Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 3 2025 Prospective Evaluation of the Safety and Compression Performance of Novel Compression Denim Jeans in Healthy Volunteers and Patients With Lymphedema e80971 EN Daiki Ousaka Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Yamada Departments of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Sakano Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Kirino Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Miyake Department of Rehabilitation, Lymphedema Treatment Center, Kousei Hospital Takumi Takahashi Division of Business Management, Matsuoka Corporation Akihiro Matsuoka Division of Production Engineering, Matsuoka Corporation Shintaro Yamada Division of Sales, Kaihara Corporation Akira Shinaoka Department of Lymphatics and Edematology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Oozawa Department of Clinical Safety, Okayama University Hospital Objectives: The treatment of lower-extremity lymphedema, whether congenital or acquired, remains challenging. Long-term management aimed at reducing complications and maximizing quality of life is essential. Compression stockings are crucial in this management; however, their application is limited by patient experience (ease of wear, texture, breathability, and appearance). This highlights the need to evaluate alternative compression garments that maintain therapeutic efficacy while improving patient adherence.<br> Methods: We developed a novel compression denim product (Flow plus Jeans®) using advanced sewing technology. Its baseline performance (compression ability) was evaluated by measuring pressure gradients at three points (ankle, calf, and thigh) using a mannequin-based compression testing system and compared with those of existing stockings. Thereafter, a safety assessment was conducted on healthy volunteers to evaluate potential adverse effects, including changes in lower limb circumference, signs of deep vein thrombosis (DVT) via ultrasound, and skin complications. A clinical trial in patients with lymphedema was then performed to compare its efficacy with that of conventional compression stockings.<br> Results: Baseline performance testing with a mannequin revealed that Flow plus Jeans demonstrated compression levels and pressure gradients at three calf points comparable to those of standard compression stockings. A safety study involving nine healthy volunteers confirmed that Flow plus Jeans caused no significant changes in lower-limb circumferences after three days of wear, with no cases of DVT or skin complications. In a subsequent clinical trial involving nine female patients with lymphedema, the jeans showed non-inferiority to existing stockings concerning lower-limb circumference measurements at six points (pre-use vs. six months post-use), with patient-reported experiences assessed via questionnaires. Notably, patients reported enhanced satisfaction regarding the jeans' fashionability, which could serve as an incentive for long-term adherence.<br> Conclusion: Our findings suggest that Flow plus Jeans represent a promising novel option for the long-term management of lymphedema, offering an alternative that balances medical efficiency with improved patient satisfaction and demonstrates safety in healthy individuals. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Lymphatic flow dynamics under exercise load assessed with thoracic duct ultrasonography 14323 EN Akira Shinaoka Department of Lymphatics and Edematology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yoshihiro Kimata Department of Plastic and Reconstructive surgery, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine The thoracic duct (TD) is the largest lymphatic vessel proximal to the venous system. It undergoes morphological changes in response to lymph flow from the periphery, with automatic contraction controlling the dynamics to propel lymph toward the venous system. Recent advancements in ultrasonography have facilitated non-invasive observations of the TD�fs terminal, including its valve and wall motions. Observations of TD movements allow predictions of lymphatic flow dynamics. However, no studies have yet documented the changes in the TD under exercise-induced lymph flow enhancement in humans. Here, using 18-MHz high-frequency ultrasonography, we demonstrate for the first time that the TD diameter significantly expands under exercise load. This study analyzed 20 participants; the maximum TD diameters at rest and post-exercise were 2.69 �} 1.06 mm and 3.41 �} 1.32 mm, respectively (p = 0.00000056). While various methods exist for observing the TD, our approach�\dynamically monitoring the TD diameter using sonography in real time and correlating it with lymphatic flow dynamics�\offers a novel contribution. