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1. Serious Games in Academic Education – A Multi-dimensional Sustainability Analysis of Additive Versus Conventional Manufacturing Technologies in a Fictitious Enterprise Project

Author

Rauch, Christiane, Maurer, Oliver, Lang, Sven-Erik, Bähre, Dirk, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Haddar, Mohamed, Editorial Board Member, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Kohl, Holger, editor, Seliger, Günther, editor, and Dietrich, Franz, editor

Published
2023
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4. Additional file 1: of Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting

Author

Alten, Rieke, Burkhardt, Harald, Feist, Eugen, KrĂźger, Klaus, Juergen Rech, Rubbert-Roth, Andrea, Voll, Reinhard, Yedid Elbez, and Rauch, Christiane

Abstract

is a figure showing mean change from baseline in HAQ-DI scores in response to abatacept administered in combination with one csDMARD from the (a) ATTAIN, (b) ASSURE, and (c) ARRIVE studies (PDF 183 kb)

Published
2018
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5. Additional file 3: of Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting

Author

Alten, Rieke, Burkhardt, Harald, Feist, Eugen, KrĂźger, Klaus, Juergen Rech, Rubbert-Roth, Andrea, Voll, Reinhard, Yedid Elbez, and Rauch, Christiane

Abstract

is a table presenting safety profile data of csDMARDs administered in combination with abatacept in the ATTAIN, ASSURE and ARRIVE studies (PDF 35 kb)

Published
2018
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6. Additional file 2: of Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting

Author

Alten, Rieke, Burkhardt, Harald, Feist, Eugen, KrĂźger, Klaus, Juergen Rech, Rubbert-Roth, Andrea, Voll, Reinhard, Yedid Elbez, and Rauch, Christiane

Subjects
musculoskeletal diseases, sense organs, skin and connective tissue diseases
Abstract

is a figure showing mean change from baseline in DAS28 (CRP) at 6Â months in response to abatacept administered in combination with one csDMARD from the (a) ATTAIN and (b) ARRIVE studies (PDF 101 kb)

Published
2018
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7. Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Author

