16 research outputs found

    Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study

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    Background: Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization. Methods: The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression. Results: From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]). Conclusions: Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population

    Instant Blood-Mediated Inflammatory Reaction in Hepatocyte Transplantation: Current Status and Future Perspectives

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    Hepatocyte transplantation (HT) is emerging as a promising alternative to orthotopic liver transplantation (OLT) in patients with certain liver-based metabolic disease and acute liver failure. Hepatocytes are generally infused into the portal venous system, from which they migrate into the liver cell plates of the native organ. One of the major hurdles to the sustained success of this therapy is early cell loss, with up to 70% of hepatocytes lost immediately following infusion. This is largely thought to be due to the instant blood-mediated inflammatory reaction (IBMIR), resulting in the activation of complement and coagulation pathways. Transplanted hepatocytesproduce and release tissue factor (TF), which activates the coagulation pathway, leading to the formation of thrombin and fibrin clots. Thrombin can further activate a number of complement proteins, leading to the activation of the membrane attack complex (MAC) and subsequent hepatocyte cell death. Inflammatory cells including granulocytes, monocytes, Kupffer cells, and natural killer (NK) cells have been shown to cluster around transplanted hepatocytes, leading to their rapid clearance shortly after transplantation. Current researchaims to improve cell engraftment and prevent early cell loss. This has been proven successful in vitro using pharmacological interventions such as melagatran, low-molecular-weight dextran sulphate, and N-acetylcysteine(NAC). Effective inhibition of IBMIR would significantly improve hepatocyte engraftment, proliferation, and function, providing successful treatment for patients with liver-based metabolic diseases
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