885 results on '"Talbot K"'
Search Results
2. The sensory and affective components of pain: are they differentially modifiable dimensions or inseparable aspects of a unitary experience? A systematic review
- Author
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Talbot, K., Madden, V.J., Jones, S.L., and Moseley, G.L.
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- 2019
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3. Rivaroxaban and apixaban induce clotting factor Xa fibrinolytic activity
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Carter, R.L.R., Talbot, K., Hur, W.S., Meixner, S.C., Van Der Gugten, J.G., Holmes, D.T., Côté, H.C.F., Kastrup, C.J., Smith, T.W., Lee, A.Y.Y., and Pryzdial, E.L.G.
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- 2018
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4. International outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder – USA and Canada, 2013–2014
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HARVEY, R. R., MARSHALL, K. E. HEIMAN, BURNWORTH, L., HAMEL, M., TATARYN, J., CUTLER, J., MEGHNATH, K., WELLMAN, A., IRVIN, K., ISAAC, L., CHAU, K., LOCAS, A., KOHL, J., HUTH, P. A., NICHOLAS, D., TRAPHAGEN, E., SOTO, K., MANK, L., HOLMES-TALBOT, K., NEEDHAM, M., BARNES, A., ADCOCK, B., HONISH, L., CHUI, L., TAYLOR, M., GAULIN, C., BEKAL, S., WARSHAWSKY, B., HOBBS, L., TSCHETTER, L. R., SURIN, A., LANCE, S., WISE, M. E., WILLIAMS, I., and GIERALTOWSKI, L.
- Published
- 2017
5. Theme 01 - Epidemiology and Informatics.
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Opie-Martin, S., Bredin, A., Grey, E., Talbot, K., Al-Chalabi, A., McFarlane, R., Caravaca Puchades, A., Chio, A., Corcia, P., Galvin, M., Heverin, M., Hobin, F., Holmdahl, O., Ingre, C., Lamaire, N., Mac Domhnaill, É., McDonough, H., Manera, U., McDermott, C., and Mouzouri, M.
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AMYOTROPHIC lateral sclerosis ,EPIDEMIOLOGY ,LIBRARY users ,NEURODEGENERATION - Abstract
The document titled "Theme 01 - Epidemiology and Informatics" provides a comprehensive overview of research conducted by multiple authors on the topics of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The authors explore various aspects of these neurodegenerative diseases, including epidemiology, informatics, and clinical characteristics. The document features a wide range of contributors from different countries, highlighting the global nature of ALS and FTD research. This resource would be valuable for library patrons interested in studying the epidemiology and informatics of ALS and FTD. [Extracted from the article]
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- 2023
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- View/download PDF
6. Thrombolysis by chemically modified coagulation factor Xa
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Pryzdial, E.L.G., Meixner, S.C., Talbot, K., Eltringham‐Smith, L.J., Baylis, J.R., Lee, F.M.H., Kastrup, C.J., and Sheffield, W.P.
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- 2016
- Full Text
- View/download PDF
7. Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation
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Giacomelli, E, Vahsen, BF, Calder, EL, Xu, Y, Scaber, J, Gray, E, Dafinca, R, Talbot, K, and Studer, L
- Subjects
Neurons ,Amyotrophic Lateral Sclerosis ,Induced Pluripotent Stem Cells ,Genetics ,Molecular Medicine ,Humans ,Cell Biology ,Neuroglia ,Article - Abstract
Neurodegenerative diseases are characterized by progressive cell loss leading to disruption of the structure and function of the central nervous system. Amyotrophic lateral sclerosis (ALS) was among the first of these disorders modeled in patient-specific iPSCs, and recent findings have translated into some of the earliest iPSC-inspired clinical trials. Focusing on ALS as an example, we evaluate the status of modeling neurodegenerative diseases using iPSCs, including methods for deriving and using disease-relevant neuronal and glial lineages. We further highlight the remaining challenges in exploiting the full potential of iPSC technology for understanding and potentially treating neurodegenerative diseases such as ALS.
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- 2023
8. Creatine kinase and prognosis in amyotrophic lateral sclerosis: a literature review and multi-centre cohort analysis
- Author
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Gao, J., Dharmadasa, T., Malaspina, A., Shaw, P.J., Talbot, K., Turner, M.R., and Thompson, A.G.
- Abstract
Background\ud \ud Amyotrophic lateral sclerosis (ALS) is a prognostically heterogeneous neurodegenerative disease. Blood creatine kinase (CK) level has been inconsistently reported as a prognostic biomarker and raised levels in some ALS patients have been presumed to reflect muscle wasting, which is also variable.\ud \ud \ud \ud Methods\ud \ud MEDLINE was systematically searched for papers related to CK in ALS and the relevant studies were reviewed. Using data from 222 ALS patients in a multi-centre, prospective, longitudinal cohort, survival analyses using Kaplan–Meier and Cox proportional hazards models were undertaken in relation to CK and other prognostic factors.\ud \ud \ud \ud Results\ud \ud Twenty-five studies investigating CK in ALS were identified, of which 10 specifically studied the link between CK and survival. Five studies observed no association, four found that higher CK levels were associated with longer survival and one, the opposite. In our cohort (n = 222), 39% of patients had a CK level above the laboratory reference range. Levels were higher in males compared to females (p
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- 2022
9. Dysbindin-1 and Its Protein Family : With Special Attention to the Potential Role of Dysbindin-1 in Neuronal Functions and the Pathophysiology of Schizophrenia
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Talbot, K., Ong, W.- Y., Blake, D. J., Tang, J., Louneva, N., Carlson, G. C., Arnold, S. E., Lajtha, Abel, editor, Javitt, Daniel, editor, and Kantrowitz, Joshua, editor
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- 2009
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10. Atypical TDP-43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP
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Cooper‐Knock, J., Julian, T.H., Feneberg, E., Highley, J.R., Sidra, M., Turner, M.R., Talbot, K., Ansorge, O., Allen, S.P., Moll, T., Shelkovnikova, T., Castelli, L., Hautbergue, G.M., Hewitt, C., Kirby, J., Wharton, S.B., Mead, R.J., and Shaw, P.J.
- Abstract
We describe an autosomal dominant, multi-generational, amyotrophic lateral sclerosis (ALS) pedigree in which disease co-segregates with a heterozygous p.Y374X nonsense mutation within TDP-43. Mislocalization of TDP-43 and formation of insoluble TDP-43-positive neuronal cytoplasmic inclusions is the hallmark pathology in >95% of ALS patients. Neuropathological examination of the single case for which CNS tissue was available indicated typical TDP-43 pathology within lower motor neurons, but classical TDP-43-positive inclusions were absent from motor cortex. The mutated allele is transcribed and translated in patient fibroblasts and motor cortex tissue, but overall TDP-43 protein expression is reduced compared to wild-type controls. Despite absence of TDP-43-positive inclusions we confirmed deficient TDP-43 splicing function within motor cortex tissue. Furthermore, urea fractionation and mass spectrometry of motor cortex tissue carrying the mutation revealed atypical TDP-43 protein species but not typical C-terminal fragments. We conclude that the p.Y374X mutation underpins a monogenic, fully penetrant form of ALS. Reduced expression of TDP-43 combined with atypical TDP-43 protein species and absent C-terminal fragments extends the molecular phenotypes associated with TDP-43 mutations and with ALS more broadly. Future work will need to include the findings from this pedigree in dissecting the mechanisms of TDP-43-mediated toxicity.
