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410 results on '"SASAKI, Makoto"'

2. Healthy lifestyle practice correlates with decreased obesity prevalence in individuals with high polygenic risk: TMM CommCohort study

Author

Sutoh, Yoichi, Hachiya, Tsuyoshi, Otsuka-Yamasaki, Yayoi, Komaki, Shohei, Minabe, Shiori, Ohmomo, Hideki, Sasaki, Makoto, and Shimizu, Atsushi

Abstract

Obesity and overweight, fundamental components of the metabolic syndrome, predispose individuals to lifestyle-related diseases. The extent to which adopting healthy lifestyles can reduce obesity risk, even in those with a high genetic risk, remains uncertain. Our aim was to assess the extent to which lifestyle modifications can improve outcomes in individuals with a high polygenic score (PGS) for obesity. We quantified the genetic risk of obesity using PGSs. Four datasets from the Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) were employed in the study. One dataset (n= 9958) was used to select the best model for calculating PGS. The remaining datasets (total n= 69,341) were used in a meta-analysis to validate the model and to evaluate associated risks. The odds ratio (OR) for obesity risk in the intermediate (11th–90th percentiles in the dataset) and high PGS categories (91st–100th) was 2.27 [95% confidence intervals: 2.12–2.44] and 4.83 [4.45–5.25], respectively, compared to that in the low PGS category (1st–10th). Trend analysis showed that an increase in leisure-time physical activity was significantly associated with reduced obesity risk across all genetic risk categories, representing an OR of 0.9 [0.87–0.94] even among individuals in the high PGS category. Similarly, sodium intake displayed a positive association with obesity across all genetic risk categories, yielding an OR of 1.24 [1.17–1.31] in the high PGS category. The risk of obesity was linked to the adoption of healthy lifestyles, even in individuals with high PGS. Our results may provide perspectives for integrating PGSs into preventive medicine.

Published
2025
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6. Convergent and Scalable Second-Generation Synthesis of the Fully Functionalized HIJKLMN-Ring Segment of Caribbean Ciguatoxin C-CTX-1

Author

Sasaki, Makoto, Ohba, Miyu, Murakami, Ako, and Umehara, Atsushi

Abstract

A highly convergent and scalable second-generation synthesis of the fully functionalized HIJKLMN-ring segment of Caribbean ciguatoxin C-CTX-1, the primary toxin responsible for ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic regions, has been accomplished. Key aspects of the synthetic approach include the efficient syntheses of the HI- and KLM-ring fragments on gram scales, a convergent fragment coupling toward the HIJKLM-ring skeleton based on the Suzuki–Miyaura coupling strategy, and optimized iron hydride-catalyzed hydrogen atom transfer-mediated olefin coupling conditions for constructing the N-ring.

Published
2024
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8. Total Synthesis of (−)-Zearalenone and (−)-Zearalanone: A Macrocyclization Strategy by Ni/Zr/Cr-Mediated Reductive Ketone Coupling

Author

Umehara, Atsushi, Kawakita, Ko-hei, and Sasaki, Makoto

Abstract

The total synthesis of the resorcylic acid lactones (−)-zearalenone and (−)-zearalanone is described. Our synthetic strategy relies on Ni-, Zr-, and Cr-mediated intramolecular reductive ketone coupling to create 14-membered macrolactones. Notably, the use of CrCl2in addition to Ni/Zr-mediated reductive ketone coupling conditions was key for the success of the macrocyclization.

Published
2024
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9. ComPair-2: a next-generation medium-energy gamma-ray telescope prototype

Author

den Herder, Jan-Willem A., Nikzad, Shouleh, Nakazawa, Kazuhiro, Caputo, Regina, Kierans, Carolyn, Cannady, Nicholas, Falcone, Abe, Fukazawa, Yasushi, Jadhav, Manoj, Kerr, Matthew, Kirschner, Nicolas, Kumar, Kavic, Laviron, Adrien, Leys, Richard, McEnery, Julie, Metcalfe, Jessica, Metzler, Zachary, Miller, Nathan, Mitchell, John, Parker, Lucas, Peric, Ivan, Perkins, Jeremy, Phlips, Bernard, Racusin, Judith, Sasaki, Makoto, Segal, Kenneth N., Shy, Daniel, Steinhebel, Amanda L., Striebig, Nicolas, Suda, Yusuke, Tajima, Hiroyasu, Valverde, Janeth, Violette, Daniel P., Woolf, Richard, and Zoglauer, Andreas

Published
2024
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10. The 2023 balloon flight of the ComPair instrument

Author

den Herder, Jan-Willem A., Nikzad, Shouleh, Nakazawa, Kazuhiro, Smith, Lucas D., Cannady, Nicholas, Caputo, Regina, Kierans, Carolyn, Kirschner, Nicholas, Liceaga-Indart, Iker, McEnery, Julie, Metzler, Zachary, Moiseev, A. A., Parker, Lucas, Perkins, Jeremy, Sasaki, Makoto, Schoenwald, Adam J., Shy, Daniel, Valverde, Janeth, Wasti, Sambid, Woolf, Richard, Bolotnikov, Aleksey, Caligiure, Thomas J., Crosier, A. Wilder, Fried, Jack, Ghosh, Priyarshini, Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Kong, Emily, Mitchell, John, Phlips, Bernard, Sleator, Clio, Thompson, D. J., Wulf, Eric, and Zajczyk, Anna

Published
2024
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11. Results from the CsI calorimeter onboard the 2023 ComPair balloon flight

Author

den Herder, Jan-Willem A., Nikzad, Shouleh, Nakazawa, Kazuhiro, Shy, Daniel, Woolf, Richard S., Sleator, Clio, Phlips, Bernard, Grove, J. Eric, Wulf, Eric A., Johnson-Rambert, Mary, Davis, Mitch, Kong, Emily, Caligiure, Thomas, Crosier, A. Wilder, Bolotnikov, Aleksey, Cannady, Nicholas, Carini, Gabriella A., Caputo, Regina, Fried, Jack, Ghosh, Priyarshini, Griffin, Sean, Hays, Elizabeth, Herrmann, Sven, Kierans, Carolyn, Kirschner, Nicholas, Liceaga-Indart, Iker, Metzler, Zachary, McEnery, Julie, Mitchell, John, Moiseev, A. A., Parker, Lucas, Dellapenna, Alfred, Perkins, Jeremy S., Sasaki, Makoto, Schoenwald, Adam J., Smith, Lucas D., Valverde, Janeth, Wasti, Sambid, and Zajczyk, Anna

Published
2024
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13. Urgent colonoscopy is not necessary in case of colonic diverticular bleeding without extravasation on contrast-enhanced computed tomography.

Author

Sugiyama, Tomoya, Kojima, Yuki, Hirata, Yoshikazu, Ebi, Masahide, Yoshimine, Takashi, Adachi, Kazunori, Yamaguchi, Yoshiharu, Izawa, Shinya, Hijikata, Yasutaka, Funaki, Yasushi, Ogasawara, Naotaka, Sasaki, Makoto, Ohashi, Wataru, Sobue, Satoshi, and Kasugai, Kunio

Abstract

Acute lower gastrointestinal bleeding (ALGIB) increase with age and the administration of antiplatelet drugs. Colonic diverticular bleeding (CDB) is the most common cause of ALGIB, and endoscopic hemostasis is an effective treatment for massive CDB. But in patients without extravasation on contrast-enhanced computed tomography (CECT), the efficacy of urgent colonoscopy (UCS) is controversial from the point of the clinical course, including rebleeding rate. We aimed to establish a potential strategy including UCS for CDB patients without extravasation on CECT. Patients from two centers treated for CDB without extravasation on CECT between July 2014 and July 2019 were retrospectively identified (n = 282). Seventy-four underwent UCS, and 208 received conservative management. We conducted two analyses. The first analysis investigates the risk factors of rebleeding rate within 5 days after administration (very early rebleeding), and no UCS (NUCS) was not the independent factor of the very early rebleeding. The second analysis is whether UCS positively influenced the clinical course after hospitalization. The prevalence of very early rebleeding and early rebleeding (6–30 days from admission), patients requiring blood transfusion within 0–5 days and 6–30 days post-admission, and duration of hospitalization were examined as clinical course factors between UCS and NUCS group. There was no significant difference between the UCS and non-UCS groups in the clinical course factors. UCS for the CDB patients without extravasation was not improved rebleeding rate and clinical course. UCS is not necessary in case of CDB patient without extravasation on CECT. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

