WADA TAKESHI
| Faculty of Medicine Surgery Anesthesiology and Critical Care Medicine | Professor |
| Hokkaido University Hospital | Professor |
Last Updated :2025/06/07
■Researcher basic information
Researchmap personal page
Home Page URL
Researcher number
- 30455646
J-Global ID
Research Keyword
Educational Organization
- Bachelor's degree program, Departments of Medicine, School of Medicine
- Master's degree program, Graduate School of Medicine
- Doctoral (PhD) degree program, Graduate School of Medicine
■Career
Career
- Jul. 2024 - Present
北海道大学大学院医学研究院, 侵襲制御医学分野 救急医学教室, 教授 - Aug. 2020 - Jun. 2024
北海道大学大学院医学研究院, 侵襲制御医学講座救急医学教室, 助教 - Apr. 2019 - Jul. 2020
Hokkaido University, Hokkaido University Hospital, 助教 - Apr. 2013 - Mar. 2019
Hokkaido University, 先進急性期医療センター救急科, 助教 - Dec. 2016 - Feb. 2018
Brigham & Women's Hospital/Harvard Medical School,, Department of Surgery,, Research fellow - Apr. 2010 - Mar. 2013
Nippon Medical School, Medical School, 助教・医員 - Apr. 2007 - Mar. 2010
Hokkaido University, 先進急性期医療センター救急科, 医員
Committee Memberships
- Jan. 2023 - Present
日本救急医学会, 脳死・臓器組織移植に関する委員会 - Apr. 2022 - Present
日本救急医学会, 学会主導研究評価特別委員会 - Apr. 2021 - Present
日本救急医学会, 教育・統括委員会委員 - Apr. 2021 - Present
日本救急医学会, 評議員 - Apr. 2020 - Present
日本救急医学会, 多施設共同試験特別委員会 - Apr. 2020 - Present
日本集中治療医学会, 評議員 - Oct. 2019 - Present
日本脳神経外傷学会, 学術評議員, Society - Apr. 2019 - Present
日本外傷学会, 評議員, Society - Sep. 2019 - Aug. 2023
International Society on Thrombosis & Haemostasis, Co-chair (Scientific and Standardization Committee on Disseminated Intravascular Coagulation), Society
■Research activity information
Papers
- The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024.
Nobuaki Shime, Taka-Aki Nakada, Tomoaki Yatabe, Kazuma Yamakawa, Yoshitaka Aoki, Shigeaki Inoue, Toshiaki Iba, Hiroshi Ogura, Yusuke Kawai, Atsushi Kawaguchi, Tatsuya Kawasaki, Yutaka Kondo, Masaaki Sakuraya, Shunsuke Taito, Kent Doi, Hideki Hashimoto, Yoshitaka Hara, Tatsuma Fukuda, Asako Matsushima, Moritoki Egi, Shigeki Kushimoto, Takehiko Oami, Kazuya Kikutani, Yuki Kotani, Gen Aikawa, Makoto Aoki, Masayuki Akatsuka, Hideki Asai, Toshikazu Abe, Yu Amemiya, Ryo Ishizawa, Tadashi Ishihara, Tadayoshi Ishimaru, Yusuke Itosu, Hiroyasu Inoue, Hisashi Imahase, Haruki Imura, Naoya Iwasaki, Noritaka Ushio, Masatoshi Uchida, Michiko Uchi, Takeshi Umegaki, Yutaka Umemura, Akira Endo, Marina Oi, Akira Ouchi, Itsuki Osawa, Yoshiyasu Oshima, Kohei Ota, Takanori Ohno, Yohei Okada, Hiromu Okano, Yoshihito Ogawa, Masahiro Kashiura, Daisuke Kasugai, Ken-Ichi Kano, Ryo Kamidani, Akira Kawauchi, Sadatoshi Kawakami, Daisuke Kawakami, Yusuke Kawamura, Kenji Kandori, Yuki Kishihara, Sho Kimura, Kenji Kubo, Tomoki Kuribara, Hiroyuki Koami, Shigeru Koba, Takehito Sato, Ren Sato, Yusuke Sawada, Haruka Shida, Tadanaga Shimada, Motohiro Shimizu, Kazushige Shimizu, Takuto Shiraishi, Toru Shinkai, Akihito Tampo, Gaku Sugiura, Kensuke Sugimoto, Hiroshi Sugimoto, Tomohiro Suhara, Motohiro Sekino, Kenji Sonota, Mahoko Taito, Nozomi Takahashi, Jun Takeshita, Chikashi Takeda, Junko Tatsuno, Aiko Tanaka, Masanori Tani, Atsushi Tanikawa, Hao Chen, Takumi Tsuchida, Yusuke Tsutsumi, Takefumi Tsunemitsu, Ryo Deguchi, Kenichi Tetsuhara, Takero Terayama, Yuki Togami, Takaaki Totoki, Yoshinori Tomoda, Shunichiro Nakao, Hiroki Nagasawa, Yasuhisa Nakatani, Nobuto Nakanishi, Norihiro Nishioka, Mitsuaki Nishikimi, Satoko Noguchi, Suguru Nonami, Osamu Nomura, Katsuhiko Hashimoto, Junji Hatakeyama, Yasutaka Hamai, Mayu Hikone, Ryo Hisamune, Tomoya Hirose, Ryota Fuke, Ryo Fujii, Naoki Fujie, Jun Fujinaga, Yoshihisa Fujinami, Sho Fujiwara, Hiraku Funakoshi, Koichiro Homma, Yuto Makino, Hiroshi Matsuura, Ayaka Matsuoka, Tadashi Matsuoka, Yosuke Matsumura, Akito Mizuno, Sohma Miyamoto, Yukari Miyoshi, Satoshi Murata, Teppei Murata, Hiromasa Yakushiji, Shunsuke Yasuo, Kohei Yamada, Hiroyuki Yamada, Ryo Yamamoto, Ryohei Yamamoto, Tetsuya Yumoto, Yuji Yoshida, Shodai Yoshihiro, Satoshi Yoshimura, Jumpei Yoshimura, Hiroshi Yonekura, Yuki Wakabayashi, Takeshi Wada, Shinichi Watanabe, Atsuhiro Ijiri, Kei Ugata, Shuji Uda, Ryuta Onodera, Masaki Takahashi, Satoshi Nakajima, Junta Honda, Tsuguhiro Matsumoto
Journal of intensive care, 13, 1, 15, 15, 14 Mar. 2025, [International Magazine]
English, The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions. - Utility of sepsis-induced coagulopathy among disseminated intravascular coagulation diagnostic criteria: A multicenter retrospective validation study.
Satoshi Gando, Takeshi Wada, Kazuma Yamakawa, Toshikazu Abe, Seitato Fujishima, Shigeki Kushimoto, Toshihiko Mayumi, Hiroshi Ogura, Daizoh Saitoh, Atsushi Shiraishi, Yutaka Umemura, Yasuhiro Otomo
Thrombosis and haemostasis, 03 Feb. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: The criteria for diagnosing sepsis-induced coagulopathy (SIC) may overlap with those of Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC). We aimed to determine if the diagnostic criteria for SIC overlap with those for the JAAM DIC diagnosis of International Society on Thrombosis and Haemostasis (ISTH) DIC and whether patients have the same prognosis when diagnosed using these criteria. METHODS: This multicenter retrospective study included patients with sepsis diagnosed using the JAAM and ISTH DIC and SIC criteria on days 1 and 4. The established ISTH DIC criteria was reference standard for primary outcome that compared the characteristics of SIC and JAAM DIC. Secondary outcomes were multiple organ dysfunction syndrome (MODS), ventilator- and intensive care unit-free days, and in-hospital mortality. RESULTS: A total of 1,438 patients were included in this study. On day 1, the JAAM DIC and SIC criteria diagnosed almost all patients with ISTH DIC (98% and 94%, respectively), predicting ISTH DIC (area under the receiver operating curve [AUC]: 0.740 vs. 0.752, P = 0.523) and MODS (AUC: 0.686 vs. 0.697, P = 0.546) on day 4 and progressing to ISTH DIC in the same proportion (28.6 vs. 30.1%, P = 0.622). There were no differences in survival probabilities (P = 0.196) or secondary outcomes between patients diagnosed using JAAM DIC and SIC criteria on day 1. CONCLUSION: SIC and JAAM DIC diagnoses were equal among patients with sepsis, suggesting that SIC criteria add little to current DIC scoring systems. - 特有の病態と治療 播種性血管内凝固症候群の診断と治療
高橋 正樹, 和田 剛志
集中治療医学レビュー, 2025-'26, 279, 285, (株)総合医学社, Feb. 2025
Japanese - Disseminated intravascular coagulation is associated with a poor outcome in patients with out-of-hospital cardiac arrest receiving VA-ECMO.
Satoshi Gando, Takumi Tsuchida, Takeshi Wada
Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs, 06 Jan. 2025, [Domestic magazines]
English, Scientific journal, We tested the hypothesis that disseminated intravascular coagulation (DIC) predicts a poor prognosis in patients with out-of-hospital cardiac arrest (OHCA) treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Fifty-seven patients with cardiogenic OHCA who immediately underwent VA-ECMO upon admission to the emergency department were divided into 27 non-DIC and 30 DIC patients. DIC scores were calculated on admission and 24 h later (day 1). The primary outcome measure was the all-cause in-hospital mortality. The basic characteristics did not differ between the two groups; however, patients with DIC showed higher in-hospital mortality rates. Receiver operating characteristic curve analysis showed a moderate predictive ability of DIC scores on day 1 for in-hospital mortality. A lower probability of survival was observed in patients with DIC. The adjusted odds ratio for DIC on day 1 of in-hospital death was 5.67, confirmed by the adjusted hazard ratio of 3.472. The results indicate an association between DIC diagnosis 24 h following VA-ECMO induction for OHCA and poor outcome in these patients. - The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024.
Nobuaki Shime, Taka-Aki Nakada, Tomoaki Yatabe, Kazuma Yamakawa, Yoshitaka Aoki, Shigeaki Inoue, Toshiaki Iba, Hiroshi Ogura, Yusuke Kawai, Atsushi Kawaguchi, Tatsuya Kawasaki, Yutaka Kondo, Masaaki Sakuraya, Shunsuke Taito, Kent Doi, Hideki Hashimoto, Yoshitaka Hara, Tatsuma Fukuda, Asako Matsushima, Moritoki Egi, Shigeki Kushimoto, Takehiko Oami, Kazuya Kikutani, Yuki Kotani, Gen Aikawa, Makoto Aoki, Masayuki Akatsuka, Hideki Asai, Toshikazu Abe, Yu Amemiya, Ryo Ishizawa, Tadashi Ishihara, Tadayoshi Ishimaru, Yusuke Itosu, Hiroyasu Inoue, Hisashi Imahase, Haruki Imura, Naoya Iwasaki, Noritaka Ushio, Masatoshi Uchida, Michiko Uchi, Takeshi Umegaki, Yutaka Umemura, Akira Endo, Marina Oi, Akira Ouchi, Itsuki Osawa, Yoshiyasu Oshima, Kohei Ota, Takanori Ohno, Yohei Okada, Hiromu Okano, Yoshihito Ogawa, Masahiro Kashiura, Daisuke Kasugai, Ken-Ichi Kano, Ryo Kamidani, Akira Kawauchi, Sadatoshi Kawakami, Daisuke Kawakami, Yusuke Kawamura, Kenji Kandori, Yuki Kishihara, Sho Kimura, Kenji Kubo, Tomoki Kuribara, Hiroyuki Koami, Shigeru Koba, Takehito Sato, Ren Sato, Yusuke Sawada, Haruka Shida, Tadanaga Shimada, Motohiro Shimizu, Kazushige Shimizu, Takuto Shiraishi, Toru Shinkai, Akihito Tampo, Gaku Sugiura, Kensuke Sugimoto, Hiroshi Sugimoto, Tomohiro Suhara, Motohiro Sekino, Kenji Sonota, Mahoko Taito, Nozomi Takahashi, Jun Takeshita, Chikashi Takeda, Junko Tatsuno, Aiko Tanaka, Masanori Tani, Atsushi Tanikawa, Hao Chen, Takumi Tsuchida, Yusuke Tsutsumi, Takefumi Tsunemitsu, Ryo Deguchi, Kenichi Tetsuhara, Takero Terayama, Yuki Togami, Takaaki Totoki, Yoshinori Tomoda, Shunichiro Nakao, Hiroki Nagasawa, Yasuhisa Nakatani, Nobuto Nakanishi, Norihiro Nishioka, Mitsuaki Nishikimi, Satoko Noguchi, Suguru Nonami, Osamu Nomura, Katsuhiko Hashimoto, Junji Hatakeyama, Yasutaka Hamai, Mayu Hikone, Ryo Hisamune, Tomoya Hirose, Ryota Fuke, Ryo Fujii, Naoki Fujie, Jun Fujinaga, Yoshihisa Fujinami, Sho Fujiwara, Hiraku Funakoshi, Koichiro Homma, Yuto Makino, Hiroshi Matsuura, Ayaka Matsuoka, Tadashi Matsuoka, Yosuke Matsumura, Akito Mizuno, Sohma Miyamoto, Yukari Miyoshi, Satoshi Murata, Teppei Murata, Hiromasa Yakushiji, Shunsuke Yasuo, Kohei Yamada, Hiroyuki Yamada, Ryo Yamamoto, Ryohei Yamamoto, Tetsuya Yumoto, Yuji Yoshida, Shodai Yoshihiro, Satoshi Yoshimura, Jumpei Yoshimura, Hiroshi Yonekura, Yuki Wakabayashi, Takeshi Wada, Shinichi Watanabe, Atsuhiro Ijiri, Kei Ugata, Shuji Uda, Ryuta Onodera, Masaki Takahashi, Satoshi Nakajima, Junta Honda, Tsuguhiro Matsumoto
Acute medicine & surgery, 12, 1, e70037, 2025, [International Magazine]
English, Scientific journal, The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions. - The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024
伸朗 志馬, 孝明 中田, 智昭 矢田部, 一馬 山川, 善孝 青木, 茂亮 井上, 敏明 射場, 裕司 小倉, 佑亮 河合, 敦 川口, 達也 川崎, 豊 近藤, 正明 櫻谷, 俊介 對東, 研人 土井, 英樹 橋本, 嘉孝 原, 龍将 福田, 麻子 松嶋, 盛時 江木, 成樹 久志本, 毅彦 大網, 知也 菊谷, 玄 相川, 誠 青木, 正幸 赤塚, 英樹 淺井, 智一 阿部, 優 雨宮, 嶺 石澤, 唯史 石原, 忠賢 石丸, 佑介 糸洲, 拓保 井上, 尚史 今長谷, 春樹 井村, 直也 岩崎, 典敬 生塩, 雅俊 内田, 倫子 内, 岳志 梅垣, 穣 梅村, 彰 遠藤, 真里奈 大井, 玲 大内, 樹輝 大沢, 良康 大島, 浩平 太田, 孝則 大野, 遥平 岡田, 弘 岡野, 新史 小川, 正広 柏浦, 大介 春日井, 謙一 狩野, 遼 上谷, 章 河内, 定俊 川上, 大裕 川上, 雄介 川村, 研二 神鳥, 悠貴 岸原, 翔 木村, 健児 久保, 知己 栗原, 博之 小網, 祐樹 小谷, 茂 木庭, 威仁 佐藤, 蓮 佐藤, 悠輔 澤田, 瑶 志田, 忠長 島田, 元洋 志水, 一茂 清水, 拓人 白石, 達 新貝, 亜希仁 丹保, 岳 杉浦, 健輔 杉本, 裕史 杉本, 朋宏 壽原, 元裕 関野, 健司 其田, 真帆子 對東, 希 高橋, 淳 竹下, 親宗 武田, 淳子 立野, 愛子 田中, 昌憲 谷, 篤 谷河, 昊 陳, 拓見 土田, 悠介 堤, 健史 恒光, 亮 出口, 健一 鉄原, 毅郎 寺山, 由貴 戸上, 崇彰 十時, 吉則 友田, 俊一郎 中尾, 宏樹 長澤, 安寿 中谷, 信人 中西, 典宏 西岡, 満暁 錦見, 智子 野口, 豪 野浪, 理 野村, 克彦 橋本, 淳司 畠山, 康貴 濵井, 麻由 彦根, 遼 久宗, 智也 廣瀬, 良太 福家, 遼 藤井, 直輝 藤江, 潤 藤永, 好寿 藤浪, 翔 藤原, 拓 舩越, 康一郎 本間, 佑斗 牧野, 裕司 松浦, 綾華 松岡, 義 松岡, 洋輔 松村, 彰人 水野, 颯真 宮本, ゆかり 三好, 慧 村田, 哲平 村田, 泰匡 薬師寺, 俊祐 安尾, 浩平 山田, 博之 山田, 良 山元, 良平 山本, 哲也 湯本, 裕治 吉田, 尚大 吉廣, 聡志 吉村, 旬平 吉村, 寛 米倉, 侑起 若林, 剛志 和田, 伸一 渡辺, 篤宏 井尻, 圭 宇賀田, 周司 宇田, 隆太 小野寺, 正樹 高橋, 聡志 中島, 純太 本多, 承大 松本
Journal of the Japanese Society of Intensive Care Medicine, 31, Supplement, S1165, S1313, Japanese Society of Intensive Care Medicine, 25 Dec. 2024
Scientific journal - 日本版敗血症診療ガイドライン2024
志馬 伸朗, 中田 孝明, 矢田部 智昭, 山川 一馬, 青木 善孝, 井上 茂亮, 射場 敏明, 小倉 裕司, 河合 佑亮, 川口 敦, 川崎 達也, 近藤 豊, 櫻谷 正明, 對東 俊介, 土井 研人, 橋本 英樹, 原 嘉孝, 福田 龍将, 松嶋 麻子, 江木 盛時, 久志本 成樹, 大網 毅彦, 菊谷 知也, 相川 玄, 青木 誠, 赤塚 正幸, 淺井 英樹, 阿部 智一, 雨宮 優, 石澤 嶺, 石原 唯史, 石丸 忠賢, 糸洲 佑介, 井上 拓保, 今長谷 尚史, 井村 春樹, 岩崎 直也, 生塩 典敬, 内田 雅俊, 内 倫子, 梅垣 岳志, 梅村 穣, 遠藤 彰, 大井 真里奈, 大内 玲, 大沢 樹輝, 大島 良康, 太田 浩平, 大野 孝則, 岡田 遥平, 岡野 弘, 小川 新史, 柏浦 正広, 春日井 大介, 狩野 謙一, 上谷 遼, 河内 章, 川上 定俊, 川上 大裕, 川村 雄介, 神鳥 研二, 岸原 悠貴, 木村 翔, 久保 健児, 栗原 知己, 小網 博之, 小谷 祐樹, 木庭 茂, 佐藤 威仁, 佐藤 蓮, 澤田 悠輔, 志田 瑶, 島田 忠長, 志水 元洋, 清水 一茂, 白石 拓人, 新貝 達, 丹保 亜希仁, 杉浦 岳, 杉本 健輔, 杉本 裕史, 壽原 朋宏, 関野 元裕, 其田 健司, 對東 真帆子, 高橋 希, 竹下 淳, 武田 親宗, 立野 淳子, 田中 愛子, 谷 昌憲, 谷河 篤, 陳 昊, 土田 拓見, 堤 悠介, 恒光 健史, 出口 亮, 鉄原 健一, 寺山 毅郎, 戸上 由貴, 十時 崇彰, 友田 吉則, 中尾 俊一郎, 長澤 宏樹, 中谷 安寿, 中西 信人, 西岡 典宏, 錦見 満暁, 野口 智子, 野浪 豪, 野村 理, 橋本 克彦, 畠山 淳司, 濱井 康貴, 彦根 麻由, 久宗 遼, 廣瀬 智也, 福家 良太, 藤井 遼, 藤江 直輝, 藤永 潤, 藤浪 好寿, 藤原 翔, 舩越 拓, 本間 康一郎, 牧野 佑斗, 松浦 裕司, 松岡 綾華, 松岡 義, 松村 洋輔, 水野 彰人, 宮本 颯真, 三好 ゆかり, 村田 慧, 村田 哲平, 薬師寺 泰匡, 安尾 俊祐, 山田 浩平, 山田 博之, 山元 良, 山本 良平, 湯本 哲也, 吉田 裕治, 吉廣 尚大, 吉村 聡志, 吉村 旬平, 米倉 寛, 若林 侑起, 和田 剛志, 渡辺 伸一, 井尻 篤宏, 宇賀田 圭, 宇田 周司, 小野寺 隆太, 高橋 正樹, 中島 聡志, 本多 純太, 松本 承大, 日本版敗血症診療ガイドライン2024特別委員会, 日本集中治療医学会, 日本救急医学会
日本救急医学会雑誌, 35, S1, S1, S149, (一社)日本救急医学会, Dec. 2024
Japanese - Complication frequency of mechanical chest compression devices: A single-center, blinded study using retrospective data
Takumi Tsuchida, Takashi Kamiishi, Hiroaki Usubuchi, Akiko Semba, Masaki Takahashi, Asumi Mizugaki, Mariko Hayamizu, Mineji Hayakawa, Takeshi Wada
Resuscitation Plus, 20, 100786, 100786, Elsevier BV, Dec. 2024
Scientific journal - 敗血症による相対的副腎不全からたこつぼ心筋症、Vf stormを呈した汎下垂体機能低下症の一例
原 大希, 棟方 裕貴, 高氏 修平, 土田 拓見, 和田 剛志
日本救急医学会雑誌, 35, 11, 721, 721, (一社)日本救急医学会, Nov. 2024
Japanese - Simultaneous prognostic score validation in patients with out-of-hospital cardiac arrest by a post-hoc analysis based on national multicenter registry.
