RESUMO
Prior studies reveal adverse effects of transfusion on cardiac surgery, but little is known of transfusion impact on heart transplantation. First-time, single-organ adult heart transplant recipients between January 1, 2010, and December 31, 2020, were included, stratified above or below a model for end-stage liver disease excluding international normalized ratio (MELD-XI) score of 9.4, and propensity score matched to their nearest neighbor. A 90 day landmark analysis within each cohort was also performed. Unadjusted analysis showed transfusion recipients, MELD-XI ≥9.4, were more likely to experience post-heart transplantation mortality (Hazard Ratio (HR), 1.352 [95% Confidence Interval (CI), 1.239-1.477], p < 0.001), persisting after adjustment for potential confounders (adjusted HR, 1.211 [95% CI, 1.100-1.335], p < 0.001) and after propensity-score matching (HR, 1.174 [95% CI, 1.045-1.319], p = 0.007). Post-transplant length of stay was longer (25.9 vs. 23.2 days, p < 0.001). Post-transplant dialysis was more common (18.7 vs. 15.9%, p = 0.009). There was no survival difference on 90 day landmarked analysis (p = 0.108). With MELD-XI <9.4, there was slight survival detriment among transfusion recipients on univariable analysis (HR, 1.111 [95% CI, 1.001-1.234], p = 0.049) but not on multivariable analysis (adjusted HR, 1.061 [95% CI, 0.952-1.181], p = 0.285). There was similar survival after propensity-score matching (HR, 1.032 [95% CI, 0.903-1.180], p = 0.642) and on landmark analysis (p = 0.581). Ultimately, transfusion was associated with worse post-heart transplantation outcomes among recipients with a MELD-XI ≥9.4.
RESUMO
Kaposi sarcoma is the most common cancer in human immunodeficiency virus-positive individuals and is caused by Kaposi sarcoma-associated herpesvirus (KSHV). It is believed that a small number of latently infected Kaposi sarcoma tumor cells undergo spontaneous lytic reactivation to produce viral progeny for infection of new cells. Here, we use matched donor-derived human dermal blood and lymphatic endothelial cells (BEC and LEC, respectively) to show that KSHV-infected BECs progressively lose viral genome as they proliferate. In sharp contrast, KSHV-infected LECs predominantly entered lytic replication, underwent cell lysis, and released new virus. Continuous lytic cell lysis and de novo infection allowed LEC culture to remain infected for a prolonged time. Because of the strong propensity of LECs toward lytic replication, LECs maintained virus as a population, despite the death of individual host cells from lytic lysis. The master regulator of lymphatic development, Prox1, bound the promoter of the RTA gene to upregulate its expression and physically interacted with RTA protein to coregulate lytic genes. Thus, LECs may serve as a proficient viral reservoir that provides viral progeny for continuous de novo infection of tumor origin cells, and potentially BECs and mesenchymal stem cells, which give rise to Kaposi sarcoma tumors. Our study reveals drastically different host cell behaviors between BEC and LEC and defines the underlying mechanisms of the lymphatic cell environment supporting persistent infection in Kaposi sarcoma tumors. SIGNIFICANCE: This study defines the mechanism by which Kaposi's sarcoma could be maintained by virus constantly produced by lymphatic cells in HIV-positive individuals.