Author

Ueda, Takeshi, Koyama, Fumikazu, Sugita, Akira, Ikeuchi, Hiroki, Futami, Kitaro, Fukushima, Kouhei, Nezu, Riichiro, Iijima, Hideki, Mizushima, Tsunekazu, Itabashi, Michio, Watanabe, Kazuhiro, Hata, Keisuke, Shinagawa, Takahide, Matsuoka, Katsuyoshi, Takenaka, Kento, Sasaki, Makoto, Nagayama, Manabu, Yamamoto, Hironori, Shinozaki, Masaru, and Fujiya, Mikihiro

Abstract

Background and Aims Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. Methods We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. Results In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. Conclusions Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O’Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie

Abstract

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P< 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2Aand FURIN) and variants (such as at GRK5and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Published
2022
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19. Development of the ComPair gamma-ray telescope prototype

Author

den Herder, Jan-Willem A., Nikzad, Shouleh, Nakazawa, Kazuhiro, Shy, Daniel, Kierans, Carolyn, Cannady, Nicolas, Caputo, Regina, Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Kong, Emily, Kirschner, Nicholas, Liceaga-Indart, Iker, McEnery, Julie, Mitchell, John, Moiseev, A. A., Parker, Lucas, Perkins, Jeremy S., Phlips, Bernard, Sasaki, Makoto, Schoenwald, Adam J., Sleator, Clio, Smith, Jacob, Smith, Lucas D., Wasti, Sambid, Woolf, Richard, Wulf, Eric, and Zajczyk, Anna

Published
2022
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22. Performance of cone-beam computed tomography imaging during megavoltage beam irradiation under phase-gated conditions.

Author

Iramina, Hiraku, Nakamura, Mitsuhiro, Sasaki, Makoto, and Mizowaki, Takashi

Abstract

• Kilovoltage imaging during beam delivery under phase-gated condition was performed. • Gated cone-beam computed tomography images were reconstructed. • CT-number error and noise were quantified under various parameters. • Iterative reconstruction algorithm improved these values even under low frame rates. • Acquired images showed good target detectability under phase-gated condition. Target positions should be acquired during beam delivery for accurate lung stereotactic body radiotherapy. We aimed to perform kilovoltage (kV) imaging during beam irradiation (intra-irradiation imaging) under phase-gated conditions and evaluate its performance. Catphan 504 and QUASAR respiratory motion phantoms were used to evaluate image quality and target detectability, respectively. TrueBeam STx linac and the Developer Mode was used. The imaging parameters were 125 kVp and 1.2 mAs/projection. Flattened megavoltage (MV) X-ray beam energies 6, 10 and 15 MV and un-flattened beam energies 6 and 10 MV were used with field sizes of 5 × 5 and 15 × 15 cm2 and various frame rates for intra-irradiation imaging. In addition, using a QUASAR phantom, intra-irradiation imaging was performed during intensity-modulated plan delivery. The root-mean-square error (RMSE) of the CT-number for the inserted rods, image noise, visual assessment, and contrast-to-noise ratio (CNR) were evaluated. The RMSEs of intra-irradiation cone-beam computed tomography (CBCT) images under gated conditions were 50–230 Hounsfield Unit (HU) (static < 30 HU). The noise of the intra-irradiation CBCT images under gated conditions was 15–35 HU, whereas that of the standard CBCT images was 8.8–27.2 HU. Lower frame rates exhibited large RMSEs and noise; however, the iterative reconstruction algorithm (IR) was effective at improving these values. Approximately 7 fps with the IR showed an equivalent CNR of 15 fps without the IR. The target was visible on all the gated intra-irradiation CBCT images. Several image quality improvements are required; however, intra-irradiated CBCT images showed good visual target detection. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Sabater‐Lleal, Maria, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Chen, Ming‐Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John‐Bjarne, Rosendaal, Frits R, Heit, John A, Psaty, Bruce M, Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Smith, Nicholas L, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Wiggins, Kerri L, Yang, Qiong, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Abstract

Multi‐phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes.

Published
2022
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24. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Sabater‐Lleal, Maria, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Chen, Ming‐Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John‐Bjarne, Rosendaal, Frits R, Heit, John A, Psaty, Bruce M, Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Smith, Nicholas L, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Wiggins, Kerri L, Yang, Qiong, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Abstract

Multi‐phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Summary statistics from genome wide‐association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI‐1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi‐trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9obtained after applying Bonferroni correction for the number of multi‐trait combinations performed (n= 27). Across the 27 multi‐trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

Published
2022
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25. Convergent Synthesis of the HIJKLMN-Ring Fragment of Caribbean Ciguatoxin C-CTX-1 by a Late-Stage Reductive Olefin Coupling Approach

Author

Sasaki, Makoto, Iwasaki, Kotaro, Arai, Keisuke, Hamada, Naoya, and Umehara, Atsushi

Abstract

The convergent synthesis of the HIJKLMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the major causative toxin for ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic areas, is disclosed. The synthesis features a late-stage iron-catalyzed hydrogen atom transfer-initiated reductive olefin coupling to install the N-ring and a Suzuki–Miyaura coupling/thioacetalization strategy for the convergent assembly of the hexacyclic HIJKLM-ring skeleton.The convergent synthesis of the HIJKLMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the major causative toxin for ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic areas, is disclosed. Highlights of the synthesis are Suzuki–Miyaura coupling/thioacetalization strategy for convergent assembly of the HIJKLM-ring skeleton and a late-stage hydrogen atom transfer-initiated reductive olefin coupling to construct the terminal N-ring.

Published
2022
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26. Small-Intestinal Metastasis from Lung Carcinoma

Author

Ogasawara, Naotaka, Ono, Satoshi, Sugiyama, Tomoya, Adachi, Kazunori, Yamaguchi, Yoshiharu, Izawa, Shinya, Ebi, Masahide, Funaki, Yasushi, Sasaki, Makoto, and Kasugai, Kunio

Abstract

A 62-year-old man was referred to our hospital because of abdominal pain. Computed tomography revealed an approximately 7-cm-diameter tumor in the left abdomen with metastatic lymph nodes, an approximately 1-cm-diameter round tumor in contact with the subclavian artery in the apical lobe of the right lung, and mediastinal lymph node enlargement in contact with the superior vena cava. Esophagogastroduodenoscopy and colonoscopy revealed no abnormalities. Double-balloon endoscopy revealed a whole circumferential ulcer in the jejunum approximately 20 cm from the ligament of Treitz. Biopsy analysis of an ulcer specimen revealed a poorly differentiated carcinoma. Immunohistochemical staining of the specimen showed that it was positive for thyroid transcription factor 1 and cytokeratin 7 and negative for cytokeratin 20, GATA-binding protein 3, caudal-type homeobox protein 2, and paired box 8. Positron emission tomography revealed positive findings in the small-intestinal tumor, nearby mesenteric lymph nodes, lymph nodes around the abdominal aorta, lung tumor, and mediastinal lymph node in the apical lobe of the right lung. Accordingly, the patient was diagnosed as having a lung carcinoma with small-intestinal metastasis (T1b, N3, M1c; cStage IVB). Pathological examination helped distinguish the primary small-intestinal tumor from the metastatic small-intestinal tumor and detect the tumor origin.

