Faculty Bibliography

BACKGROUND:Extended-course enoxaparin is increasingly used after bariatric surgery to prevent venous thromboembolism (VTE), the leading cause of death after bariatric surgery. Direct oral anticoagulants are widely used for extended thromboprophylaxis outside of bariatric surgery and offered to patients in our program who cannot tolerate or obtain enoxaparin. We evaluated the safety and efficacy of apixaban 2.5 mg twice daily relative to a weight-based dose of enoxaparin 40 mg or 60 mg twice daily for 30 days after discharge following sleeve gastrectomy. METHODS:Patients aged ≥18 years who underwent laparoscopic sleeve gastrectomy from 2019 to 2024 at a single high-volume urban academic center were included. Bleeding and thrombosis outcomes within 30 days were compared between patients receiving enoxaparin 40 mg twice daily or apixaban 2.5 mg twice daily. Weighted modified Poisson analyses were used to obtain covariate balance and assess differences in bleeding and thrombosis events. RESULTS:A total of 5921 patients were included for analysis (5274 enoxaparin 40 mg twice daily, 486 enoxaparin 60 mg twice daily, and 161 apixaban 2.5 mg twice daily). The 30-day thrombosis rate was significantly lower with enoxaparin versus apixaban (.1% versus 1.9%, P < .001). The composite outcome (VTE, portomesenteric venous thrombosis, and major/minor bleeding) was also significantly lower with enoxaparin versus apixaban (1.7% versus 5.6%, P < .01). In adjusted analyses, apixaban was associated with a relative risk of 12.09 for thrombosis (95% confidence interval [CI], 5.71-31.18), 1.93 for bleeding (95% CI, 1.27-3.00), and 2.59 (95% CI, 2.06-3.27) for any adverse outcome relative to enoxaparin. CONCLUSION/CONCLUSIONS:Enoxaparin is associated with both lower thrombosis and bleeding rates compared with apixaban for extended thromboprophylaxis after sleeve gastrectomy.

Hypothermic machine perfusion (HMP) has surged in popularity for donor kidney preservation. Continuous-HMP (cHMP) has shown clear benefits over static cold storage (SCS), whereas randomized trials on short-duration end-ischemic-HMP (eiHMP) have not. We assessed whether HMP modulates injury from increasing cold-preservation-time and analyzed the impact of HMP on short- and long-term outcomes, using OPTN data (2010-2024) on single-kidney-transplant recipients (n=137,835). Multivariable non-linear (restricted cubic spline) regression with interaction terms were used. Median cold-preservation-time was long (17.3hrs,IQR:12.0-22.9), especially in the eiHMP cohort (median=23.0hrs,IQR:17.3-30.5). HMP was associated with significant reductions in DGF (cHMP:aOR=0.484,95%CI=0.467-0.501; eiHMP:aOR=0.459,95%CI=0.435-0.485; transport-only-HMP:aOR=0.535,95%CI=0.512-0.558) and LOS. Interaction analyses revealed HMP mitigated the negative effect of increasing cold-preservation-time compared with SCS. cHMP showed benefit across all cold-preservation-times, whereas eiHMP was beneficial only at longer cold-preservation-times. HMP was also associated with improved 5-year graft and patient survival. In conclusion, HMP reduces the negative impact of each additional hour of cold-preservation-time. Therefore, the treatment effect is not fixed and increases as cold-preservation-time increases, likely explaining the lack of benefit in trials of short-duration eiHMP. The association with improved 5-year graft survival and mortality provides IDEAL stage 4 evidence. This study addresses questions beyond the reach of randomized trials but of clear clinical relevance.