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- 2022
11. Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis
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Johnson, JO, Chia, R, Miller, DE, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, AE, Topp, SD, Gibbs, JR, Cookson, MR, Sabir, MS, Dalgard, CL, Troakes, C, Jones, AR, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, IP, Dobson-Stone, C, Kwok, JB, Bonkowski, ES, Palvadeau, R, Tienari, PJ, Morrison, KE, Shaw, PJ, Al-Chalabi, A, Brown, RH, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, IJ, Perlman, SJ, Glass, I, Scott, AI, Shaw, CE, Basak, AN, Landers, JE, Chiò, A, Crawford, TO, Smith, BN, Traynor, BJ, Fallini, C, Gkazi, AS, Scotter, EL, Kenna, KP, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, ten Asbroek, ALMA, McKenna-Yasek, D, McLaughlin, RL, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D’Alfonso, S, Mazzini, L, Comi, GP, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, KL, Nicholson, GA, Leblond-Manry, C, Rouleau, GA, Hardiman, O, Veldink, JH, van den Berg, LH, Pall, H, Turner, MR, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, JD, Ratti, A, Adeleye, A, Soltis, AR, Alba, C, Viollet, C, Bacikova, D, Hupalo, DN, Sukumar, G, Pollard, HB, Wilkerson, MD, Martinez, EM, Ahmed, S, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, England, BK, Faghri, F, Feldman, E, Floeter, MK, Fratta, P, Geiger, JT, Gerhard, G, Gibson, SB, Hardy, J, Harms, MB, Heiman-Patterson, TD, Hernandez, DG, Jansson, L, Kirby, J, Kowall, NW, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering-Brown, S, Pioro, EP, Pletnikova, O, Pliner, HA, Pulst, SM, Ravits, JM, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Scholz, SW, Sendtner, M, Sidle, KC, Simmons, Z, Singleton, AB, Smith, N, Stone, DJ, Troncoso, JC, Valori, M, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Angelocola, SM, Ausiello, FP, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, TA, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, FL, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D’Errico, E, DeMarco, G, Dubbioso, R, Ferrarese, C, Ferraro, PM, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, FO, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, MG, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, MR, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson J.O., Chia R., Miller D.E., Li R., Kumaran R., Abramzon Y., Alahmady N., Renton A.E., Topp S.D., Gibbs J.R., Cookson M.R., Sabir M.S., Dalgard C.L., Troakes C., Jones A.R., Shatunov A., Iacoangeli A., Al Khleifat A., Ticozzi N., Silani V., Gellera C., Blair I.P., Dobson-Stone C., Kwok J.B., Bonkowski E.S., Palvadeau R., Tienari P.J., Morrison K.E., Shaw P.J., Al-Chalabi A., Brown R.H., Calvo A., Mora G., Al-Saif H., Gotkine M., Leigh F., Chang I.J., Perlman S.J., Glass I., Scott A.I., Shaw C.E., Basak A.N., Landers J.E., Chio A., Crawford T.O., Smith B.N., Traynor B.J., Fallini C., Gkazi A.S., Scotter E.L., Kenna K.P., Keagle P., Tiloca C., Vance C., Colombrita C., King A., Pensato V., Castellotti B., Baas F., Ten Asbroek A.L.M.A., McKenna-Yasek D., McLaughlin R.L., Polak M., Asress S., Esteban-Perez J., Stevic Z., D'Alfonso S., Mazzini L., Comi G.P., Del Bo R., Ceroni M., Gagliardi S., Querin G., Bertolin C., Van Rheenen W., Rademakers R., Van Blitterswijk M., Lauria G., Duga S., Corti S., Cereda C., Corrado L., Soraru G., Williams K.L., Nicholson G.A., Leblond-Manry C., Rouleau G.A., Hardiman O., Veldink J.H., Van Den Berg L.H., Pall H., Turner M.R., Talbot K., Taroni F., Garcia-Redondo A., Wu Z., Glass J.D., Ratti A., Adeleye A., Soltis A.R., Alba C., Viollet C., Bacikova D., Hupalo D.N., Sukumar G., Pollard H.B., Wilkerson M.D., Martinez E.M., Ahmed S., Arepalli S., Baloh R.H., Bowser R., Brady C.B., Brice A., Broach J., Campbell R.H., Camu W., Cooper-Knock J., Ding J., Drepper C., Drory V.E., Dunckley T.L., Eicher J.D., England B.K., Faghri F., Feldman E., Floeter M.K., Fratta P., Geiger J.T., Gerhard G., Gibson S.B., Hardy J., Harms M.B., Heiman-Patterson T.D., Hernandez D.G., Jansson L., Kirby J., Kowall N.W., Laaksovirta H., Landeck N., Landi F., Le Ber I., Lumbroso S., Macgowan D.J.L., Maragakis N.J., Mouzat K., Murphy N.A., Myllykangas L., Nalls M.A., Orrell R.W., Ostrow L.W., Pamphlett R., Pickering-Brown S., Pioro E.P., Pletnikova O., Pliner H.A., Pulst S.M., Ravits J.M., Rivera A., Robberecht W., Rogaeva E., Rollinson S., Rothstein J.D., Scholz S.W., Sendtner M., Sidle K.C., Simmons Z., Singleton A.B., Smith N., Stone D.J., Troncoso J.C., Valori M., Van Damme P., Van Deerlin V.M., Van Den Bosch L., Zinman L., Angelocola S.M., Ausiello F.P., Barberis M., Bartolomei I., Battistini S., Bersano E., Bisogni G., Borghero G., Brunetti M., Cabona C., Canale F., Canosa A., Cantisani T.A., Capasso M., Caponnetto C., Cardinali P., Carrera P., Casale F., Colletti T., Conforti F.L., Conte A., Conti E., Corbo M., Cuccu S., Dalla Bella E., D'Errico E., Demarco G., Dubbioso R., Ferrarese C., Ferraro P.M., Filippi M., Fini N., Floris G., Fuda G., Gallone S., Gianferrari G., Giannini F., Grassano M., Greco L., Iazzolino B., Introna A., La Bella V., Lattante S., Liguori R., Logroscino G., Logullo F.O., Lunetta C., Mandich P., Mandrioli J., Manera U., Manganelli F., Marangi G., Marinou K., Marrosu M.G., Martinelli I., Messina S., Moglia C., Mosca L., Murru M.R., Origone P., Passaniti C., Petrelli C., Petrucci A., Pozzi S., Pugliatti M., Quattrini A., Ricci C., Riolo G., Riva N., Russo M., Sabatelli M., Salamone P., Salivetto M., Salvi F., Santarelli M., Sbaiz L., Sideri R., Simone I., Simonini C., Spataro R., Tanel R., Tedeschi G., Ticca A., Torriello A., Tranquilli S., Tremolizzo L., Trojsi F., Vasta R., Vacchiano V., Vita G., Volanti P., Zollino M., Zucchi E., Johnson, J. O., Chia, R., Miller, D. E., Li, R., Kumaran, R., Abramzon, Y., Alahmady, N., Renton, A. E., Topp, S. D., Gibbs, J. R., Cookson, M. R., Sabir, M. S., Dalgard, C. L., Troakes, C., Jones, A. R., Shatunov, A., Iacoangeli, A., Al Khleifat, A., Ticozzi, N., Silani, V., Gellera, C., Blair, I. P., Dobson-Stone, C., Kwok, J. B., Bonkowski, E. S., Palvadeau, R., Tienari, P. J., Morrison, K. E., Shaw, P. J., Al-Chalabi, A., Brown, R. H., Calvo, A., Mora, G., Al-Saif, H., Gotkine, M., Leigh, F., Chang, I. J., Perlman, S. J., Glass, I., Scott, A. I., Shaw, C. E., Basak, A. N., Landers, J. E., Chio, A., Crawford, T. O., Smith, B. N., Traynor, B. J., Fallini, C., Gkazi, A. S., Scotter, E. L., Kenna, K. P., Keagle, P., Tiloca, C., Vance, C., Colombrita, C., King, A., Pensato, V., Castellotti, B., Baas, F., Ten Asbroek, A. L. M. A., McKenna-Yasek, D., Mclaughlin, R. L., Polak, M., Asress, S., Esteban-Perez, J., Stevic, Z., D'Alfonso, S., Mazzini, L., Comi, G. P., Del Bo, R., Ceroni, M., Gagliardi, S., Querin, G., Bertolin, C., Van Rheenen, W., Rademakers, R., Van Blitterswijk, M., Lauria, G., Duga, S., Corti, S., Cereda, C., Corrado, L., Soraru, G., Williams, K. L., Nicholson, G. A., Leblond-Manry, C., Rouleau, G. A., Hardiman, O., Veldink, J. H., Van Den Berg, L. H., Pall, H., Turner, M. R., Talbot, K., Taroni, F., Garcia-Redondo, A., Wu, Z., Glass, J. D., Ratti, A., Adeleye, A., Soltis, A. R., Alba, C., Viollet, C., Bacikova, D., Hupalo, D. N., Sukumar, G., Pollard, H. B., Wilkerson, M. D., Martinez, E. M., Ahmed, S., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Cooper-Knock, J., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., England, B. K., Faghri, F., Feldman, E., Floeter, M. K., Fratta, P., Geiger, J. T., Gerhard, G., Gibson, S. B., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kirby, J., Kowall, N. W., Laaksovirta, H., Landeck, N., Landi, F., Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E. P., Pletnikova, O., Pliner, H. A., Pulst, S. M., Ravits, J. M., Rivera, A., Robberecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Scholz, S. W., Sendtner, M., Sidle, K. C., Simmons, Z., Singleton, A. B., Smith, N., Stone, D. J., Troncoso, J. C., Valori, M., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Angelocola, S. M., Ausiello, F. P., Barberis, M., Bartolomei, I., Battistini, S., Bersano, E., Bisogni, G., Borghero, G., Brunetti, M., Cabona, C., Canale, F., Canosa, A., Cantisani, T. A., Capasso, M., Caponnetto, C., Cardinali, P., Carrera, P., Casale, F., Colletti, T., Conforti, F. L., Conte, A., Conti, E., Corbo, M., Cuccu, S., Dalla Bella, E., D'Errico, E., Demarco, G., Dubbioso, R., Ferrarese, C., Ferraro, P. M., Filippi, M., Fini, N., Floris, G., Fuda, G., Gallone, S., Gianferrari, G., Giannini, F., Grassano, M., Greco, L., Iazzolino, B., Introna, A., La Bella, V., Lattante, S., Liguori, R., Logroscino, G., Logullo, F. O., Lunetta, C., Mandich, P., Mandrioli, J., Manera, U., Manganelli, F., Marangi, G., Marinou, K., Marrosu, M. G., Martinelli, I., Messina, S., Moglia, C., Mosca, L., Murru, M. R., Origone, P., Passaniti, C., Petrelli, C., Petrucci, A., Pozzi, S., Pugliatti, M., Quattrini, A., Ricci, C., Riolo, G., Riva, N., Russo, M., Sabatelli, M., Salamone, P., Salivetto, M., Salvi, F., Santarelli, M., Sbaiz, L., Sideri, R., Simone, I., Simonini, C., Spataro, R., Tanel, R., Tedeschi, G., Ticca, A., Torriello, A., Tranquilli, S., Tremolizzo, L., Trojsi, F., Vasta, R., Vacchiano, V., Vita, G., Volanti, P., Zollino, M., Zucchi, E., Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Palvadeau, Robin, Johnson, Janel O., Chia, Ruth, Miller, Danny E., Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E., Topp, Simon D., Gibbs, J. Raphael, Cookson, Mark R., Sabir, Marya S., Dalgard, Clifton L., Troakes, Claire, Jones, Ashley R., Shatunov, Aleksey, Lacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P., Dobson-Stone, Carol, Kwok, John B., Bonkowski, Emily S., Tienari, Pentti J., Morrison, Karen E., Shaw, Pamela J., Al-Chalabi, Ammar, Jr, Robert H. Brown, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J., Perlman, Seth J., Glass, Ian, Scott, Anna, I., Landers, John E., Chio, Adriano, Crawford, Thomas O., Smith, Bradley N., Traynor, Bryan J., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, HUS Neurocenter, Department of Neurosciences, Clinicum, Neurologian yksikkö, TRIMM - Translational Immunology Research Program, Pentti Tienari / Principal Investigator, Human Genetics, ARD - Amsterdam Reproduction and Development, ANS - Complex Trait Genetics, Johnson, Janel O, Miller, Danny E, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Jones, Ashley R, Iacoangeli, Alfredo, Blair, Ian P, Kwok, John B, Bonkowski, Emily S, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Brown, Robert H, Chang, Irene J, Perlman, Seth J, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, Mclaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesú, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexi, Broach, Jame, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, Demarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta
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Hereditary sensory neuropathy ,L-serine ,Mutations ,Deoxysphingolipids ,Accumulation ,Enzyme complex ,Juvenile amyotrophic lateral sclerosis ,Serine C-Palmitoyltransferase ,Whole Exome Sequencing ,0302 clinical medicine ,Medicine ,Family history ,Amyotrophic lateral sclerosis ,Child ,Index case ,Exome sequencing ,Original Investigation ,0303 health sciences ,Neurosciences and neurology ,3. Good health ,Child, Preschool ,Failure to thrive ,Female ,medicine.symptom ,Life Sciences & Biomedicine ,L-SERINE ,Comments ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Amyotrophic Lateral Sclerosis ,Genetic Predisposition to Disease ,Humans ,Mutation ,Young Adult ,Clinical Neurology ,NO ,03 medical and health sciences ,DEOXYSPHINGOLIPIDS ,Internal medicine ,Exome Sequencing ,Online First ,Juvenile ,Preschool ,030304 developmental biology ,ACCUMULATION ,Science & Technology ,SPTLC1 ,business.industry ,MUTATIONS ,Research ,3112 Neurosciences ,medicine.disease ,HEREDITARY SENSORY NEUROPATHY ,juvenile ,3111 Biomedicine ,Neurology (clinical) ,Neurosciences & Neurology ,ALS ,genetic ,business ,030217 neurology & neurosurgery ,Amyotrophic Lateral Sclerosi - Abstract
Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder., This genetic association study identifies genetic variants associated with juvenile amyotrophic lateral sclerosis., Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
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- 2021
12. Indwelling Tunneled Pleural Catheters in Patients with Hepatic Hydrothorax A Single-Center Analysis for Outcomes and Complications
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AL-Habeeb, F.F., primary, Carle-Talbot, K., additional, Rakocevic, N., additional, Zhang, T., additional, Mitchell, M., additional, and Amjadi, K., additional
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- 2022
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13. The clinical landscape for SMA in a new therapeutic era
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Talbot, K and Tizzano, E F
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- 2017
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14. The SMA Trust: the role of a disease-focused research charity in developing treatments for SMA
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Christie-Brown, V, Mitchell, J, and Talbot, K
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- 2017
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15. Prevalence of depression in amyotrophic lateral sclerosis/motor neuron disease: multi-attribute ascertainment and trajectories over 30 months.
