Abstract:Patients considering renal transplantation face an increasingly complex array of choices as a result of the revised kidney transplant allocation system. Decision aids have been shown to improve patient decision making through the provision of detailed, relevant, individualized clinical data. A mobile iOS based application (app) including animated patient education and individualized risk adjusted outcomes following kidney transplants with varying donor characteristics and DSA waiting times was piloted in 2 large US transplant programs with a diverse group of renal transplant candidates (N=81).The majority (86%) of patients felt that the app improved their knowledge and was culturally appropriate for their race/ethnicity (67%-85%). Patients scored significantly higher on transplant knowledge testing (9.1/20 to 13.8/20 p<0.001) after viewing the app, including patients with low health literacy (8.0 to 13.0 p<0.001). Overall knowledge of and interest in living and deceased donor kidney transplantation increased. This pilot project confirmed the benefit and cultural acceptability of this educational tool, and further refinement will explore how to better communicate the risks and benefits of non-standard donors.

General DNA hypomethylation is associated with Alzheimer’s disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities. To assess a possible human significance of findings, we examined the methylation at 12 CpGs sites in the bace-1 promoter, using genome-wide DNA methylation data from 740 postmortem human brains. Thus, we found significant associations of bace-1 promoter methylation with β-amyloid load among persons with AD dementia, and PHFtau tangle density. Our results support a plausible causal role for the earliest amyloid beta accumulation to provoke DNA hypomethylation, influencing AD pathological outcomes.

Background The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. Methods Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 min after portal venous (PVR) and hepatic arterial reperfusion (HAR) and analyzed by LC-MS for energetic cofactors (ATP/ADP/AMP, NADH/NAD+, NADPH/NADP+, FAD+, GSSG/GSH). Energy status was correlated to posttransplant outcome. In addition, 4 discarded human DCD livers were subjected to ex vivo reperfusion, modeling reperfusion injury and were similarly analyzed for energetic cofactors. Results A rapid shift towards higher energy adenine nucleotides was observed following clinical reperfusion, with a 2.45-, 3.17- and 2.12-fold increase in ATP:ADP, ATP:AMP and energy charge (EC) after PVR, respectively. Seven of the 19 grafts developed early allograft dysfunction (EAD). Correlation with peritransplant cofactors revealed a significant difference in EC between EAD and normal functioning grafts (0.09 vs. 0.31, P<0.05). In the simulated reperfusion model, a similar trend in adenine nucleotide changes was observed. Conclusion A preserved energy status appears critical in the peritransplant period. Levels of adenine nucleotides change rapidly following reperfusion and ratios of ATP/ADP/AMP following reperfusion are significantly correlated to graft function. Using these markers as a viability test in combination with ex vivo reperfusion may provide a useful predictor of outcome that incorporates donor, preservation and reperfusion factors.

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The influence of African American (AA) recipient race on outcomes following simultaneous pancreas‐kidney transplantation (SPKT) is uncertain. Methods From 11/01 to 2/19, we retrospectively studied 158 Caucasian (C) and 57 AA patients (pts) undergoing SPKT. Results The AA group had fewer patients on peritoneal dialysis (30% C vs. 14% AA), more patients with longer dialysis duration (28% C vs. 51% AA), more sensitized (PRA ≥20%) patients (6% C vs. 21% AA), and more patients with pretransplant C‐peptide levels ≥2.0 ng/ml (11% C vs. 35% AA, all P < .05). With a mean 9.2 year follow‐up, patient survival (65% C vs. 77% AA, P = .098) slightly favored the AA group, whereas kidney (55% C vs. 60% AA) and pancreas (48% C vs. 54% AA) graft survival rates (GSRs) were comparable. Death‐censored kidney (71% C vs. 68% AA) and pancreas (both 62%) GSRs demonstrated that death with a functioning graft (DWFG) was more common in C vs. AA patients (23% C vs. 12% AA, P = .10). The incidence of death‐censored dual graft loss (usually rejection) was 7% C versus 21% AA (P = .005). Conclusions Following SPKT, AA patients are at a greater risk for dual immunological graft loss whereas C patients are at greater risk for DWFG.

The RBD-specific subtype of PD may also have a different risk factor profile.

Background: With a drastic shortage of addiction medicine specialists-and an ever-growing number of patients with opioid use disorder (OUD)-there is a dire need for more clinicians to feel confident in prevention and management of OUD and obtain a DEA-X waiver to prescribe medications to treat OUD. Here we determine if it is feasible to certify 4th year medical students with DEA-X waiver training as a component of the PROUD (Prevent and Reduce Opioid Use Disorder) curriculum, and if PROUD enhanced preparedness for medical students to manage OUD as interns. Methods: We implemented a sequential mixed-methods IRB approved study to assess feasibility (completing all required components of DEA-X waiver training) and impact of PROUD (measured by knowledge growth, enhancement for residency, and utilization of training during internship). Students completed 11 hours of required OUD training. Quantitative data included pre-/postknowledge and curriculum satisfaction assessments as well as long-term impact with follow up survey as interns. Qualitative data was collected by survey and semi-structured focus groups. Results: All 120 graduating medical students completed the required components of the curriculum. Knowledge improved on the Provider Clinical Support Services (12.9-17.3, p < 0.0001) and Brief Opioid Overdose Knowledge assessments (10.15-10.81, p < 0.0001). Course satisfaction was high: 90% recommended online modules; 85% recommended training overall. Six qualitative themes emerged: (1) curriculum content was practical, (2) online modules allowed flexibility, (3) in-person seminars ensured authenticity, (4) timing at the transition to residency was optimal, (5) curriculum enhanced awareness and confidence, and ( 6) training was applicable to future careers. At 3 months, 60% reported using their training during internship; 64% felt more prepared to treat OUD than peers. Conclusions: PROUD trained 4th year medical students in opioid stewardship. As interns, students felt ready to serve as change agents to prevent, diagnose, and treat OUD.

BACKGROUND: Allograft nephrectomy (AN) has been associated with considerable perioperative morbidity. We aimed to determine if preoperative angiographic kidney embolization (PAKE) to induce graft thrombosis before AN improves outcomes. STUDY DESIGN: We reviewed adult kidney transplant alone patients who underwent AN at a single center from 2002 to 2020 and compared perioperative outcomes for patients with and without PAKE. RESULTS: Eighty patients underwent AN, including 54 (67.5%) with PAKE before AN and 26 (32.5%) with AN alone. PAKE was associated with significantly reduced blood loss (PAKE: mean 266 ± 292 mL vs AN alone: 495 ± 689 mL; p = 0.04) and reduced transfusion requirements (PAKE: mean 0.5 ± 0.8 packed red blood cell units vs AN alone: 1.6 ± 2.6 units; p = 0.004) despite similar preoperative hemoglobin levels. Mean operating time (PAKE: 142 ± 43 minutes vs AN alone: 202 ± 111 minutes; p = 0.001) and length of hospital stay (PAKE: 4.3 ± 2.0 days vs AN alone: 9.3 ± 9.4 days; p = 0.0003) also favored PAKE, as did the surgical complication rate (PAKE: 6/54 [11%] vs AN alone: 9/26 [35%], p = 0.02). Long-term patient survival after AN was comparable in both groups. CONCLUSIONS: PAKE was associated with lower intraoperative blood loss, fewer transfusions, reduced operating time, shorter length of stay, and fewer surgical complications compared with AN alone at our center.