subject to biopsy to exclude steatosis and the recipients usually belong to the low-risk group. Future research is needed to evaluate the impact of donors subgrouped by various higher BMI on graft and patient-related outcomes as well as to capture data of the discarded grafts from obese donors; hence, selection criteria for the grafts that could be used for transplantation from obese donors is identified.