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.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Purpose: Tracheal resection with end-to-end anastomosis (TREE) has many advantages over conservative treatment in terms of long-term results; however, this method requires improved safety and accessibility. We aimed to combine expanded venovenous extracorporeal membrane oxygenation (ECMO) during TREE surgery. Materials and Methods: Between May 2006 and December 2022, 41 patients diagnosed with tracheal stenosis or tracheal tumors underwent TREE. The non-ECMO and ECMO groups were classified based on the presence or absence of intraoperative ECMO support. Results: Reconstruction length was slightly longer in the ECMO group than in the non-ECMO group, but there was no statistical significance (p=0.082). There was no significant difference between the two groups in terms of operative time (p=0.698), estimated blood loss (p=0.210), and duration of mechanical ventilation (p=0.713). There was a significant difference in intensive care unit stay between the two groups (p=0.013) due to the postoperative maintenance of ECMO. There were no cases of early mortality in either group during hospitalization (p>0.999). Conclusion ECMO support could assist in more challenging cases as it makes surgery easier in difficult patient scenarios.

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.

Purpose: To investigate ocular manifestation of immune reconstitution inflammatory syndrome (IRIS) in HIV patients after starting highly active antiretroviral therapy (HAART) and its relationship to T cell immunity. Methods: HIV patients with ocular IRIS after HAART were retrospectively reviewed. Clinical presentations with previous opportunistic infection, duration from initiation of HAART to IRIS, blood CD4+, CD8+ T cell count, and HIV RNA copies before HAART and at IRIS were analyzed. Results: Among 19 patients (27 eyes) included, the most common previous opportunistic infection was cytomegalovirus (17 patients, 89.5%) followed by tuberculosis choroiditis (2 patients, 10.5%). The clinical manifestations included vitritis (20 eyes, 74.0%), retinitis (14 eyes, 51.9%), and anterior uveitis (5 eyes, 18.5%). The median duration from initiation of HAART to IRIS was 70 days. CD4+ T cell count before HAART increased at IRIS (p < 0.001). CD8+ T cell count before HAART was negatively correlated with duration from HAART to IRIS (p < 0.001). The cutoff value of CD8+ T cell count for discerning early or late onset of ocular IRIS was 258/mm3 (p = 0.001). When divided into two groups by CD8+ T cell count of 258/mm3, 90% patients with CD8+ T cell count higher than 258/mm3 before HAART developed ocular IRIS within 70 days. Conclusions There was a negative relationship between CD8+ T cell count before HAART and duration from HAART to ocular IRIS. Ocular IRIS with higher CD8+ T cell count before HAART developed earlier after HAART initiation compared to those with lower CD8+ T cell count.

Purpose: Tracheal resection with end-to-end anastomosis (TREE) has many advantages over conservative treatment in terms of long-term results; however, this method requires improved safety and accessibility. We aimed to combine expanded venovenous extracorporeal membrane oxygenation (ECMO) during TREE surgery. Materials and Methods: Between May 2006 and December 2022, 41 patients diagnosed with tracheal stenosis or tracheal tumors underwent TREE. The non-ECMO and ECMO groups were classified based on the presence or absence of intraoperative ECMO support. Results: Reconstruction length was slightly longer in the ECMO group than in the non-ECMO group, but there was no statistical significance (p=0.082). There was no significant difference between the two groups in terms of operative time (p=0.698), estimated blood loss (p=0.210), and duration of mechanical ventilation (p=0.713). There was a significant difference in intensive care unit stay between the two groups (p=0.013) due to the postoperative maintenance of ECMO. There were no cases of early mortality in either group during hospitalization (p>0.999). Conclusion ECMO support could assist in more challenging cases as it makes surgery easier in difficult patient scenarios.

