Outcomes associated with antithrombotic strategies in heart failure with reduced ejection fraction and sinus rhythm following acute ischemic stroke.

Purpose: Insufficient data exist regarding the benefit of long-term antiplatelet vs. anticoagulant therapy in the prevention of recurrent ischemic stroke in patients with ischemic stroke and heart failure with reduced ejection fraction (HFrEF). Therefore, this study aimed to compare longitudinal outcomes associated with antiplatelet vs. anticoagulant use in a cohort of patients with stroke and with an ejection fraction of ≤40%. Methods: We retrospectively analyzed single-center registry data (2015-2021) of patients with ischemic stroke, HFrEF, and sinus rhythm. Time to the primary outcome of recurrent ischemic stroke, major bleeding, or death was assessed using the adjusted Cox proportional hazards model and was compared between patients treated using anticoagulation (±antiplatelet) vs. antiplatelet therapy alone after propensity score matching using an intention-to-treat (ITT) approach, with adjustment for residual measurable confounders. Sensitivity analyses included the multivariable Cox proportional hazards model using ITT and as-treated approaches without propensity score matching. Results: Of 2,974 screened patients, 217 were included in the secondary analyses, with 130 patients matched according to the propensity score for receiving anticoagulation treatment for the primary analysis, spanning 143 patient-years of follow-up. After propensity score matching, there was no significant association between anticoagulation and the primary outcome [hazard ratio (HR) 1.10, 95% confidence interval (CI): 0.56-2.17]. Non-White race (HR 2.26, 95% CI: 1.16-4.41) and the presence of intracranial occlusion (HR 2.86, 95% CI: 1.40-5.83) were independently associated with the primary outcome, while hypertension was inversely associated (HR 0.42, 95% CI: 0.21-0.84). There remained no significant association between anticoagulation and the primary outcome in sensitivity analyses. Conclusion: In HFrEF patients with an acute stroke, there was no difference in outcomes of antithrombotic strategies. While this study was limited by non-randomized treatment allocation, the results support future trials of stroke patients with HFrEF which may randomize patients to anticoagulation or antiplatelet.

Discovery and characterization of novel trans-spliced products of human polyoma JC virus late transcripts from PML patients.

Although the human neurotropic polyomavirus, JC virus (JCV), was isolated almost a half century ago, understanding the molecular mechanisms governing its biology remains highly elusive. JCV infects oligodendrocytes and astrocytes in the central nervous system (CNS) and causes a rare fatal brain disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals including AIDS. It has a small circular DNA genome (∼5 kb) and generates two primary transcripts from its early and late coding regions, producing several predicted alternatively spliced products mainly by cis-splicing. Here, we report the discovery and characterization of two novel open reading frames (ORF1 and ORF2) associated with JCV late transcripts, generated by an unusual splicing process called trans-splicing. These ORFs result from (i) the trans-splicing of two different lengths of the 5'-short coding region of VP1 between the coding regions of agnoprotein and VP2 after replacing the intron located between these two coding regions and (ii) frame-shifts occurring within the VP2 coding sequences terminated by a stop codon. ORF1 and ORF2 are capable of encoding 58 and 72 aa long proteins respectively and are expressed in infected cells and PML patients. Each ORF protein shares a common coding region with VP1 and has a unique coding sequence of their own. When the expression of the unique coding regions of ORFs is blocked by a stop codon insertion in the viral background, the mutant virus replicates less efficiently when compared to wild-type, suggesting that the newly discovered ORFs play critical roles in the JCV life cycle.