Association between calculated panel reactive antibody and waitlist outcomes in the 2018 heart allocation system.

BACKGROUND: The impact of heart transplant (HT) waitlist candidate sensitization on waitlist outcomes in the US is unknown. METHODS: Adult waitlist outcomes in OPTN (October 2018-September 2022) by calculated panel reactive antibody (cPRA) were modeled to identify thresholds of clinical significance. The primary outcome was the rate of HT by cPRA category (low: 0-35, middle: >35-90, high: >90) assessed using multivariable competing risk analysis (compete: waitlist removal for death or clinical deterioration). The secondary outcome was waitlist removal for death or clinical deterioration. RESULTS: The elevated cPRA categories were associated with lower rates of HT. Candidates in the middle (35-90) and high cPRA categories (>90) had an adjusted 24% lower rate (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.80-0.92) and 61% lower rate (HR 0.39 95% CI. 0.33-0.47) of HT than the lowest category, respectively. Waitlist candidates in the high cPRA category listed in the top acuity strata (Statuses 1, 2) had increased rates of delisting for death or deterioration compared to those in the low cPRA category (adjusted HR 2.9, 95% CI 1.5-5.5), however, elevated cPRA (middle, high) was not associated with an increased rate of death and delisting when the cohort was considered as a whole. CONCLUSIONS: Elevated cPRA was associated with reduced rates of HT across all waitlist acuity tiers. Among HT waitlist candidates listed at the top acuity strata, the high cPRA category was associated with increased rates of delisting due to death or deterioration. Elevated cPRA may require consideration for critically ill candidates under continuous allocation.

Differential donor management of pediatric vs adult organ donors and potential impact on pediatric lung transplantation.

BACKGROUND: Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates. METHODOLOGY: We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management. RESULTS: We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor. CONCLUSIONS: In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs.

Estratificação de risco dos pacientes na fila de espera para cirurgia bariátrica no Hospital do Servidor Público Municipal para elaboração de pontuação do Protocolo de Gravidade SOS (Score de Obesidade do Servidor) / Risk stratification of patients on the waiting list for bariatric surgery at the Hospital do Servidor Público Municipal to prepare a score for the SOS Severity Protocol (Server Obesity Score)

A obesidade é confirmada como um dos principais fatores de risco de doenças cardiovasculares, diabetes mellitus e doença renal crônica, entre outros. Na projeção para os próximos 12 anos, o Brasil terá 41% de sua população adulta com obesidade, segundo a nova edição do Atlas Mundial da Obesidade 2023. O número é confirmado para 2035 a partir das tendências projetadas na prevalência de obesidade. Para os adultos, o crescimento será de 2,8% por ano, enquanto nas crianças, fator mais preocupante, o crescimento anual será de 4,4%. O objetivo deste estudo é a estratificação de risco dos pacientes que estão aguardando cirurgia bariátrica pelo HSPM (Hospital do Servidor Público Municipal), através do protocolo SOS (Score de Obesidade do Servidor), ao definir critérios de gravidade e priorização desses pacientes, correlacionando a obesidade ao grau de disfunções orgânicas dos mesmos. Em nosso serviço o tempo na fila de espera para a cirurgia bariátrica gira em torno de 6 a 7 anos, para todos os pacientes, não levando em consideração as comorbidades e riscos destes indivíduos, e no Brasil não há até hoje nenhum protocolo de priorização por comorbidades descrito para a cirurgia bariátrica. Foi realizada a estratificação de gravidade dos pacientes que aguardam pela cirurgia bariátrica no HSPM, com elaboração de pontuação de risco alto (maior ou igual que cinco pontos: prioridade vermelha), médio (3 a 4 pontos: prioridade amarela) e baixo (0 a 2 pontos: prioridade verde), através do protocolo SOS (Score de Obesidade do Servidor). Palavras-chave: Cirurgia bariátrica. Obesidade. Listas de espera. Priorização. Manejo de Obesidade.

