Transplantation
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Graft quality before transplantation is a major factor influencing chronic rejection. Organ preservation and ischemia/reperfusion play an important role in the induction of organ injury. Although both suppression of metabolism by hypothermic preservation and preconditioning before ischemia limit injury, understanding the biochemical signaling pathways will allow us to optimize graft preservation further. ⋯ Pharmacologic activation of AMPK demonstrated its ability to activate endothelial nitric oxide synthase and inhibit nuclear factor-kB, thereby limiting endothelial dysfunction and inflammation. Further, studies in knock-out mice lacking ENTDP1 and NT5E (enzymes catalyzing formation and degradation of AMP, respectively) demonstrated a clear protective role for AMP in ischemia/reperfusion. AMPK activation before or during organ preservation might be a promising pharmacologic approach to limit organ injury and maintain graft quality before transplantation.
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Multicenter Study
Analysis of the lung allocation score estimation of risk of death in patients with pulmonary arterial hypertension using data from the REVEAL Registry.
Waitlist mortality for patients with pulmonary arterial hypertension (PAH) has not improved after implementation of the lung allocation score (LAS). We analyzed data from patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) as a means to compare observed mortality with predicted mortality from the LAS to identify key prognostic parameters that may be incorporated into the LAS to improve waitlist mortality for patients with PAH. ⋯ The LAS is reevaluated every 6 months after the initial 3-year trial period. Our results suggest that an LAS model that includes both 6-MWD and mRAP better discriminates waitlist urgency for patients with PAH than the current LAS.