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1. Differences in Characteristics Between Physical Frailty Assessments in Chronic Obstructive Pulmonary Disease: A Multicenter Cross-Sectional Observational Study

Author

Tanaka Y, Hanada M, Kitagawa C, Suyama K, Shiroishi R, Rikitomi N, Tsuda T, Utsunomiya Y, Tanaka T, Shingai K, Yanagita Y, and Kozu R

Subjects
cardiovascular health study, short physical performance battery, chronic lung disease, physical function, Diseases of the respiratory system, RC705-779
Abstract

Yasutomo Tanaka,1,2 Masatoshi Hanada,1,2 Chika Kitagawa,3 Kazuaki Suyama,4 Ryota Shiroishi,5 Naoto Rikitomi,3 Toru Tsuda,6 Yoshiaki Utsunomiya,5 Takako Tanaka,1 Kazuya Shingai,1 Yorihide Yanagita,7 Ryo Kozu1,2 1Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 2Department of Rehabilitation Medicine, Nagasaki University Hospital, Nagasaki, Japan; 3Nagasaki Pulmonary Rehabilitation Clinic, Nagasaki, Japan; 4Tagami Hospital, Nagasaki, Japan; 5Utsunomiya Medical Clinic, Fukuoka, Japan; 6Kirigaoka Tsuda Hospital, Fukuoka, Japan; 7Department of Physical Therapy, School of Health Science, Toyohashi Sozo University, Aichi, JapanCorrespondence: Ryo Kozu, Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8520, Japan, Tel/Fax +81 95 819 7963, Email ryokozu@nagasaki-u.ac.jpPurpose: Assessment for frailty is important as it enables timely intervention to prevent or delay poor prognosis in chronic obstructive pulmonary disease (COPD). The aims of this study, in a sample of outpatients with COPD, were to (i) assess the prevalence of physical frailty using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria and the Short Physical Performance Battery (SPPB) and the degree of agreement between the findings of the two assessments and (ii) identify factors associated with the disparity in the results obtained with these instruments.Patients and Methods: This was a multicenter cross-sectional study of individuals with stable COPD enrolled in four institutions. Frailty was assessed using the J-CHS criteria and the SPPB. Weighted Cohen’s kappa (k) statistic was performed to investigate the magnitude of agreement between the instruments. We divided participants into two groups depending on whether there was agreement or non-agreement between the results of the two frailty assessments. The two groups were then compared with respect to their clinical data.Results: A total of 103 participants (81 male) were included in the analysis. The median age and FEV1 (%predicted) were 77 years and 62%, respectively. The prevalence of frailty and pre-frail was 21% and 56% with the J-CHS criteria and 10% and 17% with the SPPB. The degree of agreement was fair (k = 0.36 [95% CI: 0.22– 0.50], P< 0.001). There were no significant differences in the clinical characteristics between the agreement group (n = 44) and the non-agreement group (n = 59).Conclusion: We showed that the degree of agreement was fair with the J-CHS criteria detecting a higher prevalence than the SPPB. Our findings suggest that the J-CHS criteria may be useful in people with COPD with the aim of providing interventions to reverse frailty in the early stages.Keywords: cardiovascular health study, Short Physical Performance Battery, chronic lung disease, physical function

Published
2023

2. Association between airflow limitation severity and reduced bone mineral density in Japanese men

Author

Watanabe K, Onoue A, Kubota K, Higashi N, Hayashi T, Tsuda T, and Omori H

Subjects
chronic obstructive pulmonary disease, comorbidity, bone mineral density, osteoporosis, air flow limitation, pulmonary function, Diseases of the respiratory system, RC705-779
Abstract

Kazuhiko Watanabe,1 Ayumi Onoue,1 Kenichi Kubota,2 Noritaka Higashi,2 Toshinari Hayashi,3 Tohru Tsuda,4 Hisamitsu Omori1 1Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0976, Japan; 2Department of Respiratory Medicine, Japanese Red Cross Kumamoto Health Care, Kumamoto 861-8528, Japan; 3Tokorozawa Respiratory Clinic, Tokorozawa, Saitama, Japan; 4Kirigaoka Tsuda Hospital, Kitakyusyu, Fukuoka, JapanCorrespondence: Hisamitsu OmoriDepartment of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuo-ku Kumamoto, Kumamoto 862-0976, JapanTel +81 96 373 5462Fax +81 96 373 5462Email omorih@gpo.kumamoto-u.ac.jpIntroduction: This study aimed to assess the association between airflow limitation (AL) severity and reduced bone mineral density (BMD) in Japanese men.Subjects and methods: This cross-sectional study included 290 subjects aged over 40 years (mean age 72.0, SD 11.6), who underwent a comprehensive health examination, including spirometry and measurement of BMD at the left femoral neck using dual-energy X-ray absorptiometry (DXA), between 2016 and 2017 at Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of −2.5 SD]), or osteoporosis (YAM ≦ 70% [≦ −2.5 SD]). Reduced BMD was defined as osteopenia, osteoporosis, or medication used for osteoporosis. Logistic regression analysis was used to assess the association between AL severity and the reduced BMD.Results: The prevalence of reduced BMD in subjects with moderate-to-severe AL (76.2%) was significantly higher than in those without AL (47.9%) (p=0.030). In logistic regression models adjusted for age, body mass index, pack-years, physical activity, and alcohol drinking, the risk of reduced BMD (odds ratio: 3.87; 95% confidence interval: 1.20–12.49; p=0.024) was significantly higher in subjects with moderate-to-severe AL than in those with normal pulmonary function.Conclusion: Present results suggest that reduced BMD is associated with AL severity in Japanese men.Keywords: chronic obstructive pulmonary disease, comorbidity, bone mineral density, osteoporosis, airflow limitation, pulmonary function

Published
2019

3. Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial

Author

Machida K, Kawayama T, Kinoshita M, Ichinose M, Tsuda T, Takata S, Koto H, Yoshida M, Ashihara Y, Kawashima M, Suna H, and Inoue H

Subjects
anti-cholinergic, bronchodilator, imidafenacin, lung function, COPD, Diseases of the respiratory system, RC705-779
Abstract

Kentaro Machida,1,* Tomotaka Kawayama,2,* Masaharu Kinoshita,3,* Masakazu Ichinose,4 Tohru Tsuda,5 Shohei Takata,6 Hiroshi Koto,7 Makoto Yoshida,8 Yoshinori Ashihara,9 Masaru Kawashima,10 Hideaki Suna,10 Hiromasa Inoue1 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; 2Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan; 3Nagata Hospital, Yanagawa 832-0059, Japan; 4Department of Respiratory Medicine, Tohoku University, Graduate School of Medicine, Sendai 980-8574, Japan; 5Kirigaoka Tsuda Hospital, Kitakyushu 802-0052 Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka-Higashi Medical Center, Koga 811-3195, Japan; 7Division of Respiratory Medicine, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka 815-8588, Japan; 8Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka 811-1394, Japan; 9Division of Respiratory Medicine, Oita Nakamura Hospital, Oita 870-0022, Japan; 10ONO Pharmaceutical Co. Ltd., Osaka 541-8564, Japan*These authors contributed equally to this workCorrespondence: Hiromasa InoueDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, JapanTel +81 99 275 6481Fax +81 99 275 6482Email inoue-pulm@umin.netBackground: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers.Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and

