Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell–derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster.Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.