Transplantation Direct最新文献

Background: Autophagy is a highly conserved cellular process. In the context of hepatic ischemia/reperfusion injury (HIRI), dysregulation of autophagy may lead to hepatocyte dysfunction. Therefore, we conducted a comprehensive transcriptomics analysis to investigate the biomolecular mechanisms underlying autophagy in HIRI.

Methods: Bioinformatics were used to analyze the GSE112713 data set, with the objective of identifying the differential expression of autophagy-related genes (DEARGs). The expression and diagnostic potential of DEARGs were validated using in vitro models and receiver operating characteristic curves. Additionally, potential therapeutic drugs targeting DEARGs were predicted.

Results: Transcriptome bioinformatics analysis revealed widespread dysregulation of autophagy in HIRI. Seven DEARGs (IL6, JUN, HSPA1A, PPP1R15A, ERN1, DNAJB1, and HSPA1B) were confirmed in vitro. Based on these findings, we predicted potential drugs that may mitigate HIRI by modulating autophagy.

Conclusions: The present study identified 7 DEARGs (IL6, JUN, HSPA1A, PPP1R15A, ERN1, DNAJB1, and HSPA1B) in HIRI, which provides a reliable therapeutic target for HIRI.

Background: On March 9, 2023, the Composite Allocation Score (CAS) was introduced for all lung transplantation (LT) candidates. We analyzed waitlist and posttransplant outcomes after CAS implementation.

Methods: Using the United Network for Organ Sharing registry (2022-2024), adult patients listed for isolated LT were divided into 2 eras: era 1 (pre-CAS: March 1, 2022-March 8, 2023) and era 2 (post-CAS: March 9, 2023-September 30, 2024). Competing risk regression analyzed waitlist events. Recipient/donor characteristics and mortality risk factors were assessed with Cox models. Survival was evaluated with Kaplan-Meier analysis.

Results: Among 6398 LTs, 2598 (40.6%) occurred in era 2. More Black patients (16.9% versus 15%, P = 0.04) and those with a high school education (35.4% versus 33.4%, P = 0.0003) were transplanted. ABO type O patients were less likely to undergo LT (42.5% versus 46.6%, P = 0.04). Era 2 had longer transport distances (231 versus 202 miles, P < 0.0001), ischemic times (5.1 versus 4.9 h, P < 0.0001), and increased use of flights (79.1% versus 72.8%, P < 0.0001). Donation after circulatory death (9.4% versus 6.2%, P < 0.0001) and normothermic regional perfusion (2.2% versus 1.2%, P = 0.02) usage rose. Waitlist times decreased (29 versus 31 d, P = 0.009), with improved outcomes (sub-hazard ratio, 0.70; P < 0.0001). Era 2 showed superior 6-mo and 1-y survival (P < 0.0001) and reduced rejection treatment (2.6% versus 14.5%, P < 0.0001).

Conclusions: The implementation of CAS was associated with reduced waitlist mortality, improved access for marginalized groups, and enhanced survival. Lungs were procured from greater distances with an increased use of donation after circulatory death with normothermic regional perfusion or ex vivo perfusion. Disparities remain for ABO type O patients, warranting closer follow-up.

Background: A recent Organ Procurement and Transplant Network policy change removes hepatitis C virus (HCV) status and race from the Kidney Donor Profile Index (KDPI) calculation, thereby lowering the KDPI of HCV nucleic acid testing positive (NAT⁺) kidneys and increasing their allocation priority. However, even in the era of direct-acting antivirals, high KDPI HCV NAT⁺ kidneys exhibited higher discard rates compared with their HCV NAT^- counterparts, and outcome data for this "high-risk" group remain limited. This study aims to address this knowledge gap by providing comprehensive outcome data to better inform organ allocation and selection decisions under the new KDPI framework.

Methods: Using national transplant data from 2015 to 2023, we analyzed adult deceased donor kidney transplants stratified by KDPI and HCV NAT status. An exact matching model was used to identify the matched HCV NAT^- group.

Results: No significant differences were observed in delayed graft function, rejection, or patient and graft survival between high KDPI HCV NAT⁺ and matched HCV NAT^- recipients. High KDPI HCV NAT⁺ kidneys were more often allocated regionally or nationally, with 67.6% occurring in 4 regions. Their recipients were more likely to have a high school education and shorter wait times. After the policy change, >90% of prior high KDPI HCV NAT⁺ kidneys will no longer be classified as high KDPI.

