111 results on '"Koitabashi N"'
Search Results
2. Leptin is essential in maintaining normal vascular compliance independent of body weight
- Author
-
Sikka, G, Yang, R, Reid, S, Benjo, A, Koitabashi, N, Camara, A, Baraban, E, O'Donnell, C P, Berkowitz, D E, and Barouch, L A
- Published
- 2010
- Full Text
- View/download PDF
3. P4481A robust increase in glucose uptake independently of insulin exacerbates rather than ameliorates cardiac dysfunction under septic condition
- Author
-
Umbarawan, Y., primary, Iso, T., additional, Syamsunarno, M.R.A.A., additional, Koitabashi, N., additional, and Kurabayashi, M., additional
- Published
- 2017
- Full Text
- View/download PDF
4. Leptin is essential in maintaining normal vascular compliance independent of body weight
- Author
-
Sikka, G, primary, Yang, R, additional, Reid, S, additional, Benjo, A, additional, Koitabashi, N, additional, Camara, A, additional, Baraban, E, additional, O'Donnell, C P, additional, Berkowitz, D E, additional, and Barouch, L A, additional
- Published
- 2009
- Full Text
- View/download PDF
5. Phosphodiesterase 5 inhibition blocks pressure overload-induced cardiac hypertrophy independent of the calcineurin pathway
- Author
-
Hsu, S., primary, Nagayama, T., additional, Koitabashi, N., additional, Zhang, M., additional, Zhou, L., additional, Bedja, D., additional, Gabrielson, K. L., additional, Molkentin, J. D., additional, Kass, D. A., additional, and Takimoto, E., additional
- Published
- 2008
- Full Text
- View/download PDF
6. Mitochondrial transcription factors regulate SERCA2 gene transcription
- Author
-
WATANABE, A, primary, ARAI, M, additional, KOITABASHI, N, additional, YAMAZAKI, M, additional, NIWANO, K, additional, and KURABAYASHI, M, additional
- Published
- 2006
- Full Text
- View/download PDF
7. Pressure mediated hypertrophy and mechanical stretch up-regulate expression of the long form of leptin receptor (ob-Rb) in rat cardiac myocytes
- Author
-
Matsui Hiroki, Yokoyama Tomoyuki, Tanaka Chie, Sunaga Hiroaki, Koitabashi Norimichi, Takizawa Takako, Arai Masashi, and Kurabayashi Masahiko
- Subjects
Obesity ,Cardiac hypertrophy ,Pressure overload ,Cytology ,QH573-671 - Abstract
Abstract Background Hyperleptinemia is known to participate in cardiac hypertrophy and hypertension, but the relationship between pressure overload and leptin is poorly understood. We therefore examined the expression of leptin (ob) and the leptin receptor (ob-R) in the pressure-overloaded rat heart. We also examined gene expressions in culture cardiac myocytes to clarify which hypertension-related stimulus induces these genes. Results Pressure overload was produced by ligation of the rat abdominal aorta, and ob and ob-R isoform mRNAs were measured using a real-time polymerase chain reaction (PCR). We also measured these gene expressions in neonatal rat cardiac myocytes treated with angiotensin II (ANGII), endothelin-1 (ET-1), or cyclic mechanical stretch. Leptin and the long form of the leptin receptor (ob-Rb) gene were significantly increased 4 weeks after banding, but expression of the short form of the leptin receptor (ob-Ra) was unchanged. ob-Rb protein expression was also detected by immunohistochemistry in hypertrophied cardiac myocytes after banding. Meanwhile, plasma leptin concentrations were not different between the control and banding groups. In cultured myocytes, ANGII and ET-1 increased only ob mRNA expression. However, mechanical stretch activated both ob and ob-Rb mRNA expression in a time-dependent manner, but ob-Ra mRNA was unchanged by any stress. Conclusions We first demonstrated that both pressure mediated hypertrophy and mechanical stretch up-regulate ob-Rb gene expression in heart and cardiac myocytes, which are thought to be important for leptin action in cardiac myocytes. These results suggest a new local mechanism by which leptin affects cardiac remodeling in pressure-overloaded hearts.
- Published
- 2012
- Full Text
- View/download PDF
8. Clinical characteristics and short-term outcomes of patients with critical acute pulmonary embolism requiring extracorporeal membrane oxygenation: from the COMMAND VTE Registry-2.
- Author
-
Takabayashi K, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, Ono K, and Kimura T
- Abstract
Background: Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database., Methods: We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO., Results: Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only., Conclusions: The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
9. Incidence of Chronic Thromboembolic Pulmonary Hypertension After Pulmonary Embolism in the Era of Direct Oral Anticoagulants: From the COMMAND VTE Registry-2.
- Author
-
Ikeda N, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, and Kimura T
- Subjects
- Humans, Female, Male, Incidence, Aged, Middle Aged, Japan epidemiology, Risk Factors, Chronic Disease, Anticoagulants adverse effects, Anticoagulants administration & dosage, Anticoagulants therapeutic use, Administration, Oral, Risk Assessment, Time Factors, Pulmonary Embolism epidemiology, Pulmonary Embolism drug therapy, Pulmonary Embolism diagnosis, Registries, Hypertension, Pulmonary epidemiology, Hypertension, Pulmonary drug therapy, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary etiology
- Abstract
Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication post-acute pulmonary embolism (PE). The assessment of CTEPH incidence and risk factors post-acute PE in the era of direct oral anticoagulants remains insufficient., Methods and Results: The COMMAND VTE Registry-2 (contemporary management and outcomes in patients with venous thromboembolism registry-2) is a multicenter registry that recruited consecutive patients with acute symptomatic venous thromboembolism from 31 centers across Japan. The primary outcome was to demonstrate the detection rate of CTEPH after acute PE in routine clinical practice. Out of the 5197 patients with venous thromboembolism included in the COMMAND VTE Registry-2, 2787 were diagnosed with acute PE. Following a median follow-up duration of 747 days, 48 cases of CTEPH were detected, and the cumulative diagnosis of CTEPH in routine clinical practice was 2.3% at 3 years. Independent risk factors for the detection of CTEPH by multivariable Cox regression analysis included women (hazard ratio [HR] 2.09 [95% CI, 1.05-4.14]), longer interval from symptom onset to diagnosis of PE (each 1 day, HR 1.04 [95% CI, 1.01-1.07]), hypoxemia at diagnosis (HR 2.52 [95% CI, 1.26-5.04]), right heart load (HR 9.28 [95% CI, 3.19-27.00]), lower D-dimer value (each 1 μg/mL, HR 0.96 [95% CI, 0.92-0.99]), and unprovoked PE (HR 2.77 [95% CI, 1.22-6.30])., Conclusions: In the direct oral anticoagulant era, the cumulative diagnosis of CTEPH after acute PE was 2.3% at 3 years, and several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population after acute PE.
- Published
- 2024
- Full Text
- View/download PDF
10. Edoxaban, Rivaroxaban, or Apixaban for Cancer-Associated Venous Thromboembolism in the Real World: Insights from the COMMAND VTE Registry-2.
- Author
-
Sueta D, Yamashita Y, Morimoto T, Chatani R, Nishimoto Y, Kaneda K, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Shioyama W, Dohke T, Nishikawa R, Kimura T, and Tsujita K
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Japan epidemiology, Incidence, Recurrence, Aged, 80 and over, Risk Factors, Treatment Outcome, Venous Thromboembolism drug therapy, Venous Thromboembolism epidemiology, Venous Thromboembolism diagnosis, Venous Thromboembolism prevention & control, Registries, Rivaroxaban therapeutic use, Rivaroxaban adverse effects, Neoplasms complications, Neoplasms drug therapy, Hemorrhage chemically induced, Pyridines therapeutic use, Pyridines adverse effects, Pyrazoles therapeutic use, Pyrazoles adverse effects, Factor Xa Inhibitors therapeutic use, Factor Xa Inhibitors adverse effects, Pyridones therapeutic use, Pyridones adverse effects, Thiazoles therapeutic use, Thiazoles adverse effects
- Abstract
Background: Real-world data on clinical characteristics and outcomes related to the use of different direct oral anticoagulants (DOACs) for cancer-associated venous thromboembolism (VTE) is lacking., Methods: The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan from January 2015 to August 2020. Our study population comprised 1,197 patients with active cancer who were divided into the edoxaban ( N = 643, 54%), rivaroxaban ( N = 297, 25%), and apixaban ( N = 257, 22%) groups., Results: The cumulative 5-year incidence of recurrent VTE (9.3, 10.2, and 8.5%, respectively, p = 0.82) and all-cause death (67.5, 66.8, and 63.8%, respectively, p = 0.22) did not differ among the groups. Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. The cumulative 5-year incidence of major and clinically relevant bleeding was significantly lower in the rivaroxaban group than those in the other groups (22.6, 14.0, and 22.8%, p = 0.04; and 37.6, 26.8, and 38.3%, p = 0.01, respectively). After adjusting for confounders, in the rivaroxaban group, the risk for major bleeding was numerically lower (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.40-1.01) and that of clinically relevant all bleeding was significantly lower (HR: 0.67, 95% CI: 0.48-0.92) than those in the edoxaban group., Conclusion: The risks of recurrent VTE and all-cause death did not differ significantly among the different DOACs ; however, the risk of bleeding events could differ, with a potentially lower risk of bleeding with rivaroxaban., Competing Interests: Y.Y. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and grant support from Bayer Healthcare and Daiichi-Sankyo. T.M. reports lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Y.N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. K.K. received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. N.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. S.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Y.O. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and research funds from Bayer Healthcare and Daiichi-Sankyo. K.T. 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., Medtronic Japan Co., Ltd. All other authors have reported that they have no relationships relevant to the contents of this article to disclose., (Thieme. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
11. Initial anticoagulation therapy with single direct oral anticoagulant in patients with intermediate-high risk acute pulmonary embolism: From the COMMAND VTE Registry-2.