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Young, C. A., Ealing, J., McDermott, C. J., Williams, T. L., Al-Chalabi, A., Majeed, T., Talbot, K., Harrower, T., Faull, C., Malaspina, A., Annadale, J., Mills, R. J., and Tennant, A.
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MOTOR neuron diseases ,AMYOTROPHIC lateral sclerosis ,ANTIDEPRESSANTS ,MENTAL depression ,NEUROLOGICAL disorders - Abstract
Objective: Evidence is equivocal about the prevalence of depression in amyotrophic lateral sclerosis (ALS). This study uses a multi-attribute ascertainment of the prevalence of depression and examines this prevalence over time. Methods: Patients with ALS were recruited into the Trajectories of Outcome in Neurological Conditions (TONiC-ALS) study. Caseness was identified by the Modified-Hospital Anxiety and Depression Scale (M-HADS). In addition, participants provided data on co-morbidities and medication use. A combination of the three was used to derive the estimate for the prevalence of depression, treated or untreated. Longitudinal data were analyzed by trajectory analysis of interval level M-HADS-Depression data. Results: Among 1120 participants, the mean age was 65.0 years (SD 10.7), 60.4% male, and the median duration since diagnosis was 9 months (IQR 4–24). Caseness of probable depression at baseline, defined by M-HADS-Depression, was 6.45% (95%CI: 5.1–8.0). Taken together with antidepressant medication and co-morbidity data, the prevalence of depression was 23.1% (95%CI: 20.7–25.6). Of those with depression, 17.8% were untreated. Trajectory analysis identified three groups, one of which contained the most cases; the level of depression for each group remained almost constant over time. Conclusion: Depression affects almost a quarter of those with ALS, largely confined to a single trajectory group. Prevalence estimates based on screening for current depressive symptoms substantially under-estimate the population experiencing depression. Future prevalence studies should differentiate data based on current symptoms from those including treated patients. Both have their place in assessing depression and the response by the health care system, including medication, depending upon the hypothesis under test. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Src kinase as a mediator of convergent molecular abnormalities leading to NMDAR hypoactivity in schizophrenia
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Banerjee, A, Wang, H-Y, Borgmann-Winter, K E, MacDonald, M L, Kaprielian, H, Stucky, A, Kvasic, J, Egbujo, C, Ray, R, Talbot, K, Hemby, S E, Siegel, S J, Arnold, S E, Sleiman, P, Chang, X, Hakonarson, H, Gur, R E, and Hahn, C-G
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- 2015
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17. Comfort perception of 3D printed orthotics in individuals with symptomatic pes planus
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Ho, M., primary, Nguyen, J., additional, Heales, L., additional, Kean, C., additional, Kong, P.W., additional, Talbot, K., additional, and Stanton, R., additional
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- 2021
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18. Theme 05 - Human Cell Biology and Pathology (including iPSC studies).
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Dafinca, R., Tosat Bitrian, C., Scaber, J., Talbot, K., Hunt, G., Yildiz, O., Schroth, J., Spargo, T., Henson, S., Ibrahim, Z., Al-Chalabi, A., Barnes, M., Iacoangeli, A., Malaspina, A., Motaln, H., Čerček, U., Goswami, A., Rogelj, B., Clément, V., and Roy, V.
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HUMAN biology ,CYTOLOGY ,SINGLE-strand DNA breaks ,PATHOLOGY ,AMYOTROPHIC lateral sclerosis ,FRONTOTEMPORAL lobar degeneration - Abstract
ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity. J Cell Sci. 2015; 128: 4151 - 9. 4 Paré B, Gros-Louis F. Potential skin involvement in ALS: revisiting Charcot's observation - a review of skin abnormalities in ALS. ALS-linked SOD1 mutants enhance neurite outgrowth and branching in adult motor neurons. Progressive motor neuron pathology and the role of astrocytes in a human stem cell model of VCP-related ALS. [Extracted from the article]
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- 2022
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19. Motor neuron disease: current management and future prospects
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Simon, N. G., Huynh, W., Vucic, S., Talbot, K., and Kiernan, M. C.
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- 2015
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20. A Muscle-Type Tropomyosin in Human Fibroblasts: Evidence for Expression by an Alternative RNA Splicing Mechanism
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MacLeod, A. R., Houlker, C., Reinach, F. C., Smillie, L. B., Talbot, K., Modi, G., and Walsh, F. S.
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- 1985
21. RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets
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Kent, O A, Fox-Talbot, K, and Halushka, M K
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- 2013
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22. Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis
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Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, Zucchi, Elisabetta, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta
- Abstract
Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, setting, and participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main outcomes and measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis
- Published
- 2021
23. Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials
- Author
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van Eijk, Ruben P. A, Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J. C, Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen C, Counsell C, Farrin A, Al-Chalabi A, Dickie B, Kelly J, Leigh PN, Murphy CL, Payan C, Reynolds G, Shaw P, Steen IN, Thornhill M, Waters J, Zajicek J, Shaw PJ, Young CA, Morrison KE, Dhariwal S, Hornabrook R, Savage L, Burn DJ, Khoo TK, Dougherty A, Wijesekera L, Ellis CM, Ali R, O'Hanlon K, Panicker J, Pate L, Ray P, Wyatt L, Copeland L, Ealing J, Hamdalla H, Leroi I, Murphy C, O'Keeffe F, Oughton E, Partington L, Paterson P, Rog D, Sathish A, Sexton D, Smith J, Vanek H, Dodds S, Williams TL, Clarke J, Eziefula C, Howard R, Orrell R, Sidle K, Sylvester R, Barrett W, Merritt C, Talbot K, Turner MR, Whatley C, Williams C, Williams J, Cosby C, Hanemann CO, Imam I, Phillips C, Timings L, Crawford SE, Hewamadduma C, Hibberd R, Hollinger H, McDermott C, Mills G, Rafiq M, Taylor A, Waines E, Walsh T, Addison-Jones R, Birt J, Hare M, Majid T, Tortelli R, D'Errico E, Bartolomei I, Barbarossa E, Depau B, Costantino E, D'Amico E, Uncini A, Manzoli C, Quatrale R, Sette E, Montanari E, Merello M, Zarcone D, Mascolo M, Vignolo M, Messina S, Morelli C, Marinou K, Papetti L, Lunetta C, Gorni K, De Cicco D, Pipia C, Sola P, Georgoulopoulou E, Sagnelli A, Tedeschi, Gioacchino, Oggioni G, Nasuelli N, D'Ascenzo C, Cima V, Aiello M, Rizzi R, Rinaldi E, Luigetti M, Conte A, Torzini A, Greco G, Mutani R, Fuda G, Tommasi MA, van Eijk, Ruben P. A, Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J. C, Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen, C, Counsell, C, Farrin, A, Al-Chalabi, A, Dickie, B, Kelly, J, Leigh, Pn, Murphy, Cl, Payan, C, Reynolds, G, Shaw, P, Steen, In, Thornhill, M, Waters, J, Zajicek, J, Shaw, Pj, Young, Ca, Morrison, Ke, Dhariwal, S, Hornabrook, R, Savage, L, Burn, Dj, Khoo, Tk, Dougherty, A, Wijesekera, L, Ellis, Cm, Ali, R, O'Hanlon, K, Panicker, J, Pate, L, Ray, P, Wyatt, L, Copeland, L, Ealing, J, Hamdalla, H, Leroi, I, Murphy, C, O'Keeffe, F, Oughton, E, Partington, L, Paterson, P, Rog, D, Sathish, A, Sexton, D, Smith, J, Vanek, H, Dodds, S, Williams, Tl, Clarke, J, Eziefula, C, Howard, R, Orrell, R, Sidle, K, Sylvester, R, Barrett, W, Merritt, C, Talbot, K, Turner, Mr, Whatley, C, Williams, C, Williams, J, Cosby, C, Hanemann, Co, Imam, I, Phillips, C, Timings, L, Crawford, Se, Hewamadduma, C, Hibberd, R, Hollinger, H, Mcdermott, C, Mills, G, Rafiq, M, Taylor, A, Waines, E, Walsh, T, Addison-Jones, R, Birt, J, Hare, M, Majid, T, Tortelli, R, D'Errico, E, Bartolomei, I, Barbarossa, E, Depau, B, Costantino, E, D'Amico, E, Uncini, A, Manzoli, C, Quatrale, R, Sette, E, Montanari, E, Merello, M, Zarcone, D, Mascolo, M, Vignolo, M, Messina, S, Morelli, C, Marinou, K, Papetti, L, Lunetta, C, Gorni, K, De Cicco, D, Pipia, C, Sola, P, Georgoulopoulou, E, Sagnelli, A, Tedeschi, Gioacchino, Oggioni, G, Nasuelli, N, D'Ascenzo, C, Cima, V, Aiello, M, Rizzi, R, Rinaldi, E, Luigetti, M, Conte, A, Torzini, A, Greco, G, Mutani, R, Fuda, G, and Tommasi, Ma
- Subjects
Oncology ,R853.C55 ,medicine.medical_specialty ,Genotype ,Neuroprotective Agent ,Clinical Neurology ,Nerve Tissue Proteins ,Review ,Amyotrophic Lateral Sclerosis ,C9orf72 Protein ,Lithium Carbonate ,Neuroprotective Agents ,Proportional Hazards Models ,Proteins ,Pharmacogenetics ,Randomized Controlled Trials as Topic ,Neurology (clinical) ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Journal Article ,030212 general & internal medicine ,Amyotrophic lateral sclerosis ,business.industry ,Protein ,Pharmacogenetic ,medicine.disease ,Clinical trial ,RC0346 ,Meta-analysis ,Nerve Tissue Protein ,Proportional Hazards Model ,business ,030217 neurology & neurosurgery ,Meta-Analysis ,Amyotrophic Lateral Sclerosi - Abstract
OBJECTIVE\ud \ud To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders.\ud \ud METHODS\ud \ud Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype.\ud \ud RESULTS\ud \ud Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3).\ud \ud CONCLUSIONS\ud \ud This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials.
