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Endothelial cell rescue therapy of multiorgan failure after severe sepsis

Research Project

Project/Area Number 22390337
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionTokyo Women's Medical University (2011-2012)
Tokyo Medical and Dental University (2010)

Principal Investigator

ISOTANI Eiji  東京女子医科大学, 医学部, 教授 (90251529)

Co-Investigator(Kenkyū-buntansha) OOTOMO Yasuhiro  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (40176946)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords集中治療医学 / 敗血症 / DIC / トロンボモジュリン / アンチトロンビンIII / 内皮細胞障害 / 他臓器不全 / マウス敗血症モデル / 急性肺障害 / 多臓器不全
Research Abstract

Introduction: It is expected that recombinant human soluble thrombomodulin (rTM) not only reverses hyper-coagulative status through activating protein C but also prevents multiple organ failure. rTM may improve both physiological scores and the amount of mediators, and reduces the mortality of sepsis and DIC patients in 28 days. We started a new protocol by adding rTM for sepsis and disseminated intravascular coagulation patients. We introduce the preliminary report in this paper.Material & Methods: We enrolled and analyzed 21 patients who were treated for DIC accompanied by sepsis from May to October 2008. Our primary endpoint was mortality in 28 days. As composite outcomes, we followed Acute Physiology and Chronic Health Evaluation (APATCHE II) score, Sequential Organ Failure Assessment (SOFA) score, acute phase DIC score, and serum soluble thrombomodulin, TNF-α, IL-1β, IL-6, HMGB-1, protein C, protein S levels during 10 days. Statistical analysis was performed by Wilcoxon rank-sum test. P < 0.05 was regarded as statistically significant.Results: We found that all scores and mediators improved after administration of rTM in Day 10, but there was no significant improvement in at 28 days. Median of each score or mortality was as follows; APATCH II score: 32 at Day 1 to 26 at Day 10 (p=0.0048), SOFA score: 12 to 8 (p=0.0096), acute phase DIC score: 5 to 3 (p

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (33 results)

All 2012 2011 2010 Other

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (16 results) Book (5 results) Remarks (2 results)

  • [Journal Article] Pathophysiology of acute respiratory distress syndrome2012

    • Author(s)
      Eiji Isotani
    • Journal Title

      Crit Care Med.

      Volume: 40(7) Pages: 2233-2234

    • Related Report
      2012 Final Research Report
  • [Journal Article] vharacteristics of normovolemia and normotension therapy after subarachnoid hemorrhage2012

    • Author(s)
      Sato Y, Isotani E, Kubota Y, Otomo Y, Ohno Y. Circulatory
    • Journal Title

      focusing on pulmonary edema

      Volume: 154(12) Pages: 2195-202

    • Related Report
      2012 Final Research Report
  • [Journal Article] 敗血症性 DIC 発症時の ATIII活性が転帰に及ぼす影響2012

    • Author(s)
      磯谷栄二、世良俊樹、牛澤洋人、高橋宏之、大友康裕
    • Journal Title

      バイオメディカル

      Volume: 第22巻

    • Related Report
      2012 Final Research Report
  • [Journal Article] アンチトロンビン値からみた敗血症性 DIC 患者の予後についての検討2012

    • Author(s)
      近藤景介、世良俊樹、牛澤洋人、 磯谷栄二、大友康裕
    • Journal Title

      日本救急医学会関東地方会誌

      Volume: 33 Pages: 140-141

    • Related Report
      2012 Final Research Report
  • [Journal Article] Pathophysiology of acute respiratory distress syndrome2012

    • Author(s)
      Eiji Isotani
    • Journal Title

      Crit Care Med

      Volume: 40(7) Issue: 7 Pages: 2233-4

    • DOI

      10.1097/ccm.0b013e3182514a29

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circulatory characteristics of normovolemia and normotension therapy after subarachnoid hemorrhage, focusing on pulmonary edema2012

    • Author(s)
      Sato Y
    • Journal Title

      Acta Neurochir (Wien)

