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1. Aging-associated impairment in metabolic compensation by subcutaneous adipose tissue promotes diet-induced fatty liver disease in mice

Author

Taketani H, Nishikawa T, Nakajima H, Kodo K, Sugimoto S, Aoi W, Horike S, Meguro-Horike M, Ishiba H, Seko Y, Umemura A, Yamaguchi K, Moriguchi M, Yasui K, and Itoh Y

Subjects
Nonalcoholic fatty liver disease, obesity, diabetes mellitus, aging, senescence, metabolic compensation, brown adipose tissue, beige adipocytes, adipose progenitors, cell transplantation, Specialties of internal medicine, RC581-951
Abstract

Hiroyoshi Taketani,1,* Taichiro Nishikawa,1,* Hisakazu Nakajima,2 Kazuki Kodo,2 Satoru Sugimoto,2 Wataru Aoi,3 Shin-ichi Horike,4 Makiko Meguro-Horike,4 Hiroshi Ishiba,1 Yuya Seko,1 Atsushi Umemura,1 Kanji Yamaguchi,1 Michihisa Moriguchi,1 Kohichiroh Yasui,1 Yoshito Itoh11Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan; 4Advanced Science Research Center, Kanazawa University, Kanazawa, Japan*These authors contributed equally to this workCorrespondence: Taichiro NishikawaKyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachidouri Hirokouji Agaru, Kamigyo-ku, Kyoto 602-8566, JapanTel +81 75 251 5519Fax +81 75 251 1017Email taichi@koto.kpu-m.ac.jpBackground and aims: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome, and its progression is associated with aging-associated impairment in metabolic homeostasis. Recently, energy metabolism in adipose tissue has been the subject of renewed interest, because significant energy expenditure can be induced in cells derived from white adipose tissue progenitors, in addition to brown adipose tissue (BAT). Here we evaluated whether aging-associated change in various adipose tissue depots affects the progression of NAFLD.Methods: Six-week-old male C57BL/6NCrSlc mice were fed control chow (C) or high-fat diet (60% fat; HF) for 12 or 24 weeks (12w/C, 12w/HF, 24w/C and 24w/HF groups, respectively) or switched from C to HF diet at 18 weeks of age (24w/C/HF group) and fed for a further 24 weeks. Some 24w/HF mice received a subcutaneous transplantation of adipose progenitors (106, cells/mouse) from young donor mice. Basal energy expenditure, glucose tolerance, and liver and adipose tissue histology were then evaluated. In addition, features of senescence and the capacity of adipose progenitors to “brown” were compared in mice of various ages.Results: 12w/HF mice demonstrated compensation in the forms of hypertrophy of interscapular classical BAT and the appearance of subcutaneous beige adipocytes, consistent with improved metabolic homeostasis. In contrast, 24w/HF and 24w/C/HF mice developed obesity, glucose intolerance, and severe NAFLD, with accelerated senescence and loss of adipose progenitors in subcutaneous fat tissues. Recruitment of adipose progenitors ameliorated these findings in 24w/HF mice.Conclusion: Impaired metabolic compensation in adipose tissue resulted in the progression of NAFLD, which was associated with aging-related deterioration in adipose progenitors. A new approach targeting adipose tissue progenitors might represent a potential strategy for the prevention of NAFLD.Keywords: nonalcoholic fatty liver disease, obesity, scenescence, brown adipocyte, mesenchymal stem cells, cell transplantation

Published
2019

2. Efficacy and safety of canagliflozin in type 2 diabetes mellitus patients with biopsy-proven nonalcoholic steatohepatitis classified as stage 1–3 fibrosis

Author

Seko Y, Nishikawa T, Umemura A, Yamaguchi K, Moriguchi M, Yasui K, Kimura M, Iijima H, Hashimoto T, Sumida Y, Okanoue T, and Itoh Y

Subjects
canagliflozin, Japanese, NASH, fibrosis stages, SGLT2 inhibitor, type 2 diabetes mellitus, Specialties of internal medicine, RC581-951
Abstract

Yuya Seko,1 Taichiro Nishikawa,1 Atsushi Umemura,1 Kanji Yamaguchi,1 Michihisa Moriguchi,1 Kohichiroh Yasui,1 Mayumi Kimura,2 Hiroaki Iijima,3 Toshio Hashimoto,3 Yoshio Sumida,4 Takeshi Okanoue,5 Yoshito Itoh1 1Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan; 3Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan; 4Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan; 5Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan Aim: Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is known to be associated with type 2 diabetes mellitus (T2DM) in high rate. The improvement in hepatic function due to sodium-glucose co-transporter 2 (SGLT2) inhibitors has been reported in T2DM patients with and without NAFLD. However, only a few studies have attempted to evaluate the role of SGLT2 inhibitors in T2DM patients with biopsy-proven NASH, and no detailed prospective studies including the individual hepatic fibrosis stage have been reported. Therefore, we investigated the effect of canagliflozin on hepatic function in T2DM patients with biopsy-confirmed NASH. Methods: T2DM patients with NASH (hepatic fibrosis stage 1–3 confirmed via liver biopsy, n=10) were enrolled and received canagliflozin (100 mg) once a day for 12 weeks. The primary end point was change in serum alanine aminotransferase (ALT) levels from baseline to week 12. Secondary end points were liver function/fibrosis markers, metabolic parameters, and safety. Results: The change in ALT from baseline to week 12 was -23.9 U/L (95% CI –48.1 to 0.3, P=0.0526). Significant improvements in several hepatic function/fibrosis markers, such as aspartate aminotransferase, fibrosis-4 index, and FM-fibro index, and metabolic parameters including hemoglobin A1c and body weight were found. No serious or liver-related adverse events were reported. Regarding individual patients, different trends in ALT-lowering effects between stage 1 and stage 2/3 subjects were observed; the degree of ALT-lowering effect tended to be greater in the stage 1 group than in the stage 2/3 group. Conclusion: Our results suggest that canagliflozin is effective and well-tolerated in patients with T2DM and NASH. Canagliflozin may be useful for the treatment of T2DM patients with NASH, especially those in early stages of NASH. Keywords: canagliflozin, Japanese, NASH, fibrosis stages, SGLT2 inhibitor, type 2 diabetes mellitus

Published
2018

6. Starting Neurohormonal Antagonists in Patients with Acute Heart Failure with Mid-Range and Preserved Ejection Fraction

Author

Seko, Y., Kato, T., Morimoto, T., Yaku, H., Inuzuka, Y., Tamaki, Y., Ozasa, N., Shiba, M., Yamamoto, E., Yoshikawa, Y., Yamashita, Y., Kitai, T., Koichiro Kuwahara, and Kimura, T.

