Analysis of muscle injury in severe condition focusing on TITIN

2024 Fiscal Year Final Research Report

• Project/Area Number: 21H03030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Yokohama City University (2022-2024); Teikyo University (2021)
• Principal Investigator: Nakamura Kensuke 横浜市立大学, 附属病院, 准教授 (50466760)
• 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)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: PICS / ICU-AW / TITIN / CIM

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%.

Free Research Field

救急集中治療

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。