Published
2022
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27. Gastric Plexiform Fibromyxoma Resected Using Nonexposed Endoscopic Wall-Inversion Surgery: A Case Report

Author

Ebi, Masahide, Nagao, Kazuhiro, Sugiyama, Tomoya, Yamamoto, Kazuhiro, Saito, Takuya, Kurahashi, Shintaro, Yamaguchi, Yoshiharu, Adachi, Kazunori, Tamura, Yasuhiro, Izawa, Shinya, Funaki, Yasushi, Ogasawara, Naotaka, Sasaki, Makoto, Tsuzuki, Toyonori, and Kasugai, Kunio

Abstract

Gastric plexiform fibromyxoma is extremely rare. In our case, upper gastrointestinal endoscopy of a 41-year-old woman patient revealed a 1-cm submucosal tumor (SMT) in the greater curvature of the lower body of the stomach. On contrast-enhanced computed tomography, the tumor was hypervascular in the arterial phase with continuous enhancement in the post-venous phase. On endoscopic ultrasonography, it had a low echo pattern. The preoperative diagnosis was a gastric SMT with a rich vasculature; however because the biosy specimen did not contain tumor tissue, a malignant tumor could not be excluded. The patient underwent nonexposed endoscopic wall-inversion surgery (NEWS), and the tumor was completely resected. Immunohistochemical examination revealed that the tumor was positive for D2-40 and α-smooth muscle actin, but negative for c-kit, discovered on gastrointestinal stromal tumor-1, desmin, S100, Melan-A, signal transducer and activator of transcription 6, insulinoma-associated protein 1, CXCL13, ETS transcription factor, follicular dendritic cell, anaplastic lymphoma kinase, human melanoma black, h-caldesmon, and CD1a, 10, 21, 23, 31, 34, 68, and 163. Approximately, 1–2% of the tumor cell nuclei were Ki-67-positive. Finally, we diagnosed the tumor as a plexiform fibromyxoma. In conclusion, NEWS is an effective method for the treatment of SMTs with a diameter of <3 cm.

Published
2022
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28. Tenecteplase versus alteplase for large vessel occlusion recanalization (T-FLAVOR): Trial protocol

Author

Kawano, Hiroyuki, Hirano, Teruyuki, Inoue, Manabu, Fukuda-Doi, Mayumi, Iwasaki, Koji, Omae, Katsuhiro, Tanaka, Kanta, Yamamoto, Haruko, Koga, Masatoshi, Sakai, Nobuyuki, Nagao, Takehiko, Sasaki, Makoto, Hayakawa, Naoki, and Toyoda, Kazunori

Abstract

Background Tenecteplase has higher fibrin specificity with a longer half-life and the potential to achieve higher rates of recanalization than alteplase. A critical limitation of tenecteplase is no commercial use in Japan and no experience with its administration to Japanese patients.Hypothesis Tenecteplase is superior to alteplase in achieving recanalization on the initial angiogram when administered ≤4.5-hour of stroke onset in patients planned for mechanical thrombectomy (MT) in Japan where alteplase at the unique dose of 0.6mg/kg is officially used.Methods The Tenecteplase versus alteplase For LArge Vessel Occlusion Recanalization (T-FLAVOR) trial is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, masked-endpoint, superiority study. Eligibility criteria include acute ischemic stroke with pre-stroke modified Rankin Scale score ≤3 and large vessel occlusion (internal carotid artery, middle cerebral artery, or basilar artery) eligible for intravenous thrombolysis ≤4.5-hour and MT ≤6-hour of stroke onset. After completing the safety confirmation phase involving three patients who received non-masked tenecteplase (0.25 mg/kg), 220 patients will be randomized to two groups (1:1), intravenous alteplase (0.6mg/kg,n= 110) or tenecteplase (0.25mg/kg, n= 110), prior to MT.Outcomes In the safety confirmation phase, the primary outcome is symptomatic intracranial hemorrhage (sICH) ≤24-36-hour. In the randomized, comparative phase, the primary efficacy outcome is substantial angiographic reperfusion (mTICI grade 2b/2c/3) or absence of retrievable thrombus on the initial angiogram. The primary safety outcome is sICH ≤24-36-hour and 90-day mortality.Discussion T-FLAVOR may help determine if tenecteplase should be recommended as a routine clinical strategy before MT for Japanese stroke patients.Trial registration jRCTs051210055

Published
2022
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29. The return of individual genomic results to research participants: design and pilot study of Tohoku Medical Megabank Project

Author

Kawame, Hiroshi, Fukushima, Akimune, Fuse, Nobuo, Nagami, Fuji, Suzuki, Yoichi, Sakurai-Yageta, Mika, Yasuda, Jun, Yamaguchi-Kabata, Yumi, Kinoshita, Kengo, Ogishima, Soichi, Takai, Takako, Kuriyama, Shinichi, Hozawa, Atsushi, Nakaya, Naoki, Nakamura, Tomohiro, Minegishi, Naoko, Sugawara, Junichi, Suzuki, Kichiya, Tomita, Hiroaki, Uruno, Akira, Kobayashi, Tomoko, Aizawa, Yayoi, Tokutomi, Tomoharu, Yamamoto, Kayono, Ohneda, Kinuko, Kure, Shigeo, Aoki, Yoko, Katagiri, Hideki, Ishigaki, Yasushi, Sawada, Shojiro, Sasaki, Makoto, and Yamamoto, Masayuki

Abstract

Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results, we extracted the potential challenges and obstacles. Major challenges include the determination of genes/disorders based on the current medical system in Japan, the storage of results, prevention of misunderstanding, and collaboration of medical professionals. To overcome these challenges, we plan to conduct multilayer pilot studies, which deal with different disorders/genes. We finally chose familial hypercholesterolemia (FH) as a target disease for the first pilot study. Of the 665 eligible candidates, 33.5% were interested in the pilot study and provided consent after an educational “genetics workshop” on the basic genetics and medical facts of FH. The genetics professionals disclosed the results to the participants. All positive participants were referred to medical care, and a serial questionnaire revealed no significant psychosocial distress after the disclosure. Return of genomic results to research participants was implemented using a well-prepared protocol. To further elucidate the impact of different disorders, we will perform multilayer pilot studies with different disorders, including actionable pharmacogenomics and hereditary tumor syndromes.

Published
2022
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31. Magnetic Resonance Imaging-Guided Thrombolysis (0.6 mg/kg) Was Beneficial for Unknown Onset Stroke Above a Certain Core Size: THAWS RCT Substudy.

Author

Toyoda, Kazunori, Inoue, Manabu, Yoshimura, Sohei, Yamagami, Hiroshi, Sasaki, Makoto, Fukuda-Doi, Mayumi, Kimura, Kazumi, Asakura, Koko, Miwa, Kaori, Kanzawa, Takao, Ihara, Masafumi, Kondo, Rei, Shiozawa, Masayuki, Ohtaki, Masafumi, Kamiyama, Kenji, Itabashi, Ryo, Iwama, Toru, Aoki, Junya, Minematsu, Kazuo, and Yamamoto, Haruko

Published
2021
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34. Tu1651 COMPARISON OF THE FINDINGS OF A FOOD FREQUENCY QUESTIONNAIRE-BASED SURVEY AND DIET PHOTOGRAPHY IN PATIENTS WITH AND WITHOUT IRRITABLE BOWEL SYNDROME.