Conclusions: Our findings support the safe utilization of previously high KDPI HCV NAT⁺ kidneys after a policy change. Although the revised KDPI may assist clinicians in identifying higher-quality organs, its impact on existing sociodemographic disparities and overall organ utilization rate remains uncertain.

Background: Right-sided living donor nephrectomy presents a challenge because of the shorter renal vein length, which may complicate vascular anastomosis during transplantation. We hypothesized that the use of a narrow anvil stapler could optimize vein preservation by allowing safer and more effective transection closer to the inferior vena cava. This study aimed to compare the effectiveness of the Signia Small Diameter Reload Short with Curved Tip (SDR) and the Tri-Staple 2.0 Reload (TSR) in preserving renal vein length and to evaluate their impact on donor and recipient outcomes.

Methods: We conducted a retrospective observational cohort study of 39 right-sided donor nephrectomies performed at 2 institutions between May 2019 and December 2024. Patients were divided into 2 groups based on the stapler used: TSR (n = 16) and SDR (n = 23). Inverse probability of treatment weighting was applied to adjust for baseline differences, resulting in a final analysis of 11 TSR and 23 SDR cases. We evaluated renal vein length and overall surgical outcomes.

Results: The SDR group had significantly longer renal vein lengths than the TSR group (23.0 ± 4.0 versus 17.5 ± 3.9 mm, P < 0.001). However, there were no significant differences in operative time, estimated blood loss, or perioperative complications in both donors and recipients. Warm ischemia time, rewarming time, and total ischemia time were also comparable between groups. Early postoperative serum creatinine levels did not differ significantly between recipient groups.

Conclusions: The SDR stapler provided a significant technical advantage in preserving renal vein length in right-sided donor nephrectomy. However, this did not translate into improved recipient outcomes, suggesting that surgical precision and vascular adaptation play a more critical role in transplantation success than vein length alone. Nonetheless, the ability to preserve greater vein length remains a potential advantage, particularly in challenging cases.

Background: Nonhuman primate models are essential in preclinical transplantation studies. Although many advances in medical and surgical therapies have been achieved in liver transplantation research using rodent models, nonhuman primate models have not been widely used because of their technical complexity. As scientific inquiries into tolerance-free and ischemia-free models of transplantation continue to progress, it is vital to establish a standard nonhuman primate model. We attempted to establish a feasible and stable nonhuman primate model for orthotopic liver transplantation using baboons.

Methods: Orthotopic allogeneic liver transplantations were performed in 3 cynomolgus macaques and 5 baboons. Portocaval shunts and extracorporeal bypasses were performed as previously described for cynomolgus macaques. In baboon models, minimization of the anhepatic time was attempted without the bypass technique. Survival, postoperative clinical course, histopathology, and liver enzyme levels were assessed.

Results: The first 2 macaques were euthanized because of gastric necrosis and pneumonia. The third had bypass failure of circulation and developed coagulopathy, which occurred at the end of the study during surgery. In baboons, all 5 recipients survived for >2 mo. The first 3 recipients, whose bile ducts were reconstructed with choledocholedochostomy (duct-to-duct), showed elevated liver function and bile duct enzymes. Therefore, choledochojejunostomy was performed in the other 2 cases, revealing normal liver function postoperatively.

Conclusions: We report successful and consistently stable outcomes of nonhuman primate liver transplantation in baboons. In addition to existing cynomolgus macaque models, our method offers a promising approach and contributes to further clinical adaptation of translational studies.

Background: Ex vivo machine perfusion (MP) has transformed organ preservation, offering significant benefits in liver transplantation (LT), particularly with high-risk donor grafts. However, adoption in the United States has been limited. We aimed to examine early adoption trends, surgeon perceptions, and barriers to implementing MP in the United States after Food and Drug Administration approval of MP platforms.

Methods: A 23-question electronic survey was distributed to members of the American Society of Transplant Surgeons between October and November 2022, capturing attitudes and practices related to MP adoption. Responses from 96 surgeons representing 77 LT centers across 11 Organ Procurement and Transplantation Network regions were analyzed.

