76 results on '"Bosello SL"'
Search Results
2. A3.3 Micro-RNA-34a and micro-RNA-155 unbalance is associated to IL-6/IL-6R pathway in CD14 cells and skin compartment of systemic sclerosis patients
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Alivernini, S, Bosello, SL, Tolusso, B, Benvenuto, R, Mangoni, A, Bui, L, Canestri, S, Di Mario, C, and Ferraccioli, G
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- 2015
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3. Interleukin-6 and IgA-rheumatoid factor are crucial for baseline erosiveness, and anti-citrullinated peptide antibodies for radiographic progression in early rheumatoid arthritis treated according to a treat-to-target strategy
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Fedele, AL, primary, Petricca, L, additional, Tolusso, B, additional, Alivernini, S, additional, Canestri, S, additional, Di Mario, C, additional, Bosello, SL, additional, Ferraccioli, G, additional, and Gremese, E, additional
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- 2018
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4. OP0343 The intestinal involvement in systemic sclerosis is characterized by a peculiar gut microbiota
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Natalello, G, primary, Bosello, SL, additional, Sterbini, F Paroni, additional, Palladini, A, additional, Canestrari, GB, additional, Parisi, F, additional, Lorenzis, E De, additional, Berardi, G, additional, Posteraro, B, additional, Sanguinetti, M, additional, and Ferraccioli, G, additional
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- 2017
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5. FRI0319 Predictors of complete remission in polymyalgia rheumatica
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Birra, D, primary, Zoli, A, additional, Peluso, G, additional, Bosello, SL, additional, Gremese, E, additional, and Ferraccioli, G, additional
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- 2017
- Full Text
- View/download PDF
6. FUNZIONE CARDIORESPIRATORIA, ARTERIAL STIFFNESS E LIVELLI DI NT-PRO BNP IN PAZIENTI AFFETTI DA ARTRITE REUMATOIDE ALL’ESORDIO
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Galiano, N, Zoli, Angelo, Comerci, G, Bosello, Sl, Fedele, Al, Forni, F, Loperfido, F, Ferraccioli, G., Zoli, Angelo (ORCID:0000-0003-1597-058X), Bosello, Sl (ORCID:0000-0002-4837-447X), Galiano, N, Zoli, Angelo, Comerci, G, Bosello, Sl, Fedele, Al, Forni, F, Loperfido, F, Ferraccioli, G., Zoli, Angelo (ORCID:0000-0003-1597-058X), and Bosello, Sl (ORCID:0000-0002-4837-447X)
- Abstract
n/a
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- 2012
7. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study
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Gremese, Elisa, Salaffi, F, Bosello, Sl, Ciapetti, A, Bobbio Pallavicini, F, Caporali, R, Ferraccioli, Gianfranco, Gremese, Elisa (ORCID:0000-0002-2248-1058), Bosello, Sl (ORCID:0000-0002-4837-447X), Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428), Gremese, Elisa, Salaffi, F, Bosello, Sl, Ciapetti, A, Bobbio Pallavicini, F, Caporali, R, Ferraccioli, Gianfranco, Gremese, Elisa (ORCID:0000-0002-2248-1058), Bosello, Sl (ORCID:0000-0002-4837-447X), and Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428)
- Abstract
BACKGROUND: To assess whether, in the real world of three early arthritis clinics, early referral could allow the best outcome, ie, remission, to be reached, and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa. METHODS: 1795 patients with early arthritis (symptom duration ≤12 months) were entered into a prospective follow-up study. 711 patients (39.6%) were diagnosed with rheumatoid arthritis (RA). Each RA patient was treated according to the local algorithm, in three tertiary referral centres (representing a small province, a medium sized province and a metropolitan area, respectively). Remission, defined using the disease activity score in 28 joints (DAS28 <2.6) and American College of Rheumatology (ACR) criteria, was the major outcome evaluated at the 12-month follow-up. RESULTS: DAS28 remission was achieved in 34.3% (range 19.5-49%) of RA patients and ACR remission in 15.2% (range 8.5-20.6%). At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome: being in very early rheumatoid arthritis (VERA; less than 12 weeks symptom duration at the time of first treatment) and being on disease-modifying antirheumatic drugs (DMARD) within 3 months from disease onset. Among RA patients in remission, only 10% of VERA subjects received an anti-TNF blocker compared with 32.2% of non-VERA patients (p=0.002, OR 0.23, 95% CI 0.09 to 0.64). CONCLUSIONS: In a real-world setting, the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome, ie, remission of RA. Moreover, VERA represents a window of opportunity in terms of cost saving.
