Left atrial appendage closure in patients with failure of anticoagulation therapy: A multicenter comparative study on the hybrid strategy using DOACs and VKAs.

Background: Patients with non-valvular atrial fibrillation (nvAF) who experienced a cardioembolic (CE) event despite adequate oral anticoagulation (OAC) are at high risk of recurrence and the combination between percutaneous left atrial appendage closure (LAAC) and long-term OAC may be a valuable option. The aim of this study was to compare the safety and the efficacy of post-LAAC long-term assumption of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in this population.

Lack of Lloviu Virus Disease Development in Ferret Model.

The first isolate of the emerging filovirus Lloviu virus (LLOV) was obtained in 2022. No animal disease models have been established. We assessed the pathogenic potential of LLOV in ferrets after intranasal, intramuscular, or aerosol exposure.

A Hamster Model for the Evaluation of Marburg Virus Countermeasures.

Wild-type filoviruses including Marburg virus (MARV) cause disease in humans, nonhuman primates, and some immunodeficient mouse strains but generally not in immunocompetent rodents and ferrets. However, disease in immunocompetent rodents can be achieved by serial passaging of the virus as demonstrated by the mouse-, hamster-, and guinea pig-adapted strains of MARV, which often cause lethal disease in the respective rodent species. These disease models present valuable first screening models for medical countermeasure evaluation against MARV, including monoclonal antibody therapies and vaccines.

Generation, Recovery, and Propagation of a Recombinant Vesicular Stomatitis Virus Expressing the Marburg Virus Glycoprotein.

Vesicular stomatitis virus (VSV)-based vaccination has shown protective efficacy against filovirus infection. Following the approval of a VSV-based vaccine against Ebola virus, there have been efforts toward applying the same platform for other filoviruses, including Marburg virus (MARV) and Sudan virus. Because these vaccines express filovirus glycoproteins, they are also a valuable tool to study filovirus entry under biosafety level 2 conditions.

A fatty acid-ordered plasma membrane environment is critical for Ebola virus matrix protein assembly and budding.

Plasma membrane (PM) domains and order phases have been shown to play a key role in the assembly, release, and entry of several lipid-enveloped viruses. In the present study, we provide a mechanistic understanding of the Ebola virus (EBOV) matrix protein VP40 interaction with PM lipids and their effect on VP40 oligomerization, a crucial step for viral assembly and budding. VP40 matrix formation is sufficient to induce changes in the PM fluidity.

Combination of High-Dose Daptomycin and Ceftriaxone for Cardiac Implantable Electronic Device Infections: A 10-Year Experience.

Purpose: Cardiac implantable electronic device (CIED) infections are increasingly common. Gram-positive bacteria such as coagulase negative staphylococci and Staphylococcus aureus are the most commonly involved pathogens. The aim of this study was to describe the characteristics and outcome of patients with CIED infections who underwent device removal and were empirically treated with high dose (8-12 mg/kg daily) daptomycin (DAP) in combination with ceftriaxone (CRO).

Vaccine Platform Comparison: Protective Efficacy against Lethal Marburg Virus Challenge in the Hamster Model.

Marburg virus (MARV), a filovirus, was first identified in 1967 in Marburg, Germany, and Belgrade, former Yugoslavia. Since then, MARV has caused sporadic outbreaks of human disease with high case fatality rates in parts of Africa, with the largest outbreak occurring in 2004/05 in Angola. From 2021 to 2023, MARV outbreaks occurred in Guinea, Ghana, New Guinea, and Tanzania, emphasizing the expansion of its endemic area into new geographical regions.

A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus.

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 helper T (Th) cells induced by bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions.

Marburg virus exploits the Rab11-mediated endocytic pathway in viral-particle production.

Filoviruses produce viral particles with characteristic filamentous morphology. The major viral matrix protein, VP40, is trafficked to the plasma membrane and promotes viral particle formation and subsequent viral egress. In the present study, we assessed the role of the small GTPase Rab11-mediated endocytic pathway in Marburg virus (MARV) particle formation and budding.

Pathogenic differences of cynomolgus macaques after Taï Forest virus infection depend on the viral stock propagation.

Taï Forest virus (TAFV) is a negative-sense RNA virus in the Filoviridae family. TAFV has caused only a single human infection, but several disease outbreaks in chimpanzees have been linked to this virus. Limited research has been done on this human-pathogenic virus.

A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus.

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 helper T (Th) cells induced by bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions.

