MELD 3.0 in Advanced Chronic Liver Disease.

The MELD (model for end-stage liver disease) 3.0 score was developed to replace the MELD-Na score that is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the United States. The MELD 3.0 calculator includes new inputs from patient sex and serum albumin levels and has new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is expected that use of MELD 3.0 scores will reduce overall waitlist mortality modestly and improve access for female liver transplant candidates. The utility of MELD 3.0 and PELDcre (pediatric end-stage liver disease, creatinine) scores for risk stratification in cirrhotic patients undergoing major abdominal surgery, placement of a transjugular intrahepatic portosystemic shunt, and other interventions requires further study. This article reviews the background of the MELD score and the rationale to create MELD 3.0 as well as potential implications of using this newer risk stratification tool in clinical practice.

Impact of removing donation service area and region from pancreas allocation.

On March 15, 2021, the Organ Procurement and Transplantation Network (OPTN) replaced donation service area (DSA) and OPTN region as units of pancreas (PA) allocation with a 250 nautical mile (NM) circle with proximity points. We analyzed OPTN data for kidney-pancreas (KP) and PA candidates, transplants, and donors in the 2 years pre-policy (March 16, 2019, to March 14, 2021) and post-policy (March 15, 2021, to March 14, 2023). As expected, more transplants occurred at hospitals outside the recovering organ procurement organization's DSA post-policy (KP: 32.1% vs 57.3%, P < .001; PA: 61.6% vs 69.3%, P = .09), but the majority stayed within 250 NM (KP: 79.7% vs 85.0%, P < .001; PA: 55.4% vs 61.5%, P = .19). Median preservation time increased from 9.5 to 10.3 hours for KP (P < .001); there was little change for PA (8.5 vs 8.6 hours; P = .99). There were no statistically significant differences in 1-year posttransplant patient mortality or graft failure after implementation for KP (mortality: 3.6% vs 3.2%, P = .60; kidney graft failure: 4.9% vs 5.0%, P = .95; PA graft failure: 9.5% vs 8.9%, P = .65) or PA (mortality: 1.7% vs 2.2%, P = .72; PA graft failure: 12.2% vs 12.6%, P = .88). The removal of DSA and OPTN region from PA allocation has resulted in broader distribution with minimal impact on preservation time or posttransplant outcomes.

OPTN/SRTR 2022 Annual Data Report: Lung.

For the first time since the COVID-19 pandemic, the annual number of lung transplants performed in the United States increased. The year 2022, encompassed in this report, marks the last full calendar year where the Lung Allocation Score was used for ranking transplant candidates based on their estimated transplant benefit and donor lung allocation in the United States. In March 2023, a major change in transplant allocation policy occurred with the implementation of the Composite Allocation Score. Transplant rates have increased over the past decade, although there is variability among age, diagnosis, racial and ethnic, and blood groups. Over half of candidates received a lung transplant within 3 months of placement on the waiting list, with nearly 75% of candidates accessing transplant by 1 year. Pretransplant mortality rates remained stable, with approximately 13% of lung transplant candidates dying or being removed from the waiting list within a year of listing. Posttransplant survival remained stable; however, variability exists by age, diagnosis, and racial and ethnic groups.

Transplanting old organs promotes senescence in young recipients.

In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the capacity to induce senescence in naïve cells. We hypothesized that the engraftment of old organs may induce senescence in younger recipients, promoting age-related pathologies. When performing isogeneic cardiac transplants between age-mismatched C57BL/6 old donor (18 months) mice and young and middle-aged C57BL/6 (3- or 12- month-old) recipients , we observed augmented frequencies of senescent cells in draining lymph nodes, adipose tissue, livers, and hindlimb muscles 30 days after transplantation. These observations went along with compromised physical performance and impaired spatial learning and memory abilities. Systemic levels of the senescence-associated secretory phenotype factors, including mitochondrial DNA (mt-DNA), were elevated in recipients. Of mechanistic relevance, injections of mt-DNA phenocopied effects of age-mismatched organ transplantation on accelerating aging. Single treatment of old donor animals with senolytics prior to transplantation attenuated mt-DNA release and improved physical capacities in young recipients. Collectively, we show that transplanting older organs induces senescence in transplant recipients, resulting in compromised physical and cognitive capacities. Depleting senescent cells with senolytics, in turn, represents a promising approach to improve outcomes of older organs.

