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1. Novel insights into the management of rheumatoid arthritis: one year in review 2024

Author

Molteni, E, Adinolfi, A, Bondi, V, Delvino, P, Sakellariou, G, Trentanni, C, Ughi, N, Pozzi, M, Scire, C, Molteni E., Adinolfi A., Bondi V., Delvino P., Sakellariou G., Trentanni C., Ughi N., Pozzi M. R., Scire C. A., Molteni, E, Adinolfi, A, Bondi, V, Delvino, P, Sakellariou, G, Trentanni, C, Ughi, N, Pozzi, M, Scire, C, Molteni E., Adinolfi A., Bondi V., Delvino P., Sakellariou G., Trentanni C., Ughi N., Pozzi M. R., and Scire C. A.

Abstract

New evidence from 2023 has slightly shifted some perspectives on rheumatoid arthritis (RA) management. Glucocorticoids have reaffirmed their role as bridging therapy, while novel studies on JAK inhibitors have examined efficacy, mechanism of action, and their potential in high-risk populations, bolstering our understanding with real-world data. Additionally, among treatment strategies, achieving low disease activity has emerged as comparable to achieving remission in the long term, and new insights have been gained regarding tapering both biological and conventional synthetic DMARDs. Furthermore, novel approaches have been proposed for managing difficult-to-treat RA and pre-RA. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Published
2024

2. Cohort Enrichment Strategies for Progressive Interstitial Lung Disease in Systemic Sclerosis From European Scleroderma Trials and Research

Author

Hoffmann-Vold A. -M., Brunborg C., Airo P., Ananyeva L. P., Czirjak L., Guiducci S., Hachulla E., Li M., Mihai C., Riemekasten G., Sfikakis P. P., Valentini G., Kowal-Bielecka O., Allanore Y., Distler O., Vacca A., Giollo A., Balbir-Gurman A., Gheorghiu A. M., Marcoccia A., Herrick A., Radic M., Stamenkovic B., Anic B., Granel B., Ribi C., Selmi C. F., Carlos de la Puente M., de Souza Muller C., Denton C., Kayser C., Tanaseanu C. -M., Majewski D., Rimar D., Krasowska D., Veale D., Walker U., Kerzberg E., Rezus E., Zanatta E., Siegert E., De Langhe E., Oksel F., Ingegnoli F., Cantatore F. P., Szucs G., Cuomo G., Seskute G., Litinsky V., Castellvi I., Morovic-Vergles J., Sibilia J., Henes J., Solanki K., Perdan-Pirkmajer K., Herrmann K., Saketkoo L. A., Stamp L., Mouthon L., Salvador M. J., Pozzi M. R., Uprus M., Vanthuyne M., Engelhart M., Kohm M., Iudici M., Inanc M., Fathi N., Pamuk N., Garcia de la Pena Lefebv P., Carreira P. E., Bancel D. F., Moroncini L., Montecucco C., Ancuta C., Sunderkotter C., Muller-Ladner U., Rosato E., Kucharz E. J., Iannone F., Del Galdo F., Poormoghim H., Kotter I., Distler J., Cutolo M., Tikly M., Damjanov N., Hunzelmann N., Vlachoyiannopoulos P., Hasler P., Sarzi Puttini P., Wiland P., Becvar R., Yavuz S., Zdrojewski Z., Pellerito R., Foti R., Ionescu R. M., Adler S., Kahl S., Moiseev S., Stebbings S., Rednic S., Negrini S., Heitmann S., Ullman S., Agachi S., Martin T., Schmeiser T., Riccieri V., Smith V., Bernardino V., Ortiz-Santamaria V., Hsu V. M., Abdel Atty Mohamed W. A., Hoffmann-Vold, A. -M., Brunborg, C., Airo, P., Ananyeva, L. P., Czirjak, L., Guiducci, S., Hachulla, E., Li, M., Mihai, C., Riemekasten, G., Sfikakis, P. P., Valentini, G., Kowal-Bielecka, O., Allanore, Y., Distler, O., Vacca, A., Giollo, A., Balbir-Gurman, A., Gheorghiu, A. M., Marcoccia, A., Herrick, A., Radic, M., Stamenkovic, B., Anic, B., Granel, B., Ribi, C., Selmi, C. F., Carlos de la Puente, M., de Souza Muller, C., Denton, C., Kayser, C., Tanaseanu, C. -M., Majewski, D., Rimar, D., Krasowska, D., Veale, D., Walker, U., Kerzberg, E., Rezus, E., Zanatta, E., Siegert, E., De Langhe, E., Oksel, F., Ingegnoli, F., Cantatore, F. P., Szucs, G., Cuomo, G., Seskute, G., Litinsky, V., Castellvi, I., Morovic-Vergles, J., Sibilia, J., Henes, J., Solanki, K., Perdan-Pirkmajer, K., Herrmann, K., Saketkoo, L. A., Stamp, L., Mouthon, L., Salvador, M. J., Pozzi, M. R., Uprus, M., Vanthuyne, M., Engelhart, M., Kohm, M., Iudici, M., Inanc, M., Fathi, N., Pamuk, N., Garcia de la Pena Lefebv, P., Carreira, P. E., Bancel, D. F., Moroncini, L., Montecucco, C., Ancuta, C., Sunderkotter, C., Muller-Ladner, U., Rosato, E., Kucharz, E. J., Iannone, F., Del Galdo, F., Poormoghim, H., Kotter, I., Distler, J., Cutolo, M., Tikly, M., Damjanov, N., Hunzelmann, N., Vlachoyiannopoulos, P., Hasler, P., Sarzi Puttini, P., Wiland, P., Becvar, R., Yavuz, S., Zdrojewski, Z., Pellerito, R., Foti, R., Ionescu, R. M., Adler, S., Kahl, S., Moiseev, S., Stebbings, S., Rednic, S., Negrini, S., Heitmann, S., Ullman, S., Agachi, S., Martin, T., Schmeiser, T., Riccieri, V., Smith, V., Bernardino, V., Ortiz-Santamaria, V., Hsu, V. M., and Abdel Atty Mohamed, W. A.

Subjects
interstitial lung disease, Pulmonary and Respiratory Medicine, enrichment, systemic sclerosis, clinical trial, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Abstract

BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, repre-sentativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline $10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria. RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 + 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.CHEST 2023; 163(3):586-598

Published
2023
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4. Late Skin Fibrosis in Systemic Sclerosis: A Study from the EUSTAR Cohort

Author

Michael Hughes 1 2, Suiyuan Huang 3 4, Juan Jose Alegre-Sancho 5, Patricia E Carreira 6, Merete Engelhart 7, Eric Hachulla 8, Joerg Henes 9, Eduardo Kerzberg 10, Maria Rosa Pozzi 11, Gabriela Riemekasten 12, Vanessa Smith 13, Gabriella Szücs 14, Marie Vanthuyne 15, Elisabetta Zanatta 16, Oliver Distler 17, Armando G Gabrielli 18, Anna-Maria Hoffmann-Vold 19, Virginia D Steen 20, Dinesh Khanna 3 21, EUSTAR Airò P, Allanore A, Ananieva Lp, Anic B, Balbir-Gurman A, Becvar R, Benvenuti F, Cantatore F P, Chung L S, Cuomo G, Cutolo M, Czirják L, Damjanov N, de Vries-Bouwstra J, Del Galdo F, Distler J, Eyerich K, Farge D, Foti R, Gheorghiu A M, Giollo A, Heitmann S, Herrick A, Hesselstrand R, Hsu I M, Hunzelmann N, Iannone F, Iudici M, Ionescuc M R, Ingegnoli F, Jose J, Joven B E, Kerzberg E, Kucharz E J, Kuwana M, Langhe E D, Launay D, Lefebvre P, Litinsky I, García de la Peña Lefebvre P, González-Martín J J, Li M, Loyo E, Martin T, Matucci-Cerinic M, Maurer B, Moroncini G, Mouthon L, Müller Cs, Müller-Ladner U, Novak S, Pastor P, Pecher A-C, Pellerito R, Pozzi M R, Oksel F, Rednic S, Rezus E, Riccieri V, Rosato E, Saketkoo L A, Salvador M J, Schmeiser T, Selmi C F, Sibilia J, Siegert E, Solanki K, Sommerlatte S, Spertini F, Stamenkovic B, Stamp L, Tanaseanu C-M, Tikly M, Tineo C, Ullman S, Üprus M, Vanthuyne M, Veale D, Walker U, Wiland P, Yargucu F, Yavuz S, University of Zurich, Michael Hughes, 1 2, Suiyuan Huang, 3 4, Juan Jose Alegre-Sancho, 5, Patricia, E Carreira 6, Merete Engelhart, 7, Eric Hachulla, 8, Joerg Henes, 9, Eduardo Kerzberg, 10, Maria Rosa Pozzi, 11, Gabriela Riemekasten, 12, Vanessa Smith, 13, Gabriella Szücs, 14, Marie Vanthuyne, 15, Elisabetta Zanatta, 16, Oliver Distler, 17, Armando, G Gabrielli 18, Anna-Maria Hoffmann-Vold, 19, Virginia, D Steen 20, Dinesh Khanna, 3 21, EUSTAR Airò, P, Allanore, A, Ananieva, Lp, Anic, B, Balbir-Gurman, A, Becvar, R, Benvenuti, F, Cantatore, F P, Chung, L S, Cuomo, G, Cutolo, M, Czirják, L, Damjanov, N, de Vries-Bouwstra, J, Del Galdo, F, Distler, J, Eyerich, K, Farge, D, Foti, R, Gheorghiu, A M, Giollo, A, Heitmann, S, Herrick, A, Hesselstrand, R, Hsu, I M, Hunzelmann, N, Iannone, F, Iudici, M, Ionescuc, M R, Ingegnoli, F, Jose, J, Joven, B E, Kerzberg, E, Kucharz, E J, Kuwana, M, Langhe, E D, Launay, D, Lefebvre, P, Litinsky, I, García de la Peña Lefebvre, P, González-Martín, J J, Li, M, Loyo, E, Martin, T, Matucci-Cerinic, M, Maurer, B, Moroncini, G, Mouthon, L, Müller, C, Müller-Ladner, U, Novak, S, Pastor, P, Pecher, A-C, Pellerito, R, Pozzi, M R, Oksel, F, Rednic, S, Rezus, E, Riccieri, V, Rosato, E, Saketkoo, L A, Salvador, M J, Schmeiser, T, Selmi, C F, Sibilia, J, Siegert, E, Solanki, K, Sommerlatte, S, Spertini, F, Stamenkovic, B, Stamp, L, Tanaseanu, C-M, Tikly, M, Tineo, C, Ullman, S, Üprus, M, Vanthuyne, M, Veale, D, Walker, U, Wiland, P, Yargucu, F, and Yavuz, S

Subjects
Rheumatology, Cohort enrichment, 10051 Rheumatology Clinic and Institute of Physical Medicine, Late disease, Systemic sclerosis, Pharmacology (medical), 610 Medicine & health, Fibrosis, Clinical trial design, Scleroderma, Skin
Abstract

Objectives The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. Methods We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. Results One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. Conclusions Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Published
2022

5. Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study

Author

Giacomo Maria Guidelli, Viapiana, O., Luciano, N., Santis, M., Boffini, N., Quartuccio, L., Birra, D., Conticini, E., Chimenti, M. S., Bazzani, C., Bruschi, E., Riva, M., Canziani, L. M., Bianchi, G., Pozzi, M. R., Limonta, M., Gorla, R., Perricone, R., Frediani, B., Moscato, P., Vita, S., Dagna, L., Rossini, M., and Selmi, C.

