Emerging Roles of Exosomes in Stroke Therapy.

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell-derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on (1) the therapeutic potential of exosomes in stroke treatment, (2) the optimization process of upstream and downstream production, and (3) preclinical application in a stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

Survival after live donor versus deceased donor liver transplantation: propensity score-matched study.

BACKGROUND: For individuals with advanced liver disease, equipoise in outcomes between live donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) is uncertain. METHODS: A retrospective cohort study was performed using data extracted from the Scientific Registry of Transplant Recipients. Adults who underwent first-time DDLT or LTDL in the United States between 2002 and 2020 were paired using propensity-score matching with 1:10 ratio without replacement. Patient and graft survival were compared using the model for end-stage liver disease (MELD) score for stratification. RESULTS: After propensity-score matching, 31 522 DDLT and 3854 LDLT recipients were included. For recipients with MELD scores ≤15, LDLT was associated with superior patient survival (HR = 0.92; 95% c.i. 0.76 to 0.96; P = 0.013). No significant differences in patient survival were observed for MELD scores between 16 and 30. Conversely, for patients with MELD scores >30, LDLT was associated with higher mortality (HR 2.57; 95% c.i. 1.35 to 4.62; P = 0.003). Graft survival was comparable between the two groups for MELD ≤15 and for MELD between 21 and 30. However, for MELD between 16 and 20 (HR = 1.15; 95% c.i. 1.00 to 1.33; P = 0.04) and MELD > 30 (HR = 2.85; 95% c.i. 1.65 to 4.91; P = 0.001), graft survival was considerably shorter after LDLT. Regardless of MELD scores, re-transplantation rate within the first year was significantly higher after LDLT. CONCLUSIONS: In this large propensity score-matched study using national data, comparable patient survival was found between LDLT and DDLT in recipients with MELD scores between 16 and 30. Conversely, for patients with MELD > 30, LDLT was associated with worse outcomes. These findings underscore the importance of transplant selection for patients with high MELD scores.

Donor-recipient race-ethnicity concordance and patient survival after liver transplantation.

INTRODUCTION: We assessed the association between patient survival after liver transplantation (LT) and donor-recipient race-ethnicity (R/E) concordance. METHODS: The Scientific Registry of Transplant Recipients (SRTR) was retrospectively analyzed using data collected between 2002 and 2019. Only adults without history of prior organ transplant and recipients of LT alone were included. The primary outcome was patient survival. Donors and recipients were categorized into five R/E groups: White/Caucasian, African American/Black, Hispanic/Latino, Asian, and Others. Statistical analyses were performed using Kaplan-Meier survival curves and Cox Proportional Hazards models, adjusting for donor and recipient covariates. RESULTS: 85,427 patients were included. Among all the R/E groups, Asian patients had the highest 5-year survival (81.3%; 95% CI = 79.9-82.7), while African American/Black patients had the lowest (71.4%; 95% CI = 70.3-72.6) (P < 0.001). Lower survival rates were observed in recipients who received discordant R/E grafts irrespective of their R/E group. The fully adjusted hazard ratio for death was statistically significant in African American/Black (aHR 1.07-1.18-1.31; P < 0.01) and in White∕Caucasian patients (aHR 1.00-1.04-1.07; P = 0.03) in the presence of donor-recipient R/E discordance. CONCLUSION: Disparities in post-LT outcomes might be influenced by biological factors in addition to well-known social determinants of health.