120 results on '"Muraoka, N."'
Search Results
2. Risk of Ischemic Heart Disease in Patients After Conccurent Chemoradiotherapy for Lung and Esophageal Cancer: A Case-Control Study
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Harada, H., primary, Oyakawa, T., additional, Omae, K., additional, Muraoka, N., additional, Mori, K., additional, Onozawa, Y., additional, Yasui, H., additional, Takahashi, T., additional, Nishimura, T., additional, Iida, K., additional, and Naito, T., additional
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- 2019
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3. Fatigue strength assessment of SUS316 by small bulge fatigue (SBF) test
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Komazaki, S., primary, Jojima, R., additional, Muraoka, N., additional, Nogami, S., additional, Kamaya, M., additional, Hisaka, C., additional, Fujiwara, M., additional, and Nitta, A., additional
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- 2018
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4. Prevalence of intestinal parasites and genotyping of Giardia intestinalis in pet shop puppies in east Japan
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Itoh, N., Itagaki, T., Kawabata, T., Konaka, T., Muraoka, N., Saeki, H., Kanai, K., Chikazawa, S., Hori, Y., Hoshi, F., and Higuchi, S.
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- 2011
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5. Proposal for a Highly Efficient Cogeneration System Using an Atmospheric Pressure Turbine Coupled With Biomass Gasification
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Tsujikawa, Y., primary, Kaneko, K., additional, and Muraoka, N., additional
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- 2009
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6. Abstract No. 241: Analyzing Aortic Arch-Configuration Using Multidetector-Low Computed Tomography To Prepare a Generalized Stent-Graft
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Shimizu, Y., primary, Muraoka, N., additional, and Sakai, T., additional
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- 2008
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7. Abstract No. 267: Volumetric Efficacy of Portal Vein Embolization: Comparative Study between the Unilateral and Contralateral Approach
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Muraoka, N., primary, Sakai, T., additional, Shimizu, Y., additional, Yoshikawa, J., additional, Ihara, N., additional, and Kimura, H., additional
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- 2008
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8. Accidental injury by a grass strimmer: an unusual fatality
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Ng'walali, P.M., primary, Muraoka, N., additional, Yonemitsu, K., additional, Higuchi, A., additional, and Tsunenari, S., additional
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- 2001
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9. Medico-legal implications of acute subdural haematoma in boxing
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Ng'walali, P.M, primary, Muraoka, N, additional, Honjyo, K, additional, Hamada, K, additional, Kibayashi, K, additional, and Tsunenari, S, additional
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- 2000
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10. Modifying effect of ginger on mutagenicity in pan fried chicken
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Muraoka, N., primary, Uchida, N., additional, Hosoi, Y., additional, and Aoki, M., additional
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- 1995
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11. Unusual homicide by air gun with pellet embolisation
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Ng`walali, P. M., Ohtsu, Y., Muraoka, N., and Tsunenari, S.
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- 2001
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12. <Articles>Contribution of the Japanese Classical Scholars to the Development of modern Historiography
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Muraoka, N.
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- 1928
13. Earthquake damage detection using high-resolution satellite images
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Yamazaki, F., primary, Kouchi, K., additional, Kohiyama, M., additional, Muraoka, N., additional, and Matsuoka, M., additional
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14. Earthquake damage detection using high-resolution satellite images.
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Yamazaki, F., Kouchi, K., Kohiyama, M., Muraoka, N., and Matsuoka, M.
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- 2004
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15. Treatment of Notoedres cati infestation in cats with selamectin.
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Itoh, N., Muraoka, N., Aoki, M., and Itagaki, T.
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PARASITES , *CATS - Abstract
Examines the treatment of notoedres cati infestitation in cats with selamectin. Identification of other ectoparasites; Observation of cats for general and local adverse reactions after treatment; Evaluation of microscopic skin scrapings.
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- 2004
16. Mutagenicity of cooked foods, V. Mutagenicity of grilled rice
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Muraoka, N
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- 1986
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17. Mutagenicity in cooked foods. Effect of cooking oils on the formation of mutagenicity in sauteed fish
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Muraoka, N
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- 1991
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18. Mutagenicity of cooked foods. Effect of cooking conditions on the formation of mutagenicity in sauteed meats
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Muraoka, N
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- 1987
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19. Mutagenicity of Japanese meals
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Muraoka, N
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- 1984
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20. Extraction of heterocyclic amines from cooked food by using blue resin
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Ohara, Y., Hayatsu, T., Saito, Y., Mifune, M., Tanake, Y., Muraoka, N., and Hayatsu, H.
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- 1988
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21. Mutagenicity in cooked foods. Effect of flavoring method and cooking oils on the formation of mutagenicity in sauteed meats
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Hisoaka, S., Fujii, K., Ohno, Y., and Muraoka, N.
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- 1988
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22. Mutagenicity in cooked foods. Antimutagenic effect of vegetables and fruits on the mutagenicity in pan-fried chicken
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Hisaoka, S. and Muraoka, N.
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- 1991
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23. Edoxaban for 12 vs. 3 months in cancer-associated isolated distal deep vein thrombosis according to different doses: insights from the ONCO DVT study.
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Chatani R, Yamashita Y, Morimoto T, Muraoka N, Umetsu M, Nishimoto Y, Takada T, Ogihara Y, Nishikawa T, Ikeda N, Otsui K, Sueta D, Tsubata Y, Shoji M, Shikama A, Hosoi Y, Tanabe Y, Tsukahara K, Nakanishi N, Kim K, Ikeda S, Mushiake K, Kadota K, Ono K, and Kimura T
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- Humans, Female, Male, Middle Aged, Aged, Time Factors, Treatment Outcome, Risk Factors, Hemorrhage chemically induced, Recurrence, Drug Administration Schedule, Incidence, Double-Blind Method, Venous Thrombosis diagnosis, Venous Thrombosis epidemiology, Venous Thrombosis drug therapy, Thiazoles administration & dosage, Thiazoles adverse effects, Pyridines administration & dosage, Pyridines adverse effects, Factor Xa Inhibitors administration & dosage, Factor Xa Inhibitors adverse effects, Neoplasms complications
- Abstract
Background: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk., Methods and Results: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N = 151) and those with a reduced edoxaban dose (30 mg/day; N = 450) and evaluated the clinical outcomes for the 12- and 3-month treatments. The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P = 0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P = 0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P = 0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than in the 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P = 0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P = 0.89; OR, 0.97; 95% CI, 0.49-1.91), signalling there was a potential interaction (P = 0.07)., Conclusions: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy., Trial Registration Number: NCT03895502 (ONCO DVT Trial): https://classic.clinicaltrials.gov/ct2/show/NCT03895502., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2024
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24. Home Treatment for Active Cancer Patients With Low-Risk Pulmonary Embolism - A Predetermined Companion Report From the ONCO PE Trial.