Subjects
rheumatoid arthritis, Sulfonamides, Immunology, Settore MED/16, baricitinib, dmards, rheumatoid arthritis, Arthritis, Rheumatoid, Methotrexate, Treatment Outcome, Rheumatology, Purines, Antirheumatic Agents, baricitinib, Azetidines, Humans, Pyrazoles, Immunology and Allergy, Drug Therapy, Combination, dmards
Abstract

Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life.We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC).Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation.Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Published
2021
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7. POS0914 LATE SKIN FIBROSIS IN SYSTEMIC SCLEROSIS: A STUDY FROM THE EUSTAR COHORT

Author

Hughes, M., primary, Huang, S., additional, Alegre Sancho, J. J., additional, Carreira, P., additional, Engelhart, M., additional, Hachulla, E., additional, Henes, J., additional, Kerzberg, E., additional, Pozzi, M. R., additional, Riemekasten, G., additional, Smith, V., additional, Szucs, G., additional, Vanthuyne, M., additional, Zanatta, E., additional, Distler, O., additional, Gabrielli, A., additional, Hoffmann-Vold, A. M., additional, Steen, V., additional, and Khanna, D., additional

Published
2022
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8. Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: A real-life multicentre study

Author

Guidelli, G, Viapiana, O, Luciano, N, De Santis, M, Boffini, N, Quartuccio, L, Birra, D, Conticini, E, Chimenti, M, Bazzani, C, Bruschi, E, Riva, M, Canziani, L, Bianchi, G, Pozzi, M, Limonta, M, Gorla, R, Perricone, R, Frediani, B, Moscato, P, De Vita, S, Dagna, L, Rossini, M, Selmi, C, Guidelli G. M., Viapiana O., Luciano N., De Santis M., Boffini N., Quartuccio L., Birra D., Conticini E., Chimenti M. S., Bazzani C., Bruschi E., Riva M., Canziani L. M., Bianchi G., Pozzi M. R., Limonta M., Gorla R., Perricone R., Frediani B., Moscato P., De Vita S., Dagna L., Rossini M., Selmi C., Guidelli, G, Viapiana, O, Luciano, N, De Santis, M, Boffini, N, Quartuccio, L, Birra, D, Conticini, E, Chimenti, M, Bazzani, C, Bruschi, E, Riva, M, Canziani, L, Bianchi, G, Pozzi, M, Limonta, M, Gorla, R, Perricone, R, Frediani, B, Moscato, P, De Vita, S, Dagna, L, Rossini, M, Selmi, C, Guidelli G. M., Viapiana O., Luciano N., De Santis M., Boffini N., Quartuccio L., Birra D., Conticini E., Chimenti M. S., Bazzani C., Bruschi E., Riva M., Canziani L. M., Bianchi G., Pozzi M. R., Limonta M., Gorla R., Perricone R., Frediani B., Moscato P., De Vita S., Dagna L., Rossini M., and Selmi C.

Abstract

Objective Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. Methods We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). Results Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. Conclusion Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Published
2021

9. POS0316 MODELLING SHORT-TERM FVC CHANGES FROM SENSCIS TO LONG-TERM FVC COURSE IN SSc-ILD DEMONSTRATES CLINICALLY MEANINGFUL REDUCTION OF FVC DECLINE AND SURVIVAL BENEFITS

Author

Hoffmann-Vold, A. M., primary, Huscher, D., additional, Airò, P., additional, Zanatta, E., additional, Carreira, P., additional, Allanore, Y., additional, Müller-Ladner, U., additional, Giollo, A., additional, Pozzi, M. R., additional, Souza Muller, C., additional, Bečvář, R., additional, Iudici, M., additional, Majewski, D., additional, Gabrielli, A., additional, Alves, M., additional, Schoof, N., additional, and Distler, O., additional

Published
2021
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10. Risk of acute arterial and venous thromboembolic events in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Author

Bettiol, A., Sinico, R. A., Schiavon, F., Monti, S., Bozzolo, E. P., Franceschini, F., Govoni, M., Lunardi, C., Guida, G., Lopalco, G., Paolazzi, G., Vacca, A., Gregorini, G., Leccese, P., Piga, M., Conti, F., Fraticelli, P., Quartuccio, L., Alberici, F., Salvarani, C., Bettio, S., Negrini, S., Selmi, C., Sciascia, S., Moroni, G., Colla, L., Manno, C., Urban, M. L., Vannacci, A., Pozzi, M. R., Fabbrini, P., Polti, S., Felicetti, M., Marchi, M. R., Padoan, R., Delvino, P., Caporali, R., Montecucco, C., Dagna, L., Cariddi, A., Toniati, P., Tamanini, S., Furini, F., Bortoluzzi, A., Tinazzi, E., Delfino, L., Badiu, I., Rolla, G., Venerito, V., Iannone, F., Berti, A., Bortolotti, R., Racanelli, V., Jeannin, G., Padula, A., Cauli, A., Priori, R., Gabrielli, A., Bond, M., Tedesco, M., Pazzola, G., Tomietto, P., Pellecchio, M., Marvisi, C., Maritati, F., Palmisano, A., Dejaco, C., Willeit, J., Kiechl, S., Olivotto, I., Willeit, P., Prisco, D., Vaglio, A., Emmi, G., Bargagli, E., Becatti, M., Beccalli, M., Bello, F., Bozzao, F., Canti, V., Cassia, M. A., Cassone, G., Catanoso, M., Chieco-Bianchi, F., Clari, R., Coladonato, L., De Santis, M., Di Scala, G., Fagni, F., Fenaroli, P., Fiorillo, C., Floris, A., Fornaro, M., Galli, E., Generali, E., Giliberti, M., Lascaro, N., Leccese, I., Mattioli, I., Olivieri, B., Osti, N., Peyronel, F., Radin, M., Righetti, G., Salvati, S., Silvestri, E., Susca, N., Tamburini, C., Taurisano, G., Trezzi, B., Trivioli, G., Bettiol, A, Sinico, R, Schiavon, F, Monti, S, Bozzolo, E, Franceschini, F, Govoni, M, Lunardi, C, Guida, G, Lopalco, G, Paolazzi, G, Vacca, A, Gregorini, G, Leccese, P, Piga, M, Conti, F, Fraticelli, P, Quartuccio, L, Alberici, F, Salvarani, C, Bettio, S, Negrini, S, Selmi, C, Sciascia, S, Moroni, G, Colla, L, Manno, C, Urban, M, Vannacci, A, Pozzi, M, Fabbrini, P, Polti, S, Felicetti, M, Marchi, M, Padoan, R, Delvino, P, Caporali, R, Montecucco, C, Dagna, L, Cariddi, A, Toniati, P, Tamanini, S, Furini, F, Bortoluzzi, A, Tinazzi, E, Delfino, L, Badiu, I, Rolla, G, Venerito, V, Iannone, F, Berti, A, Bortolotti, R, Racanelli, V, Jeannin, G, Padula, A, Cauli, A, Priori, R, Gabrielli, A, Bond, M, Tedesco, M, Pazzola, G, Tomietto, P, Pellecchio, M, Marvisi, C, Maritati, F, Palmisano, A, Dejaco, C, Willeit, J, Kiechl, S, Olivotto, I, Willeit, P, Prisco, D, Vaglio, A, and Emmi, G

Subjects
Pulmonary and Respiratory Medicine, Burden of disease, Humans, Churg-Strauss Syndrome, Granulomatosis with Polyangiitis, Venous Thromboembolism, Venous Thrombosis, Churg-strauss syndrome, Criminology, NO, 03 medical and health sciences, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Vascular inflammation, business.industry, Conflict of interest, Cytoplasmic antibody, medicine.disease, 030228 respiratory system, Wegener granulomatosis, arterial and venous thromboembolic events, Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome), Organ involvement, business, Production team
Abstract

Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss syndrome) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by respiratory manifestations and systemic organ involvement [1]. Particularly, cardiac manifestations occur in 40–60% of patients, representing the leading cause of mortality [2]. Recent reports suggest that venous thromboembolic events might also represent a consistent burden of disease [3, 4], as already known for the other AAVs [5–7], possibly due to eosinophil-mediated vascular inflammation [5]. Nevertheless, the occurrence of arterial and venous thrombotic events (AVTE) has never been systematically explored in EGPA. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Alessandra Bettiol Conflict of interest: Renato Alberto Sinico Conflict of interest: Franco Schiavon Conflict of interest: Sara Monti Conflict of interest: Enrica Paola Bozzolo Conflict of interest: Franco Franceschini Conflict of interest: Marcello Govoni Conflict of interest: Claudio Lunardi Conflict of interest: Giuseppe Guida Conflict of interest: Giuseppe Lopalco Conflict of interest: Giuseppe Paolazzi Conflict of interest: Angelo Vacca Conflict of interest: Gina Gregorini Conflict of interest: Pietro Leccese Conflict of interest: Matteo Piga Conflict of interest: Fabrizio Conti Conflict of interest: Paolo Fraticelli Conflict of interest: Luca Quartuccio Conflict of interest: Federico Alberici Conflict of interest: Carlo Salvarani Conflict of interest: Silvano Bettio Conflict of interest: Simone Negrini Conflict of interest: Carlo Selmi Conflict of interest: Savino Sciascia Conflict of interest: Gabriella Moroni Conflict of interest: Loredana Colla Conflict of interest: Carlo Manno Conflict of interest: Maria Letizia Urban Conflict of interest: Alfredo Vannacci Conflict of interest: Maria Rosa Pozzi Conflict of interest: Paolo Fabbrini Conflict of interest: Stefano Polti Conflict of interest: Mara Felicetti Conflict of interest: Maria Rita Marchi Conflict of interest: Roberto Padoan Conflict of interest: Paolo Delvino Conflict of interest: Roberto Caporali Conflict of interest: Carlomaurizio Montecucco Conflict of interest: Lorenzo Dagna Conflict of interest: Adriana Cariddi Conflict of interest: Paola Toniati Conflict of interest: Dr. Tamanini reports other from Glaxo Smith Kline, outside the submitted work. Conflict of interest: Federica Furini Conflict of interest: Alessandra Bortoluzzi Conflict of interest: Elisa Tinazzi Conflict of interest: Lorenzo Delfino Conflict of interest: Iuliana Badiu Conflict of interest: Giovanni Rolla Conflict of interest: Vincenzo Venerito Conflict of interest: Florenzo Iannone Conflict of interest: Alvise Berti Conflict of interest: Roberto Bortolotti Conflict of interest: Vito Racanelli Conflict of interest: Guido Jeannin Conflict of interest: Angela Padula Conflict of interest: Alberto Cauli Conflict of interest: Roberta Priori Conflict of interest: Armando Gabrielli Conflict of interest: Milena Bond Conflict of interest: Martina Tedesco Conflict of interest: Giulia Pazzola Conflict of interest: Paola Tomietto Conflict of interest: Marco Pellecchio Conflict of interest: Chiara Marvisi Conflict of interest: Federica Maritati Conflict of interest: Alessandra Palmisano Conflict of interest: Christian Dejaco Conflict of interest: Johann Willeit Conflict of interest: Stefan Kiechl Conflict of interest: Iacopo Olivotto Conflict of interest: Peter Willeit Conflict of interest: Domenico Prisco Conflict of interest: Augusto Vaglio Conflict of interest: Giacomo Emmi