Aplicação do Protocolo SOS (Score de Obesidade do Servidor) para priorização de pacientes graves em fila de espera da Cirurgia Bariátrica no Hospital do Servidor Público Municipal / Application of the SOS Protocol (Server Obesity Score) to prioritize critically ill patients on the waiting list for Bariatric Surgery at the Hospital do Servidor Público Municipal

A obesidade é uma doença crônica de magnitude global, e o seu controle é um desafio, sendo a cirurgia bariátrica o seu tratamento mais eficaz. Entretanto, a demanda superou a capacidade cirúrgica e filas de espera que ultrapassam cinco anos são visíveis e ocorrem em diversas nações. Durante a espera torna-se evidente a presença de pacientes com comorbidades graves, sujeitos a um agravamento destas e com maior chance de óbito. No Brasil, utiliza-se o critério cronológico para seleção dos pacientes aptos para realização de cirurgia bariátrica, carecendo de protocolos consolidados para avaliar a prioridade entre os pacientes. Objetivo: Aplicar o protocolo do Score de Obesidade do Servidor (SOS) e avaliar sua eficiência para priorização de pacientes na lista de espera para Cirurgia Bariátrica e Metabólica do Hospital do Servidor Público Municipal de São Paulo, mantendo a convocação dos pacientes em ordem cronológica em nossa lista. Materiais e Métodos: Estudo experimental prospectivo com aplicação do protocolo entre julho de 2022 e julho de 2023 nos 475 pacientes aguardando em fila de espera e formação de 3 grupos de preparo para cirurgia bariátrica. Os grupos de preparo foram compostos por cerca de 50% de pacientes da ordem cronológica e 50% de pacientes pontuados como prioridade pelo protocolo. Resultados: Foram convocados 137 pacientes, dos quais 75 foram convocados seguindo a ordem cronológica e 62 pacientes foram priorizados, sendo 35 com prioridade vermelha e 27 com prioridade amarela. Foram chamados todos os pacientes classificados como vermelhos em lista de espera. Conclusão: A aplicação do protocolo SOS para a priorização de pacientes com critérios de gravidade na lista de espera para Cirurgia Bariátrica e Metabólica é uma estratégia eficaz e a combinação dessa abordagem com a convocação em ordem cronológica demonstrou ser uma solução viável para gestão dessa lista de espera. Palavras-chave: Obesidade. Cirurgia bariátrica. Priorização. Listas de espera. Manejo da Obesidade.

Surgical outcomes of bridge-to-bridge therapy with extracorporeal left ventricular assist device for acute myocardial infarction in cardiogenic shock.

BACKGROUND: Extracorporeal left ventricular assist device is often required for acute myocardial infarction patients in cardiogenic shock when temporary mechanical circulatory support fails to provide hemodynamic stabilization. This study aimed to evaluate the clinical outcomes of acute myocardial infarction patients in cardiogenic shock supported by an extracorporeal left ventricular assist device. METHODS: This retrospective study enrolled 13 acute myocardial infarction patients in cardiogenic shock treated with an extracorporeal left ventricular assist device from April 2011 to July 2020. RESULTS: Twelve (92.3%) and eleven (84.6%) patients were supported using venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pumping before implantation, respectively. The median duration from acute myocardial infarction to extracorporeal left ventricular assist device implantation was 7 (3.5-24.5) days. The overall in-hospital mortality rate was 30.8% (n = 4). Extracorporeal left ventricular assist device was explanted in one patient for cardiac recovery; eight (61.5%) patients were approved as heart transplant candidates in whom the extracorporeal left ventricular assist device was exchanged for a durable left ventricular assist device; two (15.4%) expired while waiting for a heart transplant, and two (15.4%) received a successful transplant. The 1- and 3-year overall survival rates after extracorporeal left ventricular assist device implantation were 68.3% and 49.9%, respectively. CONCLUSIONS: The operative mortality after extracorporeal left ventricular assist device implantation in acute myocardial infarction patients in cardiogenic shock was favorable. Our strategy of early hemodynamic stabilization with extracorporeal left ventricular assist device implantation in these patients as a bridge-to-bridge therapy was effective in achieving better survival.

Trends in Survival for Pediatric Transplantation.