Takumi Tsuchida, Kota Ono, Masaki Takahashi, Mariko Hayamaizu, Asumi Mizugaki, Kunihiko Maekawa, Takeshi Wada, Mineji Hayakawa
Scientific reports, 14, 1, 18745, 18745, 13 Aug. 2024, [International Magazine]
English, Scientific journal, Using a nationwide multicenter prospective registry in Japan's data, we calculated prognostic and predictive scores, including the Out-of-Hospital Cardiac Arrest (OHCA); Cardiac Arrest Hospital Prognosis (CAHP); Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH < 7.2, Lactate > 7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥ 85 years, Still resuscitation, and Extracardiac cause (NULL-PLEASE); revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST); and MIRACLE2 scores, for adult patients with cardiac arrest. The MIRACLE2 score was validated with the modified MIRACLE2 score, which excludes information of pupillary reflexes. Each score was calculated only for the cases with no missing data for the variables used. These scores' accuracies were compared using neurological outcomes 30 days after out-of-hospital cardiac arrest (OOHCA). Patients with a cerebral performance category scale of 1 or 2 were designated as having favorable neurological outcomes. Each score's discrimination ability was evaluated by the receiver operating characteristic curve's area under the curve (AUC). To assess in detail in areas of high specificity and high sensitivity, which are areas of interest to clinicians, partial AUCs were also used. The analysis included 11,924 hospitalized adult patients. The AUCs of the OHCA, MIRACLE2, CAHP, rCAST, and NULL-PLEASE scores for favorable neurological outcomes were 0.713, 0.727, 0.785, 0.761, and 0.831, respectively. The CAHP and NULL-PLEASE scores were significantly more accurate than the rest. Accuracies did not differ significantly between the CAHP and NULL-PLEASE scores. The NULL-PLEASE score was significantly better at discriminating favorable neurological prognoses at 30 days in patients with OOHCA compared to other scoring systems. - Practical approach to thrombocytopenia in patients with sepsis: a narrative review.
Kasumi Satoh, Takeshi Wada, Akihito Tampo, Gaku Takahashi, Kota Hoshino, Hironori Matsumoto, Takayuki Taira, Satoshi Kazuma, Takamitsu Masuda, Takashi Tagami, Hiroyasu Ishikura
Thrombosis journal, 22, 1, 67, 67, 22 Jul. 2024, [International Magazine]
English, Scientific journal, Thrombocytopenia frequently occurs in patients with sepsis. Disseminated intravascular coagulation (DIC) may be a possible cause of thrombocytopenia owing to its high prevalence and association with poor outcomes; however, it is important to keep the presence of other diseases in mind in sepsis practice. Thrombotic microangiopathy (TMA), which is characterized by thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (HUS), and complement-mediated HUS, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. TMA has become widely recognized in recent years because of the development of specific treatments. Previous studies have reported a remarkably lower prevalence of TMA than DIC; however, its epidemiology is not well defined, and there may be cases in which TMA is not correctly diagnosed, resulting in poor outcomes. Therefore, it is important to differentiate DIC from TMA. Nevertheless, differentiating between DIC and TMA remains a challenge as indicated by previous reports that most patients with TMA can be diagnosed as DIC using the universal coagulation scoring system. Several algorithms to differentiate sepsis-related DIC from TMA have been suggested, contributing to improving the care of septic patients with thrombocytopenia; however, it may be difficult to apply these algorithms to patients with coexisting DIC and TMA, which has recently been reported. This review describes the disease characteristics, including epidemiology, pathophysiology, and treatment, of DIC, TMA, and other diseases with thrombocytopenia and proposes a novel practical approach flow, which is characterized by the initiation of the diagnosis of TMA in parallel with the diagnosis of DIC. This practical flow also refers to the longitudinal diagnosis and treatment flow with TMA in mind and real clinical timeframes. In conclusion, we aim to widely disseminate the results of this review that emphasize the importance of incorporating consideration of TMA in the management of septic DIC. We anticipate that this practical new approach for the diagnostic and treatment flow will lead to the appropriate diagnosis and treatment of complex cases, improve patient outcomes, and generate new epidemiological evidence regarding TMA. - Proposal and Validation of a Clinically Relevant Modification of the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Diagnostic Criteria for Sepsis.
Kazuma Yamakawa, Yutaka Umemura, Katsunori Mochizuki, Tadashi Matsuoka, Takeshi Wada, Mineji Hayakawa, Toshiaki Iba, Yasuhiro Ohtomo, Kohji Okamoto, Toshihiko Mayumi, Toshiaki Ikeda, Hiroyasu Ishikura, Hiroshi Ogura, Shigeki Kushimoto, Daizoh Saitoh, Satoshi Gando
Thrombosis and haemostasis, 10 May 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria were launched nearly 20 years ago. Following the revised conceptual definition of sepsis and subsequent omission of systemic inflammatory response syndrome (SIRS) score from the latest sepsis diagnostic criteria, we omitted the SIRS score and proposed a modified version of JAAM DIC criteria, the JAAM-2 DIC criteria. OBJECTIVES: To validate and compare performance between new JAAM-2 DIC criteria and conventional JAAM DIC criteria for sepsis. METHODS: We used three datasets containing adult sepsis patients from a multicenter nationwide Japanese cohort study (J-septic DIC, FORECAST, and SPICE-ICU registries). JAAM-2 DIC criteria omitted the SIRS score and set the cutoff value at ≥3 points. Receiver operating characteristic (ROC) analyses were performed between the two DIC criteria to evaluate prognostic value. Associations between in-hospital mortality and anticoagulant therapy according to DIC status were analyzed using propensity score weighting to compare significance of the criteria in determining introduction of anticoagulants against sepsis. RESULTS: Final study cohorts of the datasets included 2,154, 1,065, and 608 sepsis patients, respectively. ROC analysis revealed that curves for both JAAM and JAAM-2 DIC criteria as predictors of in-hospital mortality were almost consistent. Survival curves for the anticoagulant and control groups in the propensity score-weighted prediction model diagnosed using the two criteria were also almost entirely consistent. CONCLUSION: JAAM-2 DIC criteria were equivalent to JAAM DIC criteria regarding prognostic and diagnostic values for initiating anticoagulation. The newly proposed JAAM-2 DIC criteria could be potentially alternative criteria for sepsis management. - 冷凍倉庫内で受傷した腹部骨盤腔外傷,低体温症,そして凝固破綻 救えなかったか?
村上 壮一, 和田 剛志, 方波見 謙一, 高岡 憲敬, 林 真理子, 三浦 巧, 海老原 裕磨, 倉島 庸, 七戸 俊明, 平野 聡
日本外傷学会雑誌, 38, 2, 227, 227, (一社)日本外傷学会, Apr. 2024
Japanese - Effect of gender on 28-day survival rates and transfusion volume in severe trauma patients: a multicenter observational study
Takumi Tsuchida, Asumi Mizugaki, Shohei Tanaka, Akiko Semba, Takuma Nakajima, Takeshi Wada
Shock, Ovid Technologies (Wolters Kluwer Health), 25 Mar. 2024
Scientific journal, Abstract
Background
This study clarified the relationship between sex with survival and transfusion volume in severe trauma cases.
Methods
A multicenter, collaborative post-hoc analysis of patients with trauma in Japan was conducted. Patients aged ≥18 years with severe trauma indicated by an Injury Severity Score (ISS) of 16 or higher were enrolled. Patients were matched and analyzed by gender based on propensity score with factors determined at the time of injury. Subgroup analysis was performed on patients younger than 50 years and older than 50 years. The significance level was defined as p < 0.05.
Results
The 1,189 patients included in this registry were divided into adjusted groups of 226 male and female patients each. In the main analysis, 28-day survival rates in females were significantly higher than those in males (p = 0.046). In the subgroup analyses, there was no statistically significant prognostic effect of gender. Secondary outcomes, including transfusion volume, showed no significant gender-based variations. Logistic regression analyses consistently demonstrated that female sex was a significant favorable prognostic factor in all ages. This was true for the over-50 group on subgroup analysis, but no significant gender-prognosis relationship was identified in the under-50 age group. High ISS were associated with poorer outcomes across all age groups.
Conclusion
In severe trauma, survival at 28 days was significantly lower in males. However, this trend was not observed in patients aged ˂50 years. Factors other than sex hormones may be responsible for differences in posttraumatic outcomes by gender. - Phenotypic changes in immune cells induced by granulocyte and monocyte adsorptive apheresis in patients with severe COVID-19: An ex vivo study.
Ryo Hisamune, Kazuma Yamakawa, Katsuhide Kayano, Noritaka Ushio, Takeshi Wada, Kohei Taniguchi, Akira Takasu
Acute medicine & surgery, 11, 1, e70003, 2024, [International Magazine]
English, Scientific journal, AIMS: SARS-CoV-2 causes systemic immune dysfunction, leading to severe respiratory dysfunction and multiorgan dysfunction. Granulocyte and monocyte adsorptive apheresis (GMA) therapy is designed to regulate an excessive inflammatory response and has been proposed as a potential therapeutic strategy for coronavirus disease 2019 (COVID-19). We aimed to investigate a targeted subset of granulocytes and monocytes to be removed after GMA therapy in patients with severe COVID-19 infection. METHODS: We established an ex vivo experimental system to study the effects of GMA. Blood samples were collected into EDTA-treated tubes and a mixture of blood samples and cellulose acetate beads was used in GMA. After GMA, blood samples were removed, and the granulocyte and monocyte subtypes before and after GMA were determined by CyTOF mass cytometry. To analyze mass cytometry data with a self-organizing map, hierarchical clustering was used to determine the appropriate number of metaclusters from t-distributed stochastic neighbor embedding. RESULTS: We included seven patients with severe COVID-19 and four age- and sex-matched volunteers. Granulocyte subsets removed by GMA strongly expressed CD11b, CD16, and CD66b, and weakly expressed CD11c, consistent with mature and activated neutrophils. Monocyte subsets strongly expressed CD14, weakly expressed CD33 and CD45RO, and did not express CD16. These subsets were indicated to promote the release of inflammatory cytokines and activate T cells. CONCLUSIONS: The identification of the granulocyte and monocyte subsets removed after GMA in patients with severe COVID-19 may help explain the potential mechanism underlying the effectiveness of GMA in COVID-19 and other inflammatory diseases. - Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta‐analysis, and meta‐regression
Takumi Tsuchida, Yuto Makino, Takeshi Wada, Noritaka Ushio, Takaaki Totoki, Naoki Fujie, Shunsuke Yasuo, Tadashi Matsuoka, Hiroyuki Koami, Kazuma Yamakawa, Toshiaki Iba
Acute Medicine & Surgery, 11, 1, Wiley, Jan. 2024
Scientific journal, Abstract
Aims
There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta‐analysis of the use of antithrombin for sepsis and a meta‐regression analysis of antithrombin dosage.
Methods
We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all‐cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random‐effects model; further, meta‐regression and funnel plots were used to explore heterogeneity and biases.
Results
Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic‐disseminated intravascular coagulation (DIC), respectively. A meta‐analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta‐analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68–0.92; p = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52–2.37; p < 0.01). The meta‐regression analysis showed no correlation between antithrombin dosage and mortality.
Conclusion
A meta‐analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects. - 院外心停止蘇生後における神経学的予後不良群の長期予後
早水 真理子, 土田 拓見, 水柿 明日美, 高氏 修平, 本間 慶憲, 斉藤 智誉, 吉田 知由, 方波見 謙一, 和田 剛志, 前川 邦彦, 早川 峰司
日本救急医学会雑誌, 34, 12, 731, 731, (一社)日本救急医学会, Dec. 2023
Japanese - 原因不明の血小板減少症への診断的アプローチが遅れて脳出血に至ったヘパリン起因性血小板減少症の一例
加藤 諄, 本間 慶憲, 斉藤 智誉, 吉田 知由, 方波見 謙一, 和田 剛志, 前川 邦彦, 早川 峰司
日本救急医学会雑誌, 34, 12, 782, 782, (一社)日本救急医学会, Dec. 2023
Japanese - Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
Tomoyo Saito, Mineji Hayakawa, Osamu Kumano, Yoshinori Honma, Mone Murashita, Jun Kato, Syouki Fukui, Masaki Takahashi, Yuki Takahashi, Takumi Tsuchida, Asumi Mizugaki, Shuhei Takauji, Mariko Hayamizu, Tomonao Yoshida, Kenichi Katabami, Takeshi Wada, Kunihiko Maekawa
Journal of Intensive Care, 11, 1, Springer Science and Business Media LLC, 16 Nov. 2023
Scientific journal, Abstract
Background
Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes.
Methods
This study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group (< 80%), the concordant group (80–120%), and the upper group (> 120%).
Results
The overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups.
Conclusions
Discrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients.
Trial registration: Not applicable. - Phenotypes of Disseminated Intravascular Coagulation.
Takeshi Wada, Satoshi Gando
Thrombosis and haemostasis, 03 Oct. 2023, [International Magazine]
English, Scientific journal, Two phenotypes of disseminated intravascular coagulation (DIC) are systematically reviewed. DIC is classified into thrombotic and fibrinolytic phenotypes characterized by thrombosis and hemorrhage, respectively. Major pathology of DIC with thrombotic phenotype is the activation of coagulation, insufficient anticoagulation with endothelial injury, and plasminogen activator inhibitor-1-mediated inhibition of fibrinolysis, leading to microvascular fibrin thrombosis and organ dysfunction. DIC with fibrinolytic phenotype is defined as massive thrombin generation commonly observed in any type of DIC, combined with systemic pathologic hyperfibrinogenolysis caused by underlying disorder that results in severe bleeding due to excessive plasmin formation. Three major pathomechanisms of systemic hyperfibrinogenolysis have been considered: (1) acceleration of tissue-type plasminogen activator (t-PA) release from hypoxic endothelial cells and t-PA-rich storage pools, (2) enhancement of the conversion of plasminogen to plasmin due to specific proteins and receptors that are expressed on cancer cells and endothelial cells, and (3) alternative pathways of fibrinolysis. DIC with fibrinolytic phenotype can be diagnosed by DIC diagnosis followed by the recognition of systemic pathologic hyperfibrin(ogen)olysis. Low fibrinogen levels, high fibrinogen and fibrin degradation products (FDPs), and the FDP/D-dimer ratio are important for the diagnosis of systemic pathologic hyperfibrin(ogen)olysis. Currently, evidence-based treatment strategies for DIC with fibrinolytic phenotypes are lacking. Tranexamic acid appears to be one of the few methods to be effective in the treatment of systemic pathologic hyperfibrin(ogen)olysis. International cooperation for the elucidation of pathomechanisms, establishment of diagnostic criteria, and treatment strategies for DIC with fibrinolytic phenotype are urgent issues in the field of thrombosis and hemostasis. - Differences in acute outcomes of suicide patients by psychiatric disorder: Retrospective observational study
Takumi Tsuchida, Masaki Takahashi, Asumi Mizugaki, Hisashi Narita, Takeshi Wada
Medicine, 102, 38, e35065, e35065, Ovid Technologies (Wolters Kluwer Health), 22 Sep. 2023
Scientific journal, Suicide is a social problem with significant economic losses, the victims of which are mainly from the productive population. There are numerous reports on the assessment of suicide risk, but most focus on long-term management. Therefore, factors influencing the severity of physical impairments in the acute phase and the prognosis of suicidal patients have not been sufficiently investigated. This is a single-center retrospective observational study. We collected data on suicidal patients admitted to our emergency department. The effect of age, gender, psychiatric history, method of suicide, alcohol consumption, and hospital admission on the outcome of suicide was assessed. Outcomes were assessed using the hospital mortality scale and the cerebral performance category scale for in-hospital mortality within 28 days. Methods of suicide with a high mortality rate (hanging, jumping, carbon monoxide poisoning, and burns) were defined as lethal methods. A detailed risk assessment of outcomes was performed for patients with schizophrenia, mood disorders, and somatoform disorders. We identified 340 suicide patients from computerized medical records and analyzed 322 records without missing data. The non-survivor group predominantly comprised older adults, men, and patients without a history of psychiatric treatment. Contrastingly, more patients drank alcohol before suicide in the survivor group. In the subgroup analysis, patients with schizophrenia had unfavorable neurological outcomes. Patients with mood disorders had worse in-hospital mortality than other psychiatric patients, as did patients who chose the lethal method. By disease, patients with stress-related and somatoform disorders tended to have higher survival rates, although their psychiatric hospitalization rates were lower. Conversely, patients with mood disorders had a higher rate of hospital visits but a lower survival rate. The results suggest that usual outpatient treatment alone may not be sufficient to reduce suicide mortality in patients with mood disorders who are considered to be at high risk of suicide. - Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.
Ryo Yamamoto, Kazuma Yamakawa, Akira Endo, Koichiro Homma, Yasunori Sato, Ryo Takemura, Takeshi Yamagiwa, Keiki Shimizu, Daiki Kaito, Masayuki Yagi, Taku Yonemura, Takayuki Shibusawa, Ginga Suzuki, Takahiro Shoji, Naoya Miura, Jiro Takahashi, Chihiro Narita, Saori Kurata, Kazunobu Minami, Takeshi Wada, Yoshihisa Fujinami, Yohei Tsubouchi, Mai Natsukawa, Jun Nagayama, Wataru Takayama, Ken Ishikura, Kyoko Yokokawa, Yasuo Fujita, Hirofumi Nakayama, Hideki Tokuyama, Kota Shinada, Takayuki Taira, Shoki Fukui, Noritaka Ushio, Masaki Nakane, Eisei Hoshiyama, Akihito Tampo, Hisako Sageshima, Hiroki Takami, Shinichi Iizuka, Hitoshi Kikuchi, Jun Hagiwara, Takashi Tagami, Yumi Funato, Junichi Sasaki, Study Group Er-Oxytrac
BMJ open, 13, 9, e074475, 15 Sep. 2023, [International Magazine]
English, Scientific journal, INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914). - Delayed neurologic improvement and long-term survival of patients with poor neurologic status after out-of-hospital cardiac arrest: a retrospective cohort study in Japan
Mariko Hayamizu, Akira Kodate, Hisako Sageshima, Takumi Tsuchida, Yoshinori Honma, Asumi Mizugaki, Tomonao Yoshida, Tomoyo Saito, Kenichi Katabami, Takeshi Wada, Kunihiko Maekawa, Mineji Hayakawa
Resuscitation, 109790, 109790, Elsevier BV, Apr. 2023
Scientific journal - Sepsis-related coagulopathy treatment based on the disseminated intravascular coagulation diagnostic criteria: a post-hoc analysis of a prospective multicenter observational study.
Takeshi Wada, Kazuma Yamakawa, Daijiro Kabata, Toshikazu Abe, Seitaro Fujishima, Shigeki Kushimoto, Toshihiko Mayumi, Hiroshi Ogura, Daizoh Saitoh, Atsushi Shiraishi, Yasuhiro Otomo, Satoshi Gando
Journal of intensive care, 11, 1, 8, 8, 05 Mar. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of "high disease severity" in addition to "sepsis with DIC" has recently proved important in identifying appropriate targets for anticoagulant therapy. The aims of this study were to characterize "severe" sepsis DIC patients and to identify the patient population benefiting from anticoagulant therapy. METHODS: This retrospective sub-analysis of a prospective multicenter study included 1,178 adult patients with severe sepsis from 59 intensive care units in Japan from January 2016 to March 2017. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination. RESULTS: In total, we analyzed 1013 patients. The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of < 1.5 and that this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with a high DIC score and high PT-INR. Furthermore, we identified a DIC score ≥ 5 and PT-INR ≥ 1.5 as the clinical threshold for identification of optimal targets for anticoagulant therapy. CONCLUSIONS: The combined use of the DIC score and PT-INR helps in selecting the optimal patient population for anticoagulant therapy in sepsis-induced DIC. The results obtained from this study will provide valuable information regarding the study design of randomized controlled trials examining the effects of anticoagulant therapy for sepsis. TRIAL REGISTRATION: UMIN-CTR, UMIN000019742. Registered on November 16, 2015. - Gender-related differences in the coagulofibrinolytic responses and long-term outcomes in patients with isolated traumatic brain injury: A 2-center retrospective study
Takumi Tsuchida, Takeshi Wada, Ryuta Nakae, Yu Fujiki, Takahiro Kanaya, Yasuhiro Takayama, Go Suzuki, Yasutaka Naoe, Shoji Yokobori
Medicine, 102, 6, e32850, e32850, Ovid Technologies (Wolters Kluwer Health), 10 Feb. 2023
Scientific journal - Sepsis-induced disseminated intravascular coagulation: an international estrangement of disease concept.
Noritaka Ushio, Takeshi Wada, Yuichiro Ono, Kazuma Yamakawa
Acute medicine & surgery, 10, 1, e00843, 2023, [International Magazine]
English, Scientific journal, Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation, which can be caused by infectious and noninfectious insults, such as trauma, postcardiac arrest syndrome, and malignant diseases. At present, diagnosis and treatment of DIC clearly differ between Japan and Western countries; in Japan, DIC has long been considered a therapeutic target, and much evidence on DIC has been published. However, there has recently been no international consensus on whether DIC should be a therapeutic target with anticoagulant therapy. This review describes the coagulofibrinolytic system abnormalities associated with sepsis and discusses related management strategies. It also explores the reasons why DIC is perceived differently in different regions. There is a major discrepancy between diagnostic and treatment options in Japan, which are based on holistic assessments of trials, as well as the results of post hoc subgroup analyses and observational studies, and those in Western countries, which are based mainly on the results of sepsis mega trials, especially randomized controlled trials. The differences might also be due to various patient factors in each region, especially racial characteristics in thrombolytic mechanisms, and differences in interpretation of evidence for candidate drugs. Hence, Japanese researchers need to distribute their high-quality clinical research data not only to Japan but also to the rest of the world. - Hyperfibrinolysis and fibrinolysis shutdown in patients with traumatic brain injury.