Mehta, Puja, Holder, Susan, Fisher, Benjamin, Vincent, Tonia, Nadesalingam, Kavitha, Maciver, Helen, Shingler, Wendy, Bakshi, Jyoti, Hassan, Sadon, D'Cruz, David, Chan, Antoni, Litwic, Anna E., McCrae, Fiona, Seth, Rakhi, Nandagudi, Anupama, Jury, Elizabeth, Isenberg, David, Karjigi, Uma, Paul, Anupam, Rees, Frances, O'Dowd, Emma, Kinnear, William, Johnson, Simon, Lanyon, Peter, Stevens, Richard, Narayan, Nehal, Marguerie, Christopher, Robinson, Helena, Ffolkes, Lorrette, Worsnop, Fiona, Ostlere, Lucy, Kiely, Patrick, Dharmapalaiah, Chethana, Hassan, Nada, Bharadwaj, Anurag, Skibinska, Malgorzata, Gendi, Nagui, Davies, Emma J., Akil, Mohammed, Kilding, Rachael, Ramachandran Nair, Jagdish, Walsh, Maeve, Farrar, Wendy, Thompson, Robert N., Borukhson, Liubov, McFadyen, Charles, Singh, Deepwant, Rajagopal, Vivek, Chan, Angela Marie L., Wearn Koh, Li, Christie, Jennifer D., Croot, Lorraine, Gayed, Mary, Disney, Benjamin, Singhal, Saket, Grindulis, Karl, Reynolds, Timothy D., Conway, Katie, Williams, Debbie, Quin, John, Dean, Gillian, Churchill, Duncan, Walker-Bone, Karen E., Goff, Iain, Reynolds, Gary, Grove, Matthew, Patel, Priya, Lazarus, Mark N., Roncaroli, Frederico, Gabriel, Carolyn, Kinderlerer, Anne R., Nikiphorou, Elena, Hall, Frances C., Bruce, Ellen, Gray, Leanne, Krutikov, Maria, Wig, Surabhi, Bruce, Ian, D'Agostino, Maria A., Wakefield, Richard, Berner Hammer, Hilde, Vittecoq, Olivier, Galeazzi, Mauro, Balint, Peter, Filippucci, Emilio, Moller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Gaillez, Corine, Kerselaers, Wendy, Van Holder, Karina, Le Bars, Manuela, Stone, Millicent A., Williams, Francis, Wolber, Lisa, Karppinen, Jaro, Maatta, Juhani, Thompson, Ben, Atchia, Ismael, Lorenzi, Alice, Raftery, Graham, Platt, Phil, Platt, Philip N., Pratt, Arthur, Turmezei, Thomas D., Treece, Graham M., Gee, Andrew H., Poole, Kenneth E., Chandratre, Priyanka N., Roddy, Edward, Clarson, Lorna, Richardson, Jane, Hider, Samantha, Mallen, Christian, Lieberman, Abigail, Prouse, Peter J., Mahendran, Prini, Samarawickrama, Amanda, Ottery, Faith D., Yood, Robert, Wolfson, Marsha, Ang, Andrea, Riches, Philip, Thomson, Janet, Nuki, George, Humphreys, Jennifer, Verstappen, Suzanne M., Chipping, Jacqueline, Hyrich, Kimme, Marshall, Tarnya, Symmons, Deborah P., Roy, Matthew, Kirwan, John R., Marshall, Robert W., Matcham, Faith, Scott, Ian C., Rayner, Lauren, Hotopf, Matthew, Kingsley, Gabrielle H., Scott, David L., Steer, Sophia, Ma, Margaret H., Dahanayake, Chanaka, Kingsley, Gabrielle, Cope, Andrew, Wernham, Aaron, Ward, Lorna, Carruthers, David, Deeming, Alison, Buckley, Christopher, Raza, Karim, De Pablo, Paola, Carpenter, Lewis, Jayakumar, Keeranur, Solymossy, Csilla, Dixey, Josh, Young, Adam, Singh, Animesh, Penn, Henry, Ellerby, Nicholas, Mattey, Derek L., Packham, Jonathan, Dawes, Peter, Hider, Samantha L., Ng, Nora, Humby, Frances, Bombardieri, Michele, Kelly, Stephen, Di Cicco, Maria, Dadoun, Sabrina, Hands, Rebecca, Rocher, Vidalba, Kidd, Bruce, Pyne, Dev, Pitzalis, Costantino, Poore, Sophie, Hutchinson, David, Low, Audrey, Lunt, Mark, Mercer, Louise, Galloway, James, Davies, Rebecca, Watson, Kath, Dixon, Will, Symmons, Deborah, Watson, Kath D., Dixon, William G., Hyrich, Kimme L., Malik, Saadia P., Kelly, Clive, Hamilton, Jennifer, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Harris, Helen E., Tweedie, Fiona, Skaparis, Yiannis, White, Marie, Scott, Nicola, Samson, Kay, Mercieca, Cecilia, Clarke, Shane, Warner, Alexander J., Verstappen, Suzanne, Chan, Esther, Woodhead, Felix A., Nisar, Mohamed, Arthanari, S., Dawson, Julie, Sathi, Nav, Ahmad, Yasmeen, Koduri, Gouri, Cumming, Jo, Stannett, Peter, Hull, Richard, Metsios, George, Stavropoulos Kalinoglou, Antonios, Veldhuijzen van Zanten, Jet J., Nightingale, Peter, Koutedakis, Yiannis, Kitas, George D., Williams, Peter, Walsh, David, Perry, Elizabeth, de-Soyza, Anthony, Moullaali, Thomas, Eggleton, Paul, Stavropoulos-Kalinoglou, Antonios, Sandoo, Aamer, de Pablo, Paola, Maggs, Fiona, Faizal, Abdul, Pugh, Mark, Jobanputra, Paresh, Kehoe, Oksana, Cartwright, Alison, Askari, Ayman, El Haj, Alicia, Middleton, Jim, Aynsley, Sarah, Hardy, Jacob, Veale, Douglas, Fearon, Ursula, Wilson, Gerry, Muthana, Munitta, Fossati, G., Healy, L., Nesbitt, A., Becerra, Elena, Leandro, Maria J., De La Torre, Inmaculada, Cambridge, Geraldine, Nelson, P. N., Roden, D., Shaw, M., Davari Ejtehadi, Hora, Nevill, A., Freimanis, G., Hooley, P., Bowman, S., Alavi, A., Axford, J., Veitch, A. M., Tugnet, N., Rylance, P. B., Hawtree, Sarah, Mark Wilkinson, J., Wilson, Anthony G., Woon Kam, Ngar, Filter, Andrew, Croft, Adam P., Naylor, Amy, Zimmermann, Birgit, Hardie, Debbie, Desanti, Guillaume, Jaurez, Maria, Muller-Ladner, Ulf, Filer, Andrew, Neumann, Elena, Movahedi, Mohammad, Ray, David W., Burmester, Gerd R., Matucci-Cerinic, Marco, Navarro-Blasco, Francisco, Kary, Sonja, Unnebrink, Kristina, Kupper, Hartmut, Mukherjee, Sandeep, Cornell, Patricia, Richards, Selwyn, Rahmeh, Fouz, Thompson, Paul W., Westlake, Sarah L., Javaid, Muhammad K., Batra, Rajbir, Chana, Jasroop, Round, Gemma, Judge, Andrew, Taylor, Peter, Patel, Sanjeev, Cooper, Cyrus, Ravindran, Vinod, Bingham, Clifton O., Weinblatt, Michael E., Mendelsohn, Alan, Kim, Lilianne, Mack, Michael, Lu, Jiandong, Baker, Daniel, Westhovens, Rene, Hewitt, Jamie, Han, Chenglong, Keystone, Edward C., Fleischmann, Roy, Smolen, Josef, Emery, Paul, Genovese, Mark, Doyle, Mittie, Hsia, Elizabeth C., Hart, Jennifer C., Harland, Dave, Gibbons, Carl, Pang, Hok, Huertas, Catherine, Diamantopoulos, Alex, Dejonckheere, Fred, Clowse, M., Wolf, D., Stach, C., Kosutic, G., Williams, S., Terpstra, I., Mahadevan, U., Ferraccioli, G., Samborski, W., Berenbaum, F., Davies, O., Koetse, W., Bennett, B., Burkhardt, H., Luijtens, K., van der Heijde, Desiree, Mariette, X., van Vollenhoven, Ronald F., Bykerk, V., de Longueville, M., Arendt, C., Cush, J., Khan, Afsha, Maclaren, Zoe, Dubash, Sayam, Chalam, Venkat C., Sheeran, Tom, Price, Tom, Baskar, Sangeetha, Mulherin, Diarmuid, Molloy, Cauline, Keay, Fiona, Heritage, Caroline, Douglas, Barbara, Schiff, Michael H., Khanna, Dinesh, Furst, Daniel E., Maldonado, Michael A., Li, Wanying, Sasso, Eric H., Emerling, Daniel, Cavet, Guy, Ford, Kerri, Mackenzie-Green, Bronwen, Collins, David, Price, Elizabeth, Williamson, Lyn, Golla, Janardhana, Vagadia, Vipul, Morrison, Elaine, Tierney, Ann, Wilson, Hilary, Hunter, John, Reddy, Venkat, Moore, Samantha, Ehrenstein, Michael, Benson, Claire, Wray, Maria, Cairns, Andrew, Wright, Gary, Pendleton, Adrian, McHenry, Michelle, Taggart, Allister, Bell, Aubrey, Bosworth, Ailsa, Cox, Maureen, Johnston, Graeme, Shah, Preeti, O'Brien, Anne, Jones, Peter, Sargeant, Ify, Bukhari, Marwan, Nusslein, Hubert, Alten, Rieke, Lorenz, Hannes M., Boumpas, Dimitrios, Nurmohamed, Michael T., Bensen, William, Peter, Hans-Hartmut, Rainer, Franz, Pavelka, Karel, Chartier, Melanie, Poncet, Coralie, Rauch, Christiane, Lempp, Heidi, Hofmann, Darija, Adu, Aderonke, Congreve, Carron, Dobson, Joanne, Rose, Diana, Simpson, Carol, Wykes, Til, Ibrahim, Fowzia, Schiff, Michael, Nash, Peter, Durez, Patrick, Kaine, Jeffrey, Delaet, Ingrid, Kelly, Sheila, Maldonado, Michael, Patel, Salil, Jones, Graeme, Sebba, Anthony, Lepley, Denise, Devenport, Jenny, Bernasconi, Corrado, Smart, Devi, Mpofu, Chiedzo, Gomez-Reino, Juan J., Verma, Inderjeet, Kaur, Jaspreet, Syngle, Ashit, Krishan, Pawan, Vohra, Kanchan, Kaur, Ladbans, Garg, Nidhi, Chhabara, Monica, Gibson, Kellie, Woodburn, James, Telfer, Scott, Buckley, Felicity, Finckh, Axel, Huizinga, Tom W., Jansen, Jeroen P., Rubbert-Roth, Andrea, Scali, Juan J., Kremer, Joel M., Pitts, Laura, Vernon, Emma, Sharif, Mohammed I., Das, Sudipto, Helliwell, Philip, Sokoll, Katharina, and Vital, Edward M.