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background The clinical benefits of neurohormonal antagonist in patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) were uncertain. This study aimed to evaluate the prognostic effect of starting angiotensin-converting enzyme inhibitors (ACE-I) / angiotensin II receptor blockers (ARB) and β-blocker during HF hospitalization in these patients. Methods We analyzed 858 consecutive patients with HFmrEF (EF:40–49%) or HFpEF (EF≥50%), who were hospitalized for acute decompensated HF, were discharged alive, and were not taking ACE-I/ARB or β-blockers at admission. The study population was classified into four groups according to the status of prescription of ACE-I/ARB and β-blocker at discharge: no neurohormonal antagonist (N=342, 39.9%), ACE-I/ARB only (N=128, 14.9%), β-blocker only (N=189, 22.0%), and both ACE-I/ARB and β-blocker (N=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. Results The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the β-blocker only group, and 16.4% in the both ACE-I/ARB and β-blocker group (P Conclusions In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and β-blocker was associated with a reduced risk of a composite of all-cause death or HF hospitalization compared with not starting ACE-I/ARB or β-blocker. Funding Acknowledgement Type of funding sources: None.

Published
2021
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10. The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Author

Huisman, M. V., Rothman, K. J., Paquette, M., Teutsch, C., Diener, H. -C., Dubner, S. J., Halperin, J. L., C. S., Ma, Zint, K., Elsaesser, A., Bartels, D. B., Lip, G. Y. H., Abban, D., Abdul, N., Abelson, M., Ackermann, A., Adams, F., Adams, L., Adragao, P., Ageno, W., Aggarwal, R., Agosti, S., Marin, J. A., Aguilar, F., Aguilar Linares, J. A., Aguinaga, L., Ahmad, Z., Ainsworth, P., Al Ghalayini, K., Al Ismail, S., Alasfar, A., Alawwa, A., Al-Dallow, R., Alderson, L., Alexopoulos, D., Ali, A., Ali, M., Aliyar, P., Al-Joundi, T., Al Mahameed, S., Almassi, H., Almuti, K., Al-Obaidi, M., Alshehri, M., Altmann, U., Alves, A. R., Al-Zoebi, A., Amara, W., Amelot, M., Amjadi, N., Ammirati, F., Andrawis, N., Angoulvant, D., Annoni, G., Ansalone, G., Antonescu, S. A., Ariani, M., Arias, J. C., Armero, S., Arora, R., Arora, C., Ashcraft, W., Aslam, M. S., Astesiano, A., Audouin, P., Augenbraun, C., Aydin, S., Azar, R., Azim, A., Aziz, S., Backes, L. M., Baig, M., Bains, S., Bakbak, A., Baker, S., Bakhtiar, K., Bala, R., Banayan, J., Bandh, S., Bando, S., Banerjee, S., Bank, A., Barbarash, O., Baron, G., Barr, C., Barrera, C., Barton, J., Kes, V. B., Baula, G., Bayeh, H., Bazargani, N., Behrens, S., Bell, A., Benezet-Mazuecos, J., Benhalima, B., Berdague, P., Berg van den, B. J., Bergen van, P. F. M. M., Berngard, E., Bernstein, R., Berrospi, P., Berti, S., Bertomeu, V., Berz, A., Bettencourt, P., Betzu, R., Beyer-Westendorf, J., Bhagwat, R., Black, T., Blanco Ibaceta, J. H., Bloom, S., Blumberg, E., Bo, M., Bockisch, V., Bohmer, E., Bongiorni, M. G., Boriani, G., Bosch, R., Boswijk, D. J., Bott, J., Bottacchi, E., Kalan, M. B., Brandes, A., Bratland, B., Brautigam, D., Breton, N., Brouwers, P. J. A. M., Browne, K., Bruguera, J., Brunehaut, M., Brunschwig, C., Buathier, H., Buhl, A., Bullinga, J., Butcher, K., Cabrera Honorio, J. W., Caccavo, A., Cadinot, D., Cai, S., Calvi, V., Camm, J., Candeias, R., Capo, J., Capucci, A., Cardoso, J. N., Duarte Vera, Y. C., Carlson, B., Carvalho, P., Cary, S., Casanova, R., Casu, G., Cattan, S., Cavallini, C., Cayla, G., Cha, T. J., Cha, K. S., Chaaban, S., Chae, J. K., Challappa, K., Chand, S., Chandrashekar, H., Chang, M., Charbel, P., Chartier, L., Chatterjee, K., Cheema, A., Chen, S. -A., Chevallereau, P., Chiang, F. -T., Chiarella, F., Chih-Chan, L., Cho, Y. K., Choi, D. J., Chouinard, G., Danny, Chow, H. F., Chrysos, D., Chumakova, G., Jose Roberto Chuquiure Valenzuela, E. J., Cieza-Lara, T., Nica, V. C., Ciobotaru, V., Cislowski, D., Citerne, O., Claus, M., Clay, A., Clifford, P., Cohen, S., Cohen, A., Colivicchi, F., Collins, R., Compton, S., Connors, S., Conti, A., Buenostro, G. C., Coodley, G., Cooper, M., Corbett, L., Corey, O., Coronel, J., Corrigan, J., Cotrina Pereyra, R. Y., Cottin, Y., Coutu, B., Cracan, A., Crean, P., Crenshaw, J., Crijns, H. J. G. M., Crump, C., Cucher, F., Cudmore, D., Cui, L., Culp, J., Darius, H., Dary, P., Dascotte, O., Dauber, I., Davee, T., Davies, R., Davis, G., Davy, J. -M., Dayer, M., De La Briolle, A., de Mora, M., De Teresa, E., De Wolf, L., Decoulx, E., Deepak, S., Defaye, P., Del-Carpio Munoz, F., Brkljacic, D. D., Deluche, L., Destrac, S., Deumite, N. J., Di