Published
2019

4. Impaired comprehension of metaphorical expressions in very mild Alzheimer’s disease

Author

Fujimoto N, Nakamura H, Tsuda T, Wakutani Y, and Takao T

Subjects
nonliteral language, simile, multiple-choice, pragmatics, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Norimasa Fujimoto,1 Hikaru Nakamura,2 Tetsuya Tsuda,3 Yosuke Wakutani,4 Takeo Takao4 1Department of Rehabilitation, Kurashiki Heisei Hospital, Kurashiki, Okayama, Japan; 2Department of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama, Japan; 3Department of Communication Sciences and Disorders, Prefectural University of Hiroshima, Mihara, Hiroshima, Japan; 4Department of Neurology, Kurashiki Heisei Hospital, Kurashiki, Okayama, Japan Background: Brain-damaged patients often have difficulty understanding non-literal language. However, whether patients with Alzheimer’s disease (AD) have comprehension deficits of metaphorical expressions, in contrast with non-metaphorical (literal) expressions, remains unclear.Patients and methods: The subjects were 40 AD patients; 20 had mild AD (17–23 points on the Mini-Mental State Examination [MMSE]), and 20 had very mild AD (≥24 points). Twenty normal elderly controls were also enrolled as a control group. Thirty sentences that contained novel similes (Items) were prepared. For each Item, four explanatory choices, consisting of one correct response and three foils, were provided. The participants were asked to choose the written statement that best represented the Item’s meaning. In addition, all the subjects completed the Token Test.Results: The patients with mild AD had significantly lower scores than the normal controls on both the simile comprehension test and the Token Test. However, the patients with very mild AD exhibited significantly lower scores on the simile comprehension test, but not on the Token Test. The distributions of error types for the simile test differed between the mild AD group and the other groups. The mild AD patients made more errors that were “far” from the correct responses.Conclusion: Patients with AD are more likely to have comprehension deficits of metaphorical expressions than comprehension deficits of non-metaphorical expressions. Pragmatic language dysfunction may precede formal language dysfunction during the progression of AD.Keywords: non-literal language, simile, multiple-choice, pragmatics

Published
2019

5. Electrochemistry of vanadium(II) and the electrodeposition of aluminum-vanadium alloys in the aluminum chloride-1-ethyl-3-methylimidazolium chloride molten salt

Author

Tsuda T. and Hussey C.L.

Subjects
electrochemistry, vanadium, aluminium-vanadium alloys, molten salts, Mining engineering. Metallurgy, TN1-997
Abstract

The electrochemical behavior of vanadium(II) was examined in the 66.7-33.3 mole percent aluminum chloride-1-ethyl-3-methylimidazolium chloride molten salt containing dissolved VCl2 at 353 K. Voltammetry experiments revealed that V(II) could be electrochemically oxidized to V(III) and V(IV). However at slow scan rates the V(II)/V(III) electrode reaction is complicated by the rapid precipitation of V(III) as VCl3. The reduction of V(II) occurs at potentials considerably negative of the Al(III)/Al electrode reaction, and Al-V alloys cannot be electrodeposited from this melt. However electrodeposition experiments conducted in VCl2-saturated melt containing the additive, 1-ethyl-3-methylimidazolium tetrafluoroborate, resulted in Al-V alloys. The vanadium content of these alloys increased with increasing cathodic current density or more negative applied potentials. X-ray analysis of Al-V alloys that were electrodeposited on a rotating copper wire substrate indicated that these alloys did not form or contain an intermetallic compound, but were non-equilibrium or metastable solid solutions. The chloride-pitting corrosion properties of these alloys were examined in aqueous NaCl by using potentiodynamic polarization techniques. Alloys containing ~10 a/o vanadium exhibited a pitting potential that was 0.3 V positive of that for pure aluminum.

Published
2003
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6. Order/disorder in electrodeposited aluminum-titanium alloys

Author

Stafford G.R., Tsuda T., and Hussey C.L.

Subjects
Mining engineering. Metallurgy, TN1-997
Abstract

The composition, morphology, and crystallographic microstructure of Al-Ti alloys electrodeposited from two different chloroaluminate molten salt electrolytes were examined. Alloys containing up to 28 % atomic fraction Ti were electrodeposited at 150 °C from 2:1 AlCl3-NaCl with controlled additions of Ti2+. The apparent limit on alloy composition is proposed to be due to a mechanism by which Al3Ti forms through the reductive decomposition of [Ti(AlCl4)3]-. The composition of Al-Ti alloys electrodeposited from the AlCl3-EtMeImCl melt at 80 °C is limited by the diffusion of Ti2+ to the electrode surface. Alloys containing up to 18.4 % atomic fraction Ti are only obtainable at high Ti2+ concentrations in the melt and low current densities. Alloys electrodeposited from the higher temperature melt have an ordered L12 crystal structure while alloys of similar composition but deposited at lower temperature are disordered fcc. The appearance of antiphase boundaries in the ordered alloys suggests that the deposit may be disordered initially and then orders in the solid state, subsequent to the charge transfer step and adatom incorporation into the lattice. This is very similar to the disorder-trapping observed in rapidly solidified alloys. The measured domain size is consistent with a mechanism of diffusion-controlled doman growth at the examined deposition temperatures and times.

Published
2003
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7. Integrated ICN and CDN Slice as a Service

Author

Benkacem, Ilias, Bagaa, M., Taleb, T., Nguyen, Q. N., Tsuda, T., and Sato, T.

Subjects
Computer Science - Networking and Internet Architecture
Abstract

In this article, we leverage Network Function Virtualization (NFV) and Multi-Access Edge Computing (MEC) technologies, proposing a system which integrates ICN (Information-Centric Network) with CDN (Content Delivery Network) to provide an efficient content delivery service. The proposed system combines the dynamic CDN slicing concept with the NDN (Named Data Network) based ICN slicing concept to avoid core network congestion. A dynamic CDN slice is deployed to cache content at optimal locations depending on the nature of the content and the geographical distributions of potential viewers. Virtual cache servers, along with supporting virtual transcoders, are placed across a cloud belonging to multiple-administrative domains, forming a CDN slice. The ICN slice is, in turn, used for the regional distribution of content, leveraging the name-based access and the autonomic in-network content caching. This enables the delivery of content from nearby network nodes, avoiding the duplicate transfer of content and also ensuring shorter response times. Our experiments demonstrate that integrated ICN/CDN is better than traditional CDN in almost all aspects, including service scalability, reliability, and quality of service.

Published
2022

8. Gate-tunable spin-charge conversion and a role of spin-orbit interaction in graphene

Author

Dushenko, S., Ago, H., Kawahara, K., Tsuda, T., Kuwabata, S., Takenobu, T., Shinjo, T., Ando, Y., and Shiraishi, M.

Subjects
Condensed Matter - Materials Science, Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

The small spin-orbit interaction of carbon atoms in graphene promises a long spin diffusion length and potential to create a spin field-effect transistor. However, for this reason, graphene was largely overlooked as a possible spin-charge conversion material. We report electric gate tuning of the spin-charge conversion voltage signal in a single-layer graphene. Using spin pumping from yttrium iron garnet ferrimagnetic insulator and ionic liquid top gate we determined that the inverse spin Hall effect is the dominant spin-charge conversion mechanism in a single-layer graphene. From the gate dependence of the electromotive force we showed dominance of the intrinsic over Rashba spin-orbit interaction: a long-standing question in graphene research., Comment: 13 pages, 5 figures (to appear in Phys. Rev. Lett.)