Subjects
cardiovascular system
Abstract

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interest

Published
2017

8. Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting

Author

Alten, Rieke, Burkhardt, Harald, Feist, Eugen, Krueger, Klaus, Rech, Juergen, Rubbert-Roth, Andrea, Voll, Reinhard E., Elbez, Yedid, Rauch, Christiane, Alten, Rieke, Burkhardt, Harald, Feist, Eugen, Krueger, Klaus, Rech, Juergen, Rubbert-Roth, Andrea, Voll, Reinhard E., Elbez, Yedid, and Rauch, Christiane

Abstract

Background: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce. Methods: In this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION). Patients with moderate-to-severe RA received abatacept in combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or leflunomide for 6 months to 2 years according to the study design. Change from baseline in physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein) (DAS28 (CRP); ATTAIN, ARRIVE, and ACTION), American College of Rheumatology response rates (ATTAIN), and safety were assessed for individual and pooled csDMARD combinations for each trial. A meta-analysis was also performed on pooled data for HAQ-DI and DAS28 (CRP) across interventional trials. Results: Across all four studies, 731 patients received abatacept plus one non-MTX csDMARD (hydroxychloroquine n = 152; sulfasalazine n = 123; azathioprine n = 59; and leflunomide n = 397) and 2382 patients received abatacept plus MTX. Mean changes from baseline in HAQ-DI scores for abatacept plus MTX (all csDMARDs pooled) vs abatacept plus a nonMTX csDMARD were -0.54 vs -0.44 (ATTAIN), -0.43 vs -0.43 (ASSURE), and -0.39 vs -0.36 (ARRIVE). Mean changes from baseline in DAS28 (CRP) and ACR response rates were also similar with abatacept plus MTX or non-MTX csDMARDs. Data for individual non-MTX csDMARDs (pooled across studies) and real-world data were consistent with these findings.

Published
2018

10. Efficacy and prognostic factors of treatment retention with intravenous abatacept for rheumatoid arthritis:24-month results from an international, prospective, real-world study

Author

Nüßlein, Hubert G, Alten, Rieke, Galeazzi, Mauro, Lorenz, Hanns Martin, Nurmohamed, Michael T, Bensen, William G, Burmester, Gerd R, Peter, Hans Hartmut, Peichl, Peter, Pavelka, Karel, Chartier, Mélanie, Poncet, Coralie, Rauch, Christiane, Le Bars, Manuela, Rheumatology, and ICaR - Circulation and metabolism

Subjects
Adult, Male, Time Factors, Administration, Intravenous, Aged, Blood Sedimentation, Female, Humans, Immunosuppressive Agents, Kaplan-Meier Estimate, Middle Aged, Patient Acuity, Prognosis, Rheumatoid Factor, Treatment Outcome, Abatacept, Arthritis, Rheumatoid, Arthritis, Rheumatoid, Administration, Intravenous
Abstract

OBJECTIVES: To evaluate retention of abatacept over 24 months in patients with rheumatoid arthritis (RA) in routine clinical practice across Europe and Canada.METHODS: ACTION (AbataCepT In rOutiNe clinical practice) was a prospective, observational, multicentre study of adult patients with moderate-to-severe RA who, at their physician's discretion, initiated treatment with intravenous abatacept. Enrolment occurred from May 2008 to December 2010, with up to 30 months of follow-up. The primary endpoint was the abatacept retention rate over 24 months. Crude abatacept retention rate was estimated using the Kaplan-Meier method. Prognostic factors of abatacept retention in patients with ≥1 prior biologic failure were derived from a Cox proportional hazards regression model, accounting for clustered data.RESULTS: A total of 1137 patients were enrolled (1573 patient-years on abatacept); most (89.2%) had experienced prior biologic failure. The overall crude abatacept retention rate at 24 months was 54.4% (95% confidence interval: 51.3, 57.4). Positivity for both rheumatoid factor and anti-cyclic citrullinated antibody, previous exposure to one or no anti-tumour necrosis factor agents, and cardiovascular comorbidity were prognostic of higher abatacept retention. Erythrocyte sedimentation rate ≥51 mm/hour and introduction of corticosteroid use at abatacept initiation were predictors of lower abatacept retention. Abatacept retention varied according to country. Abatacept was well tolerated without any unexpected safety signals.CONCLUSIONS: In a real-world setting, intravenous abatacept treatment retention was more than 50% at 24 months. The identification of prognostic factors of abatacept retention could support individualised biologic treatment strategies in patients with moderate-to-severe RA.

Published
2016

12. Baseline autoantibodies preferentially impact abatacept efficacy in patients with rheumatoid arthritis who are biologic naïve: 6-month results from a real-world, international, prospective study

Author

Alten, Rieke, primary, Nüßlein, Hubert G, additional, Mariette, Xavier, additional, Galeazzi, Mauro, additional, Lorenz, Hanns-Martin, additional, Cantagrel, Alain, additional, Chartier, Melanie, additional, Poncet, Coralie, additional, Rauch, Christiane, additional, and Le Bars, Manuela, additional

Published
2017
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13. Decreased use of glucocorticoids in biological-experienced patients with rheumatoid arthritis who initiated intravenous abatacept: results from the 2-year ACTION study

Author

Alten, Rieke, primary, Nüßlein, Hubert, additional, Galeazzi, Mauro, additional, Lorenz, Hanns-Martin, additional, Nurmohamed, Michael T, additional, Bensen, William G, additional, Burmester, Gerd R, additional, Peter, Hans-Hartmut, additional, Pavelka, Karel, additional, Chartier, Mélanie, additional, Poncet, Coralie, additional, Rauch, Christiane, additional, Elbez, Yedid, additional, and Le Bars, Manuela, additional

Published
2016
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14. Prognostic factors for abatacept retention in patients who received at least one prior biologic agent: an interim analysis from the observational, prospective ACTION study

Author

Nüßlein, Hubert G., primary, Alten, Rieke, additional, Galeazzi, Mauro, additional, Lorenz, Hanns-Martin, additional, Nurmohamed, Michael T., additional, Bensen, William G., additional, Burmester, Gerd R., additional, Peter, Hans-Hartmut, additional, Pavelka, Karel, additional, Chartier, Melanie, additional, Poncet, Coralie, additional, Rauch, Christiane, additional, and Le Bars, Manuela, additional