Legge, S., Dibon, O., Diemberger, I., Dillinger, J., Dionisio, P., Naydenov, S., Dotani, I., Dotcheva, E., D'Souza, A., Dubrey, S., Ducrocq, X., Dupljakov, D., Duthinh, V., Dutra, O. P., Dutta, D., Duvilla, N., Dy, J., Dziewas, R., Eaton, C., Eaves, W., Ebinger, M., Eck van, J. W. M., Edwards, T., Egocheaga, I., Ehrlich, C., Eisenberg, S., El Hallak, A., El Jabali, A., El Mahmoud, R., El Shahawy, M., Eldadah, Z., Elghelbazouri, F., Elhag, O., El-Hamdani, M., Elias, D., Ellery, A., El-Sayed, H., Elvan, A., Erickson, B., Espaliat, E., Essandoh, L., Everington, T., Evonich, R., Ezhov, A., Facila, L., Farsad, R., Fayard, M., Fedele, F., Gomes Ferreira, L. G., Ferreira, D., Santos, J. F., Ferrier, A., Finsen, A., First, B., Fisher, R., Floyd, J., Folk, T., Fonseca, C., Fonseca, L., Forman, S., Forsgren, M., Foster, M., Foster, N., Frais, M., Frandsen, B., Frappe, T., Freixa, R., French, W., Freydlin, M., Frickel, S., Fruntelata, A. G., Fujii, S., Fujino, Y., Fukunaga, H., Furukawa, Y., Gabelmann, M., Gabris, M., Gadsboll, N., Galin, P., Galinier, M., Ganim, R., Garcia, R., Quintana, A. G., Gartenlaub, O., Genz, C., Georger, F., Georges, J. -L., Georgeson, S., Ghanbasha, A., Giedrimas, E., Gierba, M., Gillespie, E., Giniger, A., Gkotsis, A., Gmehling, J., Gniot, J., Goethals, P., Goldberg, R., Goldmann, B., Goldscher, D., Golitsyn, S., Gomez Lopez, E. A., Gomez Mesa, J. E., Gonzalez, E., Cocina, E. G., Juanatey, C. G., Gorbunov, V., Gordon, B., Gorka, H., Gornick, C., Gorog, D., Goss, F., Gotte, A., Goube, P., Goudevenos, I., Goulden, D., Graham, B., Grande, A., Greco, C., Green, M., Greer, G., Gremmler, U., Grena, P., Grinshstein, Y., Grond, M., Gronda, E., Grondin, F., Gronefeld, G., Groot de, J. R., Guardigli, G., Guarnieri, T., Caiedo, C. G., Guignier, A., Gulizia, M., Gumbley, M., Gupta, D., Hack, T., Haerer, W., Hakas, J., Hall, C., Hampsey, J., Hananis, G., Hanbali, B., Handel, F., Hargrove, J., Hargroves, D., Harris, K., Hartley, D., Haruna, T., Hata, Y., Hayek, E., Healey, J., Hearne, S., Heggelund, G., Hemels, M. E. W., Hemery, Y., Henein, S., Henz, B., Her, S. -H., Hermany, P., Hernandes, M. E., Higashino, Y., Hill, M., Hisadome, T., Hishida, E., Hitchcock, J., Hoffer, E., Hoghton, M., Holmes, C., Hong, S. K., Houppe Nousse, M. -P., Howard, V., Hsu, L. F., Huang, C. -H., Huckins, D., Huehnergarth, K., Huizenga, A., Huntley, R., Hussein, G., Hwang, G. -S., Igbokidi, O., Iglesias, I., Ikpoh, M., Imberti, D., Ince, H., Indolfi, C., Ionova, T., Ip, J., Irles, D., Iseki, H., Ismail, Y., Israel, N., Isserman, S., Iteld, B., Ivanchura, G., Iyer, R., Iyer, V., Iza Villanueva, R. O., Jackson-Voyzey, E., Jaffrani, N., Jager, F., Jain, M., James, M., Jamon, Y., Jang, S. W., Pereira Jardim, C. A., Jarmukli, N., Jeanfreau, R., Jenkins, R., Jiang, X., Jiang, H., Jiang, T., Jiang, N., Jimenez, J., Jobe, R., Joffe, I., Johansson, B., Jones, N., Moura Jorge, J. C., Jouve, B., Jundi, M., Jung, W., Jung, B. C., Jung, K. T., Kabbani, S., Kabour, A., Kafkala, C., Kajiwara, K., Kalinina, L., Kampus, P., Kanda, J., Kapadia, S., Karim, A., Karolyi, L., Kashou, H., Kastrup, A., Katsivas, A., Kaufman, E., Kawai, K., Kawajiri, K., Kazmierski, J., Keeling, P., Kerfes, G. A., Kerr Saraiva, J. F., Ketova, G., Khaira, A., Khalid, M., Khludeeva, E., Khripun, A., Kim, D. I., Kim, D. K., Kim, N. H., Kim, K. S., Kim, Y. -H., Kim, J. B., Kim, J. S., Kinova, E., Klein, A., Kleinschnitz, C., Kmetzo, J., Kneller, G. L., Knezevic, A., Koch, S., Koenig, K., Angela Koh, S. M., Kohrmann, M., Koons, J., Korabathina, R., Korennova, O., Koschutnik, M., Kosinski, E., Kovacic, D., Kowalczyk, J., Koziolova, N., Kragten, J. A., Krause, L. U., Kreidieh, I., Krenning, B. J., Krishnaswamy, K., Krysiak, W., Kuck, K. -H., Kumar, S., Kumler, T., Kuniss, M., Kuo, J. -Y., Kuppers, A., Kurrelmeyer, K., Kwan, T., Kyo, E., Labovitz, A., Lacroix, A., Lam, A., Lanas Zanetti, F. T., Landau, C., Landini, G., Lang, W., Larsen, T. B., Laske, V., Lavandier, K., Law, N., Lee, M. H., Lee, D., Leitao, A., Lejay, D., Lelonek, M., Lenarczyk, R., Leprince, P., Lequeux, B., Leschke, M., Ley, N., Li, Z., Li, Y., Li, X., Li, W., Liang, J., Lieber, I., Lillestol, M., Limon Rodriguez, R. H., Lin, H., Lip, G., Litchfield, J., Liu, Z., Liu, X., Liu, Y., Liu, F., Liu, W., Llamas Esperon, G. A., Llisterri, J. L., Lo, T., Lo, E., Lobos, J. M., Lodde, B. -P., Loiselet, P., Lopez-Sendon, J., Lorga Filho, A. M., Lori, I., Luo, M., Lupovitch, S., Lyrer, P., Zuhairy, H. M., Ma, C., Ma, G., Ma, H., Madariaga, I., Maeno, K., Magnin, D., Mahmood, S., Mahood, K., Maid, G., Mainigi, S., Makaritsis, K., Maldonado Villalon, J. A., Malhotra, R., Malik, A., Mallecourt, C., Mallik, R., Manning, R., Manolis, A., Mantas, I., Manzur