著者

Makoto Takeyama Sen Yachi Yuji Nishimoto Ichizo Tsujino Junichi Nakamura Naoto Yamamoto Hiroko Nakata Satoshi Ikeda Michihisa Umetsu Shizu Aikawa Hiroya Hayashi Hirono Satokawa Yoshinori Okuno Eriko Iwata Yoshito Ogihara Nobutaka Ikeda Akane Kondo Takehisa Iwai Norikazu Yamada Tomohiro Ogawa Takao Kobayashi Makoto Mo Yugo Yamashita

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

pp.JE20220201, (Released:2022-11-12)

参考文献数

53

被引用文献数

2 2

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Background: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited.Methods: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study.Results: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk.Conclusion: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

著者

Hiroya Hayashi Yasuhiro Izumiya Toshifumi Ishida Yuichiro Arima Ou Hayashi Minoru Yoshiyama Kenichi Tsujita Daiju Fukuda

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0353, (Released:2023-11-25)

参考文献数

43

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Background: Resistance exercise is beneficial in patients with lower extremity arterial disease. Muscle-derived exosomes contain many types of signaling molecules, including microRNAs (miRNAs). Here, we tested the hypothesis that exosomal miRNAs secreted by growing muscles promote an angiogenic response in endothelial cells (ECs).Methods and Results: Skeletal muscle-specific conditional Akt1 transgenic (Akt1-TG) mice, in which skeletal muscle growth can be induced were used as a model of resistance training. Remarkable skeletal muscle growth was observed in mice 2 weeks after gene activation. The protein amount in exosomes secreted by growing muscles did not differ between Akt1-TG and control mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway frequency analysis of 4,665 target genes, identified using an miRNA array miRNAs, revealed a significant increase in Akt and its downstream signaling pathway genes. Among the upregulated miRNAs, miR1, miR133, and miR206 were significantly upregulated in the serum of Akt1-TG mice. miR206 was also increased in insulin-like growth factor (IGF)-1-stimulated hypertrophied myotubes. Exogenous supplementation of exosomal miR206 to human umbilical vein ECs promoted angiogenesis, as assessed using the spheroid assay, and increased the expression of angiogenesis-related transcripts.Conclusions: Exosomal miR206 is upregulated in the blood of Akt1-TG mice and in IGF-stimulated cultured myotubes. Exogenous supplementation of miR206 promoted an angiogenic response in ECs. Our data suggest that miR206 secreted from growing muscles acts on ECs and promotes angiogenesis.

著者

Yugo Yamashita Yuuki Maruyama Hirono Satokawa Yuji Nishimoto Ichizo Tsujino Hideki Sakashita Hiroko Nakata Yoshinori Okuno Yoshito Ogihara Sen Yachi Naoki Toya Masami Shingaki Satoshi Ikeda Naoto Yamamoto Shizu Aikawa Nobutaka Ikeda Hiroya Hayashi Shingo Ishiguro Eriko Iwata Michihisa Umetsu Akane Kondo Takehisa Iwai Takao Kobayashi Makoto Mo Norikazu Yamada on behalf of the Taskforce of VTE and COVID-19 in Japan Study

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-21-0169, (Released:2021-05-20)

参考文献数

33

被引用文献数

30

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Background:Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.Methods and Results:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m2, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE.Conclusions:Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.

著者

Makoto Takeyama Sen Yachi Yuji Nishimoto Ichizo Tsujino Junichi Nakamura Naoto Yamamoto Hiroko Nakata Satoshi Ikeda Michihisa Umetsu Shizu Aikawa Hiroya Hayashi Hirono Satokawa Yoshinori Okuno Eriko Iwata Yoshito Ogihara Nobutaka Ikeda Akane Kondo Takehisa Iwai Norikazu Yamada Tomohiro Ogawa Takao Kobayashi Makoto Mo Yugo Yamashita

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

vol.33, no.3, pp.150-157, 2023-03-05 (Released:2023-03-05)

参考文献数

53

被引用文献数

2

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Background: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited.Methods: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study.Results: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk.Conclusion: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.