Published
2020

12. Tocilizumab in the treatment of patients with rheumatoid arthritis in real clinical practice: Results of an Italian observational study

Author

Caporali, R., Idolazzi, L., Bombardieri, S., Ferraccioli, G., Gerli, R., Govoni, M., Matucci-Cerinic, M., Pomponio, G., Salaffi, F., Tirri, R., Benaglio, F., Bianchino, L., Sarzi-Puttini, P., Adami, S., Afeltra, A., Altomonte, L., Arrigoni, E., Bagnato, G., Bianchi, G., Bucci, R. N., Caminiti, M., Cantini, F., Caputo, D., Carlino, G., Clerico, P., Colombelli, P., Corsaro, S. M., D Alessandro, G., Riso, L., Silva, S., D Errico, T., Di Matteo, L., Ferri, C., Foti, R., Fusaro, E., Gabrielli, A., Giacomelli, R., Lunardi, C., Malavolta, N., Martin Martin, L. S., Massarotti, M. S., Mazzone, A., Meschini, C., Migliore, A., Minisola, G., Monti, G., Muratore, M., Paoletti, F., Pappone, N., Passiu, G., Mario Pirisi, Pistone, G., Pozzi, M. R., Prandini, P., Provenzano, G., Ricioppo, A., Romeo, N., Russo, R., Saviola, G., Semeraro, A., Tartarelli, G., Tomietto, P., Valentini, G., Zuccaro, C., Caporali, Roberto, Idolazzi, Luca, Bombardieri, Stefano, Ferraccioli, Gianfranco, Gerli, Roberto, Govoni, Marcello, Matucci-Cerinic, Marco, Pomponio, Giovanni, Salaffi, Fausto, Tirri, Rosella, Benaglio, Francesca, Bianchino, Laura, Sarzi-Puttini, Piercarlo, Caporali, R., Adami, S., Afeltra, A., Altomonte, L., Arrigoni, E., Bagnato, G., Bianchi, G., Bombardieri, S., Bucci, R. N., Caminiti, M., Cantini, F., Caputo, D., Carlino, G., Clerico, P., Colombelli, P., Corsaro, S. M., D'Alessandro, G., De Riso, L., De Silva, S., D'Errico, T., Di Matteo, L., Ferraccioli, G., Ferri, C., Foti, R., Fusaro, E., Gabrielli, A., Gerli, R., Giacomelli, R., Govoni, M., Lunardi, C., Malavolta, N., Martin Martin, L. S., Massarotti, M. S., Matucci-Cerinic, M., Mazzone, A., Meschini, C., Migliore, A., Minisola, G., Monti, G., Muratore, M., Paoletti, F., Pappone, N., Passiu, G., Pirisi, M., Pistone, G., Pozzi, M. R., Prandini, P., Provenzano, G., Ricioppo, A., Romeo, N., Russo, R., Salaffi, F., Sarzi-Puttini, P., Saviola, G., Semeraro, A., Tartarelli, G., Tomietto, P., Valentini, G., and Zuccaro, C.

Subjects
Rheumatology, Interleukin-6, Immunology, Immunology and Allergy, Tocilizumab, Monotherapy, Rheumatoid arthriti
Abstract

Objective To describe the effectiveness and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in a cohort of patients with rheumatoid arthritis (RA) recruited in clinical practice. Methods TRUST was an observational study in RA patients who started treatment with TCZ in the 6 months prior to site activation and were still on treatment at start of study; patients were followed up to 12 months after the first TCZ infusion. Results 322 RA patients were enrolled in 59 Italian centres (mean age: 55.8 years; mean disease duration: 120.5 months; baseline DAS28: 5.3). After 6 months of TCZ treatment, patients achieving low disease activity (DAS28 ≤3.2; 57.52%) or disease remission (DAS28 < 2.6; 38.05%) were 216 out of 226 patients with available DAS28 (p < 0.001). No statistically significant differences were found in mean DAS28 and HAQ score changes from baseline (start of TCZ treatment) to study end between patients previously inadequately responding to disease-modifyinganti-rheumatic drugs (DMARD-IR) or to DMARDs plus tumour necrosis factor inhibitors (DMARD +TNFi-IR): both patient populations responded to TCZ. A statistically significant decrease in mean VAS Fatigue score (48.4 vs. 34.7; p=0.0025) at month 6 was observed. In patients treated with TCZ as monotherapy (32.61%), DAS28, VAS fatigue and HAQ scores decreased from baseline to any post-baseline time point. Overall, 62 patients (19.3%) prematurely discontinued TCZ treatment, 24 (7.5%) for safety reasons. Drug-related adverse events occurred in 92 patients (28.6%) (mostly 3 hypercholesterolaemia and leucopenia) and drug-related serious adverse events in 11 patients (3.4%). Conclusion This study confirms the good effectiveness and safety profile of TCZ in real life RA patient care.

Published
2017

13. What have multicentre registries across the world taught us about the disease features of systemic sclerosis?

Author

Proudman S. M., Huq M., Stevens W., Wilson M. E., Sahhar J., Baron M., Hudson M., Pope J., Allanore Y., Distler O., Kowal-Bielecka O., Matucci-Cerinic M., H. L. Low A., Teng G. G., Law W. G., Santosa A., Nikpour M., Hill C., Lester S., Nash P., Ngian G. -S., Proudman S., Rischmueller M., Roddy J., Strickland G., Thakkar V., Walker J., Zochling J., Markland J., Robinson D., Jones N., Khalidi N., Docherty P., Kaminska E., Masetto A., Sutton E., Mathieu J. -P., Ligier S., Grodzicky T., LeClercq S., Thorne C., Gyger G., Smith D., Fortin P. R., Larche M., Abu-Hakima M., Rodriguez-Reyna T. S., Cabral A. R., Fritzler M., Avouac J., Walker U. A., Guiducci S., Riemekasten G., Air P., Hachulla E., Valentini G., Carreira P. E., Cozzi F., Gurman A. B., Braun-Moscovici Y., Damjanov N., Ananieva L. P., Scorza R., Jimenez S., Busquets J., Li M., Muller-Ladner U., Maurer B., Tyndall A., Lapadula G., Iannone F., Becvar R., Sierakowsky S., Cutolo M., Sulli A., Cuomo G., Vettori S., Rednic S., Nicoara I., Vlachoyiannopoulos P., Montecucco C., Caporali R., Novak S., Czirjak L., Varju C., Chizzolini C., Kucharz E. J., Kotulska A., Kopec-Medrek M., Widuchowska M., Rozman B., Mallia C., Coleiro B., Gabrielli A., Farge D., Hij A., Hesselstrand R., Scheja A., Wollheim F., Martinovic D., Govoni M., Lo Monaco A., Hunzelmann N., Pellerito R., Bambara L. M., Caramaschi P., Black C., Denton C., Henes J., Santamaria V. O., Heitmann S., Krasowska D., Seidel M., Oleszowsky M., Burkhardt H., Himsel A., Salvador M. J., Stamenkovic B., Stankovic A., Tikly M., Starovoytova M. N., Engelhart M., Strauss G., Nielsen H., Damgaard K., Szucs G., Mendoza A. Z., de la Puente Buijdos C., Giraldo W. A. S., Midtvedt O., Garen T., Launay D., Valesini G., Riccieri V., Ionescu R. M., Opris D., Groseanu L., Wigley F. M., Mihai C. M., Cornateanu R. S., Ionitescu R., Gherghe A. M., Gorga M., Dobrota R., Bojinca M., Schett G., Distler J. H., Meroni P., Zeni S., Mouthon L., De Keyser F., Smith V., Cantatore F. P., Corrado A., Ullman S., Iversen L., Pozzi M. R., Eyerich K., Hein R., Knott E., Szechinski J., Wiland P., Szmyrka-Kaczmarek M., Sokolik R., Morgiel E., Krummel-Lorenz B., Saar P., Aringer M., Gunther C., Anic B., Baresic M., Mayer M., Radominski S. C., de Souza Muller C., Azevedo V. F., Agachi S., Groppa L., Chiaburu L., Russu E., Zenone T., Stebbings S., Highton J., Stamp L., Chapman P., O'Donnell J., Solanki K., Doube A., Veale D., O'Rourke M., Loyo E., Rosato E., Pisarri S., Tanaseanu C. -M., Popescu M., Dumitrascu A., Tiglea I., Chirieac R., Ancuta C., Furst D. E., Kafaja S., Garcia de la Pena Lefebvre P., Rubio S. R., Exposito M. V., Sibilia J., Chatelus E., Gottenberg J. E., Chifflot H., Litinsky I., Venalis A., Butrimiene I., Venalis P., Rugiene R., Karpec D., Kerzberg E., Montoya F., Cosentino V., Low A. H. L., Teng G., Chan G., Lim A. Y. N., Ng S. C., Proudman, S. M., Huq, M., Stevens, W., Wilson, M. E., Sahhar, J., Baron, M., Hudson, M., Pope, J., Allanore, Y., Distler, O., Kowal-Bielecka, O., Matucci-Cerinic, M., H. L. Low, A., Teng, G. G., Law, W. G., Santosa, A., Nikpour, M., Hill, C., Lester, S., Nash, P., Ngian, G. -S., Proudman, S., Rischmueller, M., Roddy, J., Strickland, G., Thakkar, V., Walker, J., Zochling, J., Markland, J., Robinson, D., Jones, N., Khalidi, N., Docherty, P., Kaminska, E., Masetto, A., Sutton, E., Mathieu, J. -P., Ligier, S., Grodzicky, T., Leclercq, S., Thorne, C., Gyger, G., Smith, D., Fortin, P. R., Larche, M., Abu-Hakima, M., Rodriguez-Reyna, T. S., Cabral, A. R., Fritzler, M., Avouac, J., Walker, U. A., Guiducci, S., Riemekasten, G., Air, P., Hachulla, E., Valentini, G., Carreira, P. E., Cozzi, F., Gurman, A. B., Braun-Moscovici, Y., Damjanov, N., Ananieva, L. P., Scorza, R., Jimenez, S., Busquets, J., Li, M., Muller-Ladner, U., Maurer, B., Tyndall, A., Lapadula, G., Iannone, F., Becvar, R., Sierakowsky, S., Cutolo, M., Sulli, A., Cuomo, G., Vettori, S., Rednic, S., Nicoara, I., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Kucharz, E. J., Kotulska, A., Kopec-Medrek, M., Widuchowska, M., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Hij, A., Hesselstrand, R., Scheja, A., Wollheim, F., Martinovic, D., Govoni, M., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Bambara, L. M., Caramaschi, P., Black, C., Denton, C., Henes, J., Santamaria, V. O., Heitmann, S., Krasowska, D., Seidel, M., Oleszowsky, M., Burkhardt, H., Himsel, A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Starovoytova, M. N., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szucs, G., Mendoza, A. Z., de la Puente Buijdos, C., Giraldo, W. A. S., Midtvedt, O., Garen, T., Launay, D., Valesini, G., Riccieri, V., Ionescu, R. M., Opris, D., Groseanu, L., Wigley, F. M., Mihai, C. M., Cornateanu, R. S., Ionitescu, R., Gherghe, A. M., Gorga, M., Dobrota, R., Bojinca, M., Schett, G., Distler, J. H., Meroni, P., Zeni, S., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Szechinski, J., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anic, B., Baresic, M., Mayer, M., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Zenone, T., Stebbings, S., Highton, J., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Rosato, E., Pisarri, S., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Chirieac, R., Ancuta, C., Furst, D. E., Kafaja, S., Garcia de la Pena Lefebvre, P., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Kerzberg, E., Montoya, F., Cosentino, V., Low, A. H. L., Teng, G., Chan, G., Lim, A. Y. N., and Ng, S. C.