- Author
-
Shigeno R, Kim K, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, Furukawa Y, and Kimura T
- Abstract
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. Kaneda received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Morimoto reports lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb 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. Koitabashi received lecture fees from Bayer Healthcare and grant support from Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Published
- 2024
- Full Text
- View/download PDF
12. Sacubitril/valsartan improves diastolic left ventricular stiffness with increased titin phosphorylation via cGMP-PKG activation in diabetic mice.
- Author
-
Furukawa N, Matsui H, Sunaga H, Nagata K, Hirayama M, Obinata H, Yokoyama T, Ohno K, Kurabayashi M, and Koitabashi N
- Subjects
- Animals, Phosphorylation drug effects, Mice, Male, Diastole drug effects, Diabetic Cardiomyopathies drug therapy, Diabetic Cardiomyopathies metabolism, Diabetic Cardiomyopathies physiopathology, Mice, Inbred C57BL, Heart Ventricles drug effects, Heart Ventricles metabolism, Heart Ventricles physiopathology, Ventricular Dysfunction, Left drug therapy, Ventricular Dysfunction, Left metabolism, Ventricular Dysfunction, Left etiology, Angiotensin Receptor Antagonists pharmacology, Protein Kinases, Valsartan pharmacology, Connectin metabolism, Cyclic GMP-Dependent Protein Kinases metabolism, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Experimental physiopathology, Drug Combinations, Biphenyl Compounds pharmacology, Biphenyl Compounds therapeutic use, Cyclic GMP metabolism, Aminobutyrates pharmacology
- Abstract
Titin, a giant sarcomeric protein, regulates diastolic left ventricular (LV) passive stiffness as a molecular spring and could be a therapeutic target for diastolic dysfunction. Sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor, has been shown to benefit patients with heart failure with preserved ejection fraction. The effect of Sac/Val is thought to be due to the enhancement of the cGMP/PKG pathway via natriuretic peptide. In this study, the effects of Sac/Val on LV diastolic dysfunction are demonstrated in a mouse diabetic cardiomyopathy model focusing on titin phosphorylation. Sac/Val-treated diabetic mice showed a greater increase in myocardial levels of cGMP-PKG than Val-treated and control mice. Conductance catheter analysis showed a significant reduction in LV stiffness in diabetic mice, but not in non-diabetic mice. Notably, diastolic LV stiffness was significantly reduced in Sac/Val-treated diabetic hearts compared with Val-treated or vehicle-treated diabetic mice. The phosphorylation level of titin (N2B), which determines passive stiffness and modulates active contraction, was higher in Sac/Val-treated hearts compared with Val-treated hearts in diabetic mice. Given that alteration of titin phosphorylation through PKG contributes to myocardial stiffness, the beneficial effects of Sac/Val in heart failure might be partly attributed to the induction of titin phosphorylation., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
13. Association Between White Blood Cell Counts at Diagnosis and Clinical Outcomes in Venous Thromboembolism - From the COMMAND VTE Registry-2.
- Author
-
Ikeda S, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, Ono K, and Kimura T
- Abstract
Background: White blood cell (WBC) counts were reported to be a risk factor for acute adverse events in patients with venous thromboembolism (VTE). However, there are limited data on VTE patients without active cancer., Methods and Results: The COMMAND VTE Registry-2 was a multicenter study enrolling 5,197 consecutive patients with acute symptomatic VTE. We divided 3,668 patients without active cancer into 4 groups based on WBC count quartiles (Q1-Q4) at diagnosis: Q1, ≤5,899 cells/μL; Q2, 5,900-7,599 cells/μL, Q3, 7,600-9,829 cells/μL; and Q4, ≥9,830 cells/μL. Patients in Q4 more often presented with pulmonary embolism (PE) than patients in Q1, Q2, and Q3 (68% vs. 37%, 53%, and 61%, respectively; P<0.001). The proportion of massive PEs among all PEs was higher in Q4 than in Q1, Q2, and Q3 (21% vs. 3.4%, 5.8%, and 11%, respectively; P<0.001). Compared with Q1, Q2, and Q3, patients in Q4 had a higher cumulative 5-year incidence of all-cause death (17.0%, 15.2%, 16.1%, and 22.8%, respectively; P<0.001) and major bleeding (10.9%, 11.0%, 10.3%, and 14.4%, respectively; P=0.002). The higher mortality risk of Q4 relative to Q2 was consistent regardless of the presentations of VTEs., Conclusions: An elevated WBC count on VTE diagnosis was associated with a higher risk of mortality and major bleeding regardless of VTE presentation, suggesting the potential usefulness of WBC counts for further risk stratification.
- Published
- 2024
- Full Text
- View/download PDF
14. Selection of Home Treatment and Identification of Low-Risk Patients With Pulmonary Embolism Based on Simplified Pulmonary Embolism Severity Index Score in the Era of Direct Oral Anticoagulants.
- Author
-
Nishikawa R, Yamashita Y, Morimoto T, Kaneda K, Chatani R, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Ono K, and Kimura T
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Risk Assessment, Administration, Oral, Japan epidemiology, Risk Factors, Home Care Services, Patient Selection, Aged, 80 and over, Treatment Outcome, Pulmonary Embolism drug therapy, Pulmonary Embolism mortality, Pulmonary Embolism diagnosis, Severity of Illness Index, Registries, Anticoagulants administration & dosage, Anticoagulants therapeutic use, Anticoagulants adverse effects
- Abstract
Background: The simplified Pulmonary Embolism Severity Index (sPESI) score could help identify low-risk patients with pulmonary embolism for home treatment. However, the application of the sPESI score and selection for home treatment have not been fully evaluated in the direct oral anticoagulants era., Methods and Results: The COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) Registry-2 is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism. The current study population consists of 2496 patients with hemodynamically stable pulmonary embolism (2100 patients [84%] treated with direct oral anticoagulants), who were divided into 2 groups: sPESI scores of 0 and ≥1. We investigated the 30-day mortality, home treatment prevalence, and factors predisposing to home treatment using the Kaplan-Meier method and logistic regression model. Patients with an sPESI score of 0 accounted for 612 (25%) patients, and only 17% among 532 patients with out-of-hospital pulmonary embolism were treated at home. The cumulative 30-day mortality was lower in patients with an sPESI score of 0 than the score of ≥1 (0% and 4.8%, log-rank P <0.001). There was no patient with 30-day mortality with an sPESI score of 0. Independent factors for home treatment among out-of-hospital pulmonary embolism patients with an sPESI score of 0 were no transient risk factors for venous thromboembolism, no cardiac biomarker elevation, and direct oral anticoagulants use in the acute phase., Conclusions: The 30-day mortality rate was notably low in an sPESI score of 0. Nevertheless, only a minority of patients with an sPESI score of 0 were treated at home between 2015 and 2020 after the introduction of direct oral anticoagulants for venous thromboembolismin Japan.
- Published
- 2024
- Full Text
- View/download PDF
15. External validation of the Pulmonary Embolism-Syncope, Anemia, and Renal Dysfunction bleeding score for early major bleeding in patients with acute pulmonary embolism: from the COMMAND VTE Registry-2.