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- 2017
24. Amyotrophic lateral sclerosis with a heterozygous D91A SOD1 variant and classical ALS-TDP neuropathology
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Feneberg, E, Turner, MR, Ansorge, O, and Talbot, K
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Male ,Heterozygote ,SOD1 ,Autopsy ,Neuropathology ,03 medical and health sciences ,0302 clinical medicine ,Superoxide Dismutase-1 ,Medicine ,Humans ,030212 general & internal medicine ,Heterozygous carrier ,Amyotrophic lateral sclerosis ,Allele frequency ,Genetics ,business.industry ,Carrier state ,Amyotrophic Lateral Sclerosis ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,TDP-43 Proteinopathies ,Antisense oligonucleotides ,Mutation ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
SOD1 mutations are a frequent cause of autosomal dominant familial amyotrophic lateral sclerosis (fALS).1 The D91A SOD1 variant is unique in its association with an atypical form of autosomal recessive fALS in Scandinavia. ALS has also been described in heterozygous D91A carriers,2 but it remains uncertain whether this is pathogenic, given that the D91A carrier state exists in European populations with an allele frequency of 0.007 ([gnomad.broadinstitute.org/][1]), and the observation that ALS does not co-segregate with the heterozygous carrier status in D91A-associated fALS.3 It is generally accepted that dominant SOD1 cases are neuropathologically distinct from sporadic ALS, because of the absence of the TDP-43 proteinopathy found in 97% of all ALS cases, suggesting that different pathogenic mechanisms are involved.4 With the advent of trials of antisense oligonucleotides in SOD1-related ALS it is critical to establish if D91A SOD1 is pathogenic in the heterozygous state, to ensure appropriate recruitment of patients to clinical trials. Here we report a case of corticobulbar ALS in an individual heterozygous for the D91A variant, with autopsy findings of widespread TDP-43 proteinopathy typical of sporadic ALS (figure). [1]: https://gnomad.broadinstitute.org/
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- 2020
25. A triaging blood test for neurology? Serum neurofilament levels in a cohort of GP referrals
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Turner, M, Robertson, J, Gray, E, Thompson, A, Feneberg, E, and Talbot, K
- Published
- 2020
26. Synergistic Deposition of C4d by Complement‐Activating and Non‐activating Antibodies in Cardiac Transplants
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Murata, K., Fox‐Talbot, K., Qian, Z., Takahashi, K., Stahl, G.L, Baldwin, W.M, and Wasowska, B.A
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- 2007
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27. Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum
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Crow, YJ, Marshall, H, Rice, G, Seabra, L, Jenkinson, EM, Baranano, K, Battini, R, Berger, A, Blair, E, Blauwblomme, T, Bolduc, F, Boddaert, N, Buckard, J, Burnett, H, Calvert, S, Caumes, R, Ng, AC-H, Chiang, D, Clifford, DB, Cordelli, DM, Burca, A, Demic, N, Desguerre, I, De Waele, L, Di Fonzo, A, Dunham, SR, Dyack, S, Elmslie, F, Ferrand, M, Fisher, G, Karimiani, EG, Ghoumid, J, Gibbon, F, Goel, H, Hilmarsen, HT, Hughes, I, Jacob, A, Jones, EA, Kumar, R, Leventer, RJ, MacDonald, S, Maroofian, R, Mehta, SG, Metz, I, Monfrini, E, Neumann, D, Noetzel, M, O'Driscoll, M, Ounap, K, Panzer, A, Parikh, S, Prabhakar, P, Ramond, F, Sandford, R, Saneto, R, Soh, C, Stutterd, CA, Subramanian, GM, Talbot, K, Thomas, RH, Toro, C, Touraine, R, Wakeling, E, Wassmer, E, Whitney, A, Livingston, JH, O'Keefe, RT, Badrock, AP, Crow, YJ, Marshall, H, Rice, G, Seabra, L, Jenkinson, EM, Baranano, K, Battini, R, Berger, A, Blair, E, Blauwblomme, T, Bolduc, F, Boddaert, N, Buckard, J, Burnett, H, Calvert, S, Caumes, R, Ng, AC-H, Chiang, D, Clifford, DB, Cordelli, DM, Burca, A, Demic, N, Desguerre, I, De Waele, L, Di Fonzo, A, Dunham, SR, Dyack, S, Elmslie, F, Ferrand, M, Fisher, G, Karimiani, EG, Ghoumid, J, Gibbon, F, Goel, H, Hilmarsen, HT, Hughes, I, Jacob, A, Jones, EA, Kumar, R, Leventer, RJ, MacDonald, S, Maroofian, R, Mehta, SG, Metz, I, Monfrini, E, Neumann, D, Noetzel, M, O'Driscoll, M, Ounap, K, Panzer, A, Parikh, S, Prabhakar, P, Ramond, F, Sandford, R, Saneto, R, Soh, C, Stutterd, CA, Subramanian, GM, Talbot, K, Thomas, RH, Toro, C, Touraine, R, Wakeling, E, Wassmer, E, Whitney, A, Livingston, JH, O'Keefe, RT, and Badrock, AP
- Abstract
Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 56 probands were compound heterozygotes, with parental consanguinity reported in only three families. Forty nine of 56 probands were either heterozygous (46) or homozygous (three) for a mutation involving one of seven nucleotides that facilitate a novel intramolecular interaction between the 5' end and 3' extension of precursor-U8. There was no obvious genotype-phenotype correlation to explain the marked variability in age at onset. Complementing recently published functional analyses in a zebrafish model, these data suggest that LCC most often occurs due to combinatorial severe and milder mutations, with the latter mostly affecting 3' end processing of precursor-U8.
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- 2020
28. Corrigendum to: Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and homing of bone marrow-derived angiogenic cells
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Sarkar, K, primary, Rey, S, additional, Zhang, X, additional, Sebastian, R, additional, Marti, G P, additional, Fox-Talbot, K, additional, Cardona, A V, additional, Du, J, additional, Tan, Y S, additional, Liu, L, additional, Lay, F, additional, Gonzalez, F J, additional, Harmon, J W, additional, and Semenza, G L, additional
- Published
- 2021
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29. Amyotrophic lateral sclerosis: cell degeneration or system degeneration?: 14M
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Talbot, K.
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- 2013
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30. Coagulation factor X Arg386 specifically affects activation by the intrinsic pathway: a novel patient mutation
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VANDEN HOEK, A. L., TALBOT, K., CARTER, I. S. R., VICKARS, L., CARTER, C. J., JACKSON, S. C., MacGILLIVRAY, R. T. A., and PRYZDIAL, E. L. G.
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- 2012
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31. Systematic review of methodology used in ultrasound studies aimed at creating charts of fetal size
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Ioannou, C, Talbot, K, Ohuma, E, Sarris, I, Villar, J, Conde-Agudelo, A, and Papageorghiou, A T
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- 2012
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32. What is the place of the Artificial Urinary Sphincter in 2012?: 57
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MOON, D. and TALBOT, K.
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- 2012
33. Spinal muscular atrophy
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Talbot, K.