Published
2015
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16. 100. Predictors of Retention with Abatacept in Patients who Have Failed One or More Biologic Agents: Results from the International, Real-World Action Study

Author

Nüßlein, Hubert, primary, Alten, Rieke, additional, Galeazzi, Maurizio, additional, Lorenz, Hannes M., additional, Nurmohamed, Michael T., additional, Bensen, William, additional, Burmester, Gerd R., additional, Peter, Hans-Hartmut, additional, Pavelka, Karel, additional, Chartier, Melanie, additional, Poncet, Coralie, additional, Rauch, Christiane, additional, and Le Bars, Manuela, additional

Published
2014
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17. Real-world effectiveness of abatacept for rheumatoid arthritis treatment in European and Canadian populations: a 6-month interim analysis of the 2-year, observational, prospective ACTION study

Author

Nüßlein, Hubert G, primary, Alten, Rieke, additional, Galeazzi, Mauro, additional, Lorenz, Hanns-Martin, additional, Boumpas, Dimitrios, additional, Nurmohamed, Michael T, additional, Bensen, William G, additional, Burmester, Gerd R, additional, Peter, Hans-Hartmut, additional, Rainer, Franz, additional, Pavelka, Karel, additional, Chartier, Melanie, additional, Poncet, Coralie, additional, Rauch, Christiane, additional, and Bars, Manuela Le, additional

Published
2014
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18. Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Author

