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医学部 医学科 病態解析医学講座救急・災害医学分野 |
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准教授 |
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論文 【 表示 ／ 非表示 】
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Anthrax toxins exacerbate sepsis-induced coagulopathy and endothelial dysfunction in a baboon model of anthrax. 査読あり 国際誌
Keshari RS, Silasi R, Byrum SD, Popescu NI, Regmi G, Abe T, Lupu C, Georgescu C, Taylor VE, Province D, Edmondson RD, Mackintosh SG, Avaritt NL, Kovats S, Farris AD, Simmons JH, McCarty OJT, Tackett AJ, Lupu F
Journal of thrombosis and haemostasis : JTH 24 ( 2 ) 732 - 746 2026年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND: Anthrax, caused by Bacillus anthracis, leads to severe sepsis due to multiple virulence factors, including toxins and bacterial cell wall components, which disrupt immune responses and induce cytotoxic effects. However, the relative contributions of toxins vs bacterial overload during systemic disease remain unclear. OBJECTIVES: We aimed to investigate the differential effects of toxigenic B anthracis Sterne strains and nontoxigenic ΔSterne strains on coagulation, complement activation, immune response, endothelial function, and organ damage in a baboon model of anthrax. METHODS: Healthy baboons were intravenously infused with a sublethal dose (1 × 108 colony-forming units/kg) of either B anthracis Sterne or ΔSterne strains. Animals were monitored for 7 days and assessed for vital signs, hematologic parameters, coagulation markers, endothelial dysfunction, complement activation, and proteomic profiles. RESULTS: The toxigenic Sterne strain induced more severe systemic effects than the ΔSterne strain, including prolonged bacterial persistence, enhanced coagulopathy, increased complement activation, endothelial dysfunction, neutrophil activation, and neutrophil extracellular trap formation. Coagulopathy was evidenced by elevated protease-antithrombin complexes, prolonged clotting times, fibrinogen consumption, and thrombocytopenia. Proteomic analysis of plasma revealed stronger upregulation of proteins involved in innate immunity, metabolism, coagulation, and cell death pathways in Sterne animals compared with ΔSterne-challenged animals. CONCLUSION: Our findings suggest that anthrax toxins contribute to the exacerbation of pathological host responses during anthrax sepsis, including coagulopathy, complement activation, endothelial dysfunction, and organ injury. These observations provide insight into the role of toxins in intensifying disease severity beyond bacterial burden alone. Therapeutic strategies targeting coagulation and complement pathways, while preserving endothelial function, may help mitigate anthrax-induced sepsis.
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Novel Integration of Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy in Pediatric Patients With Severe Burns: A Case Report. 査読あり 国際誌
Matsuoka H, Abe T, Yonaha T, Yano T, Taniguchi M, Nagano T, Tsuneyoshi I, Ochiai H
Cureus 18 ( 2 ) e102924 2026年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) represent critical complications that significantly burden the management of pediatric patients with extensive burns. We present a case of a four-year-old boy who sustained severe burns covering 56% of his total body (Burn Index 29). The patient developed ARDS on Day 3, which led to the initiation of venovenous extracorporeal membrane oxygenation (ECMO) on Day 5. Following the subsequent development of AKI and fluid overload, continuous renal replacement therapy (CRRT) was introduced on Day 6. To overcome the limitations of vascular access common in pediatric patients, a novel integrated approach was employed by connecting the CRRT circuit to a unique bypass between the ECMO limbs. This integrated system allowed for seamless treatment and effective fluid management, resulting in the resolution of pulmonary edema and a significant improvement in respiratory function. The patient was successfully weaned from ECMO on Day 10 and CRRT on Day 13, eventually being discharged on Day 90 following multiple skin grafting procedures. This case highlights that the integration of CRRT into an ECMO bypass line is a simple, safe, and effective modality for the life-saving treatment of pediatric severe burns complicated by multi-organ failure.