Published
2016
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10. P2.23-02 Prospective Observational Study of Cachexia and Its Effect on Systemic Therapy in Patients with Previously-Untreated Advanced NSCLC (NEJ050A)

Author

Furuya, N., primary, Miura, K., additional, Shukuya, T., additional, Morita, R., additional, Kisohara, A., additional, Mouri, A., additional, Watanabe, S., additional, Tanaka, H., additional, Hirata, A., additional, Hakozaki, T., additional, Hamai, K., additional, Matsumoto, N., additional, Watanabe, K., additional, Ashinuma, H., additional, Miyauchi, E., additional, Sugano, K., additional, Hosokawa, S., additional, Asahina, H., additional, Koyama, R., additional, Tamura, T., additional, Kanaji, N., additional, Nakagawa, T., additional, Kamimura, M., additional, Isobe, K., additional, Tsuda, T., additional, Morita-Tanaka, S., additional, Arai, D., additional, Nagashima, H., additional, Jingu, D., additional, Ibe, T., additional, Usui, K., additional, Matsumoto, M., additional, Masui, Y., additional, Miyazaki, M., additional, Morita, S., additional, Kobayashi, K., additional, and Takahashi, K., additional

Published
2023
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16. 1467 Highly concentrated trehalose induces prohealing senescence-like state in fibroblasts via CDKN1A/p21

Author

Muto, J., primary, Fukuda, S., additional, Watanabe, K., additional, Dai, X., additional, Tsuda, T., additional, Kiyoi, T., additional, Kameda, K., additional, Kawakami, R., additional, Mori, H., additional, Shiraishi, K., additional, Murakami, M., additional, Imamura, T., additional, Higashiyama, S., additional, Fujisawa, Y., additional, Mizukami, Y., additional, and Sayama, K., additional

Published
2023
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17. Ca+ ion layer observed by a resonance scattering lidar at Syowa in the Antarctic

Author

Ejiri, M., Nishiyama, T., Tsuda, T., Tsutsumi, M., Tsuno, K., Makoto, A., Takuya D, K., Ogawa, T., Satoshi, W., and Nakamura, T.

Abstract

Layers of metal ions in the mesosphere and lower-thermosphere (MLT) are produced by meteoric ablation. The meteoric metal ions have relatively long chemical lifetime in the MLT region and behave as plasma affected by neutral atmosphere dynamics. Ca+ is one of meteoric metal ion and only one ion, which can be measured its vertical profile from the ground by a lidar sounding. Ca+ lidar observations have been conducted at the low and mid latitudes in the northern hemisphere only. A resonance scattering lidar developed by the National Institute of Polar Research (NIPR) was installed at Syowa (69S, 40E), Antarctic in 2017 and successfully obtained Ca+ density profiles 6 nights in total in Spring of 2017 and 2018. The averaged Ca+ layer observed at Syowa were with a FWHM of ~7 km, peak altitude of ~94 km, and peak density of ~10 cm-3. The Ca+ layers were observed in the main supply height region by meteor, however the layer was not always existing but sometimes disappeared. Temporal variation of Ca+ density is compared with meteoric, geomagnetic, and gravity wave activities. In this presentation, we will discuss a main reason of Ca+ layer disappearance with considering chemical lifetime of Ca+ below 100 km., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Published
2023
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18. Initial results of short-wavelength infrared imaging spectrograph and monochromatic imager, NIRAS-2 and NIRAC, installed at KHO/UNIS, Longyearbyen, Svalbard (78.1°N, 16.0°E)

Author

Nishiyama, T., Kagatani, M., Furutachi, S., Ogawa, Y., Tsuda, T., Iwasa, Y., Tsuchiya, F., Dalin, P., Nozawa, S., and Sigernes, F.

Abstract

A new ground-based optical observation of aurora and airglow in short-wavelength infrared (SWIR) of 1.05-1.35 μm has been initiated at The Kjell Henriksen Observatory (KHO), Longyearbyen (78.1°N, 16.0°E) since November 2022. Two state-of-the-art instruments, a SWIR imaging spectrograph and a monochromatic imager, are being operated to focus on study on dayside magnetosphere-ionosphere-atmosphere coupling processes in the high polar regions.The 2-D imaging spectrograph, NIRAS-2, measures SWIR auroral emissions such as N2+Meinel band (0,0), N21st Positive bands (0,1), and OI- line with time resolution of 30 seconds. Using high spectral resolution mode, N2+ ion rotational temperature would be estimated. For upper mesosphere, OH (8,5) band was measured and its rotational temperature can be estimated with10-min resolutions and errors less than 5 K. In addition, one more important thing is that this OH emission band is almost completely uncontaminated by aurora. On the other hand, the brand-new SWIR camera, NIRAC, can visualize two-dimensional structures of not only aurora (N2+) but also even weak airglow (OH) with a cadence of less than 30 seconds. This is the monochromatic imaging of SWIR aurora for the first time so far, and the NIRAC is used as a twin instrument to the NIRAS-2 to help in interpreting meridional scan data obtained from the NIRAS-2. Taking geographical advantage of the observatory, 24-hours continuous observations can be expected near the winter solstice. Initial results of NIRAS-2 and NIRAC are presented and then we will discuss the observational strategies and future collaborations., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Published
2023
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20. Usefulness of echocardiographic parameters in predicting the incidence of ischemic stroke in Japanese patients with non-valvular atrial fibrillation

Author

Tezuka, Y, primary, Akao, M, additional, Suzuki, S, additional, Yamashita, T, additional, Kodani, E, additional, Tsuda, T, additional, Hayashi, K, additional, Furusho, H, additional, Sawano, M, additional, Fukuda, K, additional, Nakai, M, additional, Sasahara, Y, additional, Miyamoto, Y, additional, Tomita, H, additional, and Okumura, K, additional

Published
2022
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30. Solution-Processable Hole-Transporting Polymers: Synthesis, Doping Study and Crosslinking Induced by UV-Irradiation or Huisgen-Click Cycloaddition

Author

Caldera-Cruz, E., Zhang, K., Tsuda, T., Tkachov, R., Beryozkina, T., Kiriy, N., Voit, B., Kiriy, A., Caldera-Cruz, E., Zhang, K., Tsuda, T., Tkachov, R., Beryozkina, T., Kiriy, N., Voit, B., and Kiriy, A.

Abstract

A pair of hole-conducting polymers comprising 3,6-linked carbazole and meta-linked anisole derivatives having solubilizing moieties to enable their solution processability, and complementarily reactive side-groups (azide and alkyne) for cross-linking, are synthesized and characterized. The polymers can be cross-linked either by thermal annealing at relatively low temperatures in the 85–110 °C range, or by UV irradiation. A general applicability of the latter for a photolithographic patterning of the hole conducting polymer is proven. The polymers have an ionization potential (IP) of 5.8 eV, close to the IP of a small molecule hole-conductor tris(4-carbazoyl-9-ylphenyl)amine (TCTA). In combination with a strong dopant hexacyano-trimethylene-cyclopropane (CN6CP), but not with commercial 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), the polymers can be efficiently p-doped to increase their conductivity by 5–6 orders of magnitude, as measured in devices with a lateral setup. Taken together, these characteristics suggest that the synthesized polymers are promising candidates for their use in solution-processable organic light-emitting diodes as hole-injection layer and hole-transporting layer materials, which will be verified in the upcoming work. © 2022 The Authors. Advanced Materials Interfaces published by Wiley-VCH GmbH.