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- 2012
8. Arthritis in systemic vasculitis: a retrospective analysis
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Carbonella, A, Berardi, G, Gremese, Elisa, Bosello, Silvia Laura, Petricca, L, Parisi, F, Zoli, Angelo, Ferraccioli, G., Gremese, Elisa (ORCID:0000-0002-2248-1058), Bosello, Sl (ORCID:0000-0002-4837-447X), Zoli, Angelo (ORCID:0000-0003-1597-058X), Carbonella, A, Berardi, G, Gremese, Elisa, Bosello, Silvia Laura, Petricca, L, Parisi, F, Zoli, Angelo, Ferraccioli, G., Gremese, Elisa (ORCID:0000-0002-2248-1058), Bosello, Sl (ORCID:0000-0002-4837-447X), and Zoli, Angelo (ORCID:0000-0003-1597-058X)
- Abstract
N/A
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- 2014
9. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study
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Gremese, Elisa, Salaffi, F, Bosello, Silvia Laura, Ciapetti, A, Bobbio Pallavicini, F, Caporali, R, Ferraccioli, Gianfranco, Gremese, Elisa (ORCID:0000-0002-2248-1058), Bosello, Sl (ORCID:0000-0002-4837-447X), Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428), Gremese, Elisa, Salaffi, F, Bosello, Silvia Laura, Ciapetti, A, Bobbio Pallavicini, F, Caporali, R, Ferraccioli, Gianfranco, Gremese, Elisa (ORCID:0000-0002-2248-1058), Bosello, Sl (ORCID:0000-0002-4837-447X), and Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428)
- Abstract
To assess whether, in the real world of three early arthritis clinics, early referral could allow the best outcome, ie, remission, to be reached, and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa.
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- 2013
10. The human salivary proteome: a critical overview of the results obtained by different proteomic platforms
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Castagnola, Massimo, Cabras, T, Iavarone, Federica, Fanali, Chiara, Nemolato, S, Peluso, G, Bosello, Silvia Laura, Faa, G, Ferraccioli, Gianfranco, Messana, I., Castagnola, Massimo (ORCID:0000-0002-0959-7259), Iavarone, Federica (ORCID:0000-0002-2074-5531), Bosello, Sl (ORCID:0000-0002-4837-447X), Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428), Castagnola, Massimo, Cabras, T, Iavarone, Federica, Fanali, Chiara, Nemolato, S, Peluso, G, Bosello, Silvia Laura, Faa, G, Ferraccioli, Gianfranco, Messana, I., Castagnola, Massimo (ORCID:0000-0002-0959-7259), Iavarone, Federica (ORCID:0000-0002-2074-5531), Bosello, Sl (ORCID:0000-0002-4837-447X), and Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428)
- Abstract
The development of new separation techniques and different mass spectrometry instrumental devices, as well as the great availability of specific reactants, offers ample choice to scientists for carrying out high-throughput proteomic studies and being competitive in the field today. However, the different options available often do not provide comparable results, which can be linked to factors such as the strategy adopted, the nature of the sample and the instrumental availability. In this critical review, the results obtained so far in the study of human saliva by different proteomic approaches will be compared and discussed.
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- 2012
11. A vascular endothelial growth factor deficiency characterises scleroderma lung disease
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De Santis, Mario, Bosello, Silvia Laura, Capoluongo, Ettore Domenico, Inzitari, Rosanna, Peluso, Giusy, Lulli, Paola, Zizzo, Gaetano, Bocci, Mario, Tolusso, Barbara, Zuppi, Cecilia, Castagnola, Massimo, Ferraccioli, Gianfranco, Bosello, Sl (ORCID:0000-0002-4837-447X), Capoluongo, Ettore Domenico (ORCID:0000-0001-9872-0572), Tolusso, Barbara (ORCID:0000-0002-9108-6609), Zuppi, Cecilia (ORCID:0000-0003-4710-4934), Castagnola, Massimo (ORCID:0000-0002-0959-7259), Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428), De Santis, Mario, Bosello, Silvia Laura, Capoluongo, Ettore Domenico, Inzitari, Rosanna, Peluso, Giusy, Lulli, Paola, Zizzo, Gaetano, Bocci, Mario, Tolusso, Barbara, Zuppi, Cecilia, Castagnola, Massimo, Ferraccioli, Gianfranco, Bosello, Sl (ORCID:0000-0002-4837-447X), Capoluongo, Ettore Domenico (ORCID:0000-0001-9872-0572), Tolusso, Barbara (ORCID:0000-0002-9108-6609), Zuppi, Cecilia (ORCID:0000-0003-4710-4934), Castagnola, Massimo (ORCID:0000-0002-0959-7259), and Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428)
- Abstract
Objectives Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. Methods BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. Results VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. Conclusions Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.
