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2019 Fiscal Year Annual Research Report

自然免疫炎症反応・凝固線溶反応の心停止蘇生後臓器不全への関与

Research Project

Project/Area Number 17H04361
Research InstitutionHokkaido University

Principal Investigator

丸藤 哲  北海道大学, 医学研究院, 名誉教授 (30125306)

Project Period (FY) 2017-04-01 – 2020-03-31
Keywords心停止 / 臓器不全 / 自然免疫炎症反応 / 凝固線溶反応
Outline of Annual Research Achievements

2020年度末までに健常成人対照10症例と患者45症例となり解析を実施した。
その結果以下を確認する事ができた。
1)心停止蘇生に伴いdamage-associated molecular patterns (DAMPs)の代表であるヒストンH3が3時間後高値となり約24時間高値が持続する、2)多臓器不全(multiple organ dysfunction syndrome, MOD)をsequential organ failure assessment (SOFA)スコア>=12と定義し多臓器不全合併の有無で検討を加えると、MODS群のヒストン値は蘇生後0および3時間において非MODS群よりも有意に高値を呈した(0h; 2.25 vs 5.60, p=0.036: 3h; 3.6 vs 12.6, p=0.044)MODS群の播種性血管内凝固症候群(disseminated intravascular coagulation, DIC)スコア値は非MODS群と比較して有意に高値である(1 vs 4, p=0.012)、4)MODS群の病院死亡率は非MODS群よりも有意に高い (16 vs 33%, p=0.0132)(値は median)。
すでに心停止蘇生に伴う、1)大量のトロンビン産生に引き続くプラスミン産生、3)プラスミン産生は傷害血管内皮細胞から遊離したtissue-type plasminogen activator (t-PA)が原因と考えられる、4)t-PAの速やかな上昇後に線溶抑制因子であるplasminogen activator inhibitor-1 (PAI-1)が上昇する、事を確認している。
以上から、心停止蘇生に伴いDICが起こり、その原因として虚血/再灌流に伴う傷害細胞・組織から遊離したDAMPs(ヒストン)が想定される。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

  • Research Products

    (25 results)

All 2021 2020

All Journal Article (21 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 21 results,  Open Access: 21 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Current spectrum of causative pathogens in sepsis: A prospective nationwide cohort study in Japan2021

    • Author(s)
      Umemura Yutaka、Ogura Hiroshi、Takuma Kiyotsugu、Fujishima Seitato、Abe Toshikazu、Kushimoto Shigeki、Hifumi Toru、Hagiwara Akiyoshi、Shiraishi Atsushi、Otomo Yasuhiro、Saitoh Daizoh、Mayumi Toshihiko、Yamakawa Kazuma、Gando Satoshi
    • Journal Title

      International Journal of Infectious Diseases

      Volume: 103 Pages: 343~351

    • DOI

      10.1016/j.ijid.2020.11.168

    • Peer Reviewed / Open Access
  • [Journal Article] ISTH interim guidance on recognition and management of coagulopathy in COVID‐192020

    • Author(s)
      Thachil Jecko、Tang Ning、Gando Satoshi、Falanga Anna、Cattaneo Marco、Levi Marcel、Clark Cary、Iba Toshiaki
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Pages: 1023~1026

    • DOI

      10.1111/jth.14810

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Type and dose of heparin in Covid‐19: Reply2020

    • Author(s)
      Thachil Jecko、Tang Ning、Gando Satoshi、Falanga Anna、Levi Marcel、Clark Cary、Iba Toshiaki、Cattaneo Marco
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Pages: 2063~2064

    • DOI

      10.1111/jth.14870

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Laboratory haemostasis monitoring in COVID‐192020

    • Author(s)
      Thachil Jecko、Tang Ning、Gando Satoshi、Falanga Anna、Levi Marcel、Clark Cary、Iba Toshiaki
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Pages: 2058~2060