Subjects
0301 basic medicine, medicine.medical_specialty, Pediatrics, Survival, Immunology, Disease, Scleroderma, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Immunology and Allergy, Medicine, Multicentre registrie, 030203 arthritis & rheumatology, Clinical features, Cohort study, Multicentre registries, Systemic sclerosis, business.industry, Interstitial lung disease, Autoantibody, Clinical features, medicine.disease, 030104 developmental biology, Clinical feature, Cohort, business, Cohort study, Rheumatism
Abstract

Introduction The aim of this study is to compare the clinical features, mortality and causes of death of systemic sclerosis (SSc) patients in four large multicentre registries. Methods Patients seen at least once in the Australian Scleroderma Cohort Study (ASCS) (n = 1714), the Canadian Scleroderma Research Group (CSRG) (n = 1628), the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) Network (n = 13,996) and the Systemic Sclerosis Cohort in Singapore (SCORE) (n = 500) before August 2016 were included. Clinical manifestations and survival in cohorts and disease subtypes were compared. Results Among 17,838 SSc patients, most were female (86.1%), Caucasian (84.6%) and had the limited cutaneous subtype (lcSSc) (65.0%). The anti-centromere autoantibody was the most prevalent (37.6%). More patients in SCORE had the diffuse subtype (dcSSc) (49.3%) and Scl-70 autoantibody (38.8%) (pConclusions This meta-cohort of SSc patients, the largest reported to date, provides insights into the impact of race and sex on disease manifestations and survival and confirms the early mortality in this disease.

Published
2017
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14. Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database

Author

Avouac, Jerome, Walker, Ulrich, Tyndall, Alan, Kahan, André, Matucci Cerinic, Marco, Allanore, Yannick, Miniati, I., Müller, A., Iannone, F., Giacomelli, R., Distler, O., Becvar, R., Sierakowsky, S., Kowal Bielecka, O., Coelho, P., Cabane, J., Cutolo, M., Shoenfeld, Y., Rovensky, J., Riemekasten, G., Nicoara, I., Vlachoyiannopoulos, P., Caporali, R., Jiri, S., Inanc, M., Gorska, I. Zimmermann, Carreira, P., Novak, S., Czirjak, L., Ramos, F. Oliveira, Jendro, M., Chizzolini, C., Kucharz, E. J., Richter, J., Cozzi, F., Rozman, B., Mallia, C. M., Gabrielli, A., Farge, D., Kiener, H. P., Schöffel, D., Sticherling, M., Airo, P., Wollheim, F., Martinovic, D., Trotta, F., Hunzelmann, N., Jablonska, S., Reich, K., Bombardieri, S., Siakka, P., Pellerito, R., Bambara, L. M., Morovic Vergles, J., Denton, C., Hinrichs, R., Van Den Hoogen, F., Damjanov, N., Kötter, I., Ortiz, V., Heitmann, S., Krasowska, D., Seidel, M., Hasler, P., Van Laar, J. M., Kaltwasser, J. P., Foeldvari, I., Juan Mas, A., Bajocchi, G., Wislowska, M., Pereira Da Silva, J. A., Jacobsen, S., Worm, M., Graniger, W., Kuhn, A., Stankovic, A., Cossutta, R., Majdan, M., Rajcevska, L. Damjanovska, Tikly, M., Nasonov, E. L., Steinbrink, K., Herrick, A., Müller Ladner, U., Dinc, A., Scorza, R., Sondergaard, K., Indiveri, F., Nielsen, H., Szekanecz, Z., Silver, R. M., Antivalle, M., Espinosa, I. B., García De La Pena Lefebvre, P., Midtvedt, O., Launay, D., Valesini, F., Tuvik, P., Ionescu, R. M., Del Papa, N., Pinto, S., Wigley, F., Mihai, C., Capranu, M. Sinziana, Sunderkötter, C., Jun, J. B., Derk, C., Alhasani, S., Distler, J. H., Ton, E., Soukup, T., Seibold, J., Zeni, S., Nash, P., Mouthon, L., De Keyser, F., Duruöz, M. T., Cantatore, F. P., Strauss, G., Von Mülhen, C. A., Pozzi, M. R., Eyerich, K., Szechinski, J., Keiserman, M., Houssiau, F. A., Rom Ivorra, J. A., Krummel Lorenz, B., Aringer, M., Westhovens, R., Bellisai, F., Mayer, M., Stoeckl, F., Üprus, M., Volpe, A., Buslau, M., Yavuz, S., Granel, B., Feijó, A. Valderílio, Del Galdo, F., Popa, S., Zenone, T., Machado, X. Ricardo, Pileckyte, M., Stebbings, S., Mathieu, A., Tulli, A., Tourinho, T., Souza, R., Acayaba De Toledo, R., Stamp, L., Solanki, K., Veale, D., Neto, J. Francisco Marques, Bagnato, G. F., Loyo, E., Toloza, S., Li, M., Mohamed, W. Ahmed Abdel Atty, Cobankara, V., Olas, J., Salsano, F., Oksel, F., Tanaseanu, C. M., Foti, R., Ancuta, C., Vonk, M., Caramashi, P., Beretta, L., Balbir, A., Shine, B., Chiàla, A., Simic, K. Pasalic, Ghio, M., Stamenkovic, B., Rednic, S., Host, N., Hachulla, E., Furst, D. E., VALENTINI, Gabriele, Avouac, Jerome, Walker, Ulrich, Tyndall, Alan, Kahan, André, Matucci Cerinic, Marco, Allanore, Yannick, Miniati, I., Müller, A., Iannone, F., Giacomelli, R., Distler, O., Becvar, R., Sierakowsky, S., Kowal Bielecka, O., Coelho, P., Cabane, J., Cutolo, M., Shoenfeld, Y., Valentini, Gabriele, Rovensky, J., Riemekasten, G., Nicoara, I., Vlachoyiannopoulos, P., Caporali, R., Jiri, S., Inanc, M., Gorska, I. Zimmermann, Carreira, P., Novak, S., Czirjak, L., Ramos, F. Oliveira, Jendro, M., Chizzolini, C., Kucharz, E. J., Richter, J., Cozzi, F., Rozman, B., Mallia, C. M., Gabrielli, A., Farge, D., Kiener, H. P., Schöffel, D., Sticherling, M., Airo, P., Wollheim, F., Martinovic, D., Trotta, F., Hunzelmann, N., Jablonska, S., Reich, K., Bombardieri, S., Siakka, P., Pellerito, R., Bambara, L. M., Morovic Vergles, J., Denton, C., Hinrichs, R., Van Den Hoogen, F., Damjanov, N., Kötter, I., Ortiz, V., Heitmann, S., Krasowska, D., Seidel, M., Hasler, P., Van Laar, J. M., Kaltwasser, J. P., Foeldvari, I., Juan Mas, A., Bajocchi, G., Wislowska, M., Pereira Da Silva, J. A., Jacobsen, S., Worm, M., Graniger, W., Kuhn, A., Stankovic, A., Cossutta, R., Majdan, M., Rajcevska, L. Damjanovska, Tikly, M., Nasonov, E. L., Steinbrink, K., Herrick, A., Müller Ladner, U., Dinc, A., Scorza, R., Sondergaard, K., Indiveri, F., Nielsen, H., Szekanecz, Z., Silver, R. M., Antivalle, M., Espinosa, I. B., García De La Pena Lefebvre, P., Midtvedt, O., Launay, D., Valesini, F., Tuvik, P., Ionescu, R. M., Del Papa, N., Pinto, S., Wigley, F., Mihai, C., Capranu, M. Sinziana, Sunderkötter, C., Jun, J. B., Derk, C., Alhasani, S., Distler, J. H., Ton, E., Soukup, T., Seibold, J., Zeni, S., Nash, P., Mouthon, L., De Keyser, F., Duruöz, M. T., Cantatore, F. P., Strauss, G., Von Mülhen, C. A., Pozzi, M. R., Eyerich, K., Szechinski, J., Keiserman, M., Houssiau, F. A., Rom Ivorra, J. A., Krummel Lorenz, B., Aringer, M., Westhovens, R., Bellisai, F., Mayer, M., Stoeckl, F., Üprus, M., Volpe, A., Buslau, M., Yavuz, S., Granel, B., Feijó, A. Valderílio, Del Galdo, F., Popa, S., Zenone, T., Machado, X. Ricardo, Pileckyte, M., Stebbings, S., Mathieu, A., Tulli, A., Tourinho, T., Souza, R., Acayaba De Toledo, R., Stamp, L., Solanki, K., Veale, D., Neto, J. Francisco Marque, Bagnato, G. F., Loyo, E., Toloza, S., Li, M., Mohamed, W. Ahmed Abdel Atty, Cobankara, V., Olas, J., Salsano, F., Oksel, F., Tanaseanu, C. M., Foti, R., Ancuta, C., Vonk, M., Caramashi, P., Beretta, L., Balbir, A., Shine, B., Chiàla, A., Simic, K. Pasalic, Ghio, M., Stamenkovic, B., Rednic, S., Host, N., Hachulla, E., Furst, D. E., Chizzolini, Carlo, and Westhovens, Rene

Subjects
Male, Systemic disease, Databases, Factual, Cross-sectional study, Joint Diseases/etiology/pathology/physiopathology, Systemic inflammation, Joint involvement, Scleroderma, systemic sclrosis, systemic inflemmetion, joint involvement, Tendons, Systemic sclerosi, Scleroderma, Localized, 0302 clinical medicine, data base, Immunopathology, joint radiography, Immunology and Allergy, Joints/pathology, scleroderma, 030212 general & internal medicine, nuclear magnetic resonance imaging, Range of Motion, Articular, skin and connective tissue diseases, rheumatic disease, ddc:616, interstitial lung disease, Joint contracture, Clinical Trials as Topic, Synovitis, Inflammation/etiology/pathology/physiopathology, integumentary system, article, Tendons/pathology, Middle Aged, musculoskeletal system, cohort analysis, Connective tissue disease, priority journal, Joint, Synoviti, Systemic sclerosis, Female, medicine.symptom, Joint Diseases, Human, musculoskeletal diseases, Adult, medicine.medical_specialty, hand radiography, Immunology, Scleroderma, Localized/etiology/*pathology, Auto-immunity, transplantation and immunotherapy [N4i 4], 03 medical and health sciences, SYSTEMIC SCLEROSIS, JOINT INVOLVEMENT, SYNOVITIS, JOINT CONTRACTURE, TENDON FRICTION RUB, Tendon friction rub, Rheumatology, Internal medicine, medicine, Humans, Health care ethics [NCEBP 5], Tendon, Aged, 030203 arthritis & rheumatology, Cross-Sectional Studie, Inflammation, skin disease, Scleroderma, Systemic, business.industry, echography, medicine.disease, major clinical study, tenosynovitis, Synovitis/etiology/pathology, clinical feature, body regions, Cross-Sectional Studies, Evaluation of complex medical interventions [NCEBP 2], Scleroderma, Systemic/complications/pathology/physiopathology, Joints, disease duration, business, Joint Disease, disease activity
Abstract

Objective.To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc).Methods.This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs.Results.We recruited 7286 patients with SSc; their mean age was 56 ± 14 years, disease duration 10 ± 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable.Conclusion.Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.