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Protective effects of factor XI inhibition by abelacimab in a baboon model of live Staphylococcus aureus sepsis. 査読あり 国際誌
Silasi R, Keshari RS, Abe T, Byrum SD, Regmi G, Lupu C, Georgescu C, Simmons JH, Shamanaev A, Moellmer SA, Puy C, Shatzel JJ, Province D, Edmondson RD, Mackintosh SG, Avaritt NL, Bloomfield D, Gailani D, Tackett AJ, McCarty OJT, Lupu F
Journal of thrombosis and haemostasis : JTH 23 ( 10 ) 3370 - 3385 2025年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND: Sepsis remains a major clinical challenge characterized by dysregulated immune response, coagulation abnormalities, and multiorgan failure, leading to high morbidity and mortality. OBJECTIVES: This study investigated the therapeutic potential of abelacimab, a monoclonal antibody targeting the plasma zymogen factor (F)XI, in a new baboon model of Staphylococcus aureus sepsis. METHODS: Healthy Papio anubis baboons were randomly assigned to control or abelacimab treatment groups. Both groups (n = 6, each) were intravenously infused with a median lethal (LD50) dose of live S aureus. The treatment group was administered abelacimab 30 minutes after the onset of bacterial infusion. Hematologic, coagulation, inflammatory, and organ function parameters were monitored for 7 days or until the animal exhibited signs of irreversible organ failure. Proteomic analysis was conducted to elucidate the underlying mechanisms by which abelacimab offered protection. RESULTS: All 6 abelacimab-treated baboons survived until the 7-day endpoint, while 3 out of 6 untreated controls succumbed to sepsis within 102 hours. Abelacimab significantly attenuated sepsis-induced coagulopathy without signs of bleeding, as evidenced by biochemical tests and pathology analysis. Treated animals exhibited decreased proinflammatory cytokines, diminished neutrophil activation, and preservation of endothelial integrity, collectively conferring robust protection against organ damage. Proteomic analysis revealed that abelacimab modulated pathways related to coagulation, inflammation, and tissue injury, contributing to improved survival outcomes. CONCLUSION: FXI inhibition by abelacimab offers significant protection by attenuating activation of coagulation, reducing inflammation, and preventing organ failure. Targeting FXI may be a promising therapeutic strategy for managing sepsis by addressing multiple facets of its complex pathophysiology.
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Saito K, Abe T, Tanohata R, Nagano T, Ochiai H
Journal of rural medicine : JRM 20 ( 2 ) 92 - 101 2025年4月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本農村医学会
<b>Objective:</b> Providing emergency care to serious patients in rural areas remains challenging. Intentional transit practice involves transporting a serious patient to a nearby hospital while requesting the Helicopter Emergency Medical Services (HEMS). This study aims to evaluate its effectiveness on earlier primary medical interventions and the decision of the destination hospital.<b>Patient and Methods:</b> We conducted a single-center, retrospective observational study at a HEMS base hospital in a rural area of Japan. The study participants included patients who underwent the intentional transit practice between April 2012 and March 2019. We compared actual times to estimated times for each case treated with the HEMS alone (HEMS-alone model). Outcomes were the time from ambulance call to reaching the physician (physician reaching time), arrival at the final destination facility (destination hospital arrival time), and helicopter waiting time at the landing zone (helicopter waiting time). Subgroup analyses by region and an analysis of the relationship between diagnostic tests performed at the transit hospital and the type of destination facility were performed.<b>Results:</b> Eighty-seven patients were eligible for analysis. Compared to the HEMS-alone model, the intentional transit practice reduced the physician reaching time (median [interquartile] min) (26 [21–32] vs. 37 [29–47], <i>P</i><0.0001) while increasing the destination hospital arrival time and the helicopter waiting time (71 [58–93] vs. 65 [59–80], <i>P</i>=0.03; 24 [18–34] vs. 19 [18–21], <i>P</i><0.0001; respectively). Subgroup analysis showed a consistent result for physician reaching time but heterogeneity in the other time courses by region. Diagnostic tests were related to transportation to facilities other than the HEMS base hospital.<b>Conclusion:</b> The intentional transit practice is beneficial for providing primary care earlier than the HEMS alone and for transport to more specific facilities. However, it delays arrival at the destination facility and increases helicopter waiting time.
DOI： 10.2185/jrm.2024-038
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Complement system activation through the alternative pathway associates with disseminated intravascular coagulation to increase mortality in sepsis. 査読あり 国際誌
Abe T, Saito K, Nagano T, Yamada Y, Ochiai H
Thrombosis research 247 109281 - 109281 2025年3月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND: Sepsis-induced disseminated intravascular coagulation (DIC) increases mortality in sepsis patients. Complement system activation is concomitant with sepsis-induced DIC; however, it is unclear how these two pathologies influence clinical parameters of sepsis individually and in combination, and which of the complement pathways activation is predominantly associated with mortality. METHODS: In this ancillary analysis of a prospective observational study, 49 adult sepsis patients were assigned to four groups according to the absence/presence of DIC and complement activation. Effects of complement activation and DIC on clinical demographics including parameters of DIC, systemic severities, and 60-days all-cause mortality were assessed by comparing the groups. We analyzed each complement pathway by comparing Bb, C3a/C3 ratio, SC5b-9/C3 ratio, C4d, C4d/C4 ratio, C3a, C5a, and SC5b-9 between survivors/non-survivors both in all the patients and in the DIC+ subgroup. RESULTS: Complement system activation induced thrombocytopenia and enhanced sepsis severity measured as APACHE2 and SOFA scores. 60-days all-cause mortality was different between groups, with 0 % in the complement activation alone group, 14 % in the DIC alone group and 66 % in the combined DIC and complement activation group. Bb and C3a/C3 and SC5b-9/C3 ratios were higher in non-survivors, with Bb and SC5b-9/C3 ratio still higher in DIC+ non-survivors. CONCLUSION: Complement activation worsen the severity of sepsis and cause thrombocytopenia. Co-occurrence of complement activation and DIC increased sepsis mortality. The alternative pathway of complement activation plays a major role in sepsis mortality.