    • DOI

      10.1111/jth.14866

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DOACs and “newer” hemophilia therapies in COVID‐19: Reply2020

    • Author(s)
      Thachil Jecko、Tang Ning、Gando Satoshi、Falanga Anna、Cattaneo Marco、Levi Marcel、Clark Cary、Iba Toshiaki
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Pages: 1795~1796

    • DOI

      10.1111/jth.14841

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Defining trauma‐induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH2020

    • Author(s)
      Moore HB, Gando Satoshi、Iba Toshiaki、Kim Paul Y.、Yeh Calvin H.、Brohi Karim、Hunt Beverley J.、Levy Jerrold H.、Draxler Dominik F.、Stanworth Simon、G?rlinger Klaus、Neal Matthew D.、Schreiber Martin A.、Barrett Christopher D.、Medcalf Robert L.、Moore Ernest E.、Mutch Nicola J.
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Pages: 740~747

    • DOI

      10.1111/jth.14690

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significance of body temperature in elderly patients with sepsis2020

    • Author(s)
      Shimazui Takashi、on behalf of the JAAM FORECAST Group、Nakada Taka-aki、Walley Keith R.、Oshima Taku、Abe Toshikazu、Ogura Hiroshi、Shiraishi Atsushi、Kushimoto Shigeki、Saitoh Daizoh、Fujishima Seitaro、Mayumi Toshihiko、Shiino Yasukazu、Tarui Takehiko、Hifumi Toru、Otomo Yasuhiro、Gando Satoshi
    • Journal Title

      Critical Care

      Volume: 24 Pages: 387-387

    • DOI

      10.1186/s13054-020-02976-6

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The SIRS criteria have better performance for predicting infection than qSOFA scores in the emergency department2020

    • Author(s)
      Gando Satoshi、The Japanese Association for Acute Medicine (JAAM) Sepsis Prognostication in Intensive Care Unit and Emergency Room (SPICE) (JAAM SPICE) Study Group、Shiraishi Atsushi、Abe Toshikazu、Kushimoto Shigeki、Mayumi Toshihiko、Fujishima Seitaro、Hagiwara Akiyoshi
    • Journal Title

      Scientific Reports

      Volume: 10 Pages: 8095-8095

    • DOI

      10.1038/s41598-020-64314-8

    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics and outcomes of bacteremia among ICU-admitted patients with severe sepsis2020

    • Author(s)
      Komori Akira、JAAM FORECAST group、Abe Toshikazu、Kushimoto Shigeki、Ogura Hiroshi、Shiraishi Atsushi、Saitoh Daizoh、Fujishima Seitaro、Mayumi Toshihiko、Naito Toshio、Hifumi Toru、Shiino Yasukazu、Nakada Taka-aki、Tarui Takehiko、Otomo Yasuhiro、Gando Satoshi
    • Journal Title

      Scientific Reports

      Volume: 10 Pages: 2983-2983

    • DOI

      10.1038/s41598-020-59830-6

    • Peer Reviewed / Open Access
  • [Journal Article] A multicenter prospective validation study on disseminated intravascular coagulation in trauma‐induced coagulopathy2020

    • Author(s)
      Gando Satoshi、Shiraishi Atsushi、Wada Takeshi、Yamakawa Kazuma、Fujishima Seitaro、Saitoh Daizoh、Kushimoto Shigeki、Ogura Hiroshi、Abe Toshikazu、Otomo Yasuhiro
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Pages: 2232~2244

    • DOI

      10.1111/jth.14931

    • Peer Reviewed / Open Access
  • [Journal Article] Risk modifiers of acute respiratory distress syndrome in patients with non-pulmonary sepsis: a retrospective analysis of the FORECAST study2020

    • Author(s)
      Iriyama Hiroki、on behalf of JAAM FORECAST group、Abe Toshikazu、Kushimoto Shigeki、Fujishima Seitaro、Ogura Hiroshi、Shiraishi Atsushi、Saitoh Daizoh、Mayumi Toshihiko、Naito Toshio、Komori Akira、Hifumi Toru、Gando Satoshi
    • Journal Title

