Faculty Bibliography

BACKGROUND:Despite excellent outcomes of heart transplants from hepatitis C virus (HCV)-positive donors (D+), many candidates are not listed to even consider HCV D+ offers. METHODS:Using the Scientific Registry of Transplant Recipients, we identified adult (age ≥18 years) heart transplant candidates prevalent on the waitlist between 2018 and March 2023. We compared the likelihood of waitlist mortality or heart transplant by candidate willingness to consider HCV D+ offers using competing risk regression. RESULTS:We identified 19,415 heart transplant candidates, 68.9% of whom were willing to consider HCV D+ offers. Candidates willing to consider HCV D+ offers had a 37% lower risk of waitlist mortality (subhazard ratio [SHR], 0.63; 95% confidence interval [CI], 0.56-0.70; P < .001) than candidates not willing to consider HCV D+ offers, after adjustment for covariates and center-level clustering. Over the same period, heart transplant candidates willing to consider HCV D+ offers had a 21% higher likelihood of receiving a transplant (SHR, 1.21; 95% CI, 1.7-1.26; P < .001). As a result, among candidates willing to consider HCV D+ offers, 74.9% received a transplant and 6.1% died/deteriorated after 3 years, compared to 68.3% and 9.1%, respectively, of candidates not willing to consider HCV D+ offers. Lower waitlist mortality also was observed on subgroup analyses of candidates on temporary and durable mechanical circulatory support. CONCLUSIONS:Willingness to consider HCV D+ heart offers was associated with a 37% lower risk of waitlist mortality and a 21% higher likelihood of receiving a transplant. We urge providers to encourage candidates to list as being willing to consider offers from donors with hepatitis C to optimize their waitlist outcomes and access to transplantation.

BACKGROUND:In recent years, changes to US organ allocation have aimed to improve equity and accessibility across regions. The Organ Procurement and Transplantation Network plans to adopt continuous liver distribution, prioritizing candidates based on a weighted composite allocation score (CAS) incorporating proximity, ABO types, medical urgency, and pediatric priority. The Liver Committee has requested research on CAS variations that account for geographical heterogenicity. METHODS:We describe a method for designing a geographically heterogeneous CAS with targeted broader sharing (CAS-TBS) to balance the highly variable geographic distributions of liver transplant listings and liver donations. CAS-TBS assigns each donor hospital to either broader sharing or nearby sharing, adjusting donor-candidate distance allocation points accordingly. RESULTS:We found that to reduce geographic disparity in the median Model for End-stage Liver Disease at transplant (MMaT), >75% of livers recovered in regions 2 and 10 should be distributed with broader sharing, whereas 95% of livers recovered in regions 5 and 1 should be distributed with nearby sharing. In a 3-y simulation of liver allocation, CAS-TBS decreased MMaT by 2.1 points in high-MMaT areas such as region 5 while increasing MMaT only by 0.65 points in low-MMaT areas such as region 3. CAS-TBS significantly decreased median transport distance from 202 to 167 nautical miles under acuity circles and decreased waitlist deaths. CONCLUSIONS:Our CAS-TBS design methodology could be applied to design geographically heterogeneous allocation scores that reflect transplant community values and priorities within the continuous distribution project of the Organ Procurement and Transplantation Network. In our simulations, the incremental benefit of CAS-TBS over CAS was modest.

BACKGROUND:HLA-DQ mismatch has been identified as a predictor of de novo donor-specific HLA antibody formation and antibody-mediated rejection. There are insufficient data to guide the incorporation of DQ mismatch into organ allocation decisions. METHODS:We used a retrospective longitudinal cohort of adult living donor kidney transplant recipients from 11 centers across the United States for whom high-resolution class II typing was available. HLA-DQαβ heterodimer allele mismatch was quantified for all donor-recipient pairs, and outcome data were obtained through linkage with the Scientific Registry of Transplant Recipients. RESULTS:We studied 3916 donor-recipient pairs. Recipient characteristics were notable for a median age of 51 (38-61) y, primarily unsensitized, with 74.5% of the cohort having 0% calculated panel-reactive antibody, and 60.4% with private insurance, for a median follow-up time of 5.86 y. We found that the HLA-DQαβ allele and HLA-DR antigen mismatch were each individually associated with an increased hazard of all-cause graft failure (adjusted hazard ratio [aHR] DQ = 1.03 1.14 1.28; aHR DR = 1.03 1.15 1.328), death-censored graft failure (aHR DQ =1.01 1.19 1.40; aHR DR = 0.099 1.18 1.39), and rejection. Having 2 HLA-DQαβ allele mismatches further increased the hazard of rejection even when controlling for HLA-DR mismatch (aHR 1.03 1.68 2.74). CONCLUSIONS:HLA-DQαβ allele mismatch predicted allograft rejection even when controlling for HLA-DR antigen mismatch and were both independently associated with increased risk of graft failure or rejection in adult living kidney transplant recipients. Given the strong burden of disease arising from the HLA-DQ antibody formation, we suggest that HLA-DQαβ should be prioritized over HLA-DR in donor selection.