Ryuta Nakae, Yasuo Murai, Takeshi Wada, Yu Fujiki, Takahiro Kanaya, Yasuhiro Takayama, Go Suzuki, Yasutaka Naoe, Hiroyuki Yokota, Shoji Yokobori
Scientific reports, 12, 1, 19107, 19107, 09 Nov. 2022, [International Magazine]
English, Scientific journal, Traumatic brain injury (TBI) is associated with coagulation/fibrinolysis disorders. We retrospectively evaluated 61 TBI cases transported to hospital within 1 h post-injury. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were measured on arrival and 3 h, 6 h, 12 h, 1 day, 3 days and 7 days after injury. Multivariate logistic regression analysis was performed to identify prognostic factors for coagulation and fibrinolysis. Plasma TAT levels peaked at admission and decreased until 1 day after injury. Plasma D-dimer levels increased, peaking up to 3 h after injury, and decreasing up to 3 days after injury. Plasma PAI-1 levels increased up to 3 h after injury, the upward trend continuing until 6 h after injury, followed by a decrease until 3 days after injury. TAT, D-dimer, and PAI-1 were elevated in the acute phase of TBI in cases with poor outcome. Multivariate logistic regression analysis showed that D-dimer elevation from admission to 3 h after injury and PAI-1 elevation from 6 h to 1 day after injury were significant negative prognostic indicators. Post-TBI hypercoagulation, fibrinolysis, and fibrinolysis shutdown were activated consecutively. Hyperfibrinolysis immediately after injury and subsequent fibrinolysis shutdown were associated with poor outcome. - 病院の規模が院外心停止患者の予後に与える影響
土田 拓見, 大野 浩太, 前川 邦彦, 和田 剛志, 早水 真理子, 早川 峰司
日本集中治療医学会雑誌, 29, Suppl.1, 461, 461, (一社)日本集中治療医学会, Nov. 2022
Japanese - Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.
Akira Endo, Kazuma Yamakawa, Takashi Tagami, Yutaka Umemura, Kyosuke Takahashi, Hiroki Nagasawa, Yuichi Araki, Mitsuaki Kojima, Toshiki Sera, Masayuki Yagi, Ryo Yamamoto, Jiro Takahashi, Masaki Nakane, Chikashi Takeda, Chihiro Narita, Satoshi Kazuma, Hiroko Okura, Hiroyuki Takahashi, Takeshi Wada, Shu Tahara, Ayaka Matsuoka, Todani Masaki, Atsushi Shiraishi, Keiichiro Shimoyama, Yuta Yokokawa, Rintaro Nakamura, Hisako Sageshima, Yuichiro Yanagida, Kunihiko Takahashi, Yasuhiro Otomo
Trials, 23, 1, 799, 799, 24 Sep. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. METHODS: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80-85 mmHg (high-target) and 65-70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients' condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. DISCUSSION: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020. - Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score-matched analysis.
Satoshi Gando, Atsushi Shiraishi, Takeshi Wada, Kazuma Yamakawa, Seitaro Fujishima, Daizoh Saitoh, Shigeki Kushimoto, Hiroshi Ogura, Toshikazu Abe, Toshihiko Mayumi, Junichi Sasaki, Joji Kotani, Naoshi Takeyama, Ryosuke Tsuruta, Kiyotsugu Takuma, Shin-Ichiro Shiraishi, Yasukazu Shiino, Taka-Aki Nakada, Kohji Okamoto, Yuichiro Sakamoto, Akiyoshi Hagiwara, Satoshi Fujimi, Yutaka Umemura, Yasuhiro Otomo
Medicine, 101, 32, e29711, 12 Aug. 2022, [International Magazine]
English, Scientific journal, Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score-matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified. - Association of Histones With Coagulofibrinolytic Responses and Organ Dysfunction in Adult Post-cardiac Arrest Syndrome
Asumi Mizugaki, Takeshi Wada, Takumi Tsuchida, Satoshi Gando
Frontiers in Cardiovascular Medicine, 9, 885406, 885406, Frontiers Media SA, 28 Jun. 2022, [International Magazine]
English, Scientific journal, Background
Patients successfully resuscitated from cardiac arrest often develop organ dysfunction caused by systemic inflammation and increased coagulation, leading to disseminated intravascular coagulation (DIC). The involvement of histones in DIC and organ dysfunction in patients with sepsis and trauma has been previously reported, raising the probability that histones may also be associated with pathophysiology in patients after cardiac arrest and resuscitation. This study evaluated the relationship between histones and organ dysfunction related to coagulofibrinolytic changes in patients with post-cardiac arrest syndrome (PCAS).
Methods
This prospective single-center observational study assessed 35 adult patients with PCAS who were divided into two groups, i.e., 15 patients with multiple organ dysfunction syndrome (MODS) and 20 patients without MODS. MODS was defined as a sequential organ failure assessment score of ≥12. The plasma levels of histones and coagulofibrinolytic markers, including soluble fibrin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, plasmin-alpha 2-plasmin inhibitor complex (PIC), and soluble thrombomodulin, were measured in patients with PCAS immediately after admission to the emergency department, and 3 and 24 h after arriving at the hospital.
Results
PCAS patients with MODS had higher DIC scores [4 (3.0–5.0) vs. 1 (0.0–3.0), p = 0.012] and higher mortality rates (66.7% vs. 20.0%, p = 0.013) than those without MODS. Moreover, patients with MODS exhibited higher histone levels than those without MODS during the early phase of the post-resuscitation period. Severe endothelial injury and higher thrombin and plasmin generation were observed in the MODS group. Plasma levels of histones were positively correlated with those of soluble fibrin immediately after resuscitation (rho = 0.367, p = 0.030) and PIC 3 h after arriving at the hospital (rho = 0.480, p = 0.005). This correlation was prominent in the patient population with MODS (soluble fibrin: rho = 0.681, p = 0.005, PIC: rho = 0.742, p = 0.002).
Conclusions
This study demonstrated that elevated histone levels were associated with increased levels of thrombin, and subsequent plasmin generation in PCAS patients, especially those with MODS. Further studies are required to elucidate the causal relationship between histones and organ dysfunction related to DIC in PCAS. - Age-related differences in the survival benefit of the administration of antithrombin, recombinant human thrombomodulin, or their combination in sepsis.
Takeshi Wada, Kazuma Yamakawa, Daijiro Kabata, Toshikazu Abe, Hiroshi Ogura, Atsushi Shiraishi, Daizoh Saitoh, Shigeki Kushimoto, Seitaro Fujishima, Toshihiko Mayumi, Toru Hifumi, Yasukazu Shiino, Taka-Aki Nakada, Takehiko Tarui, Yasuhiro Otomo, Kohji Okamoto, Yutaka Umemura, Joji Kotani, Yuichiro Sakamoto, Junichi Sasaki, Shin-Ichiro Shiraishi, Kiyotsugu Takuma, Ryosuke Tsuruta, Akiyoshi Hagiwara, Tomohiko Masuno, Naoshi Takeyama, Norio Yamashita, Hiroto Ikeda, Masashi Ueyama, Satoshi Fujimi, Satoshi Gando
Scientific reports, 12, 1, 9304, 9304, 03 Jun. 2022, [International Magazine]
English, Scientific journal, Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60-70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50-60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60-70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis. - Residual persistence of cytotoxicity lymphocytes and regulatory T cells in patients with severe coronavirus disease 2019 over a 1-year recovery process.
Yumi Mitsuyama, Kazuma Yamakawa, Katsuhide Kayano, Miho Maruyama, Yutaka Umemura, Takeshi Wada, Satoshi Fujimi
Acute medicine & surgery, 9, 1, e803, 2022, [International Magazine]
English, Scientific journal, AIM: To clarify the immune cellular changes in critically ill patients recovering from coronavirus disease 2019 (COVID-19). METHODS: The immune response of peripheral blood mononuclear cells from patients with severe COVID-19 in different stages of recovery (3, 6, and 12 months from hospitalization) was evaluated by single-cell mass cytometry. Immunological changes in patients were compared with those in age-matched healthy donors. RESULTS: Three patients with severe COVID-19 were compared with four healthy donors. In the patients, there was an increase in the cell density of CD4- and CD8-positive T lymphocytes, and B cells, over the course of the recovery period. CD4- and CD8-positive T lymphocytes expressing T-bet and granzyme B (Gzm B) in patients were abundant during all recovery periods. The level of regulatory T cells remained high throughout the year. The levels of natural killer (NK) cells in patients were higher than in those in the healthy donors, and the frequency of CD16+ NK cells expressing Gzm B increased throughout the year. CONCLUSION: Patients recovering from severe COVID-19 showed persistence of cytotoxic lymphocytes, NK cells, and regulatory T cells throughout the posthospitalization year of recovery. - Association of antithrombin with development of trauma-induced disseminated intravascular coagulation and outcomes.
Takeshi Wada, Atsushi Shiraishi, Satoshi Gando, Daijiro Kabata, Kazuma Yamakawa, Seitaro Fujishima, Daizoh Saitoh, Shigeki Kushimoto, Hiroshi Ogura, Toshikazu Abe, Toshihiko Mayumi, Yasuhiro Otomo
Frontiers in immunology, 13, 1026163, 1026163, 2022, [International Magazine]
English, Scientific journal, INTRODUCTION: Trauma activates the innate immune system to modulate hemostasis and minimize the damage caused by physiological bodily responses, including the activation of coagulation. Sufficiently severe trauma overwhelms physiological responses and elicits the systemic inflammatory response syndrome, which leads to the onset of disseminated intravascular coagulation (DIC), characterized by dysregulated inflammatory coagulofibrinolytic responses. Impaired anticoagulant mechanisms, including antithrombin, constitutes the pathology of DIC, while the dynamics of antithrombin and relevance to outcomes in trauma-induced coagulopathy have not been fully elucidated. This study investigated the associations of antithrombin activity with DIC onset and outcomes in severely injured patients. METHODS: This retrospective sub-analysis of a multicenter, prospective study included patients with an injury severity score ≥16. We characterized trauma patients with low antithrombin activity (antithrombin <80% on hospital arrival, n = 75) in comparison with those who had normal antithrombin activity (antithrombin ≥80%, n = 200). Global markers of coagulation and fibrinolysis, molecular biomarkers for thrombin generation (soluble fibrin [SF]), and markers of anticoagulation (antithrombin) were evaluated to confirm the associations of antithrombin with DIC development and outcomes, including in-hospital mortality and the multiple organ dysfunction syndrome (MODS). RESULTS: Patients with low antithrombin activity had higher prevalence of shock, transfusion requirements, and in-hospital mortality. Higher DIC scores and more severe organ dysfunction were observed in the low AT group compared to that in the normal AT group. Antithrombin activity on arrival at the hospital was an independent predictor of the development of DIC in trauma patients, and levels of SF increased with lower antithrombin values (antithrombin activity > 85%). Antithrombin activity at 3 h showed good predictive performance for in-hospital mortality, and a multivariable Cox proportional-hazard regression model with a cross-product term between the antithrombin and DIC showed that the in-hospital mortality in patients with DIC increased with decreased antithrombin activity. A multivariable logistic regression model showed that the odds for the development of MODS in patients with DIC increased with lower antithrombin values. CONCLUSION: Decreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC. - Neutrophil phenotypes implicated in the pathophysiology of post-traumatic sepsis.
Asumi Mizugaki, Takeshi Wada, Takumi Tsuchida, Yoshitaka Oda, Katsuhide Kayano, Kazuma Yamakawa, Shinya Tanaka
Frontiers in medicine, 9, 982399, 982399, 2022, [International Magazine]
English, Scientific journal, BACKGROUND: The disruption of immune homeostasis after trauma is a major cause of post-traumatic organ dysfunction and/or sepsis. Recently, a variety of neutrophil phenotypes with distinct functions have been identified and suggested as involved in various clinical conditions. The association between neutrophil phenotypes and post-traumatic immunodeficiency has also been reported, yet the specific neutrophil phenotypes and their functional significance in post-traumatic sepsis have not been fully clarified. Therefore, we sought to investigate neutrophil phenotypic changes in a murine model, as these may hold prognostic value in post-traumatic sepsis. MATERIALS AND METHODS: Third-degree burns affecting 25% of the body surface area were used to establish trauma model, and sepsis was induced 24 h later through cecal ligation and puncture (CLP). The Burn/CLP post-traumatic sepsis model and the Sham/CLP control model were established to assess the immunological status after trauma. Histopathological evaluation was performed on the spleen, liver, kidneys, and lung tissues. Immunological evaluation included the assessment of neutrophil markers using mass cytometry as well as cytokine measurements in serum and ascitic fluid through multiplex analysis using LUMINEX®. RESULTS: The Burn/CLP group had a lower survival rate than the Sham/CLP group. Histopathological examination revealed an impaired immune response and more advanced organ damage in the Burn/CLP group. Furthermore, the Burn/CLP group exhibited higher levels of transforming growth factor-beta 1 in the blood and generally lower levels of cytokines than the Sham/CLP group. CD11b, which is involved in neutrophil adhesion and migration, was highly expressed on neutrophils in the Burn/CLP group. The expression of CD172a, which is related to the inhibition of phagocytosis, was also upregulated on neutrophils in the Burn/CLP group. The expression of sialic acid-binding lg-like lectin F and CD68 also differed between the two groups. CONCLUSION: Different neutrophil phenotypes were observed between Burn/CLP and Sham/CLP groups, suggesting that neutrophils are implicated in the immune imbalance following trauma. However, further studies are needed to prove the causal relationships between neutrophil phenotypes and outcomes, including survival rate and organ dysfunction. - Antithrombin activity levels for predicting long-term outcomes in the early phase of isolated traumatic brain injury.
Masaki Takahashi, Takeshi Wada, Ryuta Nakae, Yu Fujiki, Takahiro Kanaya, Yasuhiro Takayama, Go Suzuki, Yasutaka Naoe, Shoji Yokobori
Frontiers in immunology, 13, 981826, 981826, 2022, [International Magazine]
English, Scientific journal, Coagulopathy management is an important strategy for preventing secondary brain damage in patients with traumatic brain injury (TBI). Antithrombin (AT) is a natural anticoagulant that controls coagulation and inflammation pathways. However, the significance of AT activity levels for outcomes in patients with trauma remains unclear. This study aimed to investigate the relationship between AT activity levels and long-term outcomes in patients with TBI; this was a sub-analysis of a prior study that collected blood samples of trauma patients prospectively in a tertiary care center in Kawaguchi City, Japan. We included patients with isolated TBI (iTBI) aged ≥16 years admitted directly to our hospital within 1 h after injury between April 2018 and March 2021. General coagulofibrinolytic and specific molecular biomarkers, including AT, were measured at 1, 3, 6, 12, and 24 h after injury. We analyzed changes in the AT activity levels during the study period and the impact of the AT activity levels on long-term outcomes, the Glasgow Outcome Scale-Extended (GOSE), 6 months after injury. 49 patients were included in this study; 24 had good neurological outcomes (GOSE 6-8), and 25 had poor neurological outcomes (GOSE 1-5). Low AT activity levels were shown within 1 h after injury in patients in the poor GOSE group; this was associated with poor outcomes. Furthermore, AT activity levels 1 h after injury had a strong predictive value for long-term outcomes (area under the receiver operating characteristic curve of 0.871; 95% CI: 0.747-0.994). Multivariate logistic regression analysis with various biomarkers showed that AT was an independent factor of long-term outcome (adjusted odds ratio: 0.873; 95% CI: 0.765-0.996; p=0.043). Another multivariate analysis with severity scores showed that low AT activity levels were associated with poor outcomes (adjusted odds ratio: 0.909; 95% CI: 0.822-1.010; p=0.063). We demonstrated that the AT activity level soon after injury could be a predictor of long-term neurological prognosis in patients with iTBI. - Protocol for a Sepsis Model Utilizing Fecal Suspension in Mice: Fecal Suspension Intraperitoneal Injection Model.
Takumi Tsuchida, Takeshi Wada, Asumi Mizugaki, Yoshitaka Oda, Katsuhide Kayano, Kazuma Yamakawa, Shinya Tanaka
Frontiers in medicine, 9, 765805, 765805, 2022, [International Magazine]
English, Scientific journal, Background: Various animal models of sepsis have been developed to optimize sepsis treatment. However, therapeutic agents that were successful in animal models were rarely effective in human clinical trials. The cecal ligation and puncture (CLP) model is currently the gold standard for sepsis studies. However, its limitations include the high variability among researchers and the difficulty in comparing animals with different cecum shapes and sizes. In this study, we established a protocol for the creation of a simple and accessible sepsis rodent model using fecal suspensions that minimized differences in technical effects among researchers and individual differences in animals. Methods: A mouse model of sepsis using fecal suspension intraperitoneal injection (FSI) was created using fresh stool excreted within 24 h. The collected fresh stool was dissolved in saline solution and filtered. The obtained fecal suspension was injected intraperitoneally into the mice. Moreover, fecal suspensions with different concentrations were prepared, and the survival rates were compared among the fecal suspensions for each concentration. To assess the validity of the FSI as a sepsis model, CLP and FSI with similar mortality rates were compared pathologically, physiologically, immunologically, and bacteriologically. Histopathological comparison was evaluated by hematoxylin-eosin and Gram staining of the parenchymal organs. Physiological evaluation was performed by comparing the respiratory rate, body temperature, and blood gas analysis results. Immunological assessment was performed using multiplex analysis. Bacteriological comparisons were performed by culturing ascites fluid. Results: The FSI model increased mortality in proportion to the fecal suspension concentration. The mortality rate was reduced with antibiotic administration. In various comparative experiments conducted using the FSI and CLP models, both models showed findings consistent with sepsis. Furthermore, the FSI model showed less variability among the individuals in each test. Conclusion: This is the first detailed and accurate report of a protocol for creating a sepsis model using fecal suspension. The FSI model is a minimally invasive and accessible sepsis rodent model. Its clinical validity as a sepsis model was proven via histological, physiological, microbiological, and immunological evaluation methods. The FSI model minimizes individual differences between mice and helps to conduct accurate studies after the onset of sepsis. - Prolonged enhancement of cytotoxic T lymphocytes in the post-recovery state of severe COVID-19.
Yumi Mitsuyama, Kazuma Yamakawa, Katsuhide Kayano, Miho Maruyama, Takeshi Wada, Satoshi Fujimi
Journal of intensive care, 9, 1, 76, 76, 20 Dec. 2021, [International Magazine]
English, We evaluated the peripheral blood immune responses of lymphocytes in severe Coronavirus disease 2019 (COVID-19) patients in different stages of recovery using single-cell mass cytometry. The patients with prolonged hospitalization did not show recovery of B lymphocyte counts and CD4-positive T lymphocyte counts but did show abundant CD8-positive T lymphocytes. CD4 and CD8 T cells expressing high levels of T-bet and Granzyme B were more abundant in post-recovery patients. This study showed that cytotoxic Th1 and CD8 T cells are recruited to the peripheral blood long after recovery from COVID-19. - 胃気腫症を認め後腹膜膿瘍を伴う敗血症性ショックに対して緊急開腹手術による治療が奏功した一例
本間 慶憲, 早川 峰司, 前川 邦彦, 和田 剛志, 方波見 謙一, 吉田 知由, 斎藤 智誉, 早水 真理子, 水柿 明日美, 定本 圭弘, 執行 亜希子
日本救急医学会雑誌, 32, 12, 2579, 2579, (一社)日本救急医学会, Nov. 2021
Japanese - Fibrinolytic system activation immediately following trauma was quickly and intensely suppressed in a rat model of severe blunt trauma.
Mineji Hayakawa, Takumi Tsuchida, Yoshinori Honma, Asumi Mizugaki, Takayoshi Ooyasu, Tomonao Yoshida, Tomoyo Saito, Kenichi Katabami, Takeshi Wada, Kunihiko Maekawa
Scientific reports, 11, 1, 20283, 20283, 13 Oct. 2021, [International Magazine]
English, Scientific journal, In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation-suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble-Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed. - 心停止蘇生後の低リン血症は予後不良因子である
高橋 正樹, 和田 剛志, 中嶋 拓磨, 執行 亜希子, 田中 祥平, 田原 就, 吉田 知由, 方波見 謙一, 前川 邦彦, 早川 峰司
日本集中治療医学会雑誌, 28, Suppl.2, 451, 451, (一社)日本集中治療医学会, Sep. 2021
Japanese - The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).