OBJECTIVES: Progress in pediatric transplantation measured in the context of waitlist and posttransplant survival is well documented but falls short of providing a complete perspective for children and their families. An intent-to-treat analysis, in which we measure survival from listing to death regardless of whether a transplant is received, provides a more comprehensive perspective through which progress can be examined. METHODS: Univariable and multivariable Cox regression was used to analyze factors impacting intent-to-treat survival in 12 984 children listed for heart transplant, 17 519 children listed for liver transplant, and 16 699 children listed for kidney transplant. The Kaplan-Meier method and log-rank test were used to assess change in waitlist, posttransplant, and intent-to-treat survival. Wait times and transplant rates were compared by using χ2 tests. RESULTS: Intent-to-treat survival steadily improved from 1987 to 2017 in children listed for heart (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.96-0.97), liver (HR 0.95, 95% CI 0.94-0.97), and kidney (HR 0.97, 95% CI 0.95-0.99) transplant. Waitlist and posttransplant survival also improved steadily for all 3 organs. For heart transplant, the percentage of patients transplanted within 1 year significantly increased from 1987 to 2017 (60.8% vs 68.7%); however, no significant increase was observed in liver (68.9% vs 72.5%) or kidney (59.2% vs 62.7%) transplant. CONCLUSIONS: Intent-to-treat survival, which is more representative of the patient perspective than individual metrics alone, steadily improved for heart, liver, and kidney transplant over the study period. Further efforts to maximize the donor pool, improve posttransplant outcomes, and optimize patient care while on the waitlist may contribute to future progress.

Assessing the accuracy of the lung allocation score.

BACKGROUND: The United States (US) Lung Allocation Score (LAS) relies on the performance of 2 survival models that estimate waitlist and post-transplant survival. These models were developed using data from 2005 to 2008, and it is unknown if they remain accurate. METHODS: We performed an observational cohort study of US lung transplantation candidates and recipients greater than 12 years of age between February 19, 2015 and February 19, 2019. We evaluated the LAS waitlist and post-transplant models with the concordance probability estimate and by comparing predicted vs observed 1-year restricted mean survival times by risk decile. We then compared a nonparametric estimate of the observed LAS with the predicted LAS for each percentile of recipients. RESULTS: The waitlist model ranked candidates (N = 11,539) in the correct risk order 72% of the time (95% CI 71%-73%), and underestimated candidate one-year survival by 136 days for the highest risk decile (p < 0.001). The post-transplant model ranked recipients (N = 9,377) in the correct risk order 57% of the time (95% CI 55-58%), and underestimated recipient one-year survival by 70 days for the highest risk decile (p < 0.001). Overall, the LAS at transplant explained only 56% of the variation in observed outcomes, and was increasingly inaccurate at higher predicted values. CONCLUSIONS: The waitlist and the post-transplant models that constitute the LAS are inaccurate, limiting the ability of the system to rank candidates on the waitlist in the correct order. The LAS should therefore be updated and the underlying models should be modernized.

Impact of using higher-risk donor hearts for candidates with pre-transplant mechanical circulatory support.

BACKGROUND: We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS). METHODS: In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9,915 adult candidates on MCS underwent HTx from January 1, 2010 to March 31, 2019. Multi-organ, re-transplant, and congenital heart disease patients were excluded. Higher-risk donor organs met at least one of the following criteria: left ventricular ejection fraction <50%, donor to recipient predicted heart mass ratio <0.86, donor age >55 years, or ischemic time >4 hours. Primary outcome was 1 year post-transplant survival. RESULTS: Among HTx recipients, 3688 (37.2%) received higher-risk donor hearts. Candidates supported with pre-HTx extracorporeal membrane oxygenation or biventricular assist device (n = 374, 3.8%) who received higher-risk donor hearts had comparable 1 year survival (HR: 1.14, 95% CI: [0.67-1.93], p = 0.64) to recipients of standard-risk donor hearts, when adjusted for recipient age and sex. In candidates supported with intra-aortic balloon pump (n = 1391, 14.6%), transplantation of higher-risk donor hearts did not adversely affect 1 year survival (HR: 0.80, 95% CI: [0.52-1.22], p = 0.30). Patients on durable left ventricular assist devices (LVAD) who received higher-risk donor hearts had comparable 1 year survival to continued LVAD support on the waitlist, but mortality was increased compared to those who received standard-risk donor hearts (HR: 1.37, 95% CI: [1.11-1.70], p = 0.004). CONCLUSIONS: Patients requiring pre-HTx temporary MCS who received higher-risk donor hearts had comparable 1 year post-transplant survival to those who received standard-risk donor hearts. Stable patients on durable LVADs may benefit from waiting for standard-risk donor hearts.