- Author
-
Nishimoto Y, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, Sato Y, Watanabe T, Yamada T, Fukunami M, and Kimura T
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Japan epidemiology, Risk Assessment, Risk Factors, Reproducibility of Results, Anticoagulants adverse effects, Anticoagulants therapeutic use, Predictive Value of Tests, Time Factors, Aged, 80 and over, Acute Disease, Kidney Diseases diagnosis, Kidney Diseases complications, Decision Support Techniques, Hemorrhage diagnosis, Pulmonary Embolism diagnosis, Pulmonary Embolism epidemiology, Registries, Anemia diagnosis, Anemia complications
- Abstract
Background: There is no established risk score for anticoagulant-related bleeding during the acute phase in patients with pulmonary embolism (PE). The PE-Syncope, Anemia, and Renal Dysfunction (PE-SARD) bleeding score was developed to predict early major bleeding but has not yet been fully externally validated., Objectives: To externally validate the PE-SARD bleeding score., Methods: Using the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) Registry-2 database, which enrolled 5197 consecutive acute symptomatic venous thromboembolism patients among 31 centers in Japan between January 2015 and August 2020, we identified acute PE patients. We divided them into 3 groups by the score: high-risk (>2.5 points), intermediate-risk (1-2.5 points), and low-risk (0 points). The discriminating and calibration performances of the score for 30-day major bleeding were assessed. Subgroup analyses based on active cancer were also performed., Results: Of 2781 eligible patients, the high-risk group accounted for 557 patients (20%), intermediate-risk group for 1412 (51%), and low-risk group for 812 (29%). Major bleeding occurred in 121 patients within 30 days. The cumulative 30-day incidence of major bleeding substantially increased in the higher risk categories by the score (high-risk group, 8.2% [95% CI, 5.9%-10.5%]; intermediate-risk group, 4.6% [95% CI, 3.5%-5.7%]; and low-risk group, 1.8% [95% CI, 0.8%-2.7%]). The discriminating power of the score was modest with a C statistic of 0.65 (95% CI, 0.61-0.70), with a good calibration performance with a score of <4 points, except for that in active cancer patients., Conclusion: The PE-SARD bleeding score had a modest discriminating performance with a limited calibration performance in acute PE patients without active cancer., Competing Interests: Declaration of competing interests Y.N. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo. Y.Y. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. T.M. reports lecturer’s fees from Bristol Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol Myers Squibb and Kowa; advisory board for Sanofi. K. Kaneda received lecture fees from Bristol Myers Squibb, Pfizer, and Daiichi Sankyo. N.I. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, and Daiichi Sankyo. S.I. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, and Daiichi Sankyo. Y.O. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Bayer Healthcare and Daiichi Sankyo. N.K. received lecture fees from Bayer Healthcare and grant support from Pfizer. All other authors declare that they have no conflict of interest., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
16. Temporal Changes in Long-Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era.
- Author
-
Kaneda K, Yamashita Y, Morimoto T, Chatani R, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, Ono K, and Kimura T
- Subjects
- Humans, Male, Female, Japan epidemiology, Aged, Middle Aged, Administration, Oral, Incidence, Time Factors, Treatment Outcome, Risk Factors, Venous Thromboembolism epidemiology, Venous Thromboembolism drug therapy, Venous Thromboembolism diagnosis, Warfarin adverse effects, Warfarin therapeutic use, Registries, Anticoagulants adverse effects, Anticoagulants therapeutic use, Recurrence, Hemorrhage chemically induced, Hemorrhage epidemiology, Factor Xa Inhibitors adverse effects, Factor Xa Inhibitors therapeutic use
- Abstract
Background: There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long-term outcomes from the warfarin era to the DOAC era., Methods and Results: We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010-2014) and Registry 2: 5197 patients in the DOAC era (2015-2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P <0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P =0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P =0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P =0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P =0.63)., Conclusions: Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.
- Published
- 2024
- Full Text
- View/download PDF
17. Effect of genetic factors on the interindividual variability of warfarin dosage requirements in Japanese patients after adjusting for renal function.
- Author
-
Nishiba H, Nagamine A, Yashima H, Takahashi Y, Higuchi Y, Sekizaki N, Nakamura H, Araki T, Takama N, Koitabashi N, Nakajima T, Kaneko Y, Ohyama Y, Yokoyama T, Imai K, Kurabayashi M, Yamamoto K, and Obayashi K
- Subjects
- Humans, Female, Male, Aged, Middle Aged, Asian People genetics, Japan, International Normalized Ratio, Dose-Response Relationship, Drug, Glomerular Filtration Rate, Vitamin K Epoxide Reductases genetics, Aged, 80 and over, Cytochrome P450 Family 4 genetics, Genotype, Adult, East Asian People, Warfarin administration & dosage, Anticoagulants administration & dosage, Polymorphism, Single Nucleotide
- Abstract
Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1 , CYP2C9 , CYP2C19 , CYP4F2 , GGCX , and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [ VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19
* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (β = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and β = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.- Published
- 2024
- Full Text
- View/download PDF
18. Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: insight from the COMMAND VTE Registry-2.
- Author
-
Mabuchi H, Nishikawa R, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Ono K, Nakagawa Y, and Kimura T
- Subjects
- Humans, Aged, Male, Female, Japan epidemiology, Middle Aged, Secondary Prevention methods, Incidence, Anticoagulants therapeutic use, Anticoagulants adverse effects, Anticoagulants administration & dosage, Aged, 80 and over, Administration, Oral, Venous Thromboembolism epidemiology, Venous Thromboembolism prevention & control, Venous Thromboembolism drug therapy, Registries, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Recurrence
- Abstract
Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
19. Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis.
- Author
-
Ikeda S, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, Ono K, and Kimura T
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Registries, Anticoagulants therapeutic use, Adult, Venous Thromboembolism drug therapy, Phenotype, Latent Class Analysis
- Abstract
Background: Patients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies., Methods: In the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups., Results: This LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04)., Conclusion: The current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm COMMAND VTE Registry-2: Unique identifier, UMIN000044816 COMMAND VTE Registry: Unique identifier, UMIN000021132., 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 fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb, and Kowa, and the advisory board for Sanofi. Dr. Kaneda received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, 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. Koitabashi received lecture fees from Bayer Healthcare and grant support from Pfizer. 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.)
- Published
- 2024
- Full Text
- View/download PDF
20. Pyothorax and Constrictive Pericarditis after Chemoradiotherapy for Esophageal Cancer.
- Author
-
Ishibashi Y, Takama N, Ohtaki Y, Koitabashi N, Kurabayashi M, and Ishii H
- Subjects
- Humans, Male, Aged, Fatal Outcome, Pericarditis, Constrictive etiology, Pericarditis, Constrictive diagnosis, Pericarditis, Constrictive therapy, Esophageal Neoplasms therapy, Chemoradiotherapy adverse effects, Empyema, Pleural etiology, Empyema, Pleural therapy
- Abstract
A 75-year-old man underwent chemoradiotherapy for advanced esophageal cancer. After nine years, he was hospitalized for left pyothorax. Consequently, the patient underwent drainage and window opening surgery. He experienced cardiopulmonary arrest but was resuscitated. Based on cardiac catheterization data, the patient was diagnosed with constrictive pericarditis. Unfortunately, extracorporeal circulation did not improve his condition, and he ultimately died. An autopsy revealed adhesion between the pericardium and pleura, especially the pericardium in contact with the left thoracic cavity, which was markedly thickened. This suggests that constrictive pericarditis, a latent complication of chemoradiotherapy, is aggravated by pyothorax.
- Published
- 2024
- Full Text
- View/download PDF
21. Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.
- Author
-
Ogihara Y, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Sato T, Nishikawa R, Kimura T, and Dohi K
- Subjects
- Humans, Aged, Anticoagulants adverse effects, Administration, Oral, Recurrence, Hemorrhage chemically induced, Hemorrhage drug therapy, Registries, Venous Thromboembolism drug therapy, Venous Thromboembolism chemically induced
- Abstract
Introduction: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE)., Materials and Methods: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg., Results: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41)., Conclusions: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshito Ogihara reports a relationship with Bayer Healthcare that includes: funding grants and speaking and lecture fees. Yoshito Ogihara reports a relationship with Daiichi Sankyo Co Ltd. that includes: funding grants and speaking and lecture fees. Yoshito Ogihara reports a relationship with Bristol Myers Squibb that includes: speaking and lecture fees. Yoshito Ogihara reports a relationship with Pfizer that includes: speaking and lecture fees. Yugo Yamashita reports a relationship with Bayer Healthcare that includes: funding grants and speaking and lecture fees. Yugo Yamashita reports a relationship with Daiichi-Sankyo that includes: funding grants and speaking and lecture fees. Yugo Yamashita reports a relationship with Bristol Myers Squibb that includes: speaking and lecture fees. Yugo Yamashita reports a relationship with Pfizer that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Daiichi Sankyo that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Japan Lifeline that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Kowa that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Kyocera that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Novartis that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Toray that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Sanofi that includes: consulting or advisory. Kazuhisa Kaneda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Kazuhisa Kaneda reports a relationship with Pfizer that includes: speaking and lecture fees. Kazuhisa Kaneda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Pfizer that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Norimichi Koitabashi reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Norimichi Koitabashi reports a relationship with Pfizer that includes: funding grants. Kaoru Dohi reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Pfizer that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Daiichi Sankyo that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
22. Home Treatment for Active Cancer Patients With Low-Risk Pulmonary Embolism - A Predetermined Companion Report From the ONCO PE Trial.
- Author
-
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.
- Published
- 2024
- Full Text
- View/download PDF
23. Cancer-associated venous thromboembolism in the direct oral anticoagulants era: Insight from the COMMAND VTE Registry-2.
- Author
-
Chatani R, Yamashita Y, Morimoto T, Mushiake K, Kadota K, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Ogihara Y, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, and Kimura T
- Subjects
- Humans, Anticoagulants therapeutic use, Retrospective Studies, Hemorrhage complications, Registries, Recurrence, Venous Thromboembolism drug therapy, Venous Thromboembolism etiology, Venous Thromboembolism epidemiology, Neoplasms complications, Neoplasms drug therapy
- Abstract
Background: There is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era., Objectives: To investigate the status of cancer-associated VTE in the DOAC era., Methods: This multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without., Results: The cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11-1.66)., Conclusions: The current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era., 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 lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray and manuscript fees from Bristol-Myers Squibb and Kowa; he was on the advisory board for Sanofi. Dr. Kaneda received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi-Sankyo. Dr. Ogihara received research funding from Bayer Healthcare. Dr. Koitabashi received lecture fees from Bayer Healthcare and grant support from Pfizer. All other authors reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. Clinical and molecular delineation of classical-like Ehlers-Danlos syndrome through a comprehensive next-generation sequencing-based screening system.