Moritoki Egi, Hiroshi Ogura, Tomoaki Yatabe, Kazuaki Atagi, Shigeaki Inoue, Toshiaki Iba, Yasuyuki Kakihana, Tatsuya Kawasaki, Shigeki Kushimoto, Yasuhiro Kuroda, Joji Kotani, Nobuaki Shime, Takumi Taniguchi, Ryosuke Tsuruta, Kent Doi, Matsuyuki Doi, Taka-Aki Nakada, Masaki Nakane, Seitaro Fujishima, Naoto Hosokawa, Yoshiki Masuda, Asako Matsushima, Naoyuki Matsuda, Kazuma Yamakawa, Yoshitaka Hara, Masaaki Sakuraya, Shinichiro Ohshimo, Yoshitaka Aoki, Mai Inada, Yutaka Umemura, Yusuke Kawai, Yutaka Kondo, Hiroki Saito, Shunsuke Taito, Chikashi Takeda, Takero Terayama, Hideo Tohira, Hideki Hashimoto, Kei Hayashida, Toru Hifumi, Tomoya Hirose, Tatsuma Fukuda, Tomoko Fujii, Shinya Miura, Hideto Yasuda, Toshikazu Abe, Kohkichi Andoh, Yuki Iida, Tadashi Ishihara, Kentaro Ide, Kenta Ito, Yusuke Ito, Yu Inata, Akemi Utsunomiya, Takeshi Unoki, Koji Endo, Akira Ouchi, Masayuki Ozaki, Satoshi Ono, Morihiro Katsura, Atsushi Kawaguchi, Yusuke Kawamura, Daisuke Kudo, Kenji Kubo, Kiyoyasu Kurahashi, Hideaki Sakuramoto, Akira Shimoyama, Takeshi Suzuki, Shusuke Sekine, Motohiro Sekino, Nozomi Takahashi, Sei Takahashi, Hiroshi Takahashi, Takashi Tagami, Goro Tajima, Hiroomi Tatsumi, Masanori Tani, Asuka Tsuchiya, Yusuke Tsutsumi, Takaki Naito, Masaharu Nagae, Ichiro Nagasawa, Kensuke Nakamura, Tetsuro Nishimura, Shin Nunomiya, Yasuhiro Norisue, Satoru Hashimoto, Daisuke Hasegawa, Junji Hatakeyama, Naoki Hara, Naoki Higashibeppu, Nana Furushima, Hirotaka Furusono, Yujiro Matsuishi, Tasuku Matsuyama, Yusuke Minematsu, Ryoichi Miyashita, Yuji Miyatake, Megumi Moriyasu, Toru Yamada, Hiroyuki Yamada, Ryo Yamamoto, Takeshi Yoshida, Yuhei Yoshida, Jumpei Yoshimura, Ryuichi Yotsumoto, Hiroshi Yonekura, Takeshi Wada, Eizo Watanabe, Makoto Aoki, Hideki Asai, Takakuni Abe, Yutaka Igarashi, Naoya Iguchi, Masami Ishikawa, Go Ishimaru, Shutaro Isokawa, Ryuta Itakura, Hisashi Imahase, Haruki Imura, Takashi Irinoda, Kenji Uehara, Noritaka Ushio, Takeshi Umegaki, Yuko Egawa, Yuki Enomoto, Kohei Ota, Yoshifumi Ohchi, Takanori Ohno, Hiroyuki Ohbe, Kazuyuki Oka, Nobunaga Okada, Yohei Okada, Hiromu Okano, Jun Okamoto, Hiroshi Okuda, Takayuki Ogura, Yu Onodera, Yuhta Oyama, Motoshi Kainuma, Eisuke Kako, Masahiro Kashiura, Hiromi Kato, Akihiro Kanaya, Tadashi Kaneko, Keita Kanehata, Ken-Ichi Kano, Hiroyuki Kawano, Kazuya Kikutani, Hitoshi Kikuchi, Takahiro Kido, Sho Kimura, Hiroyuki Koami, Daisuke Kobashi, Iwao Saiki, Masahito Sakai, Ayaka Sakamoto, Tetsuya Sato, Yasuhiro Shiga, Manabu Shimoto, Shinya Shimoyama, Tomohisa Shoko, Yoh Sugawara, Atsunori Sugita, Satoshi Suzuki, Yuji Suzuki, Tomohiro Suhara, Kenji Sonota, Shuhei Takauji, Kohei Takashima, Sho Takahashi, Yoko Takahashi, Jun Takeshita, Yuuki Tanaka, Akihito Tampo, Taichiro Tsunoyama, Kenichi Tetsuhara, Kentaro Tokunaga, Yoshihiro Tomioka, Kentaro Tomita, Naoki Tominaga, Mitsunobu Toyosaki, Yukitoshi Toyoda, Hiromichi Naito, Isao Nagata, Tadashi Nagato, Yoshimi Nakamura, Yuki Nakamori, Isao Nahara, Hiromu Naraba, Chihiro Narita, Norihiro Nishioka, Tomoya Nishimura, Kei Nishiyama, Tomohisa Nomura, Taiki Haga, Yoshihiro Hagiwara, Katsuhiko Hashimoto, Takeshi Hatachi, Toshiaki Hamasaki, Takuya Hayashi, Minoru Hayashi, Atsuki Hayamizu, Go Haraguchi, Yohei Hirano, Ryo Fujii, Motoki Fujita, Naoyuki Fujimura, Hiraku Funakoshi, Masahito Horiguchi, Jun Maki, Naohisa Masunaga, Yosuke Matsumura, Takuya Mayumi, Keisuke Minami, Yuya Miyazaki, Kazuyuki Miyamoto, Teppei Murata, Machi Yanai, Takao Yano, Kohei Yamada, Naoki Yamada, Tomonori Yamamoto, Shodai Yoshihiro, Hiroshi Tanaka, Osamu Nishida
Journal of intensive care, 9, 1, 53, 53, 25 Aug. 2021, [International Magazine]
English, The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines. - Simultaneous external validation of various cardiac arrest prognostic scores: a single-center retrospective study.
Takumi Tsuchida, Kota Ono, Kunihiko Maekawa, Takeshi Wada, Kenichi Katabami, Tomonao Yoshida, Mineji Hayakawa
Scandinavian journal of trauma, resuscitation and emergency medicine, 29, 1, 117, 117, 14 Aug. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: This study aimed to compare and validate the out-of-hospital cardiac arrest (OHCA); cardiac arrest hospital prognosis (CAHP); non-shockable rhythm, unwitnessed arrest, long no-flow or long low-flow period, blood pH < 7.2, lactate > 7.0 mmol/L, end-stage chronic kidney disease, age ≥ 85 years, still resuscitation, and extracardiac cause (NULL-PLEASE) clinical; post-cardiac arrest syndrome for therapeutic hypothermia (CAST); and revised CAST (rCAST) scores in OHCA patients treated with recent cardiopulmonary resuscitation strategies. METHODS: We retrospectively collected data on adult OHCA patients admitted to our emergency department between February 2015 and July 2018. OHCA, CAHP, NULL-PLEASE clinical, CAST, and rCAST scores were calculated based on the data collected. The predictive abilities of each score were tested using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: We identified 236 OHCA patients from computer-based medical records and analyzed 189 without missing data. In OHCA patients without bystander witnesses, CAHP and OHCA scores were not calculated. Although the predictive abilities of the scores were not significantly different, the NULL-PLEASE score had a large AUC of ROC curve in various OHCA patients. Furthermore, in patients with bystander-witnessed OHCA, the NULL-PLEASE score had large partial AUCs of ROC from sensitivity 0.8-1.0 and specificity 0.8-1.0. CONCLUSIONS: The NULL-PLEASE score had a high, comprehensive predictive ability in various OHCA patients. Furthermore, the NULL-PLEASE score had a high predictive ability for good and poor neurological outcomes in patients with bystander-witnessed OHCA. - Pathomechanisms Underlying Hypoxemia in Two COVID-19-Associated Acute Respiratory Distress Syndrome Phenotypes: Insights from Thrombosis and Hemostasis.
Satoshi Gando, Takeshi Wada
Shock (Augusta, Ga.), 24 Jun. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: The pathomechanisms of hypoxemia and treatment strategies for type H and type L acute respiratory distress syndrome (ARDS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) have not been elucidated. MAIN TEXT: SARS-CoV-2 mainly targets the lungs and blood, leading to ARDS, and systemic thrombosis or bleeding. Angiotensin II-induced coagulopathy, SARS-CoV-2-induced hyperfibrin(ogen)olysis, and pulmonary and/or disseminated intravascular coagulation due to immunothrombosis contribute to COVID-19-associated coagulopathy. Type H ARDS is associated with hypoxemia due to diffuse alveolar damage-induced high right-to-left shunts. Immunothrombosis occurs at the site of infection due to innate immune inflammatory and coagulofibrinolytic responses to SARS-CoV-2, resulting in microvascular occlusion with hypoperfusion of the lungs. Lung immunothrombosis in type L ARDS results from neutrophil extracellular traps containing platelets and fibrin in the lung microvasculature, leading to hypoxemia due to impaired blood flow and a high ventilation/perfusion (VA/Q) ratio. COVID-19-associated ARDS is more vascular centric than the other types of ARDS. D-dimer levels have been monitored for the progression of microvascular thrombosis in COVID-19 patients. Early anticoagulation therapy in critical patients with high D-dimer levels may improve prognosis, including the prevention and/or alleviation of ARDS. CONCLUSIONS: Right-to-left shunts and high VA/Q ratios caused by lung microvascular thrombosis contribute to hypoxemia in type H and L ARDS, respectively. D-dimer monitoring-based anticoagulation therapy may prevent the progression to and/or worsening of ARDS in COVID-19 patients. - Effects of The Prone Position on Regional Neutrophilic Lung Inflammation According To 18F-FDG PET In An Experimental Ventilator-Induced Lung Injury Model.
Susumu Nakahashi, Hiroshi Imai, Nobutake Shimojo, Yasuhiro Magata, Takahiro Einama, Mineji Hayakawa, Takeshi Wada, Yuji Morimoto, Satoshi Gando
Shock (Augusta, Ga.), 57, 2, 298, 308, 08 Jun. 2021, [International Magazine]
English, Scientific journal, ABSTRACT: Ventilator-induced lung injury (VILI) can be life-threatening and it is important to prevent the development of VILI. It remains unclear whether the prone position affects neutrophilic inflammation in the lung regions in vivo, which plays a crucial role in the pathogenesis of VILI. This study aimed to assess the relationship between the use of the prone position and the development of VILI-associated regional neutrophilic lung inflammation. Regional neutrophilic lung inflammation and lung aeration during low tidal volume mechanical ventilation were assessed using in vivo 2-deoxy-2-[ (18)F] fluoro-D-glucose (18F-FDG) positron emission tomography and computed tomography in acutely experimentally injured rabbit lungs (lung injury induced by lung lavage and excessive ventilation). Direct comparisons were made among three groups: control, supine, and prone position. After approximately 7 hours, tissue-normalized 18F-FDG uptake differed significantly between the supine and prone positions (SUP: 0.038 ± 0.014 vs. PP: 0.029 ± 0.008, P = 0.038), especially in the ventral region (SUP: 0.052 ± 0.013 vs. PP: 0.026 ± 0.007, P = 0.003). The use of the prone position reduced lung inhomogeneities, which was demonstrated by the correction of the disproportionate rate of voxel gas over the given lung region. The progression of neutrophilic inflammation was affected by the interaction between the total strain (for aeration) and the inhomogeneity. The prone position is effective in slowing down the progression of VILI-associated neutrophilic inflammation. Under low-tidal-volume ventilation, the main drivers of the its effect may be homogenization of lung tissue and that of mechanical forces. - Disseminated intravascular coagulation immediately after trauma predicts a poor prognosis in severely injured patients.
Takeshi Wada, Atsushi Shiraishi, Satoshi Gando, Kazuma Yamakawa, Seitaro Fujishima, Daizoh Saitoh, Shigeki Kushimoto, Hiroshi Ogura, Toshikazu Abe, Toshihiko Mayumi, Junichi Sasaki, Joji Kotani, Naoshi Takeyama, Ryosuke Tsuruta, Kiyotsugu Takuma, Norio Yamashita, Shin-Ichiro Shiraishi, Hiroto Ikeda, Yasukazu Shiino, Takehiko Tarui, Taka-Aki Nakada, Toru Hifumi, Kohji Okamoto, Yuichiro Sakamoto, Akiyoshi Hagiwara, Tomohiko Masuno, Masashi Ueyama, Satoshi Fujimi, Yutaka Umemura, Yasuhiro Otomo
Scientific reports, 11, 1, 11031, 11031, 26 May 2021, [International Magazine]
English, Scientific journal, Trauma patients die from massive bleeding due to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype in the early phase, which transforms to DIC with a thrombotic phenotype in the late phase of trauma, contributing to the development of multiple organ dysfunction syndrome (MODS) and a consequently poor outcome. This is a sub-analysis of a multicenter prospective descriptive cross-sectional study on DIC to evaluate the effect of a DIC diagnosis on the survival probability and predictive performance of DIC scores for massive transfusion, MODS, and hospital death in severely injured trauma patients. A DIC diagnosis on admission was associated with a lower survival probability (Log Rank P < 0.001), higher frequency of massive transfusion and MODS and a higher mortality rate than no such diagnosis. The DIC scores at 0 and 3 h significantly predicted massive transfusion, MODS, and hospital death. Markers of thrombin and plasmin generation and fibrinolysis inhibition also showed a good predictive ability for these three items. In conclusion, a DIC diagnosis on admission was associated with a low survival probability. DIC scores obtained immediately after trauma predicted a poor prognosis of severely injured trauma patients. - Pathophysiology of Coagulopathy Induced by Traumatic Brain Injury Is Identical to That of Disseminated Intravascular Coagulation With Hyperfibrinolysis.
Takeshi Wada, Atsushi Shiraishi, Satoshi Gando, Kazuma Yamakawa, Seitaro Fujishima, Daizoh Saitoh, Shigeki Kushimoto, Hiroshi Ogura, Toshikazu Abe, Toshihiko Mayumi, Junichi Sasaki, Joji Kotani, Naoshi Takeyama, Ryosuke Tsuruta, Kiyotsugu Takuma, Shin-Ichiro Shiraishi, Yasukazu Shiino, Taka-Aki Nakada, Kohji Okamoto, Yuichiro Sakamoto, Akiyoshi Hagiwara, Satoshi Fujimi, Yutaka Umemura, Yasuhiro Otomo
Frontiers in medicine, 8, 767637, 767637, 2021, [International Magazine]
English, Scientific journal, Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI. Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival. Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = -0.441, p = 0.017), but not with blood pressure (rho = -0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality. Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI. - Thromboplasminflammation in COVID-19 Coagulopathy: Three Viewpoints for Diagnostic and Therapeutic Strategies.
Satoshi Gando, Takeshi Wada
Frontiers in immunology, 12, 649122, 649122, 2021, [International Magazine]
English, Scientific journal, Thromboplasminflammation in coronavirus disease 2019 (COVID-19) coagulopathy consists of angiotensin II (Ang II)-induced coagulopathy, activated factor XII (FXIIa)- and kallikrein, kinin system-enhanced fibrinolysis, and disseminated intravascular coagulation (DIC). All three conditions induce systemic inflammation via each pathomechanism-developed production of inflammatory cytokines. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) downregulates angiotensin-converting enzyme 2, leading to an increase in Ang II levels. Ang II-induced coagulopathy comprising platelet activation, thrombin generation, plasminogen activator inhibitor-1 expression and endothelial injury causes thrombosis via the angiotensin II type 1 receptor. SARS-CoV-2 RNA and neutrophil extracellular trap (NET) DNA activate FXII, resulting in plasmin generation through FXIIa- and kallikrein-mediated plasminogen conversion to plasmin and bradykinin-induced tissue-type plasminogen activator release from the endothelium via the kinin B2 receptor. NETs induce immunothrombosis at the site of infection (lungs), through histone- and DNA-mediated thrombin generation, insufficient anticoagulation control, and inhibition of fibrinolysis. However, if the infection is sufficiently severe, immunothrombosis disseminates into the systemic circulation, and DIC, which is associated with the endothelial injury, occurs. Inflammation, and serine protease networks of coagulation and fibrinolysis, militate each other through complement pathways, which exacerbates three pathologies of COVID-19 coagulopathy. COVID-19 coagulopathy causes microvascular thrombosis and bleeding, resulting in multiple organ dysfunction and death in critically ill patients. Treatment targets for improving the prognosis of COVID-19 coagulopathy include thrombin, plasmin, and inflammation, and SARS-CoV-2 infection. Several drugs are candidates for controlling these conditions; however, further advances are required to establish robust treatments based on a clear understanding of molecular mechanisms of COVID-19 coagulopathy. - Coagulopathy Induced by Veno-Arterial Extracorporeal Membrane Oxygenation Is Associated With a Poor Outcome in Patients With Out-of-Hospital Cardiac Arrest.
Takumi Tsuchida, Takeshi Wada, Satoshi Gando
Frontiers in medicine, 8, 651832, 651832, 2021, [International Magazine]
English, Scientific journal, Background: In recent years, the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiopulmonary arrest who do not respond to conventional resuscitation, has increased. However, despite the development of VA-ECMO, the outcomes of resuscitated patients remain poor. The poor prognosis may be attributed to deterioration owing to the post-cardiac arrest syndrome (PCAS); this includes the systemic inflammatory response and coagulation activation caused by the extracorporeal circulation (VA-ECMO circuit) itself. This study aimed to evaluate the coagulofibrinolytic changes caused by VA-ECMO and to identify predictive factors of poor prognosis. Methods: We analyzed 151 cases of PCAS with witnessed cardiac arrest. As biomarkers, platelet counts, prothrombin time ratio, fibrin/fibrinogen degradation products, fibrinogen, antithrombin, and lactate were recorded from blood samples from the time of delivery to the third day of hospitalization. The maximum (max) and minimum (min) values of each factor during the study period were calculated. To evaluate the impact of VA-ECMO on patients with PCAS, we performed propensity score matching between the patients who received and did not receive VA-ECMO. Sub-analysis was performed for the group with VA-ECMO. Results: There were significant differences in all baseline characteristics and demographics except the time from detection to hospital arrival, percentage of cardiopulmonary resuscitations (CPR) by witnesses, and the initial rhythm between the groups. Propensity score matching adjusted for prehospital factors demonstrated that the patients who received VA-ECMO developed significantly severe coagulation disorders. In a sub-analysis, significant differences were noted in the prothrombin time ratio min, fibrinogen max, antithrombin max, and lactate min between survivors and non-survivors. In particular, the prothrombin time ratio min and antithrombin max were strongly correlated with poor outcome. Conclusion: In the present study, significant coagulopathy was observed in patients who received VA-ECMO for CPR. In particular, in patients receiving VA-ECMO, the minimum prothrombin time ratio and maximum antithrombin by day 3 of hospitalization were strongly correlated with poor outcomes. These results suggest that VA-ECMO-induced coagulopathy can be a promising therapeutic target for patients resuscitated by VA-ECMO. - The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020)
江⽊ 盛時, ⿊⽥ 泰弘, ⼭⽥ 亨, ⼭⽥ 博之, ⼭元 良, 吉⽥ 健史, 吉⽥ 悠平, 吉村 旬平, 四本 ⻯⼀, ⽶倉 寛, 和⽥ 剛志, 渡邉 栄三, ⼩⾕ 穣治, ⻘⽊ 誠, 浅井 英樹, 安部 隆国, 五⼗嵐 豊, 井⼝ 直也, ⽯川 雅⺒, ⽯丸 剛, 磯川 修太郎, 板倉 隆太, 今⻑⾕ 尚史, 志⾺ 伸朗, 井村 春樹, ⼊野⽥ 崇, 上原 健司, ⽣塩 典敬, 梅垣 岳志, 江川 裕⼦, 榎本 有希, 太⽥ 浩平, ⼤地 嘉史, ⼤野 孝則, ⾕⼝ 巧, ⼤邉 寛幸, 岡 和幸, 岡⽥ 信⻑, 岡⽥ 遥平, 岡野 弘, 岡本 潤, 奥⽥ 拓史, ⼩倉 崇以, ⼩野寺 悠, ⼩⼭ 雄太, 鶴⽥ 良介, ⾙沼 関志, 加古 英介, 柏浦 正広, 加藤 弘美, ⾦⾕ 明浩, ⾦⼦ 唯, ⾦畑 圭太, 狩野 謙⼀, 河野 浩幸, 菊⾕ 知也, ⼟井 研⼈, 菊地 ⻫, 城⼾ 崇裕, ⽊村 翔, ⼩網 博之, ⼩橋 ⼤輔, ⿑⽊ 巌, 堺 正仁, 坂本 彩⾹, 佐藤 哲哉, 志賀 康浩, ⼟井 松幸, 下⼾ 学, 下⼭ 伸哉, 庄古 知久, 菅原 陽, 杉⽥ 篤紀, 鈴⽊ 聡, 鈴⽊ 祐⼆, 壽原 朋宏, 其⽥ 健司, ⾼⽒ 修平, 中⽥ 孝明, ⾼島 光平, ⾼橋 ⽣, ⾼橋 洋⼦, ⽵下 淳, ⽥中 裕記, 丹保 亜希仁, ⾓⼭ 泰⼀朗, 鉄原 健⼀, 徳永 健太郎, 富岡 義裕, 中根 正樹, 冨⽥ 健太朗, 富永 直樹, 豊﨑 光信, 豊⽥ 幸樹年, 内藤 宏道, 永⽥ 功, ⻑⾨ 直, 中村 嘉, 中森 裕毅, 名原 功, 藤島 清太郎, 奈良場 啓, 成⽥ 知⼤, ⻄岡 典宏, ⻄村 朋也, ⻄⼭ 慶, 野村 智久, 芳賀 ⼤樹, 萩原 祥弘, 橋本 克彦, 旗智 武志, ⼩倉 裕司, 細川 直登, 浜崎 俊明, 林 拓也, 林 実, 速⽔ 宏樹, 原⼝ 剛, 平野 洋平, 藤井 遼, 藤⽥ 基, 藤村 直幸, 舩越 拓, 升⽥ 好樹, 堀⼝ 真仁, 牧 盾, 增永 直久, 松村 洋輔, 真⼸ 卓也, 南 啓介, 宮崎 裕也, 宮本 和幸, 村⽥ 哲平, 柳井 真知, 松嶋 ⿇⼦, ⽮野 隆郎, ⼭⽥ 浩平, ⼭⽥ 直樹, ⼭本 朋納, 吉廣 尚⼤, ⽥中 裕, ⻄⽥ 修, 松⽥ 直之, ⼭川 ⼀⾺, 原 嘉孝, ⼤下 慎⼀郎, ⻘⽊ 善孝, 稲⽥ ⿇⾐, 梅村 穣, ⽮⽥部 智昭, 河合 佑亮, 近藤 豊, 斎藤 浩輝, 櫻⾕ 正明, 對東 俊介, 武⽥ 親宗, 寺⼭ 毅郎, 東平 ⽇出夫, 橋本 英樹, 林⽥ 敬, 安宅 ⼀晃, ⼀⼆三 亨, 廣瀬 智也, 福⽥ ⿓将, 藤井 智⼦, 三浦 慎也, 安⽥ 英⼈, 阿部 智⼀, 安藤 幸吉, 飯⽥ 有輝, ⽯原 唯史, 井上 茂亮, 井⼿ 健太郎, 伊藤 健太, 伊藤 雄介, 稲⽥ 雄, 宇都宮 明美, 卯野⽊ 健, 遠藤 功⼆, ⼤内 玲, 尾崎 将之, ⼩野 聡, 射場 敏明, 桂 守弘, 川⼝ 敦, 川村 雄介, ⼯藤 ⼤介, 久保 健児, 倉橋 清泰, 櫻本 秀明, 下⼭ 哲, 鈴⽊ 武志, 関根 秀介, 垣花 泰之, 関野 元裕, ⾼橋 希, ⾼橋 世, ⾼橋 弘, ⽥上 隆, ⽥島 吾郎, 巽 博⾂, ⾕ 昌憲, ⼟⾕ ⾶⿃, 堤 悠介, 川崎 達也, 内藤 貴基, ⻑江 正晴, ⻑澤 俊郎, 中村 謙介, ⻄村 哲郎, 布宮 伸, 則末 泰博, 橋本 悟, ⻑⾕川 ⼤祐, 畠⼭ 淳司, 久志本 成樹, 原 直⼰, 東別府 直紀, 古島 夏奈, 古薗 弘隆, 松⽯ 雄⼆朗, 松⼭ 匡, 峰松 佑輔, 宮下 亮⼀, 宮武 祐⼠, 森安 恵実
Journal of the Japanese Society of Intensive Care Medicine, 27, Suppl., 263, 263, The Japanese Society of Intensive Care Medicine, Dec. 2020
Japanese - A multicenter prospective validation study on disseminated intravascular coagulation in trauma-induced coagulopathy.