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- 2012
12. PTPN22 1858C>T polymorphism distribution in Europe and association with rheumatoid arthritis: case-control study and meta-analysis
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Totaro, Mc, Tolusso, Barbara, Napolioni, V, Faustini, Francesca, Canestri, S, Mannocci, Alice, Gremese, Elisa, Bosello, Sl, Alivernini, Stefano, Ferraccioli, Gianfranco, Tolusso, Barbara (ORCID:0000-0002-9108-6609), Gremese, Elisa (ORCID:0000-0002-2248-1058), Alivernini, Stefano (ORCID:0000-0002-7383-4212), Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428), Totaro, Mc, Tolusso, Barbara, Napolioni, V, Faustini, Francesca, Canestri, S, Mannocci, Alice, Gremese, Elisa, Bosello, Sl, Alivernini, Stefano, Ferraccioli, Gianfranco, Tolusso, Barbara (ORCID:0000-0002-9108-6609), Gremese, Elisa (ORCID:0000-0002-2248-1058), Alivernini, Stefano (ORCID:0000-0002-7383-4212), and Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428)
- Abstract
The PTPN22 rs2476601 polymorphism is associated with rheumatoid arthritis (RA); nonetheless, the association is weaker or absent in some southern European populations. The aim of the study was to evaluate the association between the PTPN22 rs2476601 polymorphism and RA in Italian subjects and to compare our results with those of other European countries, carrying out a meta-analysis of European data.
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- 2011
13. beta-thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up
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De Santis, Maria, Inzitari, Rosanna, Bosello, Silvia Laura, Peluso, Giusy, Fanali, Chiara, Iavarone, Federica, Zizzo, Gaetano, Cabras, T, Messana, I, Fuso, Leonello, Varone, Francesco, Pagliari, Gabriella, Castagnola, Massimo, Ferraccioli, Gianfranco, Bosello, Sl (ORCID:0000-0002-4837-447X), Iavarone, Federica (ORCID:0000-0002-2074-5531), Fuso, Leonello (ORCID:0000-0002-1198-6712), Castagnola, Massimo (ORCID:0000-0002-0959-7259), Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428), De Santis, Maria, Inzitari, Rosanna, Bosello, Silvia Laura, Peluso, Giusy, Fanali, Chiara, Iavarone, Federica, Zizzo, Gaetano, Cabras, T, Messana, I, Fuso, Leonello, Varone, Francesco, Pagliari, Gabriella, Castagnola, Massimo, Ferraccioli, Gianfranco, Bosello, Sl (ORCID:0000-0002-4837-447X), Iavarone, Federica (ORCID:0000-0002-2074-5531), Fuso, Leonello (ORCID:0000-0002-1198-6712), Castagnola, Massimo (ORCID:0000-0002-0959-7259), and Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428)
- Abstract
Background: beta-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins beta(4), beta(4) sulfoxide, and beta(10) in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters. Methods: beta-thymosins concentrations were determined by Reverse Phase-High Performance Liquid Chromatography-Electrospray-Mass Spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls. Results: Thymosin beta(4), beta(4) sulfoxide, and beta(10) were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin beta(4) levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin beta(4) levels seem to have a protective role against lung tissue damage. Thymosin beta(4) sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis. Conclusions: We describe for the first time beta-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin beta(4) seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status
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- 2011
14. Real-life efficacy and safety of nintedanib in systemic sclerosis-interstitial lung disease: data from an Italian multicentre study
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Corrado Campochiaro, Giacomo De Luca, Maria-Grazia Lazzaroni, Giuseppe Armentaro, Amelia Spinella, Barbara Vigone, Barbara Ruaro, Anna Stanziola, Devis Benfaremo, Enrico De Lorenzis, Beatrice Moccaldi, Silvia Laura Bosello, Giovanna Cuomo, Lorenzo Beretta, Elisabetta Zanatta, Dilia Giuggioli, Nicoletta Del Papa, Paolo Airo, Marco Confalonieri, Gianluca Moroncini, Lorenzo Dagna, Marco Matucci-Cerinic, Campochiaro, C, De Luca, G, Lazzaroni, Mg, Armentaro, G, Spinella, A, Vigone, B, Ruaro, B, Stanziola, A, Benfaremo, D, De Lorenzis, E, Moccaldi, B, Bosello, Sl, Cuomo, G, Beretta, L, Zanatta, E, Giuggioli, D, Del Papa, N, Airo, P, Confalonieri, M, Moroncini, G, Dagna, L, Matucci-Cerinic, M., Campochiaro, C., De Luca, G., Lazzaroni, M. -G., Armentaro, G., Spinella, A., Vigone, B., Ruaro, B., Stanziola, A., Benfaremo, D., De Lorenzis, E., Moccaldi, B., Bosello, S. L., Cuomo, G., Beretta, L., Zanatta, E., Giuggioli, D., Del Papa, N., Airo, P., Confalonieri, M., Moroncini, G., and Dagna, L.