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- 1999
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34. Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis
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Turner, M R, Wicks, P, Brownstein, C A, Massagli, M P, Toronjo, M, Talbot, K, and Al-Chalabi, A
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- 2011
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35. Catastrophic hyperkalaemia following administration of suxamethonium chloride to a patient with undiagnosed amyotrophic lateral sclerosis
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Turner, MR, Lawrence, H, Arnold, I, Ansorge, O, and Talbot, K
- Published
- 2011
36. An Unusual Presentation of Pneumocystis Jirovecii Pneumonia Presenting as Multiples Masses and Nodules
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Carle-Talbot, K., primary and McGovern Murphy, F., additional
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- 2020
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37. EXPRESSION OF THE SMA DETERMINING FACTOR, SURVIVAL MOTOR NEURON, MODULATES THE ALS PHENOTYPE
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Turner, B., Parkinson, N., Bäumer, D., Alfazema, N., Davies, K., Atkin, J., Horne, M., and Talbot, K.
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- 2010
38. Review: Neuromuscular synaptic vulnerability in motor neurone disease: amyotrophic lateral sclerosis and spinal muscular atrophy
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Murray, L. M., Talbot, K., and Gillingwater, T. H.
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- 2010
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39. Primary angiitis of the CNS mimicking a spinal cord tumour
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Baumer, D., Flossmann, E., Cudlip, S., Quaghebeur, G., Jeans, A., and Talbot, K.
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- 2008
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40. Royal academy of medicine in Ireland section of surgery: Proceedings of registrar’s prize meeting held 22nd January, 1996
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Kennedy, J. G., Kasser, J. R., Glimcher, M. J., Salih, E. J., Neary, P., Condon, C., Kilbaugh, T., Redmond, H. P., Bouchier-Hayes, D., Fulton, G. J., Davies, M. G., Svendsen, E., Lefkowitz, R. J., Koch, W. J., Hagen, P -O., Fulton, G. J., Davies, M. G., Svendsen, E., Lefkowitz, R. J., Koch, W. J., Hagen, P -O., Johnston, S. M., Lipsett, P. A., Fox-Talbot, K. M., Lillemoe, K. D., Pitt, H. A., Kelly, J. L., O’Suilleabhain, C. B., Horgan, A. F., O’Riordain, M. G., Mannick, J. A., Rodrick, M. L., Chen, G., Kelly, C., Leahy, A., Bouchier-Hayes, D. J., Kelly, P., O’Riordain, D. S., Horgan, P. G., Keane, F. B., Tanner, W. A., Rothwell, J. F., Staunton, M. J., O’Mahony, L., Gaffney, E. F., Mealy, K., Hennessy, T. P. J., Coveney, E., Clary, B., Philip, R., and Kim Lyerly, H.
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- 1998
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41. TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but absence of copy number variation
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Bäumer, D, Parkinson, N, and Talbot, K
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- 2009
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42. Coagulation factor Xa derivative, Xa33/13, enhances plasminogen activation and clot lysis: OC-MO-118
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Talbot, K, Meixner, S C, and Pryzdial, E LG
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- 2009
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43. Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background
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Cox, M. M., Tucker, A. M., Tang, J., Talbot, K., Richer, D. C., Yeh, L., and Arnold, S. E.
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- 2009
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44. Psychiatric disorders prior to amyotrophic lateral sclerosis
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Turner, M, Goldacre, R, Talbot, K, and Goldacre, MJ
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Male ,Time Factors ,Databases, Factual ,England ,Case-Control Studies ,Mental Disorders ,Amyotrophic Lateral Sclerosis ,Humans ,Female ,Comorbidity ,Brief Communication ,Brief Communications - Abstract
It is recognized that neuropsychiatric conditions are overrepresented in amyotrophic lateral sclerosis (ALS) patient kindreds and psychiatric symptoms may precede the onset of motor symptoms. Using a hospital record linkage database, hospitalization with a diagnosis of schizophrenia, bipolar disorder, depression, or anxiety was significantly associated with a first diagnosis of ALS within the following year. This is likely to specifically reflect the clinicopathological overlap of ALS with frontotemporal dementia. A diagnosis of depression was significantly associated with a first record of ALS ≥5 years later, in keeping with growing evidence for major depressive disorder as an early marker of cerebral neurodegeneration. Ann Neurol 2016;80:935-938.
- Published
- 2016
45. Combined electro-acoustic stimulation: a beneficial union?
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Talbot, K. N. and Hartley, D. E.H.
- Published
- 2008
46. Age-dependent and -independent behavioral deficits in Tg2576 mice
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Deacon, R. M.J., Cholerton, L. L., Talbot, K., Nair-Roberts, R. G., Sanderson, D. J., Romberg, C., Koros, E., Bornemann, K. D., and Rawlins, J. N.P.
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- 2008
- Full Text
- View/download PDF
47. Asymmetrical late onset motor neuropathy associated with a novel mutation in the small heat shock protein HSPB1 (HSP27)
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James, P A, Rankin, J, and Talbot, K
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- 2008
- Full Text
- View/download PDF
48. Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis
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Allen, S., Hall, B., Castelli, L., Francis, L., Woof, R., Siskos, A., Kouloura, E., Gray, E., Thompson, A., Talbot, K., Higginbottom, A., Myszczynska, M., Allen, C., Stopford, M., Hemingway, J., Bauer, C., Webster, C., De Vos, K., Turner, M., Hautbergue, G., Ferraiuolo, L., and Shaw, P.
- Abstract
As clinical evidence supports a negative impact of dysfunctional energy metabolism on the disease progression in amyotrophic lateral sclerosis, it is vital to understand how the energy metabolic pathways are altered and whether they can be restored to slow disease progression. Possible approaches include increasing or re-routing catabolism of alternative fuel sources to supplement the glycolytic and mitochondrial pathways such as glycogen, ketone bodies and nucleosides. To analyse the basis of the catabolic defect in amyotrophic lateral sclerosis we have employed a novel phenotypic metabolic array. We have profiled fibroblasts and induced neuronal progenitor derived human iAstrocytes from C9orf72 amyotrophic lateral sclerosis patients compared to normal controls, measuring the rates of production of reduced nicotinamide adenine dinucleotides from 91 potential energy substrates. This approach has shown for the first time that C9orf72 human iAstrocytes and fibroblasts have an adenosine to inosine deamination defect caused by reduction of adenosine deaminase, which is also observed in iAstrocytes from sporadic patients. Patient derived iAstrocyte lines were more susceptible to adenosine-induced toxicity, which could be mimicked by inhibiting adenosine deaminase in control lines. Furthermore, adenosine deaminase inhibition in control iAstrocytes led to increased motor neuron toxicity in co-cultures, similar tothe levels observed with patient derived iAstrocytes. Bypassing metabolically the adenosine deaminase defect by inosine supplementation was beneficial bioenergetically in vitro, increasing\ud glycolytic energy output and leading to an increase in motor neuron survival in co-cultures with iAstrocytes. Inosine supplementation, in combination with modulation of the level of adenosine deaminase may represent a beneficial therapeutic approach to evaluate in patients with amyotrophic lateral sclerosis.