Satoshi Gando, Atsushi Shiraishi, Takeshi Wada, Kazuma Yamakawa, Seitaro Fujishima, Daizoh Saitoh, Shigeki Kushimoto, Hiroshi Ogura, Toshikazu Abe, Yasuhiro Otomo
Journal of thrombosis and haemostasis : JTH, 18, 9, 2232, 2244, Sep. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Trauma-induced coagulopathy (TIC) may progress to disseminated intravascular coagulation (DIC) due to dysregulated inflammatory and coagulofibrinolytic responses to trauma. OBJECTIVES: We explored how DIC and TIC elicit the same coagulofibrinolytic changes which lead to massive transfusion. METHODS: Severely injured trauma patients with an injury severity score ≥ 16 were prospectively included. Platelet counts, global markers of coagulation and fibrinolysis and specific markers of thrombin and plasmin generation, anticoagulation, endothelial injury, and inhibition of fibrinolysis were measured at presentation to the emergency department (0 hour) and 3 hour after arrival. The patients were subdivided into those with and without DIC and those with and without TIC using the 0-hour data. Time courses of specific markers and the frequency of massive transfusion were evaluated. The association of various variables with DIC development was also confirmed. RESULTS: Two hundred and seventy-six patients were eligible for the analyses. The severity of injury (odds ratio; 1.038, P = .022) and thrombin generation (odds ratio; 1.014, P = .024) were associated with the development of DIC. Both DIC and TIC patients showed increased thrombin generation, insufficient anticoagulation controls, endothelial injury and increased fibrinolysis followed by elevated plasminogen activator inhibitor-1 levels at 0 and 3 hours. The frequency of massive transfusion was higher in both DIC (33.6% vs 7.9%, P < .001) and TIC (50.0% vs 13.3%, P < .001) patients than in those without DIC or TIC, respectively. CONCLUSIONS: Disseminated intravascular coagulation and TIC evoked the same coagulofibrinolytic responses in severely injured trauma patients immediately after trauma and needed massive transfusion. - Microparticles and Nucleosomes Are Released From Parenchymal Cells Destroyed After Injury in a Rat Model of Blunt Trauma
Mineji Hayakwa, Takayoshi Ooyasu, Yoshihiro Sadamoto, Tomoyo Saito, Tomonao Yoshida, Kenichi Katabami, Takeshi Wada, Kunihiko Maekawa, Masahiro Ieko
Clinical and Applied Thrombosis/Hemostasis, 26, SAGE Publications Inc., 2020
English, Scientific journal - Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers
Tomoyo Saito, Mineji Hayakawa, Yoshinori Honma, Asumi Mizugaki, Tomonao Yoshida, Kenichi Katabami, Takeshi Wada, Kunihiko Maekawa
Clinical and Applied Thrombosis/Hemostasis, 26, 107602962093300, 107602962093300, SAGE Publications, 01 Jan. 2020
Scientific journal, The association between severity of fibrinolysis, ascertained by rotational thromboelastometry to diagnose hyperfibrinolysis in patients with out-of-hospital cardiac arrest (OHCA), and conventional fibrinolysis markers (ie, tissue-plasminogen activator [t-PA], plasminogen, α2-plasmin inhibitor [α2-PI], and plasminogen activator inhibitor [PAI]) with key roles in the fibrinolytic system was investigated. This prospective observational study included 5 healthy volunteers and 35 patients with OHCA from the Hokkaido University Hospital. Blood samples were drawn immediately upon admission to the emergency department. Assessments of the extrinsic pathway using tissue factor activation (EXTEM) and of fibrinolysis by comparison with EXTEM after aprotinin addition (APTEM) were undertaken. Conventional coagulation and fibrinolysis markers were measured in the stored plasma samples. Significant hyperfibrinolysis observed in EXTEM disappeared in APTEM. Patients exhibited significantly higher levels of fibrinogen/fibrin degradation products, plasmin–α2-PI complex, and t-PA but lower levels of fibrinogen, plasminogen, and α2-PI than healthy controls. The PAI level was unchanged. Fibrinolytic parameters of EXTEM correlated with levels of lactate and conventional fibrinolysis markers, especially t-PA. Increased t-PA activity and decreased plasminogen and α2-PI significantly correlated with increased severity of fibrinolysis (hyperfibrinolysis). - Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients: a single-centre propensity score-matched analysis.
Yuki Itagaki, Mineji Hayakawa, Kunihiko Maekawa, Tomoyo Saito, Akira Kodate, Yoshinori Honma, Asumi Mizugaki, Tomonao Yoshida, Takayoshi Ohyasu, Kenichi Katabami, Takeshi Wada
World journal of emergency surgery : WJES, 15, 7, 7, 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background: Fibrinogen plays an important role in haemostasis during the early phase of trauma, and low fibrinogen levels after severe trauma are associated with haemostatic impairment, massive bleeding, and poor outcomes. Aggressive fibrinogen supplementation may improve haemostatic function, as fibrinogen levels deteriorate before other routine coagulation parameters in this setting. Therefore, we evaluated whether early administration of fibrinogen concentrate (FC) was associated with improved survival in severe trauma patients. Methods: This single-centre retrospective study evaluated patients with severe trauma (injury severity score ≥ 16) who were admitted to our emergency department between January 2010 and July 2018. The exclusion criteria included age < 18 years, cardiac arrest before emergency department arrival, cervical spinal cord injury not caused by a high-energy accident, and severe burn injuries. The FC and control groups included trauma patients who received and did not receive FC within 1 h after emergency department arrival, respectively. Propensity scores were used to balance the two groups based on the trauma and injury severity score (TRISS), heart rate at emergency department admission, and age. The primary outcome was the in-hospital survival rate. Results: The propensity scoring model had a c-statistic of 0.734, the Hosmer-Lemeshow chi-squared value was 7.036 (degrees of freedom = 8), and the non-significant p value of 0.533 indicated a good model fit. The propensity score matching created 31 matched pairs of patients, who had appropriately balanced characteristics. The FC group had a significantly higher in-hospital survival rate than the control group (log-rank p = 0.013). The FC group also used significantly higher amounts of red blood cells and fresh frozen plasma within 6 h after emergency department admission. However, the two groups had similar transfusion amounts between 6 and 24 h after emergency department admission. Conclusions: The present study revealed that early FC administration was associated with a favourable survival rate among severe trauma patients. Therefore, FC may be useful for the early management of trauma-induced coagulopathy and may improve outcomes in this setting. - Trauma-induced coagulopathy: The past, present, and future: A comment.
Takeshi Wada, Kazuma Yamakawa
Journal of thrombosis and haemostasis : JTH, 17, 9, 1571, 1574, Sep. 2019, [Peer-reviewed], [International Magazine]
English - Altered monocyte and NK cell phenotypes correlate with posttrauma infection.
Seshadri A, Brat GA, Yorkgitis BK, Giangola M, Keegan J, Nguyen JP, Li W, Nakahori Y, Wada T, Hauser C, Salim A, Askari R, Lederer JA
The journal of trauma and acute care surgery, 87, 2, 337, 341, Aug. 2019, [Peer-reviewed] - Disseminated intravascular coagulation in cardiac arrest and resuscitation.
Gando S, Wada T
Journal of thrombosis and haemostasis : JTH, 17, 8, 1205, 1216, Aug. 2019, [Peer-reviewed] - Diagnosis of sepsis-induced disseminated intravascular coagulation and coagulopathy.
Toshiaki Iba, Yutaka Umemura, Eizo Watanabe, Takeshi Wada, Kei Hayashida, Shigeki Kushimoto
Acute medicine & surgery, 6, 3, 223, 232, Jul. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Disseminated intravascular coagulation (DIC) is a frequent complication in sepsis. Once patients develop DIC, the mortality rate increases significantly. Moreover, recent studies have suggested that coagulation disorder plays a significant role in the development of organ dysfunction in sepsis. Thus, the early detection of DIC is vital in sepsis care, and the Japanese Association for Acute Medicine established a set of original diagnostic criteria in 2006 (JAAM DIC). Since then, the usefulness of the JAAM DIC has been repeatedly reported, and these criteria have been widely adopted in emergency and critical care settings in Japan. Different criteria have also been released by the International Society on Thrombosis and Haemostasis (ISTH overt-DIC), and the latter criteria are presently considered to be the international standard. Compared with the JAAM DIC, the ISTH overt-DIC criteria are stricter and the timing of diagnosis is later. This discrepancy is because of conceptual differences. As many physicians think sepsis-associated DIC is the target of anticoagulant therapies in Japan, the JAAM DIC criteria were designed to allow the early initiation of treatment. As other countries do not provide DIC-specific treatments, early diagnosis is not necessary, and this situation has led to a significant gap. However, as overt-DIC is a late-phase coagulation disorder, a need for early detection has been advocated, and members of the ISTH have recently proposed the category of sepsis-induced coagulopathy. In this review, we introduce the strengths and weaknesses of the major criteria including JAAM-DIC, ISTH overt-DIC, sepsis-induced coagulopathy, and Japanese Society on Thrombosis and Haemostasis-DIC. - Sepsis-associated disseminated intravascular coagulation and its differential diagnoses.
Toshiaki Iba, Eizo Watanabe, Yutaka Umemura, Takeshi Wada, Kei Hayashida, Shigeki Kushimoto, Hideo Wada
Journal of intensive care, 7, 32, 32, 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Disseminated intravascular coagulation (DIC) is a common complication in sepsis. Since DIC not only promotes organ dysfunction but also is a strong prognostic factor, its diagnosis at the earliest possible timing is important. Thrombocytopenia is often present in patients with DIC but can also occur in a number of other critical conditions. Of note, many of the rare thrombocytopenic diseases require prompt diagnoses and specific treatments. To differentiate these diseases correctly, the phenotypic expressions must be considered and the different disease pathophysiologies must be understood. There are three major players in the background characteristics of thrombocytopenia: platelets, the coagulation system, and vascular endothelial cells. For example, the activation of coagulation is at the core of the pathogenesis of sepsis-associated DIC, while platelet aggregation is the essential mechanism in thrombotic thrombocytopenic purpura and endothelial damage is the hallmark of hemolytic uremic syndrome. Though each of the three players is important in all thrombocytopenic diseases, one of the three dominant players typically establishes the individual features of each disease. In this review, we introduce the pathogeneses, symptoms, diagnostic measures, and recent therapeutic advances for the major diseases that should be immediately differentiated from DIC in sepsis. - Disseminated intravascular coagulation with increased fibrinolysis during the early phase of isolated traumatic brain injury
Takeshi Wada, Satoshi Gando, Kunihiko Maekaw, Kenichi Katabami, Hisako Sageshima, Mineji Hayakawa, Atsushi Sawamura
Critical Care, 21, 1, 219, BioMed Central Ltd., 22 Aug. 2017, [Peer-reviewed]
English, Scientific journal - Disseminated intravascular coagulation with increased fibrinolysis during the early phase of isolated traumatic brain injury
Takeshi Wada, Satoshi Gando, Kunihiko Maekaw, Kenichi Katabami, Hisako Sageshima, Mineji Hayakawa, Atsushi Sawamura
CRITICAL CARE, 21, Aug. 2017, [Peer-reviewed]
English, Scientific journal - Differences in coagulofibrinolytic changes between post-cardiac arrest syndrome of cardiac causes and hypoxic insults: a pilot study.
Wada T, Gando S, Mizugaki A, Kodate A, Sadamoto Y, Murakami H, Maekawa K, Katabami K, Ono Y, Hayakawa M, Sawamura A, Jesmin S, Ieko M
Acute medicine & surgery, 4, 3, 371, 372, Jul. 2017, [Peer-reviewed] - Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients
Yuichi Ono, Mineji Hayakawa, Kunihiko Maekawa, Akira Kodate, Yoshihiro Sadamoto, Naoki Tominaga, Hiromoto Murakami, Tomonao Yoshida, Kenichi Katabami, Takeshi Wada, Hisako Sageshima, Atsushi Sawamura, Satoshi Gando
RESUSCITATION, 111, 62, 67, Feb. 2017, [Peer-reviewed]
English, Scientific journal - Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome.
Wada T
Frontiers in medicine, 4, 156, 2017, [Peer-reviewed] - Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest
Takeshi Wada, Satoshi Gando, Yuichi Ono, Kunihiko Maekawa, Kenichi Katabami, Mineji Hayakawa, Atsushi Sawamura
Thrombosis Journal, 14, 1, 43, BioMed Central Ltd., 21 Sep. 2016, [Peer-reviewed]
English, Scientific journal - Septic DIC の病態と Immunothrombosis
丸藤哲, 和田剛志, 小野雄一, 前川邦彦, 方波見謙一, 早川峰司, 澤村淳
ICUとCCU, 40, 171, 178, 2016, [Peer-reviewed]
Japanese, Scientific journal - Activated protein C does not increase in the early phase of trauma with disseminated intravascular coagulation: Comparison with acute coagulopathy of trauma-shock
Subrina Jesmin, Satoshi Gando, Takeshi Wada, Mineji Hayakawa, Atsushi Sawamura
Journal of Intensive Care, 4, 1, 1, BioMed Central Ltd., 2016, [Peer-reviewed]
English - Should laryngeal tubes or masks be used for out-of-hospital cardiac arrest patients?
Yuichi Ono, Mineji Hayakawa, Kunihiko Maekawa, Asumi Mizugaki, Kenichi Katabami, Takeshi Wada, Atsushi Sawamura, Satoshi Gando
AMERICAN JOURNAL OF EMERGENCY MEDICINE, 33, 10, 1360, 1363, Oct. 2015, [Peer-reviewed]
English, Scientific journal - Effects of prehospital epinephrine administration on neurological outcomes in patients with out-of-hospital cardiac arrest
Yuichi Ono, Mineji Hayakawa, Takeshi Wada, Atsushi Sawamura, Satoshi Gando
Journal of Intensive Care, 3, 1, 29, BioMed Central Ltd., 24 Jun. 2015, [Peer-reviewed]
English, Scientific journal - Pharmacokinetics and the optimal regimen for levofloxacin in critically ill patients receiving continuous hemodiafiltration
Takeshi Wada, Masaki Kobayashi, Yuichi Ono, Asumi Mizugaki, Kenichi Katabami, Kunihiko Maekawa, Daisuke Miyamoto, Yuichiro Yanagida, Mineji Hayakawa, Atsushi Sawamura, Ken Iseki, Satoshi Gando
Journal of Intensive Care, 3, 1, 22, BioMed Central Ltd., 08 May 2015, [Peer-reviewed]
English - Rapid Evaluation of Fibrinogen Levels Using the CG02N Whole Blood Coagulation Analyzer
Mineji Hayakawa, Satoshi Gando, Yuichi Ono, Asumi Mizugaki, Kenichi Katabami, Kunihiko Maekawa, Daisuke Miyamoto, Takeshi Wada, Yuichiro Yanagida, Atsushi Sawamura
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 41, 3, 267, 271, Apr. 2015, [Peer-reviewed]
English, Scientific journal - NOBLE-COLLIP DRUM TRAUMA INDUCES DISSEMINATED INTRAVASCULAR COAGULATION BUT NOT ACUTE COAGULOPATHY OF TRAUMA-SHOCK
Mineji Hayakawa, Satoshi Gando, Yuichi Ono, Takeshi Wada, Yuichiro Yanagida, Atsushi Sawamura, Masahiro Ieko
SHOCK, 43, 3, 261, 267, Mar. 2015, [Peer-reviewed]
English, Scientific journal - Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study.
Hayakawa M, Gando S, Ono Y, Wada T, Yanagida Y, Sawamura A
Seminars in Thrombosis and Hemostasis, 41, 1, 35, 42, Feb. 2015, [Peer-reviewed]
English, Scientific journal - Fibrinogen Level Deteriorates before Other Routine Coagulation Parameters and Massive Transfusion in the Early Phase of Severe Trauma: A Retrospective Observational Study
Mineji Hayakawa, Satoshi Gando, Yuichi Ono, Takeshi Wada, Yuichiro Yanagida, Atsushi Sawamura
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 41, 1, 35, 42, Feb. 2015, [Peer-reviewed]
English, Scientific journal - 4D flow preliminary investigation of a direct carotid cavernous fistula due to a ruptured intracavernous aneurysm
Shunsuke Nakagawa, Yasuo Murai, Takeshi Wada, Kojiro Tateyama
BMJ Case Reports, 2015, BMJ Publishing Group, 22 Jan. 2015, [Peer-reviewed]
English, Scientific journal - Spontaneous Angiographic Regression of Cerebral Arteriovenous Malformations: Angiographic Disappearance is not the Real Cure
Fumihiro Matano, Yasuo Murai, Shunsuke Nakagawa, Takeshi Wada, Takayuki Kitamura, Akira Teramoto
TURKISH NEUROSURGERY, 25, 1, 168, 173, Jan. 2015, [Peer-reviewed]
English, Scientific journal - Effects of rikkunshito (traditional Japanese medicine) on enteral feeding and the plasma ghrelin level in critically ill patients: A pilot study
Mineji Hayakawa, Yuichi Ono, Takeshi Wada, Yuichiro Yanagida, Atsushi Sawamura, Hiroshi Takeda, Satoshi Gando
Journal of Intensive Care, 2, 1, 53, BioMed Central Ltd., 02 Sep. 2014, [Peer-reviewed]
English, Scientific journal - Effectiveness of end-expiratory lung volume measurements during the lung recruitment maneuver for patients with atelectasis
Susumu Nakahashi, Satoshi Gando, Takehiko Ishikawa, Takeshi Wada, Yuichiro Yanagida, Nobuhiko Kubota, Shinji Uegaki, Mineji Hayakawa, Atsushi Sawamura
JOURNAL OF CRITICAL CARE, 28, 4, 534.e1, 5, Aug. 2013, [Peer-reviewed]
English, Scientific journal - Effectiveness of end-expiratory lung volume measurements during the lung recruitment maneuver for patients with atelectasis
Susumu Nakahashi, Satoshi Gando, Takehiko Ishikawa, Takeshi Wada, Yuichiro Yanagida, Nobuhiko Kubota, Shinji Uegaki, Mineji Hayakawa, Atsushi Sawamura
JOURNAL OF CRITICAL CARE, 28, 4, 534E1, 5, Aug. 2013, [Peer-reviewed]
English, Scientific journal - Normal prothrombinase activity, increased systemic thrombin activity, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: Comparison with acute coagulopathy of trauma-shock
Yuichiro Yanagida, Satoshi Gando, Atsushi Sawamura, Mineji Hayakawa, Shinji Uegaki, Nobuhiko Kubota, Taeko Homma, Yuichi Ono, Yoshinori Honma, Takeshi Wada, Subrina Jesmin
SURGERY, 154, 1, 48, 57, Jul. 2013, [Peer-reviewed]
English, Scientific journal - Coagulofibrinolytic changes in patients with disseminated intravascular coagulation associated with post-cardiac arrest syndrome- Fibrinolytic shutdown and insufficient activation of fibrinolysis lead to organ dysfunction
Takeshi Wada, Satoshi Gando, Asumi Mizugaki, Yuichiro Yanagida, Subrina Jesmin, Hiroyuki Yokota, Masahiro Ieko
THROMBOSIS RESEARCH, 132, 1, E64, E69, Jul. 2013, [Peer-reviewed]
English, Scientific journal - The role of angiogenic factors and their soluble receptors in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with critical illness
Takeshi Wada, Subrina Jesmin, Satoshi Gando, Yuichiro Yanagida, Asumi Mizugaki, Sayeeda Nusrat Sultana, Sohel Zaedi, Hiroyuki Yokota
JOURNAL OF INFLAMMATION-LONDON, 10, 1, 6, Feb. 2013, [Peer-reviewed]
English, Scientific journal - Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome
Takeshi Wada, Subrina Jesmin, Satoshi Gando, Yuichiro Yanagida, Asumi Mizugaki, Sayeeda N. Sultana, Sohel Zaedi, Hiroyuki Yokota
Critical Care, 16, 5, R171, 29 Sep. 2012, [Peer-reviewed]
English, Scientific journal - Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma
Takeshi Wada, Subrina Jesmin, Satoshi Gando, Sayeeda N. Sultana, Sohel Zaedi, Hiroyuki Yokota
Critical Care, 16, 2, R63, 20 Apr. 2012, [Peer-reviewed]
English, Scientific journal - Time-Dependent Alterations of VEGF and Its Signaling Molecules in Acute Lung Injury in a Rat Model of Sepsis
Subrina Jesmin, Sohel Zaedi, A. M. Shahidul Islam, S. Nusrat Sultana, Yoshio Iwashima, Takeshi Wada, Naoto Yamaguchi, Michiaki Hiroe, Satoshi Gando
INFLAMMATION, 35, 2, 484, 500, Apr. 2012, [Peer-reviewed]
English, Scientific journal - Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma
Takeshi Wada, Subrina Jesmin, Satoshi Gando, Sayeeda N. Sultana, Sohel Zaedi, Hiroyuki Yokota
CRITICAL CARE, 16, 2, 2012, [Peer-reviewed]
English, Scientific journal - Effects of intrapulmonary percussive ventilation for acute respiratory failure.