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pulmonary fibrosi ,Settore MED/16 - REUMATOLOGIA ,Rheumatology ,pulmonary fibrosis ,biological therapy ,Immunology ,scleroderma, systemic ,therapeutics ,Immunology and Allergy ,scleroderma ,systemic - Abstract
IntroductionNintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting.MethodsPatients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction. The following parameters were recorded: SSc clinical features, NTD tolerability, pulmonary function tests and modified Rodnan skin score (mRSS).Results90 patients with SSc-ILD (65% female, mean age 57.6±13.4 years, mean disease duration 8.8±7.6 years) were identified. The majority were positive for anti-topoisomerase I (75%) and 77 (85%) patients were on immunosuppressants. A significant decline in %predicted forced vital capacity (%pFVC) in the 12 months prior to NTD introduction was observed in 60%. At 12 months after NTD introduction, follow-up data were available for 40 (44%) patients and they showed a stabilisation in %pFVC (64±14 to 62±19, p=0.416). The percentage of patients with significant lung progression at 12 months was significantly lower compared with the previous 12 months (60% vs 17.5%, p=0.007). No significant mRSS change was observed. Gastrointestinal (GI) side effects were recorded in 35 (39%) patients. After a mean time of 3.6±3.1 months, NTD was maintained after dose adjustment in 23 (25%) patients. In nine (10%) patients, NTD was stopped after a median time of 4.5 (1–6) months. During the follow-up, four patients died.ConclusionsIn a real-life clinical scenario, NTD, in combination with immunosuppressants, may stabilise lung function. GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in patients with SSc-ILD.
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- 2023
15. Tumour-associated antigens in systemic sclerosis patients with interstitial lung disease: association with lung involvement and cancer risk
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Franca Forni, G. Canestrari, Tommaso Pirronti, L. Mirone, G. Berardi, Giacomo De Luca, Clara Di Mario, M. Rucco, Miriam Correra, Gianfranco Ferraccioli, Silvia Laura Bosello, Francesco Danza, De Luca, G, Bosello, Sl, Berardi, G, Rucco, M, Canestrari, G, Correra, M, Mirone, L, Forni, F, Di Mario, C, Danza, Fm, Pirronti, T, and Ferraccioli, G
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Lung Diseases ,Male ,Pathology ,Vital capacity ,Settore MED/16 - REUMATOLOGIA ,Lung Neoplasms ,systemic sclerosis ,Vital Capacity ,Comorbidity ,Systemic scleroderma ,Severity of Illness Index ,Gastroenterology ,Scleroderma ,Carcinoembryonic antigen ,Risk Factors ,Medicine ,Pharmacology (medical) ,Lung ,biology ,Incidence ,Interstitial lung disease ,Middle Aged ,respiratory system ,neoplasia ,medicine.anatomical_structure ,Disease Progression ,Female ,Carbohydrate ,medicine.medical_specialty ,cancer ,lung involvement ,tumour-associated antigens ,Aged ,Antigens, Tumor-Associated, Carbohydrate ,Biomarkers ,Carcinoembryonic Antigen ,Case-Control Studies ,Follow-Up Studies ,Humans ,Lung Diseases, Interstitial ,Multivariate Analysis ,Scleroderma, Systemic ,Malignancy ,FEV1/FVC ratio ,Rheumatology ,Internal medicine ,Antigens ,business.industry ,Tumor-Associated ,Systemic ,Cancer ,medicine.disease ,respiratory tract diseases ,biology.protein ,Interstitial ,business - Abstract
Objective: To evaluate the serum levels of tumour-associated antigens (TAAs) in patients with SSc and interstitial lung disease (ILD) and to define whether their levels mirror the severity and the progression of lung damage. Methods: Data from 80 SSc patients with ILD were collected at baseline and after 2 years as well as from 40 SSc controls without ILD. The occurrence of any malignancy was recorded. Results: At baseline, an increase of at least one TAA was present in 35 SSc patients with ILD compared with 6 SSc patients without ILD (P < 0.0001); this was associated with lower forced vital capacity (FVC) and higher interstitial and alveolar scores. Levels of carbohydrate antigen 15-3 and carcinoembryonic antigen inversely correlated with FVC and directly correlated with alveolar and interstitial scores and their levels were higher in patients who presented a progression of lung damage after 2 years. During 4 years of follow-up, a malignancy was detected in seven patients who already had an increase of at least one TAA. Values of TAAs increased over time in patients who developed cancer, while their trend remained stable in the others. At multivariate analysis, to have three or more TAAs emerged as a strong independent predictor of the development of malignancies [relative risk 24.1 (95% CI 1.8, 315.0), P = 0.02]. Conclusion: TAAs can be elevated in the sera of SSc patients and correlate with the degree of lung damage, suggesting a role as severity biomarkers. Close follow-up is necessary in SSc patients because of the increased cancer risk overall in patients with increased TAAs.
