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Management and Outcomes in the Oldest-Old Population with Glioblastoma
- Fabio Y. Moraes, Andrea Lo, Erin R. Morgan, Barbara-Ann Millar, David B. Shultz, Catherine Maurice, Craig Harlos, Paul Kongkham, Mark Bernstein, Gelareh Zadeh, Normand Laperriere, Warren Mason, Alejandro Berlin
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 45 / Issue 2 / March 2018
- Published online by Cambridge University Press:
- 18 December 2017, pp. 199-205
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Objectives: Glioblastoma is a lethal disease in the elderly population. We aimed to evaluate disease and treatment outcomes in the oldest-old patients. Methods: Patients >80 years old with histologically confirmed glioblastoma treated between 2004 and 2009 were identified. We included patients managed with best supportive care (BSC), temozolomide (TMZ) alone, radiotherapy (RT) alone, or concomitantly with TMZ (CRT). Survival outcomes were analyzed using the Kaplan–Meier method. Results: Ultimately, 48 patients were analyzed. Median age and Eastern Cooperative Oncology Group (ECOG) Performance Status were 82 years and 2, respectively. The median Age-Adjusted Charlson Index (AAC) was 6. Gross total and subtotal resections were performed in 16.7% and 18.8% of patients, respectively. Biopsy followed by RT alone was the treatment modality for 23/48 (47.9%), while 17/48 (35.4%) received surgery followed by RT alone or CRT. A total of 8 (16.7%) were managed with BSC after biopsy. Median overall survival (OS) and progression-free survival (PFS) were 4.1 (95% confidence interval [95% CI] 3.3-4.9) and 2.7 (95% CI 1.5-3.9) months, respectively. Improved median OS was observed in those treated with surgical resection followed by RT alone or CRT (7.1 months), compared to biopsy followed by RT alone (4.2 months) or BSC (2.0 months; p=0.002). Surgical resection, age≤85, and AAC<6 were associated with better OS (p=0.032, p=0.031, and p=0.02, respectively). Cause of death was neurological progression in 56% of cases. RT was well-tolerated. Conclusions: PFS and OS outcomes remain poor in the oldest-old patients (>80 years old). Younger age, lower AAC, surgical resection, and adjuvant treatment were associated with improved OS.
Contributors
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- By Amelia Evoli, Ami K. Mankodi, Ana Ferreiro, Anders Oldfors, Anne K. Lampe, Anneke J. van der Kooi, Bernard Brais, Bertrand Fontaine, Bjarne Udd, Carina Wallgren-Pettersson, Caroline A. Sewry, Carsten G. Bönnemann, Cecilia Jimenez-Mallebera, Chad Heatwole, Charles A. Thornton, Corrado Angelini, David Hilton-Jones, Doreen Fialho, Duygu Selcen, Edward J. Cupler, Emma Ciafaloni, Enrico Bertini, Eric A. Shoubridge, Eric Logigian, Erin O’Ferrall, Eugenio Mercuri, Franco Taroni, Frank L. Mastaglia, Frederic Relaix, George Karpati, Giovanni Meola, Gisèle Bonne, Hannah R. Briemberg, Hanns Lochmüller, Heinz Jungbluth, Ichizo Nishino, Jenny E. Morgan, John Day, John Vissing, John T. Kissel, Kate Bushby, Leslie Morrison, Maria J. Molnar, Marianne de Visser, Marinos C. Dalakas, Mary Kay Floeter, Mariz Vainzof, Maxwell S. Damian, Michael G. Hanna, Michael Rose, Michael Sinnreich, Michael Swash, Miranda D. Grounds, Mohammed Kian Salajegheh, Nigel G. Laing, Patrick F. Chinnery, Rabi Tawil, Rénald Gilbert, Richard Orrell, Robert C. Griggs, Roberto Massa, Saiju Jacob, Shannon L. Venance, Stefano Di Donato, Stella Mitrani-Rosenbaum, Stephen Gee, Stuart Viegas, Susan C. Brown, Tahseen Mozaffar, Tanja Taivassalo, Valeria A. Sansone, Violeta Mihaylova, Yaacov Anziska, Zohar Argov
- George Karpati, McGill University, Montréal
- Edited by David Hilton-Jones, Kate Bushby, Robert C. Griggs
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- Book:
- Disorders of Voluntary Muscle
- Published online:
- 26 February 2010
- Print publication:
- 21 January 2010, pp vii-x
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Neurobehavioral effects of HIV-1 infection in China and the United States: A pilot study
- LUCETTE A. CYSIQUE, HUA JIN, DONALD R. FRANKLIN, ERIN E. MORGAN, CHUAN SHI, XIN YU, ZUNYOU WU, MICHAEL J. TAYLOR, THOMAS D. MARCOTTE, SCOTT LETENDRE, CHRISTOPHER AKE, IGOR GRANT, ROBERT K. HEATON, THE HNRC GROUP
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- Journal:
- Journal of the International Neuropsychological Society / Volume 13 / Issue 5 / September 2007
- Published online by Cambridge University Press:
- 14 August 2007, pp. 781-790