Author

Yamamoto, Sayuri, Yamahata, Akiko, MIzuta, Fumi, Haruta, Kayo, Igari, Hiroki, Adachi, Kazunori, Yamaguchi, Yoshiharu, Hamano, Kouichi, Tamura, Yasuhiro, Izumi, Junko, Mano, Mamiko, Izawa, Shinya, Usami, Jun, Ebi, Masahide, Wakita, Yoshinori, Funaki, Yasushi, Ohashi, Wataru, Ogasawara, Naotaka, Sasaki, Makoto, and Sasanabe, Ryujiro

Published
2024
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36. Magnetic Resonance Imaging–Guided Thrombolysis (0.6 mg/kg) Was Beneficial for Unknown Onset Stroke Above a Certain Core Size

Author

Toyoda, Kazunori, Inoue, Manabu, Yoshimura, Sohei, Yamagami, Hiroshi, Sasaki, Makoto, Fukuda-Doi, Mayumi, Kimura, Kazumi, Asakura, Koko, Miwa, Kaori, Kanzawa, Takao, Ihara, Masafumi, Kondo, Rei, Shiozawa, Masayuki, Ohtaki, Masafumi, Kamiyama, Kenji, Itabashi, Ryo, Iwama, Toru, Aoki, Junya, Minematsu, Kazuo, Yamamoto, Haruko, and Koga, Masatoshi

Published
2021
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37. The bleeding with antithrombotic therapy study 2: Rationale, design, and baseline characteristics of the participants

Author

Takagi, Masahito, Tanaka, Kanta, Miwa, Kaori, Sasaki, Makoto, Koga, Masatoshi, Hirano, Teruyuki, Kamiyama, Kenji, Yagita, Yoshiki, Nagakane, Yoshinari, Hoshino, Haruhiko, Terasaki, Tadashi, Yakushiji, Yusuke, Kudo, Kohsuke, Ihara, Masafumi, Yoshimura, Sohei, Yamaguchi, Yoshitaka, Shiozawa, Masayuki, and Toyoda, Kazunori

Abstract

Aims The bleeding risk of current antithrombotic strategies in clinical settings, including recently developed agents, needs to be clarified.Methods and Design In an investigator-initiated, prospective, multicentre, observational study, patients with cerebrovascular or cardiovascular diseases who were taking oral antiplatelet or anticoagulant agents were enrolled. Compulsory multimodal magnetic resonance images were acquired at baseline to assess cerebral small vessel disease. Six-month follow-up will be performed for two years. The primary outcome is major bleeding as defined by the International Society on Thrombosis and Hemostasis.Results Between October 2016 and March 2019, 5306 patients (71.7 ± 11.2 years old, 1762 women) were enrolled. Previous intracranial haemorrhage was documented in 181 patients (3.4%), cerebrovascular disease (including asymptomatic) requiring antithrombotic therapy in 5006 patients (94.3%), and atrial fibrillation in 1061 patients (20.0%). At entry, 3726 patients (70.2%) were taking antiplatelet agents alone, including 551 (10.4%) using dual antiplatelet agents, 1317 (24.8%) taking anticoagulants alone, and the remaining 263 (5.0%) taking both. The leading antiplatelet agent was clopidogrel (2014 patients), and the leading combination of dual antiplatelet medication was clopidogrel plus aspirin (362). Use of direct oral anticoagulants (1029 patients, 19.4%) exceeded warfarin use (554, 10.4%). The number of pivotal bleeding events exceeded 200 in April 2020.Conclusions This study is expected to provide the incidence of bleeding complications of recent oral antithrombotics in clinical practice and identify their associations with underlying small vessel disease and other biomarkers. Novel risk stratification models for bleeding risk will be able to be created based on the study results.

Published
2020
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38. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Author