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- 2015
16. Prognostic Role of Ventricular Ectopic Beats in Systemic Sclerosis: A Prospective Cohort Study Shows ECG Indexes Predicting the Worse Outcome
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G. Canestrari, Giacomo De Luca, Francesca Augusta Gabrielli, F. Parisi, Filippo Crea, Gianfranco Ferraccioli, Leonarda Galiuto, G. Berardi, Silvia Laura Bosello, M. Rucco, Francesco Loperfido, De Luca, G, Bosello, Sl, Gabrielli, Fa, Berardi, G, Parisi, F, Rucco, M, Canestrari, G, Loperfido, F, Galiuto, L, Crea, F, and Ferraccioli, G
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Male ,Multivariate analysis ,Settore MED/16 - REUMATOLOGIA ,Pulmonology ,systemic sclerosis ,medicine.medical_treatment ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Sudden Cardiac Death ,Sudden cardiac death ,Scleroderma ,Diagnostic Radiology ,Electrocardiography ,0302 clinical medicine ,Heart Rate ,Tachycardia ,Ultrasound Imaging ,Medicine and Health Sciences ,heart involvement ,Prospective Studies ,Prospective cohort study ,Connective Tissue Diseases ,lcsh:Science ,Multidisciplinary ,Ejection fraction ,medicine.diagnostic_test ,Radiology and Imaging ,Heart ,Right bundle branch block ,Middle Aged ,Implantable cardioverter-defibrillator ,Prognosis ,Ventricular Premature Complexes ,Defibrillators, Implantable ,Treatment Outcome ,Bioassays and Physiological Analysis ,Echocardiography ,Ambulatory ,Cardiology ,Female ,Anatomy ,arrhythmias ,Arrhythmia ,Research Article ,Adult ,medicine.medical_specialty ,Imaging Techniques ,Immunology ,Research and Analysis Methods ,Autoimmune Diseases ,03 medical and health sciences ,Rheumatology ,Diagnostic Medicine ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Intensive care medicine ,Aged ,030203 arthritis & rheumatology ,Scleroderma, Systemic ,business.industry ,Electrophysiological Techniques ,lcsh:R ,Biology and Life Sciences ,medicine.disease ,Dyspnea ,Electrocardiography, Ambulatory ,Cardiovascular Anatomy ,Clinical Immunology ,lcsh:Q ,Cardiac Electrophysiology ,Clinical Medicine ,business - Abstract
Background: Arrhythmias are frequent in Systemic Sclerosis (SSc) and portend a bad prognosis, accounting alone for 6% of total deaths. Many of these patients die suddenly, thus prevention and intensified risk-stratification represent unmet medical needs. The major goal of this study was the definition of ECG indexes of poor prognosis. Methods: We performed a prospective cohort study to define the role of 24h-ECG-Holter as an additional risk-stratification technique in the identification of SSc-patients at high risk of life-threatening arrhythmias and sudden cardiac death (SCD). One-hundred SSc-patients with symptoms and/or signs suggestive of cardiac involvement underwent 24h-ECG-Holter. The primary end-point was a composite of SCD or need for implantable cardioverter defibrillator (ICD). Results: Fifty-six patients (56%) had 24h-ECG-Holter abnormalities and 24(24%) presented frequent ventricular ectopic beats (VEBs). The number of VEBs correlated with high-sensitive cardiac troponin T (hs-cTnT) levels and inversely correlated with left-ventricular ejection fraction (LV-EF) on echocardiography. During a mean follow-up of 23.1±16.0 months, 5 patients died suddenly and two required ICD-implantation. The 7 patients who met the composite end-point had a higher number of VEBs, higher levels of hs-cTnT and NT-proBNP and lower LV-EF (p = 0.001 for all correlations). All these 7 patients had frequent VEBs, while LV-EF was not reduced in all and its range was wide. At ROC curve, VEBs>1190/24h showed 100% of sensitivity and 83% of specificity to predict the primary end-point (AUROC = 0.92,p1190/24h had lower LV-EF and higher hs-cTnT levels and, at multivariate analysis, the presence of increased hs-cTnT and of right bundle branch block on ECG emerged as independent predictors of VEBs>1190/24h. None of demographic or disease-related characteristics emerged as predictors of poor outcome. Conclusions: VEBS>1190/24h identify patients at high risk of life-threatening arrhythmic complications. Thus, 24h-ECG-Holter should be considered a useful additional risk-stratification test to select SSc-patients at high-risk of SCD, in whom an ICD-implantation could represent a potential life-saving intervention.