      Journal of Intensive Care

      Volume: 8 Pages: 7-7

    • DOI

      10.1186/s40560-020-0426-9

    • Peer Reviewed / Open Access
  • [Journal Article] History of diabetes may delay antibiotic administration in patients with severe sepsis presenting to emergency departments2020

    • Author(s)
      Abe Toshikazu、Suzuki Tomoharu、Kushimoto Shigeki、Fujishima Seitaro、Sugiyama Takehiro、Iwagami Masao、Ogura Hiroshi、Shiraishi Atsushi、Saitoh Daizoh、Mayumi Toshihiko、Iriyama Hiroki、Komori Akira、Nakada Taka-aki、Shiino Yasukazu、Tarui Takehiko、Gando Satoshi
    • Journal Title

      Medicine

      Volume: 99 Pages: e19446~e19446

    • DOI

      10.1097/MD.0000000000019446

    • Peer Reviewed / Open Access
  • [Journal Article] The significance of disseminated intravascular coagulation on multiple organ dysfunction during the early stage of acute respiratory distress syndrome2020

    • Author(s)
      Gando Satoshi、Fujishima Seitaro、Saitoh Daizoh、Shiraishi Atsushi、Yamakawa Kazuma、Kushimoto Shigeki、Ogura Hiroshi、Abe Toshikazu、Mayumi Toshihiko、Sasaki Junichi、Kotani Joji、Takeyama Naoshi、Tsuruta Ryosuke、Takuma Kiyotsugu、Yamashita Norio、Shiraishi Shin-ichiro
    • Journal Title

      Thrombosis Research

      Volume: 191 Pages: 15~21

    • DOI

      10.1016/j.thromres.2020.03.023

    • Peer Reviewed / Open Access
  • [Journal Article] Underlying disorders of disseminated intravascular coagulation: Communication from the ISTH SSC Subcommittees on Disseminated Intravascular Coagulation and Perioperative and Critical Care Thrombosis and Hemostasis2020

    • Author(s)
      Squizzato Alessandro、Gallo Andrea、Levi Marcel、Iba Toshiaki、Levy Jerrold H.、Erez Offer、ten Cate Hugo、Solh Ziad、Gando Satoshi、Vicente Vicente、Di Nisio Marcello
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Pages: 2400~2407

    • DOI

      10.1111/jth.14946

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identifying Septic Shock Populations Benefitting From Polymyxin B Hemoperfusion: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model2020

    • Author(s)
      Nakata Hidekazu、Yamakawa Kazuma、Kabata Daijiro、Umemura Yutaka、Ogura Hiroshi、Gando Satoshi、Shintani Ayumi、Shiraishi Atsushi、Saitoh Daizoh、Fujishima Seitaro、Mayumi Toshihiko、Kushimoto Shigeki、Abe Toshikazu、Shiino Yasukazu、Nakada Taka-aki、Tarui Takehiko、Hifumi Toru
    • Journal Title

      Shock

      Volume: 54 Pages: 667~674

    • DOI

      10.1097/SHK.0000000000001533

    • Peer Reviewed / Open Access
  • [Journal Article] Clinical characteristics of patients with severe sepsis and septic shock in relation to bacterial virulence of beta‐hemolytic Streptococcus and Streptococcus pneumoniae2020

    • Author(s)
      Hifumi Toru、Fujishima Seitaro、Ubukata Kimiko、Hagiwara Akiyoshi、Abe Toshikazu、Ogura Hiroshi、Shiraishi Atsushi、Kushimoto Shigeki、Saitoh Daizoh、Mayumi Toshihiko、Ikeda Hiroto、Ueyama Masashi、Otomo Yasuhiro、Okamoto Kohji、Umemura Yutaka、Kotani Joji、Gando Satoshi、the JAAM FORECAST group
    • Journal Title