Thomalla, Götz, Boutitie, Florent, Ma, Henry, Koga, Masatoshi, Ringleb, Peter, Schwamm, Lee H, Wu, Ona, Bendszus, Martin, Bladin, Christopher F, Campbell, Bruce C V, Cheng, Bastian, Churilov, Leonid, Ebinger, Martin, Endres, Matthias, Fiebach, Jochen B, Fukuda-Doi, Mayumi, Inoue, Manabu, Kleinig, Timothy J, Latour, Lawrence L, Lemmens, Robin, Levi, Christopher R, Leys, Didier, Miwa, Kaori, Molina, Carlos A, Muir, Keith W, Nighoghossian, Norbert, Parsons, Mark W, Pedraza, Salvador, Schellinger, Peter D, Schwab, Stefan, Simonsen, Claus Z, Song, Shlee S, Thijs, Vincent, Toni, Danilo, Hsu, Chung Y, Wahlgren, Nils, Yamamoto, Haruko, Yassi, Nawaf, Yoshimura, Sohei, Warach, Steven, Hacke, Werner, Toyoda, Kazunori, Donnan, Geoffrey A, Davis, Stephen M, Gerloff, Christian, Acosta, Boris Raul, Aegidius, Karen, Albiker, Christian, Alegiani, Anna, Almendrote, Miriam, Alonso, Angelika, Althaus, Katharina, Amarenco, Pierre, Amiri, Hemasse, Anders, Bettina, Aniculaesei, Adriana, Appleton, Jason, Arenillas, Juan, Back, Christina, Bähr, Christian, Bardutzky, Jürgen, Baronnet-Chauvet, Flore, Bathe-Peters, Rouven, Bayer-Karpinska, Anna, Becerra, Juan L., Beck, Christoph, Belchí Guillamon, Olga, Benoit, Amandine, Berhoune, Nadia, Bindila, Daniela, Birchenall, Julia, Blanc-Lasserre, Karine, Blanco Gonzales, Miguel, Bobinger, Tobias, Bodechtel, Ulf, Bodiguel, Eric, Bojaryn, Urszula, Bonnet, Louise, Bouamra, Benjamin, Bourgeois, Paul, Boutitie, Florent, Breuer, Lorenz, Breynaert, Ludovic, Broughton, David, Brouns, Raf, Brugirard, Sébastian, Bruneel, Bart, Buggle, Florian, Cakmak, Serkan, Calleja, Ana, Calvet, David, Carrera, David, Chen, Hsin-Chieh, Cheng, Bastian, Cheripelli, Bharath, Cho, Tae-Hee, Choe, Chi-un, Choy, Lillian, Christensen, Hanne, Ciatipis, Mareva, Cloud, Geoffrey, Cogez, Julien, Cortijo, Elisa, Crozier, Sophie, Damgaard, Dorte, Dani, Krishna, De Coene, Beatrijs, De Hollander, Isabel, De Keyser, Jacques, De Klippel, Nina, De Maeseneire, Charlotte, De Smedt, Ann, del Mar Castellanos Rodrigo, Maria, Deltour, Sandrine, Demeestere, Jelle, Derex, Laurent, Desfontaines, Philippe, Dittrich, Ralf, Dixit, Anand, Dobbels, Laurens, Domigo, Valérie, Dorado, Laura, Druart, Charlotte, Dupont, Kristina Hougaard, Dusart, Anne, Dziewas, Rainer, Ebinger, Martin, Ebner, Matthias, Edjali-Goujon, Myriam, Eisele, Philipp, El Tawil, Salwa, Elhfnawy, Ahmed, Endres, Matthias, Etexberria, Ana, Evans, Nicholas, Fandler, Simon, Fazekas, Franz, Felix, Sandra, Fiebach, Jochen B., Fiehler, Jens, Filipov, Alexandra, Filipski, Katharina, Fleischmann, Robert, Foerch, Christian, Ford, Ian, Gaenslen, Alexandra, Galinovic, Ivana, Gancedo, Elena Meseguer, Ganeshan, Ramanan, García Esperón, Carlos, Garrido, Alicia, Gattringer, Thomas, Geraghty, Olivia, Geran, Rohat, Gerloff, Christian, Gerner, Stefan, Godon-Hardy, Sylvie, Göhler, Jos, Golsari, Amir, Gomis, Meritxell, Gorriz, David, Gramse, Verena, Grau, Laia, Griebe, Martin, Guerrero, Cristina, Guerzoglu, Damla, Guettier, Sophie, Guiraud, Vincent, Gumbinger, Christoph, Gunreben, Ignaz, Haertig, Florian, Hametner, Christian, Hanseeuw, Bernard, Hansen, Andreas, Hansen, Jakob, Harbo, Thomas, Harloff, Andreas, Harmel, Peter, Häusler, Karl Georg, Heinen, Florian, Held, Valentin, Hellwig, Simon, Hemelsoet, Dimitri, Hennerici, Michael, Herm, Juliane, Hermans, Sylvia, Hernández, María, Hervas Vicente, Jose, Hjort, Niels, Hobeanu, Cristina, Hobohm, Carsten, Höfner, Elmar, Hohenbichler, Katharina, Hommel, Marc, Hoppe, Julia, Hornberger, Eva, Hoyer, Carolin, Huang, Xuya, Ipsen, Nils, Isern, Irina, Ispierto, Lourdes, Iversen, Helle, Jeppesen, Lise, Jimenez, Marta, Jungehülsing, Jan, Jüttler, Eric, Kalladka, Dheeraj, Kallmünzer, Bernd, Kar, Arindam, Kellert, Lars, Kemmling, André, Kessler, Tobias, Khan, Usman, Klein, Matthias, Kleinschnitz, Christoph, Klockziem, Matti, Knops, Michael, Koehler, Luzie, Koehrmann, Martin, Kohlfürst, Heinz, Kollmar, Rainer, Kraft, Peter, Krause, Thomas, Kristensen, Bo, Kröber, Jan M., Kurka, Natalia, Ladoux, Alexandre, Laloux, Patrice, Lamy, Catherine, Landrault, Emmanuelle, Lauer, Arne, Lebely, Claire, Leempoel, Jonathan, Lees, Kennedy, Leger, Anne, Legrand, Laurence, Lemmens, Robin, Li, Lin, Löbbe, Anna-Mareike, London, Frederic, Lopez-cancio, Elena, Lorenz, Matthias, Louw, Stephen, Lovelock, Caroline, Lozano Sánchez, Manuel, Lucente, Giuseppe, Lückl, Janos, Luna, Alain, Macha, Kosmas, Machet, Alexandre, Mackenrodt, Daniel, Madzar, Dominik, Majoie, Charles, Männer, Anika, Maqueda, Vicky, Marstrand, Jacob, Martinez, Alicia, Marzina, Annika, Mechthouff, Laura, Meden, Per, Meersman, Guy, Meier, Julia, Mellerio, Charles, Menn, Oliver, Meyer, Nadja, Michalski, Dominik, Michels, Peter, Michelsen, Lene, Millán Torne, Monica, Minnerup, Jens, Modrau, Boris, Moeller, Sebastian, Møller, Anette, Morel, Nathalie, Moreton, Fiona, Morin, Ludovic, Moulin, Thierry, Moynihan, Barry, Mueller, Anne K., Muir, Keith W., Mulero, Patricia, Mundiyanapurath, Sibu, Mutzenbach, Johannes, Nagel, Simon, Naggara, Oliver, Nallasivan, Arumugam, Navalpotro, Irene, Nave, Alexander H., Nederkoorn, Paul, Neeb, Lars, Neugebauer, Hermann, Neumann-Haefelin, Tobias, Nighoghossian, Norbert, Oberndorfer, Stefan, Opherk, Christian, Oppel, Lorenz, Oppenheim, Catherine, Orthgieß, Johannes, Ostergaard, Leif, Paindeville, Perrine, Palomeras, Ernest, Panitz, Verena, Patel, Bhavni, Peeters, Andre, Peeters, Dirk, Pellisé, Anna, Pelz, Johann, Pereira, Anthony, Pérez de la Ossa, Natalia, Perry, Richard, Petraza, Salvador, Peysson, Stéphane, Pfeilschifter, Waltraud, Pichler, Alexander, Pierskalla, Alexandra, Pledl, Hans-Werner, Poli, Sven, Pomrehn, Katrin, Poulsen, Marika, Prats, Luis, Presas, Silvia, Prohaska, Elisabeth, Puetz, Volker, Puig, Josep, Puig Alcántara, Josep, Purrucker, Jan, Quenardelle, Veronique, Ramachandran, Sankaranarayanan, Raphaelle, Soulliard, Raposo, Nicolas, Reiff, Tilman, Remmers, Michel, Renou, Pauline, Ribitsch, Martin, Richter, Hardy, Ringleb, Peter, Ritter, Martin, Ritzenthaler, Thomas, Rodier, Gilles, Rodriguez-Regent, Christine, Rodríguez-Yáñez, Manuel, Roennefarth, Maria, Roffe, Christine, Rosenbaum, Sverre, Rosso, Charlotte, Röther, Joachim, Rozanski, Michal, Ruiz de Morales, Noelia, Russo, Francesca, Rutgers, Matthieu, Sagnier, Sharmilla, Samson, Yves, Sánchez, Josep, Sauer, Tamara, Schäfer, Jan H., Schieber, Simon, Schill, Josef, Schlak, Dennis, Schlemm, Ludwig, Schmidt, Sein, Schonewille, Wouter, Schröder, Julian, Schulz, Andreas, Schurig, Johannes, Schwarting, Sönke, Schwarz, Alexander, Schwarzbach, Christopher, Seidel, Matthias, Seiler, Alexander, Sembill, Jochen, Serena Leal, Joaquin, Shetty, Ashit, Sibon, Igor, Simonsen, Claus Z., Singer, Oliver, Sivagnanaratham, Aravinth, Smets, Ide, Smith, Craig, Soors, Peter, Sprigg, Nikola, Spruegel, Maximilian, Stark, David, Steinert, Susanne, Stösser, Sebastian, Stuermlinger, Markus, Swinnen, Bart, Tamazyan, Ruben, Tembl, Jose, Terceno Izaga, Mikel, Thijs, Vincent, Thomalla, Götz, Touze, Emmanuel, Truelsen, Thomas, Turc, Guillaume, Turine, Gaetane, Tütüncü, Serdar, Tyrell, Pippa, Ustrell, Xavier, Vadot, Wilfried, Vallet, Anne-Evelyne, Vallet, Pauline, van den Berg, Lucie, van den Berg, Sophie, van Eendenburg, Cecile, Van Hooff, Robbert-Jan, van Sloten, Isabelle, Vanacker, Peter, Vancaester, Evelien, Vanderdonckt, Patrick, Vandermeeren, Yves, Vanhee, Frederik, Veltkamp, Roland, Vestergaard, Karsten, Viguier, Alain, Vilas, Dolores, Villringer, Kersten, Voget, Dieke, von Schrader, Jörg, von Weitzel, Paul, Warburton, Elisabeth, Weber, Claudia, Weber, Jörg, Wegscheider, Karl, Wegscheider, Mirko, Weimar, Christian, Weinstich, Karin, Weise, Christopher, Weise, Gesa, Willems, Chris, Winder, Klemens, Wittayer, Matthias, Wolf, Marc, Wolf, Martin, Wolff, Valerie, Wollboldt, Christian, Wollenweber, Frank, Wouters, Anke, Yalo, Bertrand, Yger, Marion, Younan, Nadia, Yperzeele, Laetita, Zegarac, Vesna, Zeiner, Pia, Ziemann, Ulf, Zonneveld, Thomas, Zuber, Mathieu, Akutsu, Tsugio, Aoki, Junya, Aoki, Junya, Arakawa, Shuji, Doijiri, Ryosuke, Egashira, Yusuke, Enomoto, Yukiko, Fukuda-Doi, Mayumi, Furui, Eisuke, Furuta, Konosuke, Gotoh, Seiji, Hamasaki, Toshimitsu, Hasegawa, Yasuhiro, Hirano, Teryuki, Homma, Kazunari, Ichijyo, Masahiko, Ide, Toshihiro, Igarashi, Shuichi, Iguchi, Yasuyuki, Ihara, Masafumi, Ikenouchi, Hajime, Inoue, Manabu, Inoue, Tsuyoshi, Itabashi, Ryo, Ito, Yasuhiro, Iwama, Toru, Kamiyama, Kenji, Kamiyoshi, Shoko, Kanai, Haruka, Kanematsu, Yasuhisa, Kanzawa, Takao, Kimura, Kazumi, Kitayama, Jiro, Kitazono, Takanari, Koga, Masatoshi, Kondo, Rei, Kudo, Kohsuke, Kusumi, Masayoshi, Kuwahara, Ken, Matsumoto, Shoji, Matsuoka, Hideki, Mihara, Ban, Minematsu, Kazuo, Miura, Ken, Miwa, Kaori, Morita, Naomi, Mouri, Wataru, Murata, Kayo, Nagakane, Yoshinari, Nakase, Taizen, Ohara, Hiromi, Ohara, Nobuyuki, Ohnishi, Hideyuki, Ohta, Hajime, Ohtaki, Masafumi, Ohtani, Ryo, Ohtsuki, Toshiho, Ohyama, Hideo, Okada, Takashi, Okada, Yasushi, Osaki, Masato, Sakai, Nobuyuki, Sanbongi, Yoshiki, Sasaki, Naoshi, Sasaki, Makoto, Sato, Shoichiro, Seki, Kenta, Shimizu, Wataru, Shiokawa, Yoshiaki, Sozu, Takashi, Suzuki, Junichiro, Suzuki, Rieko, Takagi, Yasushi, Takizawa, Shunya, Tanahashi, Norio, Tanaka, Eijiro, Tanaka, Ryota, Tateishi, Yohei, Terada, Tomoaki, Terasaki, Tadashi, Todo, Kenichi, Tokunaga, Azusa, Toyoda, Kazunori, Tsujino, Akira, Ueda, Toshihiro, Uesaka, Yoshikazu, Uotani, Mihoko, Urabe, Takao, Watanabe, Masao, Yagita, Yoshiki, Yakushiji, Yusuke, Yamamoto, Haruko, Yasui, Keizo, Yonehara, Toshiro, Yoshimura, Sohei, Yoshimura, Shinichi, Aarnio, K., Alemseged, F., Anderson, C., Ang, T., Archer, M.L., Attia, J., Bailey, P., Balabanski, A., Barber, A., Barber, P.A., Bernhardt, J., Bivard, A., Blacker, D., Bladin, C.F., Brodtmann, A., Cadilhac, D., Campbell, B.C.V., Carey, L., Celestino, S., Chan, L., Chang, W.H., ChangI, A., Chen, C.H., Chen, C.-I., Chen, H.F., Chen, T.C., Chen, W.H., Chen, Y.Y., Cheng, C.A., Cheong, E., Chiou, Y.W., Choi, P.M., Chu, H.J., Chuang, C.S., Chung, T.C., Churilov, L., Clissold, B., Connelly, A., Coote, S., Coulton, B., Cowley, E., Cranefield, J., Curtze, S., D'Este, C., Davis, S.M., Day, S., Desmond, P.M., Dewey, H.M., Ding, C., Donnan, G.A., Drew, R., Eirola, S., Field, D., Frost, T., Garcia-Esperon, C., George, K., Gerraty, R., Grimley, R., Guo, Y.C., Hankey, G., Harvey, J., Ho, S.C., Hogan, K., Howells, D., Hsiao, P.M., Hsu, C.H., Hsu, C.T., Hsu, C.-S., Hsu, J.P., Hsu, Y.D., Hsu, Y.T., Hu, C.J., Huang, C.C., Huang, H.Y., Huang, M.Y., Huang, S.C., Huang, W.S., Jackson, D., Jeng, J.S., Jiang, S.K., Kaauwai, L., Kasari, O., King, J., Kleinig, T.J., Koivu, M., Kolbe, J., Krause, M., Kuan, C.W., Kung, W.L., Kyndt, C., Lau, C.L., Lee, A., Lee, C.Y., Lee, J.T., Lee, Y., Lee, Y.C., Levi, C., Levi, C.R., Lien, L.M., Lim, J.C., Lin, C.C., Lin, C.H., Lin, C.M., Lin, D., Liu, C.H., Liu, J., Lo, Y.C., Loh, P.S., Low, E., Lu, C.H., Lu, C.J., Lu, M.K., Ly, J., Ma, H., Macaulay, L., Macdonnell, R., Mackey, E., Macleod, M., Mahadevan, J., Maxwell, V., McCoy, R., McDonald, A., McModie, S., Meretoja, A., Mishra, S., Mitchell, P.J., Miteff, F., Moore, A., Muller, C., Ng, F., Ng, F.C., Ng, J-L., O'Brian, W., O'Collins, V., Oxley, T.J., Parsons, M.W., Patel, S., Peng, G.S., Pesavento, L., Phan, T., Rodrigues, E., Ross, Z., Sabet, A., Sallaberger, M., Salvaris, P., Shah, D., Sharma, G., Sibolt, G., Simpson, M., Singhal, S., Snow, B., Spratt, N., Stark, R., Sturm, J., Sun, M.C., Sun, Y., Sung, P.S., Sung, Y.F., Suzuki, M., Tan, M., Tang, S.C., Tatlisumak, T., Thijs, V., Tiainen, M., Tsai, C.H., Tsai, C.K., Tsai, C.L., Tsai, H.T., Tsai, L.K., Tseng, C.H., Tseng, L.T., Tsoleridis, J., Tu, H., Tu, H.T-H., Vallat, W., Virta, J., Wang, W.C., Wang, Y.T., Waters, M., Weir, L., Wijeratne, T., Williams, C., Wilson, W., Wong, A.A., Wong, K., Wu, T.Y., Wu, Y.H., Yan, B., Yang, F.C., Yang, Y.W., Yassi, N., Yeh, H.L., Yeh, J.H., Yeh, S.J., Yen, C.H., Young, D., Ysai, C.L., Zhang, W.W., Zhao, H., Zhao, L., Althaus-Knaurer, Katharina, Bendszus, Martin, Berrouschot, Jörg, Bluhmki, Erich, Bovi, Paolo, Chatellier, Gilles, Cove, Lynda, Davis, Stephen, Dixit, A., Donnan, Geoffrey, Dziewas, Rainer, Ehrenkrona, Christina, Eschenfelder, Christoph, Fatar, Marc, Francisco Arenillas, Juan, Gruber, Franz, Hacke, Werner, Kala, Lalit, Kapeller, Peter, Kaste, Markku, Kessler, Christof, Köhrmann, Martin, Laage, Rico, Lees, Kennedy R., Leys, Didier, Luna Rodriguez, Alain, Mas, Jean-Louis, Mikulik, Robert, Molina, Carlos, Muddegowda, Girish, Muir, Keith, Niederkorn, Kurt, Nuñez, Xavier, Oppenheim, Catherine, Poli, Sven, Ringleb, Peter, Schellinger, Peter, Schwab, Stefan, Serena, Joaquin, Sobesky, Jan, Steiner, Thorsten, Svenson, Ann-Sofie, Toni, Danilo, Veltkamp, Roland, von Kummer, Rüdiger, Wahlgren, Nils, Wardlaw, Joanna, Betensky, Rebecca A., Boulouis, Gregoire, Carandang, Raphael A., Copen, William A., Cougo, Pedro, Cutting, Shawna, Drake, Kendra, Ford, Andria L., Hallenbeck, John, Harris, Gordon J., Hoesch, Robert, Hsia, Amie, Kase, Carlos, Latour, Lawrence, Lauer, Arne, Lev, Michael H., Muzikansky, Alona, Nagaraja, Nandakumar, Schwamm, Lee H., Searls, Eric, Song, Shlee S., Starkman, Sidney, Warach, Steven, Wu, Ona, Yoo, Albert J., and Zand, Ramin