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Chatani R, Yamashita Y, Morimoto T, Muraoka N, Shioyama W, Shibata T, Nishimoto Y, Ogihara Y, Doi K, Oi M, Shiga T, Sueta D, Kim K, Tanabe Y, Koitabashi N, Takada T, Ikeda S, Nakagawa H, Mitsuhashi T, Shoji M, Sakamoto J, Hisatake S, Ogino Y, Fujita M, Nakanishi N, Dohke T, Hiramori S, Nawada R, Kaneda K, Mushiake K, Yamamoto H, Kadota K, Ono K, and Kimura T
- Abstract
Background: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events., Conclusions: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.
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- 2024
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25. The impact of renal function on clinical outcomes of patients with cancer-associated isolated distal deep vein thrombosis: Insights from the ONCO DVT study.
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Sueta D, Yamashita Y, Morimoto T, Muraoka N, Umetsu M, Nishimoto Y, Takada T, Ogihara Y, Nishikawa T, Ikeda N, Otsui K, Tsubata Y, Shoji M, Shikama A, Hosoi Y, Tanabe Y, Chatani R, Tsukahara K, Nakanishi N, Kim K, Ikeda S, Mo M, Kimura T, and Tsujita K
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- Humans, Kidney, Venous Thromboembolism, Neoplasms complications, Venous Thrombosis drug therapy, Venous Thrombosis etiology, Kidney Diseases, Pyridines, Thiazoles
- Abstract
Background: The multicenter, open-label, randomized clinical trial ONCO DVT compared 3-month and 12-month edoxaban treatment regimens for isolated distal deep vein thrombosis (DVT) and suggested potential benefits of prolonged edoxaban treatment in terms of thrombotic risk. However, the risk-benefit balance of prolonged edoxaban treatment in patients with renal function remains unclear., Objectives: To compare the safety and efficacy of 3-month and 12-month edoxaban treatment regimens in patients with cancer-associated isolated distal DVT and different renal functions., Methods: This pre-specified subgroup analysis of the ONCO DVT study included 601 patients divided into subgroups according to renal function using a 50 mL/min creatinine clearance (Ccr) cutoff. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) and VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months., Results: Among the 601 patients, 131 (21.8 %) comprised the renal dysfunction subgroup. The primary endpoint occurred in 6 (9.7 %) and 1 (1.4 %) patients in the 3-month and 12-month edoxaban groups in the renal dysfunction subgroup, respectively, and in 16 (6.6 %) and 2 (0.9 %) patients in the no renal dysfunction subgroup, respectively. The major secondary endpoint occurred in 9 (14.5 %) and 7 (10.1 %) patients in the 12-month and 3-month edoxaban groups in the renal dysfunction subgroup, and in 13 (5.3 %) and 21 (9.3 %) patients in the no renal dysfunction subgroup, respectively., Conclusions: A 12-month edoxaban regiment was superior to a 3-month treatment in terms of thrombotic risk irrespective of renal function. A higher bleeding risk was not identified in patients with renal dysfunction who received prolonged edoxaban treatment., Competing Interests: Declaration of competing interest Dr. Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Morimoto reports lecturer's fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; advisory board for Novartis and Teijin. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. Dr. Ogihara received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Bayer Healthcare and Daiichi Sankyo. Dr. Dohi received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Daiichi Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi Sankyo. Dr. Tsubata received lecture fees from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical and Daiichi Sankyo, and grant support from Daiichi Sankyo, AstraZeneca and Ono Pharmaceutical. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi Sankyo. Dr. Mo received lecture fees from Bayer Healthcare. Dr. Tsujita received significant research grant from AMI Co., Ltd., Bayer Yakuhin, Ltd., Bristol-Myers K.K., EA Pharma Co., Ltd., MOCHIDA PHARMACEUTICAL CO., LTD., and scholarship fund from AMI Co., Ltd., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Edwards Lifesciences Corporation, Johnson & Johnson K.K., ONO PHARMACEUTICAL CO., LTD., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and honoraria from Amgen K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co. Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., and belongs to the endowed departments donated by Abbott Japan Co., Ltd., Boston Scientific Japan K.K., Fides-one, Inc., GM Medical Co., Ltd., ITI Co., Ltd., Kaneka Medix Co., Ltd., NIPRO CORPORATION, TERUMO Co, Ltd., Abbott Medical Co., Ltd., Cardinal Health Japan, Fukuda Denshi Co., Ltd., Japan Lifeline Co., Ltd., Medical Appliance Co., Ltd., Medtoronic Japan Co., Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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26. Impact of a Cancer History on Cardiovascular Events Among Patients With Myocardial Infarction Who Received Revascularization.
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Takeuchi T, Kosugi S, Ueda Y, Ikeoka K, Yamane H, Takayasu K, Ohashi T, Fukushima T, Horiuchi K, Iehara T, Sakamoto M, Ukai K, Minami S, Mizumori Y, Muraoka N, Nakamura M, Ozaki T, Mishima T, Abe H, Inoue K, and Matsumura Y
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- Humans, Retrospective Studies, Aftercare, Patient Discharge, Coronary Angiography, Treatment Outcome, Risk Factors, Myocardial Revascularization methods, Myocardial Infarction etiology, Percutaneous Coronary Intervention adverse effects, Neoplasms etiology
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Background: It remains controversial whether a cancer history increases the risk of cardiovascular (CV) events among patients with myocardial infarction (MI) who undergo revascularization., Methods and results: Patients who were confirmed as type 1 acute MI (AMI) by coronary angiography were retrospectively analyzed. Patients who died in hospital or those not undergoing revascularization were excluded. Patients with a cancer history were compared with those without it. A cancer history was examined in the in-hospital cancer registry. The primary outcome was a composite of cardiac death, recurrent type 1 MI, post-discharge coronary revascularization, heart failure hospitalization, and stroke. Among 551 AMI patients, 55 had a cancer history (cancer group) and 496 did not (non-cancer group). Cox proportional hazards model revealed that the risk of composite endpoint was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.13-2.82). Among the cancer group, patients who were diagnosed as AMI within 6 months after the cancer diagnosis had a higher risk of the composite endpoint than those who were diagnosed as AMI 6 months or later after the cancer diagnosis (adjusted HR: 5.43; 95% CI: 1.55-19.07)., Conclusions: A cancer history increased the risk of CV events after discharge among AMI patients after revascularization.