      Acute Medicine & Surgery

      Volume: 7 Pages: 513-513

    • DOI

      10.1002/ams2.513

    • Peer Reviewed / Open Access
  • [Journal Article] Demographics, Treatments, and Outcomes of Acute Respiratory Distress Syndrome: the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) Study2020

    • Author(s)
      Gando Satoshi、Saitoh Daizoh、Kushimoto Shigeki、Ogura Hiroshi、Abe Toshikazu、Shiraishi Atsushi、Mayumi Toshihiko、Sasaki Junichi、Kotani Joji、Takeyama Naoshi、Tsuruta Ryosuke
    • Journal Title

      Shock

      Volume: 53 Pages: 544~549

    • DOI

      10.1097/SHK.0000000000001416

    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study2020

    • Author(s)
      Komori Akira、for the JAAM SPICE Study Group、Abe Toshikazu、Yamakawa Kazuma、Ogura Hiroshi、Kushimoto Shigeki、Saitoh Daizoh、Fujishima Seitaro、Otomo Yasuhiro、Gando Satoshi
    • Journal Title

      BMC Geriatrics

      Volume: 20 Pages: 485-485

    • DOI

      10.1186/s12877-020-01893-1

    • Peer Reviewed / Open Access
  • [Journal Article] Epidemiology of sepsis and septic shock in intensive care units between sepsis-2 and sepsis-3 populations: sepsis prognostication in intensive care unit and emergency room (SPICE-ICU)2020

    • Author(s)
      Abe Toshikazu、for the JAAM SPICE Study Group、Yamakawa Kazuma、Ogura Hiroshi、Kushimoto Shigeki、Saitoh Daizoh、Fujishima Seitaro、Otomo Yasuhiro、Kotani Joji、Umemura Yutaka、Sakamoto Yuichiro、Sasaki Junichi、Shiino Yasukazu、Takeyama Naoshi、Tarui Takehiko、Shiraishi Shin-ichiro、Gando Satoshi
    • Journal Title

      Journal of Intensive Care

      Volume: 8 Pages: 44-44

    • DOI

      10.1186/s40560-020-00465-0

    • Peer Reviewed / Open Access
  • [Journal Article] COVID-19と凝固線溶系異常(第1回) 新型コロナウイルス感染症と凝固線溶系2020

    • Author(s)
      丸藤, 哲
    • Journal Title

      Thrombosis Medicine

      Volume: 10 Pages: 314-319

    • Peer Reviewed / Open Access
  • [Journal Article] 外国人救急医療の集約化には中国語通訳の準備と整形外科と消化器科のバックアップ体制が必要である2020

    • Author(s)
      増井 伸高、丸藤 哲, 松田 知倫
    • Journal Title

      日本救急医学会雑誌

      Volume: 31 Pages: 2168-2168

    • Peer Reviewed / Open Access
  • [Presentation] 教育講演 生体侵襲とDIC-敗血症、外傷、心停止2020

    • Author(s)
      丸藤 哲
    • Organizer
      第14回日本血栓止血学会学術標準化委員会
    • Invited
  • [Presentation] A multicenter prospective validation study and disseminated intravascular coagulation in trauma-induced coagulopathy2020

    • Author(s)
      丸藤 哲
    • Organizer
      ISTH 2020 Virtual Congress
    • Int'l Joint Research
  • [Presentation] Invited speaker, Activation of the coagulation system during COVID-19 - insight in the pathophysiology2020

    • Author(s)
      丸藤 哲
    • Organizer
      Euroanesthesia
    • Int'l Joint Research / Invited
  • [Book] Trauma Induced Coagulopathy2021

    • Author(s)
      Gando S, Wada T
    • Total Pages
      802
    • Publisher
      Springer International Publishing

URL: 

Published: 2021-12-27  

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