Cardiac Ct-Guided Exclusion of Left Atrial Appendage Thrombus Prior to Electrical Cardioversion for Atrial Fibrillation

Introduction: Transesophageal echo (TEE) is routinely used to exclude left atrial appendage (LAA) thrombus prior to direct current cardioversion (DCCV) for atrial fibrillation (AF). However, the COVID-19 pandemic accelerated the use of non-invasive modalities such as cardiac computed tomography (CCT) to avoid aerosolizing viral particles during intubation, such as with introduction of a TEE probe. CCT is not routinely used as a clinical strategy to exclude LAA thrombus prior to DCCV. Therefore, we sought to determine the feasibility of CCT-guided DCCV.Hypothesis: CCTguided elective cardioversion for atrial arrhythmias is a feasible modality to rule out left atrial appendage thrombus. Method(s): We identified patients at Abbott Northwestern Hospital who underwent CCT in lieu of or in addition to TEE within 24 hours of elective DCCV for AF or atrial flutter from March 2020 to February 2022. Thirty-day outcomes were collected including cerebrovascular accident (CVA), myocardial infarction, cardiovascular death, re-hospitalization, arrhythmia recurrence, and overall mortality. Delayed imaging, 90 seconds after arterial phase, was obtained to exclude LAA thrombus. Result(s): Thirty-two patients were included in our analysis, 10 (31%) were female. Ten (31%) presented with new-onset of AF. CCT did not identify LAA thrombus in any patient. Post-DCCV, the mean time to arrhythmia recurrence was 16.5 days (SD: 9.3). At 30 days, 11 (34%) had been rehospitalized but mostly for elective procedures. There was no CVA or mortality reported at the 30-day follow-up. Conclusion(s): CCT-guided elective cardioversion for atrial arrhythmias was evaluated for feasibility in a small pilot. In patients who had no LAA thrombus on CCT and subsequently underwent cardioversion, there were no CCT-related complications, CVA, or deaths at 30 days. Many patients benefit from early DCCV rather than waiting with uninterrupted anticoagulation. CCT guidance is a feasible alternative to TEE but needs further prospective comparison to TEE and uninterrupted anticoagulation in this clinical setting.

COVID-19 outcomes in fingolimod- or siponimod - treated patients: clinical trial and post marketing cases

Introduction: Understanding how immunomodulatory therapies influence COVID-19 outcomes in people living with multiple sclerosis (PlwMS) is vital to patients and physicians alike. Aims and Objective: Evaluate COVID-19 outcomes in PlwMS receiving either fingolimod or siponimod. Method(s): The Novartis clinical trial (CT) and safety databases were reviewed to identify confirmed (CT: confirmed if patient is SARS COV-2 positive;post-marketing [PM]: considered as reported) or suspected cases of COVID-19 in PlwMS receiving either fingolimod or siponimod (CT cut-off: fingolimod 04-Aug- 2021, siponimod 29-Oct-2021;PM cut-off: fingolimod 28-Feb- 2022, siponimod 25-Mar-2022). Result(s): For fingolimod, there were 1054 cases comprising of 45 suspected (PM=45) and 1009 confirmed cases (CT=9;PM=1,000) of COVID-19 (mean age in years: 17 [CT], 43 [PM];female: 71% [715/1009;CT=4, PM=711];male: 25% [254/1009;CT=5, PM=249] and not reported: 4% [40/1009;PM=40]). Of these, 35% (358/1009;CT=8, PM=349) were from Europe, 30% (305/1009;PM=305) from the US and 34% (347/1009;CT=1, PM=346) from the rest of the world (ROW). Hospitalisation was required for 13% of patients (130/1009;PM=130);1% (13/1009;PM=13) had a fatal outcome;and 43% (437/1009;CT=9, PM=428) recovered or were recovering at the most recent follow-up. For siponimod there were 321 cases comprising of 6 suspected (CT=1;PM=5) and 315 confirmed cases (CT=53;PM=262) of COVID-19 (mean age in years: 49 [CT], 53 [PM];female: 68% [214/315;CT=34, PM=180];male: 28% [88/315;CT=19, PM=69] and not reported: 4% [13/315;PM=13]). Of these, 53% (168/315;CT=6, PM=162) were from the US;30% (96/315;CT=46, PM=50) from Europe;and 16% (51/315;CT=1, PM=50) from the ROW. Hospitalisation was required for 19% of patients (60/315;CT=15, PM=45);2% (7/315;CT=3, PM=4) had a fatal outcome;and where information was provided 42% (131/315 CT=50, PM=81) recovered or were recovering at the most recent follow-up. Conclusion(s): Available data indicates that most COVID-19 cases among PlwMS treated with fingolimod or siponimod were nonserious. Among PlwMS exposed to disease-modifying therapies (DMTs), the reported hospitalisation and mortality rates are 12.8%-21.5% and 1.62%-3.5%, respectively (Reder et al 2021;Sormani et al 2022). Thus, hospitalisation and fatality rates with siponimod and fingolimod in these series of Novartis reported cases were similar to those observed in PlwMS on other DMTs.

