Thrombocytopenia is commonly seen in myelodysplastic syndrome (MDS) patients, and bleeding complications are a major cause of morbidity and mortality. Thrombocytopenia is an independent factor for decreased survival and has been incorporated in newer prognostic scoring systems. The mechanisms of thrombocytopenia are multifactorial and involve a differentiation block of megakaryocytic progenitor cells, leading to dysplastic, hypolobated and microscopic appearing megakaryocytes or increased apoptosis of megakaryocytes and their precursors. Dysregulated thrombopoietin (TPO) signaling and increased platelet destruction through immune or nonimmune mechanisms are frequently observed in MDS. The clinical management of patients with low platelet counts remains challenging and approved chemotherapeutic agents such as lenalidomide and azacytidine can also lead to a transient worsening of thrombocytopenia. Platelet transfusion is the only supportive treatment option currently available for clinically significant thrombocytopenia. The TPO receptor agonists romiplostim and eltrombopag have shown clinical activity in clinical trials in MDS. In addition to thrombopoietic effects, eltrombopag can inhibit leukemic cell proliferation via TPO receptor-independent effects. Other approaches such as treatment with cytokines, immunomodulating drugs and signal transduction inhibitors have shown limited activity in selected groups of MDS patients. Combination trials of approved agents with TPO agonists are ongoing and hold promise for this important clinical problem.

Post-irradiation complications including thrombus formation result from increased procoagulant activity of vascular endothelial cells and elevated levels of von Willebrand factor (VWF) contribute to this process. We have previously demonstrated that irradiation induction of the VWF is mediated through interaction of NF-Y transcription factor with its cognate binding site in the VWF promoter. We have also demonstrated that irradiation increases the association of NF-Y with histone acetyltransferase p300/CBP-associated factor (PCAF). We now report that irradiation decreases the association of NF-Y with histone deacetylase 1 (HDAC1). We demonstrate that irradiation-induced changes in association of NF-Y with HDAC1 and PCAF lead to increased PCAF recruitment to the VWF promoter, increased association of acetylated histone H4 with the VWF promoter and subsequently increased transcription. We also demonstrate that this process is correlated to dephosphorylation of HDAC1 and is inhibited by calyculin A, an inhibitor of protein phosphatase1.

Background Amiodarone is commonly used in atrial fibrillation (AF). Long-term use of amiodarone is associated with significant toxicities, especially in elderly patients. However, in the short term after hospitalization of AF, it remains uncertain whether the use of amiodarone will increase mortality. Methods We conducted a retrospective cohort study including patients (Age≥60 years old) who were hospitalized between 07/01/2004 and 06/30/2019 with a primary diagnosis of AF and left ventricular ejection fraction (LVEF) ≥50%. Patients who were prescribed amiodarone during hospitalization but not before are considered as amiodarone group (348 patients). Patients who weren't prescribed amiodarone are considered as non-amiodarone group (2260 patients). Univariate analysis solely analyzed amiodarone use on the all-cause mortality (Kaplan-Meier Curve), and possible confounders were adjusted in the multivariate analysis including age, gender, diabetes mellitus (DM), hypertension (HTN), coronary artery disease (CAD), as well as LVEF, left atrium internal diameter, use of other rate control medications (e.g. beta-blocker). The proportional-hazard assumption was tested by Log-rank test and a 2-sided P value of <0.05 is considered statistically significant. The hazard ratio and 95% confidence interval (CI) were calculated. Results Patients' baseline characteristics were listed in Table 1. Both Univariate and Multivariate analysis showed amiodarone group had higher in-hospital (hazard ratio 2.06; p=0.036) and 100-day mortality (hazard ratio 1.86; p=0.028). Other rate control medication use was also associated with increased mortality but not statistically significant. The results are showed in Figure 1. Conclusion Amiodarone use in elderly patients with preserved ejection fraction is associated with increased short-term all-cause mortality after hospitalization of AF. Figure 1. KM Curve & ForestPlot of Mortality Funding Acknowledgement Type of funding source: None