Different combinations of the GLIM criteria for patients awaiting a liver transplant: Poor performance for malnutrition diagnosis but a potentially useful prognostic tool.

BACKGROUND & AIMS: Studies using the Global Leadership Initiative on Malnutrition (GLIM) criteria for patients with liver cirrhosis are limited. This study aimed to assess the impact of malnutrition according to the GLIM criteria on the outcomes of patients awaiting a liver transplant (LTx) and compare these criteria with Subjective Global Assessment (SGA). METHODS: This retrospective observational study included adult patients awaiting LTx. Patient clinical data, nutritional status according to various tools including SGA, and resting energy expenditure were assessed. The distinct phenotypic and etiologic criteria provided 36 different GLIM combinations. The GLIM criteria and SGA were compared using the kappa coefficient. The variables associated with mortality before and after the LTx and with a longer length of stay (LOS) after LTx (≥18 days) were assessed by Cox regression and logistic regression analyses, respectively. RESULTS: A total of 152 patients were included [median age 52.0 (interquartile range: 46.5-59.5) years; 66.4% men; 63.2% malnourished according to SGA]. The prevalence of malnutrition according to the GLIM criteria ranged from 0.7% to 30.9%. The majority of the GLIM combinations exhibited poor agreement with SGA. Independent predictors of mortality before and after LTx were presence of ascites or edema (p = 0.011; HR:2.58; CI95%:1.24-5.36), GLIM 32 (PA-phase angle + MELD) (p = 0.026; HR:2.08; CI95%:1.09-3.97), GLIM 33 (PA + MELD-Na≥12) (p = 0.018; HR:2.17; CI95%:1.14-4.13), and GLIM 34 (PA + Child-Pugh) (p = 0.043; HR:1.96; CI95%:1.02-3.77). Malnutrition according to GLIM 28 (handgrip strength + Child-Pugh) was independently associated with a longer LOS (p = 0.029; OR:7.21; CI95%:1.22-42.50). CONCLUSION: The majority of GLIM combinations had poor agreement with SGA, and 4 of the 36 GLIM combinations were independently associated with adverse outcomes.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

Influence of broader geographic allograft sharing on outcomes and cost in smaller lung transplant centers.

OBJECTIVE: On November 24, 2017, Organ Procurement and Transplantation Network implemented a change to lung allocation replacing donor service area with a 250 nautical mile radius around donor hospitals. We sought to evaluate the experience of a small to medium size center following implementation. METHODS: Patients (47 pre and 54 post) undergoing lung transplantation were identified from institutional database from January 2016 to October 2019. Detailed chart review and analysis of institutional cost data was performed. Univariate analysis was performed to compare eras. RESULTS: Similar short-term mortality and primary graft dysfunction were observed between groups. Decreased local donation (68% vs 6%; P < .001), increased travel distance (145 vs 235 miles; P = .004), travel cost ($8626 vs $14,482; P < .001), and total procurement cost ($60,852 vs $69,052; P = .001) were observed postimplementation. We also document an increase in waitlist mortality postimplementation (6.9 vs 31.6 per 100 patient-years; P < .001). CONCLUSIONS: Following implementation of the new allocation policy in a small to medium size center, several changes were in accordance with policy intention. However, concerning shifts emerged, including increased waitlist mortality and resource utilization. Continued close monitoring of transplant centers stratified by size and location are paramount to maintaining global availability of lung transplantation to all Americans regardless of geographic residence or socioeconomic status.

Avoiding delays in time to renal transplantation: Pretransplant thyroid malignancy does not affect patient or graft survival after renal transplantation.