Nakahashi S, Hayakawa M, Katabami K, Wada T, Sawamura A, Ishikawa T, Gando S
Journal of Japanese Society of Intensive Care Medicine., 19, 2, 191, 196, 2012, [Peer-reviewed]
ICU患者の急性呼吸不全に対する肺内高頻度振動換気法（経気道的陽圧加圧振動法）の血液ガス改善効果の主要因は、同法に特有の”振動”である事を明らかにした前向き介入試験報告である。 - Imbalance Between Macrophage Migration Inhibitory Factor and Cortisol Induces Multiple Organ Dysfunction in Patients with Blunt Trauma
Mineji Hayakawa, Kenichi Katabami, Takeshi Wada, Yousuke Minami, Masahiro Sugano, Hidekazu Shimojima, Nobuhiko Kubota, Shinji Uegaki, Atsushi Sawamura, Satoshi Gando
INFLAMMATION, 34, 3, 193, 197, Jun. 2011, [Peer-reviewed]
English, Scientific journal - SIVELESTAT (SELECTIVE NEUTROPHIL ELASTASE INHIBITOR) IMPROVES THE MORTALITY RATE OF SEPSIS ASSOCIATED WITH BOTH ACUTE RESPIRATORY DISTRESS SYNDROME AND DISSEMINATED INTRAVASCULAR COAGULATION PATIENTS
Mineji Hayakawa, Kenichi Katabami, Takeshi Wada, Masahiro Sugano, Hirokatsu Hoshino, Atsushi Sawamura, Satoshi Gando
SHOCK, 33, 1, 14, 18, Jan. 2010, [Peer-reviewed]
English, Scientific journal - Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma
Atsushi Sawamura, Mineji Hayakawa, Satoshi Gando, Nobuhiko Kubota, Masahiro Sugano, Takeshi Wada, Ken-ichi Katabami
THROMBOSIS RESEARCH, 124, 6, 706, 710, Dec. 2009, [Peer-reviewed]
English, Scientific journal - Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality
Atsushi Sawamura, Mineji Hayakawa, Satoshi Gando, Nobuhiko Kubota, Masahiro Sugano, Takeshi Wada, Ken-ichi Katabami
THROMBOSIS RESEARCH, 124, 5, 608, 613, Nov. 2009, [Peer-reviewed]
English, Scientific journal
Other Activities and Achievements
- 【外傷性凝固障害と外傷性DIC】外傷性凝固障害と外傷性DICにおけるトロンビン産生 臨床的検討
高橋 正樹, 和田 剛志, Thrombosis Medicine, 13, 1, 19, 24, Mar. 2023
(株)先端医学社, Japanese - 【循環器集中治療の最前線】重症疾患に合併したDIC
土田 拓見, 和田 剛志, 循環器内科, 93, 1, 40, 46, Jan. 2023
(有)科学評論社, Japanese - 【徹底ガイドDICのすべて 2022-'23】基礎病態と治療 頭部外傷
高橋 正樹, 和田 剛志, 救急・集中治療, 34, 2, 740, 747, Jul. 2022
(株)総合医学社, Japanese - 【徹底ガイドDICのすべて 2022-'23】基礎病態と治療 心停止後症候群
土田 拓見, 和田 剛志, 救急・集中治療, 34, 2, 755, 761, Jul. 2022
(株)総合医学社, Japanese - 播種性血管内凝固の診断と治療
高橋 正樹, 和田 剛志, 集中治療医学レビュー, 2022-'23, 287, 293, May 2022
(株)総合医学社, Japanese - 【敗血症診療を知る-J-SSCG2020のポイント】敗血症におけるDIC診断と治療
和田 剛志, 射場 敏明, 医学のあゆみ, 279, 12-13, 1175, 1179, Dec. 2021
医歯薬出版(株), Japanese - 外傷性凝固障害はDICなのか、それとも活性化プロテインC仮説なのか 過去の病態論争と現在のコンセンサス、そして未来の方向性
和田 剛志, 日本外傷学会雑誌, 35, 3, 209, 218, Jul. 2021
(一社)日本外傷学会, Japanese - 重症熱傷における予後予測因子の検討
高橋 正樹, 水柿 明日美, 吉田 知由, 方波見 謙一, 和田 剛志, 前川 邦彦, 早川 峰司, 日本救急医学会雑誌, 32, 6, 295, 302, Jun. 2021
(一社)日本救急医学会, Japanese - 日本版敗血症診療ガイドライン2020
江木 盛時, 小倉 裕司, 矢田部 智昭, 安宅 一晃, 井上 茂亮, 射場 敏明, 垣花 泰之, 川崎 達也, 久志本 成樹, 黒田 泰弘, 小谷 穣治, 志馬 伸朗, 谷口 巧, 鶴田 良介, 土井 研人, 土井 松幸, 中田 孝明, 中根 正樹, 藤島 清太郎, 細川 直登, 升田 好樹, 松嶋 麻子, 松田 直之, 山川 一馬, 原 嘉孝, 大下 慎一郎, 青木 善孝, 稲田 麻衣, 梅村 穣, 河合 佑亮, 近藤 豊, 斎藤 浩輝, 櫻谷 正明, 對東 俊介, 武田 親宗, 寺山 毅郎, 東平 日出夫, 橋本 英樹, 林田 敬, 一二三 亨, 廣瀬 智也, 福田 龍将, 藤井 智子, 三浦 慎也, 安田 英人, 阿部 智一, 安藤 幸吉, 飯田 有輝, 石原 唯史, 井手 健太郎, 伊藤 健太, 伊藤 雄介, 稲田 雄, 宇都宮 明美, 卯野木 健, 遠藤 功二, 大内 玲, 尾崎 将之, 小野 聡, 桂 守弘, 川口 敦, 川村 雄介, 工藤 大介, 久保 健児, 倉橋 清泰, 櫻本 秀明, 下山 哲, 鈴木 武志, 関根 秀介, 関野 元裕, 高橋 希, 高橋 世, 高橋 弘, 田上 隆, 田島 吾郎, 巽 博臣, 谷 昌憲, 土谷 飛鳥, 堤 悠介, 内藤 貴基, 長江 正晴, 長澤 俊郎, 中村 謙介, 西村 哲郎, 布宮 伸, 則末 泰博, 橋本 悟, 長谷川 大祐, 畠山 淳司, 原 直己, 東別府 直紀, 古島 夏奈, 古薗 弘隆, 松石 雄二朗, 松山 匡, 峰松 佑輔, 宮下 亮一, 宮武 祐士, 森安 恵実, 山田 亨, 山田 博之, 山元 良, 吉田 健史, 吉田 悠平, 吉村 旬平, 四本 竜一, 米倉 寛, 和田 剛志, 渡邉 栄三, 青木 誠, 浅井 英樹, 安部 隆国, 五十嵐 豊, 井口 直也, 石川 雅巳, 石丸 剛, 磯川 修太郎, 板倉 隆太, 今長谷 尚史, 井村 春樹, 入野田 崇, 上原 健司, 生塩 典敬, 梅垣 岳志, 江川 裕子, 榎本 有希, 太田 浩平, 大地 嘉史, 大野 孝則, 大邉 寛幸, 岡 和幸, 岡田 信長, 岡田 遥平, 岡野 弘, 岡本 潤, 奥田 拓史, 小倉 崇以, 小野寺 悠, 小山 雄太, 貝沼 関志, 加古 英介, 柏浦 正広, 加藤 弘美, 金谷 明浩, 金子 唯, 金畑 圭太, 狩野 謙一, 河野 浩幸, 菊谷 知也, 菊地 斉, 城戸 崇裕, 木村 翔, 小網 博之, 小橋 大輔, 齊木 巌, 堺 正仁, 坂本 彩香, 佐藤 哲哉, 志賀 康浩, 下戸 学, 下山 伸哉, 庄古 知久, 菅原 陽, 杉田 篤紀, 鈴木 聡, 鈴木 祐二, 壽原 朋宏, 其田 健司, 高氏 修平, 高島 光平, 高橋 生, 高橋 洋子, 竹下 淳, 田中 裕記, 丹保 亜希仁, 角山 泰一朗, 鉄原 健一, 徳永 健太郎, 富岡 義裕, 冨田 健太朗, 富永 直樹, 豊崎 光信, 豊田 幸樹年, 内藤 宏道, 永田 功, 長門 直, 中村 嘉, 中森 裕毅, 名原 功, 奈良場 啓, 成田 知大, 西岡 典宏, 西村 朋也, 西山 慶, 野村 智久, 芳賀 大樹, 萩原 祥弘, 橋本 克彦, 旗智 武志, 浜崎 俊明, 林 拓也, 林 実, 速水 宏樹, 原口 剛, 平野 洋平, 藤井 遼, 藤田 基, 藤村 直幸, 舩越 拓, 堀口 真仁, 牧 盾, 増永 直久, 松村 洋輔, 真弓 卓也, 南 啓介, 宮崎 裕也, 宮本 和幸, 村田 哲平, 柳井 真知, 矢野 隆郎, 山田 浩平, 山田 直樹, 山本 朋納, 吉廣 尚大, 田中 裕, 西田 修, 日本版敗血症診療ガイドライン2020特別委員会, 日本救急医学会雑誌, 32, S1, S1, S411, Feb. 2021
(一社)日本救急医学会, Japanese - 【どんな薬剤・合併症・病態・患者背景にも対応できる 周術期の薬の使い方パーフェクトガイド】(第5章)病態に応じた周術期での注意点 播種性血管内凝固症候群(DIC)
土田 拓見, 和田 剛志, 薬事, 63, 3, 559, 566, Feb. 2021
(株)じほう, Japanese - 日本版敗血症診療ガイドライン2020
江木 盛時, 小倉 裕司, 矢田部 智昭, 安宅 一晃, 井上 茂亮, 射場 敏明, 垣花 泰之, 川崎 達也, 久志本 成樹, 黒田 泰弘, 小谷 穣治, 志馬 伸朗, 谷口 巧, 鶴田 良介, 土井 研人, 土井 松幸, 中田 孝明, 中根 正樹, 藤島 清太郎, 細川 直登, 升田 好樹, 松嶋 麻子, 松田 直之, 山川 一馬, 原 嘉孝, 大下 慎一郎, 青木 善孝, 稲田 麻衣, 梅村 穣, 河合 佑亮, 近藤 豊, 斎藤 浩輝, 櫻谷 正明, 對東 俊介, 武田 親宗, 寺山 毅郎, 東平 日出夫, 橋本 英樹, 林田 敬, 一二三 亨, 廣瀬 智也, 福田 龍将, 藤井 智子, 三浦 慎也, 安田 英人, 阿部 智一, 安藤 幸吉, 飯田 有輝, 石原 唯史, 井手 健太郎, 伊藤 健太, 伊藤 雄介, 稲田 雄, 宇都宮 明美, 卯野木 健, 遠藤 功二, 大内 玲, 尾崎 将之, 小野 聡, 桂 守弘, 川口 敦, 川村 雄介, 工藤 大介, 久保 健児, 倉橋 清泰, 櫻本 秀明, 下山 哲, 鈴木 武志, 関根 秀介, 関野 元裕, 高橋 希, 高橋 世, 高橋 弘, 田上 隆, 田島 吾郎, 巽 博臣, 谷 昌憲, 土谷 飛鳥, 堤 悠介, 内藤 貴基, 長江 正晴, 長澤 俊郎, 中村 謙介, 西村 哲郎, 布宮 伸, 則末 泰博, 橋本 悟, 長谷川 大祐, 畠山 淳司, 原 直己, 東別府 直紀, 古島 夏奈, 古薗 弘隆, 松石 雄二朗, 松山 匡, 峰松 佑輔, 宮下 亮一, 宮武 祐士, 森安 恵実, 山田 亨, 山田 博之, 山元 良, 吉田 健史, 吉田 悠平, 吉村 旬平, 四本 竜一, 米倉 寛, 和田 剛志, 渡邉 栄三, 青木 誠, 浅井 英樹, 安部 隆国, 五十嵐 豊, 井口 直也, 石川 雅巳, 石丸 剛, 磯川 修太郎, 板倉 隆太, 今長谷 尚史, 井村 春樹, 入野田 崇, 上原 健司, 生塩 典敬, 梅垣 岳志, 江川 裕子, 榎本 有希, 太田 浩平, 大地 嘉史, 大野 孝則, 大邉 寛幸, 岡 和幸, 岡田 信長, 岡田 遥平, 岡野 弘, 岡本 潤, 奥田 拓史, 小倉 崇以, 小野寺 悠, 小山 雄太, 貝沼 関志, 加古 英介, 柏浦 正広, 加藤 弘美, 金谷 明浩, 金子 唯, 金畑 圭太, 狩野 謙一, 河野 浩幸, 菊谷 知也, 菊地 斉, 城戸 崇裕, 木村 翔, 小網 博之, 小橋 大輔, 齊木 巌, 堺 正仁, 坂本 彩香, 佐藤 哲哉, 志賀 康浩, 下戸 学, 下山 伸哉, 庄古 知久, 菅原 陽, 杉田 篤紀, 鈴木 聡, 鈴木 祐二, 壽原 朋宏, 其田 健司, 高氏 修平, 高島 光平, 高橋 生, 高橋 洋子, 竹下 淳, 田中 裕記, 丹保 亜希仁, 角山 泰一朗, 鉄原 健一, 徳永 健太郎, 富岡 義裕, 冨田 健太朗, 富永 直樹, 豊崎 光信, 豊田 幸樹年, 内藤 宏道, 永田 功, 長門 直, 中村 嘉, 中森 裕毅, 名原 功, 奈良場 啓, 成田 知大, 西岡 典宏, 西村 朋也, 西山 慶, 野村 智久, 芳賀 大樹, 萩原 祥弘, 橋本 克彦, 旗智 武志, 浜崎 俊明, 林 拓也, 林 実, 速水 宏樹, 原口 剛, 平野 洋平, 藤井 遼, 藤田 基, 藤村 直幸, 舩越 拓, 堀口 真仁, 牧 盾, 増永 直久, 松村 洋輔, 真弓 卓也, 南 啓介, 宮崎 裕也, 宮本 和幸, 村田 哲平, 柳井 真知, 矢野 隆郎, 山田 浩平, 山田 直樹, 山本 朋納, 吉廣 尚大, 田中 裕, 西田 修, 日本版敗血症診療ガイドライン2020特別委員会, 日本集中治療医学会雑誌, 28, Suppl., S1, S411, Feb. 2021
(一社)日本集中治療医学会, Japanese - 出血性病態とトラネキサム酸(第3回) CRASH-3試験とトラネキサム酸
和田 剛志, Thrombosis Medicine, 10, 4, 299, 303, Dec. 2020
(株)先端医学社, Japanese - 日本版敗血症診療ガイドライン2020:Now Open! 敗血症性DICの診断と治療
射場 敏明, 久志本 成樹, 梅村 穣, 渡邉 栄三, 和田 剛志, 林田 敬, 日本版敗血症診療ガイドライン2020特別委員会, 日本救急医学会雑誌, 31, 11, 919, 919, Nov. 2020
(一社)日本救急医学会, Japanese - 【災害医療2020 大規模イベント、テロ対応を含めて】(第IV章)災害現場での医療判断と対応 各種ショックへの対応
和田 剛志, 土田 拓見, 日本医師会雑誌, 149, 特別1, S150, S154, Jun. 2020
(公社)日本医師会, Japanese - 線溶亢進型DIC(第4回) 心停止蘇生と線溶亢進型DIC
和田 剛志, Thrombosis Medicine, 10, 2, 138, 142, Jun. 2020
(株)先端医学社, Japanese - 救急・集中治療領域におけるDIC診療 正しい凝固・線溶検査の理解に基づく病態の理解
和田 剛志, 日本血栓止血学会誌, 31, 2, 207, 207, May 2020
(一社)日本血栓止血学会, Japanese - 【集中治療医学レビュー 最新主要文献と解説 2020-'21】I章 集中治療管理 血液凝固線溶系管理
和田 剛志, 集中治療医学レビュー, 2020-'21, 64, 70, Mar. 2020
(株)総合医学社, Japanese - 外尿道口の出血を伴わない尿道損傷の1例
執行亜希子, 早川峰司, 田中祥平, 中嶋拓磨, 高橋正樹, 田原就, 土田拓見, 定本圭弘, 川原翔太, 本間慶憲, 大安孝允, 早水真理子, 斉藤智誉, 吉田知由, 方波見謙一, 和田剛志, 前川邦彦, 日本集中治療医学会北海道支部学術集会プログラム・抄録集(Web), 4th, 2020 - 敗血症と血管内皮細胞障害(第1回) 敗血症と血管内皮細胞障害
和田 剛志, Thrombosis Medicine, 9, 4, 361, 365, Dec. 2019
(株)先端医学社, Japanese - 【ICU治療指針 II】血液・凝固線溶系疾患と管理 血液・凝固線溶系疾患 好中球減少
土田 拓見, 和田 剛志, 救急・集中治療, 31, 3, 974, 977, Dec. 2019
(株)総合医学社, Japanese - 【ICU治療指針 II】血液・凝固線溶系疾患と管理 血液・凝固線溶系管理 血液・凝固線溶系の検査と評価
土田 拓見, 和田 剛志, 救急・集中治療, 31, 3, 981, 985, Dec. 2019
(株)総合医学社, Japanese - 【死戦期における血液凝固線溶系の病態生理】重症頭部外傷の血液凝固線溶系
和田 剛志, Thrombosis Medicine, 9, 1, 23, 29, Mar. 2019
(株)先端医学社, Japanese - 【血栓止血の臨床-研修医のために[第2版]】血小板減少を伴う血栓性疾患 DICの治療 感染症、救命救急領域、外科領域
和田 剛志, 日本血栓止血学会誌, 30, 1, 218, 222, Feb. 2019
(一社)日本血栓止血学会, Japanese - 集中治療管理 血液凝固線溶系管理
和田 剛志, 集中治療医学レビュー, 2018-'19, 66, 72, Feb. 2018
(株)総合医学社, Japanese - Factors associated with postintensive care syndrome: Medical care and the ICU environment
和田剛志, Intensivist, 10, 1, 47‐60, 01 Jan. 2018
Japanese - ショック時の多臓器障害症候群を考える 神経内分泌系・自律神経系・免疫系の連関は多臓器不全に関与する?
和田剛志, 救急・集中治療, 29, 5-6, 391‐396, 20 May 2017
Japanese - Precious experience of research abroad in Boston
WADA Takeshi, Japanese Journal of Thrombosis and Hemostasis, 28, 6, 760, 762, 2017
The Japanese Society on Thrombosis and Hemostasis, Japanese - 神経内分泌系・自律神経系・免疫系の連関は多臓器不全に関与する? (ショック管理 : ショックと臓器障害連関のメカニズム) -- (ショック時の多臓器障害症候群を考える)
和田 剛志, 救急・集中治療, 29, 5, 391, 396, 2017
総合医学社, Japanese - "PHONE FIRST" IS ASSOCIATED WITH DECREASED INTACT SURVIVAL IN OUT-OF-HOSPITAL CARDIAC ARREST
Kunihiko Maekawa, Mineji Hayakawa, Yuichi Ono, Tomonao Yoshida, Kenichi Katabami, Takeshi Wada, AtsUshi Sawamura, Satoshi Gando, CRITICAL CARE MEDICINE, 44, 12, Dec. 2016
English, Summary international conference - RETHINKING NW: WHEN IT WORKS, IT WORKS. WHEN IT DOESN'T, IT REALLY DOESN'T.