- Author
-
Yamaguchi T, Yamada K, Nagai S, Nishikubo T, Koitabashi N, Minami-Hori M, Matsushima M, Shibata Y, Ishiguro H, Sanai H, Fujikawa T, Takiguchi Y, Matsumoto KI, and Kosho T
- Abstract
Classical-like Ehlers-Danlos syndrome (clEDS) is an autosomal recessive disorder caused by complete absence of tenascin-X resulting from biallelic variation in TNXB . Thus far, 50 patients from 43 families with biallelic TNXB variants have been identified. Accurate detection of TNXB variants is challenging because of the presence of the pseudogene TNXA , which can undergo non-allelic homologous recombination. Therefore, we designed a genetic screening system that is performed using similar operations to other next-generation sequencing (NGS) panel analyses and can be applied to accurately detect TNXB variants and the recombination of TNXA -derived sequences into TNXB . Using this system, we identified biallelic TNXB variants in nine unrelated clEDS patients. TNXA -derived variations were found in >75% of the current cohort, comparable to previous reports. The current cohort generally exhibited similar clinical features to patients in previous reports, but had a higher frequency of gastrointestinal complications (e.g., perforation, diverticulitis, gastrointestinal bleeding, intestinal obstruction, rectal/anal prolapse, and gallstones). This report is the first to apply an NGS-based screening for TNXB variants and represents the third largest cohort of clEDS, highlighting the importance of increasing awareness of the risk of gastrointestinal complications., Competing Interests: TY, TF, YT, and TK are members of the endowed chair named “Division of Clinical Sequencing, Shinshu University School of Medicine”, which is sponsored by BML, Inc. and Life Technologies Japan Ltd., a subsidiary of Thermo Fisher Scientific Inc. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yamaguchi, Yamada, Nagai, Nishikubo, Koitabashi, Minami-Hori, Matsushima, Shibata, Ishiguro, Sanai, Fujikawa, Takiguchi, Matsumoto and Kosho.)
- Published
- 2023
- Full Text
- View/download PDF
25. Acute pulmonary thromboembolism after messenger RNA vaccination against coronavirus disease 2019: A case report.
- Author
-
Ishibashi Y, Takama N, Fujii T, Takizawa D, Amanai S, Kuno T, Aihara K, Koitabashi N, and Ishii H
- Abstract
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is defined as thrombosis after inoculation of adenovirus vector vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VITT rarely occurs with messenger RNA vaccines, and the use of heparin for VITT is also controversial. A 74-year-old female patient with no risk factors for thrombosis was brought to our hospital after loss of consciousness. Nine days before admission, she had received the third vaccine against SARS-CoV-2 (mRNA1273, Moderna). Immediately after transport, cardiopulmonary arrest occurred, prompting extracorporeal membrane oxygenation (ECMO). Pulmonary angiography showed translucent images of both pulmonary arteries, resulting in the diagnosis of acute pulmonary thromboembolism. Unfractionated heparin was administered, but D-dimer subsequently became negative. Pulmonary thrombosis remained in large volume, indicating that heparin was ineffective. Treatment was shifted to anticoagulant therapy using argatroban, which increased D-dimer level and improved respiratory status. The patient was successfully weaned from ECMO and ventilator. Anti-platelet factor 4 antibody examined after treatment initiation showed negative results; however, VITT was considered as an underlying condition because of the time of onset after vaccination, the ineffectiveness of heparin, and the absence of other causes of thrombosis. In case heparin is not effective, argatroban can be an alternative therapy against thrombosis., Learning Objective: During the coronavirus disease 2019 pandemic, treatment with vaccine against severe acute respiratory syndrome coronavirus 2 has been widely performed. Vaccine-induced immune thrombotic thrombocytopenia is the most common thrombosis after adenovirus vector vaccines. However, thrombosis can also occur after messenger RNA vaccination. Though commonly used for thrombosis, heparin may be ineffective. Non-heparin anticoagulants should be considered., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
26. Drug-coated balloons for the treatment of stent edge restenosis.
- Author
-
Nagasaka T, Amanai S, Ishibashi Y, Aihara K, Ohyama Y, Takama N, Koitabashi N, and Ishii H
- Subjects
- Humans, Stents adverse effects, Treatment Outcome, Coated Materials, Biocompatible, Angioplasty, Balloon, Coronary, Drug-Eluting Stents adverse effects, Percutaneous Coronary Intervention, Coronary Restenosis diagnostic imaging, Coronary Restenosis etiology, Coronary Restenosis therapy
- Abstract
Background: Drug-coated balloon (DCB) is a device for treating patients with in-stent restenosis; however, there are scant data on its efficacy for stent edge restenosis (SER). This study aimed to investigate the clinical outcomes of DCB use for treating SER compared with new-generation drug-eluting stent (DES) implantation., Method: From December 2013 to January 2019, patients who underwent DES implantation or DCB for SER were enrolled. Clinical outcomes were analyzed, and propensity score with matching was conducted. The primary outcome was target-vessel revascularization (TVR). The secondary outcomes were the incidence of all-cause mortality, major adverse cardiovascular events (MACE), and target lesion revascularization (TLR)., Result: A total of 291 patients with SER were included: 160 were treated with DCB, and 131 with new-generation DES. DCB treatment for SER treatment was associated with a lower risk of TVR than DES [hazard ratio, 0.549; 95% confidence interval (CI), 0.339-0.891] at a median follow-up of 1080 days (interquartile range; 729-1080 days). Propensity score matching (PSM) was performed to adjust for baseline clinical and lesion characteristics. After PSM, no significant difference in the risk of TVR was observed (hazard ratio, 0.965; 95% CI, 0.523-1.781). Similarly, the risk for all-cause death (hazard ratio, 0.507; 95% CI, 0.093-2.770), MACE (hazard ratio: 0.812; 95% CI, 0.451-1.462), and TLR (hazard ratio: 0.962; 95% CI, 0.505-1.833) were comparable between the two groups., Conclusion: DCB treatment efficacy for SER was similar to that of new-generation DES after PSM. DCB is a significant alternative to obtain comparable results with new-generation DES for the treatment of SER., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
27. Chronic left ventricular apical thrombosis complicating isolated left ventricular noncompaction in a patient with human immunodeficiency virus infection.
- Author
-
Kato T, Koitabashi N, Sano Y, Yanagisawa K, Ogawa Y, Saitoh T, and Ishii H
- Subjects
- Humans, Thrombosis complications, Thrombosis diagnostic imaging, Heart Defects, Congenital, HIV Infections complications
- Published
- 2023
- Full Text
- View/download PDF
28. Comprehensive genetic screening for vascular Ehlers-Danlos syndrome through an amplification-based next-generation sequencing system.
- Author
-
Yamaguchi T, Hayashi S, Hayashi D, Matsuyama T, Koitabashi N, Ogiwara K, Noda M, Nakada C, Fujiki S, Furutachi A, Tanabe Y, Yamanaka M, Ishikawa A, Mizukami M, Mizuguchi A, Sugiura K, Sumi M, Yamazawa H, Izawa A, Wada Y, Fujikawa T, Takiguchi Y, Wakui K, Takano K, Nishio SY, and Kosho T
- Subjects
- Pregnancy, Female, Humans, Collagen Type III genetics, DNA Copy Number Variations, Genetic Testing, Ehlers-Danlos Syndrome diagnosis, Ehlers-Danlos Syndrome genetics, Ehlers-Danlos Syndrome, Type IV
- Abstract
Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys-Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
29. Status of adult outpatients with congenital heart disease in Japan: The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease Registry.
