Transplantation Direct最新文献

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.

Background: Organ rejection after solid organ transplantation remains a major challenge. The sentinel skin flap (SSF), a vascularized skin flap procured from the donor and transplanted alongside solid organs, has shown promise for early detection of rejection. The radial forearm free flap (RFFF) has a long history of use in reconstructive surgery and offers distinct advantages as SSF in organ donation procedures (ODPs). Until now, the SSF has been procured using the traditional RFFF way. However, an easier, quicker, and safer way is beneficial for logistical and financial reasons. This study presents a modified RFFF procurement technique for ODPs that is simple, quick, and reproducible and can be executed by surgeons who are not familiar with the original RFFF.

Methods: The traditional RFFF procurement technique was modified using deceased donor models, leading to the development of an SSF technique tailored for application during ODPs.

Results: A modified technique was developed and presented, enabling SSF procurement to be completed within 40 min. During the procedure, the donor's arm was positioned above the head or at a 90-degree angle, allowing the creation of a sterile field without interfering with the anesthesiology or organ procurement team. Donor-site closure was achieved using running sutures, ensuring an optimal cosmetic outcome.

Conclusions: We present a modified RFFF procurement technique, designed to obtain an SSF during ODPs, that we believe can also be executed by surgeons not familiar with this flap, ensuring that the procedure does not interfere with or impede the organ procurement procedure.

Background: Kidney delayed graft function (K-DGF) is associated with worse outcomes in simultaneous pancreas-kidney (SPK) recipients. However, its potential association with specific infections, rejection, and early complications remains unclear.

Methods: We compared recipients with K-DGF to those without K-DGF among all adult SPK recipients transplanted at our center between January 2000 and December 2022 who had >2 wk of pancreas graft survival. Outcomes of interest included common posttransplant infections, including urinary tract infection (UTI), pneumonia, cytomegalovirus, BK, surgical wound infection, infected intra-abdominal fluid collection, graft rejection, and death-censored graft failure (DCGF) within the first year of transplant. We also looked for the need for early laparotomy within 90 d.

Results: Seven hundred sixty-five SPK recipients were included, of whom 85 (11.1%) developed K-DGF. In Cox regression analysis, after adjustment for multiple key variables, K-DGF was associated/related with increased risk for UTI (adjusted hazard ratio [aHR], 1.76; 95% confidence interval [CI], 1.06-0.94; P = 0.03), infected intra-abdominal fluid collection (aHR, 2.14; 95% CI, 1.13-4.04; P = 0.02), and need for relaparotomy within 90 d (aHR, 2.07; 95% CI, 1.27-3.37; P = 0.003). K-DGF was also associated with increased risk for pancreas DCGF (aHR, 4.88; 95% CI, 1.90-12.51; P < 0.001). K-DGF was not associated with risk for other common infections of interest or graft rejection.

Conclusions: K-DGF among SPK recipients is associated with an increased risk of UTI, infected intra-abdominal fluid collection, and the need for early relaparotomy, along with pancreas DCGF. Close monitoring and appropriate management are warranted in this higher-risk patient population.

Background: The relevance of cold agglutinins in lung transplantation (LTx) recipients is unclear. While there is typically no intentionally induced hypothermia, the cold preservation of organs could potentially lead to microvascular injury and vascular occlusion after implantation and reperfusion in the presence of cold agglutinins. This study aims to analyze the impact of cold agglutinins in lung transplant recipients on short- and long-term outcomes after LTx.

Methods: We retrospectively analyzed the medical records of 251 patients who underwent LTx at our institution between March 2003 and June 2023. One hundred seventy-three patients were included in the study. Statistical analysis was performed using SPSS and GraphPad software.

Results: One hundred seventy-three of 251 (69%) of the lung transplant recipients were tested for cold agglutinins, which were positive in 78 of 173 (45%) patients. Most had a temperature amplitude of 4 °C; a broader temperature amplitude was detected in 9 of 78 (12%) patients. While there was no effect on overall long-term survival, cold agglutinins were associated with an increased incidence of reperfusion edema (P = 0.0002), severe primary graft dysfunction grade 2/3 (PGD2/3; P = 0.001), and early postoperative thromboembolism (P = 0.04). Multivariate analysis revealed PGD2/3 and thromboembolism as independent predictors of reduced long-term survival (P = 0.003 and P = 0.003, respectively). Plasmapheresis shortly before LTx in selected patients with a high cold agglutinin titer and broad temperature amplitude removed the cold agglutinins for at least 2 mo with good patient outcomes.

