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58. Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE

Author

Weitz, J.I., Haas, S., Ageno, W., Goldhaber, S.Z., Turpie, A.G.G., Goto, S., Angchaisuksiri, P., Nielsen, J.D., Kayani, G., Farjat, A.E., Schellong, S., Bounameaux, H., Mantovani, L.G., Prandoni, P., Kakkar, A.K., Loualidi, A., Colak, A., Bezuidenhout, A., Abdool-Carrim, A., Azeddine, A., Beyers, A., Dees, A., Mohamed, A., Aksoy, A., Abiko, A., Watanabe, A., Krichell, A., Fernandez, A.A., Tosetto, A., Khotuntsov, A., Oropallo, A., Slocombe, A., Kelly, A., Clark, A., Gad, A., Arouni, A., Schmidt, A., Berni, A., Kleiban, A.J., Machowski, A., Kazakov, A., Galvez, A., Lockman, A., Falanga, A., Chauhan, A., Riera-Mestre, A., Mazzone, A., D'Angelo, A., Herdy, A., Kato, A., Salem, A.A.E.E.M., Husin, A., Erdelyi, B., Jacobson, B., Amann-Vesti, B., Battaloglu, B., Wilson, B., Cosmi, B., Francois, B.J., Toufek, B., Hunt, B., Natha, B., Mustafa, B., Kho, B.C.S., Carine, B., Zidel, B., Dominique, B., Christophe, B., Trimarco, B., Luo, C., Cuneo, C.A., Diaz, C.J.S., Schwencke, C., Cader, C., Yavuz, C., Zaidman, C.J., Lunn, C., C. -C., W., Toh, C.H., Chiang, C.-., Elisa, C., Hsia, C.-., Huang, C.-., Kwok, C.-.K., Ward, C., Opitz, C., Jeanneret-Gris, C., C. Y., H., Bidi, C.L., Smith, C., Brauer, C., Lodigiani, C., Francis, C., Wu, C., Staub, D., Theodoro, D., Poli, D., Acevedo, D.-., Adler, D., Jimenez, D., Keeling, D., Scott, D., Imberti, D., Creagh, D., Helene, D.-., Hagemann, D., Le Roux, D., Skowasch, D., Belenky, D., Dorokhov, D., Petrov, D., Zateyshchikov, D., Prisco, D., Moller, D., Kucera, D., Esheiba, E.M., Panchenko, E., Dominique, E., Dogan, E., Kubat, E., Diaz, E.D., Tse, E.W.C., Yeo, E., Hashas, E., Grochenig, E., Tiraferri, E., Blessing, E., Michele, E.O., Usandizaga, E., Porreca, E., Ferroni, F., Nicolas, F., Ayala-Paredes, F., Koura, F., Henry, F., Cosmi, F., Erdkamp, F., Kamalov, G., Dalmau, G.-., Damien, G., Klein, G., Shah, G., Hollanders, G., Merli, G., Plassmann, G., Platt, G., Poirier, G., Sokurenko, G., Haddad, G., Ali, G., Agnelli, G., Gan, G.G., Kaye-Eddie, G., Le Gal, G., Allen, G., Esperon, G.A.L., Jean-Paul, G., Gerofke, H., Elali, H., Burianova, H., Ohler, H.