Mehta, Puja, Holder, Susan, Fisher, Benjamin, Vincent, Tonia, Nadesalingam, Kavitha, Maciver, Helen, Shingler, Wendy, Bakshi, Jyoti, Hassan, Sadon, D'Cruz, David, Chan, Antoni, Litwic, Anna E., McCrae, Fiona, Seth, Rakhi, Nandagudi, Anupama, Jury, Elizabeth, Isenberg, David, Karjigi, Uma, Paul, Anupam, Rees, Frances, O'Dowd, Emma, Kinnear, William, Johnson, Simon, Lanyon, Peter, Stevens, Richard, Narayan, Nehal, Marguerie, Christopher, Robinson, Helena, Ffolkes, Lorrette, Worsnop, Fiona, Ostlere, Lucy, Kiely, Patrick, Dharmapalaiah, Chethana, Hassan, Nada, Bharadwaj, Anurag, Skibinska, Malgorzata, Gendi, Nagui, Davies, Emma J., Akil, Mohammed, Kilding, Rachael, Ramachandran Nair, Jagdish, Walsh, Maeve, Farrar, Wendy, Thompson, Robert N., Borukhson, Liubov, McFadyen, Charles, Singh, Deepwant, Rajagopal, Vivek, Chan, Angela Marie L., Wearn Koh, Li, Christie, Jennifer D., Croot, Lorraine, Gayed, Mary, Disney, Benjamin, Singhal, Saket, Grindulis, Karl, Reynolds, Timothy D., Conway, Katie, Williams, Debbie, Quin, John, Dean, Gillian, Churchill, Duncan, Walker-Bone, Karen E., Goff, Iain, Reynolds, Gary, Grove, Matthew, Patel, Priya, Lazarus, Mark N., Roncaroli, Frederico, Gabriel, Carolyn, Kinderlerer, Anne R., Nikiphorou, Elena, Hall, Frances C., Bruce, Ellen, Gray, Leanne, Krutikov, Maria, Wig, Surabhi, Bruce, Ian, D'Agostino, Maria A., Wakefield, Richard, Berner Hammer, Hilde, Vittecoq, Olivier, Galeazzi, Mauro, Balint, Peter, Filippucci, Emilio, Moller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Gaillez, Corine, Kerselaers, Wendy, Van Holder, Karina, Le Bars, Manuela, Stone, Millicent A., Williams, Francis, Wolber, Lisa, Karppinen, Jaro, Maatta, Juhani, Thompson, Ben, Atchia, Ismael, Lorenzi, Alice, Raftery, Graham, Platt, Phil, Platt, Philip N., Pratt, Arthur, Turmezei, Thomas D., Treece, Graham M., Gee, Andrew H., Poole, Kenneth E., Chandratre, Priyanka N., Roddy, Edward, Clarson, Lorna, Richardson, Jane, Hider, Samantha, Mallen, Christian, Lieberman, Abigail, Prouse, Peter J., Mahendran, Prini, Samarawickrama, Amanda, Ottery, Faith D., Yood, Robert, Wolfson, Marsha, Ang, Andrea, Riches, Philip, Thomson, Janet, Nuki, George, Humphreys, Jennifer, Verstappen, Suzanne M., Chipping, Jacqueline, Hyrich, Kimme, Marshall, Tarnya, Symmons, Deborah P., Roy, Matthew, Kirwan, John R., Marshall, Robert W., Matcham, Faith, Scott, Ian C., Rayner, Lauren, Hotopf, Matthew, Kingsley, Gabrielle H., Scott, David L., Steer, Sophia, Ma, Margaret H., Dahanayake, Chanaka, Kingsley, Gabrielle, Cope, Andrew, Wernham, Aaron, Ward, Lorna, Carruthers, David, Deeming, Alison, Buckley, Christopher, Raza, Karim, De Pablo, Paola, Carpenter, Lewis, Jayakumar, Keeranur, Solymossy, Csilla, Dixey, Josh, Young, Adam, Singh, Animesh, Penn, Henry, Ellerby, Nicholas, Mattey, Derek L., Packham, Jonathan, Dawes, Peter, Hider, Samantha L., Ng, Nora, Humby, Frances, Bombardieri, Michele, Kelly, Stephen, Di Cicco, Maria, Dadoun, Sabrina, Hands, Rebecca, Rocher, Vidalba, Kidd, Bruce, Pyne, Dev, Pitzalis, Costantino, Poore, Sophie, Hutchinson, David, Low, Audrey, Lunt, Mark, Mercer, Louise, Galloway, James, Davies, Rebecca, Watson, Kath, Dixon, Will, Symmons, Deborah, Watson, Kath D., Dixon, William G., Hyrich, Kimme L., Malik, Saadia P., Kelly, Clive, Hamilton, Jennifer, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Harris, Helen E., Tweedie, Fiona, Skaparis, Yiannis, White, Marie, Scott, Nicola, Samson, Kay, Mercieca, Cecilia, Clarke, Shane, Warner, Alexander J., Verstappen, Suzanne, Chan, Esther, Woodhead, Felix A., Nisar, Mohamed, Arthanari, S., Dawson, Julie, Sathi, Nav, Ahmad, Yasmeen, Koduri, Gouri, Cumming, Jo, Stannett, Peter, Hull, Richard, Metsios, George, Stavropoulos Kalinoglou, Antonios, Veldhuijzen van Zanten, Jet J., Nightingale, Peter, Koutedakis, Yiannis, Kitas, George D., Williams, Peter, Walsh, David, Perry, Elizabeth, de-Soyza, Anthony, Moullaali, Thomas, Eggleton, Paul, Stavropoulos-Kalinoglou, Antonios, Sandoo, Aamer, de Pablo, Paola, Maggs, Fiona, Faizal, Abdul, Pugh, Mark, Jobanputra, Paresh, Kehoe, Oksana, Cartwright, Alison, Askari, Ayman, El Haj, Alicia, Middleton, Jim, Aynsley, Sarah, Hardy, Jacob, Veale, Douglas, Fearon, Ursula, Wilson, Gerry, Muthana, Munitta, Fossati, G., Healy, L., Nesbitt, A., Becerra, Elena, Leandro, Maria J., De La Torre, Inmaculada, Cambridge, Geraldine, Nelson, P. N., Roden, D., Shaw, M., Davari Ejtehadi, Hora, Nevill, A., Freimanis, G., Hooley, P., Bowman, S., Alavi, A., Axford, J., Veitch, A. M., Tugnet, N., Rylance, P. B., Hawtree, Sarah, Mark Wilkinson, J., Wilson, Anthony G., Woon Kam, Ngar, Filter, Andrew, Croft, Adam P., Naylor, Amy, Zimmermann, Birgit, Hardie, Debbie, Desanti, Guillaume, Jaurez, Maria, Muller-Ladner, Ulf, Filer, Andrew, Neumann, Elena, Movahedi, Mohammad, Ray, David W., Burmester, Gerd R., Matucci-Cerinic, Marco, Navarro-Blasco, Francisco, Kary, Sonja, Unnebrink, Kristina, Kupper, Hartmut, Mukherjee, Sandeep, Cornell, Patricia, Richards, Selwyn, Rahmeh, Fouz, Thompson, Paul W., Westlake, Sarah L., Javaid, Muhammad K., Batra, Rajbir, Chana, Jasroop, Round, Gemma, Judge, Andrew, Taylor, Peter, Patel, Sanjeev, Cooper, Cyrus, Ravindran, Vinod, Bingham, Clifton