Faculty Bibliography

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.

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: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.

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.

RATIONALE & OBJECTIVE/UNASSIGNED:Coronavirus disease (COVID)-19 has likely impacted accessibility to transplantation services among older adults (age ≥65 years). We quantified the impact of COVID-19 on kidney transplantation access for older kidney-only candidates registered on the United States (US) kidney waitlist. STUDY DESIGN/UNASSIGNED:Retrospective analysis of registry data. SETTING & PARTICIPANTS/UNASSIGNED:57,222 older adults who were part of or added to the US kidney waitlist between January 1, 2016 and February 28, 2022, identified using the Scientific Registry of Transplant Recipients (SRTR). EXPOSURES/UNASSIGNED:Four COVID-19 waves and one nonwave period based on the national incidence of COVID-19 in the US (initial: March 15-May 30, 2020; winter 2020-2021: December 1, 2020-January 31, 2021; delta: August 1, 2021-September 30, 2021; omicron: December 1, 2021-February 28, 2022; nonwave: inter-wave periods). OUTCOMES/UNASSIGNED:Waitlist registrations, deceased-donor kidney transplants, living-donor kidney transplants, waitlist mortality, and waitlist removals due to deteriorating condition (hereafter referred to as removals). ANALYTICAL APPROACH/UNASSIGNED:Poisson regression for the adjusted incidence rate ratio (aIRR) of each outcome during the COVID-19 waves and the nonwave period relative to reference (January 1, 2016-December 31, 2019), adjusted for seasonality and secular trends. RESULTS/UNASSIGNED:) and has declined since; mortality rates were 139%, 107%, and 251% above expected for Black candidates, men, and candidates aged ≥75 years, respectively, during the winter 2020-2021 wave. Removals increased from 22% below expected levels (initial wave) to 26% above expected levels (omicron wave); removals were nonsignificantly higher than expected during the omicron wave for older Black and Hispanic candidates. LIMITATIONS/UNASSIGNED:The findings are not generalizable to those listed at earlier ages with prolonged waitlist times. Additionally, using national COVID-19 incidence does not consider local policy and health care variations. Lastly, aIRRs must be interpreted cautiously due to smaller daily event counts. CONCLUSIONS/UNASSIGNED:COVID-19 was associated with fewer transplants and increased mortality and removals in older kidney transplant candidates. Transplant providers should consider this impact and implement policies and practices to ensure the continuity of care. PLAIN-LANGUAGE SUMMARY/UNASSIGNED:The proportion of older adults on the kidney transplant waitlist is increasing, but the impact of COVID-19 on this population is not well characterized. In this study, we looked at incident waitlist registrations, deceased- and living-donor kidney transplants, and waitlist mortality and removals due to deteriorating condition over 4 waves of COVID-19. We found that transplantation services did not fully recover to prepandemic levels as of March 2022. Notably, racial/ethnic minorities and older men experienced lower rates of kidney transplants and higher rates of waitlist mortality, respectively, relative to White candidates and older women. Identifying vulnerable subpopulations affected by COVID-19 and its long-term impact is crucial for creating strategies to ensure the continuity of care in this population during public health emergencies.

BACKGROUND:Prognostic models are becoming increasingly relevant in clinical trials as potential surrogate endpoints, and for patient management as clinical decision support tools. However, the impact of competing risks on model performance remains poorly investigated. We aimed to carefully assess the performance of competing risk and noncompeting risk models in the context of kidney transplantation, where allograft failure and death with a functioning graft are two competing outcomes. METHODS:We included 11,046 kidney transplant recipients enrolled in 10 countries. We developed prediction models for long-term kidney graft failure prediction, without accounting (i.e., censoring) and accounting for the competing risk of death with a functioning graft, using Cox, Fine-Gray, and cause-specific Cox regression models. To this aim, we followed a detailed and transparent analytical framework for competing and noncompeting risk modelling, and carefully assessed the models' development, stability, discrimination, calibration, overall fit, clinical utility, and generalizability in external validation cohorts and subpopulations. More than 15 metrics were used to provide an exhaustive assessment of model performance. RESULTS:Among 11,046 recipients in the derivation and validation cohorts, 1,497 (14%) lost their graft and 1,003 (9%) died with a functioning graft after a median follow-up post-risk evaluation of 4.7 years (IQR 2.7-7.0). The cumulative incidence of graft loss was similarly estimated by Kaplan-Meier and Aalen-Johansen methods (17% versus 16% in the derivation cohort). Cox and competing risk models showed similar and stable risk estimates for predicting long-term graft failure (average mean absolute prediction error of 0.0140, 0.0138 and 0.0135 for Cox, Fine-Gray, and cause-specific Cox models, respectively). Discrimination and overall fit were comparable in the validation cohorts, with concordance index ranging from 0.76 to 0.87. Across various subpopulations and clinical scenarios, the models performed well and similarly, although in some high-risk groups (such as donors over 65 years old), the findings suggest a trend towards moderately improved calibration when using a competing risk approach. CONCLUSIONS:Competing and noncompeting risk models performed similarly in predicting long-term kidney graft failure.

OBJECTIVE:Liver transplant (LT) evaluation is a complex process for patients involving multi-step and parallel medical, surgical, and psychosocial assessments of a patient's appropriateness for transplant. Patients may experience difficulties in navigating the evaluation process, potentially leading to disengagement and resulting in further health decline or death prior to completing evaluation. We aimed to identify and characterize patients' perceptions of undergoing LT evaluation. METHODS:We performed fourteen 30-45 min, semi-structured interviews between 3/2021-5/2021 with patients at a large LT center. Using the constant comparison method, we individually noted themes within and across interviews and codes. RESULTS:Our analysis generated 5 thematic dimensions related to patient engagement (i.e., patient involvement/activation): (1) psychological impact of evaluation on patients' lives; (2) information received during evaluation; (3) prior medical experience of the patient; 4) communication between patients and transplant providers; and (5) support system of the patients. Among these dimensions, we identified 8 themes. CONCLUSION/CONCLUSIONS:LT patient engagement is a multi-dimensional component of LT evaluation that incorporates the psychological impact, information received, prior medical experience, communication, and support systems of patients. PRACTICAL IMPLICATIONS/CONCLUSIONS:This work can inform targeted interventions for increasing patient engagement during the LT evaluation process.

BACKGROUND/UNASSIGNED:In initial COVID-19 clinical trials, menstrual health was not formally monitored, yet anecdotal reports of menstruation changes surfaced on social media. This study aims to assess the association between COVID-19 vaccines and menstruation using Clue, a period-tracking application. STUDY DESIGN/UNASSIGNED:-test compared the mean of these changes between vaccinated and unvaccinated groups. RESULTS/UNASSIGNED:Of 7,559 participants, 6,897 (91 %) were vaccinated. Compared to PRIOR, individuals vaccinated during their menstrual period demonstrated a statistically significant increase in the DURING period length, but not AFTER1 (p = 0.463) and AFTER2 (p = 0.692). No statistically significant changes were observed in period lengths of those vaccinated in between periods or in cycle lengths overall. CONCLUSION/UNASSIGNED:A small but statistically significant change in period length was observed only in individuals vaccinated for COVID-19 during their menstrual period. Providers can better counsel menstruating individuals to reduce vaccine misinformation.