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1. Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Author

Monti, S., Craven, A., Klersy, C., Montecucco, C., Caporali, R., Watts, R., Merkel, P. A., Luqmani, R., Achilleos, K., Adler, M., Alba, M. A., Albert, D. A., Alibaz-Oner, F., Allcoat, P., Amano, K., Amarasuriya, M., Amudala, N. A., Andrews, J., Archer, A. M., Arimura, Y., Atukorala, I., Azevedo, E., Bajad, S., Baldwin, C., Barra, L. J., Baslund, B., Basu, N., Baykal, M., Berger, C., Berglin, E., Besada, E., Bhardwaj, M., Bischof, A., Blockmans, D., Blood, J., Draibe, J. B., Brand, S., Brandao, M., Bruce, I. N., Butler, A., Calabrese, L. H., Ferrer, D. C., Carette, S., Carmona, D., Ceunen, H., Chakravarty, K., Chapman, P. T., Chocova, Z., Chung, S. A., Ci, W., Cid, M. C., Clark, T. M., Clarkson, M. R., De Jesus Contreras-Rodriguez, F., Conway, R., Cooke, K., Viros, X. C., Cordeiro, A., Costa, A., Culfear, K., Daikeler, T., Danda, D., Das, S. K., Dasgupta, B., De Castro, A. M., Dehghan, N., Devassy, R., Dhindsa, N., Diamantopoulos, A. P., Direskeneli, H., Dobashi, H., Juan, D., Durrani, M., Edelsten, C., Eifert, J., Elhayek, S., Elsideeg, S., Endo, T., Erden, A., Erer, B., Eriksson, P., Erturk, Z., Espigol-Frigole, G., Felicetti, M., Ferraro, A., Ferro, J. M., Fifi-Mah, A., Flores-Suarez, L. F., Flossmann, O., Flynn, D., Fonseca, J. E., Foot, J., Foote, M., Forbess, L., Fujimoto, S., Fukuoka, K., Furtado, C., Furuta, S., Gaffo, A. L., Gallagher, P., Gao, N., Gatenby, P., Gendi, N., Geraldes, R., Gerits, A., Gioffredi, A., Gomples, L., Goncalves, M. J., Gondo, P., Graham, A., Grainger, R., Gray, D. T., Grayson, P. C., Griffiths, L., Guo, Y., Gupta, R., Gylling, M., Hajj-Ali, R. A., Hammam, N., Harigai, M., Hartley, L., Haslett, J., Hassan, A., Hatemi, G., Hellmich, B., Henckaerts, L., Henes, J. C., Hepburn, J., Herd, V., Hess, C., Hill, C., Hinojosa-Azaola, A., Hirahashi, J., Hirano, F., Hocevar, A., Holle, J., Hollinger, N., Homma, S., Howard, T., Hoyles, R. K., Hruskova, Z., Hutcheon, G., Ignacak, M., Igney-Oertel, A., Ikeda, K., Ikegaya, N., Jagadeesh, S., Jaquith, J., Jayne, D. R. W., Jewell, T., Jones, C., Joshi, A., Kalyoncu, U., Kamall, S., Kamath, S., Lai, K. S., Kaname, S., Kanchinadham, S., Karadag, O., Karube, M., Kaszuba, M., Kaur, R., Kawakami, T., Kawashima, S., Khalidi, N., Khan, A., Kikuchi, M., Kilic, L., Kimura, M., King, M. J., Klapa, S., Klocke, R., Kobayashi, T., Kobayashi, S., Komagata, Y., Kronbichler, A., Kuczia, P., Kumar, M. S., Kurosawa, M., Lamprecht, P., Langford, C. A., Lanyon, P., Laversuch, C., Lee, S. J., Leoni, S., Li, J., Liang, K., Liang, P., Liao, H., Lee, L. A., Luqmani, R. A., Lyle, A., Macdonald, M., Mackie, S. L., Madden, L., Magliano, M., Makino, H., Makol, A., Malaiya, R., Malaviya, A., Manthri, R., Maritati, F., Da