O., Weinblatt, Michael E., Mendelsohn, Alan, Kim, Lilianne, Mack, Michael, Lu, Jiandong, Baker, Daniel, Westhovens, Rene, Hewitt, Jamie, Han, Chenglong, Keystone, Edward C., Fleischmann, Roy, Smolen, Josef, Emery, Paul, Genovese, Mark, Doyle, Mittie, Hsia, Elizabeth C., Hart, Jennifer C., Harland, Dave, Gibbons, Carl, Pang, Hok, Huertas, Catherine, Diamantopoulos, Alex, Dejonckheere, Fred, Clowse, M., Wolf, D., Stach, C., Kosutic, G., Williams, S., Terpstra, I., Mahadevan, U., Ferraccioli, G., Samborski, W., Berenbaum, F., Davies, O., Koetse, W., Bennett, B., Burkhardt, H., Luijtens, K., van der Heijde, Desiree, Mariette, X., van Vollenhoven, Ronald F., Bykerk, V., de Longueville, M., Arendt, C., Cush, J., Khan, Afsha, Maclaren, Zoe, Dubash, Sayam, Chalam, Venkat C., Sheeran, Tom, Price, Tom, Baskar, Sangeetha, Mulherin, Diarmuid, Molloy, Cauline, Keay, Fiona, Heritage, Caroline, Douglas, Barbara, Schiff, Michael H., Khanna, Dinesh, Furst, Daniel E., Maldonado, Michael A., Li, Wanying, Sasso, Eric H., Emerling, Daniel, Cavet, Guy, Ford, Kerri, Mackenzie-Green, Bronwen, Collins, David, Price, Elizabeth, Williamson, Lyn, Golla, Janardhana, Vagadia, Vipul, Morrison, Elaine, Tierney, Ann, Wilson, Hilary, Hunter, John, Reddy, Venkat, Moore, Samantha, Ehrenstein, Michael, Benson, Claire, Wray, Maria, Cairns, Andrew, Wright, Gary, Pendleton, Adrian, McHenry, Michelle, Taggart, Allister, Bell, Aubrey, Bosworth, Ailsa, Cox, Maureen, Johnston, Graeme, Shah, Preeti, O'Brien, Anne, Jones, Peter, Sargeant, Ify, Bukhari, Marwan, Nusslein, Hubert, Alten, Rieke, Lorenz, Hannes M., Boumpas, Dimitrios, Nurmohamed, Michael T., Bensen, William, Peter, Hans-Hartmut, Rainer, Franz, Pavelka, Karel, Chartier, Melanie, Poncet, Coralie, Rauch, Christiane, Lempp, Heidi, Hofmann, Darija, Adu, Aderonke, Congreve, Carron, Dobson, Joanne, Rose, Diana, Simpson, Carol, Wykes, Til, Ibrahim, Fowzia, Schiff, Michael, Nash, Peter, Durez, Patrick, Kaine, Jeffrey, Delaet, Ingrid, Kelly, Sheila, Maldonado, Michael, Patel, Salil, Jones, Graeme, Sebba, Anthony, Lepley, Denise, Devenport, Jenny, Bernasconi, Corrado, Smart, Devi, Mpofu, Chiedzo, Gomez-Reino, Juan J., Verma, Inderjeet, Kaur, Jaspreet, Syngle, Ashit, Krishan, Pawan, Vohra, Kanchan, Kaur, Ladbans, Garg, Nidhi, Chhabara, Monica, Gibson, Kellie, Woodburn, James, Telfer, Scott, Buckley, Felicity, Finckh, Axel, Huizinga, Tom W., Jansen, Jeroen P., Rubbert-Roth, Andrea, Scali, Juan J., Kremer, Joel M., Pitts, Laura, Vernon, Emma, Sharif, Mohammed I., Das, Sudipto, Helliwell, Philip, Sokoll, Katharina, Vital, Edward M., Mehta, Puja, Holder, Susan, Fisher, Benjamin, Vincent, Tonia, Nadesalingam, Kavitha, Maciver, Helen, Shingler, Wendy, Bakshi, Jyoti, Hassan, Sadon, D'Cruz, David, Chan, Antoni, Litwic, Anna E., McCrae, Fiona, Seth, Rakhi, Nandagudi, Anupama, Jury, Elizabeth, Isenberg, David, Karjigi, Uma, Paul, Anupam, Rees, Frances, O'Dowd, Emma, Kinnear, William, Johnson, Simon, Lanyon, Peter, Stevens, Richard, Narayan, Nehal, Marguerie, Christopher, Robinson, Helena, Ffolkes, Lorrette, Worsnop, Fiona, Ostlere, Lucy, Kiely, Patrick, Dharmapalaiah, Chethana, Hassan, Nada, Bharadwaj, Anurag, Skibinska, Malgorzata, Gendi, Nagui, Davies, Emma J., Akil, Mohammed, Kilding, Rachael, Ramachandran Nair, Jagdish, Walsh, Maeve, Farrar, Wendy, Thompson, Robert N., Borukhson, Liubov, McFadyen, Charles, Singh, Deepwant, Rajagopal, Vivek, Chan, Angela Marie L., Wearn Koh, Li, Christie, Jennifer D., Croot, Lorraine, Gayed, Mary, Disney, Benjamin, Singhal, Saket, Grindulis, Karl, Reynolds, Timothy D., Conway, Katie, Williams, Debbie, Quin, John, Dean, Gillian, Churchill, Duncan, Walker-Bone, Karen E., Goff, Iain, Reynolds, Gary, Grove, Matthew, Patel, Priya, Lazarus, Mark N., Roncaroli, Frederico, Gabriel, Carolyn, Kinderlerer, Anne R., Nikiphorou, Elena, Hall, Frances C., Bruce, Ellen, Gray, Leanne, Krutikov, Maria, Wig, Surabhi, Bruce, Ian, D'Agostino, Maria A., Wakefield, Richard, Berner Hammer, Hilde, Vittecoq, Olivier, Galeazzi, Mauro, Balint, Peter, Filippucci, Emilio, Moller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Gaillez, Corine, Kerselaers, Wendy, Van Holder, Karina, Le Bars, Manuela, Stone, Millicent A., Williams, Francis, Wolber, Lisa, Karppinen, Jaro, Maatta, Juhani, Thompson, Ben, Atchia, Ismael, Lorenzi, Alice, Raftery, Graham, Platt, Phil, Platt, Philip N., Pratt, Arthur, Turmezei, Thomas D., Treece, Graham M., Gee, Andrew H., Poole, Kenneth E., Chandratre, Priyanka N., Roddy, Edward, Clarson, Lorna, Richardson, Jane, Hider, Samantha, Mallen, Christian, Lieberman, Abigail, Prouse, Peter J., Mahendran, Prini, Samarawickrama, Amanda, Ottery, Faith D., Yood, Robert, Wolfson, Marsha, Ang, Andrea, Riches, Philip, Thomson, Janet, Nuki, George, Humphreys, Jennifer, Verstappen, Suzanne M., Chipping, Jacqueline, Hyrich, Kimme, Marshall, Tarnya, Symmons, Deborah P., Roy, Matthew, Kirwan, John R., Marshall, Robert W., Matcham, Faith, Scott, Ian C., Rayner, Lauren, Hotopf, Matthew, Kingsley, Gabrielle H., Scott, David L., Steer, Sophia, Ma, Margaret H., Dahanayake, Chanaka, Kingsley, Gabrielle, Cope, Andrew, Wernham, Aaron, Ward, Lorna, Carruthers, David, Deeming, Alison, Buckley, Christopher, Raza, Karim, De