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- 2024
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27. A Predictive Model for Cancer-Associated Thrombosis in Japanese Cancer Patients: Findings from the J-Khorana Registry.
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Shoji M, Yamashita Y, Ishii M, Inoue H, Kato H, Fujita S, Matsui K, Tajiri K, Nameki M, Muraoka N, Nonaka A, Sugino H, Kono M, Oka T, Sueta D, Komuro I, and Tsujita K
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Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear. Objectives This study aimed to validate the Khorana VTE risk assessment score (KRS) for VTE diagnosis and establish an optimal predictive model for VTE in Japanese patients with cancer. Methods A total of 7,955 Japanese patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups according to the KRS. Using 37 explanatory variables, a total of 2,833 patients with cancer were divided into derivation and validation cohorts (5:5). A risk model for Japanese participants was developed using the derivation cohort data. Results The prevalence of VTE in low-, intermediate-, and high-score patients was 1.2, 2.5, and 4.3%, respectively. Logistic regression analysis demonstrated that cancer stage (III-IV) and KRS ≥ 2 were independent and significant predictors of VTE onset. The risk model for VTE assigned 1 point to body mass index ≥25 kg/m
2 and 2 points each to the prevalence of osteochondral cancer and D-dimer level ≥1.47 µg/mL. The areas under the curve of the risk model were 0.763 and 0.656 in the derivation and validation cohorts, respectively. Conclusion The KRS was useful in Japanese patients, and our new predictive model may be helpful for the diagnosis of VTE in Japanese patients with cancer., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)- Published
- 2024
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28. Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.
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Yamashita Y, Morimoto T, Muraoka N, Oyakawa T, Umetsu M, Akamatsu D, Nishimoto Y, Sato Y, Takada T, Jujo K, Minami Y, Ogihara Y, Dohi K, Fujita M, Nishikawa T, Ikeda N, Hashimoto G, Otsui K, Mori K, Sueta D, Tsubata Y, Shoji M, Shikama A, Hosoi Y, Tanabe Y, Chatani R, Tsukahara K, Nakanishi N, Kim K, Ikeda S, Mo M, Yoshikawa Y, and Kimura T
- Subjects
- Male, Humans, Aged, Female, Anticoagulants adverse effects, Hemorrhage complications, Venous Thromboembolism drug therapy, Venous Thromboembolism complications, Thrombosis complications, Venous Thrombosis complications, Neoplasms complications, Neoplasms drug therapy
- Abstract
Background: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding., Methods: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point., Results: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point., Conclusions: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502., Competing Interests: Disclosures Dr Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr Morimoto reports lecturer’s fees from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; article fees from Bristol Myers Squibb and Pfizer; and membership on advisory boards for Novartis and Teijin. Dr Nishimoto received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo. Dr Ogihara received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Bayer Healthcare and Daiichi Sankyo. Dr Dohi received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Daiichi Sankyo. Dr N. Ikeda received lecture fees from Bayer Healthcare, Bristol Myers Squibb, and Daiichi Sankyo. Dr Tsubata received lecture fees from AstraZeneca, Chugai Pharmaceutical, Bristol Myers Squibb, Kyowa Kirin, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, and Daiichi Sankyo, and grant support from Daiichi Sankyo, AstraZeneca, and Ono Pharmaceutical. Dr S. Ikeda received lecture fees from Bayer Healthcare, Bristol Myers Squibb, and Daiichi Sankyo. Dr Mo received lecture fees from Bayer Healthcare. The other authors report no conflicts.
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- 2023
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29. MEF2C/p300-mediated epigenetic remodeling promotes the maturation of induced cardiomyocytes.
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Kojima H, Sadahiro T, Muraoka N, Yamakawa H, Hashimoto H, Ishii R, Gosho M, Abe Y, Yamada Y, Nakano K, Honda S, Fujita R, Akiyama T, Sunagawa Y, Morimoto T, Tsukahara T, Hirai H, Fukuda K, and Ieda M
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- Epigenesis, Genetic, Epigenomics, Fibroblasts, Chromatin Assembly and Disassembly, Myocytes, Cardiac, MEF2 Transcription Factors genetics, p300-CBP Transcription Factors genetics
- Abstract
Cardiac transcription factors (TFs) directly reprogram fibroblasts into induced cardiomyocytes (iCMs), where MEF2C acts as a pioneer factor with GATA4 and TBX5 (GT). However, the generation of functional and mature iCMs is inefficient, and the molecular mechanisms underlying this process remain largely unknown. Here, we found that the overexpression of transcriptionally activated MEF2C via fusion of the powerful MYOD transactivation domain combined with GT increased the generation of beating iCMs by 30-fold. Activated MEF2C with GT generated iCMs that were transcriptionally, structurally, and functionally more mature than those generated by native MEF2C with GT. Mechanistically, activated MEF2C recruited p300 and multiple cardiogenic TFs to cardiac loci to induce chromatin remodeling. In contrast, p300 inhibition suppressed cardiac gene expression, inhibited iCM maturation, and decreased the beating iCM numbers. Splicing isoforms of MEF2C with similar transcriptional activities did not promote functional iCM generation. Thus, MEF2C/p300-mediated epigenetic remodeling promotes iCM maturation., Competing Interests: Conflict of interests M.I. holds a patent related to this work: U.S. Patent 9,517,250 entitled “Methods for Generating Cardiomyocytes,” issued on October 19, 2012., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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30. [The effect of rehabilitation and one year follow-up for a COVID-19 patient on prolonged mechanical ventilation].