Tailoring allocation policies and improving access to paediatric liver transplantation over a 16-year period.

BACKGROUND & AIMS: Mortality on the paediatric liver transplantation (pLT) waiting list (WL) is still an issue. We analysed the Italian pLT WL to evaluate the intention-to-treat (ITT) success rate and to identify factors influencing success. METHODS: All children (<18 years) listed for pLT in Italy between 2002-2018 were included (Era 1 [2002-2007]: centre-based allocation; Era 2 [2008-2014]: national allocation; Era 3 [2015-2018]: national allocation+mandatory-split policy). RESULTS: A total of 1,424 patients (median age: 2.0 [IQR 1.0-9.0] years; median weight: 12.0 kg [IQR 7-27]) were listed for pLT. Median WL time was 2 days (IQR 1-5) for Status 1 and 44 days (IQR 15-120) for non-Status 1 patients; 1,302 children (91.4%) were transplanted (67.3% with split grafts), while 50 children (3.5%) dropped off the WL (2.5% death, 1.0% clinical deterioration). Predictive factors for receiving LT included Status 1 (hazard ratio [HR] 1.66, p = 0.001), Status 1B (HR 1.96, p = 0.016), Status 2A (HR 2.15, p = 0.024) and each 1-point increase in PELD/MELD score. Children with recipient's weight >25 kg, blood group O or awaiting pLT combined with other organs had less chance of being transplanted. ITT patient survival rates were 90.5% at 1 year and 87.5% at 5 years, remaining stable across eras. Risk factors for ITT survival were re-transplantation (HR 5.83, p <0.001), Status 1 (HR 2.28, p = 0.006), Status 1B (HR 2.90, p = 0.014), Status 2A (HR 9.12, p <0.001), recipient weight <6 kg (HR 4.53, p <0.001) and low-volume activity (HR 4.38, p = 0.001). CONCLUSIONS: In Italy, continuous adaption of paediatric organ allocation policies via the introduction of national allocation, paediatric prioritisation rules and a mandatory-split policy have helped maximise the use of donors for paediatric candidates and to minimise WL mortality without compromising outcomes. IMPACT AND IMPLICATIONS: Globally, paediatric liver transplant candidates still suffer from high mortality. Over recent decades, the continuous adaption of organ allocation policies in Italy has led to excellent outcomes for children awaiting liver transplantation. The mortality rate of paediatric liver transplant candidates has been minimised to almost zero, mainly using grafts from deceased donors. Paediatric prioritisation rules, national organ exchange organisation and a mandatory-split liver policy have resulted in a unique allocation model for paediatric liver transplant candidates and represent a landmark for the paediatric transplant community.

Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

BACKGROUND & AIMS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. RESULTS: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). CONCLUSION: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

The Equitable Benefit Approach to guide the assessment of medical and psychosocial factors in liver transplant candidacy.

Lack of available organs poses a significant challenge in meeting the needs of patients with life-threatening liver disease who could benefit from liver transplantation (LT). Psychosocial vulnerability markers have been linked to post-transplant outcomes, raising questions about their use in patient selection. However, their incorporation into selection criteria raises concerns about health equity and potential discrimination. As a result, there is a pressing need to refine fair allocation systems that consider both clinical and psychosocial factors to ensure equitable access and optimize post-transplant outcomes. The Equitable Benefit Approach (EBA) proposed in this paper by the multidisciplinary group of clinical experts in LT from the Italian Society for the Study of the Liver seeks to address these concerns. It presents four procedural principles, the two allocative principles usually applied in transplantation (urgency and utility) and introduces a new one, the principle of health equity. The EBA aims to prioritize patients with the highest transplant benefit while addressing health inequalities. It emphasizes evidence-based decision-making and standardized assessment tools to reliably evaluate psychosocial risk factors. Implementing the EBA involves a multi-step process, including stakeholder engagement, prospective studies to validate its efficacy, development of institutional policies and algorithms, and ongoing monitoring and revision. By following these steps, health care providers can ensure that LT allocation decisions are transparent and responsive to evolving clinical and social contexts. Ultimately, the EBA should offer a comprehensive framework for fair patient selection in LT, considering both biomedical and psychosocial aspects.

Effect of the opioid crisis on the liver transplantation donor pool: A national analysis.

