Association between septic shock and enterocyte injury -New therapeutic target-

• Project/Area Number: 16K10942
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Nagasaki University
• Principal Investigator: SEKINO Motohiro 長崎大学, 病院(医学系), 講師 (40380927)
• Co-Investigator(Kenkyū-buntansha): 原 哲也 長崎大学, 医歯薬学総合研究科(医学系), 教授 (50304952)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 小腸粘膜細胞傷害 / 敗血症性ショック / 予後予測 / 腎機能障害 / 人工心肺 / 心臓手術 / 小腸粘膜細胞 / 腸型脂肪酸結合蛋白 / 予後 / 脂肪酸結合蛋白 / 小腸粘膜障害

Outline of Final Research Achievements

In this study, we revealed that enterocyte injury at ICU admission can serve as a predictor of mortality in septic shock patients and macroscopic tongue ischemia was associated with enterocyte injury. Additionally, no correlation was observed between endotoxemia and enterocyte injury amang patients in gram-positive septic shock. We also revealed that the levels of intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, were influenced by renal function and I-FABP was significantly eliminated by hemodialysis.

Academic Significance and Societal Importance of the Research Achievements

重症患者における小腸は「the motor of critical illness」と称され、予後悪化の原因となっていると考えられてきた。本研究は、小腸粘膜細胞傷害の指標である腸型脂肪酸結合蛋白(I-FABP)を用いて、敗血症性ショック患者の予後に関連することを明らかにした。今後、I-FABPが臨床使用されることにより予後予測および治療介入が可能となり、予後改善に繋がる可能性がある。ただし、本研究で示したようにI-FABPは、腎機能や血液透析によりその値が影響を受けるため注意が必要である。