Silva, A. M., Mason, J. C., Matara, C., Matsui, K., Matteson, E. L., Mcbride, D., Mccullough, K., Mcgeoch, L., Mclaren, J., Mcmillian, C., Mendiratta, N., Menon, A., Merinopoulos, D., Merkel, P., Messier, S., Micheletti, R. G., Mills, K., Milman, N., Minoda, M., Minz, R. W., Mock, C., Mohammad, A. J., Moiseev, S., Moitinho, M., Molloy, E., Monach, P. A., Montgomery, M., Moosig, F., Moradizadeh, M., Morgan, M., Morgan, A. W., Morgan, A. -M., Muir, A., Mukhtyar, C., Muller, A., Muratore, F., Muso, E., Nada, R., Nakajima, H., Nakajima, T., Nakano, H., Nandagudi, A., Neumann, T., Y. F., Ng, K. H., Ng, Nogueira, E. L., Nolkha, N., Nordstrom, D., Novikov, P., Nugaliyadde, A., O'Donnell, J. L., O'Donoghue, J., O'Neill, L., O'Riordan, E., Oatley, M., Okubo, K., Oliva, E., Oshikawa, H., Ota, Y., Padoan, R., Pagnoux, C., Pan, L., Panaritis, K., Park, J. K., Patel, S., Patil, P., Pazzola, G., Peall, A., Pearce, F., Pehlevan, S., Pereira, L., Pettersson, T., Pineau, C. A., Pirila, L., Poglodek, B., Ponte, C., Prieto-Gonzalez, S., Priya, S. R., Purewal, B., Purschke, S., Putaala, J., Quickert, S., Quincey, V., Raghuvanshi, S., Rajasekhar, L., Ranganathan, D., Rathi, M., Rees, D., Rees, F., Renken, U., Restuccia, G., Rhee, R. L., Rice, B., Robins, D., Robson, J., Rodrigues, M., Romao, V. C., Rotar, C., Ruediger, C., Rutgers, A., A. C., Sa, Saavedra, M. J., Sada, K. -E., Sahbudin, I., Salvarani, C., Sandhu, N., Santos, E., Sato, Y., Schafer, V. S., Schiavon, F., Schmidt, W. A., Segelmark, M., Shahin, A., Sharma, A., Shotton, J., Silva, C., Singer, O. G., Sivasuthan, G., Smolen, S., Solanich-Moreno, X., Boixader, L. S., Song, Y. W., Springer, J., Sreih, A. G., Srivastava, R., Stamp, L. K., Stevens, R., Strbian, D., Sugino, K., Sunderkotter, C., Suppiah, R., Suzuki, K., Szekanecz, Z., Sznajd, J., Taimen, K., Tak, P. P., Takeuchi, T., Takizawa, N., Tames, L., Tan, B. E., Tanaka, M., Tang, M. W., Tatlisumak, T., Tesar, V., Thomas, A., Tian, X., Tokunaga, K., Tombetti, E., Tomsic, M., Toz, B., Tsukamoto, T., Uchida, S., Unal, A. U., Urban, M. L., Usui, J., Vaglio, A., Venkatachalam, S., Vermaak, E., Viswanath, V., Wada, T., Wagh, S., Wallace, D. J., Walters, G., Walz, B., Wan, J., Wang, T., Wang, G., Warrington, K. J., Watts, R. A., Wawrzycka-Adamczyk, K., Weeratunga, P., Weisman, M. H., Wickramasinghe, S., Williams, M., Wojcik, K., Woodruff, L., Xenitidis, T., Yamada, H., Yamagata, K., Yee, C. -S., Yoon, M., Yoshida, K., Yoshifuji, H., Ytterberg, S. R., Yumura, W., Zayed, H., Zeng, X., Zhao, M. -H., Zugaj, A., Zuk, J., İç Hastalıkları, Clinical Haematology, and Translational Immunology Groningen (TRIGR)