BACKGROUND: Over the last decade there has been a surge in overdose deaths due to the opioid crisis. We sought to characterize the temporal change in overdose donor (OD) use in liver transplantation (LT), as well as associated post-LT outcomes, relative to the COVID-19 era. METHODS: LT candidates and donors listed between January 2016 and September 2022 were identified from the Scientific Registry of Transplant Recipients database. Trends in LT donors and changes related to OD were assessed pre- versus post-COVID-19 (February 2020). RESULTS: Between 2016 and 2022, most counties in the United States experienced an increase in overdose-related deaths (n = 1284, 92.3%) with many counties (n = 458, 32.9%) having more than a doubling in drug overdose deaths. Concurrently, there was an 11.2% increase in overall donors, including a 41.7% increase in the number of donors who died from drug overdose. In pre-COVID-19 overdose was the 4th top mechanism of donor death, while in the post-COVID-19 era, overdose was the 2nd most common cause of donor death. OD was younger (OD: 35 yrs, IQR 29-43 vs. non-OD: 43 yrs, IQR 31-56), had lower body mass index (≥35 kg/cm2, OD: 31.2% vs. non-OD: 33.5%), and was more likely to be HCV+ (OD: 28.9% vs. non-OD: 5.4%) with lower total bilirubin (≥1.1 mg/dL, OD: 12.9% vs. non-OD: 20.1%) (all p < .001). Receipt of an OD was not associated with worse graft survival (HR .94, 95% CI .88-1.01, p = .09). CONCLUSIONS: Opioid deaths markedly increased following the COVID-19 pandemic, substantially altering the LT donor pool in the United States.

The impact of high volumes of COVID-related lung transplant on waitlist mortality for non-COVID candidates in the United States.

Some patients with coronavirus disease 19 (COVID) develop serious, irreversible lung disease, including acute respiratory distress syndrome or pulmonary fibrosis. For select candidates, lung transplant is the only option to improve quality and length of life. Because of the severity of end-stage COVID-related lung disease, these candidates receive high allocation priority in the United States, including higher priority than many patients without COVID-related lung disease. This study assessed whether transplant centers with a large volume of COVID-related lung transplants experienced an increase in waitlist mortality for non-COVID transplant candidates. Nineteen centers were included as high-volume programs, defined as being in the top third of centers who transplanted COVID patients. Of the 2867 non-COVID patients waitlisted at these centers, there was no significant difference in waitlist mortalities of non-COVID transplant candidates between the pre-COVID transplant era (January 2018-February 2020) and during the period of high COVID transplant volume (March 2020-October 2022) (subhazard ratio: .92 [95% CI = .81-1.05], p = .22). Among high volume centers, the decision to transplant and to prioritize patients with COVID-related lung disease did not significantly impact the waitlist mortality of other candidates.

Kidney transplant candidates' perspectives on the implementation of a Canadian Willingness to Cross program: A strategy to increase access to kidney transplantation for highly sensitized patients.

BACKGROUND: Kidney transplantation is the optimal treatment for end-stage renal disease. However, highly sensitized patients (HSPs) have reduced access to transplantation, leading to increased morbidity and mortality on the waiting list. The Canadian Willingness to Cross (WTC) program proposes allowing transplantation across preformed donor specific antibodies (DSA) determined to be at a low risk of rejection under the adaptive design framework. This study collected patients' perspectives on the development of this program. METHODS: Forty-one individual interviews were conducted with kidney transplant candidates from three Canadian transplant centers in 2022. The interviews were digitally recorded and transcribed for subsequent analyses. RESULTS: Despite limited familiarity with the adaptive design, participants demonstrated trust in the researchers. They perceived the WTC program as a pathway for HSPs to access transplantation while mitigating transplant-related risks. HSPs saw the WTC program as a source of hope and an opportunity to leave dialysis, despite acknowledging inherent uncertainties. Some non-HSPs expressed concerns about fairness, anticipating increased waiting times and potential compromise in kidney graft longevity due to higher rejection risks. Participants recommended essential strategies for implementing the WTC program, including organizing informational meetings and highlighting the necessity for psychosocial support. CONCLUSION: The WTC program emerges as a promising strategy to enhance HSPs' access to kidney transplantation. While HSPs perceived this program as a source of hope, non-HSPs voiced concerns about distributive justice issues. These results will help develop a WTC program that is ethically sound for transplant candidates.

Disparity in organ distribution in Gauteng province in South Africa: Challenges and solutions.