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The HIV epidemic in China has been increasing exponentially, yet there have been no studies of the neurobehavioral effects of HIV infection in that country. Most neuroAIDS research has been conducted in Western countries using Western neuropsychological (NP) methods, and it is unclear whether these testing methods are appropriate for use in China. Twenty-eight HIV seropositive (HIV+) and twenty-three HIV seronegative (HIV−) individuals with comparable gender, age, and education distributions were recruited in Beijing and the rural Anhui province in China. Thirty-nine HIV+ and thirty-one HIV− individuals were selected from a larger U.S. cohort recruited at the HIV Neurobehavioral Research Center, in San Diego, to be matched to the Chinese sample for age, disease status, and treatment variables. The NP test battery used with the U.S. and China cohorts included instruments widely used to study HIV infection in the United States. It consisted of 14 individual test measures, each assigned to one of seven ability areas thought to be especially vulnerable to effects of HIV on the brain (i.e., verbal fluency, abstraction/executive function, speed of information processing, working memory, learning, delayed recall, and motor function). To explore the cross-cultural equivalence and validity of the NP measures, we compared our Chinese and U.S. samples on the individual tests, as well as mean scaled scores for the total battery and seven ability domains. On each NP test measure, the mean of the Chinese HIV+ group was worse than that of the HIV− group. A series of 2 × 2 analyses of variance involving HIV+ and HIV− groups from both countries revealed highly significant HIV effects on the Global and all Domain mean scaled scores. Country effects appeared on two of the individual ability areas, at least partly due to education differences between the two countries. Importantly, the absence of HIV-by-Country interactions suggests that the NP effects of HIV are similar in the two countries. The NP test battery that was chosen and adapted for use in this study of HIV in China appears to have good cross-cultural equivalence, but appropriate Chinese norms will be needed to identify disease-related impairment in individual Chinese people. To inform the development of such norms, a much larger study of demographic effects will be needed, especially considering the wide range of education in that country. (JINS, 2007, 13, 781–790.)
Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse
- LAWRENCE H. PINTO, MARTHA H. VITATERNA, KAZUHIRO SHIMOMURA, SANDRA M. SIEPKA, VICTORIA BALANNIK, ERIN L. MCDEARMON, CHIAKI OMURA, STEPHEN LUMAYAG, BRANDON M. INVERGO, BRETT GLAWE, DONALD R. CANTRELL, SAMSOON INAYAT, MARISSA A. OLVERA, KIRSTAN A. VESSEY, MAUREEN A. McCALL, DENNIS MADDOX, CATHERINE W. MORGANS, BRANDON YOUNG, MATHEW T. PLETCHER, ROBERT F. MULLINS, JOHN B. TROY, JOSEPH S. TAKAHASHI
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- Journal:
- Visual Neuroscience / Volume 24 / Issue 1 / January 2007
- Published online by Cambridge University Press:
- 12 April 2007, pp. 111-123
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We performed genome-wide chemical mutagenesis of C57BL/6J mice using N-ethyl-N-nitrosourea (ENU). Electroretinographic screening of the third generation offspring revealed two G3 individuals from one G1 family with a normal a-wave but lacking the b-wave that we named nob4. The mutation was transmitted with a recessive mode of inheritance and mapped to chromosome 11 in a region containing the Grm6 gene, which encodes a metabotropic glutamate receptor protein, mGluR6. Sequencing confirmed a single nucleotide substitution from T to C in the Grm6 gene. The mutation is predicted to result in substitution of Pro for Ser at position 185 within the extracellular, ligand-binding domain and oocytes expressing the homologous mutation in mGluR6 did not display robust glutamate-induced currents. Retinal mRNA levels for Grm6 were not significantly reduced, but no immunoreactivity for mGluR6 protein was found. Histological and fundus evaluations of nob4 showed normal retinal morphology. In contrast, the mutation has severe consequences for visual function. In nob4 mice, fewer retinal ganglion cells (RGCs) responded to the onset (ON) of a bright full field stimulus. When ON responses could be evoked, their onset was significantly delayed. Visual acuity and contrast sensitivity, measured with optomotor responses, were reduced under both photopic and scotopic conditions. This mutant will be useful because its phenotype is similar to that of human patients with congenital stationary night blindness and will provide a tool for understanding retinal circuitry and the role of ganglion cell encoding of visual information.