Subjects
Male, Outcome, Antineutrophil Cytoplasmic, 030232 urology & nephrology, 0302 clinical medicine, Risk Factors, 80 and over, Pharmacology (medical), Age of Onset, Young adult, Aged, 80 and over, education.field_of_study, age, anti-neutrophil cytoplasmic antibody-associated vasculitis, outcome, Adolescent, Adult, Aged, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, Female, Humans, Middle Aged, Morbidity, Prognosis, Retrospective Studies, Risk Assessment, Survival Rate, United Kingdom, Young Adult, Vasculitis, Systemic vasculitis, medicine.medical_specialty, Population, anti-neutrophil cytoplasmic antibody–associated vasculitis, Antibodies, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, education, Anti-neutrophil cytoplasmic antibody–associated vasculitis, Survival rate, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, business.industry, Retrospective cohort study, medicine.disease, Age of onset, business
Abstract

Objectives ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. Methods We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: Results A total of 1338 patients with AAV were included: 66% had disease onset at Conclusion Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.

Published
2021

2. Assessment of disease activity in large-vessel vasculitis: Results of an international delphi exercise

Author

Aydin, S. Z., Direskeneli, H., Merkel, P. A., Toloza, S., Blockmans, D., Sato, E. I., De Souza, A. W. S., Cabral, D., Carette, S., Famorca, L., Khalidi, N., Milman, N., Yacyshyn, E., Tesar, V., Baslund, B., Faurschou, M., Guillevin, L., Puechal, X., Aries, P., Hellmich, B., Herlyn, K., Holle, J., Lamprecht, P., Moosig, F., Neumann, T., Zwerina, J., Tomasson, G., Bambery, P., Jois, R., Rajasekhar, L., Sharma, A., Sivakumar, R., Molloy, E., Hashkes, P., Catapano, F., Cimino, L., De Fanti, A., Pipitone, N., Salvarani, C., Vaglio, A., Kobayashi, S., Suzuki, K., Flores-Suarez, L. F., Hinojosa-Azaola, A., Brouwer, E., Rutgers, A., Stegeman, C., Suppiah, R., Hollan, I., Arguis, P., Cid, M. C., Daikeler, T., Alibaz-Oner, F., Hamuryudan, V., Hatemi, G., Hazirolan, T., Inanc, M., Kalayci, M. B., Kamali, S., Kansu, T., Karaaslan, Y., Karadag, O., Keser, G., Onat, A. M., Ozbalkan, Z., Ozen, S., Ozer, H. T. E., Pamuk, O. N., Yilmaz, S. G., Basu, N., Casian, A., Chakravarty, K., D'Cruz, D., Edelsten, C., Harper, L., Jayne, D., Levy, J., Mason, J., Robson, J., Scott, D., Stanford, M., Watts, R., Albert, D., Amudala, N., Beckman, J., Chacko, B., Chung, S., Fessler, B., Giardino, A., Grayson, P., Hunder, G., Langford, C., Lerman, M., Liang, K., Litt, H., Mason, T., Matteson, E., Mikdashi, J., Mohler, E., Monach, P., Rice, B., Sreih, A., Stone, J., Tsapatsaris, N., Villa-Forte, A., Warrington, K., Yazici, Y., Ytterberg, S., Çukurova Üniversitesi, Aydin, S.Z., Direskeneli, H., Merkel, P.A., Toloza, S., Blockmans, D., Sato, E.I., De Souza, A.W.S., and Yeditepe Üniversitesi

Subjects
Vasculitis, medicine.medical_specialty, Delphi Technique, Immunology, Delphi method, Outcomes, Severity of Illness Index, Article, Disease activity, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Large vessel vasculitis, Severity of illness, medicine, Large vessel, Humans, Immunology and Allergy, 030212 general & internal medicine, computer.programming_language, Giant cell arteritis, 030203 arthritis & rheumatology, Takayasu arteritis, business.industry, medicine.disease, Clinical trial, Physical therapy, business, computer, Delphi
Abstract

PubMedID: 28864648 Objective. To arrive at consensus for candidate outcomes for disease activity assessment in largevessel vasculitis (LVV) in clinical trials. Methods.A Delphi survey including 99 items was circulated among international experts for 3 rounds. Results. Fifty-seven items were accepted for both giant cell arteritis and Takayasu arteritis. Sixty-seven percent of experts voted to have a common approach for both diseases with additional disease-specific items such as weight loss, scalp tenderness/necrosis, morning stiffness, dizziness, visual symptoms, and imaging. Conclusion. This study highlights similarities and differences in experts' perspectives for assessing clinical activity in LVV and may guide a consensus-driven core set of validated outcomes. Copyright © 2017. All rights reserved. National Institute of Arthritis and Musculoskeletal and Skin Diseases: U01 AR51874 04, U54 AR057319 National Center for Research Resources: U54 RR019497 Sponsored by the Vasculitis Clinical Research Consortium, which has received support from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research. Additional support for the work of the OMERACT Vasculitis Working Group was received through a Patient-Centered Outcomes Research Institute Pilot Project Grant. S.Z. Aydin, MD, Associate Professor, Division of Rheumatology, The Ottawa Hospital Research Institute, University of Ottawa; H. Direskeneli, MD, Professor of Rheumatology, Division of Rheumatology, Marmara University Faculty of Medicine; P.A. Merkel, MD, MPH, Professor of Medicine and Epidemiology, Division of Rheumatology, and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania. Address correspondence to Dr. P.A. Merkel, Section of Rheumatology, University of Pennsylvania, White Building, 5th Floor Penn, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: pmerkel@upenn.edu Accepted for publication June 3, 2017.