-., Wang, H., Darius, H., Gogia, H.S., Striekwold, H., Gibbs, H., Hasanoglu, H., Turker, H., Franow, H., De Raedt, H., Schroe, H., Eldin, H.S., Zidan, H., Nakamura, H., Kim, H.Y., Lawall, H., Zhu, H., Tian, H., Yhim, H.-., Cate, H., Hwang, H.G., Shim, H., Kim, I., Libov, I., Sonkin, I., Suchkov, I., Song, I.-., Kiris, I., Staroverov, I., Looi, I., De La Azuela Tenorio, I.M., Savas, I., Gordeev, I., Podpera, I., Lee, J.H., Sathar, J., Welker, J., Beyer-Westendorf, J., Kvasnicka, J., Vanwelden, J., Kim, J.Y., Svobodova, J., Gujral, J., Marino, J., Galvar, J.T., Kassis, J., Kuo, J.-., Shih, J.-., Kwon, J.H., Joh, J.H., Park, J.H., Kim, J.S., Yang, J., Krupicka, J., Lastuvka, J., Pumprla, J., Vesely, J., Souto, J.C., Correa, J.A., Duchateau, J., Fletcher, J.P., del Toro, J., Paez, J.G.C., Nielsen, J., Filho, J.D.A., Saraiva, J., Peromingo, J.A.D., Lara, J.G., Fedele, J.L., Surinach, J.M., Chacko, J., Muntaner, J.A., Benitez, J.C.A., Abril, J.M.H., Humphrey, J., Bono, J., Kanda, J., Boondumrongsagoon, J., Yiu, K.H., Chansung, K., Boomars, K., Burbury, K., Kondo, K., Karaarslan, K., Takeuchi, K., Kroeger, K., Zrazhevskiy, K., Svatopluk, K., Shyu, K.-., Vandenbosch, K., Chang, K.-., Chiu, K.-., Jean-Manuel, K., Wern, K.J., Ueng, K.-., Norasetthada, L., Binet, L., Chew, L.P., Zhang, L., Cristina, L.M., Tick, L., Schiavi, L.B., Wong, L.L.L., Borges, L., Botha, L., Capiau, L., Timmermans, L., Lopez, L.E., Ria, L., Blasco, L.M., Guzman, L.A., Cervera, L.F., Isabelle, M., Bosch, M.M., de los Rios Ibarra, M., Fernandez, M.N., Carrier, M., Barrionuevo, M.R., Gamba, M.A.A., Cattaneo, M., Moia, M., Bowers, M., Chetanachan, M., Berli, M.A., Fixley, M., Faghih, M., Stuecker, M., Schul, M., Banyai, M., Koretzky, M., Myriam, M., Gaffney, M.E., Hirano, M., Kanemoto, M., Nakamura, M., Tahar, M., Emmanuel, M., Kovacs, M., Leahy, M., Levy, M., Munch, M., Olsen, M., De Pauw, M., Gustin, M., Van Betsbrugge, M., Boyarkin, M., Homza, M., Koto, M., Abdool-Gaffar, M., Nagib, M.A.F., Dessoki, M.E., Khan, M., Mohamed, M., Kim, M.H., Lee, M.