- Author
-
Yao A, Inuzuka R, Mizuno A, Iwano H, Tatebe S, Tsukamoto Y, Sakamoto I, Watanabe H, Fukuda N, Takechi F, Adachi S, Akazawa Y, Kuwahara K, Dohi K, Ishizu T, Miyake M, Koitabashi N, Hasegawa-Tamba S, Sato S, Fujii T, Ehara E, Minamino T, Yamada H, Yamashita E, Kawamatsu N, Masuda K, Soma K, Shiraishi I, Nagai R, and Niwa K
- Subjects
- Adult, Humans, Japan epidemiology, Prospective Studies, Outpatients, Registries, Heart Defects, Congenital epidemiology, Heart Defects, Congenital surgery, Transposition of Great Vessels surgery
- Abstract
Background: The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease (JNCVD-ACHD) was founded in 2011 for the lifelong care of adult patients with congenital heart disease (ACHD patients). This network maintains the first Japanese ACHD registry., Methods and Results: From 2011 to 2019, the JNCVD-ACHD registered 54 institutions providing specialized care for ACHD patients in 32 of the 47 prefectures in Japan. The registry collected data on the disease profile for 24,048 patients from 50 institutions and the patient characteristics for 9743 patients from 24 institutions. The most common ACHDs were atrial septal defect (20.5 %), ventricular septal defect (20.5 %), tetralogy of Fallot (12.9 %), and univentricular heart (UVH)/single ventricle (SV; 6.6 %). ACHD patients without biventricular repair accounted for 37.0 % of the population. Also examined were the serious anatomical and/or pathophysiological disorders such as pulmonary arterial hypertension (3.0 %) including Eisenmenger syndrome (1.2 %), systemic right ventricle under biventricular circulation (sRV-2VC; 2.8 %), and Fontan physiology (6.0 %). The sRV-2VC cases comprised congenitally corrected transposition of the great arteries without anatomical repair (61.9 %) and transposition of the great arteries with atrial switching surgery (38.1 %). The primary etiology (86.4 %) for Fontan physiology was UVH/SV. In addition, developmental/chromosomal/genetic disorders were heterotaxy syndromes (asplenia, 0.9 %; polysplenia, 0.7 %), trisomy 21 (4.0 %), 22q11.2 deletion (0.9 %), Turner syndrome (0.2 %), and Marfan syndrome (1.1 %)., Conclusions: Although the specific management of ACHD has systematically progressed in Japan, this approach is still evolving. For ideal ACHD care, the prospective goals for the JNCVD-ACHD are to create local networks and provide a resource for multicenter clinical trials to support evidence-based practice., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
30. Long-term outcomes of intermediate coronary stenosis in patients undergoing hemodialysis after deferred revascularization based on fractional flow reserve.
- Author
-
Nagasaka T, Amanai S, Ishibashi Y, Aihara K, Ohyama Y, Takama N, Koitabashi N, and Ishii H
- Subjects
- Humans, Retrospective Studies, Stroke Volume, Treatment Outcome, Ventricular Function, Left, Renal Dialysis, Coronary Angiography, Myocardial Revascularization adverse effects, Fractional Flow Reserve, Myocardial, Coronary Stenosis diagnostic imaging, Coronary Stenosis therapy, Coronary Artery Disease
- Abstract
Objectives: This study aimed to assess the long-term outcomes of patients undergoing hemodialysis (HD) after deferred revascularization based on fractional flow reserve (FFR)., Background: FFR is a practical technique for assessing the functional severity of intermediate coronary stenosis. Prior research has revealed a satisfactory outcome in patients after the deferral of percutaneous coronary intervention for coronary lesions based on FFR measurement. However, little research has been conducted focusing on patients undergoing HD., Methods: The retrospective study comprised 225 consecutive patients with FFR assessment and deferred revascularization between January 2016 and December 2019. Based on a deferral cutoff FFR value of >0.80, we assessed the differences in all-cause death, major adverse cardiac events (MACEs), and target vessel failure (TVF) between the HD (n = 69) and non-HD groups (n = 156) during a mean ± standard deviation routine follow-up of 32.2 ± 13.4 months., Results: Although the HD group had significantly higher rates of diabetes mellitus than the non-HD group (53.6% vs. 37.2%, p = 0.021), there were no significant differences in sex, left ventricular ejection fraction, or other risk factors between the groups, nor with respect to stenosis diameter or mean FFR. The HD group had a significantly higher incidence of TVF than the non-HD group (34.8% vs. 14.1%, p < 0.001), as well as a significantly higher risk of all-cause death and MACEs., Conclusions: The study revealed that deferred revascularization in coronary lesions with an FFR value of >0.80 in patients undergoing HD was associated with poor outcomes. Therefore, it is important to carefully monitor patients with intermediate coronary stenosis undergoing HD., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
31. Oozing-type rupture caused by right ventricular intramural hematoma after right ventricular infarction.
- Author
-
Sano Y, Kato T, Takama N, Hisanaga E, Matsumoto N, Amanai S, Ishibashi Y, Aihara K, Nagasaka T, Koitabashi N, Kaneko Y, Yokoo H, and Ishii H
- Abstract
An 81-year-old man was admitted to the hospital because of decreased level of consciousness. He had bradycardia (27 beats/min). Electrocardiography showed ST-segment elevation in leads II, III, and aVF and ST-segment depression in leads aVL, V1. Transthoracic echocardiography (TTE) visualized reduced motion of the left ventricular (LV) inferior wall and right ventricular (RV) free wall. Coronary angiography revealed occlusion of the right coronary artery. A primary percutaneous coronary intervention was successfully performed with temporary pacemaker backup. On the third day, the sinus rhythm recovered, and the temporary pacemaker was removed. On the fifth day, a sudden cardiac arrest occurred. Extracorporeal cardiopulmonary resuscitation was performed. TTE showed a high-echoic effusion around the right ventricle, indicating a hematoma. The drainage was ineffective. He died on the eighth day. An autopsy showed the infarcted lesion and an intramural hematoma in the RV. However, no definite perforation of the myocardium was detected. The hematoma extended to the epicardium surface, indicative of oozing-type RV rupture induced by RV infarction. The oozing-type rupture induced by RV infarction might develop asymptomatically without influence on the vital signs of the patient. Frequent echocardiographic evaluation is essential in cases of RV infarction taking care of silent oozing-type rupture., Learning Objective: Inferior left ventricular infarction sometimes complicates right ventricular (RV) infarction. The typical manifestations of RV infarction include low blood pressure, low cardiac output, and elevated right atrium pressure. Although the frequency is low, fatal complications of oozing-type RV rupture might progress asymptomatically. Frequent echocardiographic screening is necessary to detect them., Competing Interests: Yukie Sano, Toshimitsu Kato, Noriaki Takama, Etsuko Hisanaga, Naohiro Matsumoto, Shiro Amanai, Youhei Ishibashi, Kazuhumi Aihara, Takashi Nagasaka, Norimichi Koitabashi, Yoshiaki Kaneko, Hideaki Yokoo, and Hideki Ishii declare that they have no conflicts of interest., (© 2022 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
32. Can I Stop Anticoagulation When Cancer Is in Remission?
- Author
-
Koitabashi N
- Subjects
- Blood Coagulation, Causality, Humans, Anticoagulants therapeutic use, Neoplasms drug therapy
- Published
- 2022
- Full Text
- View/download PDF
33. Ketone body and FGF21 coordinately regulate fasting-induced oxidative stress response in the heart.
- Author
-
Kawakami R, Sunaga H, Iso T, Kaneko R, Koitabashi N, Obokata M, Harada T, Matsui H, Yokoyama T, and Kurabayashi M
- Subjects
- 3-Hydroxybutyric Acid metabolism, Animals, Fibroblast Growth Factors metabolism, Liver metabolism, Mice, Oxidative Stress, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, Rats, Fasting, PPAR alpha genetics, PPAR alpha metabolism
- Abstract
Ketone body β-hydroxybutyrate (βOHB) and fibroblast growth factor-21 (FGF21) have been proposed to mediate systemic metabolic response to fasting. However, it remains elusive about the signaling elicited by ketone and FGF21 in the heart. Stimulation of neonatal rat cardiomyocytes with βOHB and FGF21 induced peroxisome proliferator-activated receptor α (PPARα) and PGC1α expression along with the phosphorylation of LKB1 and AMPK. βOHB and FGF21 induced transcription of peroxisome proliferator-activated receptor response element (PPRE)-containing genes through an activation of PPARα. Additionally, βOHB and FGF21 induced the expression of Nrf2, a master regulator for oxidative stress response, and catalase and Ucp2 genes. We evaluated the oxidative stress response gene expression after 24 h fast in global Fgf21-null (Fgf21
-/- ) mice, cardiomyocyte-specific FGF21-null (cmFgf21-/- ) mice, wild-type (WT), and Fgf21fl/fl littermates. Fgf21-/- mice but not cmFgf21-/- mice had unexpectedly higher serum βOHB levels, and higher expression levels of PPARα and oxidative stress response genes than WT mice or Fgf21fl/fl littermates. Notably, expression levels of oxidative stress response genes were significantly correlated with serum βOHB and PGC1α levels in both WT and Fgf21-/- mice. These findings suggest that fasting-induced βOHB and circulating FGF21 coordinately regulate oxidative stress response gene expression in the heart., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
34. Acute myocarditis associated with COVID-19 vaccination: A case report.
- Author
-
Nagasaka T, Koitabashi N, Ishibashi Y, Aihara K, Takama N, Ohyama Y, Yokoyama T, and Kaneko Y
- Abstract
Recently, new vaccine platforms-including mRNA vaccines for coronavirus disease 2019 (COVID-19) have been given emergency use authorization in Japan. Here, we present a rare case of myocarditis following a COVID-19 vaccine. In this case, myocarditis was confirmed by cardiac magnetic resonance imaging, endomyocardial biopsy, and troponin levels. The degree of myocardial inflammation in the endomyocardial biopsy samples was mild and the patient's clinical course was not severe. Although the pathology of myocarditis in this case was mild, further investigation would be needed. < Learning objective: Vaccination for coronavirus disease 2019 is advancing worldwide, but post-vaccination myocarditis is getting attention as a rare side effect. Although the myocarditis in this case was mild, the pathogenesis of the disease is unclear and needs to be thoroughly investigated in the vaccination.>., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 Japanese College of Cardiology. Published by Elsevier Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