Published
2017

3. Comparison of biopsy-proven giant cell arteritis in North America and Southern Europe: a population-based study

Author

Francesco Muratore, Crowson, C. S., Boiardi, L., Pinelli, A., Koster, M. J., Restuccia, G., Kermani, T. A., Matteson, E. L., Salvarani, C., and Warrington, K. J.

Subjects
Italy, Biopsy, Minnesota, Giant Cell Arteritis, Humans, Retrospective Studies
Abstract

To compare clinical characteristics, treatment and prognosis of two population-based cohorts of patients with biopsy-proven giant cell arteritis (GCA) from Olmsted County, Minnesota, USA (Olmsted cohort) and the Reggio Emilia area, Northern Italy (Reggio cohort).All patients residing in Olmsted County and the Reggio Emilia area with a new diagnosis of biopsy-proven GCA in 1986-2007 were retrospectively identified. Patients were followed from GCA diagnosis to death, migration or September 2011.The study included 110 patients in the Olmsted and 144 in the Reggio cohort. Compared with the Olmsted cohort, patients from the Reggio cohort had longer duration of symptoms prior to diagnosis (median 1.4 months vs. 0.7, p0.001) and were younger (mean 74.6 years vs. 77.8, p=0.002), more likely to have cranial symptoms (93% vs. 86%, p=0.048), permanent vision loss (21% vs. 6%, p=0.001) and systemic symptoms (67% vs. 46%, p=0.001). ESR and CRP were higher (mean 88 mm/h vs. 73, and 89.0 mg/L vs. 35.2, both p0.001) in the Reggio cohort. Patients from the Olmsted cohort received a higher initial prednisone dose (mean 53.6 mg/day vs. 49.5, p=0.001). There were no differences in relapse rates, cumulative glucocorticoid (GC) dosages at 1, 2 and 5 years, and time to first GC discontinuation.Geographical, genetic and/or environmental factors may contribute to the different clinical features at onset of GCA observed in this study.

5. Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study

Author

Sharon A. Chung, Gökhan Keser, Ayten Yazici, Zeynep Ozbalkan, R. Maughan, Servet Akar, Fatma Alibaz-Oner, Nurullah Akkoc, Kathleen McKinnon-Maksimowicz, Patrick Coit, Güher Saruhan-Direskeneli, Chris Wallace, Omer Karadag, Muge Bicakcigil, Antoine G. Sreih, Ahmet Mesut Onat, Paul A. Monach, Ying Sun, Kenan Aksu, Carol A. Langford, Mehmet Akif Ozturk, Izzet Fresko, Eren Erken, Lindsay Lally, Lindsy J. Forbess, Christian Pagnoux, Ayse Cefle, Ediz Dalkilic, Timothy J. Vyse, Veli Cobankara, Peter C. Grayson, Guillermo Reales, David Cuthbertson, Philip Seo, Gozde Yildirim Cetin, Curry L. Koening, Sibel P. Yentür, Yaşar Karaaslan, Lourdes Ortiz-Fernández, Nilufer Alpay-Kanitez, Bunyamin Kisacik, Xiufang Kong, Sibel Zehra Aydin, Enrico Tombetti, Sule Yavuz, Lindi Jiang, Fatos Onen, Allan P. Kiprianos, Nurşen Düzgün, Nader Khalidi, Justin C. Mason, Huiyong Chen, Aşkın Ateş, Angelo A. Manfredi, Murat Inanc, Sevil Kamali, Sema Kaymaz-Tahra, Steven R. Ytterberg, Timuçin Kaşifoğlu, Emire Seyahi, Elena Baldissera, Deborah S. Cunninghame-Graham, Sedat Kiraz, Jason M. Springer, Peter A. Merkel, Haner Direskeneli, Jonathan D. Wren, Kenneth J. Warrington, Carol A. McAlear, Amr H. Sawalha, Huseyin T. E. Ozer, Wallace, Chris [0000-0001-9755-1703], Apollo - University of Cambridge Repository, Ortiz-Fernandez, Lourdes, Saruhan-Direskeneli, Guher, Alibaz-Oner, Fatma, Kaymaz-Tahra, Sema, Coit, Patrick, Kong, Xiufang, Kiprianos, Allan P., Maughan, Robert T., Aydin, Sibel Z., Aksu, Kenan, Keser, Gokhan, Kamali, Sevil, Inanc, Murat, Springer, Jason, Akar, Servet, Onen, Fatos, Akkoc, Nurullah, Khalidi, Nader A., Koening, Curry, Karadag, Omer, Kiraz, Sedat, Forbess, Lindsy, Langford, Carol A., McAlear, Carol A., Ozbalkan, Zeynep, Yavuz, Sule, Cetin, Gozde Yildirim, Alpay-Kanitez, Nilufer, Chung, Sharon, Ates, Askin, Karaaslan, Yasar, McKinnon-Maksimowicz, Kathleen, Monach, Paul A., Ozer, Huseyin T. E., Seyahi, Emire, Fresko, Izzet, Cefle, Ayse, Seo, Philip, Warrington, Kenneth J., Ozturk, Mehmet A., Ytterberg, Steven R., Cobankara, Veli, Onat, Ahmet Mesut, Duzgun, Nursen, Bicakcigil, Muge, Yentur, Sibel P., Lally, Lindsay, Manfredi, Angelo A., Baldissera, Elena, Erken, Eren, Yazici, Ayten, Kisacik, Bunyamin, Kasifoglu, Timucin, Dalkilic, Ediz, Cuthbertson, David, Pagnoux, Christian, Sreih, Antoine, Reales, Guillermo, Wallace, Chris, Wren, Jonathan D., Cunninghame-Graham, Deborah S., Vyse, Timothy J., Sun, Ying, Chen, Huiyong, Grayson, Peter C., Tombetti, Enrico, Jiang, Lindi, Mason, Justin C., Merkel, Peter A., Direskeneli, Haner, Sawalha, Amr H., Ortiz-Fernandez, L., Saruhan-Direskeneli, G., Alibaz-Oner, F., Kaymaz-Tahra, S., Coit, P., Kong, X., Kiprianos, A. P., Maughan, R. T., Aydin, S. Z., Aksu, K., Keser, G., Kamali, S., Inanc, M., Springer, J., Akar, S., Onen, F., Akkoc, N., Khalidi, N. A., Koening, C., Karadag, O., Kiraz, S., Forbess, L., Langford, C. A., Mcalear, C. A., Ozbalkan, Z., Yavuz, S., Cetin, G. Y., Alpay-Kanitez, N., Chung, S., Ates, A., Karaaslan, Y., McKinnon-Maksimowicz, K., Monach, P. A., Ozer, H. T. E., Seyahi, E., Fresko, I., Cefle, A., Seo, P., Warrington, K. J., Ozturk, M. A., Ytterberg, S. R., Cobankara, V., Onat, A. M., Duzgun, N., Bicakcigil, M., Yentur, S. P., Lally, L., Manfredi, A. A., Baldissera, E., Erken, E., Yazici, A., Kisacik, B., Kasifoglu, T., Dalkilic, E., Cuthbertson, D., Pagnoux, C., Sreih, A., Reales, G., Wallace, C., Wren, J. D., Cunninghame-Graham, D. S., Vyse, T. J., Sun, Y., Chen, H., Grayson, P. C., Tombetti, E., Jiang, L., Mason, J. C., Merkel, P. A., Direskeneli, H., Sawalha, A. H., Ege Üniversitesi, [Belirlenecek], Imperial College Healthcare NHS Trust- BRC Funding, and İç Hastalıkları

Subjects
Male, 0301 basic medicine, genetic association, PROTEIN, Integrin, Genome-wide association study, Disease, DISEASE, vasculitis, Genetic Risk, ACTIVATION, 0302 clinical medicine, LEFLUNOMIDE, Polymorphism (computer science), CRITERIA, GWAS, skin and connective tissue diseases, 11 Medical and Health Sciences, Genetics (clinical), Genetics & Heredity, Genetics, PSORIASIS, genetic risk scroe, Classification, HLA, Polydom, Female, Vasculitis, Leflunomide, epigenetic, vasculitis genetic association, POLYDOM, Activation, GENETIC RISK, Human leukocyte antigen, Biology, eQTL, Polymorphism, Single Nucleotide, Article, CLASSIFICATION, 03 medical and health sciences, medicine, Psoriasis, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Tıp uygulaması, Genetic association, 030203 arthritis & rheumatology, Protein, [No Keywords], Case-control study, 06 Biological Sciences, Inflammatory Bowel Diseases, medicine.disease, Criteria, Takayasu Arteritis, 030104 developmental biology, [No Keyword], Case-Control Studies, Expression quantitative trait loci, chromatin interaction, INTEGRIN, Genome-Wide Association Study
Abstract