BACKGROUND: Despite South Africa's rich heritage as pioneers in organ transplantation, access to organs remains a major issue in the Gauteng province. This is secondary to an array of socioeconomic and political factors that have implications for organ distribution. Our aim was to assess the contribution of the public sector to solid organ transplantation in Gauteng province and compare the distribution of solid organs between the recipient groups. METHODS: This was a retrospective registry review of consented brain-dead donors from the public sector within Gauteng from January 1, 2016, to June 30, 2021, coordinated at Charlotte Maxeke Johannesburg Academic Hospital, a tertiary academic hospital. RESULTS: Records of 49 deceased donors were analyzed. Mean donor age was 31.5 years with the age group 30-39 years constituting the majority of deceased donors at 15/49 (30.6%); 10/49 (16%) were from pediatric donors. There was a significant discrepancy in allocation between public and private sector in cardiac (p = .012) and liver allocation (p < .001) and adult and pediatric recipients for all solid organs (p < .001). There was a significant increase in the rate and number (p = .0026) of pediatric kidney transplants occurring after March 1, 2020, when there was a transition to a public sector-mandated kidney transplant waitlist. CONCLUSION: Current disparities in organ distribution have a significant impact on public sector recipients, especially pediatric patients. This is likely secondary to paucity of legislation and resource limitations which would benefit from improved governmental policies and explicit pediatric prioritization policies in transplant units.

Incorporating Effects of Time Accrued on the Waiting List into Lung Transplantation Survival Models.

Rationale: U.S. lung transplant mortality risk models do not account for patients' disease progression as time accrues between mandated clinical parameter updates. Objectives: To investigate the effects of accrued waitlist (WL) time on mortality in lung transplant candidates and recipients beyond those expressed by worsening clinical status and to present a new framework for conceptualizing mortality risk in end-stage lung disease. Methods: Using Scientific Registry of Transplant Recipients data (2015-2020, N = 12,616), we modeled transitions among multiple clinical states over time: WL, posttransplant, and death. Using cause-specific and ordinary Cox regression to estimate trajectories of composite 1-year mortality risk as a function of time from waitlisting to transplantation, we quantified the predictive accuracy of these estimates. We compared multistate model-derived candidate rankings against composite allocation score (CAS) rankings. Measurements and Main Results: There were 11.5% of candidates whose predicted 1-year mortality risk increased by >10% by day 30 on the WL. The multistate model ascribed lower numerical rankings (i.e., higher priority) than CAS for those who died while on the WL (multistate mean; median [interquartile range] ranking at death, 227; 154 [57-334]; CAS median [interquartile range] ranking at death, 329; 162 [11-668]). Patients with interstitial lung disease were more likely to have increasing risk trajectories as a function of time accrued on the WL compared with other lung diagnoses. Conclusions: Incorporating the effects of time accrued on the WL for lung transplant candidates and recipients in donor lung allocation systems may improve the survival of patients with end-stage lung diseases on the individual and population levels.

Deceased donor kidneys from higher distressed communities are significantly less likely to be utilized for transplantation.

The proportion of kidneys procured for transplantation but not utilized exceeds 20% in the United States. Factors associated with nonutilization are complex, and further understanding of novel causes are critically important. We used the national Scientific Registry of Transplant Recipients data (2010-2022) to evaluate associations of Distressed Community Index (DCI) of deceased donor residence and likelihood of kidney nonutilization (n = 209 413). Deceased donors from higher distressed communities were younger, had an increased history of hypertension and diabetes, were CDC high-risk, and had higher terminal creatinine and donation after brain death. Mechanisms and circumstances of death varied significantly by DCI. The proportion of kidney nonutilization was 19.9%, which increased by DCI quintile (Q1 = 18.1% to Q5 = 21.6%). The adjusted odds ratio of nonutilization from the highest quintile DCI communities was 1.22 (95% CI = 1.16-1.28; reference = lowest DCI), which persisted stratified by donor race. Donors from highly distressed communities were highly variable by the donor service area (range: 1%-51%; median = 21%). There was no increased risk for delayed graft function or death-censored graft loss by donor DCI but modest increased adjusted hazard for overall graft loss (high DCI = 1.05; 95% CI = 1.01-1.10; reference = lowest DCI). Results indicate that donor residential distress is associated with significantly higher rates of donor kidney nonutilization with notable regional variation and minimal impact on recipient outcomes.

