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.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Purpose: This study investigated the impact of nusinersen on health-related quality of life (HRQoL), functional performance, and caregiver burden in patients with infantile-onset spinal muscular atrophy (SMA), addressing a growing interest in disease-modifying treatments. Methods: A 14-month observational study was conducted to evaluate changes in HRQoL and functional performance using the Pediatric Quality of Life Inventory (PedsQL) Infant Scales and the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT). Caregiver burden was assessed through the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). Motor function was evaluated using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Correlations between CHOP INTEND scores, functional performance, and caregiver burden were analyzed. Results: Eight patients with infantile-onset SMA and their caregivers participated, with a median treatment initiation age of 4.6 months (range, 1.1 to 15.1). CHOP INTEND scores showed significant improvement (P<0.001), whereas all PedsQL Infant Scale scores declined. Conversely, the PEDI-CAT revealed significant enhancements in daily activities, mobility, and social-cognitive domains (all P<0.001). Caregiver burden lessened across most dimensions (P<0.001), with the exception of the time-related burden (P=0.731). Higher CHOP INTEND scores correlated with improvements in PEDI-CAT domains and a reduction in caregiver burden related to sitting/play and transfer activities. Conclusion The study demonstrates the positive effects of nusinersen on functional performance and caregiver burden in patients with infantile-onset SMA. However, discrepancies were observed in HRQoL outcomes, suggesting a need for further research that includes SMA-specific outcome measures to comprehensively assess the treatment's impact on patients' lives.

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.

Objective: : Korea’s healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. Methods: : This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. Results: : Eighty-six thousand five hundred sixty-eight acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016, 2018, and between 2020 to 2021, focusing on acute subarachnoid hemorrhage (SAH), acute intracerebral hemorrhage (ICH), and acute ischemic stroke. Of these 86568 patients, 8.3% was SAH, 16.3% ICH, and 74.9% ischemic stroke. Trends showed decreasing SAH and increasing ICH cases over the years. 68.3% stroke patients had the clear onset time. 49.6% stroke patients arrived within 4.5 hours of symptom onset, with more patients treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of SAH patients, 34.6% of ICH patients, and 63.8% of ischemic stroke patients. Conclusion : The results showed that ischemic stroke was the most common subtype, followed by ICH and SAH. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and SAH compared to ICH.

Objective: : Korea’s healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. Methods: : This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. Results: : Eighty-six thousand five hundred sixty-eight acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016, 2018, and between 2020 to 2021, focusing on acute subarachnoid hemorrhage (SAH), acute intracerebral hemorrhage (ICH), and acute ischemic stroke. Of these 86568 patients, 8.3% was SAH, 16.3% ICH, and 74.9% ischemic stroke. Trends showed decreasing SAH and increasing ICH cases over the years. 68.3% stroke patients had the clear onset time. 49.6% stroke patients arrived within 4.5 hours of symptom onset, with more patients treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of SAH patients, 34.6% of ICH patients, and 63.8% of ischemic stroke patients. Conclusion : The results showed that ischemic stroke was the most common subtype, followed by ICH and SAH. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and SAH compared to ICH.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Purpose: This study investigated the impact of nusinersen on health-related quality of life (HRQoL), functional performance, and caregiver burden in patients with infantile-onset spinal muscular atrophy (SMA), addressing a growing interest in disease-modifying treatments. Methods: A 14-month observational study was conducted to evaluate changes in HRQoL and functional performance using the Pediatric Quality of Life Inventory (PedsQL) Infant Scales and the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT). Caregiver burden was assessed through the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). Motor function was evaluated using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Correlations between CHOP INTEND scores, functional performance, and caregiver burden were analyzed. Results: Eight patients with infantile-onset SMA and their caregivers participated, with a median treatment initiation age of 4.6 months (range, 1.1 to 15.1). CHOP INTEND scores showed significant improvement (P<0.001), whereas all PedsQL Infant Scale scores declined. Conversely, the PEDI-CAT revealed significant enhancements in daily activities, mobility, and social-cognitive domains (all P<0.001). Caregiver burden lessened across most dimensions (P<0.001), with the exception of the time-related burden (P=0.731). Higher CHOP INTEND scores correlated with improvements in PEDI-CAT domains and a reduction in caregiver burden related to sitting/play and transfer activities. Conclusion The study demonstrates the positive effects of nusinersen on functional performance and caregiver burden in patients with infantile-onset SMA. However, discrepancies were observed in HRQoL outcomes, suggesting a need for further research that includes SMA-specific outcome measures to comprehensively assess the treatment's impact on patients' lives.

Purpose: This study investigated the impact of nusinersen on health-related quality of life (HRQoL), functional performance, and caregiver burden in patients with infantile-onset spinal muscular atrophy (SMA), addressing a growing interest in disease-modifying treatments. Methods: A 14-month observational study was conducted to evaluate changes in HRQoL and functional performance using the Pediatric Quality of Life Inventory (PedsQL) Infant Scales and the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT). Caregiver burden was assessed through the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). Motor function was evaluated using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Correlations between CHOP INTEND scores, functional performance, and caregiver burden were analyzed. Results: Eight patients with infantile-onset SMA and their caregivers participated, with a median treatment initiation age of 4.6 months (range, 1.1 to 15.1). CHOP INTEND scores showed significant improvement (P<0.001), whereas all PedsQL Infant Scale scores declined. Conversely, the PEDI-CAT revealed significant enhancements in daily activities, mobility, and social-cognitive domains (all P<0.001). Caregiver burden lessened across most dimensions (P<0.001), with the exception of the time-related burden (P=0.731). Higher CHOP INTEND scores correlated with improvements in PEDI-CAT domains and a reduction in caregiver burden related to sitting/play and transfer activities. Conclusion The study demonstrates the positive effects of nusinersen on functional performance and caregiver burden in patients with infantile-onset SMA. However, discrepancies were observed in HRQoL outcomes, suggesting a need for further research that includes SMA-specific outcome measures to comprehensively assess the treatment's impact on patients' lives.