| Project/Area Number |
21H03030
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Yokohama City University (2022-2024)
Teikyo University (2021) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
下條 信威 筑波大学, 医学医療系, 講師 (20462210)
山川 一馬 大阪医科薬科大学, 医学部, 准教授 (50597507)
東條 健太郎 横浜市立大学, 医学部, 准教授 (80737552)
土井 研人 東京大学, 医学部附属病院, 教授 (80505892)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2022: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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| Keywords | PICS / ICU-AW / TITIN / CIM / 筋肉 / 集中治療 / エコー / 集中治療医 / ICU |
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| Outline of Research at the Start |
本研究は重症病態におけるTITINを主軸とした筋力低下に関わる筋障害の機序を解明するため、①基礎研究として羊ARDSモデルを用いて重症病態におけるTITINの崩壊と筋実質障害の関連を検討、②臨床研究として重症患者におけるTITINと筋力低下の長期的時系列推移を多施設共同前向き観察研究にて検討、③大腿直筋超音波所見と筋力低下との関連を単施設前向き観察研究にて検討するものである。
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| Outline of Final Research Achievements |
Sepsis was induced in mice by intraperitoneal administration of intestinal contents solution CS at 1 mg/g, and outcomes including body weight, grip strength, tibialis anterior muscle weight and cross-sectional area CSA, and urinary TITIN were evaluated. Observations were made using a transmission electron microscope. TITIN in urine peaked on day 1 after CS injection, and all outcomes, including TITIN, decreased in a CS dose-dependent manner. Expansion of sarcomeres between Z lines was observed. In a multicenter prospective study, 339 patients with sepsis admitted to the ICU were followed up for one year. The in-hospital mortality rate was 23%, increasing to 37% at 12 months. The mortality or PICS incidence rates at 3, 6, and 12 months were 60-70%, and the mortality rate among patients meeting PICS criteria at discharge was 89%.
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| Academic Significance and Societal Importance of the Research Achievements |
筋障害およびPICSバイオマーカーとしてのTITINの意義を明らかとして救急集中治療における同バイオマーカーの活用を世界に提案した。また多施設前向き研究にて敗血症における同PICSの発生状況を明らかとし、社会的問題としてPICSに対策する研究が急務であり今後さらなる研究推進が必要であることを示した。
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