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Ikeda Y, Oikawa O, Muraoka N, Tsukada T, Saida Y, Ro T, and Ota T
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- Male, Humans, Activities of Daily Living, Follow-Up Studies, Respiration, Artificial, COVID-19, Medicine
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We herein report the outcomes of rehabilitation intervention for a patient in his 80s with chronic obstructive pulmonary disease on prolonged mechanical ventilation after COVID-19 infection. The patient was forced to be long-term bedridden due to respirator dependence, showing notable muscle weakness and needing full assistance for all of his activities of daily living (ADL). We implemented rehabilitation for the purposes of withdrawal from mechanical ventilation and improvement of his physical function. We provided a combination program of range of motion exercise, resistance training, and gradual mobilization, such as sitting on the edge of the bed, moving between the bed and wheelchair, sitting on the wheelchair, standing and walking. After rehabilitation for 24 days, the patient was withdrawn from mechanical ventilation, his muscle strength recovered to a level of 4 (Good) on manual muscle testing (MMT) and he became able to walk using a walker. A follow-up survey one year later confirmed that he performed ADL without assistance and returned to work.
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- 2023
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31. Incidence and location of perioperative deep vein thrombosis in patients with bladder cancer undergoing radical cystectomy.
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Yamashita R, Nakamura M, Okayama Y, Kawase M, Muraoka N, Fujita A, Notsu A, Asakura K, Hashizume A, Shinsaka H, Matsuzaki M, Niwakawa M, and Oya M
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- Cystectomy adverse effects, Humans, Incidence, Postoperative Complications epidemiology, Postoperative Complications etiology, Postoperative Complications surgery, Urinary Bladder Neoplasms complications, Urinary Diversion adverse effects, Venous Thrombosis diagnostic imaging, Venous Thrombosis epidemiology, Venous Thrombosis etiology
- Abstract
Objectives: To determine the incidence and location of lower extremity deep vein thrombosis in patients undergoing radical cystectomy., Methods: We performed radical cystectomy in 137 patients with bladder cancer between August 2014 and February 2020. Since 2014, we have had a policy to screen for deep vein thrombosis using lower extremity ultrasonography both before and after radical cystectomy. We determined the incidence and location of deep vein thrombosis and classified it as either proximal or distal type. Furthermore, we explored the incidence of pulmonary embolism within 3 months after radical cystectomy., Results: After excluding six patients with a lack of ultrasonographic data, we evaluated 131 patients. Preoperative deep vein thrombosis (one proximal and 17 distal) was diagnosed in 18 patients (14%) with no symptoms. Postoperative deep vein thrombosis was diagnosed in 41 patients (31%; three proximal and 38 distal), of whom 26 (63%) had new-onset deep vein thrombosis after cystectomy. Three patients, two with proximal and one with distal type deep vein thrombosis, developed nonfatal pulmonary embolism postoperatively. Multivariate analysis showed that preoperative D-dimer levels (odds ratio 5.35, 95% confidence interval 1.74-16.50; P < 0.003), type of urinary diversion (ileal neobladder; odds ratio 11.15, 95% confidence interval 2.16-57.55; P = 0.004), and preoperative deep vein thrombosis (odds ratio 15.93, 95% confidence interval 3.82-66.30; P < 0.001) were significant risk factors for postoperative deep vein thrombosis., Conclusions: Pre- and post-radical cystectomy whole-leg ultrasonography can lead to an early perioperative diagnosis and immediate treatment of proximal deep vein thrombosis, thereby potentially preventing fatal pulmonary embolism., (© 2021 The Japanese Urological Association.)
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- 2022
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32. Corpus callosotomy in pediatric patients with non-lesional epileptic encephalopathy with electrical status epilepticus during sleep.
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Yokosako S, Muraoka N, Watanabe S, Kosugi K, Takayama Y, Iijima K, Kimura Y, Kaneko Y, Sumitomo N, Saito T, Nakagawa E, and Iwasaki M
- Abstract
Epileptic encephalopathy with electrical status epilepticus during sleep (ESES) is often refractory to medical treatment and leads to poor cognitive outcomes. Corpus callosotomy may be an effective treatment option for drug-resistant ESES with no focal etiology. We retrospectively identified three patients who underwent corpus callosotomy for drug-resistant ESES in our institution. Electroencephalography (EEG) findings and cognitive functions were evaluated before surgery, at 3 months, 6 months, 1 year, and 2 years after surgery. Age at surgery was 6 years 10 months, 7 years 9 months, and 8 years 4 months, respectively. Period between the diagnosis of ESES and surgery ranged from 7 to 25 months. All patients had no obvious structural abnormalities and presented with cognitive decline despite multiple antiseizure medications and steroid therapies. One patient showed complete resolution of ESES and an improvement of intelligence quotient after surgery. Epileptiform EEG was lateralized to one hemisphere after surgery and spike wave index (SWI) was decreased with moderate improvement in development and seizures in the other 2 patients. SWI re-exacerbated from 6 months after surgery, but without subsequent developmental regression in these 2 patients. Corpus callosotomy may become an important treatment option for drug-resistant ESES in patients with no structural abnormalities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)
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- 2021
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33. Natural History of Unruptured Visceral Artery Aneurysms Due to Segmental Arterial Mediolysis and Efficacy of Transcatheter Arterial Embolization: A Retrospective Multiinstitutional Study in Japan.