Kunihiko Maekawa, Mineji Hayakawa, Yuichi Ono, Tomonao Yoshida, Kenichi Katabami, Takeshi Wada, AtsUshi Sawamura, Satoshi Gando, CRITICAL CARE MEDICINE, 44, 12, Dec. 2016
English, Summary international conference - 救急治療薬―ここが知りたい,何故使うか,どう使うか 救急現場における治療薬への課題 抗血小板薬,抗凝固薬使用中の急性出血への対応
和田剛志, 救急医学, 40, 12, 1543‐1552, 10 Nov. 2016
Japanese - 重症多発外傷患者における脳脂肪塞栓症の検討
澤村 淳, 小館 明, 定本 圭弘, 村上 博基, 水柿 明日美, 方波見 謙一, 前川 邦彦, 宮本 大輔, 小野 雄一, 和田 剛志, 早川 峰司, 丸藤 哲, 日本外傷学会雑誌, 30, 2, 230, 230, May 2016
(一社)日本外傷学会, Japanese - PLATELET COUNT, AND GLOBAL MARKERS OF COAGULATION AND FIBRINOLYSIS DURING EARLY PHASE OF OUT-OF-HOSPITAL CARDIAC ARREST AND RESUSCITATION
S. Gando, T. Wada, Y. Ono, K. Maekawa, THROMBOSIS RESEARCH, 141, S59, S59, May 2016
English, Summary international conference - Sepsis-induced DIC and Immunothrombosis
丸藤 哲, 和田 剛志, 小野 雄一, 前川 邦彦, 方波見 謙一, 早川 峰司, 澤村 淳, ICUとCCU = Japanese journal of intensive care medicine : 集中治療医学, 40, 3, 171, 179, Mar. 2016
医学図書出版, Japanese - ゾニサミド使用後に高体温を呈した2例
吉田 知由, 早川 峰司, 本間 多恵子, 小野 雄一, 和田 剛志, 柳田 雄一郎, 澤村 淳, 丸藤 哲, 日本集中治療医学会雑誌, 22, 6, 519, 522, Nov. 2015
(一社)日本集中治療医学会, Japanese - 3D-CTA診断が可能であったクモ膜下出血症例の検討
澤村 淳, 小舘 旭, 村上 博基, 水柿 明日美, 前川 邦彦, 方波見 謙一, 小野 雄一, 宮本 大輔, 和田 剛志, 早川 峰司, 丸藤 哲, 日本救急医学会雑誌, 26, 8, 383, 383, Aug. 2015
(一社)日本救急医学会, Japanese - Role of activated protein c and soluble fibrin in the early phase of trauma with disseminated intravascular coagulation: comparison with acute coagulopathy of trauma-shock
S. Gando, A. Sawamura, M. Hayakawa, T. Wada, Y. Yanagida, D. Miyamoto, K. Maekawa, Y. Ono, A. Mizugaki, S. Jesmin, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 13, 327, 327, Jun. 2015
English, Summary international conference - 外傷性脳内出血症例のpitfall
澤村 淳, 水柿 明日美, 方波見 謙一, 前川 邦彦, 小野 雄一, 宮本 大輔, 和田 剛志, 柳田 雄一郎, 早川 峰司, 丸藤 哲, 日本外傷学会雑誌, 29, 2, 197, 197, May 2015
(一社)日本外傷学会, Japanese - PHARMACOKINETICS OF LEVOFLOXACIN IN CRITICALLY-ILL PATIENTS RECEIVING CONTINUOUS HEMODIAFILTRATION
Takeshi Wada, Masaki Kobayashi, Daisuke Miyamoto, Yuichiro Yanagida, Mineji Hayakawa, Atsushi Sawamura, Ken Iseki, Satoshi Gando, CRITICAL CARE MEDICINE, 42, 12, Dec. 2014
English, Summary international conference - THE OVERPRODUCTION OF NITRIC OXIDE INDUCED BY ANGIOGENIC AND COAGULATION FACTORS LEADS TO MULTIPLE ORGAN DYSFUNCTION SYNDROME ASSOCIATED WITH POST-CARDIAC ARREST SYNDROME
T. Wada, S. Jesmin, A. Mizugaki, K. Katabami, Y. Ono, K. Maekawa, D. Miyamoto, Y. Yanagida, M. Hayakawa, A. Sawamura, S. Gando, INTENSIVE CARE MEDICINE, 40, S272, S272, Sep. 2014
English, Summary international conference - ゾニサミド使用後に高体温を呈した2例
吉田 知由, 本間 多恵子, 小野 雄一, 和田 剛志, 柳田 雄一郎, 早川 峰司, 澤村 淳, 丸藤 哲, 日本集中治療医学会雑誌, 21, Suppl., [DP, 106, Jan. 2014
(一社)日本集中治療医学会, Japanese - Surgery Provides A Better Clinical Outcome Following Severe Traumatic Brain Injury
Atsushi Sawamura, Takeshi Wada, Yu-ichi Ono, Daisuke Miyamoto, Yuichiro Yanagida, Masahiro Sugano, Mineji Hayakawa, Satoshi Gando, CRITICAL CARE MEDICINE, 41, 12, Dec. 2013
English, Summary international conference - EFFCTS OF RIKKUNSHITO (TRADITIONAL JAPANESE MEDICINE KAMPO) ON ENTERAL FEEDLNG AND PLASMA GHRELIN CONCENTRATION IN CRITICALLY ILL PATIENTS: A DOUBLE-BLIND, RANDMIZED, CONTROLLED TRIAL
Y. Yanagida, M. Hayakawa, H. Yamamoto, T. Wada, M. Sugano, A. Sawamura, S. Gando, INTENSIVE CARE MEDICINE, 39, S242, S243, Oct. 2013
English, Summary international conference - Normal prothrombinase activity, systemic thrombin activation, and lower antithrombin levels in patients with DIC at an early phase of trauma: comparison with Acute Coagulopathy of Trauma-Shock (ACOTS)
S. Gando, Y. Yanagida, A. Sawamura, M. Hayakawa, N. Kubota, T. Wada, Y. Ono, H. Yamamoto, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 11, 1049, 1049, Jul. 2013
English, Summary international conference - 橈骨動脈グラフトを用いた多発内頸動脈瘤による頸動脈-海綿静脈洞瘻の治療 4D-flow MRI脳血流解析を含めて
中川 俊祐, 村井 保夫, 和田 剛志, 展 広智, 立山 幸次郎, 喜多村 孝幸, 寺本 明, 水成 隆之, 小林 士郎, 吉田 陽一, 日本脳神経外科救急学会プログラム・抄録集, 18th, 72, 72, 2013
(NPO)日本脳神経外科救急学会, Japanese - 院外心肺停止患者に対するECPR施行時脳低温療法の検討
松本 学, 水柿 明日美, 和田 剛志, 田上 隆, 白石 振一郎, 増野 智彦, 宮内 雅人, 辻井 厚子, 布施 明, 横田 裕行, 日本集中治療医学会雑誌, 20, Suppl., 292, 292, Jan. 2013
(一社)日本集中治療医学会, Japanese - ORGAN SPECIFIC EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) IN LIPOPOLYSACCHARIDE (LPS)-INDUCED ENDOTOXEMIA
Subrina Jesmin, Yuichiro Yanagida, Takeshi Wada, Nobutake Shimojo, Taro Mizutani, Satoshi Gando, CRITICAL CARE MEDICINE, 40, 12, U65, U65, Dec. 2012
English, Summary international conference - ANGIOGENIC FACTORS AND THEIR SOLUBLE RECEPTORS PREDICT ORGAN DYSFUNCTION AND MORTALITY IN POST-CARDIAC ARREST SYNDROME (PCAS)
Takeshi Wada, Subrina Jesmin, Satoshi Gando, Yuichiro Yanagida, Asumi Higashiyama, Sayeeda Sultana, Sohel Zaedi, Hiroyuki Yokota, CRITICAL CARE MEDICINE, 40, 12, U160, U160, Dec. 2012
English, Summary international conference - I sepsis・SIRSの概念と定義,病態 Q3 Surviving Sepsis CampaignとSSCG2008からさらなる改訂へ
WADA TAKESHI, GANDO SATOSHI, 救急・集中治療, 24, 9-10, 1015, 1019, 23 Oct. 2012
Japanese - ANGIOGEMIC FACTORS AND THEIR SOLUBLE RECEPTORS IN ACUTE LUNG INJURY (ALI/ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) IN CRITICALLY ILL PATIENTS
T. Wada, S. Jesmin, S. Gando, A. Mizugaki, Y. Yanagida, H. Yokota, INTENSIVE CARE MEDICINE, 38, S247, S247, Oct. 2012
English, Summary international conference - AMELIORATION OF ACUTE LIVER INJURY THROUGH THE SUPPRESSION OF UPREGULATED LEVELS OF ENDOTHELIN-1 AND TNF-A IN A RAT MODEL OF ENDOTOXEMIA WITH THE BLOCKADE OF PROTEASE ACTIVATED RECEPTOR-2 (PAR2)
S. Jesmin, T. Wada, S. Zaedi, N. Shimojo, S. N. Sultana, M. Moroi, T. Watanebe, S. Gando, INTENSIVE CARE MEDICINE, 38, S104, S104, Oct. 2012
English, Summary international conference - Elastase-mediated fibrinolysis in disseminated intravascular coagulation (DIC) associated with sepsis
Takeshi Wada, Satoshi Gando, Yuichiro Yanagida, Shinji Uegaki, Nobuhiko Kubota, Mineji Hayakawa, Atsushi Sawamura, Subrina Jesmin, THROMBOSIS RESEARCH, 130, S184, S184, Oct. 2012
English, Summary international conference - Angiogenic factors and their soluble receptors for predicting organ dysfunction in disseminated intravascular coagulation associated with sepsis
Takeshi Wada, Jesmin Subrina, Satoshi Gando, BRITISH JOURNAL OF ANAESTHESIA, 108, 76, 77, Mar. 2012
English, Summary international conference - IABP導入前後にBIS値の変動を認めた脳低体温療法の一症例
太田好紀, 和田剛志, 小野雄一, 白石振一郎, 松本学, 斉藤徳子, 村田広茂, 増野智彦, 新井正徳, 横田裕行, 日本集中治療医学会雑誌, 19, Supplement, 2012 - TIME-DEPENDENT ALTERATIONS OF VEGF AND ITS SIGNALING MOLECULES IN ACUTE LUNG INJURY IN A RAT MODEL OF SEPSIS
T. Wada, S. Jesmin, S. Zaedi, S. Gando, INTENSIVE CARE MEDICINE, 37, S9, S9, Sep. 2011
English, Summary international conference - Etiology and treatment for extracardiac obstructive shock
和田 剛志, 横田 裕行, The Japanese journal of acute medicine, 35, 4, 434, 437, Apr. 2011
へるす出版, Japanese - PR3-ANCA-ASSOCIATED MICROSCOPIC POLYANGITIS IN A PATIENT WITH SEPSIS
Takeshi Wada, Mineji Hayakawa, Satoshi Gando, CRITICAL CARE MEDICINE, 38, 12, U286, U286, Dec. 2010
English, Summary international conference - A pseudoaneurysm of lumbar artery by traumatic avulsion injury
WADA TAKESHI, SAWAMURA ATSUSHI, KATABAMI KEN'ICHI, SUGANO MASAHIRO, HAYAKAWA MINEJI, GANDO SATOSHI, 日本救急医学会雑誌, 21, 9, 799-803 (J-STAGE), 803, 15 Sep. 2010
Japanese - The relationship between high level of FDP (fibrin/fibrinogen degradation products) on the admission and massive bleeding in patients with blunt trauma
HAYAKAWA Mineji, WADA Takeshi, SUGANO Masahiro, SHIMOJIMA Hidekazu, UEGAKI Shinji, SAWAMURA Astushi, GANDO Satoshi, 日本救急医学会雑誌, 21, 4, 165, 171, 15 Apr. 2010
鈍的外傷による早期の死亡は大量出血によるものが大半である。その原因として，臓器損傷や血管損傷による直接的な出血と凝固障害を原因とする出血の2つの側面がある。今回，鈍的外傷患者では治療開始前の搬入直後に線溶亢進が認められ，その線溶亢進が凝固障害による大量出血と関係があるとの仮設を立て，受傷現場から直接搬入された鈍的外傷患者を対象に搬入直後の凝固線溶系の検査結果と大量出血の関係を後ろ向きに検討した。2005 年1 月1 日から2006 年12 月31 日の間に，受傷現場から北海道大学病院先進急性期医療センターに直接搬入となったabbreviated injury scale が3 以上の損傷を含む鈍的外傷症例を対象とした。対象患者の診療録から，患者背景，搬入直後の血液検査結果，輸血量などの情報を後ろ向きに収集し，大量出血群と非大量出血群に分類した。83 名が参入基準を満たした。大量出血群は17 症例，非大量出血群66 症例であった。fibrin/fibrinogen degradation products（FDP）とD-dimer に関しては，両群とも著明な高値を示し，大量出血群が非大量出血群と比較して統計学的な有意差を認めていた。ロジスティック回帰分析ではFDPのみが大量出血の独立した予測変数として選択された。大量出血予測に関するreceiver operating characteristic 曲線では，FDPが最も大きな曲線下面積を示した。鈍的外傷患者では，搬入直後にフィブリン/ フィブリノゲン分解に伴うFDPの異常高値を示しており，FDP>64.1μg/ml をカットオフ値とすることで，外傷早期の線溶亢進を原因とする大量出血を予測しうることを示した。鈍的外傷患者の搬入直後のFDP値に注目することにより，外傷早期の凝固障害に対して速やかに対応できる可能性がある。Introduction: Early death after blunt trauma is caused by massive bleeding. Our previous report demonstrated thatdisseminated intravascular coagulation with a fibrinolytic phenotype from the time of admission to the emergencydepartment until 4 hours thereafter contributes to a poor prognosis due to massive bleeding.Objective: Fibrinolysis at admission to the emergency department immediately after blunt trauma may predict massivebleeding. This study retrospectively investigated the relationship between coagulation and fibrinolysis, and massivebleeding at an early phase in patients presenting with blunt trauma.Methods: All patients with blunt trauma admitted to the emergency department, associated with, at least, one of the abbreviatedinjury scales ≥3 from January 2005 to December 2006 were enrolled in the study. The clinical backgroundsof the patients and the measured variables were retrospectively collected.Results: Eighty-three patients; 17 patients with massive bleeding and 66 patients without massive bleeding, were includedin this study. Fibrin/fibrinogen degradation products (FDP) and D-dimer levels markedly increased in bothgroups. FDP and D-dimer in the massive bleeding group were statistically higher than those in the non-massivebleeding group. A stepwise logistic regression analysis showed FDP to be an independent predictor of massivebleeding. The receiver operating characteristic curve analysis for massive bleeding showed FDP to have the largestarea under the curve and that the optimal cutoff point of FDP in order to predict massive bleeding was >64.1 μg/ml.Conclusion: Increased fibrin/fibrinogen degradation resulting in high FDP levels at an early phase of trauma istherefore considered to predict massive bleeding. The optimal cutoff point of FDP to predict massive bleeding was>64.1 μg/ml., 日本救急医学会, Japanese - 甲状腺クリーゼと診断した4例の検討
WADA TAKESHI, SAWAMURA ATSUSHI, SUGANO MASAHIRO, HENZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, HAYAKAWA MINEJI, GANDO SATOSHI, 日本集中治療医学会雑誌, 17, 2, 191, 195, 01 Apr. 2010
Four cases of thyroid crisis are herein reported. The prompt diagnosis and immediate treatment resulted in all 4 patients achieving a complete recovery from the crisis. However, one patient unfortunately died from hypoxic encephalopathy which had been caused by cardiopulmonary arrest during transportation to our hospital. As pointed out in the previous studies, all 4 patients showed signs of cardiac decompensation during the treatment. Based on the findings of these present cases as well as those of previous reports, we would like to emphasize the need for strict hemodynamic monitoring of all patients associated with thyroid crisis. Moreover, we believe that it is extremely important to evaluate the thyroid function when trauma patients demonstrate persistent and unusual tachycardia and pyrexia after the onset of injury., The Japanese Society of Intensive Care Medicine, Japanese - PR3-ANCA-Associated Microscopic Polyangitis in a Patient with Sepsis
WADA TAKESHI, SAWAMURA ATSUSHI, KATABAMI KEN'ICHI, SUGANO MASAHIRO, KUBOTA NOBUHIKO, HAYAKAWA MINEJI, GANDO SATOSHI, ICUとCCU, 34, 3, 243, 247, 10 Mar. 2010
医学図書出版, Japanese - A case of fat embolism syndrome during surgical graft replacement of the descending aorta for blunt aortic injury
NAKATA Asako, HAYAKAWA Mineji, WADA Takeshi, SUGANO Masahiro, HOSHINO Hirokatsu, SAWAMURA Atsushi, GANDO Satoshi, 日本救急医学会雑誌, 21, 1, 42, 49, 15 Jan. 2010
鈍的大動脈損傷に対する胸部下行大動脈置換術中に発症した脂肪塞栓症候群の1例を経験した。本症例では，術中から術後の急性呼吸不全と重度の全身性炎症反応症候群（systemic in-flammatory response syndrome; SIRS）の原因解明に難渋し，脂肪塞栓症候群の診断が遅延した。患者は 26 歳の男性。歩行中に乗用車にはねられ受傷した。当院搬入時は意識清明であった。画像診断で胸部下行大動脈損傷と右大腿骨骨幹部骨折を認めた。大腿骨骨折に対し創外固定を行った後，即日，人工血管置換術を施行した。ヘパリン投与後，経皮的心肺補助装置を導入し分離肺換気を開始した前後に，気道から淡血性泡沫状の分泌物を多量に認めはじめ，急速に酸素化能が悪化した。術後も手術侵襲のみでは説明が困難な SIRS と呼吸不全が遷延した。術後 5 日目に前胸部に点状出血があることに気づき，脂肪塞栓症候群を疑いステロイド治療を開始した。呼吸，循環動態はすみやかに改善した。意識障害が遷延し，第21病日にmagnetic resonance imaging（MRI）を撮影したところ，T2 star 強調画像や磁化率強調画像で，両側大脳白質や皮質下白質，脳梁，内包，視床，中脳から橋，小脳などに無数の微細な低信号を認め，脂肪塞栓症候群に典型的な画像であった。本症例では，脂肪塞栓症候群の特徴の一つである呼吸不全が人工血管置換術中に発症したため脂肪塞栓症候群の診断が遅延した。, 日本救急医学会, Japanese - FIBRINOGENOLYSIS DURING THE EARLY STAGE OF TRAUMA PREDICTS THE OCCURRENCE OF MASSIVE BLEEDING IN PATIENTS WITH BLUNT TRAUMA
M. Hayakawa, T. Wada, K. Katabami, M. Sugano, N. Henzan, H. Hoshino, A. Sawamura, S. Gando, INTENSIVE CARE MEDICINE, 35, 10, 10, Sep. 2009
English, Summary international conference - 急性期DIC診断基準による外傷早期のDICによる大量出血の予見は可能か?