BACKGROUND: Pretransplant malignancy is associated with decreased patient and graft survival. Current US guidelines recommend a 2- to 5-year, tumor-free waiting period before transplantation. No large studies have examined the specific, modern day risk of pretransplant thyroid malignancy on patient and graft survival after renal transplant. METHODS: The United Network for Organ Sharing database was queried for all adult isolated renal transplant recipients between 2003 and 2019. Patient characteristics, rates of post-transplant malignancy, and survival were compared between patients with pretransplant thyroid malignancy and without pretransplant thyroid malignancy. RESULTS: Eighty-six patients had pretransplant thyroid malignancy diagnosed after listing and before renal transplantation. Both overall and graft survival were similar between cohorts (P > .05). There was no significant association between pretransplant thyroid malignancy and patient (hazard ratio: 0.66; P = .31) or graft (hazard ratio:0.32; P = .11) survival on multivariate analysis. Waitlist duration for pretransplant thyroid malignancy patients was significantly increased (1,444 vs 438 days; P < .01), which translated to increased dialysis duration (2,234 vs 1,201 days, P < .01). Pretransplant thyroid malignancy patients did not experience increased post-transplant malignancy (P = .21). CONCLUSION: Given no association with decreased patient or allograft survival, our findings suggest that pretransplant thyroid malignancy patients are unnecessarily subjected to increased wait-list duration before transplant. We recommend an individualized approach for pretransplant thyroid malignancy patients diagnosed before or after listing.

Racial/ethnic disparities in wait-list outcomes are only partly explained by socioeconomic deprivation among children awaiting liver transplantation.

BACKGROUND AND AIMS: Racial/ethnic minority children have worse liver transplant (LT) outcomes. We evaluated whether neighborhood socioeconomic deprivation affected associations between race/ethnicity and wait-list mortality. APPROACH AND RESULTS: We included children (age <18) listed 2005-2015 in the Scientific Registry of Transplant Recipients. We categorized patients as non-Hispanic White, Black, Hispanic, and other. We matched patient ZIP codes to a neighborhood socioeconomic deprivation index (range, 0-1; higher values indicate worse deprivation). Primary outcomes were wait-list mortality, defined as death/delisting for too sick, and receipt of living donor liver transplant (LDLT). Competing risk analyses modeled the association between race/ethnicity and wait-list mortality, with deceased donor liver transplant (DDLT) and LDLT as competing risks, and race/ethnicity and LDLT, with wait-list mortality and DDLT as competing risks. Of 7716 children, 17% and 24% identified as Black and Hispanic, respectively. Compared to White children, Black and Hispanic children had increased unadjusted hazard of wait-list mortality (subhazard ratio [sHR], 1.44; 95% CI, 1.18, 1.75 and sHR, 1.48; 95% CI, 1.25, 1.76, respectively). After adjusting for neighborhood deprivation, insurance, and listing laboratory Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease, Black and Hispanic children did not have increased hazard of wait-list mortality (sHR, 1.12; 95% CI, 0.91, 1.39 and sHR, 1.21; 95% CI, 1.00, 1.47, respectively). Similarly, Black and Hispanic children had a decreased likelihood of LDLT (sHR, 0.58; 95% CI, 0.45, 0.75 and sHR, 0.61; 95% CI, 0.49, 0.75, respectively). Adjustment attenuated the effect of Black and Hispanic race/ethnicity on likelihood of LDLT (sHR, 0.79; 95% CI, 0.60, 1.02 and sHR, 0.89; 95% CI, 0.70, 1.11, respectively). CONCLUSIONS: Household and neighborhood socioeconomic factors and disease severity at wait-list entry help explain racial/ethnic disparities for children awaiting transplant. A nuanced understanding of how social adversity contributes to wait-list outcomes may inform strategies to improve outcomes.

Decreased access to pediatric liver transplantation during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has affected all aspects of the US healthcare system, including liver transplantation. The objective of this study was to understand national changes to pediatric liver transplantation during COVID-19. METHODS: Using SRTR data, we compared waitlist additions, removals, and liver transplantations for pre-COVID-19 (March-November 2016-2019), early COVID-19 (March-May 2020), and late COVID-19 (June-November 2020). RESULTS: Waitlist additions decreased by 25% during early COVID-19 (41.3/month vs. 55.4/month, p < .001) with black candidates most affected (p = .04). Children spent longer on the waitlist during early COVID-19 compared to pre-COVID-19 (140 vs. 96 days, p < .001). There was a 38% decrease in liver transplantations during early COVID-19 (IRR 0.62, 95% CI 0.49-0.78), recovering to pre-pandemic rates during late COVID-19 (IRR 1.03, NS), and no change in percentage of living and deceased donors. White children had a 30% decrease in overall liver transplantation but no change in living donor liver transplantation (IRR 0.7, 95% CI 0.50-0.95; IRR 0.96, NS), while non-white children had a 44% decrease in overall liver transplantation (IRR 0.56, 95% CI 0.40-0.77) and 81% decrease in living donor liver transplantation (IRR 0.19, 95% CI 0.02-0.76). CONCLUSIONS: The COVID-19 pandemic decreased access to pediatric liver transplantation, particularly in its early stage. There were no regional differences in liver transplantation during COVID-19 despite the increased national sharing of organs. While pediatric liver transplantation has resumed pre-pandemic levels, ongoing racial disparities must be addressed.