Jattin, F. G., Marcionni, N., Marin, F., Santana, A. M., Martinez, J., Martinez, L., Maskova, P., Hernandez, N. M., Matskeplishvili, S., Matsuda, K., Mavri, A., May, E., Mayer, N., Mazon, P., Mcclure, J., Mccormack, T., Mcgarity, W., Mcguire, M., Mcintyre, H., Mclaughlin, P., Mclaurin, B., Medina Palomino, F. A., Mehta, P., Mehzad, R., Meinel, A., Melandri, F., Mena, A., Meno, H., Menzies, D., Metcalf, K., Meyer, B., Miarka, J., Mibach, F., Michalski, D., Michel, P., Chreih, R. M., Mikdadi, G., Mikhail, M., Mikus, M., Milicic, D., Militaru, C., Miller, G., Milonas, C., Minescu, B., Mintale, I., Miralles, A., Mirault, T., Mistry, D., Mitchell, G., Miu, N. V., Miyamoto, N., Moccetti, T., Mohammed, A., Nor, A. M., Molina de Salazar, D. I., Molon, G., Molony, D., Mondillo, S., Mont, L., Moodley, R., Moore, R., Ribeiro Moreira, D. A., Mori, K., Moriarty, A., Morka, J., Moschos, N., Mota Gomes, M. A., Mousallem, N., Moya, A., Mugge, A., Mulhearn, T., Muller, J. -J., Muresan, C. M., Muse, D., Musial, W., Musumeci, F., Nadar, V., Nageh, T., Nair, P., Nakagawa, H., Nakamura, Y., Nakayama, T., Nam, K. -B., Napalkov, D., Natarajan, I., Nayak, H., Nechvatal, L., Neiman, J., Nerheim, P., Neuenschwander, F. C., Nishida, K., Nizov, A., Novikova, T., Novo, S., Nowalany-Kozielska, E., Nsah, E., Nunez Fragoso, J. C., Nyvad, O., de Los Rios Ibarra, M. O., O'Donnell, M., O'Donnell, P., D. J., Oh, Y. S., Oh, Daniel Oh, C. T., O'Hara, G., Oikonomou, K., Olalla, J. J., Olivari, Z., Oliver, R., Olympios, C., Osborne, J., Osca, J., Osman, R., Osunkoya, A., Padanilam, B., Panchenko, E., Pandey, A. S., Vicenzo de Paola, A. A., Paraschos, A., Pardell, H., Park, H. W., Park, J. S., Parkash, R., Parker, I., Parrens, E., Parris, R., Passamonti, E., Patel, J., Patel, R., Pentz, W. H., Persic, V., Perticone, F., Peters, P., Petkar, S., Pezo, L. F., Pham, D., Cao Phai, G. P., Phlaum, S., Pineau, J., Pineda-Velez, A., Pini, R., Pinter, A., Pinto, F., Pirelli, S., Pivac, N., Pizzini, A. M., Pocanic, D., Calin Podoleanu, C. G., Polanczyk, C. A., Polasek, P., Poljakovic, Z., Pollock, S., Polo, J., Poock, J., Poppert, H., Porro, Y., Pose, A., Poulain, F., Poulard, J. -E., Pouzar, J., Povolny, P., Pozzer, D., Pras, A., Prasad, N., Prevot, S., Protasov, K., Prunier, L., Puleo, J., Pye, M., Qaddoura, F., Quedillac, J. -M., Raev, D., Rahimi, S., Raisaro, A., Rama, B., Ranadive, N., Randall, K., Ranjith, N., Raposo, N., Rashid, H., Raters, C., Rauch-Kroehnert, U., Rebane, T., Regner, S., Renzi, M., Reyes Rocha, M. A., Reza, S., Ria, L., Richter, D., Rickli, H., Rickner, K., Rieker, W., Rigo, F., Ripoll, T., Fonteles Ritt, L. E., Roberts, D., Pascual, C. R., Briones, I. R., Reyes, H. R., Roelke, M., Roman, M., Romeo, F., Ronner, E., Ronziere, T., Rooyer, F. A., Rosenbaum, D., Roth, S., Rozkova, N., Rubacek, M., Rubalcava, F., Rubanenko, O., Rubin, A., Borret, M. R., Rybak, K., Sabbour, H., Morales, O. S., Sakai, T., Salacata, A., Salecker, I., Salem, A., Salfity, M., Salguero, R., Salvioni, A., Samson, M., Sanchez, G., Sandesara, C., Saporito, W. F., Sasaoka, T., Sattar, P., Savard, D., Scala, P. -J., Scemama, J., Schaupp, T., Schellinger, P., Scherr, C., Schmitz, K. -H., Schmitz, B., Schmitz, L., Schnitzler, R., Schnupp, S., Schoeniger, P., Schon, N., Schuster, S., Schwimmbeck, P., Seamark, C., Seebass, R., Seidl, K. -H., Seidman, B., Sek, J., Sekaran, L., Seko, Y., Sepulveda Varela, P. A., Sevilla, B., Shah, V., Shah, A., Shah, N., Shanes, J., Sharareh, A., Sharma, V. K., Shaw, L., Shimizu, Y., Shimomura, H., Shin, D. G., Shin, E. -S., Shite, J., Shoukfeh, M., Shoultz, C., Silver, F., Sime, I., Simmers, T. A., Singal, D., Singh, N., Siostrzonek, P., Sirajuddin, M., Skeppholm, M., Smadja, D., Smith, R., Smith, D., Soda, H., Sofley, C. W., Sokal, A., Sotolongo, R., de Souza, O. F., Sparby, J. A., Spinar, J., Sprigings, D., Spyropoulos, A., Stakos, D., Steinberg, A., Steinwender, C., Stergiou, G., Stites, H. W., Stoikov, A., Strasser, R., Streb, W., Styliadis, I., Su, G., Su, X., Suarez, R. M., Sudnik, W., Sueyoshi, A., Sukles, K., Sun, L., Suneja, R., Svensson, P., Ziekenhuis, A., Szavits-Nossan, J., Taggeselle, J., Takagi, Y., Takhar, A., Tallet, J., Tamm, A., Tanaka, S., Tanaka, K., Tang, A., Tang, S., Tassinari, T., Tayama, S., Tayebjee, M., Tebbe, U., Teixeira, J., Tesloianu, D. N., Tessier, P., The, S. H. K., Thevenin, J., Thomas, H., Timsit, S., Topkis, R., Torosoff, M., Touze, E., Traissac, T., Trendafilova, E., Troyan, B., Tsai, W. K., Tse, H. F., Tsutsui, H., Tsutsui, T., Tuininga, Y. S., Turakhia, M., Turk, S., Turner, W., Tveit, A., Twiddy, S., Tytus, R., Ukrainski, G., Valdovinos Chavez, S. B., Van De Graaff, E., Vanacker, P., Vardas, P., Vargas, M., Vassilikos, V., Vazquez, J., Venkataraman, A., Verdecchia, P., Vester, E. 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J, Zimmermann, S, Zimmermann, R, Zukerman, L, and Zwaan van der, C