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- 2016
17. A vascular endothelial growth factor deficiency characterises scleroderma lung disease
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Ettore Capoluongo, Gianfranco Ferraccioli, Silvia Laura Bosello, Massimo Castagnola, M. Bocci, Cecilia Zuppi, Barbara Tolusso, Maria De Santis, Gaetano Zizzo, Giusy Peluso, Paola Lulli, Rosanna Inzitari, De Santis, M, Bosello, Sl, Capoluongo, E, Inzitari, R, Peluso, G, Lulli, P, Zizzo, G, Bocci, M, Tolusso, B, Zuppi, C, Castagnola, M, and Ferraccioli, G
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Male ,Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Real-Time Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Scleroderma ,Pathogenesis ,chemistry.chemical_compound ,Rheumatology ,Downregulation and upregulation ,medicine ,Humans ,Immunology and Allergy ,skin and connective tissue diseases ,Settore BIO/10 - BIOCHIMICA ,Scleroderma, Systemic ,Lung ,integumentary system ,medicine.diagnostic_test ,business.industry ,Interstitial lung disease ,Middle Aged ,respiratory system ,medicine.disease ,respiratory tract diseases ,Vascular endothelial growth factor ,enothelial ,medicine.anatomical_structure ,Bronchoalveolar lavage ,Cytokine ,chemistry ,Female ,Lung Diseases, Interstitial ,business ,Bronchoalveolar Lavage Fluid - Abstract
Objectives Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. Methods BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. Results VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. Conclusions Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.
- Published
- 2012
18. Long-term retention rate, adverse event temporal patterns and rescue treatment strategies of mycophenolate mofetil in systemic sclerosis: insights from real-life.
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De Lorenzis E, Natalello G, Pellegrino G, Verardi L, Batani V, Lepri G, Stano S, Armentano G, De Pinto M, Motta F, Di Donato S, Kakkar V, Fiore S, Bisconti I, Campochiaro C, Cometi L, Tonutti A, Spinella A, Truglia S, Cavalli S, De Santis M, Giuggioli D, Del Papa N, Guiducci S, Cacciapaglia F, De Luca G, Iannone F, Ricceri V, Matucci Cerinic M, D'Agostino MA, Del Galdo F, and Bosello SL
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Background: Mycophenolate mofetil (MMF) is a mainstay for the treatment of systemic sclerosis (SSc). The occurrence and implications of MMF-related adverse events on drug retention rates in real life remain poorly defined. We aimed to determine the MMF retention rate and to investigate the causes and patterns of discontinuation, adverse events (AEs) and treatment options used after discontinuation., Methods: SSc patients who started MMF treatment underwent a retrospective longitudinal assessment for up to 5 years. We documented the incidence, predictors, and impacts of MMF treatment on gastrointestinal intolerance, infections, laboratory abnormalities, and cancer. Rescue strategies implemented after MMF discontinuation were recorded., Results: The 5-year MMF retention rate of 554 patients stood at 70.7% and 19.6% of them stopped MMF due to AEs. One out of every four patients experienced a dose reduction or discontinuation of MMF due to AEs, with gastrointestinal intolerance being the predominant cause. The 5-year cumulative incidence rates for gastrointestinal intolerance, cancer, severe infections, and laboratory toxicity leading to MMF discontinuation were 6.4%, 4.1%, 3.1%, and 2.1%, respectively. Lower respiratory tract was the most affected, with bacteria being the predominant causative agent. Intestinal and pulmonary circulation involvement were tied to elevated AE rates and MMF discontinuation. The most common approaches post-MMF cessation were "watch and wait" and switch to rituximab., Conclusions: MMF use in SSc appears to be limited by the occurrence of AEs, both in terms of persistence and dosing of the drug. Rescue options after MMF discontinuation are limited and many patients remain without immunosuppressant., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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19. A Comprehensive Natural Language Processing Pipeline for the Chronic Lupus Disease.