OPTN/SRTR 2021 Annual Data Report: Lung.

The number of lung transplants has continued to decline since 2020, a period that coincides with the onset of the COVID-19 pandemic. Lung allocation policy continues to undergo considerable change in preparation for adoption of the Composite Allocation Score system in 2023, beginning with multiple adaptations to the calculation of the Lung Allocation Score that occurred in 2021. The number of candidates added to the waiting list increased after a decline in 2020, while waitlist mortality has increased slightly with a decreased number of transplants. Time to transplant continues to improve, with 38.0% of candidates waiting fewer than 90 days for a transplant. Posttransplant survival remains stable, with 85.3% of transplant recipients surviving to 1 year; 67%, to 3 years; and 54.3%, to 5 years.

Miscalibration of lung allocation models leads to inaccurate waitlist mortality predictions.

The importance of waitlist (WL) mortality risk estimates will increase with the adoption of the US Composite Allocation Score (CAS) system. Calibration is rarely assessed in clinical prediction models, yet it is a key factor in determining access to lung transplant. We assessed the calibration of the WL-lung allocation score (LAS)/CAS models and developed alternative models to minimize miscalibration. Scientific Registry of Transplant Recipients data from 2015 to 2020 were used to assess the calibration of the WL model and for subgroups (age, sex, diagnosis, and race/ethnicity). Three recalibrated models were developed and compared: (1) simple recalibration model (SRM), (2) weighted recalibration model 1 (WRM1), and (3) weighted recalibration model 2 (WRM2). The current WL-LAS/CAS model underestimated risk for 78% of individuals (predicted mortality risk, <42%) and overpredicted risk for 22% of individuals (predicted mortality risk, ≥42%), with divergent results among subgroups. Error measures improved in SRM, WRM1, and WRM2. SRM generally preserved candidate rankings, whereas WRM1 and WRM2 led to changes in ranking by age and diagnosis. Differential miscalibration occurred in the WL-LAS/CAS model, which improved with recalibration measures. Further inquiry is needed to develop mortality models in which risk predictions approximate observed data to ensure accurate ranking and timely access to transplant. IMPACT: With changes to the lung transplant allocation system planned in 2023, evaluation of the accuracy and precision of survival models used to rank candidates for lung transplant is important. The waitlist model underpredicts risk for 78% of US transplant candidates with an unequal distribution of miscalibration across subgroups leading to inaccurate ranking of transplant candidates. This work will serve to inform future efforts to improve modeling efforts in the US lung transplant allocation system.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Impact of allele-specific anti-human leukocyte antigen class I antibodies on organ allocation.

Technological advances in the field of histocompatibility have allowed us to define anti-human leukocyte antigen (HLA) antibody specificity at the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6726 consecutive serum samples from 2953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation. Out of 17 class I HLA antigens represented by >1 allele in the LABScreen single antigen bead assay, 12 had potential allele-specific reactivity. Taking advantage of our unbiased cohort of deceased donor-candidate testing (123,135 complement-dependent cytotoxicity crossmatches between 2014 and 2017), we estimated that the presence of allele-specific antibody detected using a single antigen bead assay (median fluorescence intensity, >3000) against only the rare allele was a poor predictor of a positive complement-dependent cytotoxicity crossmatch, with a positive predictive value of 0% to 7%, compared with 52.5% in allele-concordant class I HLA antibodies against A or B locus antigens. Further, we confirmed allele-specific reactivity using flow crossmatch in 3 scenarios: A11:01/A11:02, A68:01/A68:02, and B44:02/B44:03. Our results suggest that allele-specific antibodies may unnecessarily exclude transplant candidates (up to 10%) from organ offers by overcalling unacceptable antigens; incorporation of selective reactivity pattern in allocation may promote precision matching and more equitable allocation.

Improving equity in kidney transplant allocation policies through a novel genetic metric: The Matched Donor Potential.