Digital health literacy and well-being Results of a quantitative study among university students in Austria during the coronavirus pandemic

Background Previous findings suggest that depressive and anxiety-related symptoms have doubled among students since the beginning of the coronavirus pandemic. Digital health literacy can act as a protective resource to strengthen well-being. Objectives This paper analyzes the relationship between digital health literacy, socioeconomic status, well-being and future-anxiety among students in Austria. Methods A total of 480 students from Austrian higher education institutions were surveyed via online questionnaire during the second wave of the coronavirus pandemic. Sociodemographic data, students' self-assessments of well-being, fears about the future, and digital health literacy were collected. Variance and regression analyses were used for the evaluation. Results About 50% of the students reported low well-being and distinct fears about the future. Regarding digital health literacy, the ability to assess the relevance of information showed the highest correlation with well-being. A higher socioeconomic status correlated with higher well-being as well as lower fears about the future. Conclusions The assessment of the relevance of information and connecting it with one's own life reality seems to be an important factor in promoting well-being. Individual factors such as gender or the study program are relevant for the relationship between well-being and digital health literacy.

Hitting Pause: How User Perceptions of Collaborative Playlists Evolved in the United States During the COVID-19 Pandemic

Through collaborative playlists (CPs), streaming platform users have co-curated music together for various purposes for over a decade. As the COVID-19 pandemic has transformed how people come together through technology and engage with music, CPs have also taken on new roles and value. To understand how CP usage and perception have evolved since the onset of COVID-19, we conducted a mixed-methods investigation of CPs in the United States. Survey results from primarily CP users (N=142) revealed that interest in and usage of CPs have mostly increased since the pandemic, and that the role of music in connecting with others is positively correlated with the perceived impact of COVID-19. Follow-up interviews (N=9) provided additional insights into changing perceptions and usage patterns of CPs during COVID-19;for instance, fewer collaborators per playlist reflects users' greater focus on strengthening social connections and relationships. Taken together, findings and design implications on digitally mediated co-curation further elucidate the necessity for social and collaborative experiences with music supported by CPs during COVID-19. © 2022 ACM.

Use of a Key Drivers Diagram in preparation for COVID-19 at an urban, academic anesthesiology department

Background: The 2019 novel coronavirus pandemic has had a significant impact on anesthesiology practice globally. Its high infectivity and severity of onset has led to numerous examples of healthcare systems being overwhelmed, especially at its incipience. Drawing on experiences from previous pandemics, we anticipated that our Anesthesiology Department would be faced with unique challenges due to our proximity to airway maneuvers. We set out to intentionally strategize a quality improvement framework with which to guide our departmental response. Methods: We employed a Key Drivers Diagram (KDD) model to strategically account for the numerous novel quality improvement measures implemented simultaneously in response to the pandemic. Having identified areas of interest, measurable indices were identified, and dynamic progress assessed using run charts. These were (I) protect patients and staff, (II) keep up-to-date with evolving evidence, (III) maintain communication with department, (IV) keep staff engaged, and (V) align departmental goals with institutional aims. Results: Positive trends in staff engagement were identified across participation in educational activities such as guideline development, grand round attendance, and interdepartmental meetings. Conclusions: The KDD provided a valuable framework for managing parallel quality improvement processes. It enabled leadership to identify needs, measure adequacy of response and implement changes in a rapidly evolving environment. © Journal of Hospital Management and Health Policy. All rights reserved.