-., Soliman, M., Ahmed, M.S., Bary, M.S.A., Moustafa, M.A., Hameed, M., Kanko, M., Majumder, M., Zubareva, N., Mumoli, N., Abdullah, N.A.N., Makruasi, N., Paruk, N., Kanitsap, N., Duda, N., Nordin, N., Nyvad, O., Barbarash, O., Gurbuz, O., Vilamajo, O.G., Flores, O.N., Gur, O., Oto, O., Marchena, P.J., Carroll, P., Lang, P., Maccallum, P., von Bilderling, P.B., Blombery, P., Verhamme, P., Jansky, P., Bernadette, P., De Vleeschauwer, P., Hainaut, P., Ferrini, P.M., Iamsai, P., Christian, P., Viboonjuntra, P., Rojnuckarin, P., Ho, P., Mutirangura, P., Wells, R., Martinez, R., Miranda, R.T., Kroening, R., Ratsela, R., Reyes, R.L., de Leon, R.F.D., Wong, R.S.M., Alikhan, R., Jerwan-Keim, R., Otero, R., Murena-Schmidt, R., Canevascini, R., Ferkl, R., White, R., Van Herreweghe, R., Santoro, R., Klamroth, R., Mendes, R., Prosecky, R., Cappelli, R., Spacek, R., Singh, R., Griffin, S., S. H., N., Chunilal, S., Middeldorp, S., Nakazawa, S., Toh, S.G., Christophe, S., Isbir, S., Raymundo, S., Ting, S.K., Motte, S., Aktogu, S.O., Donders, S., Cha, S.I., Nam, S.-., Marie-Antoinette, S.-., Maasdorp, S., Sun, S., Wang, S., Essameldin, S.M., Sholkamy, S.M., Kuki, S., Yoshida, S., Matsuoka, S., Mcrae, S., Watt, S., Patanasing, S., Jean-Leopold, S.-., Wongkhantee, S., Bang, S.-., Testa, S., Zemek, S., Behrens, S., Dominique, S., Mellor, S., Singh, S.S.G., Datta, S., Chayangsu, S., Solymoss, S., Everington, T., Abdel-Azim, T.A.A., Suwanban, T., Adademir, T., Hart, T., Beatrice, T., Luvhengo, T., Horacek, T., Zeller, T., Boussy, T., Reynolds, T., Biss, T., Chao, T.-., Casabella, T.S., Onodera, T., Numbenjapon, T., Gerdes, V., Cech, V., Krasavin, V., Tolstikhin, V., Bax, W.A., Malek, W.F.A., W. K., H., Pharr, W., Jiang, W., Lin, W.-., Zhang, W., Tseng, W.-., Lai, W.-., De Backer, W., Haverkamp, W., Yoshida, W., Korte, W., Choi, W., Kim, Y.-., Tanabe, Y., Ohnuma, Y., Mun, Y.-., Balthazar, Y., Park, Y., Shibata, Y., Burov, Y., Subbotin, Y., Coufal, Z., Yang, Z., Jing, Z., Pulmonary Medicine, Clinical Genetics, Internal Medicine, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Diabetes & metabolism, Weitz, J, Haas, S, Ageno, W, Goldhaber, S, Turpie, A, Goto, S, Angchaisuksiri, P, Nielsen, J, Kayani, G, Farjat, A, Schellong, S, Bounameaux, H, Mantovani, L, Prandoni, P, Kakkar, A, GARFIELD-VTE, I, Falanga, A, MUMC+: HVC Trombosezorg (8), RS: Carim - B04 Clinical thrombosis and Haemostasis, MUMC+: HVC Pieken Trombose (9), MUMC+: MA Alg Interne Geneeskunde (9), Interne Geneeskunde, and Biochemie