Published
2022

31. Thermospheric wind response to a sudden ionospheric variation in the trough:event at a pseudo-breakup during geomagnetically quiet conditions

Author

Oyama, S.-i. (Shin-ichiro), Vanhamäki, H. (Heikki), Cai, L. (Lei), Aikio, A. (Anita), Rietveld, M. (Michael), Ogawa, Y. (Yasunobu), Raita, T. (Tero), Kellinsalmi, M. (Mirjam), Kauristie, K. (Kirsti), Kozelov, B. (Boris), Shinbori, A. (Atsuki), Shiokawa, K. (Kazuo), Tsuda, T. T. (Takuo T.), Sakanoi, T. (Takeshi), Oyama, S.-i. (Shin-ichiro), Vanhamäki, H. (Heikki), Cai, L. (Lei), Aikio, A. (Anita), Rietveld, M. (Michael), Ogawa, Y. (Yasunobu), Raita, T. (Tero), Kellinsalmi, M. (Mirjam), Kauristie, K. (Kirsti), Kozelov, B. (Boris), Shinbori, A. (Atsuki), Shiokawa, K. (Kazuo), Tsuda, T. T. (Takuo T.), and Sakanoi, T. (Takeshi)

Abstract

The thermospheric wind response to a sudden westward turning of the ion velocity at a high latitude was studied by analyzing data obtained with a Fabry–Perot interferometer (FPI; 630 nm), Dynasonde, and Swarm A & C satellites during a conjunction event. The event occurred during a geomagnetically quiet period (Kp = 0 +) through the night, but some auroral activity occurred in the north. The collocated FPI and Dynasonde measured the thermospheric wind (U) and ionospheric plasma velocity (V), respectively, in the F region at the equatorward trough edge. A notable scientific message from this study is the possible role of thermospheric wind in the energy dissipation process at F-region altitude. The FPI thermospheric wind did not instantly follow a sudden V change due to thermospheric inertia in the F region. At a pseudo-breakup during the event, V suddenly changed direction from eastward to westward within 10 min. U was concurrently accelerated westward, but its development was more gradual than that of V, with U remaining eastward for a while after the pseudo-breakup. The delay of U is attributed to the thermospheric inertia. During this transition interval, U∙V was negative, which would result in more efficient generation of frictional heating than the positive U∙V case. The sign of U∙V, which is related to the relative directions of the neutral wind and plasma drift, is important because of its direct impact on ion-neutral energy exchange during collisions. This becomes especially important during substorm events, where rapid plasma velocity changes are common. The sign of U∙V may be used as an indicator to find the times and locations where thermospheric inertia plays a role in the energy dissipation process.

Published
2022

32. Plasma-neutral gas interactions in various space environments : Assessment beyond simplified approximations as a Voyage 2050 theme

Author

Yamauchi, M., De Keyser, J., Parks, G., Oyama, S. -I, Wurz, P., Abe, T., Beth, A., Daglis, I. A., Dandouras, I., Dunlop, M., Henri, P., Ivchenko, Nickolay, Kallio, E., Kucharek, H., Liu, Y. C. -M, Mann, I., Marghitu, O., Nicolaou, G., Rong, Z., Sakanoi, T., Saur, J., Shimoyama, M., Taguchi, S., Tian, F., Tsuda, T., Tsurutani, B., Turner, D., Ulich, T., Yau, A., Yoshikawa, I., Yamauchi, M., De Keyser, J., Parks, G., Oyama, S. -I, Wurz, P., Abe, T., Beth, A., Daglis, I. A., Dandouras, I., Dunlop, M., Henri, P., Ivchenko, Nickolay, Kallio, E., Kucharek, H., Liu, Y. C. -M, Mann, I., Marghitu, O., Nicolaou, G., Rong, Z., Sakanoi, T., Saur, J., Shimoyama, M., Taguchi, S., Tian, F., Tsuda, T., Tsurutani, B., Turner, D., Ulich, T., Yau, A., and Yoshikawa, I.

Abstract

In the White Paper, submitted in response to the European Space Agency (ESA) Voyage 2050 Call, we present the importance of advancing our knowledge of plasma-neutral gas interactions, and of deepening our understanding of the partially ionized environments that are ubiquitous in the upper atmospheres of planets and moons, and elsewhere in space. In future space missions, the above task requires addressing the following fundamental questions: (A) How and by how much do plasma-neutral gas interactions influence the re-distribution of externally provided energy to the composing species? (B) How and by how much do plasma-neutral gas interactions contribute toward the growth of heavy complex molecules and biomolecules? Answering these questions is an absolute prerequisite for addressing the long-standing questions of atmospheric escape, the origin of biomolecules, and their role in the evolution of planets, moons, or comets, under the influence of energy sources in the form of electromagnetic and corpuscular radiation, because low-energy ion-neutral cross-sections in space cannot be reproduced quantitatively in laboratories for conditions of satisfying, particularly, (1) low-temperatures, (2) tenuous or strong gradients or layered media, and (3) in low-gravity plasma. Measurements with a minimum core instrument package (< 15 kg) can be used to perform such investigations in many different conditions and should be included in all deep-space missions. These investigations, if specific ranges of background parameters are considered, can also be pursued for Earth, Mars, and Venus., QC 20221222

Published
2022
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33. Plasma-neutral gas interactions in various space environments:assessment beyond simplified approximations as a Voyage 2050 theme

Author

Yamauchi, M. (Masatoshi), De Keyser, J. (Johan), Parks, G. (George), Oyama, S.-i. (Shin-ichiro), Wurz, P. (Peter), Abe, T. (Takumi), Beth, A. (Arnaud), Daglis, I. A. (Ioannis A.), Dandouras, I. (Iannis), Dunlop, M. (Malcolm), Henri, P. (Pierre), Ivchenko, N. (Nickolay), Kallio, E. (Esa), Kucharek, H. (Harald), Liu, Y. C. (Yong C.-M.), Mann, I. (Ingrid), Marghitu, O. (Octav), Nicolaou, G. (Georgios), Rong, Z. (Zhaojin), Sakanoi, T. (Takeshi), Saur, J. (Joachim), Shimoyama, M. (Manabu), Taguchi, S. (Satoshi), Tian, F. (Feng), Tsuda, T. (Takuo), Tsurutani, B. (Bruce), Turner, D. (Drew), Ulich, T. (Thomas), Yau, A. (Andrew), Yoshikawa, I. (Ichiro), Yamauchi, M. (Masatoshi), De Keyser, J. (Johan), Parks, G. (George), Oyama, S.-i. (Shin-ichiro), Wurz, P. (Peter), Abe, T. (Takumi), Beth, A. (Arnaud), Daglis, I. A. (Ioannis A.), Dandouras, I. (Iannis), Dunlop, M. (Malcolm), Henri, P. (Pierre), Ivchenko, N. (Nickolay), Kallio, E. (Esa), Kucharek, H. (Harald), Liu, Y. C. (Yong C.-M.), Mann, I. (Ingrid), Marghitu, O. (Octav), Nicolaou, G. (Georgios), Rong, Z. (Zhaojin), Sakanoi, T. (Takeshi), Saur, J. (Joachim), Shimoyama, M. (Manabu), Taguchi, S. (Satoshi), Tian, F. (Feng), Tsuda, T. (Takuo), Tsurutani, B. (Bruce), Turner, D. (Drew), Ulich, T. (Thomas), Yau, A. (Andrew), and Yoshikawa, I. (Ichiro)