Conclusions: Cold agglutinins are associated with an increased incidence of reperfusion edema, PGD2/3, and early postoperative thromboembolism after LTx. Further studies are warranted to evaluate the benefits of regular screening.

Background: Hydrogen sulfide (H₂S) produced endogenously by the CTH gene-encoded cystathionine gamma-lyase protects from renal ischemia-reperfusion injury in preclinical models. Here, we hypothesized that CTH gene polymorphisms (single nucleotide polymorphism [SNP]) and recipient H₂S serum levels influence kidney graft outcomes after transplantation.

Methods: We included all consecutive recipients of a first kidney transplant in the Swiss Transplant Cohort Study and with available genotyping. In addition, 192 deceased-donor kidney transplant recipients were randomly selected to measure baseline serum H₂S levels. The primary endpoint was graft loss during follow-up.

Results: CTH SNPs were identified in up to 50% of the patients. During median follow-up (6.4 y, interquartile range: 3.9-9.8), graft loss was observed in 247 (9.8%) of 2518 patients. The incidence of graft loss was associated with the presence or absence of CTH SNPs. Specifically, rs672203 and rs10458561, increased the risk of graft loss (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.04-1.78, P = 0.02; and HR: 1.29, 95% CI: 1.0-1.66, P = 0.05; respectively), whereas rs113285275 was protective (HR: 0.78, 95% CI: 0.6-1.01, P = 0.05). Interestingly, rs672203 was associated with an increased risk of acute rejection (P = 0.05), whereas rs113285275 was associated with a lower risk of acute rejection (P = 0.01). Finally, in patients with delayed graft function, serum H₂S levels correlated with lower graft dysfunction (defined as estimated glomerular filtration rate <30 mL/min/1.73 m²) (P = 0.05).

Conclusions: Graft outcome after kidney transplantation was associated with CTH genotype and, to some extent, H₂S serum levels. Further research is needed to define the underlying protective mechanisms.

Background: Urinary extracellular vesicles (uEVs) are nanosized particles primarily excreted by the kidney. Kidney-derived uEVs (kd-uEVs) are promising noninvasive biomarkers for assessing kidney allograft health and diseases such as acute rejection (AR) after kidney transplantation. However, their release dynamics posttransplant are unclear. This pilot study investigates kd-uEV dynamics and their potential to distinguish AR from acute tubular necrosis (ATN) and nonbiopsied controls.

Methods: In the discovery cohort, urine samples from 72 donor-recipient pairs were collected pretransplant and on posttransplant days 3, 7, 180, and before for-cause biopsies. A validation cohort included 28 recipients biopsied within the first 2 wk posttransplant. Urine was stained with CD63 (uEV marker) and kidney-specific markers aquaporin 2 (AQP2) or podocalyxin (PODXL). Kd-uEVs were quantified using imaging flow cytometry, and percentages among total CD63⁺ uEVs were calculated to adjust for urine dilution.

Results: The percentage of kd-uEVs was lower in pretransplant recipients (AQP2⁺: 1.1% [Q1-Q3, 0.3%-1.7%]; PODXL⁺: 1.5% [Q1-Q3, 0.9%-2.8%]) compared with donors (AQP2⁺: 4.7% [Q1-Q3, 0.9%-11.5%], P < 0.001; PODXL⁺ 6.4% [Q1-Q3, 1.4%-9.8%], P < 0.01). Recipients' kd-uEVs remained on pretransplant levels on posttransplant day 3 but were higher on day 7 (AQP2⁺: 7.2% [Q1-Q3, 2.6%-17.4%], P < 0.001; PODXL⁺: 10.0% [Q1-Q3, 3.2%-16.3%], P < 0.001) and persisted until day 180. In the initial 2 wk after transplantation, AR cases had higher AQP2⁺ kd-uEVs (17.6% [Q1-Q3, 8.6%-32.3%]) than nonbiopsied controls (6.8% [Q1-Q3, 2.1%-11.2%], P < 0.05) and ATN (1.6% [Q1-Q3, 0.5%-6.4%], P < 0.01), with similar observations for PODXL⁺ kd-uEVs. This difference between early AR and ATN was validated in the validation cohort.

Conclusions: Kd-uEV release is prominent from day 7 posttransplant. Elevated kd-uEVs are associated with AR, distinguishing it from ATN and demonstrating their potential as noninvasive biomarkers for early AR diagnosis.