Quantitative Phase Imaging as Sensitive Screening Method for Nanoparticle-Induced Cytotoxicity Assessment.

The assessment of nanoparticle cytotoxicity is challenging due to the lack of customized and standardized guidelines for nanoparticle testing. Nanoparticles, with their unique properties, can interfere with biochemical test methods, so multiple tests are required to fully assess their cellular effects. For a more reliable and comprehensive assessment, it is therefore imperative to include methods in nanoparticle testing routines that are not affected by particles and allow for the efficient integration of additional molecular techniques into the workflow.

Ebola virus disease sequelae and viral persistence in animal models: Implications for the future.

Ebola virus disease (EVD), caused by infection with Ebola virus, results in severe, acute illness with a high mortality rate. As the incidence of outbreaks of EVD increases and with the development and approval of medical countermeasures (MCMs) against the acute disease, late phases of EVD, including sequelae, recrudescence, and viral persistence, are occuring more frequently and are now a focus of ongoing research. Existing animal disease models recapitulate acute EVD but are not suitable to investigate the mechanisms of these late disease phenomena.

Left Atrial Appendage Closure in Patients With a Mechanical Mitral Valve Prosthesis: A Multicentre Italian Pilot Study.

Background: In patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy and therapeutic international normalized ratio (INR) range, the incidence of cardiac thromboembolism is not negligible, and the subgroup of patients who have a mechanical prosthetic mitral valve (PMV) has the highest risk. We aimed to assess the long-term effects of left atrial appendage closure (LAAC) in AF patients with a mechanical PMV who experienced a failure of VKA therapy.

Methods: In this retrospective, multicentre study, patients underwent LAAC because of thrombotic events including transient ischemic attack and/or stroke, systemic embolism, and evidence of left atrial appendage thrombosis and/or sludge, despite VKA therapy, were enrolled.

A Bivalent Adenovirus-Vectored Vaccine Induces a Robust Humoral Response, but Does Not Protect Cynomolgus Macaques Against a Lethal Challenge With Sudan Virus.

The most recent Sudan virus (SUDV) outbreak in Uganda was first detected in September 2022 and resulted in 164 laboratory-confirmed cases and 77 deaths. There are no approved vaccines against SUDV. Here, we investigated the protective efficacy of ChAdOx1-biEBOV in cynomolgus macaques using a prime or a prime-boost regimen.

Bivalent VSV Vectors Mediate Rapid and Potent Protection from Andes Virus Challenge in Hamsters.

Orthohantaviruses may cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Andes virus (ANDV) is the only orthohantavirus associated with human-human transmission. Therefore, emergency vaccination would be a valuable public health measure to combat ANDV-derived infection clusters.

Hisian Lead Electrical Decay After TAVR Intervention.

We report a case of patient with a single-chamber Hisian pacemaker who developed complete atrioventricular block and significant deterioration of the ventricular threshold and sensing after transcatheter aortic valve replacement. Revision of the implantation was required, with ventricular lead extraction and replacement.

Single-dose VSV-based vaccine protects against Kyasanur Forest disease in nonhuman primates.

Kyasanur Forest disease virus (KFDV) is an endemic arbovirus in western India mainly transmitted by hard ticks of the genus . KFDV causes Kyasanur Forest disease (KFD), a syndrome including fever, gastrointestinal symptoms, and hemorrhages. There are no approved treatments, and the efficacy of the only vaccine licensed in India has recently been questioned.

Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus.

Infection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in haemorrhagic disease and high case fatality rates (>40%) in humans. Despite its public health relevance, there are no licensed vaccines or therapeutics to prevent or treat MVD. A vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) is currently in clinical development.

Useful outcome measures in INPH patients evaluation.

Introduction: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder that is potentially reversible and clinically characterized by a specific triad of symptoms, including gait disturbance, cognitive disorders, and urinary incontinence. In INPH assessment, the most commonly used test is the Timed Up and Go test (TUG), but a more comprehensive assessment would be necessary. The first aim of the present study is to verify the sensitivity of a protocol with both clinical and instrumental outcome measures for gait and balance in recognizing INPH patients.

Perspectives on Advancing Countermeasures for Filovirus Disease: Report From a Multisector Meeting.

Although there are now approved treatments and vaccines for Ebola virus disease, the case fatality rate remains unacceptably high even when patients are treated with the newly approved therapeutics. Furthermore, these countermeasures are not expected to be effective against disease caused by other filoviruses. A meeting of subject-matter experts was held during the 10th International Filovirus Symposium to discuss strategies to address these gaps.