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Shimohira M, Kondo H, Ogawa Y, Kawada H, Koganemaru M, Ikeda O, Yamamoto A, Komada T, Tanoue S, Muraoka N, Tanikake M, Hayashi S, Yamamoto S, Sato T, Mizunuma K, Ganaha F, Murakami Y, and Ishiguchi T
- Subjects
- Adult, Aged, Aged, 80 and over, Aneurysm etiology, Aneurysm pathology, Aneurysm surgery, Aneurysm, Ruptured etiology, Celiac Artery, Embolization, Therapeutic adverse effects, Female, Gastric Artery, Gastroepiploic Artery, Hepatic Artery, Humans, Japan, Male, Mesenteric Artery, Inferior, Mesenteric Artery, Superior, Middle Aged, Retrospective Studies, Splenic Artery, Tunica Media, Aneurysm therapy, Arteries, Embolization, Therapeutic methods, Viscera blood supply
- Abstract
OBJECTIVE. The purpose of this study was to clarify the natural history of unruptured visceral artery aneurysms due to segmental arterial mediolysis and the efficacy of transcatheter arterial embolization. MATERIALS AND METHODS. Patients with a pathologic or clinical diagnosis of visceral artery aneurysms due to segmental arterial mediolysis between 2005 and 2015 were enrolled. For patients with clinical diagnoses, images were collected and assessed by central radiologic review. To clarify the natural history of unruptured aneurysms, the morphologic changes were assessed. The efficacy and safety of transcatheter arterial embolization for aneurysms due to segmental arterial mediolysis were evaluated. RESULTS. Forty-five patients with 123 aneurysms due to segmental arterial mediolysis were enrolled. Among the 123 aneurysms, 70 unruptured aneurysms were evaluated for natural history. Forty-five of the 70 (64%) aneurysms had no change in morphology. Among the other 25 aneurysms, nine (13% of the 70) were reduced in size, 13 (19%) disappeared, and three (4%) were newly found at follow-up. Aneurysms of the middle colic artery were ruptured in 10 of 11 (91%) cases. Transcatheter arterial embolization was performed on 45 aneurysms and was successful in all cases but caused slight arterial injury in three cases (6.7%). CONCLUSION. At initial diagnosis, unruptured aneurysms due to segmental arterial mediolysis are likely to be stable or to resolve, but the risk of rupture of aneurysms of the middle colic artery appears high. Transcatheter arterial embolization is a useful treatment, but careful manipulation is necessary.
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- 2021
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34. Single-Institutional Experience of Chronic Intracranial Electroencephalography Based on the Combined Usage of Subdural and Depth Electrodes.
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Takayama Y, Ikegaya N, Iijima K, Kimura Y, Yokosako S, Muraoka N, Kosugi K, Kaneko Y, Yamamoto T, and Iwasaki M
- Abstract
Implantation of subdural electrodes on the brain surface is still widely performed as one of the "gold standard methods" for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. However, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.
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- 2021
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35. Dermal fibroblast-like cells reprogrammed directly from adipocytes in mouse.
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Toyosaki M, Homma K, Suzuki S, Muraoka N, Hashimoto H, Goshima N, Ieda M, and Sasaki J
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- Adipocytes metabolism, Animals, Cells, Cultured, Dermis metabolism, Fibroblasts metabolism, Male, Mice, Mice, Inbred C57BL, Transfection methods, Adipocytes cytology, Cellular Reprogramming Techniques methods, Dermis cytology, Fibroblasts cytology
- Abstract
In deep burns, early wound closure is important for healing, and skin grafting is mainly used for wound closure. However, it is difficult to achieve early wound closure in extensive total body surface area deep burns due to the lack of donor sites. Dermal fibroblasts, responsible for dermis formation, may be lost in deep burns. However, fat layers composed of adipocytes, lying underneath the dermis, are retained even in such cases. Direct reprogramming is a novel method for directly reprograming some cells into other types by introducing specific master regulators; it has exhibited appreciable success in various fields. In this study, we aimed to assess whether the transfection of master regulators (ELF4, FOXC2, FOXO1, IRF1, PRRX1, and ZEB1) could reprogram mouse adipocytes into dermal fibroblast-like cells. Our results indicated the shrinkage of fat droplets in reprogrammed mouse adipocytes and their transformation into spindle-shaped dermal fibroblasts. Reduced expression of PPAR-2, c/EBP, aP2, and leptin, the known markers of adipocytes, in RT-PCR, and enhanced expression of anti-ER-TR7, the known anti-fibroblast marker, in immunocytochemistry, were confirmed in the reprogrammed mouse adipocytes. The dermal fibroblast-like cells, reported here, may open up a new treatment mode for enabling early closure of deep burn wounds.
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- 2020
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36. Soft Matrix Promotes Cardiac Reprogramming via Inhibition of YAP/TAZ and Suppression of Fibroblast Signatures.
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Kurotsu S, Sadahiro T, Fujita R, Tani H, Yamakawa H, Tamura F, Isomi M, Kojima H, Yamada Y, Abe Y, Murakata Y, Akiyama T, Muraoka N, Harada I, Suzuki T, Fukuda K, and Ieda M
- Subjects
- Actomyosin metabolism, Animals, Genetic Vectors metabolism, Integrins metabolism, Mice, Transgenic, Myocardium cytology, Myocytes, Cardiac cytology, Myosin Type II metabolism, Sendai virus genetics, Signal Transduction, YAP-Signaling Proteins, rho GTP-Binding Proteins metabolism, rho-Associated Kinases metabolism, Adaptor Proteins, Signal Transducing metabolism, Cellular Reprogramming, Extracellular Matrix metabolism, Fibroblasts metabolism
- Abstract
Direct cardiac reprogramming holds great potential for regenerative medicine. However, it remains inefficient, and induced cardiomyocytes (iCMs) generated in vitro are less mature than those in vivo, suggesting that undefined extrinsic factors may regulate cardiac reprogramming. Previous in vitro studies mainly used hard polystyrene dishes, yet the effect of substrate rigidity on cardiac reprogramming remains unclear. Thus, we developed a Matrigel-based hydrogel culture system to determine the roles of matrix stiffness and mechanotransduction in cardiac reprogramming. We found that soft matrix comparable with native myocardium promoted the efficiency and quality of cardiac reprogramming. Mechanistically, soft matrix enhanced cardiac reprogramming via inhibition of integrin, Rho/ROCK, actomyosin, and YAP/TAZ signaling and suppression of fibroblast programs, which were activated on rigid substrates. Soft substrate further enhanced cardiac reprogramming with Sendai virus vectors via YAP/TAZ suppression, increasing the reprogramming efficiency up to ∼15%. Thus, mechanotransduction could provide new targets for improving cardiac reprogramming., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2020
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37. Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine.