BACKGROUND:Access to liver transplantation (LT) for pediatric registrants is complex and impacted by many factors. Assessing the state of pediatric LT requires understanding the balance between policy, the availability of livers, and the quantity of pediatric patients requiring LT. METHODS:Using Scientific Registry of Transplant Recipients data with Cox regression (to compare rates) and competing risk regression (to compare cumulative incidence), we evaluated pediatric patient characteristics, number of registrants transplanted, and waitlist mortality from (January 1, 2017-February 4, 2020) to (May 1, 2020-June 4, 2023) using the implementation of acuity circles to divide the eras. RESULTS:In 4314 pediatric LT registrants, transplantation rate increased in the post-policy era, compared with the pre-policy era (adjusted hazard ratio [HR], 1.05 1.12 1.20 ; P  < 0.001). When accounting for competing risks, the increase was attenuated and not statistically significant (adjusted subdistribution HR, 0.99 1.06 1.14 ; P  = 0.08); recipients were no more likely to die on the waitlist (adjusted subdistribution HR, 0.78 1.01 1.30 ; P  = 0.99). Importantly, the prevalent pediatric waitlist dropped from 396 (2017) to 225 (2023), the rate of deceased donor LT from pediatric donors increased (weighted HR, 1.20 1.31 1.42 ; P  < 0.001), and access to living donor LT increased, compared with the pre-policy era (weighted HR, 1.11 1.33 1.59 ; P  = 0.002). The transplant rate for pediatric patients did not decrease during the study period despite the introduction of acuity circles. During the study period, the prevalent waitlist shrank, access to LT from pediatric donors increased, and access to living donor LT increased. CONCLUSIONS:Comprehensive assessment following the policy change is necessary to ensure that pediatric candidates maintain priority. Changes in pediatric transplantation are modest and likely related to changes in the pool, rather than to the policy of acuity circles.

INTRODUCTION/BACKGROUND:Following implementation of the U.S. Kidney Allocation System (KAS) in 2014, deceased donor kidneys with a kidney donor profile index (KDPI) < 35% are prioritized for allocation to pediatric candidates. Early post-KAS data suggested this prioritization may have led to more frequent delayed graft function compared to pre-KAS, when pediatric allocation priority was based on donor age < 35 years. We sought to understand the impact of this allocation change on longer-term pediatric kidney transplant outcomes. METHODS:We used SRTR data to identify all deceased donor kidney transplants with pediatric recipients during two eras: "Pre-KAS" (12/1/2009-11/30/2014) and "KAS" (12/1/2015-11/30/2020). We used Cox proportional hazards models to calculate the association between study era and all-cause graft failure (graft failure or death) after adjusting for recipient characteristics. RESULTS:, p = 0.001). Results were similar in sensitivity analyses limited to recipients < 10 years old and recipients alive with a functioning graft 90 days post-transplant. CONCLUSIONS:KDPI-based prioritization of kidneys for pediatric allocation was associated with a lower risk of graft failure compared to donor age-based prioritization. Further refining donor risk scores may enable additional improvements in graft survival.

Since their early development in the 1980s, Simulated Allocation Models (SAMs) have helped policymakers forecast the impact of proposed allocation policy changes on patient outcomes before implementation. In the United States, models like the Kidney-Pancreas Simulated Allocation Model, Liver Simulated Allocation Model, and Thoracic Simulated Allocation Model have been instrumental in shaping organ allocation policies. Analogous models have emerged globally, including the ETKidney and Eurotransplant Liver Allocation System simulators for the Eurotransplant region, to address country and region-specific allocation challenges. This review categorizes and compares SAMs based on their core assumptions, data, and modeling approaches. We highlight challenges in model validation, the use of synthetic data, and model transparency. While simplifying assumptions are often necessary because of limited data, their influence on results should be clearly communicated to ensure policymakers can interpret model predictions accurately. Furthermore, model validation using both retrospective and prospective data is essential to assess performance under evolving policies. Greater transparency through open-source models, detailed reporting of assumptions, and validation efforts can enhance collaboration, reproducibility, and confidence in transplant research. By providing a global perspective on SAMs, this review aims to inform future research and policy development, promoting evidence-based policy development in organ transplantation.