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01 AR070148]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences; Imperial College, National Institute for Health Research, Biomedical Research Centre; Wellcome TrustWellcome TrustEuropean Commission [WT107881]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_00002/4], This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant R01 AR070148 to A.H.S. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. J.C.M., A.P.K., and R.M.M. acknowledge support from the Imperial College, National Institute for Health Research, Biomedical Research Centre. C.W. and G.R. acknowledge support from The Wellcome Trust (WT107881) and the Medical Research Council (MC_UU_00002/4). This work was supported by the use of study data downloaded from the dbGaP website, under dbGaP: phs000272.v1.p1, phs000431.v2.p1, phs000583.v1.p1, and phs000444.v1.p1.

Published
2021

6. The provisional OMERACT ultrasonography score for giant cell arteritis

Author

Christian Dejaco, Cristina Ponte, Sara Monti, Davide Rozza, Carlo Alberto Scirè, Lene Terslev, George A W Bruyn, Dennis Boumans, Wolfgang Hartung, Alojzija Hočevar, Marcin Milchert, Uffe Møller Døhn, Chetan B Mukhtyar, Markus Aschwanden, Philipp Bosch, Dario Camellino, Stavros Chrysidis, Giovanni Ciancio, Maria Antonietta D’Agostino, Thomas Daikeler, Bhaskar Dasgupta, Eugenio De Miguel, Andreas P Diamantopoulos, Christina Duftner, Ana Agueda, Ulrich Fredberg, Petra Hanova, Ib Tønder Hansen, Ellen-Margrethe Hauge, Annamaria Iagnocco, Nevsun Inanc, Aaron Juche, Rositsa Karalilova, Toshio Kawamoto, Kresten Krarup Keller, Helen Isobel Keen, Tanaz A Kermani, Minna J. Kohler, Matthew Koster, Raashid Ahmed Luqmani, Pierluigi Macchioni, Sarah Louise Mackie, Esperanza Naredo, Berit Dalsgaard Nielsen, Michihiro Ogasawara, Carlos Pineda, Valentin Sebastian Schäfer, Luca Seitz, Alessandro Tomelleri, Karina D Torralba, Kornelis S M van der Geest, Kenneth J Warrington, Wolfgang A Schmidt, Dejaco, C, Ponte, C, Monti, S, Rozza, D, Scire, C, Terslev, L, Bruyn, G, Boumans, D, Hartung, W, Hocevar, A, Milchert, M, Dohn, U, Mukhtyar, C, Aschwanden, M, Bosch, P, Camellino, D, Chrysidis, S, Ciancio, G, D'Agostino, M, Daikeler, T, Dasgupta, B, De Miguel, E, Diamantopoulos, A, Duftner, C, Agueda, A, Fredberg, U, Hanova, P, Hansen, I, Hauge, E, Iagnocco, A, Inanc, N, Juche, A, Karalilova, R, Kawamoto, T, Keller, K, Keen, H, Kermani, T, Kohler, M, Koster, M, Luqmani, R, Macchioni, P, Mackie, S, Naredo, E, Nielsen, B, Ogasawara, M, Pineda, C, Schafer, V, Seitz, L, Tomelleri, A, Torralba, K, Van Der Geest, K, Warrington, K, and Schmidt, W

Subjects
giant cell arteriti, Settore MED/16 - REUMATOLOGIA, giant cell arteritis, outcome assessment, health care, systemic vasculitis, ultrasonography, Immunology, health care, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Immunology and Allergy, 610 Medizin und Gesundheit, systemic vasculiti, outcome assessment
Abstract

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

Published
2022
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7. Assessing Vasculitis in Giant Cell Arteritis by Ultrasound: Results of OMERACT Patient-based Reliability Exercises