Subjects
Male, oral anticoagulation, Internationality, Middle Aged, registry, Antithrombins, Dabigatran, Stroke, Cross-Sectional Studies, Fibrinolytic Agents, Humans, Female, atrial fibrillation, Prospective Studies, Registries, Cardiology and Cardiovascular Medicine, Aged, Atrial Fibrillation
Abstract

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non–vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients’ baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score ≥2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701)

Published
2017

11. P1632Oxidative stress-responsive apoptosis inducing protein (ORAIP), a new oxidative stress marker, is associated with pulmonary hemodynamics in chronic thromboembolic pulmonary hypertension

Author

Yamagata, Y, primary, Ikeda, S, additional, Nakata, T, additional, Yonekura, T, additional, Eguchi, M, additional, Koga, S, additional, Muroya, T, additional, Koide, Y, additional, Kawano, H, additional, Yao, T, additional, Seko, Y, additional, and Maemura, K, additional

Published
2018
Full Text
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12. Optical transition energies of GaInP quantum wells with GaInP/AIInP superlattice barriers

Author

Seko, Y., Fukatsu, S., Shiraki, Y., and Fuse, M.

Subjects
Quantum wells -- Research, Superlattices as materials -- Analysis, Exciton theory -- Analysis, Physics
Abstract

Incorporation of wave functions of electrons and holes in each layer of the superlattice barriers improves the theoretical results of the optical transition energies in GaInP quantum wells having GaInP/AlInP superlattice barriers. Theoretical results agree with experimental results. These observations prove the validity of effective-mass approximation.