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Karbassi E, Fenix A, Marchiano S, Muraoka N, Nakamura K, Yang X, and Murry CE
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- Animals, Cell Culture Techniques, Humans, Metabolome, Myocytes, Cardiac cytology, Pluripotent Stem Cells cytology, Proteome, Stem Cell Transplantation methods, Tissue Engineering methods, Transcriptome, Cell Differentiation physiology, Myocytes, Cardiac physiology, Pluripotent Stem Cells physiology, Regenerative Medicine
- Abstract
Our knowledge of pluripotent stem cell (PSC) biology has advanced to the point where we now can generate most cells of the human body in the laboratory. PSC-derived cardiomyocytes can be generated routinely with high yield and purity for disease research and drug development, and these cells are now gradually entering the clinical research phase for the testing of heart regeneration therapies. However, a major hurdle for their applications is the immature state of these cardiomyocytes. In this Review, we describe the structural and functional properties of cardiomyocytes and present the current approaches to mature PSC-derived cardiomyocytes. To date, the greatest success in maturation of PSC-derived cardiomyocytes has been with transplantation into the heart in animal models and the engineering of 3D heart tissues with electromechanical conditioning. In conventional 2D cell culture, biophysical stimuli such as mechanical loading, electrical stimulation and nanotopology cues all induce substantial maturation, particularly of the contractile cytoskeleton. Metabolism has emerged as a potent means to control maturation with unexpected effects on electrical and mechanical function. Different interventions induce distinct facets of maturation, suggesting that activating multiple signalling networks might lead to increased maturation. Despite considerable progress, we are still far from being able to generate PSC-derived cardiomyocytes with adult-like phenotypes in vitro. Future progress will come from identifying the developmental drivers of maturation and leveraging them to create more mature cardiomyocytes for research and regenerative medicine.
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- 2020
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38. Surgical Management of Deep Brain Stimulator Infection without Electrode Removal: Report of Two Cases.
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Tanaka H, Rikimaru H, Rikimaru-Nishi Y, Muraoka N, Anegawa M, Ueki S, Oishi O, and Kiyokawa K
- Abstract
Objective Stimulation of the subthalamic nucleus by implanted electrodes (deep brain stimulation [DBS]) is performed to suppress symptoms of Parkinson's disease. However, postoperative wound dehiscence and infection can require removal of the implanted electrode leads. This report describes treatment of intractable unilateral wound infection in two patients without removing the DBS device. Methods First, components of the DBS system were removed except for the electrode lead and thorough debridement of the infected wound was conducted. Second, the edges of the bone defect left by removal of DBS components were smoothed to eliminate dead space. Subsequently, the electrode lead was covered by using a pericranial-frontalis-muscle flap or a bi-pedicled-scalp flap with good blood supply. Closed intrawound continuous negative pressure and irrigation treatment was conducted for 1 week after the surgery, and then the drain was removed. Results We treated two patients with wound infection after implantation of DBS electrodes. Case 1 developed a cutaneous fistula and Case 2 had wound dehiscence. After treatment by the method described above, complete wound healing was achieved in both patients. Conclusion DBS is always associated with a risk of infection or exposure of components and treatment can be very difficult. We successfully managed intractable wound infection while leaving the electrode lead in situ, so that it was subsequently possible to continue DBS for Parkinson's disease., Competing Interests: Conflict of Interest None.
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- 2020
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39. A Proteomic Perspective on Cardiomyocyte Maturation.
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Muraoka N, Sun B, and Murry CE
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- Humans, Myocytes, Cardiac, Proteomics, Induced Pluripotent Stem Cells, Pluripotent Stem Cells
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- 2019
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40. Is intracranial electroencephalography useful for planning resective surgery in intractable epilepsy with ulegyria?
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Takayama Y, Ikegaya N, Iijima K, Kimura Y, Muraoka N, Kaneko Y, Yamamoto T, and Iwasaki M
- Abstract
Objective: Intractable epilepsy patients with ulegyria could be candidates for resective surgery. Complete resection of ulegyria in the epileptogenic hemisphere is associated with favorable seizure outcome, although the risk of postoperative functional deficits is higher. The authors evaluated the extent of resection and postsurgical outcomes in epilepsy patients with ulegyria who underwent intracranial electroencephalography (iEEG) monitoring prior to resection to clarify the efficacy of iEEG-guided partial resection of ulegyria., Methods: Ten consecutive epilepsy patients with ulegyria (7 males and 3 females, age range at surgery 7-34 years) underwent iEEG prior to resective surgery between 2011 and 2017 with a minimum follow-up of 12 months (range 12-72 months). The diagnosis of ulegyria was based on the typical pattern of cortical atrophy especially at the bottom of the sulcus on MRI. An iEEG study was indicated after comprehensive preoperative evaluations, including high-field MRI, long-term video-EEG, magnetoencephalography, and FDG-PET. The resection planning was based on iEEG analysis. Total lesionectomy was not always performed, as preservation of cortical function was prioritized., Results: Ulegyria was seen in the occipital and/or parietal lobe in 9 patients and bilaterally in 5 patients. Ictal EEG onset involved the temporal neocortex in 6 patients. Intracranial electrodes were implanted unilaterally in all except 1 patient with bilateral lesions. The extent of MRI lesion was covered by the electrodes. Seizure onset zones (SOZs) and irritative zones (IZs) were identified in all patients. SOZs and IZs were completely resected in 8 patients but were only partially removed in the remaining 2 patients because the eloquent cortices and the epileptogenic zones overlapped. Ulegyria of the epileptogenic side was totally resected in 1 patient. Seizure freedom was achieved in 4 patients, including 3 after partial lesionectomy. Extended resection of the temporal neocortex was performed in 4 patients, although postoperative seizure freedom was achieved only in 1 of these patients. Visual field deficit was seen in 4 patients. Three of 5 patients with bilateral lesions achieved seizure freedom after unilateral resective surgery., Conclusions: Intracranial EEG-guided partial lesionectomy provides a reasonable chance of postoperative seizure freedom with a lower risk of functional deficits. Patients with bilateral ulegyria should not be excluded from consideration as surgical candidates.
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- 2019
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41. A Cavity Communicating with the Right Atrium.