Research Products

• [Journal Article] Association between endotoxemia and enterocyte injury and clinical course in patients with gram-positive septic shock (2019)
  • Author(s): Sekino Motohiro、Funaoka Hiroyuki、Sato Shuntaro、Egashira Takashi、Inoue Haruka、Yano Rintaro、Matsumoto Sojiro、Ichinomiya Taiga、Higashijima Ushio、Matsumoto Shuhei、Hara Tetsuya
  • Journal Title: Medicine Volume: 98 Issue: 28 Pages: e16452-e16452
  • DOI: 10.1097/md.0000000000016452
  • NAID: 120006988446
  • Peer Reviewed / Open Access
• [Journal Article] Severe Fever with Thrombocytopenia Syndrome Virus RNA in Semen, Japan (2019)
  • Author(s): Koga Satoru、Takazono Takahiro、Ando Tsuyoshi、Hayasaka Daisuke、Tashiro Masato、Saijo Tomomi、Kurihara Shintaro、Sekino Motohiro、Yamamoto Kazuko、Imamura Yoshifumi、Miyazaki Taiga、Yanagihara Katsunori、Morita Kouichi、Izumikawa Koichi、Mukae Hiroshi
  • Journal Title: Emerging Infectious Diseases Volume: 25 Issue: 11 Pages: 2127-2128
  • DOI: 10.3201/eid2511.190061
  • Peer Reviewed
• [Journal Article] Association Between Macroscopic Tongue Ischemia and Enterocyte Injury and Poor Outcome in Patients With Septic Shock (2018)
  • Author(s): Sekino Motohiro、Funaoka Hiroyuki、Sato Shuntaro、Okada Kyoko、Inoue Haruka、Yano Rintaro、Matsumoto Sojiro、Ichinomiya Taiga、Higashijima Ushio、Matsumoto Shuhei、Hara Tetsuya
  • Journal Title: SHOCK Volume: 50 Issue: 5 Pages: 530-537
  • DOI: 10.1097/shk.0000000000001122
  • Peer Reviewed
• [Journal Article] Intestinal fatty acid-binding protein levels in patients with chronic renal failure (2018)
  • Author(s): Okada Kyoko、Sekino Motohiro、Funaoka Hiroyuki、Sato Shuntaro、Ichinomiya Taiga、Murata Hiroaki、Maekawa Takuji、Nishikido Masaharu、Eishi Kiyoyuki、Hara Tetsuya
  • Journal Title: Journal of Surgical Research Volume: 230 Pages: 94-100
  • DOI: 10.1016/j.jss.2018.04.057
  • Peer Reviewed / Open Access
• [Journal Article] Severe Pneumonia Caused by Toxigenic Corynebacterium ulcerans Infection, Japan (2018)
  • Author(s): Yasuda Ikkoh、Matsuyama Hisayo、Ishifuji Tomoko、Yamashita Yoshiro、Takaki Masahiro、Morimoto Konosuke、Sekino Motohiro、Yanagihara Katsunori、Fujii Tatsuya、Iwaki Masaaki、Yamamoto Akihiko、Ariyoshi Koya、Tanaka Takeshi
  • Journal Title: Emerging Infectious Diseases Volume: 24 Issue: 3 Pages: 588-591
  • DOI: 10.3201/eid2403.171837
  • NAID: 120006987311
  • Peer Reviewed
• [Journal Article] Recovery of muscle weakness and physical function in a patient with severe ICU-acquired weakness following pulmonary embolism: A case report (2018)
  • Author(s): Morimoto Yosuke、Sekino Motohiro、Eishi Kiyoyuki、Kozu Ryo
  • Journal Title: Clinical Case Reports Volume: 6 Issue: 7 Pages: 1214-1218
  • DOI: 10.1002/ccr3.1576
  • NAID: 120006988004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock: A preliminary study (2017)
  • Author(s): Sekino Motohiro、Funaoka Hiroyuki、Sato Shuntaro、Okada Kyoko、Inoue Haruka、Yano Rintaro、Matsumoto Sojiro、Ichinomiya Taiga、Higashijima Ushio、Matsumoto Shuhei、Hara Tetsuya
  • Journal Title: Journal of Critical Care Volume: 42 Pages: 92-100
  • DOI: 10.1016/j.jcrc.2017.07.012
  • Peer Reviewed
• [Journal Article] Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock (2017)
  • Author(s): Iizuka Y、Sanui M、Sasabuchi Y、Lefor AK、Hayakawa M、Saito S、Uchino S、Yamakawa K、Kudo D、Takimoto K、Mayumi T、Azuhata T、Ito F、Yoshihiro S、Hayakawa K、Nakashima T、Ogura T、Noda E、Nakamura Y、Sekine R、Yoshikawa Y、Sekino M、et al
  • Journal Title: Critical Care Volume: 21 Issue: 1 Pages: 181-189
  • DOI: 10.1186/s13054-017-1764-4
  • Peer Reviewed / Open Access
• [Journal Article] Plasmapheresis therapy has no triglyceride-lowering effect in patients with hypertriglyceridemic pancreatitis (2017)
  • Author(s): Miyamoto K、Horibe M、Sanui M、Sasaki M、Sugiyama D、Kato S、Yamashita T、Goto T、Iwasaki E、Shirai K、Oe K、Sawano H、Oda T、Yasuda H、Ogura Y、Hirose K、Kitamura K、Chiba N、Ozaki T、Oshima T、Yamamoto T、Nagata K、Mine T、Saito K、Sekino M、et al
  • Journal Title: Intensive Care Medicine Volume: 43 Issue: 6 Pages: 949-951
  • DOI: 10.1007/s00134-017-4722-3
  • Peer Reviewed
• [Journal Article] The effect of tooth brushing, irrigation, and topical tetracycline administration on the reduction of oral bacteria in mechanically ventilated patients: a preliminary study (2016)
  • Author(s): Saki Hayashida, Madoka Funahara, Motohiro Sekino, Noriko Yamaguchi, Kosuke Kosai, Souichi Yanamoto, Katsunori Yanagihara, Masahiro Umeda
  • Journal Title: BMC Oral Health Volume: 16 Issue: 1
  • DOI: 10.1186/s12903-016-0224-x
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013 (2016)
  • Author(s): Hayakawa M, Saito S, Uchino S, Yamakawa K, Kudo D, Iizuka Y, Sanui M, Takimoto K, Mayumi T, Azuhata T, Ito F, Yoshihiro S, Hayakawa K, Nakashima T, Ogura T, Noda E, Nakamura Y, Sekine R, Yoshikawa Y, Sekino M, et al
  • Journal Title: Journal of Intensive Care Volume: 4 Issue: 1
  • DOI: 10.1186/s40560-016-0169-9
  • NAID: 120005837939
  • Peer Reviewed / Open Access
• [Journal Article] Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study (2016)
  • Author(s): Hayakawa M, Kudo D, Saito S, Uchino S, Yamakawa K, Iizuka Y, Sanui M, Takimoto K, Mayumi T, Ono K, Azuhata T, Ito F, Yoshihiro S, Hayakawa K, Nakashima T, Ogura T, Noda E, Nakamura Y, Sekine R, Yoshikawa Y, Sekino M, et al
  • Journal Title: Shock Volume: 46 Pages: 623-631
  • NAID: 120005946857
  • Peer Reviewed / Open Access
• [Presentation] 敗血症性ショックと末梢循環不全ーCold shockにどう立ち向かうのか？ー (2020)
  • Author(s): 関野元裕
  • Organizer: 第47回日本集中治療医学会学術集会
  • Invited
• [Presentation] 重症患者における腸管循環制御 (2019)
  • Author(s): 関野元裕
  • Organizer: 第40回日本循環制御医学会 総会・学術集会
  • Invited
• [Presentation] 血中腸型脂肪酸結合蛋白は人工心肺下心臓手術患者の予後予測因子となる -維持透析患者における検討- (2019)
  • Author(s): 関野元裕, 岡田恭子, 佐藤俊太朗, 江頭 崇, 矢野倫太郎, 井上陽香, 松本聡治朗, 一ノ宮大雅, 東島 潮, 松本周平, 村田寛明, 吉富 修, 前川拓治, 原 哲也
  • Organizer: 日本集中治療医学会第3回九州支部学術集会
• [Presentation] 慢性腎不全患者における血中腸型脂肪酸結合蛋白濃度に関する検討 (2018)
  • Author(s): 岡田 恭子、関野 元裕、井上 陽香、江頭 崇、矢野 倫太郎、松本 聡治朗、一ノ宮 大雅、東島 潮、松本 周平、吉富 修、前川 拓治、原 哲也
  • Organizer: 第2回 日本集中治療医学会九州支部学術集会
• [Remarks] 長崎大学研究者総覧データベースシステム
  • URL: http://research.jimu.nagasaki-u.ac.jp/IST?ISTActId=FINDJPDetail&ISTKidoKbn=&ISTErrorChkKbn=&ISTFormSetKbn=&ISTTokenChkKbn=&userId=100000495