Abstract

In the White Paper, submitted in response to the European Space Agency (ESA) Voyage 2050 Call, we present the importance of advancing our knowledge of plasma-neutral gas interactions, and of deepening our understanding of the partially ionized environments that are ubiquitous in the upper atmospheres of planets and moons, and elsewhere in space. In future space missions, the above task requires addressing the following fundamental questions: (A) How and by how much do plasma-neutral gas interactions influence the re-distribution of externally provided energy to the composing species? (B) How and by how much do plasma-neutral gas interactions contribute toward the growth of heavy complex molecules and biomolecules? Answering these questions is an absolute prerequisite for addressing the long-standing questions of atmospheric escape, the origin of biomolecules, and their role in the evolution of planets, moons, or comets, under the influence of energy sources in the form of electromagnetic and corpuscular radiation, because low-energy ion-neutral cross-sections in space cannot be reproduced quantitatively in laboratories for conditions of satisfying, particularly, (1) low-temperatures, (2) tenuous or strong gradients or layered media, and (3) in low-gravity plasma. Measurements with a minimum core instrument package (< 15 kg) can be used to perform such investigations in many different conditions and should be included in all deep-space missions. These investigations, if specific ranges of background parameters are considered, can also be pursued for Earth, Mars, and Venus.

Published
2022

37. Plasma-neutral gas interactions in various space environments: Assessment beyond simplified approximations as a Voyage 2050 theme

Author

Yamauchi, M. De Keyser, J. Parks, G. Oyama, S.-I. Wurz, P. Abe, T. Beth, A. Daglis, I.A. Dandouras, I. Dunlop, M. Henri, P. Ivchenko, N. Kallio, E. Kucharek, H. Liu, Y.C.-M. Mann, I. Marghitu, O. Nicolaou, G. Rong, Z. Sakanoi, T. Saur, J. Shimoyama, M. Taguchi, S. Tian, F. Tsuda, T. Tsurutani, B. Turner, D. Ulich, T. Yau, A. Yoshikawa, I.

Subjects
Physics::Space Physics, Astrophysics::Earth and Planetary Astrophysics
Abstract

In the White Paper, submitted in response to the European Space Agency (ESA) Voyage 2050 Call, we present the importance of advancing our knowledge of plasma-neutral gas interactions, and of deepening our understanding of the partially ionized environments that are ubiquitous in the upper atmospheres of planets and moons, and elsewhere in space. In future space missions, the above task requires addressing the following fundamental questions: (A) How and by how much do plasma-neutral gas interactions influence the re-distribution of externally provided energy to the composing species? (B) How and by how much do plasma-neutral gas interactions contribute toward the growth of heavy complex molecules and biomolecules? Answering these questions is an absolute prerequisite for addressing the long-standing questions of atmospheric escape, the origin of biomolecules, and their role in the evolution of planets, moons, or comets, under the influence of energy sources in the form of electromagnetic and corpuscular radiation, because low-energy ion-neutral cross-sections in space cannot be reproduced quantitatively in laboratories for conditions of satisfying, particularly, (1) low-temperatures, (2) tenuous or strong gradients or layered media, and (3) in low-gravity plasma. Measurements with a minimum core instrument package (< 15 kg) can be used to perform such investigations in many different conditions and should be included in all deep-space missions. These investigations, if specific ranges of background parameters are considered, can also be pursued for Earth, Mars, and Venus. © 2022, The Author(s).

Published
2022

42. Photometric behavior of Ryugu’s NIR spectral parameters

Author

Longobardo, Andrea, Palomba, E., Galiano, Anna, Dirri, Fabrizio, Zinzi, Angelo, D'Amore, Mario, Domingue, Deborah L., Kitazato, K., Yokota, Y., Schroeder, Stephan, Iwata, T., Matsuoka, M., Hiroi, T., Takir, D., Nakamura, T., Abe, M., Ohtake, M., Matsuura, S., Watanabe, S, Yoshikawa, M., Saiki, T., Okada, T., Tanaka, S., Yamamoto, Y., Takei, Y., Shirai, K., Hirata, N., Matsumoto, K., and Tsuda, T.

Subjects
Photometry, parameters, Space and Planetary Science, spectral, Ryugu, Astronomy and Astrophysics, NIR
Abstract

Context. JAXA’s Hayabusa2 mission rendezvoused the Ryugu asteroid for 1.5 years to clarify the carbonaceous asteroids’ record for Solar System origin and evolution. Aims. We studied the photometric behavior of the spectral parameters characterizing the near-infrared (NIR) spectra of Ryugu provided by the Hayabusa2/NIRS3 instrument, that is to say 1.9 µm reflectance, 2.7 and 2.8 µm band depths (ascribed to phyllosilicates), and NIR slope. Methods. For each parameter, we applied the following empirical approach: (1) retrieval of the equigonal albedo by applying the Akimov disk function (this step was only performed for the reflectance photometric correction); (2) retrieval of the median spectral parameter value at each phase angle bin; and (3) retrieval of the phase function by a linear fit. Results. Ryugu’s phase function shows a steepness similar to Ceres, according to the same taxonomy of the two asteroids. Band depths decrease with increasing phase angle: this trend is opposite to that observed on other asteroids explored by space missions and is ascribed to the very dark albedo. NIR and visible phase reddening are similar, contrary to other asteroids, where visible phase reddening is larger: this could be due to surface darkness or to particle smoothness. Albedo and band depths are globally uncorrelated, but locally anticorrelated. A correlation between darkening and reddening is observed.