      Volume: 154(12) Issue: 12 Pages: 2195-202

    • DOI

      10.1007/s00701-012-1491-1

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 敗血症性DIC発症時のATIII活性が転帰に及ぼす影響2012

    • Author(s)
      磯谷栄二
    • Journal Title

      バイオメディカル

      Volume: 22

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アンチトロンビン値からみた敗血症性DIC患者の予後についての検討2012

    • Author(s)
      近藤景介
    • Journal Title

      日本救急医学会関東地方会誌

      Volume: 33

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 組み換えヒト可溶型トロンボモジュリン(rTM)の敗血症性 DIC 患者への治療経験2011

    • Author(s)
      高橋宏之、 磯谷栄二、牛澤洋人、若林正和、庄古知久、相星淳一、加地正人、大友康裕
    • Journal Title

      ICUと CCU

      Volume: 35(7) Pages: 581-584

    • NAID

      40018968282

    • Related Report
      2012 Final Research Report
  • [Journal Article] 組み替えヒト可溶型トロンボモジュリン(rTM)の敗血症性DIC患者への治療経験2011

    • Author(s)
      高橋宏之、磯谷栄二、牛澤洋人, 他
    • Journal Title

      ICUとCCU

      Volume: 35(7) Pages: 581-584

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 敗血症性 DIC における組み換えヒト可溶型トロンボモジュリン(rTM)のランダム化比較試験2012

    • Author(s)
      牛澤洋人、 磯谷栄二、高橋宏之、世良俊樹、大友康裕
    • Organizer
      第40回日本救急医学会総会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2012-11-14
    • Related Report
      2012 Final Research Report
  • [Presentation] Prognostic factors of sepsis with disseminated intravascular coagulation (DIC) patients under administration of antithrombin III in Japan2012

    • Author(s)
      Sera T, Isotani E, Ushizawa H, Takahashi H, Otomo Y
    • Organizer
      The 25thannual congress of ESICM.
    • Place of Presentation
      Lisbon
    • Year and Date
      2012-10-15
    • Related Report
      2012 Final Research Report
  • [Presentation] Randomized controlled trial of novel recombinant human soluble thrombomodulin (rTM) for sepsis with DIC patients in Japan2012

    • Author(s)
      Ushizawa H, Isotani E, Takahashi H, Sera T, Otomo Y
    • Organizer
      The 25thannual congress of ESICM
    • Place of Presentation
      Lisbon.
    • Year and Date
      2012-10-15
    • Related Report
      2012 Final Research Report
  • [Presentation] 敗血症性 DIC に対するリコンビナントトロンボモジュリン(rTM)のランダム化試験(RCT)2012

    • Author(s)
      牛澤洋人、 磯谷栄二、世良俊樹、 大友康裕
    • Organizer
      第39回日本集中治療医学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2012-02-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 敗血症性DICに対するリコンビナントトロンボモジュリン(rTM)のランダム化試験(RCT)2012

    • Author(s)
      牛澤洋人
    • Organizer
      第15回日本臨床救急医学会
    • Place of Presentation
      熊本
    • Related Report
      2012 Annual Research Report
  • [Presentation] Prognostic factors of sepsis with disseminated intravascular coagulation (DIC) patients under administration of antithrombin III in Japan2012

    • Author(s)
      Sera T
    • Organizer
      The 25th annual congress of ESICM
    • Place of Presentation
      Lisbon
    • Related Report
      2012 Annual Research Report
  • [Presentation] Randomized controlled trial of novel recombinant human soluble thrombomodulin (rTM) for sepsis with DIC patients in Japan2012

    • Author(s)
      Ushizawa H
    • Organizer
      The 25th annual congress of ESICM
    • Place of Presentation
      Lisbon
    • Related Report
      2012 Annual Research Report
  • [Presentation] 敗血症性DICにおける組み換えヒト可溶型トロンボモジュリン(rTM)のランダム化比較試験2012