Published
1994

17. The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Author

Huisman, M, Rothman, K, Paquette, M, Teutsch, C, Diener, H, Dubner, S, Halperin, J, Ma, C, Zint, K, Elsaesser, A, Bartels, D, Lip, G, Abban, D, Abdul, N, Abelson, M, Ackermann, A, Adams, F, Adams, L, Adragão, P, Ageno, W, Aggarwal, R, Agosti, S, Marin, J, Aguilar, F, Aguilar Linares, J, Aguinaga, L, Ahmad, Z, Ainsworth, P, Al Ghalayini, K, Al Ismail, S, Alasfar, A, Alawwa, A, Al Dallow, R, Alderson, L, Alexopoulos, D, Ali, A, Ali, M, Aliyar, P, Al Joundi, T, Al Mahameed, S, Almassi, H, Almuti, K, Al Obaidi, M, Alshehri, M, Altmann, U, Alves, A, Al Zoebi, A, Amara, W, Amelot, M, Amjadi, N, Ammirati, F, Andrawis, N, Angoulvant, D, Annoni, G, Ansalone, G, Antonescu, S, Ariani, M, Arias, J, Armero, S, Arora, R, Arora, C, Ashcraft, W, Aslam, M, Astesiano, A, Audouin, P, Augenbraun, C, Aydin, S, Azar, R, Azim, A, Aziz, S, Backes, L, Baig, M, Bains, S, Bakbak, A, Baker, S, Bakhtiar, K, Bala, R, Banayan, J, Bandh, S, Bando, S, Banerjee, S, Bank, A, Barbarash, O, Barón, G, Barr, C, Barrera, C, Barton, J, Kes, V, Baula, G, Bayeh, H, Bazargani, N, Behrens, S, Bell, A, Benezet Mazuecos, J, Benhalima, B, Berdagué, P, Berg van den, B, Bergen van, P, Berngard, E, Bernstein, R, Berrospi, P, Berti, S, Bertomeu, V, Berz, A, Bettencourt, P, Betzu, R, Beyer Westendorf, J, Bhagwat, R, Black, T, Blanco Ibaceta, J, Bloom, S, Blumberg, E, Bo, M, Bockisch, V, Bøhmer, E, Bongiorni, M, Boriani, G, Bosch, R, Boswijk, D, Bott, J, Bottacchi, E, Kalan, M, Brandes, A, Bratland, B, Brautigam, D, Breton, N, Brouwers, P, Browne, K, Bruguera, J, Brunehaut, M, Brunschwig, C, Buathier, H, Buhl, A, Bullinga, J, Butcher, K, Cabrera Honorio, J, Caccavo, A, Cadinot, D, Cai, S, Calvi, V, Camm, J, Candeias, R, Capo, J, Capucci, A, Cardoso, J, Duarte Vera, Y, Carlson, B, Carvalho, P, Cary, S, Casanova, R, Casu, G, Cattan, S, Cavallini, C, Cayla, G, Cha, T, Cha, K, Chaaban, S, Chae, J, Challappa, K, Chand, S, Chandrashekar, H, Chang, M, Charbel, P, Chartier, L, Chatterjee, K, Cheema, A, Chen, S, Chevallereau, P, Chiang, F, Chiarella, F, Chih Chan, L, Cho, Y, Choi, D, Chouinard, G, Danny, N, Chow, H, Chrysos, D, Chumakova, G, José Roberto Chuquiure Valenzuela, E, Cieza Lara, T, Nica, V, Ciobotaru, V, Cislowski, D, Citerne, O, Claus, M, Clay, A, Clifford, P, Cohen, S, Cohen, A, Colivicchi, F, Collins, R, Compton, S, Connors, S, Conti, A, Buenostro, G, Coodley, G, Cooper, M, Corbett, L, Corey, O, Coronel, J, Corrigan, J, Cotrina Pereyra, R, Cottin, Y, Coutu, B, Cracan, A, Crean, P, Crenshaw, J, Crijns, H, Crump, C, Cucher, F, Cudmore, D, Cui, L, Culp, J, Darius, H, Dary, P, Dascotte, O, Dauber, I, Davee, T, Davies, R, Davis, G, Davy, J, Dayer, M, De La Briolle, A, de Mora, M, De Teresa, E, De Wolf, L, Decoulx, E, Deepak, S, Defaye, P, Del Carpio Munoz, F, Brkljacic, D, Deluche, L, Destrac, S, Deumite, N, Di Legge, S, Dibon, O, Diemberger, I, Dillinger, J, Dionísio, P, Naydenov, S, Dotani, I, Dotcheva, E, D'Souza, A, Dubrey, S, Ducrocq, X, Dupljakov, D, Duthinh, V, Dutra, O, Dutta, D, Duvilla, N, Dy, J, Dziewas, R, Eaton, C, Eaves, W, Ebinger, M, Eck van, J, Edwards, T, Egocheaga, I, Ehrlich, C, Eisenberg, S, El Hallak, A, El Jabali, A, El Mahmoud, R, El Shahawy, M, Eldadah, Z, Elghelbazouri, F, Elhag, O, El Hamdani, M, Elias, D, Ellery, A, El Sayed, H, Elvan, A, Erickson, B, Espaliat, E, Essandoh, L, Everington, T, Evonich, R, Ezhov, A, Fácila, L, Farsad, R, Fayard, M, Fedele, F, Gomes Ferreira, L, Ferreira, D, Santos, J, Ferrier, A, Finsen, A, First, B, Fisher, R, Floyd, J, Folk, T, Fonseca, C, Fonseca, L, Forman, S, Forsgren, M, Foster, M, Foster, N, Frais, M, Frandsen, B, Frappé, T, Freixa, R, French, W, Freydlin, M, Frickel, S, Fruntelata, A, Fujii, S, Fujino, Y, Fukunaga, H, Furukawa, Y, Gabelmann, M, Gabris, M, Gadsbøll, N, Galin, P, Galinier, M, Ganim, R, Garcia, R, Quintana, A, Gartenlaub, O, Genz, C, Georger, F, Georges, J, Georgeson, S, Ghanbasha, A, Giedrimas, E, Gierba, M, Gillespie, E, Giniger, A, Gkotsis, A, Gmehling, J, Gniot, J, Goethals, P, Goldberg, R, Goldmann, B, Goldscher, D, Golitsyn, S, Gomez Lopez, E, Gomez Mesa, J, Gonzalez, E, Cocina, E, Juanatey, C, Gorbunov, V, Gordon, B, Gorka, H, Gornick, C, Gorog, D, Goss, F, Götte, A, Goube, P, Goudevenos, I, Goulden, D, Graham, B, Grande, A, Greco, C, Green, M, Greer, G, Gremmler, U, Grena, P, Grinshstein, Y, Grond, M, Gronda, E, Grondin, F, Grönefeld, G, Groot de, J, Guardigli, G, Guarnieri, T, Caiedo, C, Guignier, A, Gulizia, M, Gumbley, M, Gupta, D, Hack, T, Haerer, W, Hakas, J, Hall, C, Hampsey, J, Hananis, G, Hanbali, B, Handel, F, Hargrove, J, Hargroves, D, Harris, K, Hartley, D, Haruna, T, Hata, Y, Hayek, E, Healey, J, Hearne, S, Heggelund, G, Hemels, M, Hemery, Y, Henein, S, Henz, B, Her, S, Hermany, P, Hernandes, M, Higashino, Y, Hill, M, Hisadome, T, Hishida, E, Hitchcock, J, Hoffer, E, Hoghton, M, Holmes, C, Hong, S, Houppe Nousse, M, Howard, V, Hsu, L, Huang, C, Huckins, D, Huehnergarth, K, Huizenga, A, Huntley, R, Hussein, G, Hwang, G, Igbokidi, O, Iglesias, I, Ikpoh, M, Imberti, D, Ince, H, Indolfi, C, Ionova, T, Ip, J, Irles, D, Iseki, H, Ismail, Y, Israel, N, Isserman, S, Iteld, B, Ivanchura, G, Iyer, R, Iyer, V, Iza Villanueva, R, Jackson Voyzey, E, Jaffrani, N, Jäger, F, Jain, M, James, M, Jamon, Y, Jang, S, Pereira Jardim, C, Jarmukli, N, Jeanfreau, R, Jenkins, R, Jiang, X, Jiang, H, Jiang, T, Jiang, N, Jimenez, J, Jobe, R, Joffe, I, Johansson, B, Jones, N, Moura Jorge, J, Jouve, B, Jundi, M, Jung, W, Jung, B, Jung, K, Kabbani, S, Kabour, A, Kafkala, C, Kajiwara, K, Kalinina, L, Kampus, P, Kanda, J, Kapadia, S, Karim, A, Karolyi, L, Kashou, H, Kastrup, A, Katsivas, A, Kaufman, E, Kawai, K, Kawajiri, K, Kazmierski, J, Keeling, P, Kerfes, G, Kerr