Subjects
Male, Time Factors, Settore MED/09 - Medicina Interna, 030204 cardiovascular system & hematology, PROPHYLAXIS, 0302 clinical medicine, Recurrence, Risk Factors, Cause of Death, Neoplasms, Prospective Studies, Registries, 030212 general & internal medicine, DEEP-VEIN THROMBOSIS, Cancer, Aged, 80 and over, Venous Thrombosis, Hematology, Incidence (epidemiology), Anticoagulant, Hazard ratio, Middle Aged, Treatment Outcome, Female, CLINICAL-PRACTICE GUIDELINES, Cardiology and Cardiovascular Medicine, Venous thromboembolism, Adult, medicine.medical_specialty, Registry, medicine.drug_class, Hemorrhage, Malignancy, Anticoagulation, Risk Assessment, 03 medical and health sciences, Fibrinolytic Agents, SDG 3 - Good Health and Well-being, Internal medicine, medicine, MANAGEMENT, Humans, cardiovascular diseases, Aged, business.industry, Anticoagulants, medicine.disease, Confidence interval, RISK-FACTORS, Observational study, Pulmonary Embolism, business
Abstract

Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE (ClinicalTrials.gov: NCT02155491) is a prospective, observational study of 10,684 patients with objectively diagnosed VTE from 415 sites in 28 countries. We compared baseline characteristics, VTE treatment patterns, and 1-year outcomes (mortality, recurrent VTE and major bleeding) in 1075 patients with active cancer, 674 patients with a history of cancer, and 8935 patients without cancer. Patients with active cancer and history of cancer were older than cancer-free patients, with median ages of 64.8, 68.9, and 58.4 years, respectively. The most common sites of active cancer were lung (14.5%), colorectal (11.0%), breast (10.6%), and gynaecological (10.3%). Active cancer patients had a higher incidence of upper limb and vena cava thrombosis than cancer-free patients (9.0% vs 4.8% and 5.1% vs 1.4%, respectively), and were more likely to receive parenteral anticoagulation as monotherapy than cancer-free patients (57.8% vs 12.1%), and less likely to receive DOACs (14.2% vs 50.6%). Rates of death, recurrent VTE, and major bleeding were higher in active cancer patients than in cancer-free patients, with hazard ratios (95% confidence intervals) of 14.2 (12.1-16.6), 1.6 (1.2-2.0) and 3.8 (2.9-5.0), respectively. VTE was the second most common cause of death in patients with active cancer or history of cancer. In patients with VTE, those with active cancer are at higher risk of death, recurrence, and major bleeding than those without cancer.

Published
2020

59. Improved prognosis of advanced‐stage extranodal NK/T‐cell lymphoma: results of the NKEA‐Next study.

Author

Fujimoto, A., Miyazaki, K., Taguchi, S., Asano, N., Yakushijin, K., Fujino, T., Munakata, W., Ejima, Y., Hirano, M., Kubota, N., T., Maeda, Takizawa, J., Hiramoto, N., Takeuchi, M., Sakai, R., Fukuhara, N., Yamaguchi, M., and Suzuki, R.

Subjects
HEMATOPOIETIC stem cell transplantation, LYMPHOMAS
Abstract

Although the advent of non-anthracycline-based and L-asparaginase containing chemotherapy has contributed to enhancing the prognosis of ENKL patients, recent clinical results of ENKL patients have not been well assessed. The proportion of patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) was also significantly higher in patients treated with SMILE than the other regimens (65% vs. 18%, I P i < 0.001). B Background: b Extranodal NK/T-cell lymphoma (ENKL) is a particular subtype of lymphoma that is characterized by the expression of multi-drug resistance-associated P-glycoprotein. [Extracted from the article]

Published
2023
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60. Intracellular calcium leak as a therapeutic target for RYR1-related myopathies

Author

Kushnir, A., Todd, J.J., Witherspoon, J.W., Yuan, Q., Reiken, S., Lin, H., Munce, R.H., Wajsberg, B., Melville, Z., Clarke, O.B., Wedderburn-Pugh, K., Wronska, A., Razaqyar, M.S., Chrismer, I.C., Shelton, M.O., Mankodi, A., Grunseich, C., Tarnopolsky, M.A., Tanji, K., Hirano, M., Riazi, S., Kraeva, N., Voermans, N.C., Gruber, A., Allen, C., Meilleur, K.G., Marks, A.R., Kushnir, A., Todd, J.J., Witherspoon, J.W., Yuan, Q., Reiken, S., Lin, H., Munce, R.H., Wajsberg, B., Melville, Z., Clarke, O.B., Wedderburn-Pugh, K., Wronska, A., Razaqyar, M.S., Chrismer, I.C., Shelton, M.O., Mankodi, A., Grunseich, C., Tarnopolsky, M.A., Tanji, K., Hirano, M., Riazi, S., Kraeva, N., Voermans, N.C., Gruber, A., Allen, C., Meilleur, K.G., and Marks, A.R.