Published
2010
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15. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database

Author

Maurer, B., Graf, N., Michel, B. A., Muller Ladner, U., Czirjak, L., Denton, C. P., Tyndall, A., Metzig, C., Lanius, V., Khanna, D., Distler, O., Arner, I. H., Cerinic, M. M., Guiducci, S., Walker, U., Lapadula, G., Iannone, F., Becvar, R., Sierakowsky, S., Bielecka, O. K., Cutolo, M., Sulli, A., Valentini, G., Cuomo, G., Vettori, S., Riemekasten, G., Rednic, S., Nicoara, I., Kahan, A., Allanore, Y., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Carreira, P. E., Novak, S., Varju, C., Chizzolini, C., Kucharz, E. J., Kotulska, A., Kopec Medrek, M., Widuchowska, M., Cozzi, F., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Hij, A., Airo, P., Hesselstrand, R., Scheja, A., Wollheim, F., Martinovic, D., Gurman, A. B., Braun Moscovici, Y., Govoni, Marcello, LO MONACO, Andrea, Hunzelmann, N., Pellerito, R., Bambara, L. M., Caramaschi, P., Black, C., Damjanov, N., Santamaria, V. O., Heitmann, S., Krasowska, D., Seidel, M., Oleszowsky, M., Burkhardt, H., Himsel, A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Starovoytova, M. N., Ananieva, L. P., Scorza, R., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szucs, G., Mendoza, A. Z., Buijdos, C. d. l. P., Sifuentes Giraldo, W. A., Midtvedt, O., Garen, T., Hachulla, E., Launay, D., Valesini, G., Riccieri, V., Ionescu, R. M., Opris, D., Groseanu, L., Wigley, F. M., Mihai, C. M., Cornateanu, R. S., Ionitescu, R., Gherghe, A. M., Gorga, M., Dobrota, R., Bojinca, M., Schett, G., Distler, J. H., Meroni, P., Zeni, P., Mouthon, L., Keyser, F. D., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Szechinski, J., Wiland, P., Szmyrka Kaczmarek, M., Sokolik, R., Morgiel, E., Krummel Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anic, B., Baresic, M., Mayer, M., Radominski, S. C., Muller, C. d. S., Azevedo, V. F., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Zenone, T., Highton, J., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Pisarri, S., Tanaseanu, C. M., Popescu, M., Dumitrascu, A., Tiglea, I., Chirieac, R., Ancuta, C., Furst, D. E., Kafaja, S., Lefebvre, P. G. d. l. P., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Kerzberg, E., Montoya, F., Cosentino, V., Chizzolini, Carlo, Maurer, Britta, Graf, Nicole, Michel, Beat A, Müller Ladner, Ulf, Czirják, László, Denton, Christopher P, Tyndall, Alan, Metzig, Carola, Lanius, Vivian, Khanna, Dinesh, Distler, Oliver, Tarner, Ingo H, Cerinic, Marco Matucci, Guiducci, Serena, Walker, Ulrich, Lapadula, Giovanni, Iannone, Florenzo, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Cutolo, Maurizio, Sulli, Alberto, Valentini, Gabriele, Cuomo, Giovanna, Vettori, Serena, Riemekasten, Gabriele, Rednic, Simona, Nicoara, Ileana, Kahan, André, Allanore, Yannick, Vlachoyiannopoulos, P, Montecucco, Carlomaurizio, Caporali, Roberto, Carreira, Patricia E, Novak, Srdan, Varju, Cecilia, Kucharz, Eugene J, Kotulska, Anna, Kopec Medrek, Magdalena, Widuchowska, Malgorzata, Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Hij, Adrian, Airò, Paolo, Hesselstrand, Roger, Scheja, Agneta, Wollheim, Frank, Martinovic, Duska, Gurman, Alexandra Balbir, Braun Moscovici, Yolanda, Govoni, M, Monaco, Andrea Lo, Hunzelmann, Nicola, Pellerito, Raffaele, Bambara, Lisa Maria, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Santamaria, Vera Ortiz, Heitmann, Stefan, Krasowska, Dorota, Seidel, Matthia, Oleszowsky, Mara, Burkhardt, Harald, Himsel, Andrea, Salvador, Maria J, Stamenkovic, Bojana, Stankovic, Aleksandra, Tikly, Mohammed, Starovoytova, Maya N, Ananieva, Lidia P, Scorza, Raffaella, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szücs, Gabriella, Mendoza, Antonio Zea, Buijdos, Carlos de la Puente, Giraldo, Walter A. Sifuente, Midtvedt, Øyvind, Garen, Torhild, Hachulla, Eric, Launay, David, Valesini, Guido, Riccieri, Valeria, Ionescu, Ruxandra Maria, Opris, Daniela, Groseanu, Laura, Wigley, Fredrick M, Mihai, Carmen M, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Gorga, Marilena, Dobrota, Rucsandra, Bojinca, Mihai, Schett, Georg, Distler, Jörg HW, Meroni, Pierluigi, Zeni, Silvana, Mouthon, Luc, Keyser, Filip De, Cantatore, Francesco P, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria R, Eyerich, Kilian, Hein, Rüdiger, Knott, Elisabeth, Szechinski, Jacek, Wiland, Piotr, Szmyrka Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Krummel Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Günther, Claudia, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Radominski, Sebastião C, Müller, Carolina de Souza, Azevedo, Valderílio F, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Zenone, Thierry, Highton, John, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Dougla, O’Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Pisarri, Simonetta, Tanaseanu, Cristina Mihaela, Popescu, Monica, and University of Zurich

Subjects
Genetics and Molecular Biology (all), Male, Time Factors, Databases, Factual, systemic sclerosis, 2745 Rheumatology, computer.software_genre, Biochemistry, Severity of Illness Index, Outcomes Research, Qualitative Research, Systemic Sclerosis, Adult, Cohort Studies, Creatine Kinase, Decision Support Techniques, Deglutition Disorders, Dyspnea, Female, Fibrosis, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Scleroderma, Diffuse, Sex Factors, Skin, Synovitis, Disease Progression, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), Immunology and Allergy, Medicine (all), Scleroderma, skin fibrosis, skin and connective tissue diseases, ddc:616, EUSTAR, Univariate analysis, Database, integumentary system, 10051 Rheumatology Clinic and Institute of Physical Medicine, Orvostudományok, Diffuse, Connective tissue disease, Cohort, 2723 Immunology and Allergy, Cohort study, medicine.medical_specialty, 610 Medicine & health, Klinikai orvostudományok, General Biochemistry, Genetics and Molecular Biology, NO, outcomes research, qualitative research, Databases, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Severity of illness, medicine, Factual, 2403 Immunology, business.industry, medicine.disease, business, computer
Abstract

ObjectivesTo identify predictive parameters for the progression of skin fibrosis within 1 year in patients with diffuse cutaneous SSc (dcSSc).MethodsAn observational study using the EUSTAR database was performed. Inclusion criteria were dcSSc, American College of Rheumatology (ACR) criteria fulfilled, modified Rodnan skin score (MRSS) ≥7 at baseline visit, valid data for MRSS at 2nd visit, and available follow-up of 12±2 months. Worsening of skin fibrosis was defined as increase in MRSS >5 points and ≥25% from baseline to 2nd visit. In the univariate analysis, patients with progressive fibrosis were compared with non-progressors, and predictive markers with pResultsA total of 637 dcSSc patients were eligible. Univariate analyses identified joint synovitis, short disease duration (≤15 months), short disease duration in females/patients without creatine kinase (CK) elevation, low baseline MRSS (≤22/51), and absence of oesophageal symptoms as potential predictors for progressive skin fibrosis. In the multivariate analysis, by employing combinations of the predictors, 17 models with varying prediction success were generated, allowing cohort enrichment from 9.7% progressive patients in the whole cohort to 44.4% in the optimised enrichment cohort. Using a second validation cohort of 188 dcSSc patients, short disease duration, low baseline MRSS and joint synovitis were confirmed as independent predictors of progressive skin fibrosis within 1 year resulting in a 4.5-fold increased prediction success rate.ConclusionsOur study provides novel, evidence-based criteria for the enrichment of dcSSc cohorts with patients who experience worsening of skin fibrosis which allows improved clinical trial design.

Published
2014

17. Doppler echocardiography pulmonary artery flow acceleration time: an adjunctive parameter to select candidates with suspected pulmonary hypertension to proceed to right heart catheterization

Author

Fontana, A., primary, Vincenzi, A., additional, Paciocco, G., additional, De Vito, G., additional, Marinari, A., additional, Trocino, G., additional, Ciro', A., additional, De Carlini, C., additional, Pozzi, M. R., additional, and Achilli, F., additional

Published
2013
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21. Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis.

Author

Gardinali, M, Pozzi, M R, Bernareggi, M, Montani, N, Allevi, E, Catena, L, Cugno, M, Bottasso, B, and Stabilini, R

Abstract

OBJECTIVE: To evaluate the efficacy and safety of prostaglandin (PG) E1alpha-cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc) and its effect on variables of immune activation and endothelial injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble interleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand factor (vWF), and tissue-type plasminogen activator (t-PA). METHODS: We studied 36 women with SSc, 24 of them given three 60 microg intravenous PGE1alpha-cyclodextrin infusions on 5 consecutive days at 6 week intervals during the winter. RP symptoms and healing of digital lesions were evaluated. Twenty age matched healthy women were the controls. TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA were measured after the first and last infusion of PGEE1alpha-cyclodextrin and correlated with clinical features. RESULTS: RP symptoms improved in 87% of the patients. The benefit of each 5 day cycle lasted 4 or more weeks in 75%. PGE1alpha-cyclodextrin reduced the daily frequency of RP symptoms by 20% (p < 0.05), 41% (p < 0.005), and 53% (p < 0.0005) from baseline after the 1st, 2nd, and 3rd infusions, respectively. The severity of the attacks was reduced to a limited degree. In 12 of the 14 patients with digital lesions, these healed completely. Ten patients had mild side effects during treatment (headache, increased intestinal motility, flushing). TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA plasma concentrations were significantly higher in patients with SSc than controls (p < 0.05, p < 0.001). TNF-alpha, sIL-2R, and cICAM-1 were higher in diffuse SSc and patients with lung involvement. The plasma levels of cICAM-1 and t-PA were significantly reduced after the 1st infusion of PGE1alpha-cyclodextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005). CONCLUSION: PGE1alpha-cyclodextrin reduces RP symptoms and plasma levels of the markers of endothelial injury in SSc, suggesting that an improvement of endothelial dysfunction contributes to its prolonged therapeutic effect.

Published
2001

22. Tandem linkage and unusual RNA splicing of the T-cell receptor beta-chain variable-region genes.

Author

Chou, H S, Anderson, S J, Louie, M C, Godambe, S A, Pozzi, M R, Behlke, M A, Huppi, K, and Loh, D Y

Abstract

The variable-region (V) genes of the murine T-cell receptor beta chain exist largely as single-element subfamilies. The V beta 5 and V beta 8 genes belong to the only two known three-member V beta subfamilies. We present studies on the linkage of these six genes and show that the genomic organization is that of alternating V beta 5 and V beta 8 genes. Our analysis suggests that these genes were tandemly duplicated, the unit of duplication being a pair of V beta 5 and V beta 8 genes. This tandem organization permits transcripts to initiate from the promoter of an unrearranged V beta located upstream of the rearranged V beta gene. These transcripts can generate functional beta-chain gene messages by novel RNA splicing of the upstream leader exon to the V beta coding exon of the downstream rearranged gene. We extend the analysis of the T-cell receptor genomic organization to include 12 V beta genes and suggest that all V beta genes are closely linked on chromosome 6. In addition, we discuss the possible implications of the close linkage of the V beta genes on the development of the T-cell receptor beta-chain gene repertoire.