- Published
- 2019
49. Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA
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McGuire D, Alexander J, Johansen O, Perkovic V, Rosenstock J, Cooper M, Wanner C, Kahn S, Toto R, Zinman B, Baanstra D, Pfarr E, Schnaidt S, Meinicke T, George J, von Eynatten M, Marx N, Aizenberg D, Fiorella A, Edgardo N, Belen C, Alonso P, Walter M, Maia K, Guillermo S, Leandro B, Constanza R, Alejandra N, Melina C, Ariel I, Rodrigo C, Alvarez C, Jorge M, Gabriel C, German S, Bartolacci I, Bolobanich G, Tale T, Meritano M, Echeverria M, Gerrini S, Alvarez M, Torrijos N, Berli M, Coggiola J, Castaneda G, Rode R, Milessi R, Roude A, Bono J, Caresani J, Arias V, Westberg J, Allende G, Liberman A, Bordonava A, Almagro S, Gerbaudo C, Schiavi L, Budassi N, Cecilia M, Buncuga M, Carlos S, Osvaldo T, Mercedes S, Calella P, Agustina V, Aljandro M, Alberto D, Fiorella M, Cantero M, Cariganano M, Anadon P, Cartasegna L, Gabriela M, Fernanda A, Alberto R, Chacon C, Jazmin F, Colombo H, Coni E, Mattausch S, Thomsenhall K, della Torre M, Morandini M, Berra F, Margarita H, Commendatore V, Tedesco J, Bolzan P, Cuneo C, Narcisa G, Caputi V, Pablo S, Sandra G, Pacora F, Tinari M, Jure H, Parody M, Toranzo A, Frechtel G, Yohena S, Lovecchio S, Muller C, Martin S, Olivera C, Breyaui M, Bianchi G, Garcia C, Luciana V, Florencia F, Ruben G, Gelersztein E, Rey G, Sanchez C, Fornasari L, Di Pierro L, Giacomi G, Miguel S, Laura T, Gonzalo C, Ramon C, Glenny J, Koretzky M, Porto A, Tiberio O, Ellenberg A, Saurral R, Igarzabal C, Vilamajo O, Matkovich J, de Lapertosa S, Villagra M, Cuzziol G, de la Cruz M, Pinchetti R, Mierez M, Lopez C, Gorosito V, Gabito A, Kleiban A, Grosembacher L, Adrian P, Paula R, Javier G, Kraft F, Andres F, Krynski F, Nicolas P, Marcelo F, Alfredo F, de la Fuente R, Natalia C, Luquez H, Recuero Y, Becchetti N, Ruiz M, Costantino M, Vazquez G, Guzman C, Pelatia P, Maffei L, Sassone S, Yantorno M, Prado G, Khron B, Maldonado N, Gustavo L, Veronica V, Marino J, Elizabeth A, Alejandra C, Oscar R, Azize G, Gallardo M, Escudero M, Vargas E, Ramos H, Lucero C, Najenson M, Crocci I, Chiesa A, Nardone L, Dominguez S, Zanini A, Manghi F, Grossman M, Giudice G, Romeo A, Piskorz D, Miguel C, Susana D, Noeli U, Rosa S, Martin V, Soledad A, Virginia M, Lorena G, Prado A, Veronica L, Eduardo H, Adolfo P, Florencia W, Rista L, Scolari C, Rojas N, Bertolio V, Zarandon R, Jair S, Orlando C, Sanabria H, Ignacio D, Viviana C, Marina R, Sarjanovich R, Scaro G, Huerta C, Mana M, Gutierrez M, Dain A, Gavicola R, Sessa H, Sacripanti J, Felman R, Vilarino P, Sicer M, Lagrutta M, Sala J, Casabella T, Cecilia H, Carlos B, Vines G, Javier R, Vico M, Lanchiotti P, Martella C, Torres L, Villarino A, Molina M, Martinez J, Farias C, Bertola S, Rojas M, Guzman P, Nisi J, Martinez D, Barrionuevo M, Vita N, Lopez A, Vottero E, Giuliano M, Paron L, Vogel D, Mele P, Imposti H, Dominguez A, Zaidman C, Fernando G, Beck M, Beltrame P, Chemello D, Junior R, Abreu A, Fernandes V, Saboia J, Rodrigues L, Carvalho M, Gurgel M, Gadelha D, Ramos C, Borba V, Golbert M, Pitthan M, Golbert L, Valentini R, Canani L, Gross J, Valenti A, Sartori C, Dutra O, Azevedo E, Azevedo A, Vaz R, Vaz H, da Costa F, da Costa L, Panarotto D, Lain F, Camazzola F, Dellomea B, Rech R, Pizzato P, Nunes C, Jaeger C, Silveira D, Wagner L, Machado L, Rea R, de Bem A, Alves J, Jonasson T, Malucelli F, Betti R, Lerario A, Lisboa H, Bem J, Tres G, Tavares C, Nardi A, Pozzatto M, Backes L, Reolao J, Scariot E, Ziguer E, Baldissera D, Griz L, Antunes D, Victor F, Freire K, Barros A, Costi B, Sa M, Carneiro A, Felicio J, Felicio K, Penha P, Ferreira J, Melo F, Alves A, Souza A, Costa L, Pinheiro D, Turatti L, Augusto G, Leanca C, Santomauro A, Forti A, Sena R, Marinho A, Facanha C, de Souza K, de Souza A, de Queiroz W, Leite S, Vieira S, Gubert L, Olsen A, Piazzetta G, Fuck A, Ferreira M, Fortes J, Brandao T, Alves F, Radice E, dos Santos J, de Almeida R, Franco D, Saporito W, Eliaschewitz F, de Siqueira K, Bona R, Genestreti P, de Castro D, Visconti G, Sampaio C, Palhares F, Konigsfeld H, Alves E, Feder C, Leao B, Saraiva J, Rodovalho S, Costa M, Pires N, Figueiredo E, Werner G, Garcia J, de Paiva I, Quirino B, Botelho R, da Silva R, Navarro A, Lourenco C, Pereira A, Arantes F, Boner D, Saad J, Falchetto E, Washizu E, Mandil A, Pimenta N, Tofani F, Fonseca T, Teixeira L, Maia L, Lemos M, Mouco O, Nakazone M, Weiand L, Bohn J, Hissa M, Araripe F, Carvalho F, Cancado G, Wang R, Chacra A, Fusaro A, de Mendonca E, Cercato C, Halpern A, Alves B, Braile M, Sestito R, Mustafa E, Ferreira V, Sbardellini B, de Almeida P, Guimaraes F, Piedade M, Bienert I, Braga J, Daher R, Hirakawa T, Terra E, Farias E, Figueiredo M, Lima L, Moraes K, Avelino I, Flato U, Plavnik F, Portes E, Moreira M, Vendramini M, Veloso R, Padilha M, Rodrigues A, Adam R, Santos S, Sayeg N, Guerrero D, Madeira M, Siqueira J, Pinheiro R, Villacorta A, Mellazi A, Braga T, Kaiser S, Paolino B, Lefterov I, Marinchev A, Angelova S, Klyuchkova N, Lybomirova Z, Kerekovski Y, Kuneva T, Penkova D, Levterov G, Videnova E, Georgieva P, Shinkov A, Borissova A, Vlahov J, Dakovska-Dekova L, Lucheva M, Luchev P, Temelkova M, Borisova K, Tsenov S, Andreeva V, Margaritov V, Arasheva G, Lozanov L, Borisov R, Gorcheva D, Henein S, Whatley S, Boutros M, Kalyniuk N, Berlingieri J, Nisker W, Hoag G, Hepburn D, Harvey M, Manjoo P, Yale J, Sherman M, Tsoukas M, Rehman W, Mason M, Santerre M, De Kock J, Barkhuizen F, Rooke C, Gill C, Kooy J, Burgoyne G, de Kock J, Degen G, Hockman L, Invik R, Roberts P, Ward K, Alasaad H, Susan A, Davies V, Gupta N, Milhalidis J, Grossman L, Agawal N, Yared Z, Rwaheed, Nouhad S, Nahla A, Khandwala H, Warwick A, Wadehra D, Manan A, Vecchiarelli J, Aslam N, Ferrao A, St-Maurice F, Collette R, Davey B, Nawaz S, Coutu B, Costi P, Greiss I, Mansour F, Raymond J, St-Phard W, Nadra I, Della Siega A, Barahona L, Klinke P, Contractor H, Fryer M, Chandra N, Conti B, Telzer L, Sorensen S, Lounsbury N, Martin E, Mitchell L, Pelzer E, Nelson S, Jones M, Cox J, Luco G, Trhoughton T, Labonte R, Chouinard G, Frechette A, Rheaume M, Cusson J, Faucher J, Dery V, Kelly A, Miranda B, Al-Kayssi N, Malette P, Rheault P, Fredette P, Dumas R, Palardy J, Belanger A, Boucher P, Doyon B, Charbonneau J, Bailey G, Odendaal M, Stephan K, Badenhorst J, Knight D, Thurgood A, Johnston M, Cooper-Rosen E, Jagger R, Green M, Weisnagel S, Gangloff A, Bergeron J, Pesant Y, Chevalier P, Woo V, Hurd C, Ruckert G, Lira J, Navarro G, Venegas M, Gonzalez P, Montecinos H, Vidal G, Fernandez M, Varas J, Fernandez C, Aguilar J, Marin R, Kindel C, Yovaniniz P, Gherman O, Aravena M, Carvajal J, Macias E, Corrado P, Lazcano M, Garrido B, Charme G, Carrasco J, Vignolo P, Saavedra S, Gajardo V, Saavedra C, Santamaria D, del Castillo B, Balda I, Zurvarra V, Fu G, Jiang D, Huang H, Wang M, Song J, Lu W, Lin Y, Lu Z, Shi Y, Zhong M, Zhao X, Chen D, Zhang G, He Y, Shi P, Chu K, Gao Q, Deng W, Zhang J, Zhang Y, Chen H, Liu E, Xie Y, Lin R, Tan W, Yuan Z, Wang Y, Ren J, Yu H, Luo M, Ma W, Shi W, Xu H, Xu M, Liu G, 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Kitamura H, Toriumi Y, Ishiguro H, Naganuma T, Shu S, Suzuki K, Hirota Y, Hayashi T, Hozawa K, Fukui T, Abe Y, Yamauchi K, Maruyama M, Matsumura S, Kozuma R, Nagai Y, Kihara Y, Maeda H, Nakanishi K, Iitsuka T, Hatori M, Shinozaki Y, Akiyama D, Kawabe M, Takei M, Sato A, Kawai Y, Kitajima K, Ide M, Sato N, Morisaki H, Nakashima K, Takayanagi H, Watanabe H, Iwahashi N, Tsujimoto M, Hibuse K, Hata T, Ueno K, Tatsuma H, Wakida Y, Ito T, Mizuno R, Fujita H, Konishi N, Kanehira T, Watanabe R, Miyaoka H, Okada T, Yamamoto M, Okita S, Murakami H, Todo Y, Umeoka F, Hori K, Shiraishi K, Tada F, Shimizu T, Tamai J, Sasaki C, Okuzima Y, Yasuda M, Iwaita Y, Tanaka K, Rha S, Na J, Cho D, Cho Y, Hwang E, Choi T, Won K, Kim H, Kim S, Oh D, Lee J, Choi H, Chung H, Park H, Suh Y, Kim Y, Kim N, Kim K, An J, Kim J, Park K, Kwak S, Kim M, Hwangbo Y, Lee D, Hong A, Kim L, Oh C, Moon S, Jung C, Jin J, Hyun B, Yang Y, Kong S, Yoon K, Yang H, Hong T, Oh J, Park J, Lee