Abstract

Contains fulltext : 220671.pdf (Publisher’s version ) (Closed access), RYR1 encodes the type 1 ryanodine receptor, an intracellular calcium release channel (RyR1) on the skeletal muscle sarcoplasmic reticulum (SR). Pathogenic RYR1 variations can destabilize RyR1 leading to calcium leak causing oxidative overload and myopathy. However, the effect of RyR1 leak has not been established in individuals with RYR1-related myopathies (RYR1-RM), a broad spectrum of rare neuromuscular disorders. We sought to determine whether RYR1-RM affected individuals exhibit pathologic, leaky RyR1 and whether variant location in the channel structure can predict pathogenicity. Skeletal muscle biopsies were obtained from 17 individuals with RYR1-RM. Mutant RyR1 from these individuals exhibited pathologic SR calcium leak and increased activity of calcium-activated proteases. The increased calcium leak and protease activity were normalized by ex-vivo treatment with S107, a RyR stabilizing Rycal molecule. Using the cryo-EM structure of RyR1 and a new dataset of > 2200 suspected RYR1-RM affected individuals we developed a method for assigning pathogenicity probabilities to RYR1 variants based on 3D co-localization of known pathogenic variants. This study provides the rationale for a clinical trial testing Rycals in RYR1-RM affected individuals and introduces a predictive tool for investigating the pathogenicity of RYR1 variants of uncertain significance.

Published
2020

61. Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency

Author

Hathazi, D. (Denisa), Griffin, H. (Helen), Jennings, M. J. (Matthew J.), Giunta, M. (Michele), Powell, C. (Christopher), Pearce, S. F. (Sarah F.), Munro, B. (Benjamin), Wei, W. (Wei), Boczonadi, V. (Veronika), Poulton, J. (Joanna), Pyle, A. (Angela), Calabrese, C. (Claudia), Gomez‐Duran, A. (Aurora), Schara, U. (Ulrike), Pitceathly, R. D. (Robert D. S.), Hanna, M. G. (Michael G.), Joost, K. (Kairit), Cotta, A. (Ana), Paim, J. F. (Julia Filardi), Navarro, M. M. (Monica Machado), Duff, J. (Jennifer), Mattman, A. (Andre), Chapman, K. (Kristine), Servidei, S. (Serenella), Marina, A. D. (Adela Della), Uusimaa, J. (Johanna), Roos, A. (Andreas), Mootha, V. (Vamsi), Hirano, M. (Michio), Tulinius, M. (Mar), Giri, M. (Mamta), Hoffmann, E. P. (Eric P.), Lochmüller, H. (Hanns), DiMauro, S. (Salvatore), Minczuk, M. (Michal), Chinnery, P. F. (Patrick F.), Müller, J. S. (Juliane S.), Horvath, R. (Rita), Hathazi, D. (Denisa), Griffin, H. (Helen), Jennings, M. J. (Matthew J.), Giunta, M. (Michele), Powell, C. (Christopher), Pearce, S. F. (Sarah F.), Munro, B. (Benjamin), Wei, W. (Wei), Boczonadi, V. (Veronika), Poulton, J. (Joanna), Pyle, A. (Angela), Calabrese, C. (Claudia), Gomez‐Duran, A. (Aurora), Schara, U. (Ulrike), Pitceathly, R. D. (Robert D. S.), Hanna, M. G. (Michael G.), Joost, K. (Kairit), Cotta, A. (Ana), Paim, J. F. (Julia Filardi), Navarro, M. M. (Monica Machado), Duff, J. (Jennifer), Mattman, A. (Andre), Chapman, K. (Kristine), Servidei, S. (Serenella), Marina, A. D. (Adela Della), Uusimaa, J. (Johanna), Roos, A. (Andreas), Mootha, V. (Vamsi), Hirano, M. (Michio), Tulinius, M. (Mar), Giri, M. (Mamta), Hoffmann, E. P. (Eric P.), Lochmüller, H. (Hanns), DiMauro, S. (Salvatore), Minczuk, M. (Michal), Chinnery, P. F. (Patrick F.), Müller, J. S. (Juliane S.), and Horvath, R. (Rita)

Abstract

Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6‐months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only ~ 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt‐tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.

Published
2020

68. Development of MJ-class HTS SMES for bridging instantaneous voltage dips

Author

Nagaya, S., Shikimachi, K., Ingaki, J., Ioka, S., Oshemochi, K., Ono, M., Hirano, M., Hanai, S., Maruyama, K., and Kurusu, T.