Published
1987
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23. What could we learn from the sub-analysis of a single nation cohort in a worldwide study? Lessons from the results observed in the Italian cohort of the GO-MORE trial

Author

Giacomelli, R., Ruscitti, P., Bombardieri, S., Cuomo, G., Vita, S. D., Galeazzi, M., Mecchia, M., Lagana, B., Versace, F., Cantini, F., Gerli, R., Grassi, W., Ferraccioli, G., Migliore, A., Valesini, G., Minisola, G., Paolazzi, G., Sabbadini, M. G., Sante, G. D., Puttini, P. S., Scarpellini, M., Pellerito, R., Bianchi, G., Pozzi, M. R., Triolo, G., Iacono, D., Foti, R., Varcasia, G., Amato de Paulis, Rocchetta, P. A., Liakouli, V., Cipriani, P., Giacomelli, R, Ruscitti, P., Bombardieri, S., Cuomo, G, Vita, S. D., Galeazzi, M, Mecchia, M., Lagana, B, Versace, F, Cantini, F, Gerli, R, Grassi, W, Ferraccioli, G., Migliore, A, Valesini, G, Minisola, G, Paolazzi, G, Sabbadini, M. G., Sante, G. D., Puttini, P. S., Scarpellini, M., Pellerito, R, Bianchi, G, Pozzi, M. R., Triolo, G., Iacono, D., Foti, R., Varcasia, G., De Paulis, A., Rocchetta, P. A., Liakouli, V., and Cipriani, P.

Subjects
Adult, Male, Antirheumatic Agent, Antibodies, Monoclonal, Middle Aged, Severity of Illness Index, Golimumab, Arthritis, Rheumatoid, Clinical trial, Prospective Studie, Methotrexate, Treatment Outcome, Italy, Subset analyses, Tumour necrosis factor-alpha, Biologic products, Rheumatoid arthritis, Drug Therapy, Combination, Female, Cohort Studie, Human
Abstract

GO-MORE Trial investigated the use of Golimumab (GLM) in 3280 rheumatoid arthritis (RA) patients worldwide. At present, the burden of arthritis is greater in poorer countries than in developed countries due to socioeconomic disparities, thus suggesting the usefulness of subgroup investigations. We aimed to evaluate GLM as add-on therapy for RA patients in the Italian cohort of GO-MORE trial and compared the clinical characteristics between Italian patients and the enrolled patients worldwide.

24. Tocilizumab in the treatment of patients with rheumatoid arthritis in real clinical practice: Results of an Italian observational study

Author

Caporali, R., Idolazzi, L., Bombardieri, S., Ferraccioli, G., Gerli, R., Govoni, M., Matucci-Cerinic, M., Pomponio, G., Fausto SALAFFI, Tirri, R., Benaglio, F., Bianchino, L., Sarzi-Puttini, P., Adami, S., Afeltra, A., Altomonte, L., Arrigoni, E., Bagnato, G., Bianchi, G., Bucci, R. N., Caminiti, M., Cantini, F., Caputo, D., Carlino, G., Clerico, P., Colombelli, P., Corsaro, S. M., D Alessandro, G., Riso, L., Silva, S., D Errico, T., Di Matteo, L., Ferri, C., Foti, R., Fusaro, E., Gabrielli, A., Giacomelli, R., Lunardi, C., Malavolta, N., Martin Martin, L. S., Massarotti, M. S., Mazzone, A., Meschini, C., Migliore, A., Minisola, G., Monti, G., Muratore, M., Paoletti, F., Pappone, N., Passiu, G., Pirisi, M., Pistone, G., Pozzi, M. R., Prandini, P., Provenzano, G., Ricioppo, A., Romeo, N., Russo, R., Saviola, G., Semeraro, A., Tartarelli, G., Tomietto, P., Valentini, G., and Zuccaro, C.

25. An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database

Author

Brand, M., Hollaender, R., Rosenberg, D., Scott, M., Hunsche, E., Tyndall, A., Denaro, V., Patricia E Carreira, Varju, C., Gabrielli, B., Zingarelli, S., Caramaschi, P., Simic-Pasalic, K., Müller-Ladner, U., Vasile, M., Mihai, C., Rosato, E., Vacca, A., Zenone, T., Mohamed, W. A., Ancuta, C., Zampogna, G., Rednic, S., Jabaar, N., Belloli, L., Pozzi, M. R., Foti, R., and Walker, U. A.

Subjects
Adult, Male, Scleroderma, Systemic, Time Factors, Databases, Factual, Hypertension, Pulmonary, Incidence, Middle Aged, Prognosis, Activities of Daily Living, Cost of Illness, Europe, Female, Fingers, Hospitalization, Humans, Logistic Models, Odds Ratio, Prospective Studies, Quality of Life, Recurrence, Risk Factors, Skin Ulcer
Abstract

This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU).Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010.Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids.This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

27. Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort

Author

Muriel Elhai, Nanthara Sritharan, Marouane Boubaya, Alexandra Balbir-Gurman, Elise Siegert, Eric Hachulla, Jeska de Vries-Bouwstra, Gabriela Riemekasten, Jörg H W Distler, Edoardo Rosato, Francesco Del Galdo, Fabian A Mendoza, Daniel E Furst, Carlos de la Puente, Anna-Maria Hoffmann-Vold, Armando Gabrielli, Oliver Distler, Coralie Bloch-Queyrat, Yannick Allanore, Marco Matucci Cerinic, Ulrich Walker, Florenzo Iannone, Suzana Jordan, Radim Becvar, Otylia Kowal Bielecka, Maurizio Cutolo, Giovanna Cuomo, Claudia Kedor, Simona Rednic, Jérome Avouac, P. Vlachoyiannopoulos, C. Montecucco, Jiri Stork, Murat Inanc, Patricia E. Carreira, Srdan Novak, László Czirják, Michele Iudici, Eugene J. Kucharz, Elisabetta Zanatta, Katja Perdan-Pirkmajer, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Paolo Airò, Roger Hesselstrand, Mislav Radic, Yolanda Braun-Moscovici, Andrea Lo Monaco, Nicolas Hunzelmann, Raffaele Pellerito, Alessandro Giollo, Jadranka Morovic-Vergles, Christopher Denton, Madelon Vonk, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Michaela Kohm, Ivan Foeldvari, Gianluigi Bajocchi, Maria João Salvador, Bojana Stamenkovic, Carlo Francesco Selmi, Mohammed Tikly, Lidia P. Ananieva, Ariane Herrick, Ulf Müller-Ladner, Raffaele De Palma, Merete Engelhart, Gabriela Szücs, Cristina Sobrino Grande, Øyvind Midtvedt, David Launay, Valeria Riccieri, Ruxandra Maria Ionescu, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Carlos Alberto von Mühlen, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anic, Maria Üprus, Sule Yavuz, Brigitte Granel, Carolina de Souza Müller, Joanna Busquets, Svetlana Agachi, Simon Stebbings, D'Alessandro Mathieu, Percival D. Sampaio-Barros, Lisa Stamp, Kamal Solanki, Douglas Veale, Esthela Loyo, Mengtao Li, Walid Ahmed Abdel Atty Mohamed, Antonietta Gigante, Fahrettin Oksel, Cristina-Mihaela Tanaseanu, Rosario Foti, Codrina Ancuta, Britta Maurer, Jacob van Laar, Cristiane Kayser, Nihal Fathi, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Giuseppina Abignano, Goda Seskute, Lesley Ann Saketkoo, Eduardo Kerzberg, Washington Bianchi, Ivan Castellví, Massimiliano Limonta, Doron Rimar, Maura Couto, François Spertini, Antonella Marcoccia, Sarah Kahl, Ivien M. Hsu, Thierry Martin, Sergey Moiseev, Lorinda S. Chung, Tim Schmeiser, Dominik Majewski, Zbigniew Zdrojewski, Julia Martínez-Barrio, Vera Bernardino, Sabine Sommerlatte, Yair Levy, Elena Rezus, Omer Nuri Pamuk, Piercarlo Sarzi Puttini, Hadi Poormoghim, Ina Kötter, Francis Gaches, Laura Belloli, Petros Sfikakis, Juliana Markus, Gary R Feldman, Ana-Maria Ramazan, H.U. Scherer, Marie-Elise Truchetet, Alain Lescoat, Lorenzo Dagna, J.M. van Laar, Lidia Rudnicka, Susana Oliveira, Fabiola Atzeni, Masataka Kuwana, Arsene Mekinian, Mickaël Martin, Yoshiya Tanaka, Elhai, M., Sritharan, N., Boubaya, M., Balbir-Gurman, A., Siegert, E., Hachulla, E., de Vries-Bouwstra, J., Riemekasten, G., Distler, J. H. W., Rosato, E., Del Galdo, F., Mendoza, F. A., Furst, D. E., de la Puente, C., Hoffmann-Vold, A. -M., Gabrielli, A., Distler, O., Bloch-Queyrat, C., Allanore, Y., Matucci Cerinic, M., Walker, U., Iannone, F., Jordan, S., Becvar, R., Kowal Bielecka, O., Cutolo, M., Cuomo, G., Kedor, C., Rednic, S., Avouac, J., Vlachoyiannopoulos, P., Montecucco, C., Stork, J., Inanc, M., Carreira, P. E., Novak, S., Czirjak, L., Iudici, M., Kucharz, E. J., Zanatta, E., Perdan-Pirkmajer, K., Coleiro, B., Moroncini, G., Farge Bancel, D., Airo, P., Hesselstrand, R., Radic, M., Braun-Moscovici, Y., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Giollo, A., Morovic-Vergles, J., Denton, C., Vonk, M., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Hasler, P., Kohm, M., Foeldvari, I., Bajocchi, G., Salvador, M. J., Stamenkovic, B., Selmi, C. F., Tikly, M., Ananieva, L. P., Herrick, A., Muller-Ladner, U., De Palma, R., Engelhart, M., Szucs, G., Sobrino Grande, C., Midtvedt, O., Launay, D., Riccieri, V., Ionescu, R. M., Sha, A., Gheorghiu, A. M., Sunderkotter, C., Ingegnoli, F., Mouthon, L., Smith, V., Cantatore, F. P., Ullman, S., Alberto von Muhlen, C., Pozzi, M. R., Eyerich, K., Wiland, P., Vanthuyne, M., Alegre-Sancho, J. J., Herrmann, K., De Langhe, E., Anic, B., Uprus, M., Yavuz, S., Granel, B., de Souza Muller, C., Busquets, J., Agachi, S., Stebbings, S., Mathieu, D. A., Sampaio-Barros, P. D., Stamp, L., Solanki, K., Veale, D., Loyo, E., Li, M., Abdel Atty Mohamed, W. A., Gigante, A., Oksel, F., Tanaseanu, C. -M., Foti, R., Ancuta, C., Maurer, B., van Laar, J., Kayser, C., Fathi, N., Garcia de la Pena Lefebvre, P., Sibilia, J., Litinsky, I., Abignano, G., Seskute, G., Saketkoo, L. A., Kerzberg, E., Bianchi, W., Castellvi, I., Limonta, M., Rimar, D., Couto, M., Spertini, F., Marcoccia, A., Kahl, S., Hsu, I. M., Martin, T., Moiseev, S., Chung, L. S., Schmeiser, T., Majewski, D., Zdrojewski, Z., Martinez-Barrio, J., Bernardino, V., Sommerlatte, S., Levy, Y., Rezus, E., Nuri Pamuk, O., Sarzi Puttini, P., Poormoghim, H., Kotter, I., Gaches, F., Belloli, L., Sfikakis, P., Markus, J., Feldman, G. R., Ramazan, A. -M., Scherer, H. U., Truchetet, M. -E., Lescoat, A., Dagna, L., van Laar, J. M., Rudnicka, L., Oliveira, S., Atzeni, F., Kuwana, M., Mekinian, A., Martin, M., and Tanaka, Y.

