A possible role for proinflammatory activation via cGAS-STING pathway in atherosclerosis induced by accumulation of DNA double-strand breaks.

DNA damage contributes to atherosclerosis. However, causative links between DNA double-strand breaks (DSBs) and atherosclerosis have yet to be established. Here, we investigated the role of DSBs in atherosclerosis using mice and vascular cells deficient in Ku80, a DSB repair protein. After 4 weeks of a high-fat diet, Ku80-deficient apolipoprotein E knockout mice (Ku80+/-ApoE-/-) displayed increased plaque size and DSBs in the aorta compared to those of ApoE-/- control. In the preatherosclerotic stages (two-week high-fat diet), the plaque size was similar in both the Ku80+/-ApoE-/- and ApoE-/- control mice, but the number of DSBs and mRNA levels of inflammatory cytokines such as IL-6 and MCP-1 were significantly increased in the Ku80+/-ApoE-/- aortas. We further investigated molecular links between DSBs and inflammatory responses using vascular smooth muscle cells isolated from Ku80 wild-type and Ku80+/- mice. The Ku80+/- cells displayed senescent features and elevated levels of inflammatory cytokine mRNAs. Moreover, the cytosolic DNA-sensing cGAS-STING pathway was activated in the Ku80+/- cells. Inhibiting the cGAS-STING pathway reduced IL-6 mRNA level. Notably, interferon regulatory factor 3 (IRF3), a downstream effector of the cGAS-STING pathway, was activated, and the depletion of IRF3 also reduced IL-6 mRNA levels in the Ku80+/- cells. Finally, DSBs accumulation in normal cells also activated the cGAS-STING-IRF3 pathway. In addition, cGAS inhibition attenuated DNA damage-induced IL-6 expression and cellular senescence in these cells. These results suggest that DSBs accumulation promoted atherosclerosis by upregulating proinflammatory responses and cellular senescence via the cGAS-STING (-IRF3) pathway.

Effects of Hochuekkito on Physical Activity and Appetite in Postoperative Elderly Patients with Hip Fractures: A Randomized Controlled Trial.

Objectives: Hip fracture in the elderly involves two cases of invasive damage to the body within a short period of time: the fracture itself and subsequent surgery. This situation affects physical strength and presents a major challenge during convalescent rehabilitation. This study aimed to evaluate the effects of hochuekkito, a traditional Japanese herbal medicine, on physical activity, appetite, motivation, and quality of life (QOL) during inpatient rehabilitation treatment after hip surgery. Methods: Thirty-eight patients with hip fracture who underwent postoperative convalescent rehabilitation were randomly assigned to either the hochuekkito group (n=20, daily hochuekkito administration from day 3 after surgery until discharge from hospital) or the control group (n=18). Physical activity was measured with a small tri-axial accelerometer worn by the patients; appetite was evaluated based on daily dietary calorie consumption; motivation was measured using the vitality index score; and QOL was measured using the European QOL 5-Dimensions 5-Levels questionnaire and its associated EQ-visual analog scale (EQ-VAS). All patients were assessed at day 3 (baseline) and 2, 4, 6, 8, and 10 weeks after surgery and at the time of discharge from hospital. Results: The results for the hochuekkito group were significantly higher than the control group for walking exercise at 10 weeks, vigorous activity time at 8 weeks, dietary calorie consumption at 10 weeks and at discharge, and EQ-VAS score at 6 weeks. Conclusions: In elderly hip fracture patients, a course of hochuekkito administration starting soon after surgery significantly improved QOL, physical activity, and appetite at 6 weeks after surgery.

Does atrial fibrillation ablation worsen preexisting anemia? Another anemia paradox in DOAC era.

BACKGROUND: There is a concern about worsening anemia after atrial fibrillation (AF) ablation in anemic patients. We aimed to clarify whether or not patients with anemia who are on an oral anticoagulant therapy are more likely to lose blood after AF ablation. METHODS: We studied AF patients in 3 cardiovascular centers who skipped a single dose of a direct oral anticoagulant prior to the ablation, and compared the drop in the hemoglobin level 24 hours after the procedure and bleeding complications between the patients with and without preexisting anemia. RESULTS: We identified 183 (15.7%) patients with anemia at baseline out of 1163 patients. The reduction in the hemoglobin level (-0.39±0.71 vs. -0.93±0.9 g/dL; p<0.001) was smaller in the anemic than non-anemic patients. A fall in the hemoglobin level of ≥2 g/dL, which is a guideline-defined significant hemoglobin drop, was less common in anemic patients (1.6% vs. 11.3%; p<0.001). A female gender [odds ratio (OR) 1.62, confidence interval (CI) 1.07-2.45; p=0.02], persistent or long-standing persistent versus paroxysmal AF (OR 1.67, CI 1.13-2.49; p=0.01), ORBIT score ≥3 (OR 3.5, CI 1.34-8.94; p=0.01), and preexisting anemia (OR 0.02, CI 0.004-0.14; p<0.001) were independently associated with the fall in the hemoglobin level of ≥2 g/dL. No difference was noted in the rate of major bleeding complications (1.6% vs. 1.2%; p=0.72). CONCLUSIONS: Paradoxically, patients with preexisting anemia may be less likely to lose blood following AF ablation.

Acute aortic dissection combined with cardiac tamponade in an elderly patient saved by pericardial drainage: A case report.

Acute aortic dissection combined with cardiac tamponade is fatal. The radical treatment is an aortic replacement; however, the risk is high. We suggest conservative treatment with pericardial drainage as a treatment option in elderly patients with comorbidities.

Intra-procedural anticoagulation and post-procedural hemoglobin fall in atrial fibrillation ablation with minimally interrupted direct oral anticoagulants: comparisons across 4 drugs.

PURPOSE: Thromboembolic or hemorrhagic complications related to atrial fibrillation (AF) ablation are rare, and thus, it is difficult to compare their frequency across different direct oral anticoagulants (DOACs). We aimed to compare the intra-ablation blood coagulability and post-procedural hemoglobin fall as alternatives to those complications across 4 DOACs. METHODS: We enrolled AF patients younger than 65 years old in 3 cardiovascular centers who skipped a single dose of apixaban, dabigatran, edoxaban, and rivaroxaban, prior to the ablation. Endpoints included the activated clotting time (ACT), heparin requirement during the ablation, and drop in the hemoglobin level 24 h after the procedure. RESULTS: The time-course curves of the ACT differed significantly across the patients with apixaban (N = 113), dabigatran (N = 130), edoxaban (N = 144), and rivaroxaban (N = 81), with its highest level in the dabigatran group (P < 0.001). The average ACT was greater in the dabigatran group than in the other groups (312.3 ± 34, 334.4 ± 44, 308.1 ± 41, and 305.8 ± 34.7 s; P < 0.001). A significant difference was noted in total heparin requirement across the patient groups (3990.2 ± 1167.9, 3890.4 ± 955.3, 4423.8 ± 1051.6, and 3972 ± 978.7 U/m2/h; P < 0.001), with its greatest amount in the edoxaban group. The reduction in the hemoglobin level was similar (- 0.93 ± 0.92, - 0.88 ± 0.79, - 0.89 ± 0.97, - 0.95 ± 1.23 g/dL; P = 0.94). No inter-group difference was noted in the rate of major or minor bleedings (0.9%, 2.3%, 1.4%, and 3.7%; P = 0.51), and no thromboembolic events were encountered. CONCLUSION: A difference in DOACs may have an impact on intra-ablation anticoagulation; however, it may not be on the procedural blood loss in the setting of a single skip.