Waitlist Trends in Heart-Liver Transplantation With Updated US Heart Allocation System.

BACKGROUND: In October 2018, the United States implemented a change in the donor heart allocation policy from a three-tiered to a six-tiered status system. The purpose of the current study was to examine changes in waitlist patterns among patients listed for concomitant heart-liver transplantation with implementation of the new allocation system. METHODS: Patients listed for heart-liver transplantation between January 1, 2012, and June 30, 2021, were identified from the United Network for Organ Sharing database. Patients were grouped by era according to initial list date before or after October 18, 2018. Competing risks regression for mortality, transplantation, removal from waitlist due to illness was performed according to the method of Fine and Gray. Waitlist data were censored at 3 years from initial listing. RESULTS: Overall, 523 patients were identified, of whom 310 were listed before (era 1, 59%) and 213 after (era 2, 41%) allocation change. Patients in era 1 were older, had more restrictive cardiomyopathy, and more preoperative inotrope use (all P < .05). However, patients in era 2 has longer ischemic times (3.5 ± 1.1 vs 3.1 ± 1.1 hours, P < .01) and more intraaortic balloon pump use (8.9% vs 3.9%, P = .016). Era 2 was associated with lower subdistribution hazard for death (hazard ratio 0.37; 95% CI, 0.13-1.02; P = .054) and increased transplantation (hazard ratio 1.35; 95% CI, 1.06-1.72; P = .015). CONCLUSIONS: The implementation of the US donor heart allocation policy was associated with more preoperative intraaortic balloon pump use for patients listed for heart-liver transplantation. Despite that, the modern era was associated with lower waitlist mortality and more frequent transplantation, without increased risk of delisting due to illness.

Prosthesis Choice in Dialysis Patients Undergoing Mitral Valve Replacement.

BACKGROUND: Patients with renal disease on dialysis have significant comorbidity limiting life expectancy; however, these patients may experience accelerated prosthetic valve degeneration. The purpose of this study was to examine the impact of prosthesis choice on outcomes in dialysis patients undergoing mitral valve replacement (MVR) at our high-volume academic center. METHODS: Adults undergoing MVR were retrospectively reviewed between January 2002 and November 2019. Patients were included if they had documented renal failure and dialysis requirements before presentation. Patients were stratified by mechanical vs bioprosthetic prosthesis. Death and recurrent severe valve failure (3+ or greater) or redo mitral operation were used as primary outcomes. RESULTS: There were 177 dialysis patients identified who underwent MVR. Of these, 118 (66.7%) received bioprosthetic valves, whereas 59 (33.3%) received mechanical valves. Those who received mechanical valves were younger (48 vs 61 years; P < .001) and had less diabetes (32% vs 51%; P = .019). Prevalence of endocarditis and atrial fibrillation was similar. Postoperative length of stay was not different between groups. Risk-adjusted hazard for 5-year mortality was similar between groups (P = .668). Early mortality was high, with both groups having <50% actuarial survival at 2 years. No differences were noted in rates of structural valve deterioration or reintervention. More stroke events were noted on follow-up in patients receiving mechanical valves (15% vs 6%; P = .041). Endocarditis was the leading reason for reintervention; 4 patients received repeated surgery for bioprosthetic valve failure. CONCLUSIONS: MVR in dialysis patients carries significant morbidity and increased midterm mortality. Decreased life expectancy should be considered in the tailoring of prosthesis choice to dialysis-dependent patients.

Cdc34p ubiquitin-conjugating enzyme is a component of the tombusvirus replicase complex and ubiquitinates p33 replication protein.

To identify host proteins interacting with Tomato bushy stunt virus (TBSV) replication proteins in a genome-wide scale, we have used a yeast (Saccharomyces cerevisiae) proteome microarray carrying 4,088 purified proteins. This approach led to the identification of 58 yeast proteins that interacted with p33 replication protein. The identified host proteins included protein chaperones, ubiquitin-associated proteins, translation factors, RNA-modifying enzymes, and other proteins with yet-unknown functions. We confirmed that 19 of the identified host proteins bound to p33 in vitro or in a split-ubiquitin-based two-hybrid assay. Further analysis of Cdc34p E2 ubiquitin-conjugating enzyme, which is one of the host proteins interacting with p33, revealed that Cdc34p is a novel component of the purified viral replicase. Downregulation of Cdc34p expression in yeast, which supports replication of a TBSV replicon RNA (repRNA), reduced repRNA accumulation and the activity of the tombusvirus replicase by up to fivefold. Overexpression of wild-type Cdc34p, but not that of an E2-defective mutant of Cdc34p, increased repRNA accumulation, suggesting a significant role for the ubiquitin-conjugating enzyme function of Cdc34p in TBSV replication. Also, Cdc34p was able to ubiquitinate p33 in vitro. In addition, we have shown that p33 becomes ubiquitinated in vivo. We propose that ubiquitination of p33 likely alters its function or affects the recruitment of host factors during TBSV replication.