Abstract

Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Published
2020
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39. Positional repeatability and variation in internal and external markers during volumetric-modulated arc therapy under end-exhalation breath-hold conditions for pancreatic cancer patients

Author

Sasaki, Makoto, Nakamura, Mitsuhiro, Ono, Tomohiro, Ashida, Ryo, Yoshimura, Michio, Nakata, Manabu, Mizowaki, Takashi, and Sugimoto, Naozo

Abstract

The purpose of this study was to assess the positional repeatability of internal and external markers among multiple breath-hold (BH) sessions and evaluate the positional variation of these markers within BH sessions for volumetric-modulated arc therapy (VMAT) for pancreatic cancer patients. A total of 13 consecutive pancreatic cancer patients with an internal marker were enrolled. Single full-arc coplanar VMAT was delivered under end-exhalation BH conditions while monitoring the internal marker with kilovoltage (kV) X-ray fluoroscopy. Positional repeatability of the internal and external markers was determined by the difference between the reference and zero position in all BH sessions, and positional variation was defined by the displacement from the reference position in each BH session during megavolt beam delivery. The overall positional repeatability was 0.6 ± 1.5 mm in the X-axis for the centroid of the internal marker (CoIM), −0.1 ± 2.2 mm in the Y-axis for the CoIM, and 0.8 ± 2.2 mm for the external marker. The frequency of an internal marker position appearing > 2 mm from the reference position in the Y-axis, despite the external marker position being ≤2 mm from the reference position, ranged from 0.0 to 39.9% for each patient. Meanwhile, the proportion of sessions with positional variation ≤2 mm was 93.2 and 98.7% for the CoIM and external marker, respectively. External marker motion can be used as a surrogate for pancreatic tumor motion during BH-VMAT delivery; however, margins of ~5 mm were required to ensure positional repeatability.