Published
2022

44. ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

Author

Vissing J., Jacob S., Fujita K. P., O'Brien F., Howard J. F., Mazia C. G., Wilken M., Barroso F., Saba J., Rugiero M., Bettini M., Chaves M., Vidal G., Garcia A. D., DeBleecker J., Vanden Abeele G., deKoning K., DeMey K., Mercelis R., Mahieu D., Wagemaekers L., VanDamme P., Depreitere A., Schotte C., Smetcoren C., Stevens O., VanDaele S., Vandenbussche N., Vanhee A., Verjans S., Vynckier J., D'Hont A., Tilkin P., Alves deSiqueira Carvalho A., DiasBrockhausen I., Feder D., Ambrosio D., Cesar P., Melo A. P., MartinsRibeiro R., Rocha R., Rosa B. B., Veiga T., daSilva L. A., SantosEngel M., GoncalvesGeraldo J., daPenha Ananias Morita M., NogueiraCoelho E., Paiva G., Pozo M., Prando N., MartineliTorres D. D., Butinhao C. F., Duran G., SurianeFialho T. A., Gomes daSilva T. C., MaiaGoncalves L. O., Pazetto L. E., CubasVolpe L. R., SouzaDuca L., GhellerFriedrich M. A., Guerreiro A., Mohr H., PereiraMartins M., daCruz Pacheco D., Ferreira L., Macagnan A. P., Pinto G., deCassia Santos A., Souza BulleOliveira A., Amaral deAndrade A. C., Annes M., DuarteSilva L., CavalcanteLino V., Pinto W., Assis N., Carrara F., Miranda C., Souza I., Fernandes P., Siddiqi Z., Phan C., Narayan J., Blackmore D., Mallon A., Roderus R., Watt E., Vohanka S., Bednarik J., Chmelikova M., Cierny M., Toncrova S., Junkerova BarboraKurkova J., Reguliova K., Zapletalova O., Pitha J., Novakova I., Tyblova M., Jurajdova I., Wolfova M., Andersen H., Harbo T., Vinge L., Krogh S., Mogensen A., Hojgaard J., Witting N., Mette OstergaardAutzen A., Pedersen J., Eralinna J. -P., Laaksonen M., Oksaranta O., Harrison T., Eriksson J., Rozsa C., Horvath M., Lovas G., Matolcsi J., Szabo G., Jakab G., Szabadosne B., Vecsei L., Dezsi L., Varga E., Konyane M., Antonini G., DiPasquale A., Garibaldi M., Morino S., Troili F., Fionda L., Sacca F., previous, Filla A., sub-investigators, Costabile T., Marano E., Fasanaro A., Marsili A., Puorro G., Mantegazza R., Antozzi C., Bonanno S., Camera G., Locatelli A., Maggi L., Pasanisi M., Campanella A., Evoli A., Alboini P. E., D'Amato V., Iorio R., Inghilleri M., Frasca V., Giacomelli E., Gori M., Lopergolo D., Onesti E., Gabriele M., Uzawa A., Kanai T., Kawaguchi N., Mori M., Kaneko Y., Kanzaki A., Kobayashi E., Murai H., Masaki K., Matsuse D., Matsushita T., Uehara T., Shimpo M., Jingu M., Kikutake K., Nakamura Y., Sano Y., Utsugisawa K., Nagane Y., Kamegamori I., Tsuda T., Fujii Y., Futono K., Ozawa Y., Mizugami A., Saito Y., Samukawa M., Suzuki H., Morikawa M., Kamakura S., Miyawaki E., Shiraishi H., Mitazaki T., Motomura M., Mukaino A., Yoshimura S., Asada S., Yoshida S., Amamoto S., Kobashikawa T., Koga M., Maeda Y., Takada K., Takada M., Tsurumaru M., Yamashita Y., Suzuki Y., Akiyama T., Narikawa K., Tano O., Tsukita K., Kurihara R., Meguro F., Fukuda Y., Sato M., Okumura M., Funaka S., Kawamura T., Makamori M., Takahashi M., Taichi N., Hasuike T., Higuchi E., Kobayashi H., Osakada K., Imai T., Tsuda E., Shimohama S., Hayashi T., Hisahara S., Kawamata J., Murahara T., Saitoh M., Suzuki S., Yamamoto D., Ishiyama Y., Ishiyama N., Noshiro M., Takeyama R., Uwasa K., Yasuda I., Kim B. -J., Lee C. N., Koo Y. S., Seok H. Y., Kang H. N., Ra H. J., Kim B. J., Cho E. B., Choi M. S., Lee H. L., Min J. -H., Seok J., Lee J. E., Koh D. Y., Kwon J. Y., Park S. A., Choi E. H., Hong Y. -H., Ahn S. -H., Koo D. L., Lim J. -S., Shin C. W., Hwang J. Y., Kim M., Kim S. M., Jeong H. -N., Jung J. W., Kim Y. -H., Lee H. S., Shin H. Y., Hwang E. B., Shin M., van derKooi A., deVisser M., Gibson T., Casasnovas C., AlbertiAguilo M. A., Homedes-Pedret C., Palacios N. J., DiezPorras L., VelezSantamaria V., Lazaro A., DiezTejedor E., GomezSalcedo P., Fernandez-Fournier M., LopezRuiz P., Rodriguez deRivera F. J., Sastre M., GamezCarbonell J., Sune P., SalvadoFigueras M., Gili G., Mazuela G., Illa I., CortesVicente E., Diaz-Manera J., QuerolGutierrez L. A., RojasGarcia R., Vidal N., Arribas-Ibar E., Piehl F., Hietala A., Bjarbo L., Sengun I., Meherremova A., Ozcelik P., Balkan B., Tuga C., Ugur M., Erdem-Ozdamar S., Bekircan-Kurt C. E., Acar N. P., Yilmaz E., Caliskan Y., Orsel G., Efendi H., Aydinlik S., Cavus H., Kutlu A., Becerikli G., Semiz C., Tun O., Terzi M., Dogan B., Onar M. K., Sen S., KirbasCavdar T., Veske A., Norwood F., Dimitriou A., Gollogly J., Mahdi-Rogers M., Seddigh A., Sokratous G., Maier G., Sohail F., Sadalage G., Torane P., Brown C., Shah A., Sathasivam S., Arndt H., Davies D., Watling D., Amato A., Cochrane T., Salajegheh M., Roe K., Amato K., Toska S., Wolfe G., Silvestri N., Patrick K., Zakalik K., Katz J., Miller R., Engel M., Forshew D., Bravver E., Brooks B., Sanjak M., Plevka S., Burdette M., Cunningham S., Kramer M., Nemeth J., Schommer C., Tinerney S., Juel V., Guptill J., Hobson-Webb L., Massey J., Beck K., Carnes D., Loor J., Anderson A., Pascuzzi R., Bodkin C., Kincaid J., Snook R., Guinrich S., Micheels A., Chaudhry V., Corse A., Mosmiller B., Kelley A., Ho D., Srinivasan J., Vytopil M., Jara J., Ventura N., Carter C., Donahue C., Herbert C., Scala S., Weiner E., Alam S., McKinnon J., Haar L., McKinnon N., Alcon K., McKenna K., Sattar N., Daniels K., Jeffery D., Freimer M., Hoyle J. C., Kissel J., Agriesti J., Chelnick S., Mezache L., Pineda C., Muharrem F., Karam C., Khoury J., Marburger T., Kaur H., Dimitrova D., Gilchrist J., Agrawal B., Elsayed M., Kohlrus S., Andoin A., Darnell T., Golden L., Lokaitis B., Seelbach J., Muppidi S., Goyal N., Sakamuri S., So Y. T., Paulose S., Pol S., Welsh L., Bhavaraju-Sanka R., TobonGonzalez A., Dishman L., Jones F., Gonzalez A., Padilla P., Saklad A., Silva M., Nations S., Trivedi J., Hopkins S., Kazamel M., Alsharabati M., Lu L., Nozaki K., Mumfrey-Thomas S., Woodall A., Mozaffar T., Cash T., Roy G., Mathew V., Maqsood F., Minton B., Jones H. J., Rosenfeld J., Garcia R., Echevarria L., Garcia S., Pulley M., Aranke S., Berger A. R., Shah J., Shabbir Y., Smith L., Varghese M., Gutmann L., Jerath N., Nance C., Swenson A., Olalde H., Kressin N., Sieren J., Barohn R., Dimachkie M., Glenn M., McVey A., Pasnoor M., Statland J., Wang Y., Liu T., Emmons K., Jenci N., Locheke J., Fondaw A., Johns K., Rico G., Walsh M., Herbelin L., Hafer-Macko C., Kwan J., Zilliox L., Callison K., Young V., DiSanzo B., Naunton K., Benatar M., Bilsker M., Sharma K., Cooley A., Reyes E., Michon S. -C., Sheldon D., Steele J., Howard J., Traub R., Chopra M., Vu T., Katzin L., McClain T., Harvey B., Hart A., Huynh K., Beydoun S., Chilingaryan A., Doan V., Droker B., Gong H., Karimi S., Lin F., Polaka K., Tran A., Akhter S., Malekniazi A., Tandan R., Hehir M., Waheed W., Lucy S., Weiss M., Distad J., Strom S., Downing S., Kim B., Bertorini T., Arnold T., Henderson K., Pillai R., Liu Y., Wheeler L., Hewlett J., Vanderhook M., Nowak R., Dicapua D., Keung B., Kumar A., Patwa H., Robeson K., Yang I., Nye J., Vu H., Vissing, J., Jacob, S., Fujita, K. P., O'Brien, F., Howard, J. F., Mazia, C. G., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Garcia, A. D., Debleecker, J., Vanden Abeele, G., Dekoning, K., Demey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Vandamme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Vandaele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves deSiqueira Carvalho, A., Diasbrockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Melo, A. P., Martinsribeiro, R., Rocha, R., Rosa, B. B., Veiga, T., Dasilva, L. A., Santosengel, M., Goncalvesgeraldo, J., daPenha Ananias Morita, M., Nogueiracoelho, E., Paiva, G., Pozo, M., Prando, N., Martinelitorres, D. D., Butinhao, C. F., Duran, G., Surianefialho, T. A., Gomes daSilva, T. C., Maiagoncalves, L. O., Pazetto, L. E., Cubasvolpe, L. R., Souzaduca, L., Ghellerfriedrich, M. A., Guerreiro, A., Mohr, H., Pereiramartins, M., daCruz Pacheco, D., Ferreira, L., Macagnan, A. P., Pinto, G., deCassia Santos, A., Souza BulleOliveira, A., Amaral deAndrade, A. C., Annes, M., Duartesilva, L., Cavalcantelino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova BarboraKurkova, J., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Hojgaard, J., Witting, N., Mette OstergaardAutzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Dipasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Sacca, F., Previous, Filla, A., sub-investigators, Costabile, T., Marano, E., Fasanaro, A., Marsili, A., Puorro, G., Mantegazza, R., Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Evoli, A., Alboini, P. E., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Shiraishi, H., Mitazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Okumura, M., Funaka, S., Kawamura, T., Makamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., Kim, B. -J., Lee, C. N., Koo, Y. S., Seok, H. Y., Kang, H. N., Ra, H. J., Kim, B. J., Cho, E. B., Choi, M. S., Lee, H. L., Min, J. -H., Seok, J., Lee, J. E., Koh, D. Y., Kwon, J. Y., Park, S. A., Choi, E. H., Hong, Y. -H., Ahn, S. -H., Koo, D. L., Lim, J. -S., Shin, C. W., Hwang, J. Y., Kim, M., Kim, S. M., Jeong, H. -N., Jung, J. W., Kim, Y. -H., Lee, H. S., Shin, H. Y., Hwang, E. B., Shin, M., van derKooi, A., Devisser, M., Gibson, T., Casasnovas, C., Albertiaguilo, M. A., Homedes-Pedret, C., Palacios, N. J., Diezporras, L., Velezsantamaria, V., Lazaro, A., Dieztejedor, E., Gomezsalcedo, P., Fernandez-Fournier, M., Lopezruiz, P., Rodriguez deRivera, F. J., Sastre, M., Gamezcarbonell, J., Sune, P., Salvadofigueras, M., Gili, G., Mazuela, G., Illa, I., Cortesvicente, E., Diaz-Manera, J., Querolgutierrez, L. A., Rojasgarcia, R., Vidal, N., Arribas-Ibar, E., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C. E., Acar, N. P., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Onar, M. K., Sen, S., Kirbascavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Tinerney, S., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guinrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., Mckinnon, J., Haar, L., Mckinnon, N., Alcon, K., Mckenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Hoyle, J. C., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Andoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., So, Y. T., Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobongonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., Jones, H. J., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Berger, A. R., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., Mcvey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., Disanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Howard, J., Traub, R., Chopra, M., Vu, T., Katzin, L., Mcclain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H., ANS - Neuroinfection & -inflammation, and Neurology

