Efficacy and Safety of Warfarin for the Treatment of Venous Thromboembolism　- A Multicenter Prospective Observational Cohort Study in Japan (AKAFUJI Study).

BACKGROUND: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer. CONCLUSIONS: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Water Distribution Changes in Complex Decongestive Treatment for Leg Lymphedema: Quantitative Evaluation by Direct Segmental Multi-Frequency Bioimpedance Analysis.

Background: There is a need for a simple method for the quantitative evaluation of lymphedema swelling. In this study, we performed a direct segmental multi-frequency impedance analysis in patients with leg lymphedema. Methods: The subjects were 36 patients (6 men and 30 women) with 46 lymphedema legs. The average age was 61 years. All patients had International Society of Lymphology stage II lymphedema. Swelling ratio and ultrasound subcutaneous tissue echo-free space (FS) were examined. InBody 770 was used to measure the extracellular water (ECW), intracellular water (ICW), and total body water (TBW) volumes. Changes before and after complex decongestive treatment (CDT) were examined. Results: In 26 unilateral cases, the ECW, ICW, and TBW volumes of the affected legs were higher than those of the contralateral unaffected legs, and the ECW/TBW ratio was significantly higher in the affected legs (0.41) than in the contralateral unaffected legs (0.391). There was a significant correlation between the leg swelling ratio and the ECW/TBW ratio between the affected and contralateral unaffected legs (correlation coefficient=0.882). Ultrasound findings of the 46 affected legs were classified into no FS (group 0), minimal or only horizontal FS (group 1), and cobblestone-like FS (group 2). The ECW/TBW ratio of the affected legs in each group was 0.393 (14 legs), 0.407 (10 legs), and 0.426 (22 legs) respectively, demonstrating significant differences among the 3 groups. After CDT, the amount of water decreased in the affected legs and increased in the trunks and both upper limbs. The ECW/TBW ratio decreased significantly, from 0.432 to 0.414 in the affected legs, from 0.401 to 0.392 in the unaffected legs, and from 0.413 to 0.402 in the trunks. The ECW/TBW ratio had not changed and remained below 0.4 in the upper limbs. Conclusion: The segmental water contents measured by direct segmental multi-frequency impedance analysis correlates well with the degree of lymphedema swelling, and subcutaneous echo findings and can demonstrate water distribution change before and after CDT, which is considered to be a useful quantitative evaluation method for lymphedema. (This is secondary publication from Jpn J Phlebol 2020; 31(1): 1-7.).

The Beneficial Effects of Astaxanthin on Glucose Metabolism and Modified Low-Density Lipoprotein in Healthy Volunteers and Subjects with Prediabetes.

Astaxanthin (ASTX) is an antioxidant agent. Recently, its use has been focused on the prevention of diabetes and atherosclerosis. We examined the effects of astaxanthin supplementation for 12 weeks on glucose metabolism, glycemic control, insulin sensitivity, lipid profiles and anthropometric indices in healthy volunteers including subjects with prediabetes with a randomized, placebo-controlled trial. METHODS: We enrolled 53 subjects who met our inclusion criteria and administered them with 12 mg astaxanthin or a placebo once daily for 12 weeks. Subsequently, their HbA1c levels, lipid profiles and biochemical parameters were determined. The participants also underwent a 75 g oral glucose tolerance test (OGTT), vascular endothelial function test and measurement of the visceral fat area. RESULTS: After astaxanthin supplementation for 12 weeks, glucose levels after 120 min in a 75 g OGTT significantly decreased compared to those before supplementation. Furthermore, the levels of HbA1c (5.64 ± 0.33 vs. 5.57 ± 0.39%, p < 0.05), apo E (4.43 ± 1.29 vs. 4.13 ± 1.24 mg/dL, p < 0.05) and malondialdehyde-modified low-density lipoprotein (87.3 ± 28.6 vs. 76.3 ± 24.6 U/L, p < 0.05) were also reduced, whereas total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-C (HDL-C) levels were unaltered. The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. CONCLUSIONS: our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.

Three-dimensional architecture of elastin and collagen fiber networks in the human and rat lung.

Collagen and elastin fibers are the major components of the lung connective tissue, but their spatial organization has not been well documented. We have demonstrated the three-dimensional architecture of collagen and elastin fiber networks in the human and rat lung using scanning electron microscopy. These networks in their original forms were extracted by an alkali-water maceration technique and a formic acid treatment, respectively. The collagen fibers formed a continuum extending throughout the lung and pleura. They were condensed in the alveolar mouth and subdivided into smaller fibers in the alveolar septa, thus forming basket-like networks. Sizes of the alveolar pores in the collagen fiber network of the alveolar septa became larger with age. In the collapsed lung, collagen fibers in the alveolar mouths and septa took on wavelike configurations, while in the inflated lung they became straight. The elastin fibers also formed a continuum, rich in the alveolar mouths and poor in the alveolar septa, were quite straight without any wavelike configuration. Transmission electron microscopy showed that collagen and elastin fibers were intermingled, suggesting that both fiber systems may act as parallel mechanical elements to stress or strain applied. Our results suggest that at low levels of strain the wavy collagen fibers are easily extended to allow alveolar mouths and alveoli to expand, with most of the stress being borne by adjacent elastin fibers, while at higher levels collagen fibers become straight and limit any further distension of alveolar ducts and alveoli. The elastin fiber continuum appears to permit the lung to effectively recoil or retract. The present study has also shown that alveolar pores enlarge with age, suggesting that collagen remodeling may be related to the pathogenesis of emphysema.