Author

Lene Terslev, Annamaria Iagnocco, Tanaz A. Kermani, Maria Antonietta D’Agostino, Eugenio de Miguel, Stavros Chrysidis, Sofia Ramiro, Alojzija Hočevar, Christian Dejaco, Marcin Milchert, Pierluigi Macchioni, Ulrich Fredberg, Matthew J. Koster, Bhaskar Dasgupta, George A. Bruyn, Cristina Ponte, Chetan Mukhtyar, Uffe Møller Døhn, Wolfgang A. Schmidt, Andreas P. Diamantopoulos, Wolfgang Hartung, Christina Duftner, Aaron Juche, Valentin S. Schäfer, Carlo A. Scirè, Kenneth J. Warrington, Tove Lorenzen, Greta Carrara, Schafer, V, Chrysidis, S, Dejaco, C, Duftner, C, Iagnocco, A, Bruyn, G, Carrara, G, D'Agostino, M, De Miguel, E, Diamantopoulos, A, Fredberg, U, Hartung, W, Hocevar, A, Juche, A, Kermani, T, Koster, M, Lorenzen, T, Macchioni, P, Milchert, M, Dohn, U, Mukhtyar, C, Ponte, C, Ramiro, S, Scire, C, Terslev, L, Warrington, K, Dasgupta, B, and Schmidt, W

Subjects
Vasculitis, Male, Vasculiti, medicine.medical_specialty, giant cell arteritis, ultrasound, reliability, diagnosis, vasculitis, Settore MED/16 - REUMATOLOGIA, Giant Cell Arteritis, Immunology, Sensitivity and Specificity, NO, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Diagnosis, Ultrasound Reliability, Immunology and Allergy, Internal medicine, medicine, Humans, In patient, 030212 general & internal medicine, Halo sign, Giant Cell Arteriti, Reliability (statistics), Aged, Ultrasonography, 030203 arthritis & rheumatology, reliability, ultrasound, business.industry, Ultrasound, Outcome measures, Reproducibility of Results, Middle Aged, medicine.disease, Temporal Arteries, Giant cell arteritis, Female, Radiology, medicine.symptom, business, Diagnosi
Abstract

Objective.To test the reliability of Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls.Methods.A preliminary 1-day meeting and a full 3-day meeting fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA and 2 controls. The aim was to test inter- and intrareader reliability for normal findings, halo sign, and compression sign. In both meetings, patients had established GCA. Pathology was more recent in the full meeting, which was preceded by 6 h of training. Scanning time was 15–20 min instead of 10–13 min.Results.In the preliminary exercise, interreader reliabilities were fair to moderate for the overall diagnosis of GCA (Light κ 0.29–0.51), and poor to fair for identifying vasculitis in the respective anatomical segments (Light κ 0.02–0.46). Intrareader reliabilities were moderate (Cohen κ 0.32–0.64). In the main exercise, interreader reliability was good to excellent (Light κ 0.76–0.86) for the overall diagnosis of GCA, and moderate to good (Light κ 0.46–0.71) for identifying vasculitis in the respective anatomical segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen κ 0.91) and good (Cohen κ 0.71–0.80) for the anatomical segments.Conclusion.OMERACT-derived definitions of halo and compression signs of temporal and axillary arteries are reliable in recent-onset GCA if experienced sonographers (> 300 examinations) have 15–20 min for a standardized examination with prior training and apply > 15 MHz probes.

Published
2018

8. Rituximab therapy for primary central nervous system vasculitis: A 6 patient experience and review of the literature

Author

John Huston, Carlo Salvarani, Nicolò Pipitone, Giulia Cassone, Francesco Muratore, Elena Galli, Robert D. Brown, Gene G. Hunder, Caterina Giannini, Kenneth J. Warrington, Teresa J.H. Christianson, Salvarani C., Brown R.D., Muratore F., Christianson T.J.H., Galli E., Pipitone N., Cassone G., III J.H., Giannini C., Warrington K., and Hunder G.G.

Subjects
0301 basic medicine, PCNSV, Adult, Male, medicine.medical_specialty, Adolescent, Central nervous system, Immunology, Cochrane Library, Immunosuppressive Agent, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Refractory, Retrospective Studie, Prednisone, Modified Rankin Scale, Internal medicine, Patient experience, Medicine, Immunology and Allergy, Humans, Vasculitis, Central Nervous System, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Disability, business.industry, Rituximab, Middle Aged, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, Female, business, Vasculitis, Immunosuppressive Agents, Human, medicine.drug
Abstract

Objectives To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV). Methods We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library. Results The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17–68 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0–4) was lower than that prior to treatment (median 3; range 1–5). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p = .006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment. Conclusions Our data support a potential role for RTX treatment in selected patients with PCNSV.