Subjects
0301 basic medicine, Male, Myasthenia gravi, Gastroenterology, 0302 clinical medicine, Quality of life, Activities of Daily Living, CYCLOPHOSPHAMIDE, Medicine and Health Sciences, Medicine, Receptors, Cholinergic, Acetylcholine receptor, Myasthenia gravis, Original Communication, Eculizumab, Minimal symptom expression, Refractory, Middle Aged, Acetylcholine receptor antibody, Tolerability, Neurology, Female, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, medicine.drug, Adult, medicine.medical_specialty, Clinical Neurology, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Double-Blind Method, Internal medicine, Humans, Immunologic Factors, Patient Reported Outcome Measures, Generalized myasthenia, Aged, Autoantibodies, Science & Technology, business.industry, Confidence interval, 030104 developmental biology, Quality of Life, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract

Background The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods Attainment of ‘minimal symptom expression’ was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. ‘Minimal symptom expression’ was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results At REGAIN week 26, more eculizumab-treated patients achieved ‘minimal symptom expression’ versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved ‘minimal symptom expression’ increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved ‘minimal symptom expression’ (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained ‘minimal symptom expression’ based on patient-reported outcomes. ‘Minimal symptom expression’ may be a useful tool in measuring therapy effectiveness in gMG. Trial registration ClinicalTrials.gov NCT01997229, NCT02301624.