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Oyakawa T, Muraoka N, and Iida K
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- 2019
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42. Use of direct oral anti-coagulants for the treatment of venous thromboembolism in patients with advanced cancer: a prospective observational study.
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Oyakawa T, Muraoka N, Iida K, Kusuhara M, and Mori K
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- Administration, Oral, Adult, Aged, Aged, 80 and over, Anticoagulants adverse effects, Female, Hemorrhage chemically induced, Hemorrhage epidemiology, Humans, Male, Middle Aged, Prospective Studies, Recurrence, Risk Factors, Anticoagulants administration & dosage, Neoplasms complications, Venous Thromboembolism drug therapy, Venous Thromboembolism etiology
- Abstract
Background: The efficacy of direct oral anti-coagulants (DOACs) for the treatment of venous thromboembolism (VTE) in Japanese patients with advanced cancer is largely unknown., Methods: This prospective single-center observational study enrolled Japanese patients with unresectable advanced cancer who started DOAC treatment for new-onset VTE between December 2015 and May 2018. Patients were followed for 3 months to evaluate bleeding and VTE recurrences. The primary study endpoint was major and non-major bleeding., Results: One hundred and forty-five of 147 enrolled patients were analyzed. Of these, 8 [5.5%, 95% confidence interval (CI) 2.8-10.5] and 29 patients (20%, 95% CI 14.3-27.2) experienced major and non-major bleeding, respectively. Patients with bleeding were more likely to have a poor performance status (PS) [hazard rate (HR) 2.04, 95% CI 1.15-3.63] and more frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) (HR 2.75, 95% CI 1.62-4.67) relative to those without bleeding. In a multivariate analysis, combined DOAC and NSAID use correlated significantly with bleeding (odds ratio 4.63, 95% CI 1.70-12.9, p = 0.003). Among 105 of 145 patients included in the VTE recurrence assessment, 9 experienced a VTE recurrence (8.6%, 95% CI 4.6-15.5)., Conclusions: Our findings confirm the risk of bleeding during DOAC treatment for VTE in Japanese patients with advanced cancer, particularly those with poor PS and those using NSAIDs. The risk of bleeding in these patients may be reduced by avoiding the combined use of DOACs and NSAIDs.
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- 2019
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43. Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts.
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Haginiwa S, Sadahiro T, Kojima H, Isomi M, Tamura F, Kurotsu S, Tani H, Muraoka N, Miyake N, Miyake K, Fukuda K, and Ieda M
- Subjects
- Adenoviridae genetics, Animals, Animals, Newborn, Cell Cycle Proteins drug effects, Cells, Cultured, Cyclins drug effects, Genetic Vectors administration & dosage, Heart, Mice, Rats, Regeneration, T-Box Domain Proteins genetics, T-Box Domain Proteins metabolism, T-Box Domain Proteins pharmacology, Cell Proliferation drug effects, Myocardium cytology, Myocytes, Cardiac cytology, T-Box Domain Proteins physiology
- Abstract
Cardiovascular disease is a leading cause of death worldwide. Mammalian cardiomyocytes (CMs) proliferate during embryonic development, whereas they largely lose their regenerative capacity after birth. Defined factors expressed in cardiac progenitors or embryonic CMs may activate the cell cycle and induce CM proliferation in postnatal and adult hearts. Here, we report that the overexpression of Tbx6, enriched in the cardiac mesoderm (progenitor cells), induces CM proliferation in postnatal and adult mouse hearts. By screening 24 factors enriched in cardiac progenitors or embryonic CMs, we found that only Tbx6 could induce CM proliferation in primary cultured postnatal rat CMs. Intriguingly, it did not induce the proliferation of cardiac fibroblasts. We next generated a recombinant adeno-associated virus serotype 9 vector encoding Tbx6 (AAV9-Tbx6) for transduction into mouse CMs in vivo. The subcutaneous injection of AAV9-Tbx6 into neonatal mice induced CM proliferation in postnatal and adult mouse hearts. Mechanistically, Tbx6 overexpression upregulated multiple cell cycle activators including Aurkb, Mki67, Ccna1, and Ccnb2 and suppressed the tumor suppressor Rb1. Thus, Tbx6 promotes CM proliferation in postnatal and adult mouse hearts by modifying the expression of cell cycle regulators., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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44. Cancer-associated cerebral infarction during direct oral anticoagulant treatment in cancer patients: a case series.
- Author
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Oyakawa T, Fukuda H, Muraoka N, Iida K, and Kusuhara M
- Abstract
The effect of direct oral anticoagulants (DOACs) on cancer-associated cerebral infarction (CI) is unclear. We present the clinical course of 20 consecutive patients with cancer-associated CI that developed during treatment with DOACs. The incidence rate of cancer-associated CI during the treatment with DOACs was 3.4%. The median modified Rankin scale (mRS) and Karnofsky performance status (KPS) after CI were 5 and 30, respectively. The median survival time after CI was 1 month. In the group in which the thrombus due to venous thromboembolism (VTE) was reduced before CI, the median mRS, KPS, and prognosis after CI were significantly better than in those of the group with unchanged thrombus. Cancer-associated CI also developed in patients taking DOACs and those who did not show VTE recurrence. When the VTE thrombus decreased or disappeared with DOAC treatment, the clinical course after cancer-associated CI was improved., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.
- Published
- 2019
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45. Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming.
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Muraoka N, Nara K, Tamura F, Kojima H, Yamakawa H, Sadahiro T, Miyamoto K, Isomi M, Haginiwa S, Tani H, Kurotsu S, Osakabe R, Torii S, Shimizu S, Okano H, Sugimoto Y, Fukuda K, and Ieda M
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Differentiation drug effects, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases metabolism, Cyclooxygenase 2 drug effects, Diclofenac pharmacology, Dinoprostone, Fibroblasts, GATA4 Transcription Factor metabolism, Humans, Inflammation, Interleukin-1beta, MEF2 Transcription Factors metabolism, Mice, Mice, Transgenic, T-Box Domain Proteins metabolism, Cellular Reprogramming drug effects, Cyclooxygenase 2 pharmacology, Myocytes, Cardiac drug effects, Receptors, Prostaglandin E, EP4 Subtype drug effects, Signal Transduction drug effects
- Abstract
Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging.