35. Reduced Fatty Acid Use from CD36 Deficiency Deteriorates Streptozotocin-Induced Diabetic Cardiomyopathy in Mice.
- Author
-
Umbarawan Y, Kawakami R, Syamsunarno MRAA, Obinata H, Yamaguchi A, Hanaoka H, Hishiki T, Hayakawa N, Koitabashi N, Sunaga H, Matsui H, Kurabayashi M, and Iso T
- Abstract
Cardiac dysfunction is induced by multifactorial mechanisms in diabetes. Deranged fatty acid (FA) utilization, known as lipotoxicity, has long been postulated as one of the upstream events in the development of diabetic cardiomyopathy. CD36, a transmembrane glycoprotein, plays a major role in FA uptake in the heart. CD36 knockout (CD36KO) hearts exhibit reduced rates of FA transport with marked enhancement of glucose use. In this study, we explore whether reduced FA use by CD36 ablation suppresses the development of streptozotocin (STZ)-induced diabetic cardiomyopathy. We found that cardiac contractile dysfunction had deteriorated 16 weeks after STZ treatment in CD36KO mice. Although accelerated glucose uptake was not reduced in CD36KO-STZ hearts, the total energy supply, estimated by the pool size in the TCA cycle, was significantly reduced. The isotopomer analysis with
13 C6 -glucose revealed that accelerated glycolysis, estimated by enrichment of13 C2 -citrate and13 C2 -malate, was markedly suppressed in CD36KO-STZ hearts. Levels of ceramides, which are cardiotoxic lipids, were not elevated in CD36KO-STZ hearts compared to wild-type-STZ ones. Furthermore, increased energy demand by transverse aortic constriction resulted in synergistic exacerbation of contractile dysfunction in CD36KO-STZ mice. These findings suggest that CD36KO-STZ hearts are energetically compromised by reduced FA use and suppressed glycolysis; therefore, the limitation of FA utilization is detrimental to cardiac energetics in this model of diabetic cardiomyopathy.- Published
- 2021
- Full Text
- View/download PDF
36. Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury.
- Author
-
Kawakami R, Matsui M, Konno A, Kaneko R, Shrestha S, Shrestha S, Sunaga H, Hanaoka H, Goto S, Hosojima M, Kabasawa H, Obokata M, Koitabashi N, Matsui H, Sasaki T, Saito A, Yanagita M, Hirai H, Kurabayashi M, and Iso T
- Subjects
- Animals, Humans, Mice, Acute Kidney Injury, Biomarkers urine, Fatty Acid-Binding Proteins urine, Liver Diseases
- Abstract
Urinary fatty acid binding protein 1 (FABP1, also known as liver-type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1-deficient mice with liver-specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver-derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT-R) either in a hepatocyte- or in a PTEC-specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver-derived FABP1 through a megalin-mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., (© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)
- Published
- 2021
- Full Text
- View/download PDF
37. Adaptive Servo-ventilation Therapy Results in the Prevention of Arrhythmias in Patients with Heart Failure Due to Ischemic Heart Disease.
- Author
-
Nagasaka T, Takama N, Ohyama Y, Koitabashi N, Tange S, and Kurabayashi M
- Subjects
- Aged, Aged, 80 and over, Humans, Male, Middle Aged, Respiration, Artificial, Retrospective Studies, Stroke Volume, Treatment Outcome, Ventricular Function, Left, Atrial Fibrillation, Heart Failure complications, Heart Failure prevention & control, Myocardial Ischemia complications, Myocardial Ischemia prevention & control, Sleep Apnea Syndromes
- Abstract
Objective Whether or not adaptive servo-ventilation (ASV) is effective in preventing arrhythmias in patients with heart failure (HF) due to ischemic heart disease (IHD) is unclear. This study estimated the effects of ASV therapy on arrhythmias in patients with HF due to IHD. Methods One hundred and forty-one consecutive hospitalized patients with HF due to IHD (mean age: 74.9±11.9 years old) were retrospectively assessed in this study. Of the 141 patients, 75 were treated with ASV (ASV group), and 66 were treated without ASV (Non-ASV group). We estimated the incidence of arrhythmias, including paroxysmal atrial fibrillation (PAF) and ventricular tachycardia (VT), during one-year follow-up in both groups using multivariable logistic regression models. Results Men accounted for 55.3% of the study population. There were no significant differences in the baseline clinical characteristic data between the ASV and Non-ASV groups with respect to age, sex, heart rate, risk factors, oral medication, or laboratory data, including the estimated glomerular filtration rate (eGFR), brain natriuretic peptide, and left ventricular ejection fraction. ASV therapy was associated with a reduced incidence of arrhythmia after adjusting for demographic and cardiovascular disease risk factors (odds ratio, 0.27; 95% confidence interval, 0.11 to 0.63; p<0.01; compared to the Non-ASV group). In addition, at the 1-year follow-up, an improvement (increase) in the eGFR was found in the ASV group but not in the Non-ASV group. Conclusion ASV therapy was able to prevent arrhythmias, including PAF and VT, with short-term improvements in the renal function in patients with HF due to IHD.
- Published
- 2021
- Full Text
- View/download PDF
38. Prognostic impact of elevated fatty acid-binding protein 1 in patients with heart failure.
- Author
-
Kagami K, Sunaga H, Sorimachi H, Harada T, Yoshida K, Kato T, Kurosawa K, Kawakami R, Koitabashi N, Iso T, Adachi T, Kurabayashi M, and Obokata M
- Subjects
- Biomarkers, Echocardiography, Humans, Prognosis, Fatty Acid-Binding Proteins blood, Heart Failure diagnosis
- Abstract
Aims: Few biomarkers to evaluate pathophysiological changes in extra-cardiac tissues have been identified in patients with heart failure (HF). Fatty acid-binding protein 1 (FABP), also known as liver FABP, is predominantly expressed in the liver. Circulating FABP1 has been proposed to be a sensitive biomarker for liver injury. However, little is known about the potential role of FABP1 as a biomarker for HF., Methods and Results: Measurements of serum FABP1 and echocardiography were performed in subjects with compensated HF (n = 162) and control subjects without HF (n = 20). Patients were prospectively followed-up for a composite outcome of all-cause mortality or HF hospitalization. Compared with control subjects, levels of FABP1 were elevated in HF patients [7.9 (6.4-11.7) vs. 17.6 (10.4-28.9) ng/mL, P < 0.0001]. There were significant correlations between FABP1 levels and estimated right ventricular systolic pressure and right atrial pressure. During a median follow-up of 12.0 months, there were 55 primary composite endpoints in the HF cohort. The highest FABP1 tertile was associated with a three-fold increased risk of the composite outcome compared with the lowest tertile [95% confidence interval (1.46-6.68), P = 0.003], but other conventional hepatobiliary markers did not predict the outcome. After adjusting for age, sex, atrial fibrillation, and N-terminal pro-B-type natriuretic peptide levels, serum FABP1 remained independently associated with the outcome. Adding FABP1 to the model based on clinical factors and N-terminal pro-B-type natriuretic peptide significantly improved the prognostic value (global χ
2 20.8 vs. 15.5, P = 0.01)., Conclusion: Serum FABP1 levels are elevated in compensated HF patients, and the magnitude of elevation is independently associated with pulmonary hypertension, right atrial hypertension, and worse clinical outcomes. FABP1 may serve as a new potential biomarker for the assessment of hitherto unrecognized derangement of cardio-hepatic interaction in HF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)- Published
- 2021
- Full Text
- View/download PDF
39. A case of a middle-aged patient with a ventricular septal defect complicated by severe pulmonary hypertension-stepwise surgical repair with pulmonary vasodilators.