Pablo, Paola, Carpenter, Lewis, Jayakumar, Keeranur, Solymossy, Csilla, Dixey, Josh, Young, Adam, Singh, Animesh, Penn, Henry, Ellerby, Nicholas, Mattey, Derek L., Packham, Jonathan, Dawes, Peter, Hider, Samantha L., Ng, Nora, Humby, Frances, Bombardieri, Michele, Kelly, Stephen, Di Cicco, Maria, Dadoun, Sabrina, Hands, Rebecca, Rocher, Vidalba, Kidd, Bruce, Pyne, Dev, Pitzalis, Costantino, Poore, Sophie, Hutchinson, David, Low, Audrey, Lunt, Mark, Mercer, Louise, Galloway, James, Davies, Rebecca, Watson, Kath, Dixon, Will, Symmons, Deborah, Watson, Kath D., Dixon, William G., Hyrich, Kimme L., Malik, Saadia P., Kelly, Clive, Hamilton, Jennifer, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Harris, Helen E., Tweedie, Fiona, Skaparis, Yiannis, White, Marie, Scott, Nicola, Samson, Kay, Mercieca, Cecilia, Clarke, Shane, Warner, Alexander J., Verstappen, Suzanne, Chan, Esther, Woodhead, Felix A., Nisar, Mohamed, Arthanari, S., Dawson, Julie, Sathi, Nav, Ahmad, Yasmeen, Koduri, Gouri, Cumming, Jo, Stannett, Peter, Hull, Richard, Metsios, George, Stavropoulos Kalinoglou, Antonios, Veldhuijzen van Zanten, Jet J., Nightingale, Peter, Koutedakis, Yiannis, Kitas, George D., Williams, Peter, Walsh, David, Perry, Elizabeth, de-Soyza, Anthony, Moullaali, Thomas, Eggleton, Paul, Stavropoulos-Kalinoglou, Antonios, Sandoo, Aamer, de Pablo, Paola, Maggs, Fiona, Faizal, Abdul, Pugh, Mark, Jobanputra, Paresh, Kehoe, Oksana, Cartwright, Alison, Askari, Ayman, El Haj, Alicia, Middleton, Jim, Aynsley, Sarah, Hardy, Jacob, Veale, Douglas, Fearon, Ursula, Wilson, Gerry, Muthana, Munitta, Fossati, G., Healy, L., Nesbitt, A., Becerra, Elena, Leandro, Maria J., De La Torre, Inmaculada, Cambridge, Geraldine, Nelson, P. N., Roden, D., Shaw, M., Davari Ejtehadi, Hora, Nevill, A., Freimanis, G., Hooley, P., Bowman, S., Alavi, A., Axford, J., Veitch, A. M., Tugnet, N., Rylance, P. B., Hawtree, Sarah, Mark Wilkinson, J., Wilson, Anthony G., Woon Kam, Ngar, Filter, Andrew, Croft, Adam P., Naylor, Amy, Zimmermann, Birgit, Hardie, Debbie, Desanti, Guillaume, Jaurez, Maria, Muller-Ladner, Ulf, Filer, Andrew, Neumann, Elena, Movahedi, Mohammad, Ray, David W., Burmester, Gerd R., Matucci-Cerinic, Marco, Navarro-Blasco, Francisco, Kary, Sonja, Unnebrink, Kristina, Kupper, Hartmut, Mukherjee, Sandeep, Cornell, Patricia, Richards, Selwyn, Rahmeh, Fouz, Thompson, Paul W., Westlake, Sarah L., Javaid, Muhammad K., Batra, Rajbir, Chana, Jasroop, Round, Gemma, Judge, Andrew, Taylor, Peter, Patel, Sanjeev, Cooper, Cyrus, Ravindran, Vinod, Bingham, Clifton O., Weinblatt, Michael E., Mendelsohn, Alan, Kim, Lilianne, Mack, Michael, Lu, Jiandong, Baker, Daniel, Westhovens, Rene, Hewitt, Jamie, Han, Chenglong, Keystone, Edward C., Fleischmann, Roy, Smolen, Josef, Emery, Paul, Genovese, Mark, Doyle, Mittie, Hsia, Elizabeth C., Hart, Jennifer C., Harland, Dave, Gibbons, Carl, Pang, Hok, Huertas, Catherine, Diamantopoulos, Alex, Dejonckheere, Fred, Clowse, M., Wolf, D., Stach, C., Kosutic, G., Williams, S., Terpstra, I., Mahadevan, U., Ferraccioli, G., Samborski, W., Berenbaum, F., Davies, O., Koetse, W., Bennett, B., Burkhardt, H., Luijtens, K., van der Heijde, Desiree, Mariette, X., van Vollenhoven, Ronald F., Bykerk, V., de Longueville, M., Arendt, C., Cush, J., Khan, Afsha, Maclaren, Zoe, Dubash, Sayam, Chalam, Venkat C., Sheeran, Tom, Price, Tom, Baskar, Sangeetha, Mulherin, Diarmuid, Molloy, Cauline, Keay, Fiona, Heritage, Caroline, Douglas, Barbara, Schiff, Michael H., Khanna, Dinesh, Furst, Daniel E., Maldonado, Michael A., Li, Wanying, Sasso, Eric H., Emerling, Daniel, Cavet, Guy, Ford, Kerri, Mackenzie-Green, Bronwen, Collins, David, Price, Elizabeth, Williamson, Lyn, Golla, Janardhana, Vagadia, Vipul, Morrison, Elaine, Tierney, Ann, Wilson, Hilary, Hunter, John, Reddy, Venkat, Moore, Samantha, Ehrenstein, Michael, Benson, Claire, Wray, Maria, Cairns, Andrew, Wright, Gary, Pendleton, Adrian, McHenry, Michelle, Taggart, Allister, Bell, Aubrey, Bosworth, Ailsa, Cox, Maureen, Johnston, Graeme, Shah, Preeti, O'Brien, Anne, Jones, Peter, Sargeant, Ify, Bukhari, Marwan, Nusslein, Hubert, Alten, Rieke, Lorenz, Hannes M., Boumpas, Dimitrios, Nurmohamed, Michael T., Bensen, William, Peter, Hans-Hartmut, Rainer, Franz, Pavelka, Karel, Chartier, Melanie, Poncet, Coralie, Rauch, Christiane, Lempp, Heidi, Hofmann, Darija, Adu, Aderonke, Congreve, Carron, Dobson, Joanne, Rose, Diana, Simpson, Carol, Wykes, Til, Ibrahim, Fowzia, Schiff, Michael, Nash, Peter, Durez, Patrick, Kaine, Jeffrey, Delaet, Ingrid, Kelly, Sheila, Maldonado, Michael, Patel, Salil, Jones, Graeme, Sebba, Anthony, Lepley, Denise, Devenport, Jenny, Bernasconi, Corrado, Smart, Devi, Mpofu, Chiedzo, Gomez-Reino, Juan J., Verma, Inderjeet, Kaur, Jaspreet, Syngle, Ashit, Krishan, Pawan, Vohra, Kanchan, Kaur, Ladbans, Garg, Nidhi, Chhabara, Monica, Gibson, Kellie, Woodburn, James, Telfer, Scott, Buckley, Felicity, Finckh, Axel, Huizinga, Tom W., Jansen, Jeroen P., Rubbert-Roth, Andrea, Scali, Juan J., Kremer, Joel M., Pitts, Laura, Vernon, Emma, Sharif, Mohammed I., Das, Sudipto, Helliwell, Philip, Sokoll, Katharina, and Vital, Edward M.