Quantum Dot-Conjugated SARS-CoV-2 Spike Pseudo-Virions Enable Tracking of Angiotensin Converting Enzyme 2 Binding and Endocytosis

The first step of SARS-CoV-2 infection is binding of the spike proteins receptor binding domain to the host cells ACE2 receptor on the plasma membrane. Here, we have generated a versatile imaging probe using recombinant Spike receptor binding domain conjugated to fluorescent quantum dots (QDs). This probe is capable of engaging in energy transfer quenching with ACE2-conjugated gold nanoparticles to enable monitoring of the binding event in solution. Neutralizing antibodies and recombinant human ACE2 blocked quenching, demonstrating a specific binding interaction. In cells transfected with ACE2-GFP, we observed immediate binding of the probe on the cell surface followed by endocytosis. Neutralizing antibodies and ACE2-Fc fully prevented binding and endocytosis with low nanomolar potency. Importantly, we will be able to use this QD nanoparticle probe to identify and validate inhibitors of the SARS-CoV-2 Spike and ACE2 receptor binding in human cells. This work enables facile, rapid, and high-throughput cell-based screening of inhibitors for coronavirus Spike-mediated cell recognition and entry.

Platelets contribute to disease severity in covid-19

Objective: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Platelets are key regulators of thrombosis, inflammation, immunity and are prime candidates for a role in the pathogenesis of COVID-19. The objective of this study was to analyze the platelet phenotype in COVID-19. Approach and Results: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detected in human megakaryocytes and platelets in COVID-19 patients and following incubation with the virus in vitro. We show a direct interaction between SARS-CoV-2 and megakaryocytes that alters the platelet transcriptome and platelet activity. COVID-19 platelets are hyperreactive and have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. We find transcriptomic changes mediated by SARS-CoV-2 do not occur following exposure of megakaryocytes with a coronavirus responsible for the common cold, CoV-OC43. In a cohort of 3,915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication use, and biomarkers of inflammation and thrombosis, platelet count, size, and immaturity are each associated with increased critical illness and all-cause mortality. Conclusions: Our findings demonstrate that SARS-CoV-2 virions invade megakaryocytes and platelets, inducing alterations to the platelet transcriptome and activation profile, which correlate with critical illness and mortality in hospitalized COVID-19 patients.

Effect of antiplatelet therapy on monocyte-platelet aggregates

Background : In addition to their role in thrombosis and hemostasis, platelets are key mediators of inflammation and altered immunity. Circulating monocyte-platelet aggregates (MPA) represent the crossroads between thrombosis and inflammation and may represent a therapeutic target. While antiplatelet therapy (APT) reduces platelet activity and thrombosis, its effect on MPA is uncertain. Aims : To analyze the effect of APT on MPA in vitro. Methods : The effect of different platelet-activating agonists (thromboxane analog U-46619, ADP, PAR4, collagen, and epinephrine) on MPA formation in whole blood (WB) was measured via flow cytometry. Agonist-stimulated WB was incubated in the presence of inhibitors against P-selectin, PSGL-1, PAR1 (ML161), P2Y12 (AZD1283), GPIIb/IIIa (eptifibatide), acetyl salicylic acid (ASA), and dipyridamole and assessed for MPA formation. RNA-Seq data sets of monocytes incubated with healthy platelet releasates (PR) were used to identify platelet-induced upregulation of monocyte transcripts and were validated by RT-qPCR in monocyte-PR co-incubation assays in the presence of APT. Results : Circulating MPA are increased in prothrombotic and inflammatory diseases including the most recent COVID-19. Monocytes aggregated to platelets have more CD40 and tissue factor expression than monocytes not aggregated to platelets ( P < 0.05 for each comparison). As expected, targeting P-selectin (85.4% reduction) and PSGL-1 (88.2% reduction) had the greatest attenuation of MPA. Among platelet inhibitors, P2Y12 inhibition was most effective in lowering MPA formation (30.7% reduction) (figure 1). Flow cytometry analysis of MPA. Incubation of monocytes with platelet releasate induced upregulation of inflammatory mRNA transcripts suppressor of cytokine signaling 3 ( SOCS3 ) and o ncostatin m ( OSM ). Following pretreatment of platelets with APT, both GPIIb/IIIa and P2Y12 inhibition was associated with lower expression of SOCS3 and OSM (figure 2) . SOCS3 and OSM in monocytes incubated with APT-treated PR. Conclusions : Circulating MPA represent a crossroad of platelet and monocyte activation. We show that APT is associated with both reduced MPA formation and platelet-induced monocyte activation.