Saraiva, J, Ketova, G, Khaira, A, Khalid, M, Khludeeva, E, Khripun, A, Kim, D, Kim, N, Kim, K, Kim, Y, Kim, J, Kinova, E, Klein, A, Kleinschnitz, C, Kmetzo, J, Kneller, G, Knezevic, A, Koch, S, Koenig, K, Angela Koh, S, Köhrmann, M, Koons, J, Korabathina, R, Korennova, O, Koschutnik, M, Kosinski, E, Kovacic, D, Kowalczyk, J, Koziolova, N, Kragten, J, Krause, L, Kreidieh, I, Krenning, B, Krishnaswamy, K, Krysiak, W, Kuck, K, Kumar, S, Kümler, T, Kuniss, M, Kuo, J, Küppers, A, Kurrelmeyer, K, Kwan, T, Kyo, E, Labovitz, A, Lacroix, A, Lam, A, Lanas Zanetti, F, Landau, C, Landini, G, Lang, W, Larsen, T, Laske, V, Lavandier, K, Law, N, Lee, M, Lee, D, Leitão, A, Lejay, D, Lelonek, M, Lenarczyk, R, Leprince, P, Lequeux, B, Leschke, M, Ley, N, Li, Z, Li, Y, Li, X, Li, W, Liang, J, Lieber, I, Lillestol, M, Limon Rodriguez, R, Lin, H, Litchfield, J, Liu, Z, Liu, X, Liu, Y, Liu, F, Liu, W, Llamas Esperon, G, Llisterri, J, Lo, T, Lo, E, Lobos, J, Lodde, B, Loiselet, P, López Sendón, J, Lorga Filho, A, Lori, I, Luo, M, Lupovitch, S, Lyrer, P, Zuhairy, H, Ma, G, Ma, H, Madariaga, I, Maeno, K, Magnin, D, Mahmood, S, Mahood, K, Maid, G, Mainigi, S, Makaritsis, K, Maldonado Villalon, J, Malhotra, R, Malik, A, Mallecourt, C, Mallik, R, Manning, R, Manolis, A, Mantas, I, Manzur Jattin, F, Marcionni, N, Marín, F, Santana, A, Martinez, J, Martinez, L, Maskova, P, Hernández, N, Matskeplishvili, S, Matsuda, K, Mavri, A, May, E, Mayer, N, Mazon, P, Mcclure, J, Mccormack, T, Mcgarity, W, Mcguire, M, Mcintyre, H, Mclaughlin, P, Mclaurin, B, Medina Palomino, F, Mehta, P, Mehzad, R, Meinel, A, Melandri, F, Mena, A, Meno, H, Menzies, D, Metcalf, K, Meyer, B, Miarka, J, Mibach, F, Michalski, D, Michel, P, Chreih, R, Mikdadi, G, Mikhail, M, Mikus, M, Milicic, D, Militaru, C, Miller, G, Milonas, C, Minescu, B, Mintale, I, Miralles, A, Mirault, T, Mistry, D, Mitchell, G, Miu, N, Miyamoto, N, Moccetti, T, Mohammed, A, Nor, A, Molina de Salazar, D, Molon, G, Molony, D, Mondillo, S, Mont, L, Moodley, R, Moore, R, Ribeiro Moreira, D, Mori, K, Moriarty, A, Morka, J, Moschos, N, Mota Gomes, M, Mousallem, N, Moya, A, Mügge, A, Mulhearn, T, Muller, J, Muresan, C, Muse, D, Musial, W, Musumeci, F, Nadar, V, Nageh, T, Nair, P, Nakagawa, H, Nakamura, Y, Nakayama, T, Nam, K, Napalkov, D, 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Köhrmann, M, Koons, J, Korabathina, R, Korennova, O, Koschutnik, M, Kosinski, E, Kovacic, D, Kowalczyk, J, Koziolova, N, Kragten, J, Krause, L, Kreidieh, I, Krenning, B, Krishnaswamy, K, Krysiak, W, Kuck, K, Kumar, S, Kümler, T, Kuniss, M, Kuo, J, Küppers, A, Kurrelmeyer, K, Kwan, T, Kyo, E, Labovitz, A, Lacroix, A, Lam, A, Lanas Zanetti, F, Landau, C, Landini, G, Lang, W, Larsen, T, Laske, V, Lavandier, K, Law, N, Lee, M, Lee, D, Leitão, A, Lejay, D, Lelonek, M, Lenarczyk, R, Leprince, P, Lequeux, B, Leschke, M, Ley, N, Li, Z, Li, Y, Li, X, Li, W, Liang, J, Lieber, I, Lillestol, M, Limon Rodriguez, R, Lin, H, Litchfield, J, Liu, Z, Liu, X, Liu, Y, Liu, F, Liu, W, Llamas Esperon, G, Llisterri, J, Lo, T, Lo, E, Lobos, J, Lodde, B, Loiselet, P, López Sendón, J, Lorga Filho, A, Lori, I, Luo, M, Lupovitch, S, Lyrer, P, Zuhairy, H, Ma, G, Ma, H, Madariaga, I, Maeno, K, Magnin, D, Mahmood, S, Mahood, K, Maid, G, Mainigi, S, Makaritsis, K, Maldonado Villalon, J, Malhotra, R, Malik, A, Mallecourt, C, Mallik, R, Manning, R, Manolis, A, Mantas, I, Manzur Jattin, F, Marcionni, N, Marín, F, Santana, A, Martinez, J, Martinez, L, Maskova, P, Hernández, N, Matskeplishvili, S, Matsuda, K, Mavri, A, May, E, Mayer, N, Mazon, P, Mcclure, J, Mccormack, T, Mcgarity, W, Mcguire, M, Mcintyre, H, Mclaughlin, P, Mclaurin, B, Medina Palomino, F, Mehta, P, Mehzad, R, Meinel, A, Melandri, F, Mena, A, Meno, H, Menzies, D, Metcalf, K, Meyer, B, Miarka, J, Mibach, F, Michalski, D, Michel, P, Chreih, R, Mikdadi, G, Mikhail, M, Mikus, M, Milicic, D, Militaru, C, Miller, G, Milonas, C, Minescu, B, Mintale, I, Miralles, A, Mirault, T, Mistry, D, Mitchell, G, Miu, N, Miyamoto, N, Moccetti, T, Mohammed, A, Nor, A, Molina de Salazar, D, Molon, G, Molony, D, Mondillo, S, Mont, L, Moodley, R, Moore, R, Ribeiro Moreira, D, Mori, K, Moriarty, A, Morka, J, Moschos, N, Mota Gomes, M, Mousallem, N, Moya, A, Mügge, A, Mulhearn, T, Muller, J, Muresan, C, Muse, D, Musial, W, Musumeci, F, Nadar, V, Nageh, T, Nair, P, Nakagawa, H, Nakamura, Y, Nakayama, T, Nam, K, Napalkov, D, Natarajan, I, Nayak, H, Nechvatal, L, Neiman, J, Nerheim, P, Neuenschwander, F, Nishida, K, Nizov, A, Novikova, T, Novo, S, Nowalany Kozielska, E, Nsah, E, Nunez Fragoso, J, Nyvad, O, de Los Rios Ibarra, M, O'Donnell, M, O'Donnell, P, Oh, D, Oh, Y, Daniel Oh, C, O'Hara, G, Oikonomou, K, Olalla, J, Olivari, Z, Oliver, R, Olympios, C, Osborne, J, Osca, J, Osman, R, Osunkoya, A, Padanilam, B, Panchenko, E, Pandey, A, Vicenzo de Paola, A, Paraschos, A, Pardell, H, Park, H, Park, J, Parkash, R, Parker, I, Parrens, E, Parris, R, Passamonti, E, Patel, J, Patel, R, Pentz, W, Persic, V, Perticone, F, Peters, P, Petkar, S, Pezo, L, Pham, D, Cao Phai, G, Phlaum, S, Pineau, J, Pineda Velez, A, Pini, R, Pinter, A, Pinto, F, Pirelli, S, Pivac, N, Pizzini, A, Pocanic, D, Calin Podoleanu, C, Polanczyk, C, Polasek, P, Poljakovic, Z, Pollock, S, Polo, J, Poock, J, Poppert, H, Porro, Y, Pose, A, Poulain, F, Poulard, J, Pouzar, J, 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Zhang, H, Zhao, S, Zhao, X, Zheng, Y, Zheng, Q, Zhou, J, Zimmermann, S, Zimmermann, R, Zukerman, L, Zwaan van der, C, Zwaan van der, C., and ANNONI, GIORGIO