The demand for donors' kidneys continues to increase amid a shortage of available donors. Managing policies to thoughtfully allocate this scarce resource is a complex process. Although human leukocyte antigen (HLA) matching has been shown to prolong graft survival, its relative contribution to allocation schemes is empirically compromised owing to competing priorities. We explored using a new metric, Matched Donor Potential (MDP), to facilitate improved HLA matching while promoting equity. We interrogated all active kidney waitlist patients (N = 164 427), their corresponding unacceptable antigen files, and all effective donors in the Scientific Registry of Transplant Recipients (January 1, 2016-December 31, 2017). Cause-specific hazard functions were evaluated to assess the potential impact of the MDP metric on deceased donor transplant access rates for all candidates. Access was affected by ethnicity, blood group type, and calculated Panel Reactive Antibody (cPRA). Importantly, we show that access to transplantation is influenced by the patient's own HLA makeup regardless of their ethnicity and by the HLA makeup of effective donors. The MDP metric demonstrates a high association with access to transplantation. Adjusting Cox models to include this new metric resulted in improved access to kidney transplantation for waitlist candidates of minority heritage while significantly promoting HLA matching. Thus, the MDP metric accounts for balanced, equitable organ allocation algorithms.

Does anybody really know what (the kidney median waiting) time is?

The median waiting time (MWT) to deceased donor kidney transplant is of interest to patients, clinicians, and the media but remains elusive due to both methodological and philosophical challenges. We used Organ Procurement and Transplantation Network data from January 2003 to March 2022 to estimate MWTs using various methods and timescales, applied overall, by era, and by candidate demographics. After rising for a decade, the overall MWT fell to 5.19 years between 2015 and 2018 and declined again to 4.05 years (April 2021 to March 2022), based on the Kaplan-Meier method applied to period-prevalent cohorts. MWTs differed markedly by blood type, donor service area, and pediatric vs adult status, but to a lesser degree by race/ethnicity. Choice of methodology affected the magnitude of these differences. Instead of waiting years for an answer, reliable kidney MWT estimates can be obtained shortly after a policy is implemented using the period-prevalent Kaplan-Meier approach, a theoretical but useful construct for which we found no evidence of bias compared with using incident cohorts. We recommend this method be used complementary to the competing risks approach, under which MWT is often inestimable, to fill the present information void concerning the seemingly simple question of how long it takes to get a kidney transplant in the United States.

Improving outcomes of in situ split liver transplantation in Italy over the last 25 years.

BACKGROUND & AIMS: Split liver transplant(ation) (SLT) is still considered a challenging procedure that is by no means widely accepted. We aimed to present data on 25-year trends in SLT in Italy, and to investigate if, and to what extent, outcomes have improved nationwide during this time. METHODS: The study included all consecutive SLTs performed from May 1993 to December 2019, divided into three consecutive periods: 1993-2005, 2006-2014, and 2015-2019, which match changes in national allocation policies. Primary outcomes were patient and graft survival, and the relative impact of each study period. RESULTS: SLT accounted for 8.9% of all liver transplants performed in Italy. A total of 1,715 in situ split liver grafts were included in the analysis: 868 left lateral segments (LLSs) and 847 extended right grafts (ERGs). A significant improvement in patient and graft survival (p <0.001) was observed with ERGs over the three periods. Predictors of graft survival were cold ischaemia time (CIT) <6 h (p = 0.009), UNOS status 2b (p <0.001), UNOS status 3 (p = 0.009), and transplant centre volumes: 25-50 cases vs. <25 cases (p = 0.003). Patient survival was significantly higher with LLS grafts in period 2 vs. period 1 (p = 0.008). No significant improvement in graft survival was seen over the three periods, where predictors of graft survival were CIT <6 h (p = 0.007), CIT <6 h vs. ≥10 h (p = 0.019), UNOS status 2b (p = 0.038), and UNOS status 3 (p = 0.009). Retransplantation was a risk factor in split liver graft recipients, with significantly worse graft and patient survival for both types of graft (p <0.001). CONCLUSIONS: Our analysis showed Italian SLT outcomes to have improved over the last 25 years. These results could help to dispel reservations regarding the use of this procedure. IMPACT AND IMPLICATIONS: Split liver transplant(ation) (SLT) is still considered a challenging procedure and is by no means widely accepted. This study included all consecutive in situ SLTs performed in Italy from May 1993 to December 2019. With more than 1,700 cases, it is one of the largest series, examining long-term national trends in in situ SLT since its introduction. The data presented indicate that the outcomes of SLT improved during this 25-year period. Improvements are probably due to better recipient selection, refinements in surgical technique, conservative graft-to-recipient matching, and the continuous, yet carefully managed, expansion of donor selection criteria under a strict mandatory split liver allocation policy. These results could help to dispel reservations regarding the use of this procedure.