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- 2019
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46. [(1)Indication for Invasive Monitoring in the Surgical Treatment of Epilepsy].
- Author
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Iwasaki M, Takayama Y, Iijima K, Kimura Y, Muraoka N, and Kaneko Y
- Subjects
- Electroencephalography, Humans, Epilepsy diagnosis, Epilepsy surgery
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- 2019
- Full Text
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47. Effect of Switching from the Initial Direct Oral Anticoagulant to Another One on Exacerbation of Venous Thromboembolism in Patients with Cancer: A Retrospective Study.
- Author
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Oyakawa T, Muraoka N, Iida K, and Kusuhara M
- Abstract
Objective : To determine the effect of switching from the initial direct oral anticoagulant (DOAC) to another DOAC on exacerbation of deep vein thrombosis (DVT). Materials and Methods : We retrospectively reviewed the data of patients with advanced cancer who experienced exacerbated DVT during initial treatment with DOAC due to new venous thromboembolism (VTE). After switching to another DOAC for VTE recurrence, changes in the thrombus and bleeding were evaluated for 3 months. Eighteen patients met these criteria. We compared the effect of anticoagulant switching on the switched-drug group in those 18 patients with the effect of no anticoagulant switching on the single-drug group of patients (n=78) with a similar background. Results : The recurrence rate of VTE in the switched-drug group was 6%. Non-major bleeding occurred in 11% of patients. Recurrent VTE occurred in 6% of patients in both the switched-drug and single-drug groups, respectively [risk ratio (RR): 0.9, 95% confidence interval (CI): 0.11-7.6]. Non-major bleeding occurred in 11% and 14% of patients in the switched-drug and single-drug groups, respectively (RR: 0.79, 95%CI: 0.19-3.2). Conclusion : Switching DOAC may be a treatment option for exacerbation of DVT in patients with advanced cancer.
- Published
- 2018
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48. Crizotinib-induced simultaneous multiple cardiac toxicities.
- Author
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Oyakawa T, Muraoka N, Iida K, Kusuhara M, Kawamura T, Naito T, and Takahashi T
- Subjects
- Adenocarcinoma drug therapy, Arrhythmias, Cardiac chemically induced, Female, Humans, Long QT Syndrome chemically induced, Lung Neoplasms drug therapy, Middle Aged, Pericarditis chemically induced, Proto-Oncogene Mas, Antineoplastic Agents adverse effects, Cardiotoxicity etiology, Crizotinib adverse effects, Protein Kinase Inhibitors adverse effects
- Abstract
Crizotinib is a receptor tyrosine kinase inhibitor that has several targets, including c-ros oncogene 1 and the MET proto-oncogene. Considering its known cardiac toxicity, bradycardia is often investigated following treatment with crizotinib. Our patients had bradycardia, QT prolongation, ventricular rhythm, ventricular fibrillation, and pericarditis simultaneously. The cardiotoxicity of crizotinib can sometimes be simultaneous; thus, intensive observation is needed.
- Published
- 2018
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49. Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification.
- Author
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Sadahiro T, Isomi M, Muraoka N, Kojima H, Haginiwa S, Kurotsu S, Tamura F, Tani H, Tohyama S, Fujita J, Miyoshi H, Kawamura Y, Goshima N, Iwasaki YW, Murano K, Saito K, Oda M, Andersen P, Kwon C, Uosaki H, Nishizono H, Fukuda K, and Ieda M
- Subjects
- Animals, Cell Differentiation, Cells, Cultured, Humans, Male, Mesoderm, Mice, Mice, Inbred ICR, Mice, Transgenic, T-Box Domain Proteins, Transcription Factors genetics, Cardiovascular System metabolism, Cell Lineage, Pluripotent Stem Cells metabolism, Somites cytology, Somites metabolism, Transcription Factors metabolism
- Abstract
The mesoderm arises from pluripotent epiblasts and differentiates into multiple lineages; however, the underlying molecular mechanisms are unclear. Tbx6 is enriched in the paraxial mesoderm and is implicated in somite formation, but its function in other mesoderms remains elusive. Here, using direct reprogramming-based screening, single-cell RNA-seq in mouse embryos, and directed cardiac differentiation in pluripotent stem cells (PSCs), we demonstrated that Tbx6 induces nascent mesoderm from PSCs and determines cardiovascular and somite lineage specification via its temporal expression. Tbx6 knockout in mouse PSCs using CRISPR/Cas9 technology inhibited mesoderm and cardiovascular differentiation, whereas transient Tbx6 expression induced mesoderm and cardiovascular specification from mouse and human PSCs via direct upregulation of Mesp1, repression of Sox2, and activation of BMP/Nodal/Wnt signaling. Notably, prolonged Tbx6 expression suppressed cardiac differentiation and induced somite lineages, including skeletal muscle and chondrocytes. Thus, Tbx6 is critical for mesoderm induction and subsequent lineage diversification., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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50. A Patient with a Massive Single Cardiac Metastasis of Lung Adenocarcinoma, Diagnosed via a Biopsy.
- Author
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Oyakawa T, Muraoka N, Iida K, Kusuhara M, and Naito T
- Subjects
- Adenocarcinoma diagnosis, Adenocarcinoma of Lung, Aged, Biopsy, Coronary Angiography, Heart Ventricles pathology, Humans, Lung Neoplasms diagnosis, Male, Tomography, X-Ray Computed, Adenocarcinoma secondary, Heart Neoplasms diagnosis, Heart Neoplasms secondary, Lung Neoplasms secondary
- Abstract
A patient with a history of lung adenocarcinoma was admitted because of palpitation. Transthoracic echocardiogram revealed a mass (74×42 mm) in the right ventricle. Computed tomography showed a tumor lesion in the right ventricular cavity but no other distant metastasis. Coronary angiography revealed well-developed small branches to the tumor. After right heart catheterization, a pathological analysis of a tumor biopsy demonstrated adenocarcinoma. We diagnosed the patient with right ventricular metastasis of lung cancer. With large cardiac metastasis, a tumor biopsy with a right heart catheter may help obtain a pathological diagnosis and also serve as a re-biopsy to confirm the gene mutation status.
- Published
- 2018
- Full Text
- View/download PDF
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