Purpose: To investigate ocular manifestation of immune reconstitution inflammatory syndrome (IRIS) in HIV patients after starting highly active antiretroviral therapy (HAART) and its relationship to T cell immunity. Methods: HIV patients with ocular IRIS after HAART were retrospectively reviewed. Clinical presentations with previous opportunistic infection, duration from initiation of HAART to IRIS, blood CD4+, CD8+ T cell count, and HIV RNA copies before HAART and at IRIS were analyzed. Results: Among 19 patients (27 eyes) included, the most common previous opportunistic infection was cytomegalovirus (17 patients, 89.5%) followed by tuberculosis choroiditis (2 patients, 10.5%). The clinical manifestations included vitritis (20 eyes, 74.0%), retinitis (14 eyes, 51.9%), and anterior uveitis (5 eyes, 18.5%). The median duration from initiation of HAART to IRIS was 70 days. CD4+ T cell count before HAART increased at IRIS (p < 0.001). CD8+ T cell count before HAART was negatively correlated with duration from HAART to IRIS (p < 0.001). The cutoff value of CD8+ T cell count for discerning early or late onset of ocular IRIS was 258/mm3 (p = 0.001). When divided into two groups by CD8+ T cell count of 258/mm3, 90% patients with CD8+ T cell count higher than 258/mm3 before HAART developed ocular IRIS within 70 days. Conclusions There was a negative relationship between CD8+ T cell count before HAART and duration from HAART to ocular IRIS. Ocular IRIS with higher CD8+ T cell count before HAART developed earlier after HAART initiation compared to those with lower CD8+ T cell count.

Purpose: Tracheal resection with end-to-end anastomosis (TREE) has many advantages over conservative treatment in terms of long-term results; however, this method requires improved safety and accessibility. We aimed to combine expanded venovenous extracorporeal membrane oxygenation (ECMO) during TREE surgery. Materials and Methods: Between May 2006 and December 2022, 41 patients diagnosed with tracheal stenosis or tracheal tumors underwent TREE. The non-ECMO and ECMO groups were classified based on the presence or absence of intraoperative ECMO support. Results: Reconstruction length was slightly longer in the ECMO group than in the non-ECMO group, but there was no statistical significance (p=0.082). There was no significant difference between the two groups in terms of operative time (p=0.698), estimated blood loss (p=0.210), and duration of mechanical ventilation (p=0.713). There was a significant difference in intensive care unit stay between the two groups (p=0.013) due to the postoperative maintenance of ECMO. There were no cases of early mortality in either group during hospitalization (p>0.999). Conclusion ECMO support could assist in more challenging cases as it makes surgery easier in difficult patient scenarios.

Purpose: To investigate ocular manifestation of immune reconstitution inflammatory syndrome (IRIS) in HIV patients after starting highly active antiretroviral therapy (HAART) and its relationship to T cell immunity. Methods: HIV patients with ocular IRIS after HAART were retrospectively reviewed. Clinical presentations with previous opportunistic infection, duration from initiation of HAART to IRIS, blood CD4+, CD8+ T cell count, and HIV RNA copies before HAART and at IRIS were analyzed. Results: Among 19 patients (27 eyes) included, the most common previous opportunistic infection was cytomegalovirus (17 patients, 89.5%) followed by tuberculosis choroiditis (2 patients, 10.5%). The clinical manifestations included vitritis (20 eyes, 74.0%), retinitis (14 eyes, 51.9%), and anterior uveitis (5 eyes, 18.5%). The median duration from initiation of HAART to IRIS was 70 days. CD4+ T cell count before HAART increased at IRIS (p < 0.001). CD8+ T cell count before HAART was negatively correlated with duration from HAART to IRIS (p < 0.001). The cutoff value of CD8+ T cell count for discerning early or late onset of ocular IRIS was 258/mm3 (p = 0.001). When divided into two groups by CD8+ T cell count of 258/mm3, 90% patients with CD8+ T cell count higher than 258/mm3 before HAART developed ocular IRIS within 70 days. Conclusions There was a negative relationship between CD8+ T cell count before HAART and duration from HAART to ocular IRIS. Ocular IRIS with higher CD8+ T cell count before HAART developed earlier after HAART initiation compared to those with lower CD8+ T cell count.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.