Abstract

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non–vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients’ baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score ≥2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients rece

Published
2017

40. Expression of tumour necrosis factor (TNF) ligand superfamily co-stimulatory molecules CD30L, CD27L, OX40L, and 4-1BBL in murine hearts with acute myocarditis caused by Coxsackievirus B3

Author

Seko, Y., Takahashi, N., Oshima, H., Shimozato, O., Akiba, H., Takeda, K., Kobata, T., Yagita, H., Okumura, K., Azuma, M., and Nagai, R.

Abstract

Antigen-specific T-cells infiltrate the heart and play an important role in the myocardial damage involved in acute myocarditis and dilated cardiomyopathy. To investigate the roles of the co-stimulatory molecules CD30/CD30L, CD27/CD27L, OX40/OX40L, and 4-1BB/4-1BBL, which belong to the tumor necrosis factor (TNF) receptor/ligand superfamily, in the development of acute viral myocarditis, the expression of these molecules was first analysed in the hearts of mice with acute myocarditis induced by Coxsackievirus B3 (CVB3) in vivo. Secondly, the induction of these molecules was evaluated on cultured cardiac myocytes treated with interferon (IFN)-γ and the interleukin (IL)-6 production by cultured cardiac myocytes was analysed by stimulation with monoclonal antibodies (MAbs) against these molecules in vitro. Thirdly, the effects of in vivo administration of anti-CD30L, anti-CD27L, anti-OX40L, or anti-4-1BBL MAb on the development of acute viral myocarditis were examined. CVB3-induced myocarditis resulted in the induction of CD30L and 4-1BBL on the surface of cardiac myocytes, confirmed by treatment with IFN-γ in vitro. CD27L and OX40L were constitutively expressed on cardiac myocytes in vivo and in vitro. Anti-CD30L and anti-4-1BBL MAbs stimulated IL-6 production by cardiac myocytes in vitro. Furthermore, in vivo anti-4-1BBL MAb treatment significantly decreased the myocardial inflammation, whereas the other MAbs did not. These findings suggest that TNF ligand superfamily co-stimulatory molecules, especially 4-1BBL, play an important role in the development of acute viral myocarditis and raise the possibility that immunotherapy with anti-4-1BBL MAb may be of benefit in acute viral myocarditis. Copyright © 2001 John Wiley & Sons, Ltd.

Published
2001

44. Analysis of driving behaviour under a state of reduced alertness

Author

Seko, Y., Kataoka, S., and Senoo, T.

Abstract

Drowsiness while driving is a major cause of road accident of a serious nature. An alertness index was formulated. This index was related to the performance of a subject driving on a test course and on ordinary roads and to the subject's perception of drowsiness. A description is given of characteristics of a state of reduced alertness in terms of physiological changes in the subject and the steering pattern displayed.

Published
1986
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45. Isolation and characterization of two isozymes of myosin heavy chain from canine atrium.

Author

Komuro, I, Tsuchimochi, H, Ueda, S, Kurabayashi, M, Seko, Y, Takaku, F, and Yazaki, Y

Abstract

To clarify the characteristics of myosin isozymes in the atrium, we fractionated two isoforms of myosin heavy chain (HC), atrial HC alpha (A-HC alpha) and HC beta (A-HC beta), from the canine heart by affinity chromatography, using monoclonal antibodies specific for HC alpha (CMA19) and HC beta (HMC50), respectively, and then compared their peptide composition and enzymatic properties with those of ventricular HC alpha (V-HC alpha) and HC beta (V-HC beta). The reactivity of these isozymes with three monoclonal antibodies revealed that there are at least three different epitopes between A-HC alpha and A-HC beta. Differences in the primary structure of A-HC alpha and A-HC beta were confirmed by one- and two-dimensional gel electrophoretic analyses of these peptides, produced by digestion with alpha-chymotrypsin and cyanogen bromide (CNBr). A-HC alpha and V-HC alpha were indistinguishable proteins, and A-HC beta was also very similar to V-HC beta. Furthermore, there were differences between A-HC alpha and A-HC beta in their Ca2+-activated ATPase activities. The ATPase activity of A-HC beta was lower than that of A-HC alpha and was similar to that of V-HC beta. We concluded that there are two different isozymes of myosin heavy chain in the atrium (A-HC alpha and A-HC beta), as well as in the ventricle (V-HC alpha and V-HC beta), and that A-HC beta is very similar to V-HC beta, the predominant form of ventricular myosin, in its molecular structure and enzymatic activity.

Published
1986
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