BACKGROUND/UNASSIGNED:Understanding center-level decision-making for suboptimal kidney (SOK) offers is critical to ensure utilization of all transplantable kidneys. METHODS/UNASSIGNED:We quantified center-level variation in accepting SOK deceased donor kidney transplant (DDKT) offers using 2021-2023 national registry data. SOK subtypes included: donor age >60, ultimate cold ischemia time >24 h, hepatitis C positive, terminal serum creatinine >2.0 mg/dL, donation after circulatory death, kidney donor profile index >85%, and public health service increased risk donors. Gini coefficient (Gini) was used to analyze inequality in DDKT utilization by SOK subtype. Multilevel logistic regression models were used to calculate the median odds ratio (mOR), measuring center-level variation in accepting SOK donor offers among adult centers. RESULTS/UNASSIGNED:Of all DDKTs, 72.6% were from donors with at least 1 SOK characteristic. Inequality persisted in utilization of SOK DDKTs (Gini of all SOKs: 0.53, Gini of all non-SOKs: 0.47). The 193 adult centers accepted a median (interquartile range) of 12.5% (8.4%-19.2%) offered non-SOK donors and 7.2% (4.6%-10.8%) offered SOK donors. Non-SOK donors and SOK donors were refused by a median (interquartile range) of 5 (3-10) and 9 (4-23) centers, respectively. The SOK subtypes with the least and the most center-level variance in acceptance were increased risk donor (mOR = 2.06) and cold ischemia time >36 h (mOR = 4.86), respectively. CONCLUSIONS/UNASSIGNED:Centers vary sharply in their willingness to accept certain types of SOK offers. Informing centers of their patterns of accepting specific donor phenotypes compared with their peers may motivate centers to accept more SOKs for clinically suitable recipients, thus improving patient access to DDKT.

BACKGROUND:Kidney transplantation (KT) from donors with human immunodeficiency virus (HIV-1) to recipients with HIV (HIV D+/R+) is noninferior to KT from donors without HIV (HIV D-/R+) with regard to safety. However, there may be differences in posttransplant infections. METHODS:We performed a secondary analysis of the HOPE in Action KT Study (NCT02602262) comparing the time to first clinically relevant infection within 24 months posttransplantation in 99 HIV D+/R+ versus 99 HIV D-/R+. Secondary outcomes included incidence rates, infection-related death, and timing of clinically relevant infection, each stratified by donor HIV status. RESULTS:The cumulative incidence of a clinically relevant infection at 24 months posttransplantation was 73.8% (95% confidence interval [CI]: 63.1%-81.2%) for HIV D+/R+ versus 64.7% (95% CI: 53.0%-73.4%) for HIV D-/R+. Comparing time to first clinically relevant infection in HIV D+/R+ versus HIV D-/R+, the adjusted hazard ratio (aHR) was 1.44 (95% CI: 1.01-2.04) at 24 months posttransplantation; for infections associated with hospitalization, the aHR was not significantly higher (1.21 [95% CI: .78-1.86). There were no significant differences in the number of infections, death from infection, duration, or site of infection between HIV D+/R+ versus HIV D-/R+, though viral infections were numerically more common in HIV D+/R+ (40% vs 35%). CONCLUSIONS:Although there was a statistically significant association between receipt of a kidney from a donor with HIV and time to first clinically relevant infection in the 24 months posttransplantation, there were no differences in infections associated with hospitalization. These data are overall reassuring as this emerging practice expands into clinical care. Clinical Trials Registration. NCT02602262.

BACKGROUND:Multiorgan heart and kidney transplants (HKTx) performed for patients with end-stage heart failure and chronic kidney disease have increased in recent years. However, no established protocols exist on whether a heart and kidney from the same donor should be transplanted in the same operation versus 1-2 days apart. METHODS:Using SRTR data 1993-2023, we compared same-donor HKTx recipients with both transplants performed on the same day ("simultaneous") to recipients with kidney transplants performed within 1 day of the heart transplant ("staged"). We examined differences in weighted post-transplant clinical characteristics using average treatment effect. Post-transplant mortality and graft failure was also assessed using Kaplan-Meier curves and instrumental variable analysis adjusted for recipient characteristics and year of transplant. RESULTS:, p < 0.001). Weighted patient mortality, all cause heart failure (ACHF), and all cause kidney failure (ACKF) 4 years post-transplant were slightly lower for simultaneous versus staged HKTx recipients (17.1% vs. 19.9%, 17.2% vs. 20.1%, 20.8% vs. 24.7%). However, instrumental variable analysis found no meaningful differences in adjusted patient survival, ACHF, or ACKF by HKTx type. CONCLUSION/CONCLUSIONS:Simultaneous HKTx recipients have shorter hospital stays, decreased mortality, and higher rates of graft survival post-transplant compared to staged HKTx recipients, which may reflect favorable patient factors that enable both operations to be performed on the same day rather than an inherent benefit of simultaneous HKTx, given equivalent adjusted patient mortality, ACHF, and ACKF.