    • Author(s)
      牛澤洋人
    • Organizer
      第40回日本救急医学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] The Role of Novel Recombinant Human Soluble Thrombomodulin for Sepsis and Disseminated Intravascular Coagulation Patients2011

    • Author(s)
      Isotani E, Ushizawa H, Takahashi H, Sera T, Otomo Y
    • Organizer
      MEMCVI Kos Greek
    • Year and Date
      2011-09-14
    • Related Report
      2012 Final Research Report
  • [Presentation] 敗血症性 DIC 治療におけるリコンビナントトロンボモジュリン(rTM)の臨床的効果2011

    • Author(s)
      磯谷栄二、牛澤洋人、小林正貴、高橋宏之、大友康裕
    • Organizer
      第14回日本臨床救急医学会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2011-06-04
    • Related Report
      2012 Final Research Report
  • [Presentation] 敗血症DIC治療におけるリコンビナントトロンボモジュリンの臨床的効果一各種メディエーターの推移2011

    • Author(s)
      牛澤洋人
    • Organizer
      第38回日本集中治療学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-02-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Randomized controlled trial of recombinant human soluble thrombomodulin for sepsis and disseminated intravascular coagulation patients.2011

    • Author(s)
      牛澤洋人
    • Organizer
      40^<th> Annual Meeting of Society of Critical Care Medicine
    • Place of Presentation
      San Diego
    • Year and Date
      2011-01-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] パネルディスカッション 10.術後合併症としての敗血症・DIC に対する診断と治療。敗血症に伴う多臓器不全に対する治療戦略2010

    • Author(s)
      磯谷栄二
    • Organizer
      第35回日本外科系連合学会
    • Place of Presentation
      シェラトン・グランデ・トーキョーベイ・ホテル
    • Year and Date
      2010-06-18
    • Related Report
      2012 Final Research Report
  • [Presentation] 敗血症に伴う多臓器不全に対する治療戦略2010

    • Author(s)
      磯谷栄二
    • Organizer
      第35回日本外科系連合学会
    • Place of Presentation
      浦安
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 敗血症に伴う多臓器不全に対する治療戦略2010

    • Author(s)
      磯谷栄二
    • Organizer
      第13回臨床救急医学会
    • Place of Presentation
      幕張
    • Year and Date
      2010-05-31
    • Related Report
      2012 Final Research Report
  • [Presentation] 敗血症に伴う多臓器不全に対する治療戦略2010

    • Author(s)
      磯谷栄二
    • Organizer
      第13回日本臨床救急医学会
    • Place of Presentation
      幕張
    • Year and Date
      2010-05-31
    • Related Report
      2010 Annual Research Report
  • [Book] 呼吸療法における不思議,神経原性肺水腫はなぜ起こるのか2011

    • Author(s)
      磯谷栄二, 安本和正・小谷透
    • Publisher
      アトムス
    • Related Report
      2012 Final Research Report
  • [Book] 呼吸療法における不思議50安本和正・小谷透2011

    • Author(s)
      磯谷栄二
    • Total Pages
      312
    • Publisher
      アトムス
    • Related Report
      2011 Annual Research Report
  • [Book] 呼吸療法の不思議502011

    • Author(s)
      磯谷栄二
    • Total Pages
      5
    • Publisher
      アトムス
    • Related Report
      2010 Annual Research Report
  • [Book] 可溶性トロンボモジュリン(外科), 救急・集中医療2010

    • Author(s)
      磯谷栄二
    • Publisher
      総合医学社
    • Related Report
      2012 Final Research Report
  • [Book] 救急・集中治療Vol22 DICのすべて2010

    • Author(s)
      磯谷栄二
    • Total Pages
      5
    • Publisher
      総合医学社
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.twmu.ac.jp/DNH/mce/er/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 東京女子医科大学東医療センター救急医療科ホームページ

    • URL

      http://www.twmu.ac.jp/DNH/mce/er/index.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2010-11-30   Modified: 2019-07-29  

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