Results: Forty-four respondents (48%) reported having an MP program at their institution. Adoption of MP was significantly more common in high-volume centers and those performing ≥20 donation after circulatory death (DCD) transplants annually (P < 0.001). MP utilization received strong support, with 88% endorsing its use for DCD liver allografts and 82% for donation after brain death allografts. Respondents cited MP's ability to reduce ischemic cholangiopathy, enable graft repair, and facilitate viability assessment as key benefits. Normothermic MP was preferred for high-risk donor profiles, including DCD grafts, older donors, and steatotic livers, and was associated with an increased willingness to accept medically complex grafts compared with static cold storage. Barriers to MP utilization included program costs, personnel demands, and logistical complexities. Centers with higher proportions of privately insured patients were more likely to adopt MP. Despite these challenges, 84% of respondents expressed interest in future MP adoption.

Conclusions: MP enhances graft utilization and outcomes, particularly for complex and high-risk donor livers, but widespread US adoption requires addressing financial and logistical barriers. Future efforts should focus on refining cost-effectiveness analyses, collaboration with organ procurement organizations and device companies, and developing standardized training to optimize MP integration and maximize its clinical impact on LT.

Background: Lung transplantation aims to improve health-related quality of life (HRQL) and survival. Although improvements in lung function are associated with these outcomes, the role of physical functioning is less clear. We investigated the association between changes in patient-reported physical functioning and HRQL, chronic lung allograft dysfunction (CLAD), and survival after lung transplantation.

Methods: This single-center prospective cohort study analyzed 220 lung transplant recipients who completed a 15-item Lung Transplant-Valued Life Activities (LT-VLA) before and repeatedly after transplantation. HRQL was measured using validated generic, disease-specific, and utility measures. Associations between 0.3-point changes (the minimally important difference) in LT-VLA as time-varying predictors of HRQL, CLAD, and mortality were tested using linear mixed-effects models for HRQL and Cox proportional hazard models with LT-VLA as a time-varying predictor for CLAD and mortality. Mixed-effects models treated time as a categorical variable to account for possible nonlinear changes over time. Models were adjusted for demographics, disease diagnosis, and postoperative lung function as time-varying covariates.

Results: Participants were 45% women and 75% White, with a mean age of 56 (±12) y. Each 0.3-point improvement in the LT-VLA was associated with significantly improved HRQL across all measures (adjusted P < 0.01). Each 0.3-point improvement in LT-VLA was associated with a 13% reduced hazard of CLAD (adjusted hazard ratio: 0.87, 95% confidence interval: 0.76-0.99, P = 0.03) and a 19% reduced hazard of mortality (adjusted hazard ratio: 0.81, 95% confidence interval: 0.67-0.95, P = 0.01).

Conclusions: Improvements in patient-reported physical functioning after lung transplantation are associated with improved HRQL and a reduced risk of CLAD and death, independent of allograft function. The simplicity of LT-VLA suggests that it could be a valuable monitoring or outcome measure in both clinical and research settings.

Background: Adult solid organ transplant recipients (SOTRs) have decreased responsiveness to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination and higher incidence of infection, but there are few data on the serological response in pediatric SOTR. The aim of this study was to determine serological response to SARS-CoV-2 vaccination in pediatric liver (LT) and kidney transplant (KT) recipients and compare it with adult SOTR.

Methods: A European, prospective, multicenter study was performed. Samples were taken at 7 and 32 wk following COVID-19 vaccination and serological endpoints were measured by ELISA.

Results: A total of 42 pediatric (16 post-LT and 26 post-KT) and 117 adult (all post-LT) were included. All pediatric participants and 94% adult participants received mRNA vaccines. Paediatric SOTR patients had significantly higher anti-Spike IgG levels than adult participants at week 7 (114 220.7 [59 285.92-220 058.55] versus 8756.7 [5643.69-13 586.71], P < 0.0001) and week 32 (46 113.2 [10 992.91-193 436.14] versus 8207.0 [3561.20-18 913.43], P = 0.0032). No significant difference in week 7 anti-Spike IgG response was found between pediatric LT and KT (129 434.4 [51 888.64-322 869.69] versus 105 304.5 [39 910.20-277 849.50], P = 0.9854). No differences were seen between children and adults in the rate of decline of anti-Spike IgG between weeks 7 and 32 (P = 0.8000). Male sex and hemolytic-uremic syndrome or postischemic kidney disease were associated with lower anti-Spike IgG levels at week 7 in pediatric SOTR.

Conclusions: Paediatric SOTR demonstrate greater SARS-CoV-2 vaccine responses than comparable adult SOTR patients. These data support efficacy and safety of SARS-CoV-2 vaccination in child SOTR and may alleviate vaccine hesitancy in this patient group.