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1447-6959 99 2 2023 A new lymphography protocol and interpretation principles based on functional lymphatic anatomy in lower limb lymphedema 153 158 EN Akira Shinaoka Department of Lymphatics and Edematology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Indirect lymphatic system imaging is essential for diagnosing lymphatic diseases. The basic methodology involves intradermal or subcutaneous injection of a contrast agent into the surrounding lymphatic capillary, and the flow of the contrast agent is identified using a detector. Many contrast agents that use near-infrared dye, including indocyanine green (ICG) fluorescent lymphography, are available. ICG is rapidly spreading as a convenient and safe lymphedema diagnostic method, because it does not involve radiation exposure, and the imaging equipment is more compact than other devices. The lymphatic system is a semi-open circulatory system with numerous lymphatic capillaries acting as blind ends. Anatomical information on the injection site and observation of specific lymphatic vessels and nodes is important. However, this anatomical information is lacking. Recent reports suggest that ICG fluorescent lymphography can be applied to cadavers in the same manner as living bodies. Furthermore, these reports have demonstrated the functional aspects of the capillary lymph vessel networks as well as their relationship with lymphatic vessels and lymph nodes. This review article describes the historical progression from the old to the new functional lymphatic anatomy and introduces a new functional lymphography technique for the lower limbs. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 12 1 2022 A new severity classification of lower limb secondary lymphedema based on lymphatic pathway defects in an indocyanine green fluorescent lymphography study 309 EN Akira Shinaoka Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuyo Kamiyama Department of Nursing, Kagawa Prefectural Central Hospital Kiyoshi Yamada Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Most protocols for lymphatic imaging of the lower limb conventionally inject tracer materials only into the interdigital space; however, recent studies indicate that there are four independent lymphatic vessel groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limb. Thus, three additional injection sites are needed for lymphatic imaging of the entire lower limb. We aimed to validate a multiple injection designed protocol and demonstrate its clinical benefits. Overall, 206 lower limbs undergoing indocyanine green fluorescent lymphography with the new injection protocol were registered retrospectively. To assess the influence of predictor variables on the degree of severity, multivariable logistic regression models were used with individual known risk factors. Using a generalized linear model, the area under the curve (AUC) of the conventional clinical model, comprising known severity risk factors, was compared with that of the modified model that included defects in the posterolateral and posteromedial groups. Multivariable logistic regression models showed a significant difference for the posteromedial and posterolateral groups. The AUC of the modified model was significantly improved compared to that of the conventional clinical model. Finding defects in the posteromedial and posterolateral groups is a significant criterion for judging lymphedema severity and introducing a new lymphedema severity classification. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2451-8654 19 2020 HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema 100595 EN Shinsuke Akita Department of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine Naoki Unno Department of Vascular Surgery, Hamamatsu Medical Center Jiro Maegawa Department of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of Medicin Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hidekazu Fukamizu Department of Plastic and Reconstructive Surgery, Hamamatsu University School of Medicine Yuichiro Yabuki Department of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of Medicine Akira Shinaoka Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masaki Sano Second Department of Surgery, Hamamatsu University School of Medicine Yohei Kawasaki Clinical Research Center, Chiba University Hospital Tadami Fujiwara Clinical Research Center, Chiba University Hospital Hideki Hanaoka Clinical Research Center, Chiba University Hospital Nobuyuki Mitsukawa Department of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine Introduction</br> Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery.</br> Methods and analysis</br> This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy�\one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA.</br> Ethics and dissemination</br> The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 00144827 383 2 2019 Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1 111556 EN Takashi Ohtsuki Department of Medical Technology, Graduate School of Health Sciences, Okayama University Akira Shinaoka Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kanae Kumagishi-Shinaoka Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichi Asano Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Omer Faruk Hatipoglu Department of Medical Technology, Graduate School of Health Sciences, Okayama University Junko Inagaki Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Takahashi Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiji Naruse Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1ƒÀ and tumor necrosis factor (TNF)-ƒ¿-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor ƒÈB (NF-ƒÈB) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA. No potential conflict of interest relevant to this article was reported.