Faculty Bibliography

BACKGROUND/UNASSIGNED:Fewer minoritized patients with end-stage kidney disease (ESKD) receive kidney transplantation (KT); efforts to mitigate disparities have thus far failed. Pinpointing the specific stage(s) within the transplant care continuum (being informed of KT options, joining the waiting list, to receiving KT) where disparities emerge among each minoritized population is pivotal for achieving equity. We therefore quantified racial and ethnic disparities across the KT care continuum. METHODS/UNASSIGNED:We conducted a retrospective cohort study (2015-2020), with follow-up through 12/10/2021. Patients with incident dialysis were identified using the US national registry data. The exposure was race and ethnicity (Asian, Black, Hispanic, and White). We used adjusted modified Poisson regression to quantify the adjusted prevalence ratio (aPR) of being informed of KT, and cause-specific hazards models to calculate adjusted hazard ratios (aHR) of listing, and transplantation after listing. FINDINGS/UNASSIGNED:Among 637,951 adults initiating dialysis, the mean age (SD) was 63.8 (14.6), 41.8% were female, 5.4% were Asian, 26.3% were Black, 16.6% were Hispanic, and 51.7% were White (median follow-up in years [IQR]:1.92 [0.97-3.39]). Black and Hispanic patients were modestly more likely to be informed of KT (Black: aPR = 1.02, 95% confidence interval [CI]:1.01-1.02; Hispanic: aPR = 1.03, 95% CI: 1.02-1.03) relative to White patients. Asian patients were more likely to be listed (aHR = 1.18, 95% CI: 1.15-1.21) but less likely to receive KT (aHR = 0.56, 95% CI: 0.54-0.58). Both Black and Hispanic patients were less likely to be listed (Black: aHR = 0.87, 95% CI: 0.85-0.88; Hispanic: aHR = 0.85, 95% CI: 0.85-0.88) and receive KT (Black: aHR = 0.61, 95% CI: 0.60-0.63; Hispanic: aHR = 0.64, 95% CI: 0.63-0.66). INTERPRETATION/UNASSIGNED:Improved characterization of the barriers in KT access specific to each racial and ethnic group, and the interventions to address these distinct challenges throughout the KT care continuum are needed; our findings identify specific stages most in need of mitigation. FUNDING/UNASSIGNED:National Institutes of Health.

In controlled organ donation after circulatory determination of death (cDCDD), accurate and timely death determination is critical, yet knowledge gaps persist. Further research to improve the science of defining and determining death by circulatory criteria is therefore warranted. In a workshop sponsored by the National Heart, Lung, and Blood Institute, experts identified research opportunities pertaining to scientific, conceptual, and ethical understandings of DCDD and associated technologies. This article identifies a research strategy to inform the biomedical definition of death, the criteria for its determination, and circulatory death determination in cDCDD. Highlighting knowledge gaps, we propose that further research is needed to inform the observation period following cessation of circulation in pediatric and neonatal populations, the temporal relationship between the cessation of brain and circulatory function after the withdrawal of life-sustaining measures in all patient populations, and the minimal pulse pressures that sustain brain blood flow, perfusion, activity, and function. Additionally, accurate predictive tools to estimate time to asystole following the withdrawal of treatment and alternative monitoring modalities to establish the cessation of circulatory, brainstem, and brain function are needed. The physiologic and conceptual implications of postmortem interventions that resume circulation in cDCDD donors likewise demand attention to inform organ recovery practices. Finally, because jurisdictionally variable definitions of death and the criteria for its determination may impede collaborative research efforts, further work is required to achieve consensus on the physiologic and conceptual rationale for defining and determining death after circulatory arrest.

Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using ²³Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with ²³Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up ¹H and ²³Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from ²³Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.