Cognitive Impairment and Physical Frailty in Patients With Cirrhosis.

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

Inactive status is an independent predictor of liver transplant waitlist mortality and is associated with a transplant centers median meld at transplant.

BACKGROUND: Approximately 30% of patients on the liver transplant waitlist experience at least one inactive status change which makes them temporarily ineligible to receive a deceased donor transplant. We hypothesized that inactive status would be associated with higher mortality which may differ on a transplant centers' or donor service areas' (DSA) Median MELD at Transplant (MMaT). METHODS: Multi-state models were constructed (OPTN database;06/18/2013-06/08/2018) using DSA-level and transplant center-level data where MMaT were numerically ranked and categorized into tertiles. Hazards ratios were calculated between DSA and transplant center tertiles, stratified by MELD score, to determine differences in inactive to active transition probabilities. RESULTS: 7,625 (30.2% of sample registrants;25,216 total) experienced at least one inactive status change in the DSA-level cohort and 7,623 experienced at least one inactive status change in the transplant-center level cohort (30.2% of sample registrants;25,211 total). Inactive patients with MELD≤34 had a higher probability of becoming re-activated if they were waitlisted in a low or medium MMaT transplant center or DSA. Transplant rates were higher and lower re-activation probability was associated with higher mortality for the MELD 26-34 group in the high MMaT tertile. There were no significant differences in re-activation, transplant probability, or waitlist mortality for inactivated patients with MELD≥35 regardless of a DSA's or center's MMaT. CONCLUSION: This study shows that an inactive status change is independently associated with waitlist mortality. This association differs by a centers' and a DSAs' MMaT. Prioritization through care coordination to resolve issues of inactivity is fundamental to improving access.

Waiting time and mortality rate on lung transplant candidates in Japan: a single-center retrospective cohort study.

BACKGROUND: As lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population. METHODS: We included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan-Meier method was used to model time to death. RESULTS: We included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579-1056) and 323 days (IQR 129-528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11-4.85). CONCLUSIONS: In Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time.

Kidney Disease Symptoms before and after Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Patients with kidney failure report a high symptom burden, which likely increases while on dialysis due to physical and mental stressors and decreases after kidney transplantation due to restoration of kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We leveraged a two-center prospective study of 1298 kidney transplant candidates and 521 recipients (May 2014 to March 2020). Symptom scores (0-100) at evaluation and admission for transplantation were calculated using the Kidney Disease Quality of Life Short-Form Survey, where lower scores represent greater burden, and burden was categorized as very high: 0.0-71.0; high: 71.1-81.0; medium: 81.1-91.0; and low: 91.1-100.0. We estimated adjusted waitlist mortality risk (competing risks regression), change in symptoms between evaluation and transplantation (n=190), and post-transplantation symptom score trajectories (mixed effects models). RESULTS: At evaluation, candidates reported being moderately to extremely bothered by fatigue (32%), xeroderma (27%), muscle soreness (26%), and pruritus (25%); 16% reported high and 21% reported very high symptom burden. Candidates with very high symptom burden were at greater waitlist mortality risk (adjusted subdistribution hazard ratio, 1.67; 95% confidence interval, 1.06 to 2.62). By transplantation, 34% experienced an increased symptom burden, whereas 42% remained unchanged. The estimated overall symptom score was 82.3 points at transplantation and 90.6 points at 3 months (10% improvement); the score increased 2.75 points per month (95% confidence interval, 2.38 to 3.13) from 0 to 3 months, and plateaued (-0.06 points per month; 95% confidence interval, -0.30 to 0.18) from 3 to 12 months post-transplantation. There were early (first 3 months) improvements in nine of 11 symptoms; pruritus (23% improvement) and fatigue (21% improvement) had the greatest improvements. CONCLUSIONS: Among candidates, very high symptom burden was associated with waitlist mortality, but for those surviving and undergoing kidney transplantation, symptoms improved.