HAYAKAWA MINEJI, KATABAMI KEN'ICHI, MINAMI YOSUKE, WADA TAKESHI, SUGANO MASAHIRO, SHIMOJIMA HIDEKAZU, KUBOTA NOBUHIKO, UEGAKI SHINJI, SAWAMURA ATSUSHI, GANDO SATOSHI, 日本救急医学会雑誌, 20, 8, 506, 15 Aug. 2009
Japanese - 鈍的外傷による偽性腰動脈瘤の一例
WADA TAKESHI, SAWAMURA ATSUSHI, KATANAMI KEN'ICHI, MINAMI YOSUKE, SUGANO MASAHIRO, SHIMOJIMA HIDEKAZU, KUBOTA NOBUHIKO, UEGAKI SHINJI, HAYAKAWA MINEJI, GANDO SATOSHI, 日本救急医学会雑誌, 20, 8, 479, 15 Aug. 2009
Japanese - 生体肝移植術後に出現したPRES(Posterior Reversible Encephalopathy Syndrome)の二症例
SAWAMURA JUN, KATANAMI KEN'ICHI, MINAMI YOSUKE, WADA TAKESHI, SUGANO MASAHIRO, SHIMOJIMA HIDEKAZU, UEGAKI SHINJI, KUBOTA NOBUHIKO, HAYAKAWA MINEJI, GANDO SATOSHI, 日本救急医学会雑誌, 20, 8, 527, 15 Aug. 2009
Japanese - 妊婦の劇症型A群溶血性連鎖球菌感染症の1例
KATANAMI KEN'ICHI, MINAMI YOSUKE, WADA TAKESHI, SUGANO MASAHIRO, SHIMOJIMA HIDEKAZU, KUBOTA NOBUHIKO, UEGAKI SHINJI, HAYAKAWA MINEJI, SAWAMURA ATSUSHI, GANDO SATOSHI, 日本救急医学会雑誌, 20, 8, 689, 15 Aug. 2009
Japanese - 急性循環不全を呈した劇症型心筋症の一例
SUGANO MASAHIRO, SAWAMURA ATSUSHI, KATABAMI KEN'ICHI, WADA TAKESHI, HEIANZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, HAYAKAWA MINEJI, ISHIKAWA TAKEHIKO, GANDO SATOSHI, 北海道外科雑誌, 54, 1, 78, 79, 20 Jun. 2009
Japanese - 妊婦劇症型A群溶血性連鎖球菌感染症の一例
KATABAMI KEN'ICHI, HAYAKAWA MINEJI, WADA TAKESHI, SUGANO MASAHIRO, HEIANZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, SAWAMURA ATSUSHI, ISHIKAWA TAKEHIKO, GANDO SATOSHI, 北海道外科雑誌, 54, 1, 81, 20 Jun. 2009
Japanese - 指摘されていなかった過去の右横隔膜ヘルニアに嵌頓した肝挫傷の一例
KATANAMI KEN'ICHI, HAYAKAWA MINEJI, WADA TAKESHI, SUGANO MASAHIRO, HEIANZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, SAWAMURA ATSUSHI, GANDO SATOSHI, 日本外傷学会雑誌, 23, 2, 201, 20 Apr. 2009
Japanese - 偽性腰動脈瘤の手術中に偶然発見された外傷性肝管損傷の1例
WADA TAKESHI, SAWAMURA ATSUSHI, KATANAMI KEN'ICHI, SUGANO MASAHIRO, HEIANZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, HAYAKAWA MINEJI, GANDO SATOSHI, 日本外傷学会雑誌, 23, 2, 201, 20 Apr. 2009
Japanese - 外傷急性期のフィブリノーゲン溶解と出血予測
HAYAKAWA MINEJI, KATANAMI KEN'ICHI, WADA TAKESHI, SAWAMURA ATSUSHI, GANDO SATOSHI, 日本外傷学会雑誌, 23, 2, 162, 20 Apr. 2009
Japanese - モニタリングの基本 III 代謝・体液系モニタリング 凝固線溶系
GANDO SATOSHI, SAWAMURA ATSUSHI, HAYAKAWA MINEJI, KUBOTA NOBUHIKO, HENZAN NAOMI, SUGANO MASAHIRO, WADA TAKESHI, KATABAMI KEN'ICHI, 救急医学, 33, 3, 311, 315, 10 Mar. 2009
Japanese - 急性呼吸不全患者に対するIntrapulmonary Percussive Ventilationの効果
NAKAHASHI SUSUMU, HAYAKAWA MINEJI, KATABAMI KEN'ICHI, WADA TAKESHI, KANNO MASAHIRO, HIRAYASUYAMA NAOMI, HOSHINO HIROKATSU, SAWAMURA ATSUSHI, ISHIKAWA TAKEHIKO, GANDO SATOSHI, 日本集中治療医学会雑誌, 16, Supplement, 251, 20 Jan. 2009
Japanese - SepsisによるARDS・DICに対する好中球エラスターゼ阻害薬sivelestatの効果
HAYAKAWA MINEJI, KATABAMI KEN'ICHI, WADA TAKESHI, KANNO MASAHIRO, HENZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, SAWAMURA ATSUSHI, GANDO SATOSHI, 日本集中治療医学会雑誌, 16, Supplement, 162, 20 Jan. 2009
Japanese - 敗血症を契機に発症したと思われるPR3‐ANCA陽性顕微鏡的多発血管炎の1例
WADA TAKESHI, SAWAMURA ATSUSHI, KATABAMI KEN'ICHI, KANNO MASAHIRO, HIRAYASUYAMA NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, HAYAKAWA MINEJI, ISHIKAWA TAKEHIKO, GANDO SATOSHI, 日本集中治療医学会雑誌, 16, Supplement, 301, 20 Jan. 2009
Japanese - 注射用抗菌薬Ciprofloxacin(CPFX)の敗血症における免疫能に及ぼす影響
SAWAMURA ATSUSHI, KATABAMI KEN'ICHI, WADA TAKESHI, KANNO MASAHIRO, HIRAYASUYAMA NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, HAYAKAWA MINEJI, ISHIKAWA TAKEHIKO, GANDO SATOSHI, 日本集中治療医学会雑誌, 16, Supplement, 224, 20 Jan. 2009
Japanese - Monitoring of platelets, coagulation and fibrinolysis in critical care
GANDO Satoshi, SAWAMURA Atsushi, HAYAKAWA Mineji, HOSHINO Hirokatsu, KUBOTA Nobuhiko, HENZAN Naomi, SUGANO Masahiro, WADA Takeshi, KATABAMI Ken-ichi, Nihon Kyukyu Igakukai Zasshi, 20, 1, 1, 15, 15 Jan. 2009
This report reviews the recent developments in platelet, coagulation and fibrinolysis monitoring for critically ill patients. Initially the report reviews hemorrhagic and thrombotic tendencies, diagnosis and treatment methods, and artificial apparatuses that need monitoring for platelet, coagulation and fibrinolysis. Thereafter, detailed monitoring for platelet, coagulation and fibrinolysis was introduced and discussed. Finally, the activated clotting time, a thromboelastgraph, an activated thromboelastgraph, and a waveform analysis of the clotting test were reviewed. Further developments in the management and treatment of critically ill patients by using such platelet, coagulation and fibrinolysis monitoring system are thus anticipated., Japanese Association for Acute Medicine, Japanese - SIVELESTAT IMPROVES MORTALITY RATE OF SEPTIC PATIENTS ASSOCIATED WITH ARDS AND DIC.
Mineji Hayakawa, Kenichi Katabami, Takeshi Wada, Masahiro Sugano, Naomi Henzan, Nobuhiko Kubota, Hirokatsu Hoshino, Atsushi Sawamura, Satoshi Gando, CRITICAL CARE MEDICINE, 36, 12, A142, A142, Dec. 2008
English, Summary international conference - THE RESPONSE OF ANTITHROMBIN III ACTIVITY AFTER SUPPLEMENTATION DECREASES IN PROPORTION TO THE SEVERITY OF SEPSIS AND LIVER DYSFUNCTION.
Mineji Hayakawa, Naomi Henzan, Kenichi Katabami, Takeshi Wada, Masahiro Sugano, Nobuhiko Kubota, Horokatsu Hoshino, Atsushi Sawamura, Satoshi Gando, CRITICAL CARE MEDICINE, 36, 12, A111, A111, Dec. 2008
English, Summary international conference - 注射用抗菌薬Ciprofloxacin(CPFX)のSepsisにおける免疫能に及ぼす影響
SAWAMURA ATSUSHI, KATABAMI KEN'ICHI, WADA TAKESHI, SUGANO MASAHIRO, HENZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, HAYAKAWA MINEJI, ISHIKAWA TAKEHIKO, GANDO SATOSHI, 日本外科感染症学会雑誌, 5, 5, 594, 05 Oct. 2008
Japanese - 鼻出血による出血性ショックで発症した海綿静脈洞内内頚動脈瘤の一例
WADA TAKESHI, HAYAKAWA MINEJI, KATABAMI KEN'ICHI, SUGANO MASAHIRO, HEIAN'YAMA NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, SAWAMURA ATSUSHI, GANDO SATOSHI, 日本救急医学会雑誌, 19, 8, 566, 15 Aug. 2008
Japanese - 速乾性擦式手指消毒剤ウェルパス(R)誤飲により食道炎を併発した1例
KATANAMI KEN'ICHI, HAYAKAWA MINEJI, WADA TAKESHI, SUGANO MASAHIRO, HIRAYASUYAMA NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, SAWAMURA JUN, ISHIKAWA TAKEHIKO, GANDO SATOSHI, 日本救急医学会雑誌, 19, 8, 629, 15 Aug. 2008
Japanese - 鈍的大動脈損傷に対する下行大動脈置換術中に発症した脂肪塞栓症候群の1例
NAKADA ASAKO, KATANAMI KEN'ICHI, WADA TAKESHI, SUGANO MASAHIRO, HEIANZAN NAOMI, KUBOTA NOBUHIKO, HOSHINO HIROKATSU, HAYAKAWA MINEJI, SAWAMURA ATSUSHI, GANDO SATOSHI, 日本救急医学会雑誌, 19, 8, 668, 15 Aug. 2008
Japanese
Courses
Affiliated academic society
- THE JAPAN SOCIETY OF NEUROTRAUMATOLOGY
- THE JAPANESE ASSOCIATION FOR THE SURGERY OF TRAUMA
- THE JAPANESE SOCIETY OF INTENSIVE CARE MEDICINE
- THE JAPAN NEUROSURGICAL SOCIETY
- JAPANESE ASSOCIATION FOR ACUTE MEDICINE
- Society of Critical Care Medicine
- International Society on Thrombosis and Haemostasis
- European Society of Intensive Care Medicine
- 日本臨床救急医学会
- THE JAPANESE SOCIETY ON THROMBOSIS AND HEMOSTASIS
Research Themes
- 敗血症後に生じる免疫機能不全への挑戦：顆粒球単球吸着除去による免疫調整療法
科学研究費助成事業
01 Apr. 2024 - 31 Mar. 2027
高須 朗, 山川 一馬, 久宗 遼, 和田 剛志, 谷口 高平
日本学術振興会, 基盤研究(C), 大阪医科薬科大学, 24K12168 - Trauma induces expansion and activation of a memory-like Treg population
Grants-in-Aid for Scientific Research
01 Apr. 2024 - 31 Mar. 2027
山川 一馬, 和田 剛志, 梅村 穣, 谷口 高平
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka Medical and Pharmaceutical University, 24K12188 - Innovative Therapeutic Strategies for ARDS: A Fundamental Study of Total Pulmonary Alveolar Lavage under ECMO Support
Grants-in-Aid for Scientific Research
01 Apr. 2024 - 31 Mar. 2027
生塩 典敬, 和田 剛志, 山川 一馬, 谷口 高平
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka Medical and Pharmaceutical University, 24K12209 - Development of a Bleeding Management Algorithm through analysing von Willebrand Factor and Fibrinolysis in Extracorporeal Circulation Patients
Grants-in-Aid for Scientific Research
01 Apr. 2023 - 31 Mar. 2026
雨宮 優, 梅村 穣, 和田 剛志, 中村 謙介, 山川 一馬, 日下 裕介
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka Medical and Pharmaceutical University, 23K08485 - 敗血症病態における血管内皮グリコカリックス障害の修復促進因子の解明と治療戦略構築
科学研究費助成事業
01 Apr. 2023 - 31 Mar. 2026
久宗 遼, 山川 一馬, 谷口 高平, 和田 剛志
日本学術振興会, 基盤研究(C), 大阪医科薬科大学, 23K08433 - 好中球の異質性が関与する外傷後二次性感染症の病態解明と治療法開発に向けた基盤研究
科学研究費助成事業 基盤研究(C)
01 Apr. 2022 - 31 Mar. 2025
斉藤 智誉, 和田 剛志, 山川 一馬
日本学術振興会, 基盤研究(C), 北海道大学, 22K09109 - 重度侵襲後の遷延性免疫不全PIICSにおける骨髄由来免疫抑制細胞の関与
科学研究費助成事業 基盤研究(C)
01 Apr. 2022 - 31 Mar. 2025
三嶋 隆之, 山川 一馬, 和田 剛志, 中村 謙介, 梅村 穣
日本学術振興会, 基盤研究(C), 大阪医科薬科大学, 22K09154 - CyTOFを用いた集中治療後症候群の病態解明と予防法開発に向けた基盤研究
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2021 - Mar. 2024
前川 邦彦
敗血症モデルとして盲腸結紮穿孔(CLP)と、当研究室で新たにモデルとしての妥当性を検証したfecal suspension intraperitoneal injection(FSI)モデルを作成し、①生存率評価、②サイトカイン/ケモカインのLUMINEXによる網羅的測定のための血漿検体採取・保存、③Cytometry by time-of-flightにより血中免疫細胞評価のための血液検体処理・保存、④臓器障害評価のための肺、肝、腎、脾の摘出、保存、を行った。
1-①：生存率はCLP、FSIでそれぞれ77.5％、CLPで67.5％であり、生存したマウスに対して敗血症誘導1か月後にリポポリサッカライド(LPS)10mg/kgの投与をおこなった。sham損傷後LPS投与では、31％のマウスが死亡したが、予想に反して敗血症後マウスに対するLPS投与ではCLP、FSIともに死亡は確認されなかった。病態機序解明のため、上記②-④を行い、まず免疫学的機序解析のため③の検体測定を行ったが、検体処理過程で実施者の家族にCOVID-19陽性が判明し処理継続が不能となったため、CyTOF用の検体の大半が使用不能となった。そのため、最初からの実験やり直しを検討している。
また敗血症後の免疫変化はLPSによる二次性の侵襲に対して保護的に働いている可能性が示唆されている。実験前の仮説と異なる結果であり、二次性の侵襲をLPS投与ではなく、肺炎を誘導するなど感染症による変化を確認することを検討したい。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 21K09008 - Histone/NETsを標的とした外傷性凝固障害の病態生理解明と治療法の確立
科学研究費助成事業 基盤研究(C)
01 Apr. 2020 - 31 Mar. 2023
丸藤 哲, 和田 剛志
多施設共同で集積した外傷症例276症例を対象に、外傷性凝固障害（trauma-induced coagulopathy, TIC）と外傷後の播種性血管内凝固症候群（disseminated intravascular coagulation, DIC）の凝固線溶動態は同一である、と言う仮説の証明を試みた。
TIC/DICの血小板・凝固線溶動態を比較検討し、両者が同一の病態で有ることを以下の結果から証明した。
TIC/DICともに、1）活性化プロテインCが上昇するが、トロンビン制御可能な値ではない、2）その結果外傷直後から大量のトロンビン産生が起こる、3）トロンビン産生により消費性凝固障害が起こり血小板数、アンチトロンビン、プロテインCが減少する、4）外傷直後に血管内皮細胞から遊離したtissue-type plasminogen activator (t-PA)が高値となり線溶亢進が起こるが約3時間の経過を経てplasminogen activator inhibitor-1 (PAI-1)発現が誘導され線溶抑制が生ずる、5）DIC症例は非DIC症例と比較して輸血量、新鮮凍結血漿投与量、濃厚血小板液投与量が多く（いずれもp<0.001）、病院死亡率は明らかに高値である（7.5 vs. 26.7%, p=0.001）。
さらに本研究は、DIC病態が外傷直後から起こる事を証明した事に意義があり、上記結果とともに外傷症例の治療方針に大きな示唆を与えるものと推定される。
これらの結果は、2020年7月開催（online） International Society on Thrombosis and Haemostasis Congressで報告し、同学会機関誌であるJournal of Thrombosis and Haemostais (202018:2232-44)に掲載された。
日本学術振興会, 基盤研究(C), 北海道大学, 20K09280 - 頭部外傷特異的な免疫応答と二次性感染症におけるインフラマソーム制御機構の解明
科学研究費助成事業 基盤研究(C)
01 Apr. 2020 - 31 Mar. 2023
和田 剛志
頭部外傷（TBI）後二次性敗血症モデルを作成し、sham損傷後二次性敗血症モデルと①生存率、②生菌数の比較を行った。①生存率：TBI 87% vs. sham 67%とTBI群の方が生存率が高かった。②腹水中生菌数はTBI群ではsham群と比較して有意に低値であった。以上のことから、過去の報告同様、頭部外傷後に生じる免疫応答はその後の感染症/敗血症に保護的に働いている可能性が確認された。
続いて、LUMINEXによる血清、腹水中のサイトカインの網羅的測定を行った。TBI群では、IL-6、TNFalpha、IL-17に代表される炎症性サイトカインが有意に高値である一方、IL-4、IL-10などの抗炎症性サイトカインは両群間に有意な差は認められなかった。また、TBI群ではT細胞非依存性INF gamma誘導に重要な役割を果たすIL-12P70が高値であり、実際にINF gammaの高値も確認された。
以上より、頭部外傷後に生じる敗血症病態では、顕著な炎症反応活性化が病原体の除去、生存率の改善に寄与している可能性が示唆される。
上記2つのモデルにおける免疫細胞、特に好中球、単球（マクロファージ）をはじめとする自然免疫系の変化の解析をすべく、CyTOF mass cytometry用の検体を収集し、CyTOF測定を行った。今後、クラウドデータベースOMIC上で多次元解析を行い免疫細胞機能変化と上述の病態の関連を検討する予定である。TBIで生じている免疫変化を明らかにすることにより、新たな感染症治療の治療標的を見出すことが期待される。
日本学術振興会, 基盤研究(C), 北海道大学, 20K09260 - CyTOF technologyを用いた生体侵襲後免疫変化に起因する臓器不全、敗血症発症の病態解明
Apr. 2021 - Mar. 2022
公益信託丸茂救急医学研究振興基金助成金, Principal investigator - 外傷性凝固障害(trauma-induced coagulopathy: TIC)の病態理解に基づく新診断基準の策定
Apr. 2021 - Mar. 2022
JA交通事故医療研究助成, Principal investigator - Pathophysiology of coagulation and fibrinolysis at an early phase of trauma.
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2015 - 31 Mar. 2018
Gando Satoshi, SAWAMURA Atsushi, HAYAKAWA Mineji, YANAGIDA Yuichiro, WADA Takeshi, MIYAMOTO Daisuke
To elucidate the mechanisms of trauma-induced coagulopathy, prospective and retrospective studies were performed. We demonstrated that trauma itself induces changes in coagulation and fibrinolysis, which consists of activation of coagulation (thrombin generation), insufficient anticoagulation systems (TFPI, antithrombin, protein C and thrombomodulin), and inhibition of fibrinolysis by PAI-1. The conditions are coincided with the pathophysiology of disseminated intravascular coagulation (DIC). These evidences were also confirmed by experimental studies using Noble-Collip Drum rat trauma models. Base on the results, we have published several original studies and review articles including one systematic review. To confirm these phenomenon, we, have conducted prospective multicenter study recruiting 108 institutes in Japan. The study has now completed and is waiting the publication of the obtained results in the English journal.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 15K15658 - Genomic polymorphisms of disseminated intravascular coagulation in patients with trauma and sepsis.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2013 - 31 Mar. 2017
GANDO SATOSHI, SAWAMURA ATSUSHI, HAYAKAWA MINEJI, WADA TAKESHI
As presented in the interim report of last year, we have measured damage-associated molecular patterns (DAMPs) (histone H3, H4), molecules in complement pathways (C3a, C5a), and major anticoagulant molecules, activated protein C, in patients with sepsis and trauma. In addition, we studied relationships between disseminated intravascular coagulation (DIC) and activated protein C to investigate pathophysiological roles of coagulation and fibrinolysis. Based on these results, we came to conclusion that in trauma patients with DIC, endothelial cells injury as well as reduction of activated protein C synergistically induces disseminated thrombin generation in the whole-body circulation. Disseminated thrombin generation, so-called DIC gives rise to multiple organ dysfunction, leading to worse outcome of trauma patients.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 25293364 - 補体系が関与する生体侵襲下臓器障害の病態解明とその治療体系の確立
血液医学分野 海外留学助成
Apr. 2016 - Mar. 2017
和田剛志
公益財団法人 先進医薬研究振興財団, Principal investigator, Competitive research funding - The establishment of a control system for HIF1alpha activation pathway in post-cardiac arrest syndrome.
Grants-in-Aid for Scientific Research
2013 - 2014
WADA TAKESHI
I investigated the important role of fibrinolysis which are involved in neutrophil elastase and plasmin, which is affected by plasminogen activator inhibitor-1 (PAI-1), which is induced by Hypoxia inducible factor-1α (HIF1α) in post-cardiac arrest syndrome (PCAS). The results indicated that fibrinolytic shutdown plays important roles in the development of organ dysfunction in PCAS patients. Neutrophil elastase-mediated fibrinolysis cannot overcome the fibrinolytic shutdown that occurs in DIC patients with PCAS, thus resulting in the development of multiple organ dysfunction.
In addition, I studied the relationship between the serum levels of HIF1α and the development of DIC or organ dysfunction in sepsis, severe trauma, and PCAS patients. These studies showed no significant results. This can be explained by the fact that HIF1α acts inside the cell.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 25861736 - Interaction of hypoxia, and coagulation and inflammation through HIF-α.
Grants-in-Aid for Scientific Research
2011 - 2012
GANDO Satoshi, JESMIN Saubrina, WADA Takeshi
To test the hypothesis that Hypoxia-inducible factor1-α-induced angiogenetic factors (VEGF/VEGFR1/VEGFR2, angiopoietin and Tie2) deeply involved in the pathogenesis of organ dysfunction in patients with DIC associated with trauma, sepsis, and post cardiac arrest syndrome, we investigated the relationships of these factors and DIC. The results indicated that angiogenetic factors and DIC is one of the main causes of organ dysfunctionin patients with these three insults.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 24659793 - To elucidate the pathophysiology of sepsis-associated organ dysfunction involving the Ang/Tie2 signaling pathway
Grants-in-Aid for Scientific Research(若手研究(B))
2011 - 2012
Takeshi WADA
The aim of this study was to elucidate the pathophysiology of sepsis-associated organ dysfunction involving the Ang/Tie2 signaling pathway and to establish a new therapeutic strategy for treating critical illnesses, such as sepsis, severe trauma and post-cardiac arrest syndrome. I examined the relationship between organ dysfunction associated with critical illness and angiogenic factors, including VEGF, Ang and their receptors and found that Ang2 plays a pivotal role in the development of organ dysfunction due to coagulofibrinolytic abnormalities. The findings of this study have been presented at six domestic and four international conferences and have also been published by four peerreview articles.
Ministry of Education, Culture, Sports, Science and Technology, 若手研究(B), 日本医科大学, Principal investigator, Competitive research funding, 23792091 - Elucidation of pathomechanisms of organ dysfunction caused by interaction of body insults and responses.
Grants-in-Aid for Scientific Research
2009 - 2012
GANDO Satoshi, JESMIN Saubrina, AWAMURA Atsushi, WADA Takeshi
To establish new methods to prevent and to treat organ dysfunction caused by the relationships between body insults and body responses, we have investigated pathogenesis of the interaction among three representative body insults, namely inflammation, tissue injury, and ischemia and reperfusion, and body responses to the insults. We specifiedto elucidate hypothesis that control of neuroendocrine responses could prevent organ dysfunction through the improvement of changes in coagulation and fibrinolytic response
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 21249086 - ヒストン/NETsが担う病的自然免疫反応による外傷性凝固障害病態解明研究
一般社団法人 日本損害保険協会, 2022年度交通事故医療研究助成(一般研究) - 凝固・補体遺伝子解析による敗血症性播種性血管内凝固症候群と血栓性微小血管症の併存病態解明研究
公益財団法人 武田科学振興財団, 2021年度 医学系研究助成 - 頭部外傷後免疫応答が関与する慢性外傷性脳症の病態解明と治療法開発に向けた基盤研究
公益財団法人 脳神経財団, 2021年度一般研究助成 - CyTOF technologyを用いた外傷免疫機能変化の解明-白血球の「数」から「質」の評価へ
交通事故医療研究助成
和田剛志
日本損害保険協会, Principal investigator, Competitive research funding