Published
2020
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40. Corrosion resistance of HF-treated Mg alloy stent following balloon expansion and its improvement through biodegradable polymer coating

Author

Xu, Wei, Sato, Kensuke, Koga, Yuki, Sasaki, Makoto, and Niidome, Takuro

Abstract

Abstract: Magnesium (Mg) alloy has been actively investigated as a bioresorbable scaffold (BRS) for use as a next-generation stent because of its appropriate mechanical properties and biocompatibility. However, Mg alloy quickly degrades in the physiological environment. Hydrofluoric acid (HF) treatment and surface coating with biodegradable polymer are approaches for enhancing the corrosion resistance of Mg alloy. However, there are no studies that focus on the corrosion behavior of the Mg alloy stent after balloon catheter expansion, which results in mechanical stress and is required for stent placement. In this study, the corrosion behavior of a Mg alloy stent after expansion by a balloon catheter was investigated. Compared with the bare Mg alloy stent, the HF-treated Mg alloy stent showed excellent corrosion resistance without expansion. However, balloon catheter expansion caused small fragments and cracks to appear on the surface of the HF-treated Mg alloy stent and accelerated its corrosion rate. The HF-treated Mg alloy stent was therefore further coated with poly(d,l-lactic acid) (PDLLA). As a result, the high corrosion resistance of the coated stent was maintained after its expansion along with higher biocompatibility for endothelial cell adhesion than the stent without the polymer coating. The HF-treated and PDLLA-coated platform is expected to be a BRS candidate for clinical applications. Graphic abstract:

Published
2020
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41. Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases

Author

Ishigaki, Kazuyoshi, Akiyama, Masato, Kanai, Masahiro, Takahashi, Atsushi, Kawakami, Eiryo, Sugishita, Hiroki, Sakaue, Saori, Matoba, Nana, Low, Siew-Kee, Okada, Yukinori, Terao, Chikashi, Amariuta, Tiffany, Gazal, Steven, Kochi, Yuta, Horikoshi, Momoko, Suzuki, Ken, Ito, Kaoru, Koyama, Satoshi, Ozaki, Kouichi, Niida, Shumpei, Sakata, Yasushi, Sakata, Yasuhiko, Kohno, Takashi, Shiraishi, Kouya, Momozawa, Yukihide, Hirata, Makoto, Matsuda, Koichi, Ikeda, Masashi, Iwata, Nakao, Ikegawa, Shiro, Kou, Ikuyo, Tanaka, Toshihiro, Nakagawa, Hidewaki, Suzuki, Akari, Hirota, Tomomitsu, Tamari, Mayumi, Chayama, Kazuaki, Miki, Daiki, Mori, Masaki, Nagayama, Satoshi, Daigo, Yataro, Miki, Yoshio, Katagiri, Toyomasa, Ogawa, Osamu, Obara, Wataru, Ito, Hidemi, Yoshida, Teruhiko, Imoto, Issei, Takahashi, Takashi, Tanikawa, Chizu, Suzuki, Takao, Sinozaki, Nobuaki, Minami, Shiro, Yamaguchi, Hiroki, Asai, Satoshi, Takahashi, Yasuo, Yamaji, Ken, Takahashi, Kazuhisa, Fujioka, Tomoaki, Takata, Ryo, Yanai, Hideki, Masumoto, Akihide, Koretsune, Yukihiro, Kutsumi, Hiromu, Higashiyama, Masahiko, Murayama, Shigeo, Minegishi, Naoko, Suzuki, Kichiya, Tanno, Kozo, Shimizu, Atsushi, Yamaji, Taiki, Iwasaki, Motoki, Sawada, Norie, Uemura, Hirokazu, Tanaka, Keitaro, Naito, Mariko, Sasaki, Makoto, Wakai, Kenji, Tsugane, Shoichiro, Yamamoto, Masayuki, Yamamoto, Kazuhiko, Murakami, Yoshinori, Nakamura, Yusuke, Raychaudhuri, Soumya, Inazawa, Johji, Yamauchi, Toshimasa, Kadowaki, Takashi, Kubo, Michiaki, and Kamatani, Yoichiro

Abstract

The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P< 9.58 × 10−9). East Asian–specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2(associated with coronary artery disease) and p.V326A of POT1(associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.

Published
2020
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42. Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset

Author

Koga, Masatoshi, Yamamoto, Haruko, Inoue, Manabu, Asakura, Koko, Aoki, Junya, Hamasaki, Toshimitsu, Kanzawa, Takao, Kondo, Rei, Ohtaki, Masafumi, Itabashi, Ryo, Kamiyama, Kenji, Iwama, Toru, Nakase, Taizen, Yakushiji, Yusuke, Igarashi, Shuichi, Nagakane, Yoshinari, Takizawa, Shunya, Okada, Yasushi, Doijiri, Ryosuke, Tsujino, Akira, Ito, Yasuhiro, Ohnishi, Hideyuki, Inoue, Takeshi, Takagi, Yasushi, Hasegawa, Yasuhiro, Shiokawa, Yoshiaki, Sakai, Nobuyuki, Osaki, Masato, Uesaka, Yoshikazu, Yoshimura, Shinichi, Urabe, Takao, Ueda, Toshihiro, Ihara, Masafumi, Kitazono, Takanari, Sasaki, Makoto, Oita, Akira, Yoshimura, Sohei, Fukuda-Doi, Mayumi, Miwa, Kaori, Kimura, Kazumi, Minematsu, Kazuo, and Toyoda, Kazunori

Abstract

Supplemental Digital Content is available in the text.

Published
2020
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43. Differentiation Between Multiple System Atrophy and Other Spinocerebellar Degenerations Using Diffusion Kurtosis Imaging.

Author

Ito, Kenji, Ohtsuka, Chigumi, Yoshioka, Kunihiro, Maeda, Tetsuya, Yokosawa, Suguru, Mori, Futoshi, Matsuda, Tsuyoshi, Terayama, Yasuo, and Sasaki, Makoto

Abstract

Rationale and Objective: Differentiation between multiple system atrophy (MSA) and other spinocerebellar degenerations showing cerebellar ataxia is often difficult. Hence, we investigated whether magnetic resonance diffusion kurtosis imaging (DKI) could detect pathological changes that occur in these patients and be used for differential diagnosis.Methods: Thirty-six subjects (12 patients with MSA accompanied by predominant cerebellar ataxia [MSA-C], 10 patients with spinocerebellar ataxias [SCAs] or sporadic adult-onset ataxia of unknown etiology [SAOA], and 14 healthy controls) were examined using 1.5- or 3-T magnetic resonance scanners. From the DKI data, the mean kurtosis, fractional anisotropy, and mean diffusivity values of the pontine crossing tract (PCT), middle cerebellar peduncle, and cerebellum were automatically measured, and the ratios against the values of the corpus callosum were calculated.Results: We found significant decreases in mean kurtosis and fractional anisotropy ratios in the PCT and middle cerebellar peduncle, and a significant increase in the mean diffusivity ratio in the PCT in the MSA-C group, as compared with the SCA/SAOA and control groups (p < 0.027-0.001). Among these metrics, there were no significant differences in the diagnostic performance. By contrast, the ratios in the cerebellum showed no significant differences between the MSA-C and SCA/SAOA groups but were significantly altered when compared with the controls (p < 0.001).Conclusion: Quantitative DKI analyses can be used to differentiate between patients with MSA-C and those with SCA/SAOA. [ABSTRACT FROM AUTHOR]

Published
2019
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44. Real-world efficacy of adalimumab and infliximab for refractory intestinal Behçet's disease.