書籍等出版物 【 表示 ／ 非表示 】
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ザ・トラウママニュアル
今 明秀, 軽米 寿之 他（ 担当： 共訳 , 範囲: 第18章, 第27章, 第28章, 第31章, 第33章）
メディカルサイエンス社 2017年10月
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救命救急のディシジョン・メイキング 実践のためのEBMハンドブック
今 明秀 他（ 担当： 単著 , 範囲: 第34章, 第40章）
メディカルサイエンス社 2016年5月
総ページ数：1088 記述言語：日本語 著書種別：学術書
MISC 【 表示 ／ 非表示 】
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【あなたも名医!どう診る?!診療所で出会う救急患者 ゼッタイに押さえておきたい救急対応のノウハウ】 （１章）緊急転送の前に こんなとき、どうする? ドクターヘリを呼ぶか?救急車搬送か?
安部智大
jmedmook38 【あなたも名医!どう診る?!診療所で出会う救急患者 ゼッタイに押さえておきたい救急対応のノウハウ】 ( 38 ) 45 - 53 2015年6月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア） 出版者・発行元：日本医事新報社
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【あなたも名医!どう診る?!診療所で出会う救急患者 ゼッタイに押さえておきたい救急対応のノウハウ】(1章)緊急転送の前に こんなとき、どうする? ドクターヘリを呼ぶか?救急車搬送か?
安部 智大
jmed mook ( 38 ) 45 - 53 2015年6月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（大学・研究所紀要） 出版者・発行元：(株)日本医事新報社
＜ココがポイント!＞転院搬送(以後、転送)が必要な場合は、患者の初期診療、転送先選定、患者・家族への説明など、非常に限られた時間内でやらなければならないことが多い。ドクターヘリは、転送時間が短い、転送時に医療スタッフがついている、などメリットも多い。ドクターヘリは、天候や日没後などは飛べず、機内での処置にも制約がある。シームレスな診療のために、ドクターヘリが来るまでの間にできる初期診療を開始する。(著者抄録)
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第2章 15 血尿 招待あり
今 明秀 他
救急初期診療パーフェクト―必須症候・手技をきわめる 2010年9月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア） 出版者・発行元：羊土社
講演・口頭発表等 【 表示 ／ 非表示 】
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MRIで淡蒼球に信号変化がある急性一酸化炭素中毒症例に高気圧酸素療法を行い、遅発性神経障害が発症しなかった一例
猪瀬 将之, 安部 智大, 遠藤 穣治, 落合 秀信
日本救急医学会雑誌 2025年11月 (一社)日本救急医学会
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救急専攻医による育児休業取得の実体験と職場の意識調査
長尾 一徹, 長野 健彦, 田中 達也, 安部 智大, 落合 秀信
日本救急医学会雑誌 2025年11月 (一社)日本救急医学会
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救命救急センターに常駐する精神科医の役割について
古郷 央一郎, 安部 智大, 落合 秀信, 船橋 英樹, 平野 羊嗣
日本救急医学会雑誌 2025年11月 (一社)日本救急医学会
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ジスチグミンとベタネコールの併用によりコリン作動性クリーゼを来した一例
田崎 和志, 山内 佑太, 畠中 健吾, 安部 智大, 金丸 勝弘, 落合 秀信
日本救急医学会雑誌 2025年11月 (一社)日本救急医学会
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たこつぼ型心筋症を合併したてんかん重積の症例報告と文献レビュー
徳永 啓, 田中 早紀, 東雲 崇之, 井之上 晃, 田中 達也, 齋藤 勝俊, 安部 智大, 落合 秀信
日本救急医学会雑誌 2025年11月 (一社)日本救急医学会
受賞 【 表示 ／ 非表示 】
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Star Research Award, 2025 Critical Care Congress
2025年2月 The Society of Critical Care Medicine Characterization of Sepsis Cardiomyopathy in a Nonhuman Primate Model of Sepsis
Tomohiro Abe
受賞区分：国内外の国際的学術賞