Published
2020

45. Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Author

Mantegazza, R., O'Brien, F. L., Yountz, M., Howard, J. F., Gabriel Mazia, C., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Dalila Garcia, A., De Bleecker, J., Van den Abeele, G., de Koning, K., De Mey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Van Damme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Van Daele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves de Siqueira Carvalho, A., Dias Brockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Paula Melo, A., Martins Ribeiro, R., Rocha, R., Bezerra Rosa, B., Veiga, T., Augusto da Silva, L., Santos Engel, M., Goncalves Geraldo, J., da Penha Ananias Morita, M., Nogueira Coelho, E., Paiva, G., Pozo, M., Prando, N., Torres, D. D. M., Fernanda Butinhao, C., Duran, G., Augusto Suriane Fialho, T., Gomes da Silva, T. C., Goncalves, L. O. M., Eduardo Pazetto, L., Renata Cubas Volpe, L., Souza Duca, L., Friedrich, M. A. G., Guerreiro, A., Mohr, H., Pereira Martins, M., da Cruz Pacheco, D., Ferreira, L., Paula Macagnan, A., Pinto, G., de Cassia Santos, A., Souza Bulle Oliveira, A., Amaral de Andrade, A. C., Annes, M., Duarte Silva, L., Cavalcante Lino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova, J., Kurkova, B., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Vissing, J., Hojgaard, J., Witting, N., Mette Ostergaard Autzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Di Pasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Pasquale, A., Evoli, A., Emilio Alboini, P., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Sacca, F., Filla, A., Costabile, T., Marano, E., Fasanaro, A., Marsili, A., Puorro, G., Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Okumura, M., Funaka, S., Kawamura, T., Nakamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Shiraishi, H., Miyazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., van der Kooi, A., de Visser, M., Gibson, T., Kim, B. -J., Nyoung Lee, C., Seo Koo, Y., Youl Seok, H., Nam Kang, H., Ra, H., Joon Kim, B., Bin Cho, E., Choi, M., Lee, H., Min, J. -H., Seok, J., Lee, J., Koh, D. Y., Kwon, J., Park, S., Haw Choi, E., Hong, Y. -H., Ahn, S. -H., Lim Koo, D., Lim, J. -S., Won Shin, C., Ye Hwang, J., Kim, M., Min Kim, S., Jeong, H. -N., Jung, J., Kim, Y. -H., Seok Lee, H., Young Shin, H., Bi Hwang, E., Shin, M., Casasnovas, C., Antonia Alberti Aguilo, M., Homedes-Pedret, C., Julia Palacios, N., Diez Porras, L., Velez Santamaria, V., Lazaro, A., Gamez Carbonell, J., Sune, P., Salvado Figueras, M., Gili, G., Mazuela, G., Illa, I., Cortes Vicente, E., Diaz-Manera, J., Antonio Querol Gutierrez, L., Rojas Garcia, R., Vidal, N., Arribas-Ibar, E., Diez Tejedor, E., Gomez Salcedo, P., Fernandez-Fournier, M., Lopez Ruiz, P., Rodriguez de Rivera, F. J., Sastre, M., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C., Pinar Acar, N., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Kazim Onar, M., Sen, S., Kirbas Cavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Jacob, S., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Scott, T., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guingrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., Mckinnon, J., Haar, L., Mckinnon, N., Alcon, K., Mckenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Chad Hoyle, J., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Ardoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., Y. T., So, Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobon Gonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., James Jones, H., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Ross Berger, A., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., Mcvey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., Disanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Traub, R., Chopra, M., Vu, T., Katzin, L., Mcclain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H., Mantegazza, R., O'Brien, F. L., Yountz, M., Howard, J. F., Gabriel Mazia, C., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Dalila Garcia, A., De Bleecker, J., Van den Abeele, G., de Koning, K., De Mey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Van Damme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Van Daele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves de Siqueira Carvalho, A., Dias Brockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Paula Melo, A., Martins Ribeiro, R., Rocha, R., Bezerra Rosa, B., Veiga, T., Augusto da Silva, L., Santos Engel, M., Goncalves Geraldo, J., da Penha Ananias Morita, M., Nogueira Coelho, E., Paiva, G., Pozo, M., Prando, N., Torres, D. D. M., Fernanda Butinhao, C., Duran, G., Augusto Suriane Fialho, T., Gomes da Silva, T. C., Goncalves, L. O. M., Eduardo Pazetto, L., Renata Cubas Volpe, L., Souza Duca, L., Friedrich, M. A. G., Guerreiro, A., Mohr, H., Pereira Martins, M., da Cruz Pacheco, D., Ferreira, L., Paula Macagnan, A., Pinto, G., de Cassia Santos, A., Souza Bulle Oliveira, A., Amaral de Andrade, A. C., Annes, M., Duarte Silva, L., Cavalcante Lino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova, J., Kurkova, B., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Vissing, J., Hojgaard, J., Witting, N., Mette Ostergaard Autzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Di Pasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Pasquale, A., Evoli, A., Emilio Alboini, P., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Saccà, Francesco, Filla, Alessandro, Costabile, T., Marano, E., Fasanaro, A., Marsili, Angela, Puorro, Giorgia, Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Okumura, M., Funaka, S., Kawamura, T., Nakamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Shiraishi, H., Miyazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., van der Kooi, A., de Visser, M., Gibson, T., Kim, B. -J., Nyoung Lee, C., Seo Koo, Y., Youl Seok, H., Nam Kang, H., Ra, H., Joon Kim, B., Bin Cho, E., Choi, M., Lee, H., Min, J. -H., Seok, J., Lee, J., Koh, D. Y., Kwon, J., Park, S., Haw Choi, E., Hong, Y. -H., Ahn, S. -H., Lim Koo, D., Lim, J. -S., Won Shin, C., Ye Hwang, J., Kim, M., Min Kim, S., Jeong, H. -N., Jung, J., Kim, Y. -H., Seok Lee, H., Young Shin, H., Bi Hwang, E., Shin, M., Casasnovas, C., Antonia Alberti Aguilo, M., Homedes-Pedret, C., Julia Palacios, N., Diez Porras, L., Velez Santamaria, V., Lazaro, A., Gamez Carbonell, J., Sune, P., Salvado Figueras, M., Gili, G., Mazuela, G., Illa, I., Cortes Vicente, E., Diaz-Manera, J., Antonio Querol Gutierrez, L., Rojas Garcia, R., Vidal, N., Arribas-Ibar, E., Diez Tejedor, E., Gomez Salcedo, P., Fernandez-Fournier, M., Lopez Ruiz, P., Rodriguez de Rivera, F. J., Sastre, M., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C., Pinar Acar, N., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Kazim Onar, M., Sen, S., Kirbas Cavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Jacob, S., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Scott, T., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guingrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., Mckinnon, J., Haar, L., Mckinnon, N., Alcon, K., Mckenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Chad Hoyle, J., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Ardoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., So, Y. T., Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobon Gonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., James Jones, H., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Ross Berger, A., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., Mcvey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., Disanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Traub, R., Chopra, M., Vu, T., Katzin, L., Mcclain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H., Neurology, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
0301 basic medicine, Malalties neuromusculars, Activities of daily living, Autoimmune diseases, Severity of Illness Index, Complement inhibitor, 0302 clinical medicine, CYCLOPHOSPHAMIDE, Activities of Daily Living, Outcome Assessment, Health Care, Medicine and Health Sciences, Research Articles, Malalties autoimmunitàries, General Neuroscience, Eculizumab, myasthenia, Neuromuscular diseases, Life Sciences & Biomedicine, medicine.drug, RC321-571, Research Article, Adult, medicine.medical_specialty, Cyclophosphamide, Gross motor skill, Clinical Neurology, Neurosciences. Biological psychiatry. Neuropsychiatry, Placebo, Antibodies, Monoclonal, Humanized, ACETYLCHOLINE-RECEPTOR, 03 medical and health sciences, Refractory, Double-Blind Method, Internal medicine, Myasthenia Gravis, medicine, Humans, Muscle Strength, Patient Reported Outcome Measures, RC346-429, Muscle, Skeletal, Science & Technology, business.industry, Neurosciences, medicine.disease, Myasthenia gravis, 030104 developmental biology, Complement Inactivating Agents, ANTIBODY, Monoclonal antibodies, Neurosciences & Neurology, Neurology (clinical), Neurology. Diseases of the nervous system, business, Anticossos monoclonals, 030217 neurology & neurosurgery
Abstract

OBJECTIVE: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. METHODS: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. RESULTS: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. INTERPRETATION: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. ispartof: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY vol:7 issue:8 pages:1327-1339 ispartof: location:United States status: published

Published
2020

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