Author

Sugimura, Naomi, Mizoshita, Tsutomu, Sugiyama, Tomoya, Togawa, Shozo, Miyaki, Tomokatsu, Suzuki, Taketo, Tanida, Satoshi, Kataoka, Hiromi, and Sasaki, Makoto

Abstract

Anti-tumor necrosis factor-α agents are important for managing refractory intestinal Behçet's disease. Few studies have reported the efficacy of anti-tumor necrosis factor-α monoclonal antibodies for intestinal Behçet's disease due to its rarity. The aim was to examine the efficacy of anti-tumor necrosis factor-α antibodies for intestinal Behçet's disease in real-world practice. This was a retrospective review of medical records at 4 hospitals in Japan. Global gastrointestinal symptom and endoscopic assessment scores were analyzed in intestinal Behçet's disease patients given anti-tumor necrosis factor-α agents at 3 and 12 months after the start of therapy. Of 53 intestinal Behçet's disease patients, 22 received anti-tumor necrosis factor-α monoclonal antibody treatment. At the first line, 14 were given adalimumab, and 8 were given infliximab. After 3 and 12 months of treatment, 7 and 11 patients showed complete response of gastrointestinal symptom scores, respectively, and 5 and 9 showed complete remission of the endoscopic assessment score, respectively. Three patients switched anti-tumor necrosis factor-α agents. Anti-tumor necrosis factor-α monoclonal antibodies are effective for refractory intestinal Behçet's disease in real-world situations. Switching anti-tumor necrosis factor-α agents may be useful for failure of first-line anti-tumor necrosis factor-α therapy in some refractory cases. [ABSTRACT FROM AUTHOR]

Published
2019
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47. Preoperative brain temperature imaging on proton magnetic resonance spectroscopy predicts hemispheric ischemia during carotid endarterectomy for unilateral carotid stenosis with inadequate collateral blood flow.

Author

Tsutsui, Shouta, Nanba, Takamasa, Yoshioka, Yoshichika, Sasaki, Makoto, Fujiwara, Shunrou, Kobayashi, Masakazu, Yoshida, Kenji, Miyoshi, Kenya, Sato, Shinpei, and Ogasawara, Kuniaki

Abstract

Objective Preoperative magnetic resonance (MR) angiography sometimes shows the absence of collateral flow via the circle of Willis. This study examined whether brain temperature (BT) imaging on multi-voxel proton MR spectroscopy after this finding increases the accuracy of predicting hemispheric ischemia during internal carotid artery (ICA) clamping during endarterectomy for patients with symptomatic unilateral carotid stenosis. Methods In 52 patients with ICA stenosis (≥70%) and absence of collateral blood flow via the circle of Willis on preoperative MR angiography, BT imaging was displayed using proton multi-voxel MR spectroscopy. The difference between BTs in the affected and contralateral hemispheres (BTaffected hemisphere − BTcontralateral hemisphere) in the deep white matter of the centrum semiovale was calculated and defined as hemispheric ΔBT. Development of cerebral hemispheric ischemia during ICA clamping was determined from intraoperative electroencephalography (EEG). Results Multivariate analysis revealed that high preoperative hemispheric ΔBT was significantly associated with development of EEG-defined hemispheric ischemia (95% confidence intervals [CIs], 5.376-15.452; p = 0.006). The positive-predictive value for development of EEG-defined hemispheric ischemia was significantly greater for preoperative hemispheric ΔBT following preoperative MR angiography (95%CI, 42-87%) than for preoperative MR angiography alone (95%CI, 13-37%). Conclusions For patients without collateral flow via the circle of Willis, BT imaging increases the predictive accuracy for development of hemispheric ischemia during ICA clamping during CEA. [ABSTRACT FROM AUTHOR]

Published
2018
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48. Endoscopic Resection of a Pedunculated Cavernous Hemangioma of the Sigmoid Colon: A Case Report

Author

Ogasawara, Naotaka, Suzuki, Manami, Adachi, Kazunori, Yamaguchi, Yoshiharu, Yamamoto, Sayuri, Hijikata, Yasutaka, Ebi, Masahide, Funaki, Yasushi, Sasaki, Makoto, and Kasugai, Kunio

Abstract

Hemangiomas are common benign tumors that usually occur on the head and neck in children. However, colonic hemangiomas are rare in clinical practice. Approximately 80% of colonic hemangiomas are of the cavernous type, and morphologically, ≥80% of colonic hemangiomas are sessile and semi-pedunculated. Notably, pedunculated colonic hemangiomas are rare. A 69-year-old woman presented with hematochezia and underwent colonoscopy, which revealed a soft pedunculated submucosal tumor (SMT) measuring 1.5 cm in diameter, in the sigmoid colon. The surface of the SMT resembled the surrounding normal colonic mucosa with regard to color and appearance, with multiple red patches. Narrow-band imaging revealed a few telangiectasias on the surface of the SMT. The lesion could not be definitively diagnosed based on endoscopic findings. Therefore, for more accurate diagnosis, the SMT was removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis. Histopathological examination of the specimen revealed a cavernous hemangioma with a negative resection margin. We report a case of a pedunculated cavernous hemangioma of the sigmoid colon removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis.

Published
2019
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49. Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project

Author

Takahashi, Yuji, Satoh, Mamoru, Ohmomo, Hideki, Tanaka, Fumitaka, Osaki, Takuya, Tanno, Kozo, Nasu, Takahito, Sakata, Kiyomi, Morino, Yoshihiro, Sobue, Kenji, and Sasaki, Makoto

Abstract

AbstractPurpose:Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population.Materials and methods:The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n = 30,193, age = 60.2 ± 11.5 year).Results:Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90–3.89, p < 0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28–3.14, p < 0.001).Conclusions:Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.

Published
2019
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50. A novel approach to predict acute radiation dermatitis in patients with head and neck cancer using a model based on Bayesian probability.

Author

Hamada, Keisuke, Fujibuchi, Toshioh, Arakawa, Hiroyuki, Yokoyama, Yuichi, Yoshida, Naoki, Ohura, Hiroki, Kunitake, Naonobu, Masuda, Muneyuki, Honda, Takeo, Tokuda, Satoru, and Sasaki, Makoto

Abstract

[Display omitted] • Bayesian-probability-based method predicted ARD in head and neck radiation therapy. • ARD grade was predicted using limited patient diagnostic data with normality. • High ARD grade probabilities in the treatment's planning phase were identified. • This ensured preemptive skin care, better patient outcomes, and less side effects. • V 50 provides valuable guidance to radiation oncologists when planning treatment. In this study, we aimed to establish a method for predicting the probability of each acute radiation dermatitis (ARD) grade during the head and neck Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning phase based on Bayesian probability. The skin dose volume >50 Gy (V 50), calculated using the treatment planning system, was used as a factor related to skin toxicity. The empirical distribution of each ARD grade relative to V 50 was obtained from the ARD grades of 119 patients (55, 50, and 14 patients with G1, G2, and G3, respectively) determined by head and neck cancer specialists. Using Bayes' theorem, the Bayesian probabilities of G1, G2, and G3 for each value of V 50 were calculated with an empirical distribution. Conversely, V 50 was obtained based on the Bayesian probabilities of G1, G2, and G3. The empirical distribution for each graded patient group demonstrated a normal distribution. The method predicted ARD grades with 92.4 % accuracy and provided a V 50 value for each grade. For example, using the graph, we could predict that V 50 should be ≤24.5 cm3 to achieve G1 with 70 % probability. The Bayesian probability-based ARD prediction method could predict the ARD grade at the treatment planning stage using limited patient diagnostic data that demonstrated a normal distribution. If the probability of an ARD grade is high, skin care can be initiated in advance. Furthermore, the V 50 value during treatment planning can provide radiation oncologists with data for strategies to reduce ARD. [ABSTRACT FROM AUTHOR]

Published
2023
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