- Author
-
Kanai A, Koitabashi N, Akagi S, Sorimachi H, Ishibashi Y, Nagasaka T, Takama N, Soma K, Yao A, Kasahara S, and Kurabayashi M
- Abstract
We report a case of ventricular septal defect (VSD) in which we attempted to treat pulmonary arterial hypertension (PAH) with the goal of VSD closure in an adult with suspected Eisenmenger syndrome in childhood. Four years previously (age 41 years), she was referred to our department due to repeated hemoptysis requiring further treatment of PAH. We started combination therapy with several pulmonary vasodilators. Two years later, her pulmonary vascular resistance (PVR) was improved but still not at the level where VSD closure was possible. To control the increased PA flow resulting from intensive PAH treatment and to reduce the risk of hemoptysis, we performed pulmonary artery banding (PAB). As the risk of hemoptysis decreased, a prostacyclin analog was introduced, and the dose was increased. More than 1 year after PAB, active vasoactivity testing became positive, suggesting that the pulmonary vascular lesion was now "reversible". We performed VSD closure and atrial septal defect creation even though her PVR was still high. After the operation, her exercise capacity was remarkably improved. We suggest that stepwise surgical repair with pulmonary vasodilators is an important treatment option for select patients with VSD with severe PAH. < Learning objective: Advances in pulmonary arterial hypertension (PAH) treatment have led to the use of a "treat-and-repair" strategy to close the intracardiac shunt after PAH treatment in select patients with adult congenital heart disease. In our case, ventricular septal defect (VSD) closure was achieved with stepwise surgical repair and a combination of pulmonary vasodilators, even though long-standing severe PAH with persistent hemoptysis remained. Even after a long period of exposure to high blood flow, this strategy may reduce pulmonary vascular resistance and permit eventual closure of the VSD.>., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 Japanese College of Cardiology. Published by Elsevier Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
40. DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism.
- Author
-
Furukawa N, Koitabashi N, Matsui H, Sunaga H, Umbarawan Y, Syamsunarno MRAA, Yamaguchi A, Obokata M, Hanaoka H, Yokoyama T, and Kurabayashi M
- Subjects
- Animals, Dipeptidyl-Peptidase IV Inhibitors therapeutic use, Disease Models, Animal, Fibroblast Growth Factors biosynthesis, Heart Failure drug therapy, Heart Failure metabolism, Male, Mice, Mice, Inbred C57BL, Signal Transduction, Energy Metabolism genetics, Fibroblast Growth Factors genetics, Gene Expression Regulation drug effects, Heart Failure genetics, Myocardium metabolism, Sirtuin 1 metabolism, Vildagliptin pharmacology
- Abstract
Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (vilda), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or vilda, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in vilda-treated mice. Pressure-volume analysis showed that vilda treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that vilda treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by vilda treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with vilda treatment. Vilda treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert vilda-mediated beneficial effects in stressed heart. Vilda induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.
- Published
- 2021
- Full Text
- View/download PDF
41. Pathophysiological role of fatty acid-binding protein 4 in Asian patients with heart failure and preserved ejection fraction.
- Author
-
Harada T, Sunaga H, Sorimachi H, Yoshida K, Kato T, Kurosawa K, Nagasaka T, Koitabashi N, Iso T, Kurabayashi M, and Obokata M
- Abstract
Aims: Systemic metabolic impairment is the key pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). Fatty acid-binding protein 4 (FABP4) is highly expressed in adipocytes and secreted in response to lipolytic signals. We hypothesized that circulating FABP4 levels would be elevated in patients with HFpEF, would correlate with cardiac structural and functional abnormalities, and could predict clinical outcomes., Methods and Results: Serum FABP4 measurements and echocardiography were performed in patients with HFpEF (n = 92) and those with coronary artery disease free of HF (n = 20). Patients were prospectively followed-up for a composite endpoint of all-cause mortality or HF hospitalization. Compared with patients with coronary artery disease, those with HFpEF had higher FABP4 levels [12.5 (9.1-21.0) vs. 43.5 (24.6-77.4) ng/mL, P < 0.0001]. FABP4 levels were associated with cardiac remodelling (left ventricular mass index: r = 0.29, P = 0.002; left atrial volume index: r = 0.40, P < 0.0001), left ventricular systolic and diastolic dysfunction (global longitudinal strain: r = -0.24, P = 0.01; E/e' ratio: r = 0.29, P = 0.002; and N-terminal pro-B-type natriuretic peptide: r = 0.62, P < 0.0001), and right ventricular dysfunction (tricuspid annular plane systolic excursion: r = -0.43, P < 0.0001). During a median follow-up of 9.1 months, there were 28 primary endpoints in the HFpEF cohort. Event-free survival was significantly decreased in patients with FABP4 levels ≥43.5 ng/mL than in those with FABP4 levels <43.5 ng/mL (P = 0.003)., Conclusions: Serum FABP4 levels were increased in HFpEF and were associated with cardiac remodelling and dysfunction, and poor outcomes. Thus, FABP4 could be a potential biomarker in the complex pathophysiology of HFpEF., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)
- Published
- 2020
- Full Text
- View/download PDF
42. Reduced fatty acid uptake aggravates cardiac contractile dysfunction in streptozotocin-induced diabetic cardiomyopathy.
- Author
-
Umbarawan Y, Kawakami R, Syamsunarno MRAA, Koitabashi N, Obinata H, Yamaguchi A, Hanaoka H, Hishiki T, Hayakawa N, Sunaga H, Matsui H, Kurabayashi M, and Iso T
- Subjects
- Acetylation, Animals, Ceramides metabolism, Citric Acid Cycle, Energy Metabolism, Female, Glucose metabolism, Glycolysis, Ketone Bodies metabolism, Male, Mice, Inbred C57BL, Mice, Knockout, Myocardial Contraction, Streptozocin, Ventricular Dysfunction, Left, Diabetic Cardiomyopathies metabolism, Diabetic Cardiomyopathies physiopathology, Fatty Acids metabolism
- Abstract
Diabetes is an independent risk factor for the development of heart failure. Increased fatty acid (FA) uptake and deranged utilization leads to reduced cardiac efficiency and accumulation of cardiotoxic lipids, which is suggested to facilitate diabetic cardiomyopathy. We studied whether reduced FA uptake in the heart is protective against streptozotocin (STZ)-induced diabetic cardiomyopathy by using mice doubly deficient in fatty acid binding protein 4 (FABP4) and FABP5 (DKO mice). Cardiac contractile dysfunction was aggravated 8 weeks after STZ treatment in DKO mice. Although compensatory glucose uptake was not reduced in DKO-STZ hearts, total energy supply, estimated by the pool size in the TCA cycle, was significantly reduced. Tracer analysis with
13 C6 -glucose revealed that accelerated glycolysis in DKO hearts was strongly suppressed by STZ treatment. Levels of ceramides, cardiotoxic lipids, were similarly elevated by STZ treatment. These findings suggest that a reduction in total energy supply by reduced FA uptake and suppressed glycolysis could account for exacerbated contractile dysfunction in DKO-STZ hearts. Thus, enhanced FA uptake in diabetic hearts seems to be a compensatory response to reduced energy supply from glucose, and therefore, limited FA use could be detrimental to cardiac contractile dysfunction due to energy insufficiency.- Published
- 2020
- Full Text
- View/download PDF
43. Nonbacterial Thrombotic Endocarditis-A Rare Case of Acute Libman-Sacks Endocarditis Complicated by Multiple Cerebral Infarcts: Case Report and Literature Review.
- Author
-
Kato T, Takama N, Harada T, Koitabashi N, Murakami M, Abe T, and Kurabayashi M
- Published
- 2020
- Full Text
- View/download PDF
44. Early Lifestyle Modification Is an Essential Step in Telemedicine for Heart Failure.
- Author
-
Koitabashi N, Obokata M, and Kurabayashi M
- Subjects
- Hospitalization, Humans, Life Style, Monitoring, Physiologic, Heart Failure, Telemedicine
- Published
- 2020
- Full Text
- View/download PDF
45. Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.
- Author
-
Seki M, Furukawa N, Koitabashi N, Obokata M, Conway SJ, Arakawa H, and Kurabayashi M
- Subjects
- Animals, Cell Adhesion Molecules pharmacology, Hemodynamics, Hypertension, Pulmonary metabolism, Hypoxia metabolism, Lung pathology, Male, Mice, Mice, Knockout, Muscle, Smooth, Vascular metabolism, Pulmonary Arterial Hypertension physiopathology, Pulmonary Artery pathology, Receptors, Transforming Growth Factor beta metabolism, Signal Transduction, Transforming Growth Factor beta physiology, Transforming Growth Factors metabolism, Cell Adhesion Molecules metabolism, Pulmonary Arterial Hypertension metabolism, Transforming Growth Factor beta metabolism
- Abstract
Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-β receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1fl/fl mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1fl/fl mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-β signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
- Full Text
- View/download PDF
46. Activation of cardiac AMPK-FGF21 feed-forward loop in acute myocardial infarction: Role of adrenergic overdrive and lipolysis byproducts.
- Author
-
Sunaga H, Koitabashi N, Iso T, Matsui H, Obokata M, Kawakami R, Murakami M, Yokoyama T, and Kurabayashi M
- Subjects
- Aged, Aminoimidazole Carboxamide analogs & derivatives, Aminoimidazole Carboxamide pharmacology, Angina Pectoris blood, Angina Pectoris metabolism, Animals, Catecholamines metabolism, Disease Models, Animal, Fatty Acid-Binding Proteins blood, Fatty Acids blood, Female, Fibroblast Growth Factors blood, Humans, Male, Multivariate Analysis, Myocardial Infarction blood, Myocardium metabolism, Myocardium pathology, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Recombinant Proteins pharmacology, Ribonucleotides pharmacology, Time Factors, Troponin T blood, AMP-Activated Protein Kinases metabolism, Adrenergic Agents metabolism, Fibroblast Growth Factors metabolism, Lipolysis, Myocardial Infarction metabolism
- Abstract
Fibroblast growth factor 21 (FGF21) is a metabolic hormone having anti-oxidative and anti-hypertrophic effects. However, the regulation of FGF21 expression during acute myocardial infarction (AMI) remains unclear. We tested blood samples from 50 patients with AMI and 43 patients with stable angina pectoris (sAP) for FGF21, fatty acid binding protein 4 (FABP4), a protein secreted from adipocytes in response to adrenergic lipolytic signal, and total and individual fatty acids. Compared with sAP patients, AMI patients had higher serum FGF21 levels on admission, which were significantly correlated with peak FABP4 and saturated fatty acids (SFAs) but not with peak levels of cardiac troponin T. In mice, myocardial ischemia rapidly induced FGF21 production by the heart, which accompanied activation of AMP-activated protein kinase (AMPK)-dependent pathway. Like AICAR, an activator of AMPK, catecholamines (norepinephrine and isoproterenol) and SFAs (palmitate and stearate) significantly increased FGF21 production and release by cardiac myocytes via AMPK activation. Recombinant FGF21 induced its own expression as well as members of down-stream targets of AMPK involved in metabolic homeostasis and mitochondrial biogenesis in cardiac myocytes. These findings suggest that adrenergic overdrive and resultant adipose tissue lipolysis induce cardiac AMPK-FGF21 feed-forward loop that potentially provides cardioprotection against ischemic damage.