H, Choi J, Ahn J, Han S, Park W, Jo S, Suh S, An W, Park M, Lee S, Kim D, Jin H, Seo J, Chung C, Lim J, Huh J, Park I, Yu S, Sim N, Khan S, Albakari N, Sivaraman J, Manaf K, Maharuddin I, Nagendram S, Ali N, Abdul Latiff N, Othman N, Sarip S, Chew E, Mohamed S, Aziz N, Hui K, Lin L, Velaiutham S, Khir A, Lee L, Manikam S, Chooi K, Chang M, Ooi C, Anthony J, Seganathirajah M, Ng O, Ismail N, Cheah C, Ramanathan G, Mui N, Wen F, Choo T, Bin Ruhani A, Jamaludin S, Abidin S, Nor F, Abu Hassan M, Hanari N, Ahmad N, Suan M, Zainul N, Ali S, Sridhar G, Han C, Chin A, Vin L, Kadir K, Zain A, Hussain N, Pusparajah P, Lozano F, Gomez A, Zaccari E, Vigil A, Preciado C, de Leon M, Parra M, Cervantes A, Aguirre E, Orozco E, Gonzalez S, Elizondo R, Flores E, Guerrero M, Flores F, Sanchez J, Perez F, Rodriguez J, Martinez L, Marquez D, Gutierrez B, Flores M, Real M, Campos P, Garcia P, Rios M, Romero E, Perez Z, Tarabay C, Munoz L, Farias J, Gonzalez J, Palestino N, Sanchez L, Carrillo G, Ordonez N, Pech C, Andrade M, Euan J, Ortegon M, Garcia S, Orozco J, Vazquez H, Herrera R, Perez E, Arango A, Ibarra M, Gonzales L, Esperano J, Quintana L, Salazar I, Ruiz L, Barron C, Ballesteros C, Cervera L, Hercilla E, Gomez H, Mesa J, Herrera P, Rodriguez M, Ochoa R, Mora E, Charles C, Silva R, Mijangos J, Diaz C, Zavala C, Baron P, Bernal A, Martinez F, Tlapale M, Ramirez E, Basila A, Munguia R, Tello M, Martinez M, Mulder H, van der Graaff P, Nawaz A, Keller I, Schoofs M, Smak-Gregoor P, Al-Windy N, Bulut S, de Jong J, Maas A, Schaardenburgh P, Imholz B, Heijster J, Hoogenberg K, Smit C, Kooy A, Huvers F, Landewe-Cleuren S, Kars M, van Moorsel D, Wolffenbuttel B, Lutgens H, Schutte E, Gansevoort R, Idzerda N, Westerink J, Weijmans M, Berg J, van Kleef M, Slob M, Jaspers N, Hovens M, Monajemi H, Kobielusz-Gembala I, Zmuda W, Adamczyk M, Konieczny M, Strzelecka-Sosik A, Nowacka E, Krzyzagorska E, Sekulska M, CzajkowskaKaczmarek E, Kaczmarek B, Opawska K, Dabrowska M, Kus W, Wrzesien-Kus A, Piotrowski G, Hotlos L, Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, Gmytrasiewicz M, Zambrzycki J, Krysiak-Kowaluk H, Klodawska K, Klszczewski Z, Zieleniewski J, Opadczuk P, Urbanska K, Faran-Grabowska K, Szczepanik T, Siegel A, Kleczek A, Kincel K, Nowak D, Slowik-Gomulka L, Watemborska-Matuszyk G, Lampart J, Strozik-Krecichwost A, Dziewit T, Broncel M, Wojcik-Odyniec J, Jakubczyk E, Wierzbicka K, Witowicz A, Jedrych B, Korczyk P, Socik-Pojawa M, Monteiro P, Monteiro S, Mendes P, Soares F, Mendes S, Leite L, Vicente J, Santos M, Ferreira A, Alves P, Rosario F, Garrao A, Duarte L, Rogado C, Duarte R, Laginha T, Matos P, Raposo J, Mariz J, Teixeira J, Capela C, Leitao A, Cardiga R, Alface M, Augusto S, Basto L, Cunha A, Rei D, Dantas J, Verdasca I, Andrade L, Silva A, Suarez M, Dias V, Silva J, Pereira N, Goncalves M, Goncalves A, Silveira A, Sampaio A, Dias A, Diogo M, Vilaca C, Cif A, Calin T, Elena S, Crisan C, Adina S, Ramona S, Anghel V, Simona C, Turcu L, Mihaela V, Cosma D, Cristina H, Marius-Calin H, Negrisanu G, Andreea-Andrada M, Maria-Mihaela V, Camelia T, Oana P, Monia A, Onaca A, Mircea O, Mot A, Stolea V, Elena N, Barbonta D, Cristian B, Oana S, Popescu A, Madalina M, Coman A, Anca C, Constantinescu S, Mircea C, Diaconu-Sotropa M, Ene D, Pintilei E, Mihai G, Delia R, Toarba I, Simona H, Negru D, Flaminzeanu F, Iulian C, Maria-Cristina C, Doros R, Cleo S, Sorin B, Demian L, Mihai S, Raul B, Ioana A, Nicolau A, Cosmin P, Isabela G, Elena C, Ileana T, Valuyskikh E, Miroshnichenko E, Klementyeva N, Zelman O, Chumakova G, Vigel A, Leonova N, Pergaeva Y, Stefanovskaya O, Pushkareva S, Antoshkina L, Zheleznova N, Iveitsman, Barbarash O, Zvereva T, Zhuravleva E, Zavyrylina I, Usoltceva E, Savostyanova Y, Kupriyanova T, Krivoshapova K, Kondyukova N, Inozemceva A, Argunova Y, Tsyba L, Belenky D, Mariich O, Terekhova A, Tsygankova O, Kuznetsova E, Nagibovich G, Ivchenko Y, Dobronravov V, Dobronravov A, Bush M, Trofimenko I, Vishnevsky A, Zikov V, Kositsyn D, Palzman Z, Spiridonova T, Rodina N, Polozhentsev S, Mamedova L, Panov A, Abesadze I, Alugishvili M, Ivashkin V, Drapkina O, Korneeva O, Zyatenkova E, Glinkina I, Poluboyarinova I, Gurova O, Raykhman A, Vertkin A, Rodykova I, Shamaeva K, Petrovskaya T, Uzueva E, Milovanov Y, Milovanova S, Milovanova L, Markina M, Dobrosmyslov I, Markov V, Afanasiev S, Babich E, Belokopytova N, Demyanov S, Maximov A, Maximov I, Rebrova T, Shtatolkina M, Masin A, Demko A, Chuyko O, Pronina A, Charf G, Akatova E, Urlaeva I, Nikolin O, Khovaeva Y, Ermachkova L, Burdina E, Shvalb P, Suchkov I, Pshennikov A, Gryaznov S, Rymar O, Dolinskaya Y, Bahareva Y, Mustafina S, Sherbakova L, Ovsyannikova A, Bolshakova O, Polunicheva E, Dora S, Agafyina A, Yashina A, Vasilieva I, Yakhontova P, Selivanova S, Kargapoltseva O, Shilina N, Bayramova G, Sorokin I, Astamirova K, Kuchuk P, Koniushenko D, Malykh N, Dvorkin M, Krovelets T, Konovalova K, Seeber M, van Niekerk F, Siebert H, Steenkamp W, Wiid S, Noeth M, Siebert R, Breedt J, Bouwer J, Kapp C, Venter T, Rayner B, Trinder Y, Rheeder P, Delport E, Mathijs S, Soma P, van Zyl D, Strydom M, Marais A, Badat A, Hansa S, Fourie D, Walton T, Engelbrecht J, Jansen J, Roos J, du Toit S, Lehloenya K, van Zyl L, van Zyl F, Naude M, Mookadam M, van der Merwe A, Trokis J, Lombard L, Coetzee K, Ismail S, Bruning H, Latiff G, Yasmin O, Pillay T, Mohamed Z, Dawood S, Stapelberg A, Abrahams P, Jurgens J, van Heerden P, Swart E, Botha C, Meeding J, Hemus A, Oosthuysen W, Visagie G, Fourie N, Hutton P, van der Merwe N, Chelin N, Everton T, Duki M, Ghila N, Joshi M, Hira M, Madueno F, Martinez B, Sebastian N, Mercadal L, Isbert S, Gonzalez I, Asencio J, Figueras M, Rivas M, Garcia H, Fusalba A, Geat D, Cambra G, Sastre J, Castro F, Mas A, Portillo C, Serrano I, Hernandez S, Fajardo F, Juan C, Ferrer J, Peralta F, Padin C, Mauricio D, Madorell B, San Miguel F, Pedrol N, Trescoli C, Montanana C, Gonzalo M, Capellan J, Estrella A, Martinez C, Montesinos I, Loscos A, Coronado J, Perez J, Castillo B, Alonso C, Quesada V, Teruel J, Perez S, Lama M, del Rio E, Zlova T, Ponomarenko K, Karpenko O, Bezuglova S, Mitskevych L, Kizim S, Nevolina I, Katerenchuk V, Liudmyla B, Ivan K, Rudyk I, Olena M, Anna I, Ganna B, Topchii I, Semenovykh P, Yulia Y, Mykhalchyshyn G, Kirienko D, Kobiliak N, Bodnar, Mykhalchyshyn, Pertseva N, Olena G, Tomashkevych H, Korpachev V, Prybyla O, Kovalchuk A, Kushnarova N, Zinych O, Tseluyko V, Andriy Z, Olga R, Mankovskyy B, Zherdova N, Lykhoshapko O, Logoida P, Godlevska O, Olena V, Olga C, Gyrina O, Alifer O, Dozhuk K, Pekhenko V, Gorobets N, Korneichuk A, Makarenko E, Martynyuk L, Martynuyk O, Stanislavchuk M, Larysa P, Natalia S, Botsyurko V, Kostitska I, Dzeman O, Ablitsov Y, Ivaseiko S, Konovart O, Sandurska S, Vendzilovych Y, Samoylov O, Iryna C, Rozhkivska L, Ulyanchenko I, Kateryna V, Orlenko V, Ivaskina K, Tronko M, Tronko K, Pashkovska N, Stankova N, Vynnychenko L, Bolotnikova N, Demokhova N, Reshotko D, Popova A, Dr Bogdana, Tetiana S, Svitlana D, Oksana R, Vlasenko M, Litvinova S, Semenyuk I, Fishchuk O, Mostovoy Y, Tkachenko T, Ovcharuk M, Rasputina L, Vakaliuk I, Tymochko N, Drapchak I, Petrovska L, Lai W, Yen H, Voon W, Lin T, Cheng K, Chiu C, Chu C, Hsu P, Chiang C, Li Y, Kuo C, Lin S, Chao T, Yu W, Sung S, Wang K, Lu T, Shih K, Wu C, Chiang F, Hwang J, Tsai C, Juang J, Jeng J, Tang S, Lai C, Cheng C, Hsieh I, Hsieh M, Chen C, Lee C, Pai P, Ko P, Wang T, Chen T, Wu H, Chang S, Chen K, Hsieh L, Chou C, Jiang J, Lee M, Huang J, Chen J, Chiu K, Tsai L, Chen P, Saxena M, Collier D, Vaidya B, Harman S, Ramell M, Davies M, Chatterjee S, Meakin L, Quinn M, Bain S, Mallipedhi A, Min T, Bashir J, Blagden M, Ali J, McCrimmon R, Brennan G, Malcolm E, McDonald D, Pearson E, Illsley G, Darzy K, Winocour P, Hanif W, Cockwell P, Charlton M, Thekkepat S, Howat I, Devers M, Patrick J, Wyatt N, Smith C, Singh B, Nicholas J, Gillani S, Green F, Bell E, Boyle J, MacKin S, Livingstone R, Arif A, Syed M, Hammoud J, Sparks J, Anderson M, Tumey R, Condit J, Reddy M, Abalos-Galito M, Rebecca J, Barker T, Seaton B, Campbell E, Kompanik H, Jayson L, Huffman C, Bialow M, McDonnell G, McCaffrey J, Manis C, DeLuca E, Levins J, Bartlett M, Anorga K, Franco M, Gentry P, Hodge D, Pohil