The Impact of the COVID-19 Pandemic on Cardiac Procedure Wait List Mortality in Ontario, Canada.

BACKGROUND: The novel SARS-CoV-2 (COVID-19) pandemic has dramatically altered the delivery of healthcare services, resulting in significant referral pattern changes, delayed presentations, and procedural delays. Our objective was to determine the effect of the COVID-19 pandemic on all-cause mortality in patients awaiting commonly performed cardiac procedures. METHODS: Clinical and administrative data sets were linked to identify all adults referred for: (1) percutaneous coronary intervention; (2) coronary artery bypass grafting; (3) valve surgery; and (4) transcatheter aortic valve implantation, from January 2014 to September 2020 in Ontario, Canada. Piece-wise regression models were used to determine the effect of the COVID-19 pandemic on referrals and procedural volume. Multivariable Cox proportional hazards models were used to determine the effect of the pandemic on waitlist mortality for the 4 procedures. RESULTS: We included 584,341 patients who were first-time referrals for 1 of the 4 procedures, of whom 37,718 (6.4%) were referred during the pandemic. The pandemic period was associated with a significant decline in the number of referrals and procedures completed compared with the prepandemic period. Referral during the pandemic period was a significant predictor for increased all-cause mortality for the percutaneous coronary intervention (hazard ratio, 1.83; 95% confidence interval, 1.47-2.27) and coronary artery bypass grafting (hazard ratio, 1.96; 95% confidence interval, 1.28-3.01), but not for surgical valve or transcatheter aortic valve implantation referrals. Procedural wait times were shorter during the pandemic period compared with the prepandemic period. CONCLUSIONS: There was a significant decrease in referrals and procedures completed for cardiac procedures during the pandemic period. Referral during the pandemic was associated with increased all-cause mortality while awaiting coronary revascularization.

End stage liver disease etiology & transplantation referral outcomes of major ethnic groups in British Columbia, Canada: A cohort study.

ABSTRACT: Liver disease etiology and transplantation outcomes may vary by ethnicity. We aimed to determine if disparities exist in our province.We reviewed the provincial database for liver transplant referrals. We stratified cohorts by ethnicity and analyzed disease etiology and outcomes.Four thousand nine hundred sixteen referrals included 220 South Asians, 413 Asians, 235 First Nations (Indigenous), and 2725 Caucasians. Predominant etiologies by ethnicity included alcohol (27.4%) and primary sclerosing cholangitis (PSC) (8.8%) in South Asians, hepatitis B (45.5%) and malignancy (13.9%) in Asians, primary biliary cholangitis (PBC) (33.2%) and autoimmune hepatitis (AIH) (10.8%) in First Nations, and hepatitis C (35.9%) in Caucasians. First Nations had lowest rate of transplantation (30.6%, P = .01) and highest rate of waitlist death (10.6%, P = .03). Median time from referral to transplantation (268 days) did not differ between ethnicities (P = .47). Likelihood of transplantation increased with lower body mass index (BMI) (hazard ratio [HR] 0.99, P = .03), higher model for end stage liver disease (MELD) (HR 1.02, P < .01), or fulminant liver failure (HR 9.47, P < .01). Median time from referral to ineligibility status was 170 days, and shorter time was associated with increased MELD (HR 1.01, P < .01), increased age (HR 1.01, P < .01), fulminant liver failure (HR 2.56, P < .01) or South Asian ethnicity (HR 2.54, P < .01). Competing risks analysis revealed no differences in time to transplant (P = .66) or time to ineligibility (P = .91) but confirmed increased waitlist death for First Nations (P = .04).We have noted emerging trends such as alcohol related liver disease and PSC in South Asians. First Nations have increased autoimmune liver disease, lower transplantation rates and higher waitlist deaths. These data have significance for designing ethnicity specific interventions.