Subjects
High temperature superconductors -- Research, Electrical cables -- Magnetic properties, Magnetic energy storage -- Research, Business, Electronics, Electronics and electrical industries
Abstract

The MJ-class HTS SMES is developed for bridging instantaneous voltage dips using newly developed Bi-2212 cable. Fundamental performance tests are done on bridging instantaneous voltage dips, using a 125 kW resistance and 50 kw motor as imitation loads.

Published
2004

69. Approximate Jacobian control with task-space damping for robot manipulators

Author

Cheah, C.C., Hirano, M., Kawamura, S., and Arimoto, S.

Abstract

In this note, we propose two new approximate Jacobian control laws with task-space damping for setpoint control of robot manipulators. The proposed controllers do not require exact knowledge of the Jacobian matrix and dynamics of the robots. We will show that the end-effector's position converges to a desired position in a finite task space even when the kinematics and Jacobian matrix are uncertain. Experimental results are presented to illustrate the performance of the proposed controllers. Index Terms--Approximate Jacobian, robot control, setpoint control, stability, uncertain kinematics.

Published
2004

87. Prediction of sediment load concentration in rivers using artificial neural network model

Author

Nagy, H.M., Watanabe, K., and Hirano, M.

Subjects
Sediment transport -- Models, River sediments -- Models, Neural networks -- Research, Engineering and manufacturing industries, Science and technology
Abstract

An artificial neural model is used to estimate the natural sediment discharge in rivers in terms of sediment concentration. This is achieved by training the network to extrapolate several natural streams data collected from reliable sources. The selection of water and sediment variables used in the model is based on the prior knowledge of the conventional analyses, based on the dynamic laws of flow and sediment. Choosing an appropriate neural network structure and providing field data to that network for training purpose are addressed by using a constructive back-propagation algorithm. The model parameters, as well as fluvial variables, are extensively investigated in order to get the most accurate results. In verification, the estimated sediment concentration values agree well with the measured ones. The model is evaluated by applying it to other groups of data from different rivers. In general, the new approach gives better results compared to several commonly used formulas of sediment discharge. DOI: 10.1061/(ASCE)0733-9429(2002)128:6(588) CE Database keywords: Sediment transport; Rivers; Neural networks; Sediment discharge.

Published
2002

91. Allogeneic HSCT for mitochondrial neurogastrointestinal encephalomyopathy: the first promising effective treatment option in an otherwise unrelenting progressive disease?: O398

Author

Halter, J., Schüpbach, W. M.M., Casali, C., Elhasid, R., Keith, F., Savage, D., Valcarcel, D., Collin, M., Rovelli, A., Pintos, G., Marotta, G., Sobreira, C., Nachbaur, D., Accarino, A., Beguin, Y., Dotti, M. T., Hammans, S., Illa, I., Mandel, H., Marti, R., Sue, C., Bakker, J., Zoller, H., Chinnery, P., Gratwohl, A., Hirano, M., and Orchard, K.

Published
2011

95. MITOCHONDRIAL DISEASES & METABOLIC MYOPATHIES

Author

Paradas, C., primary, Domínguez-González, C., additional, Madruga-Garrido, M., additional, Hirano, M., additional, Martí, I., additional, Munell, F., additional, Nascimento, A., additional, Olivé, M., additional, Quan, J., additional, Sardina, D., additional, and Martí, R., additional

Published
2020
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96. MITOCHONDRIAL DISEASES & METABOLIC MYOPATHIES

Author

Ali, Q. Abu, primary, Domínguez-González, C., additional, Cohen, B., additional, Berardo, A., additional, Haas, R., additional, Konersman, C., additional, McFarland, R., additional, D'Souza, G., additional, Quan, J., additional, Thompson, B., additional, and Hirano, M., additional

Published
2020
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