R, Rschultz, Leggett R, Blair L, Gisler J, Niegos F, Osburn M, Parma K, Schendel S, Stines L, Winnie M, Wu P, Canales J, Yu J, Cornett G, Beavins J, Hyde D, Zapinski D, Johnson T, Levinson D, Ahmed A, Kenny B, Kuehl A, Bates C, Jantzi C, Ananthula P, Shafer J, Louthan J, Bays A, Stapleton A, Staton P, Strum D, Taylor P, Smith A, Rapp R, Bao S, Randolph C, MacGillivray B, Schuster R, Harden T, Barnella C, Dunnam T, Whiles R, Bolick C, Brockmyre A, Plucker S, Marshall C, Poteet C, Morin D, Tavel E, Averill N, McFann A, Purcell D, Dixon T, Corey E, Goss J, Drescher R, Irfan M, Naeem M, Egelhof R, Mehta P, Koehler T, Walia J, Fernandez J, Bedel G, Preet R, Bhuchar S, Ahmed F, Onyema D, Benchabbat A, Kohanbash L, Miller P, Lalinde M, Carrithers E, Patterson R, Raube-Miceli A, Martinez A, Harris B, Levy R, Siev E, Berlin H, DiMattia M, Sugimoto D, Dugas J, Benson M, Stegemoller R, Schmoll M, Kinnaman S, O'Connor T, Powel T, Rudolph L, Lewiecki M, Best E, Chavez J, Garcia M, Cohen R, Colman D, Ocampo M, Heaney L, Rappley G, Quezada I, Santos V, Nikfarjam A, Reyes M, Rodriguez R, Josephs L, Hernandez R, Flores P, Espinoza L, Mejia W, Pedraza Z, Castaneda R, Laguerre J, Cook R, Patel R, Werner H, Blank R, Small S, Andersen J, Holmes D, Farmer M, Wiener V, Pharr W, Bray B, Beekman J, Anderson A, Andrawis N, Gabra N, Moche T, Marty S, Galvez O, Reyes R, Garcia R, Lerma G, Pliquin B, Mayfield R, Durham N, Phillips R, Baran A, Kondo N, Dempsey S, Kufs W, Laddis T, Zimmer K, Van Depol M, Dweck L, Kestler M, Werner N, Ashraf M, Quick A, Schallert G, Sligh T, Trueba P, Batista J, Martinez T, Moya J, Amarales V, Santos E, Torres P, Diaz T, Diaz J, Hodish I, Else T, Buras E, Moratis A, Valika S, Rahman A, Malalis W, Box E, Box P, Kerwood B, Nagaeva J, Metz C, Hinnant J, Griswell D, 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Colfer H, Kane L, Teklinski A, Gadowski G, Levanovich P, Saba F, Confident L, Hossain S, Steinberg B, Philippe B, Choroenthkongtrakal S, Boccalano F, Anand R, Syam V, Manohar A, Suresh P, Madhusudhan P, Patel P, Cambier P, Klonaris J, Cheng W, Fisher S, Schelle M, Reese L, McLean S, Poock J, Hoens J, Rosie A, Welshons R, Dean J, Kuhlman P, Luke R, Lohrbauer L, Cunningham M, Buday P, Lehmann M, Chrzanowski K, Fletcher A, Hargrove J, Harris F, Debs-Perez G, Maiquez A, Cordoves L, Georgescu M, Tayoun H, Munoz F, Ortiz D, Munoz G, Hamzeh I, Misra A, Zhang L, Forgosh L, Loria K, Roncari C, Hommerding J, Morris G, Lebron C, Blake K, LaVenture K, Lange C, Levinson L, Baungarten T, Edevante S, Shawley S, Moyer H, Elliott K, Iachini K, Rajan R, Davis C, Shattuck A, Simon W, Lakin G, Secrist N, Buth D, Steere D, Talbot K, Singh N, Mascolo R, Sloan S, Kmetzo J, Brown J, Carter L, Lawrence M, Arauz-Pacheco C, Lender D, Kozlow W, Cavanaugh L, Wilson J, Gujja P, Akhter F, Khan M, Mohammed A, Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
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cardiovascular disease ,type 2 diabetes mellitus ,heart failure ,chronic kidney diseases - Abstract
Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease. Methods: Participants in 27 countries with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease were randomized 1:1 to receive once daily oral linagliptin 5 mg or placebo, on top of standard of care. All hospitalization for HF (hHF), cardiovascular outcomes, and deaths were prospectively captured and centrally adjudicated. In prespecified and post hoc analyses of HF and related events, Cox proportional hazards models adjusting for region and baseline history of HF were used. Recurrent hHF events were analyzed using a negative binomial model. In a subset of participants with left ventricular ejection fraction captured within the year before randomization, HF-related outcomes were assessed in subgroups stratified by left ventricular ejection fraction > or 50%. Results: CARMELINA enrolled 6979 participants (mean age, 65.9 years; estimated glomerular filtration rate, mL/min per 1.73m(2); hemoglobin A1c, 8.0%; 62.9% men; diabetes mellitus duration, 14.8 years), including 1873 (26.8%) with a history of HF at baseline. Median follow-up was 2.2 years. Linagliptin versus placebo did not affect the incidence of hHF (209/3494 [6.0%] versus 226/3485 [6.5%], respectively; hazard ratio [HR], 0.90; 95% CI, 0.74-1.08), the composite of cardiovascular death/hHF (HR, 0.94; 95% CI, 0.82-1.08), or risk for recurrent hHF events (326 versus 359 events, respectively; rate ratio, 0.94; 95% CI, 0.75-1.20). There was no heterogeneity of linagliptin effects on hHF by history of HF at baseline, baseline estimated glomerular filtration rate or urine albumin-creatinine ratio, or prerandomization left ventricular ejection fraction. Conclusions: In a large, international cardiovascular outcome trial in participants with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease, linagliptin did not affect the risk of hHF or other selected HF-related outcomes, including among participants with and without a history of HF, across the spectrum of kidney disease, and independent of previous left ventricular ejection fraction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01897532.
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- 2019
50. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk The CARMELINA Randomized Clinical Trial
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Robins G, Colyar L, Hutchins C, Sturm D, Hart K, Phillips T, Montgomery C, Albrecht W, Fehlis K, Overman D, Box M, Villarreal-Martinez D, David-Svatek D, Ajani D, Shaikh Z, Wheeler K, Brown M, Ghosh C, Bandukwala I, Kleber S, Madden J, Bishara M, Perry K, Paoli-Bruno J, Abreu E, Espiritu R, Zmeili O, Christensen T, Grubb S, Beloff S, Caugh A, van Dijk C, Yalavarthy R, DeGraauw J, Fabian S, Gillum D, Corrigan G, Singh H, Jensen K, DeMore S, Montague T, Zieve F, Levy J, Fredrickson S, Tarkington P, Chapla P, Salacata A, Walls U, Iyer R, Nguyen K, Lettman J, Appleman B, Safavie F, Scaliem L, Eder F, Maklad S, Schlaen B, Molstead J, Hartwell J, Hubish D, Little R, Rando K, Kelly R, Drury M, Young P, Wininger S, Harman A, Daza R, Robbin S, Sanchez M, Rivera I, Garcia-Estrada M, Iglesias N, Dobs A, Andrade A, Falkowski S, Parrott T, Koon A, Wood T, Burkett E, Chavous K, Gupta A, Estes C, Loud D, Rhodes S, Chen M, Bromley L, Palma R, Kattan D, Kirk U, Tatu H, Stamatin R, Lupea S, Frasie M, Colfer H, Kane L, Teklinski A, Gadowski G, Levanovich P, Saba F, Confident L, Hossain S, Steinberg B, Philippe B, Choroenthkongtrakal S, Boccalano F, Anand R, Syam V, Manohar A, Suresh P, Madhusudhan P, Patel P, Cambier P, Klonaris J, Cheng W, Fisher S, Schelle M, Reese L, McLean S, Poock J, Hoens J, Rosie A, Welshons R, Dean J, Kuhlman P, Luke R, Lohrbauer L, Cunningham M, Buday P, Lehmann M, Chrzanowski K, Fletcher A, Hargrove J, Harris F, Debs-Perez G, Maiquez A, Cordoves L, Georgescu M, Tayoun H, Munoz F, Ortiz D, Munoz G, Hamzeh I, Misra A, Zhang L, Forgosh L, Loria K, Roncari C, Hommerding J, Morris G, Lebron C, Blake K, LaVenture K, Lange C, Levinson L, Baungarten T, Edevante S, Shawley S, Moyer H, Elliott K, Iachini K, Rajan R, Davis C, Shattuck A, Simon W, Lakin G, Secrist N, Buth D, Steere D, Talbot K, Singh N, Mascolo R, Sloan S, Kmetzo J, Brown J, Carter L, Lawrence M, Arauz-Pacheco C, Lender D, Kozlow W, Cavanaugh L, Wilson J, Gujja P, Akhter F, Khan M, Mohammed A, Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
- Abstract
IMPORTANCE Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. OBJECTIVE To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A(1c) of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] > 200mg/g), and high renal risk (reduced eGFR and micro-or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. INTERVENTIONS Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. MAIN OUTCOMES AND MEASURES Primary outcomewas time to first occurrence of the composite of CV death, nonfatalmyocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. RESULTS Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73m2; 80.1% with UACR > 30mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI,-0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P
- Published
- 2019
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