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Lilli L, Bosello SL, Antenucci L, Patarnello S, Ortolan A, Lenkowicz J, Gorini M, Castellino G, Cesario A, D'Agostino MA, and Masciocchi C
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- Humans, Chronic Disease, Data Mining methods, Natural Language Processing, Electronic Health Records, Lupus Erythematosus, Systemic
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Electronic Health Records (EHRs) contain a wealth of unstructured patient data, making it challenging for physicians to do informed decisions. In this paper, we introduce a Natural Language Processing (NLP) approach for the extraction of therapies, diagnosis, and symptoms from ambulatory EHRs of patients with chronic Lupus disease. We aim to demonstrate the effort of a comprehensive pipeline where a rule-based system is combined with text segmentation, transformer-based topic analysis and clinical ontology, in order to enhance text preprocessing and automate rules' identification. Our approach is applied on a sub-cohort of 56 patients, with a total of 750 EHRs written in Italian language, achieving an Accuracy and an F-score over 97% and 90% respectively, in the three extracted domains. This work has the potential to be integrated with EHR systems to automate information extraction, minimizing the human intervention, and providing personalized digital solutions in the chronic Lupus disease domain.
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- 2024
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20. Concordance and Prognostic Relevance of Different Definitions of Systemic Sclerosis Interstitial Lung Disease Progression.
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De Lorenzis E, Del Galdo F, Natalello G, Varone F, Di Donato S, Verardi L, Calandriello L, Kakkar V, Cerasuolo PG, Larici AR, D'Agostino MA, Bosello SL, and Richeldi L
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Rationale: Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a common complication that has varied progression rate and prognosis. Different progression definitions are available: include minimal clinically important worsening of forced vital capacity (FVC MCIW), EUSTAR (EUropean Scleroderma Trials and Research group) progression, OMERACT (Outcome Measures in Rheumatology Clinical Trials) progression, and Erice ILD working group progression. Pulmonary function and symptoms changes may act as specific confounding factors applying these definitions in SSc., Objective: To assess the concordance and prognostic value of four different definitions in SSc-ILD patients overall and specific clinical groups., Methods: Progression status in consecutive SSc-ILD patients was assessed over 24 months, 60-month disease-related mortality risk was compared between progressors and non-progressors using the four definitions., Results: Among 245 patients, 26 SSc-related deaths were reported. Mortality was linked to progression for FVC MCIW (HR 2.27, 95% CI 1.03-4.97), OMERACT (HR 2.90, 95% CI 1.28-6.57), and Erice definitions (HR 11.02, 95% CI 2.38-51.08). The association between progression and mortality was poor in patients with disease duration ≥3 years, mild functional impairment, and pulmonary artery systolic pressure (PASP)≥40 mmHg. Erice criteria appeared superior in patients with duration ≥3 years, limited cutaneous variant, and PASP<40 mmHg. OMERACT criteria performed better in diffuse cutaneous variant patients with severe functional impairment., Conclusions: The four evaluated definitions of progression in SSc-ILD are not interchangeable, resulting in up to a third of cases being classified differently based on the adopted criteria, and presenting different prognostic values, particularly within specific clinical groups.
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- 2024
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21. Rituximab retention rate in systemic sclerosis: a long term real-life multicenter study.