Subjects
Rheumatology, Immunology, Immunology and Allergy
Abstract

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

Published
2022

28. Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: A European Scleroderma Trials and Research (EUSTAR) analysis

Author

Becker, Mike, Graf, Nicole, Sauter, Rafael, Allanore, Yannick, Curram, John, Denton, Christopher P., Khanna, Dinesh, Matucci-Cerinic, Marco, Pena, Janethe de Oliveira, Pope, Janet E., Distler, Oliver, Guiducci, Serena, Walker, Ulrich, Jaeger, Veronika, Bannert, Bettina, Lapadula, Giovanni, Becvarare, Radim, Cutolo, Maurizio, Valentini, Gabriele, Siegert, Elise, Rednic, Simona, Montecucco, C., Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Popa, Sergei, Zenone, Thierry, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Visalli, Elisa, Benenati, Alessia, Amato, Giorgio, Ancuta, Codrina, Chirieac, Rodica, Villiger, Peter, Adler, Sabine, Dan, Diana, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Del Galdo, Francesco, Venalis, Algirdas, Saketkoo, Lesley Ann, Lasky, Joseph A., Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, Ege Üniversitesi, University of Zurich, Distler, Oliver, Chizzolini, Carlo, Allai, Daniela, Becker, M., Graf, N., Sauter, R., Allanore, Y., Curram, J., Denton, C. P., Khanna, D., Matucci-Cerinic, M., de Oliveira Pena, J., Pope, J. E., Distler, O., Guiducci, S., Walker, U., Jaeger, V., Bannert, B., Lapadula, G., Becvarare, R., Cutolo, M., Valentini, G., Siegert, E., Rednic, S., Montecucco, C., Carreira, P. E., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Allai, D., Kucharz, E. J., Cozzi, F., Rozman, B., Mallia, C., Gabrielli, A., Bancel, D. F., Airo, P., Hesselstrand, R., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Hunzelmann, N., Pellerito, R., Caramaschi, P., Black, C., Damjanov, N., Henes, J., Santamaria, V. O., Heitmann, S., Seidel, M., Pereira Da Silva, J. A., Stamenkovic, B., Selmi, C. F., Tikly, M., Denisov, L. N., Muller-Ladner, U., Engelhart, M., Hachulla, E., Riccieri, V., Ionescu, R. M., Mihai, C., Sunderkotter, C., Kuhn, A., Schett, G., Distler, J., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Alegre-Sancho, J. J., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anne, E., Westhovens, R., De Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Popa, S., Zenone, T., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Visalli, E., Benenati, A., Amato, G., Ancuta, C., Chirieac, R., Villiger, P., Adler, S., Dan, D., de la Pena Lefebvre, P. G., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Del Galdo, F., Venalis, A., Saketkoo, L. A., Lasky, J. A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Brucato, A. L., Lupi, E., Spertini, F., Ribi, C., Buss, G., Martin, T., Guffroy, A., Poindron, V., Chung, L., Schmeiser, T., Zebryk, P., Riso, N., Riemekasten, G., Rezus, E., and Sarzi Puttini, P.

Subjects
INVOLVEMENT, SELECTION, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, predictive factors, systemic sclerosis, 2745 Rheumatology, epidemiologic methods, morbidity, Disease, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, INTERSTITIAL LUNG-DISEASE, disease worsening, mortality, predictive factors, systemic sclerosis, predictive factor, disease worsening, DESIGN, middle aged, Medicine and Health Sciences, FIBROSIS, scleroderma, SKIN THICKNESS SCORE, mortality, skin and connective tissue diseases, Prospective cohort study, humans, lung diseases, ddc:616, education.field_of_study, heart diseases, integumentary system, clinical trials as topic, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, Interstitial lung disease, follow-up studies, ddc, female, Cohort, 2723 Immunology and Allergy, europe, Life Sciences & Biomedicine, CLINICAL-TRIALS, survival rate, medicine.medical_specialty, Population, 610 Medicine & health, disease progression, male, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Severity of illness, REGRESSION, medicine, severity of illness index, education, Survival rate, METAANALYSIS, 2403 Immunology, Science & Technology, Scleroderma, Systemic, business.industry, MORTALITY, systemic, medicine.disease, prospective studies, Clinical trial, prognosis, scleroderma, diffuse, scleroderma, systemic, Scleroderma, Diffuse, business
Abstract

PubMed: 31227488, Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ., Bayer Bayer, United Kingdom Université Paris Descartes Li Ka Shing Foundation, LKSF University of Michigan, U-M, 1Department of Rheumatology and the Centre of experimental Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Big Data institute, li Ka shing Centre for Health information and Discovery, nuffield Department of Medicine, University of Oxford, Oxford, UK 4Rheumatology a Department, Paris Descartes University, sorbonne Paris Cité, Cochin Hospital, Paris, France 5Data science and analytics, Bayer plc, Reading, UK 6UCl Division of Medicine, Royal Free Campus, london, UK 7Division of Rheumatology, Department of internal Medicine, University of Michigan scleroderma Program, University of Michigan, ann arbor, Michigan, Usa 8Department of experimental and Clinical Medicine, University of Florence, Florence, italy 9Bayer Us llC, Whippany, new Jersey, Usa 10Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Ontario, Canada Acknowledgements The R-code for the linear Mi-lassO was received from Qixuan Chen.21 Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., Contributors study conception and design, acquisition of data, analysis and interpretation of data and drafting and revising the article: OD and MB; analysis and interpretation of data: OD, MB, Rs and nG. all authors have critically reviewed and approved the final submitted version to be published. Funding This study was supported by a grant from Bayer aG. Bayer employees are coauthors of this paper and supported the study design and interpretation of the data, but otherwise Bayer had no influence on the study., Competing interests MOB declares no conflict of interest. OD has had consultancy relationships with actelion, Bayer, Biogen idec, Boehringer ingelheim, Chemomab, espeRare foundation, Genentech/Roche, GsK, inventiva, italfarmaco, lilly, medac, Medimmune, Mitsubishi Tanabe Pharma, Pharmacyclics, novartis, Pfizer, sanofi, sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from actelion, Bayer, Boehringer ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. OD has a patent for mir-29 licensed for the treatment of systemic sclerosis. DK has consultancy relationships and/or has received grant/research support from Bayer, Bristol-Myers squibb, Boehringer ingelheim, Genentech/Roche, niH, Pfizer, sanofi-aventis Pharmaceuticals, actelion Pharmaceuticals Us, Chemomab, Corbus, Covis, Cytori, eicos, eMD serono, Gilead, GlaxosmithKline, and UCB Pharma. He is a shareholder of eicos. CPD has consultancy relationships with and/or has received speakers’ bureau fees from actelion Pharmaceuticals Us, Bayer aG, GlaxosmithKline, Csl Behring, Merck serono, Roche Pharmaceuticals, Genentech and Biogen iDeC inc., inventiva, sanofi-aventis Pharmaceuticals and Boehringer ingelheim. JeP has consultancy relationships with and/or has received grant/research support from actelion, Bayer aG, Bristol-Myers squibb, Merck, Pfizer inc. and Roche. MM-C has consultancy relationships and/ or has received grant/research support from Pfizer, Bristol-Myers squibb, actelion, UCB Pharma, Bayer, Chemomab, Genentech/Roche, inventiva and lilly. Ya has consultancy relationships with and/or has received grant/research support from actelion, Pharmaceuticals Us, Bayer aG, Bristol-Myers squibb, inventiva, Medac, Pfizer inc., Roche Pharmaceuticals, Genentech and Biogen iDeC inc., sanofi-aventis Pharmaceuticals and servier. JdOP and JC are employees of Bayer. nTG has nothing to disclose.

Published
2019

29. Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the european scleroderma trials and research (eustar) cohort

Author

Wu, Wanlong, Jordan, Suzana, Graf, Nicole, Pena, Janethe de Oliveira, Curram, John, Allanore, Yannick, Matucci-Cerinic, Marco, Pope, Janet E., Denton, Christopher P., Khanna, Dinesh, Distler, Oliver, Guiducci, Serena, Walker, Ulrich, Jaeger, Veronika, Bannert, Bettina, Lapadula, Giovanni, Becvarare, Radim, Cutolo, Maurizio, Valentini, Gabriele, Siegert, Elise, Rednic, Simona, Montecucco, C., Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Popa, Sergei, Zenone, Thierry, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Visalli, Elisa, Benenati, Alessia, Amato, Giorgio, Ancuta, Codrina, Chirieac, Rodica, Villiger, Peter, Adler, Sabine, Dan, Diana, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Del Galdo, Francesco, Venalis, Algirdas, Saketkoo, Lesley Ann, Lasky, Joseph A., Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, Wu, W., Jordan, S., Graf, N., de Oliveira Pena, J., Curram, J., Allanore, Y., Matucci-Cerinic, M., Pope, J. E., Denton, C. P., Khanna, D., Distler, O., Guiducci, S., Walker, U., Jaeger, V., Bannert, B., Lapadula, G., Becvarare, R., Cutolo, M., Valentini, G., Siegert, E., Rednic, S., Montecucco, C., Carreira, P. E., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Allai, D., Kucharz, E. J., Cozzi, F., Rozman, B., Mallia, C., Gabrielli, A., Bancel, D. F., Airo, P., Hesselstrand, R., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Hunzelmann, N., Pellerito, R., Caramaschi, P., Black, C., Damjanov, N., Henes, J., Santamaria, V. O., Heitmann, S., Seidel, M., Pereira Da Silva, J. A., Stamenkovic, B., Selmi, C. F., Tikly, M., Denisov, L. N., Muller-Ladner, U., Engelhart, M., Hachulla, E., Riccieri, V., Ionescu, R. M., Mihai, C., Sunderkotter, C., Kuhn, A., Schett, G., Distler, J., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Alegre-Sancho, J. J., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anne, E., Westhovens, R., De Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Popa, S., Zenone, T., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Visalli, E., Benenati, A., Amato, G., Ancuta, C., Chirieac, R., Villiger, P., Adler, S., Dan, D., de la Pena Lefebvre, P. G., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Del Galdo, F., Venalis, A., Saketkoo, L. A., Lasky, J. A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Brucato, A. L., Lupi, E., Spertini, F., Ribi, C., Buss, G., Martin, T., Guffroy, A., Poindron, V., Chung, L., Schmeiser, T., Zebryk, P., Riso, N., Riemekasten, G., Rezus, E., Sarzi Puttini, P., Ege Üniversitesi, Chizzolini, Carlo, Allali, Danièle, University of Zurich, and Distler, Oliver

