Transplantation Direct最新文献

Background: The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients.

Methods: We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics.

Results: Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P < 0.02). Live donor and preemptive transplantation were favorable predictors of survival.

Conclusions: In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively.

Liver transplantation (LT) in patients with significant portopulmonary hypertension (PoPH) is associated with an increased risk of several complications, including graft failure. Graft loss is one of the major reasons. Living donor LT (LDLT) is not routinely performed in the United States in this patient population. In addition, ethical considerations often preclude donation from healthy donors in the setting of a procedure associated with an elevated risk of recipient morbidity and mortality. However, LDLT allows LT to be performed electively, using a superior graft with an improved probability of a good outcome. The key to success in managing these patients is establishing a multidisciplinary team that follows an institutional protocol with clear evaluation and management criteria. These criteria include screening and early diagnosis as well as treatment of PoPH with the goal of optimizing pulmonary arterial hemodynamics and maintaining right ventricular function. Any protocol should include admitting the patient to the hospital a day before surgery for placement of a pulmonary artery catheter to measure and derive relevant hemodynamic variables. A multidisciplinary team should determine the fitness for a transplant a after a careful review of the most up-to-date clinical information. Finally, the team prescribes and executes a plan for optimization and safe perioperative management of the patient. In this report, we discuss our approach to the perioperative management of a patient with significant PoPH who safely underwent LDLT with an excellent postoperative outcome.

Background: The development of a hybrid beta-cell replacement approach, referred to as a personalized, transplantable bioartificial pancreas (BAP), holds promise to treat type 1 diabetes (T1D). This interview study aimed to explore patients' expectations, needs, concerns, and considerations when considering to undergo a BAP transplantation.

Research design and methods: Semistructured interviews were conducted with 24 participants diagnosed with T1D. Data collection stopped once data saturation was reached. Audio recordings of the interviews were transcribed verbatim. The interviews were independently analyzed by 2 researchers. A qualitative content analysis using an inductive approach was used.

Results: Three main themes emerged as follow: (1) hoped-for benefits, (2) concerns and decision-making considerations, and (3) procedural aspects. First, the participants expected benefits across medical, psychological, and social domains. Over these 3 domains, 9 subthemes were identified, including improved clinical outcomes, a cure for diabetes, more headspace, emotional relief, a shift in responsibility, protection of privacy, improved flexibility in daily life, less visible diseases, and improved relationships with others. Second, concerns and considerations about undergoing a BAP transplant comprised adverse events, the functionality of the BAP, the surgery procedure, the biological materials used, the transplant location, and the intrusiveness associated with follow-up care. Finally, procedural considerations included equitable access, patient prioritization, and trust and control.

Conclusions: Incorporating insights from this study into the clinical development and implementation of the BAP is crucial to ensure alignment of the product and procedures with the needs and expectations of people with T1D.

Background: Accurate preoperative evaluation of renal function in living kidney donor candidates (LKDCs) is crucial to prevent kidney failure after nephrectomy. We examined the performance of various estimated glomerular filtration rate (eGFR) equations, including the new chronic kidney disease epidemiology collaboration (CKD-EPI) equation in LKDCs.

Methods: We analyzed 752 LKDCs who were assessed for measured GFR by inulin clearance as part of routine pretransplant examination from 2006 to 2020. CKD-EPI2012 from cystatin C (CKD-EPI12cys), CKD-EPI2021 from creatinine (CKD-EPI21cr), CKD-EPI21cr-cys, Japanese modified (JPN) eGFRcr, and JPN eGFRcys were compared in determining the suitability for LKDCs.

Results: CKD-EPI12cys had the lowest absolute and relative biases, with higher P₃₀ and P₁₀, followed by JPN eGFRcys, CKD-EPI21cr, and CKD-EPI21cr-cys. The root mean square error was least for CKD-EPI12cys, then JPN eGFRcys, CKD-EPI21cr-cys, CKD-EPI21cr, and JPN eGFRcr. CKD-EPI21cr, CKD-EPI12cys, and CKD-EPI21cr-cys estimated GFR higher, whereas JPN eGFRcr estimated GFR lower. At the threshold of 90 mL/min/1.73 m², CKD-EPI21cr had the highest percentage of misclassification at 37.37%, whereas JPN eGFRcr had the lowest percentage of misclassification at 6.91%. Using the age-adapted approach, JPN eGFRcr had the lowest percentage of misclassification into overestimation at 7.31%. All eGFR had >5.0%, and CKD-EPI21cr had the highest percentage of misclassification at 21.94%. Conversely, CKD-EPI21cr-cys had the lowest percentage of misclassification into underestimation at 3.19%, both at the threshold of 90 mL/min/1.73 m² and the age-adapted approach. JPN eGFRcr had the highest percentage at 33.38% and 40.69%, respectively.

Conclusions: In evaluating the renal function of Japanese LKDCs, the new CKD-EPI equation had a lower rate of underestimation but a relatively high rate of overestimation. New GFR estimation formulas are needed to be tailored to each ethnic group to enhance the accuracy and reliability of donor selection processes.

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.