BACKGROUND:As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS/OBJECTIVE:To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS:We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS:Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION/CONCLUSIONS:Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.

BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

The rise in the mean age of the global population has led to an increase in older kidney transplant (KT) patients. This demographic shift, coupled with the ongoing organ shortage, requires a nuanced understanding of which older adults are most suitable for KT. Recognizing the increased heterogeneity among older adults and the limitations of solely relying on chronological age, there is a need to explore alternative aging metrics beyond chronological age. In this review, we discuss the impact of older age on access to KT and postoperative outcomes. Emphasizing the need for a comprehensive evaluation that extends beyond chronological age, we explore alternative aging metrics such as frailty, sarcopenia, and cognitive function, underscoring their potential role in enhancing the KT evaluation process. Most importantly, we aim to contribute to the ongoing discourse, fostering an optimized approach to KT for the rapidly growing population of older adults.

Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer the effectiveness of a new drug through a surrogate measure of efficacy. Recently, this method has also been employed to authorise novel drugs, such as COVID-19 vaccines, and this article explores the concepts behind immunobridging trials, their advantages, issues, and significance in the context of COVID-19 and other infectious diseases. Our goal is to improve awareness among clinicians, patient groups, regulators, and health leaders of the opportunities and issues of immunobridging, so that fewer patients are left without protection from infectious diseases, particularly from major pathogens that may emerge.

BACKGROUND:Pretransplant functional, motor, cognitive, and academic deficits are common in pediatric patients requiring heart transplantation (HT); some persist post-HT. We assessed the association between these quality of life (QoL) deficits and post-HT outcomes. METHODS:Using SRTR data 2008-2023, we evaluated the functional, motor, cognitive, and academic status of pediatric HT recipients from listing to 15 years post-HT. We compared all-cause graft survival among patients with vs. without pre-HT deficits using Cox regressions. Among patients with a functioning graft at 1 year, we assessed the association between deficits at that time and subsequent graft failure. RESULTS:, p < 0.001). CONCLUSION/CONCLUSIONS:Pediatric HT recipients with decreased functional status are at higher risk for graft failure and mortality. These patients may benefit from early intervention aimed at improving functional status.

Central body fat distribution affects kidney function. Abdominal fat measurements using computed tomography (CT) may prove superior in assessing body composition-related kidney risk in living kidney donors. This retrospective cohort study including 550 kidney donors aimed to determine the association between CT-measured abdominal fat areas and kidney function before and after donor nephrectomy. Donors underwent glomerular filtration rate measurements (¹²⁵I-Iothalamate, mGFR) before and 3 months after donation. Linear regression analyses with body surface area (BSA)-standardized and crude mGFR were performed to assess the association of height-indexed tomographic fat measurements with kidney function. In age-, and sex-adjusted analyses higher levels of total abdominal, visceral, subcutaneous, and intramuscular adipose tissue index were significantly associated with lower mGFR levels before donation (BSA-standardized mGFR: visceral adipose tissue index: Βeta=-0.11, p < 0.001, subcutaneous: Βeta=-0.10, p < 0.001, intramuscular: Βeta=-1.18, p < 0.001, total abdominal: Βeta=-0.07, p < 0.001). Higher tomographic abdominal fat is associated with lower BSA-standardized mGFR after donation and a greater decrease in mGFR between screening and 3 months post-donation. This study shows that CT-measured abdominal fat area is associated with kidney function before and after living kidney donation.

BACKGROUND:Kidney transplant (KT) candidates often experience hospitalizations, increasing their delirium risk. Hospitalizations and delirium are associated with worse post-KT outcomes, yet their relationship with pre-KT outcomes is less clear. Pre-KT delirium may worsen access to KT due to its negative impact on cognition and ability to maintain overall health. METHODS:Using a prospective cohort of 2374 KT candidates evaluated at a single center (2009-2020), we abstracted hospitalizations and associated delirium records after listing via chart review. We evaluated associations between waitlist mortality and likelihood of KT with hospitalizations and hospitalized delirium using competing risk models and tested whether associations differed by gerontologic factors. RESULTS: < 0.001), with those aged ≥65 having a 61% lower likelihood of KT. CONCLUSION/CONCLUSIONS:Hospitalization and delirium are associated with worse pre-KT outcomes and have serious implications on candidates' access to KT. Providers should work to reduce preventable instances of delirium.