Abstract

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MR

19. Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Author

Paola Francesca Ajmone, Maria Luisa Poch-Olive, Jens Erik Klint Nielsen, Christiane Zweier, Giovanni Sorge, Marzia Pollazzon, Bert Callewaert, Jeroen Breckpot, Olivera Djuric, Chiara Baldo, Rikke S. Møller, Isabella Mammi, Livia Garavelli, Gioacchino Scarano, Baris Malbora, Alessandro Iodice, Lucio Giordano, Marina Grasso, Alessandro Pellicciari, Marcella Zollino, Daniele De Brasi, Aurélien Trimouille, Ebtesam M. Abdalla, Samantha A. Schrier Vergano, Ina Schanze, Sébastien Moutton, Anna Kutkowska-Kazmierczak, Agata Fiumara, Andrea Conidi, Emilia Ricci, Duccio Maria Cordelli, Roberta Epifanio, Allan Bayat, Federico Bonvicini, Magdalena Badura-Stronka, Lorenzo Iughetti, Tina Duelund Hjortshøj, Anita Rauch, Vladimir Kuburovic, Giulia Montorsi, Elvis rci Te Valera, Debora Formisano, Stefano Giuseppe Caraffi, Krzysztof Szczaluba, Daniela Santodirocco, Sabine Grønborg, Francesca Faravelli, Maria Antonietta Pisanti, Didier Lacombe, Gijs W. E. Santen, Margherita Silengo, Ivan Ivanovski, Luis G. Tone, Goran Cuturilo, Francesca Mari, Guido Cocchi, Margaret P. Adam, Simonetta Rosato, Chiara Pantaleoni, Patrizia Accorsi, Nicoletta Zanotta, Ewa Obersztyn, Maddalena Baldi, Angelo Selicorni, Alessandra Renieri, Annick Toutain, Mary Beth Dinulos, Petra Muschke, Luigina Spaccini, Luigi Tarani, Igor Prpić, Francesca Rivieri, Koenraad Devriendt, Stefania Bigoni, Robert Smigiel, Anna Luchetti, Federico Raviglione, Martin Zenker, Caterina Lo Rizzo, Salvatore Savasta, Cell biology, and Ivan Ivanovski, Olivera Djuric, Stefano Giuseppe Caraffi, Daniela Santodirocco, Marzia Pollazzon, Simonetta Rosato, Duccio Maria Cordelli, Ebtesam Abballa, Patrizia Accorsi, Margaret P. Adam, Paola Francesca Ajmone, Magdalena Badura-Stronka, Chiara Baldo, Maddalena Baldi, Allan Bayat, Stefania Bigoni, Federico Bonvicini, Jeroen Breckpot, Bert Callewaert, Guido Cocchi, Goran Cuturilo, Daniele De Brasi, Koenraad Devriendt Mary Beth Dinulos, Tina Duelund Hjortshøj, Roberta Epifanio, Francesca Faravelli, Agata Fiumara, Debora Formisano, Lucio Giordano, Marina Grasso, Sabine Grønborg, Alessandro Iodice, Lorenzo Iughetti, Vladimir Kuburovic, Anna Kutkowska-Kazmierczak, Didier Lacombe, Caterina Lo Rizzo, Anna Luchetti, Baris Malbora, Isabella Mammi, Francesca Mari, Giulia Montorsi, Sebastien Moutton, Rikke S. Møller, Petra Muschke, Jens Erik Klint Nielsen, Ewa Obersztyn, Chiara Pantaleoni, Alessandro Pellicciari, Maria Antonietta Pisanti, Igor Prpic, Maria Luisa Poch-Olive, Federico Raviglione, Alessandra Renieri, Emilia Ricci, Francesca Rivieri, Gijs W. Santen, Salvatore Savasta, Gioacchino Scarano, Ina Schanze, Angelo Selicorni, Margherita Silengo, Robert Smigiel, Luigina Spaccini, Giovanni Sorge, Krzysztof Szczaluba, Luigi Tarani, Luis Gonzaga Tone, Annick Toutain, Aurelien Trimouille, Elvis Terci Valera, Samantha Schrier Vergano, Nicoletta Zanotta, Martin Zenker, Andrea Conidi, Marcella Zollino, Anita Rauch, Christiane Zweier, Livia Garavelli

Subjects
0301 basic medicine, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, Microcephaly/diagnosis, Settore MED/03 - GENETICA MEDICA, Bioinformatics, Hirschsprung, intellectual disability, management, Mowat–Wilson syndrome, ZEB2, Hirschsprung Disease/diagnosis, BOX 1B GENE, Abnormalities, Multiple/genetics, Genotype, Intellectual disability, Medicine and Health Sciences, Missense mutation, Mowat-Wilson syndrome, Family history, Child, Genetics (clinical), BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Intellectual Disability/diagnosis, Phenotype, ZEB2 gene. Mowat-Wilson syndrome, intellectual disability, 3. Good health, SIBLINGS, Child, Preschool, Microcephaly, Female, Adult, Hirschsprung, intellectual disability, management, Mowat–Wilson syndrome, ZEB2, Adolescent, 03 medical and health sciences, Genetic variation, medicine, Humans, Abnormalities, Multiple, Hirschsprung Disease, RECURRENCE, ZFHX1B MUTATIONS, Genetic Association Studies, Genetic association, Zinc Finger E-box Binding Homeobox 2, SPECTRUM, SMAD-INTERACTING PROTEIN-1, business.industry, CLINICAL-FEATURES, ZEB2 gene. Mowat-Wilson syndrome, Biology and Life Sciences, Facies, Infant, HIRSCHSPRUNG-DISEASE, medicine.disease, Zinc Finger E-box Binding Homeobox 2/genetics, DELINEATION, Genetic Association Studies/methods, 030104 developmental biology, Mutation, business, MENTAL-RETARDATION
Abstract

PurposeMowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221. ispartof: Genetics in Medicine vol:20 issue:9 pages:965-975 ispartof: location:United States status: published

Published
2018
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20. Efficacy and prognostic factors of treatment retention with intravenous abatacept for rheumatoid arthritis: 24-month results from an international, prospective, real-world study.

Author

Nüßlein HG, Alten R, Galeazzi M, Lorenz HM, Nurmohamed MT, Bensen WG, Burmester GR, Peter HH, Peichl P, Pavelka K, Chartier M, Poncet C, Rauch C, and Le Bars M

Subjects
Administration, Intravenous, Adult, Aged, Blood Sedimentation drug effects, Female, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Kaplan-Meier Estimate, Male, Middle Aged, Patient Acuity, Prognosis, Rheumatoid Factor blood, Time Factors, Treatment Outcome, Abatacept administration & dosage, Abatacept adverse effects, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid drug therapy
Abstract

Objectives: To evaluate retention of abatacept over 24 months in patients with rheumatoid arthritis (RA) in routine clinical practice across Europe and Canada., Methods: ACTION (AbataCepT In rOutiNe clinical practice) was a prospective, observational, multicentre study of adult patients with moderate-to-severe RA who, at their physician's discretion, initiated treatment with intravenous abatacept. Enrolment occurred from May 2008 to December 2010, with up to 30 months of follow-up. The primary endpoint was the abatacept retention rate over 24 months. Crude abatacept retention rate was estimated using the Kaplan-Meier method. Prognostic factors of abatacept retention in patients with ≥1 prior biologic failure were derived from a Cox proportional hazards regression model, accounting for clustered data., Results: A total of 1137 patients were enrolled (1573 patient-years on abatacept); most (89.2%) had experienced prior biologic failure. The overall crude abatacept retention rate at 24 months was 54.4% (95% confidence interval: 51.3, 57.4). Positivity for both rheumatoid factor and anti-cyclic citrullinated antibody, previous exposure to one or no anti-tumour necrosis factor agents, and cardiovascular comorbidity were prognostic of higher abatacept retention. Erythrocyte sedimentation rate ≥51 mm/hour and introduction of corticosteroid use at abatacept initiation were predictors of lower abatacept retention. Abatacept retention varied according to country. Abatacept was well tolerated without any unexpected safety signals., Conclusions: In a real-world setting, intravenous abatacept treatment retention was more than 50% at 24 months. The identification of prognostic factors of abatacept retention could support individualised biologic treatment strategies in patients with moderate-to-severe RA.

Published
2016

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