Subjects
INVOLVEMENT, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, Time Factors, Databases, Factual, Skin Diseases/etiology/mortality/physiopathology, PREDICTION, Fibrosi, 2745 Rheumatology, Diffuse/complications/mortality/pathology, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, Kaplan-Meier Estimate, ddc:616.07, Severity of Illness Index, Scleroderma, Cohort Studies, PROGNOSTIC-FACTORS, Fibrosis, Medicine and Health Sciences, scleroderma, Lung, Skin, integumentary system, progressive skin fibrosis, Lung function decline, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, DEATH, Middle Aged, ddc, Europe, VARIABILITY, factual, Cohort, Visceral organ progression, 2723 Immunology and Allergy, Disease Progression, Female, Survival Analysi, Life Sciences & Biomedicine, Cohort study, Human, Adult, Skin/pathology, medicine.medical_specialty, databases, All-cause death, risk analysis, diffuse cutaneous systemic sclerosis, 610 Medicine & health, IMPROVEMENT, Systemic Sclerosis, Skin Diseases, THICKNESS SCORE, VALIDATION, Databases, FEV1/FVC ratio, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, Humans, Factual, Survival analysis, 2403 Immunology, Science & Technology, Proportional hazards model, business.industry, Surrogate endpoint, MORTALITY, Skin Disease, fibrosis, Progressive skin fibrosi, Lung/physiopathology, biomarkers, Diffuse cutaneous systemic sclerosi, medicine.disease, Survival Analysis, all-cause death, lung function decline, visceral organ progression, adult, cohort studies, databases, factual, disease progression, female, humans, Scleroderma, Diffuse, Cohort Studie, business
Abstract

PubMed: 30852552, Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ?7, valid mRSS at 12±3 months after baseline and ?1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ?25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ?10% (53.6% vs 34.4%; p, Bayer Bayer, 1Department of Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Clinical Development Pulmonology, Bayer Us llC, Whippany, new Jersey, Usa 4Data science and analytics, Bayer plc, Reading, UK 5Rheumatology a Department, Paris Descartes University, inseRM U1016, sorbonne, Paris Cité, Cochin Hospital, Paris, France 6Division of Rheumatology, University of Florence, Florence, italy 7Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Western Ontario, Canada 8Department of Rheumatology, Royal Free Hospital, University College london, london, UK 9scleroderma Program, Department of internal Medicine, Division of Rheumatology, University of Michigan, ann arbor, Michigan, Usa Acknowledgements The authors thank nicole schneider for excellent administration and data entry into the eUsTaR cohort. Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., This study was supported by a grant from Bayer aG.

Published
2019

30. Ferritins in malignant and non-malignant lymphoid cells

Author

Paolo Arosio, Maria Rosa Pozzi, Paolo Vezzoni, Elena Gabri, Silvia Spinazze, Sonia Levi, Vezzoni, P, Levi, SONIA MARIA ROSA, Gabri, E, Pozzi M., R, Spinazze, S, and Arosio, P.

Subjects
Pathology, medicine.medical_specialty, Lymphoma, Lymphoblast, Significant difference, Radioimmunoassay, Non malignant, Hematology, Thymus Gland, Biology, Hodgkin Disease, Peripheral blood, Ferritin, Ferritins, medicine, biology.protein, Humans, Lymph, Lymph Nodes, Lymphocytes
Abstract

Summary. Lymphoid cells from peripheral blood, thymus, malignant and non-malignant lymph nodes were analysed for ferritin content using radioimmunoassays specific for the ‘acidic’ H-subunit-rich and for ‘basic’ L-subunit-rich isoferritins, and the data were compared with the immunological characteristics of the cells. All tissues with high proportion of T or ‘null’ cells contained the lowest concentration of L-subunit-rich isoferritins, while the H-subunit-rich forms increased from low levels in the quiescent peripheral blood lymphocytes (PBL), to higher values in the immature and proliferating thymocytes and lymphoblasts, malignant or not. B-cell lymphomas contained concentrations of both ferritin types higher than those found in PBL. No significant difference was found in the isoferritin concentrations between non-malignant lymph nodes and tissues involved in Hodgkin's disease. These findings indicate that maturation stage, proliferative status and anatomical localization affect isoferritin expression in lymphoid cells.

31. Autologous fat grafting for scleroderma-induced digital ulcers. An effective technique in patients with systemic sclerosis.

Author

Bene MD, Pozzi MR, Rovati L, Mazzola I, Erba G, and Bonomi S

Subjects
Adult, Aged, Amputation, Surgical, Combined Modality Therapy, Female, Fingers pathology, Humans, Iloprost therapeutic use, Infusions, Intravenous, Italy, Male, Middle Aged, Necrosis, Scleroderma, Systemic drug therapy, Skin Ulcer pathology, Treatment Outcome, Wound Healing drug effects, Wound Healing physiology, Adipose Tissue transplantation, Fingers surgery, Hand Deformities, Acquired surgery, Plastic Surgery Procedures methods, Scleroderma, Systemic complications, Skin Ulcer surgery
Abstract

Background: Digital ulcers (DUs) occur in up to 50% of patients with Systemic Sclerosis (SSc). DUs are painful, recurring and lead to functional disability. Management of DUs includes pharmacologic and local therapy, the healing process is slow and the ulcer can become infected or evolve to gangrene. Autologous fat grafting (AFG) is a technique used to promote tissues repair. We used AFG to treat DUs refractory to conventional treatment to enhance healing process., Patients and Methods: We treated 9 SSc patients for a total of 15 ulcers. All 9 patients were treated with iv Iloprost. The purified fat tissue was injected at the border of larger ulcers or at the finger base of smaller DUs. The AFG was performed from 2 to 8 months since the ulcer onset., Results: Complete healing occured in 10 DUs and size reduction ≥50% in 2, within 8-12 weeks. In all but 2 patients the pain improved allowing a reduction of analgesics. In the majority of the cases AFG was able to hasten ulcer healing and to reduce pain and the need of pharmacological therapy. The lack of efficacy on healing and pain reduction was observed when the ulcers were long-lasting, located on legs and with concurrent atherosclerotic macroangiopathy., Conclusions: Surgical resective treatment for finger ulcers in patients affected by SSc is fraught with morbidity and long prolonged recovery. This study introduces a novel minimally invasive approach. The procedure is safe and effective, with short recovery time and local deficient vascularization improvement., (© Georg Thieme Verlag KG Stuttgart · New York.)

Published
2014
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32. Lack of TdT and immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease.

Author

Villa A, Cairo G, Pozzi MR, Schiaffonati L, Bardella L, Lucchini R, Delia D, Besana C, Biunno I, and Vezzoni P

Subjects
Hodgkin Disease enzymology, Hodgkin Disease genetics, Humans, Immunoglobulin Heavy Chains genetics, Lymph Nodes enzymology, Lymph Nodes pathology, Receptors, Antigen, T-Cell analysis, T-Lymphocytes enzymology, DNA Nucleotidylexotransferase analysis, DNA Nucleotidyltransferases analysis, Genes, Immunoglobulin, Hodgkin Disease pathology, Receptors, Antigen, T-Cell genetics
Abstract

To study the pathogenesis of Hodgkin's disease (HD), which today remains obscure, we have undertaken a combined experimental approach: determination of TdT and molecular analysis of rearrangements of immunoglobulin heavy chain (IgH), T-cell receptor (TCR) beta chain and the T-cell rearranging gamma (TRG) genes. TdT determination indicate would the presence of immature cells that are not detected in the normal lymphnode; molecular analysis of the rearrangements of these genes would reveal the presence of even a small monoclonal population of both T and B lineages in the lymphnodes. We believe that the combination of these two types of analysis can indicate whether an expanding lymphoid clone is responsible for this disease. TdT determination was negative in all 41 cases tested. Gene rearrangements were studied in 10 cases for IgH and TCR beta genes and in 5 cases for the TRG gene. No abnormal band beside the germ-line ones was detected in any of our cases, ruling out the presence of a minor neoplastic population. We can explain these results in at least three ways: first, the neoplastic population could represent less than 1% of the total, thus escaping detection by current techniques; second, the neoplastic population is not lymphoid in nature or is composed of mature cells that do not rearrange Ig and TCR genes and therefore belongs to a true non-B, non-T lineage; third, the pathogenesis of HD is completely different from that of non-Hodgkin's lymphomas (NHL) and does not involve the clonal expansion of a cell frozen at a particular maturative stage as is thought to happen in most NHL.

Published
1987
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34. Ferritins in malignant and non-malignant lymphoid cells.

Author

Vezzoni P, Levi S, Gabri E, Pozzi MR, Spinazze S, and Arosio P

Subjects
Humans, Lymph Nodes metabolism, Thymus Gland metabolism, Ferritins analysis, Hodgkin Disease metabolism, Lymphocytes metabolism, Lymphoma metabolism
Abstract

Lymphoid cells from peripheral blood, thymus, malignant and non-malignant lymph nodes were analysed for ferritin content using radioimmunoassays specific for the 'acidic' H-subunit-rich and for 'basic' L-subunit-rich isoferritins, and the data were compared with the immunological characteristics of the cells. All tissues with high proportion of T or 'null' cells contained the lowest concentration of L-subunit-rich isoferritins, while the H-subunit-rich forms increased from low levels in the quiescent peripheral blood lymphocytes (PBL), to higher values in the immature and proliferating thymocytes and lymphoblasts, malignant or not. B-cell lymphomas contained concentrations of both ferritin types higher than those found in PBL. No significant difference was found in the isoferritin concentrations between non-malignant lymph nodes and tissues involved in Hodgkin's disease. These findings indicate that maturation stage, proliferative status and anatomical localization affect isoferritin expression in lymphoid cells.

Published
1986
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35. The contribution of molecular biology in the diagnosis of human lymphomas.

Author

Vezzoni P, Cairo G, Pozzi MR, Bardella L, Schiaffonati L, Giardini R, Rilke F, Delia D, and Biunno I

Subjects
DNA, Neoplasm genetics, Genes, Humans, Immunoglobulin Heavy Chains immunology, Lymphoma genetics, Lymphoma immunology, Receptors, Antigen, T-Cell genetics, T-Lymphocytes immunology, Lymphoma diagnosis
Abstract

The relationship between T cell receptor (TCR) beta and gene immunoglobulin heavy chain locus was investigated in 25 cases of unselected human lymphomas as well as in normal and non-neoplastic lymphoid tissues. Hybridizing our blots with Jurkat 2, a clone specific for the beta chain gene of TCR, did not demonstrate extra bands in non-neoplastic tissues composed of 50-95% T-cells. On the contrary, rearranged bands were detected in six out of six cases of T-cell lymphomas. No TCR beta gene rearrangements were detected in 11 B-cell lymphomas, which in turn presented modification of the immunoglobulin heavy chain gene germline configuration. Our results suggest that TCR beta chain gene rearrangements are a good marker for human T-cell neoplasias in humans and complement the analysis with immunoglobulin genes probes. Eighth samples were devoid of any rearrangements: this group comprises cases of Hodgkin's disease T-lymphoblastic lymphomas in clinical remission and malignancies of unknown origin, as discussed in the text. We conclude that the analysis using DNA probes specific for TCR beta and IgH genes can be of aid to the pathologist in the diagnosis and classification of human lymphomas.

Published
1986

36. Relation between enzymatic activities and the degree of malignancy of human lymphomas.

Author

Vezzoni P, Giardini R, Raineri M, Pozzi MR, Lucchini R, Vezzoni MA, Clerici L, Besana C, Rugarli C, and Rilke F

Subjects
Hodgkin Disease enzymology, Humans, Lymph Nodes enzymology, Lymphoma classification, Adenosine Deaminase analysis, DNA Polymerase II analysis, L-Lactate Dehydrogenase analysis, Lymphoma enzymology, Nucleoside Deaminases analysis
Abstract

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1985
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