- Published
- 2019
- Full Text
- View/download PDF
47. Effect of Inferior Vena Cava Filter on Venous Thromboembolism Mortality in Japan - JROAD and JROAD-DPC Registry Analysis.
- Author
-
Ohyama Y, Koitabashi N, Nakamura T, Sumita Y, Nakai M, Nishimura K, Miyamoto Y, and Kurabayashi M
- Abstract
Background: Previous randomized clinical studies have raised concerns about whether inferior vena cava filter (IVCF) can benefit patients with venous thromboembolism (VTE). The present study therefore investigated whether IVCF are associated with in-hospital mortality in Japan. Methods and Results: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). Of 2,368,165 patients included in JROAD-DPC, we identified 28,238 who were hospitalized with VTE between 2012 and 2014. We compared in-hospital mortality rates between patients with or without IVCF using propensity score (PS) matching. PS were estimated using logistic regression models in which IVCF was the dependent variable. The other variables consisted of age, sex, Charlson comorbidity index, anti-thrombotic agents and clinical disease status. Patients were aged 68±16 years, and 59.7% were female. Of 28,238 patients, 6,937 (24.5%) were treated with an IVCF. The overall in-hospital mortality was 4.3%. On PS-matched analysis in-hospital mortality was significantly lower with, than without, IVCF (3.1% vs. 4.4%, P<0.001; OR, 0.65; 95% CI: 0.54-0.79). Conclusions: Having an IVCF was independently associated with lower in-hospital mortality in Japanese patients with VTE. This is in sharp contrast to the benefits of IVCF in other countries. The reasons for this difference require further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)
- Published
- 2019
- Full Text
- View/download PDF
48. Impact of uric acid on incident hypertension: Sex-specific analysis in different age groups.
- Author
-
Ohyama Y, Imai K, Obokata M, Araki M, Sumiyoshi H, Koitabashi N, Nakamura T, and Kurabayashi M
- Abstract
The aim of the present study is to evaluate the association of serum uric acid (UA) levels with the risk of incident hypertension among different age groups in men and women using a single large Japanese general cohort. The present study is based on annual health check-up program in Gunma, Japan. We studied 12,029 participants (mean age, 48 ± 9 years old; 31% women) free of prevalent cardiovascular disease and hypertension at baseline (2009). Hypertension was defined by self-report, hypertensive medication use, or measured BP > 140/90 mmHg at each visit. Discrete proportional hazards regression model was used to evaluate the association of UA level at baseline with incident hypertension through 2012 adjusted for age, gender, baseline blood pressure, and other CVD risk factors among different age decade groups in men and women. During follow-up of 3 years, 12% of the cohort (n = 1457) developed hypertension. UA was strongly associated with incident hypertension in the multivariable model in all participants. In age-stratified analysis, participants below 50 years of age in men had the significant association of UA with incident hypertension, whereas participants above 50 years did not. In women, participants above 40 years had the significant association, whereas participants below 40 years did not. The present data suggest that UA level is an independent predictor for incident hypertension among middle aged men below 50 years old and middle aged and the elderly women above 40 years., (© 2019 The Authors.)
- Published
- 2019
- Full Text
- View/download PDF
49. Peripartum Iliac Arterial Aneurysm and Rupture in a Patient with Vascular Ehlers-Danlos Syndrome Diagnosed by Next-Generation Sequencing.
- Author
-
Koitabashi N, Yamaguchi T, Fukui D, Nakano T, Umeyama A, Toda K, Funada R, Ishikawa M, Kawamura R, Okada K, Hatamochi A, Kosho T, and Kurabayashi M
- Subjects
- Adult, Aortic Dissection diagnostic imaging, Aortic Dissection pathology, Collagen Type III genetics, Ehlers-Danlos Syndrome genetics, Ehlers-Danlos Syndrome pathology, Endovascular Procedures methods, Female, Genetic Testing methods, Humans, Iliac Aneurysm diagnostic imaging, Iliac Aneurysm pathology, Iliac Artery diagnostic imaging, Iliac Artery pathology, Mutation, Peripartum Period metabolism, Pregnancy, Rupture, Spontaneous pathology, Rupture, Spontaneous surgery, Tomography, X-Ray Computed methods, Treatment Outcome, Aortic Dissection complications, Ehlers-Danlos Syndrome diagnosis, High-Throughput Nucleotide Sequencing methods, Iliac Aneurysm complications, Rupture, Spontaneous complications
- Abstract
Vascular Ehlers-Danlos syndrome (vEDS), a genetic disorder caused by mutations in procollagen type III gene (COL3A1), may lead to fatal vascular complication during peripartum period because of the arterial fragility. We experienced a case of vEDS with peripartum life-threatening arterial rapture diagnosed by next-generation sequencing (NGS) and successfully treated the vascular complications. A 25-year-old female in pregnancy at 34 weeks had sudden and acute pain in the left lower abdomen. After successful delivery, her computed tomography scan showed a dissecting aneurysm of the left common iliac artery (CIA). Four days after delivery, she presented in hemorrhagic shock induced by arterial rupture in the CIA. Since her clinical presentations inferred vEDS even in the absence of familial history, we performed NGS-based genetic screening for inherited connective tissue disorders including vEDS with informed consent. Even though we started intensive medication, her iliac aneurysm was progressively enlarging within 3 weeks. After an urgent molecular diagnosis for vEDS (a splice-site mutation), cautious endovascular therapy for her CIA aneurysm was successfully performed. This is the first report for pretreatment molecular diagnosis of vEDS using NGS in an emergent situation of severe vascular complications.
- Published
- 2018
- Full Text
- View/download PDF
50. Early increase in serum fatty acid binding protein 4 levels in patients with acute myocardial infarction.
- Author
-
Obokata M, Iso T, Ohyama Y, Sunaga H, Kawaguchi T, Matsui H, Iizuka T, Fukuda N, Takamatsu H, Koitabashi N, Funada R, Takama N, Kasama S, Kaneko Y, Yokoyama T, Murakami M, and Kurabayashi M
- Subjects
- Adipocytes metabolism, Adipocytes pathology, Aged, Animals, Biomarkers metabolism, Cells, Cultured, Female, Humans, Immunohistochemistry, Male, Mice, Myocardial Infarction pathology, Prognosis, Time Factors, Troponin I blood, Troponin T blood, Fatty Acid-Binding Proteins blood, Myocardial Infarction metabolism
- Abstract
Background: Acute myocardial infarction (AMI) induces marked activation of the sympathetic nervous system. Fatty acid binding protein 4 (FABP4) is not only an intracellular protein, but also a secreted adipokine that contributes to obesity-related metabolic complications. Here, we examined the role of serum FABP4 as a pathophysiological marker in patients with AMI., Methods and Results: We studied 106 patients presenting to the emergency unit with a final diagnosis of AMI, including 12 patients resuscitated from out-of-hospital cardiac arrest (OHCA) caused by ventricular fibrillation. FABP4 levels peaked on admission or just after percutaneous coronary intervention and declined thereafter. Regression analysis revealed no significant correlation between peak FABP4 and peak cardiac troponin T determined by Roche high-sensitive assays (hs-TnT). Notably, FABP4 levels were particularly elevated in AMI patients who were resuscitated from OHCA (median 130.2 ng/mL, interquartile range (IQR) 51.8-243.9 ng/mL) compared with those without OHCA (median 26.1 ng/ml, IQR 17.1-43.4 ng/mL), while hs-TnT levels on admission were not associated with OHCA. Immunohistochemistry of the human heart revealed that FABP4 is abundantly present in adipocytes within myocardial tissue and epicardial adipose tissue. An in vitro study using cultured adipocytes showed that FABP4 is released through a β3-adrenergic receptor (AR)-mediated mechanism., Conclusions: FABP4 levels were significantly elevated during the early hours after the onset of AMI and were robustly increased in OHCA survivors. Together with the finding that FABP4 is released from adipocytes via β3-AR-mediated lipolysis, our data provide a novel hypothesis that serum FABP4 may represent the adrenergic overdrive that accompanies acute cardiovascular disease, including AMI.
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.