Published
2018

9. Effects of aging, word frequency, and text stimulus quality on reading across the adult lifespan: Evidence from eye movements

Author

Victoria A. McGowan, Kayleigh L. Warrington, Kevin B. Paterson, Sarah J. White, and Warrington, K

Subjects
Adult, Male, Linguistics and Language, medicine.medical_specialty, Aging, genetic structures, Adolescent, Eye Movements, Longevity, Experimental and Cognitive Psychology, Sensory system, Stimulus (physiology), Audiology, Vocabulary, 050105 experimental psychology, Language and Linguistics, Visual processing, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Humans, 0501 psychology and cognitive sciences, stimulus quality, Young adult, Research Articles, Aged, 05 social sciences, Age Factors, Eye movement, Middle Aged, Middle age, Semantics, Word lists by frequency, Pattern Recognition, Visual, Reading, Word recognition, Female, Psychology, Comprehension, 030217 neurology & neurosurgery, Photic Stimulation
Abstract

Reductions in stimulus quality may disrupt the reading performance of older adults more when compared with young adults because of sensory declines that begin early in middle age. However, few studies have investigated adult age differences in the effects of stimulus quality on reading, and none have examined how this affects lexical processing and eye movement control. Accordingly, we report two experiments that examine the effects of reduced stimulus quality on the eye movements of young (18-24 years), middle-aged (41-51 years), and older (65+ years) adult readers. In Experiment 1, participants read sentences that contained a high- or low-frequency critical word and that were presented normally or with contrast reduced so that words appeared faint. Experiment 2 further investigated effects of reduced stimulus quality using a gaze-contingent technique to present upcoming text normally or with contrast reduced. Typical patterns of age-related reading difficulty (e.g., slower reading, more regressions) were observed in both experiments. In addition, eye movements were disrupted more for older than younger adults when all text (Experiment 1) or just upcoming text (Experiment 2) appeared faint. Moreover, there was an interaction between stimulus quality and word frequency (Experiment 1), such that readers fixated faint low-frequency words for disproportionately longer. Crucially, this effect was similar across all age groups. Thus, although older readers suffer more from reduced stimulus quality, this additional difficulty primarily affects their visual processing of text. These findings have important implications for understanding the role of stimulus quality on reading behavior across the lifespan. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Published
2018

10. Definitions and reliability assessment of elementary ultrasound lesions in giant cell arteritis: A study from the OMERACT large vessel vasculitis ultrasound working group

Author

Eugenio de Miguel, George A W Bruyn, Marcin Milchert, Greta Carrara, Christina Duftner, Wolfgang Hartung, Lene Terslev, Bhaskar Dasgupta, Valentin S. Schäfer, Petra Hanova, Esperanza Naredo, Wolfgang A. Schmidt, Christian Dejaco, Annamaria Iagnocco, Tanaz A. Kermani, Pierluigi Macchioni, Chetan Mukhtyar, Maria Antonietta D'Agostino, Naina Rastalsky, Carlo Alberto Scirè, Cristina Ponte, Sofia Ramiro, Ulrich Fredberg, Stavros Chrysidis, Andreas P. Diamantopoulos, Tove Lorenzen, Mattew J. Koster, Kenneth J. Warrington, Alojzija Hočevar, Uffe Møller Døhn, Chrysidis, S, Duftner, C, Dejaco, C, Schafer, V, Ramiro, S, Carrara, G, Scire, C, Hocevar, A, Diamantopoulos, A, Iagnocco, A, Mukhtyar, C, Ponte, C, Naredo, E, De Miguel, E, Bruyn, G, Warrington, K, Terslev, L, Milchert, M, D'Agostino, M, Koster, M, Rastalsky, N, Hanova, P, Macchioni, P, Kermani, T, Lorenzen, T, Dohn, U, Fredberg, U, Hartung, W, Dasgupta, B, and Schmidt, W

Subjects
Vasculitis, giant cell arteriti, medicine.medical_specialty, Settore MED/16 - REUMATOLOGIA, giant cell arteritis, systemic vasculitis, ultrasonography, Rheumatology, Immunology and Allergy, Immunology, education, NO, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Large vessel vasculitis, medicine, 030212 general & internal medicine, systemic vasculiti, Reliability (statistics), 030203 arthritis & rheumatology, business.industry, Ultrasound, medicine.disease, Giant cell arteritis, Radiology, business, Kappa, Systemic vasculitis
Abstract

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.

Published
2018

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