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De Luca G, De Lorenzis E, Campochiaro C, Cacciapaglia F, Del Papa N, Zanatta E, Airò P, Lazzaroni MG, Giuggioli D, De Santis M, Alonzi G, Stano S, Binda M, Moccaldi B, Tonutti A, Cavalli S, Batani V, Natalello G, Iannone F, D'Agostino MA, Dagna L, Matucci-Cerinic M, and Bosello SL
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Objectives: to report real-life data on rituximab retention-rate as indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients., Methods: SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized, and longitudinally monitored. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation., Results: One-hundred-fifty-two SSc-patients (mean age 47.3 ± 12.3 years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%) were evaluated over a median(IQR) time of 3.3(1.7-5.0) years. The primary indication for rituximab were interstitial lung disease (ILD)(38.8%), worsening skin fibrosis(36.8%), and arthritis(13.8%); 138 patients(90.8%) received more than one rituximab course. The 5-years rituximab retention rate was 59.9%(44.6-64.7%). Clinical response was the most common reason for rituximab discontinuation[5.7(3.7-8.4) per 100 patient-year] and was associated with a shorter disease duration[sHR 0.8(0.7-0.9)], anti-topoisomerase-I negativity[sHR 0.4(0.2-0.9)], previous digital ulcers[sHR 2.6(1.1-6.2] and no history of arthritis[sHR 0.3 (0.1-0.8)]. Treatment failure was the second cause of rituximab discontinuation[3.7(2.2-6.0) per 100 patient-year] and was associated with anti-centromere antibody positivity[sHR 2.8(1.1-7.4)] and anti-topoisomerase-I negativity[sHR 0.2(0.1-0.6)]. Adverse events(AEs) were the less common cause of discontinuation[3.1(1.7-5.2) per 100 patient-year], associated with limited cutaneous subset[sHR 3.4(1.2-9.7)] and previous mycophenolate mofetil treatment[sHR 4.5(1.2-16.3)]., Conclusion: rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
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- 2024
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22. Practice pattern for the use of intravenous iloprost for the treatment of peripheral vasculopathy in systemic sclerosis: A case-control study from the Italian national multicenter "SPRING" (Systemic Sclerosis Progression InvestiGation) Registry.
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Riccieri V, Pellegrino G, Cipolletta E, Giuggioli D, Bajocchi G, Bellando-Randone S, Dagna L, Zanframundo G, Foti R, Cacciapaglia F, Cuomo G, Ariani A, Rosato E, Lepri G, Girelli F, Zanatta E, Bosello SL, Cavazzana I, Ingegnoli F, De Santis M, Murdaca G, Abignano G, Romeo N, Della Rossa A, Caminiti M, Iuliano A, Ciano G, Beretta L, Bagnato G, Lubrano E, De Andres I, Giollo A, Saracco M, Agnes C, Lumetti F, Spinella A, Magnani L, Campochiaro C, De Luca G, Codullo V, Visalli E, Di Vico C, Gigante A, Saccon F, Grazia Lazzaroni M, Franceschini F, Generali E, Mennillo G, Barsotti S, Pagano Mariano G, Calabrese F, Furini F, Vultaggio L, Parisi S, Peroni CL, Bianchi G, Conti F, Cozzi F, D'Angelo S, Doria A, Fusaro E, Govoni M, Guiducci S, Iannone F, Salvarani C, Sebastiani GD, Ferri C, Matucci-Cerinic M, and De Angelis R
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Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data., Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group)., Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, " late " scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis., Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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23. Adherence to the Mediterranean Diet in Italian Patients With Systemic Sclerosis: An Epidemiologic Survey.
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Natalello G, Bosello SL, Campochiaro C, Abignano G, De Santis M, Ferlito A, Karadağ DT, Padula AA, Cavalli G, D'Agostino MA, Selmi C, Matucci-Cerinic M, Dagna L, and De Luca G
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Objective: Systemic sclerosis (SSc) is an orphan disease that can lead to severe involvement of the gastrointestinal tract with a significant impact on patients' quality of life (QoL). The Mediterranean diet (MD) was consistently demonstrated to have beneficial effects on chronic diseases based on biological bases. We aimed to evaluate the adherence to the MD of Italian patients with SSc to preliminarily assess its association with gastrointestinal symptoms and other disease features, mood, and QoL., Methods: In this cross-sectional study, adherence to the MD was measured in 387 patients from four SSc Italian referral centers through the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) questionnaire. We also registered patients' reported outcomes related to the QoL and mood., Results: Overall, an optimal adherence to MD was observed in 14.7% of patients with SSc, a moderate adherence in 71.3%, and a low adherence in 14.0%. In univariate analysis, poor adherence to the MD was associated with a more prominent depressive mood, time missed at work, and perception of more severe Raynaud's phenomenon and digital ulcers, whereas the 14-MEDAS score inversely correlated with depression score and reflux., Conclusion: In our cohort of patients with SSc, overall adherence to MD was moderate. Patients with lower adherence to MD also reported worse outcomes related to QoL and mood. Administration of the 14-MEDAS could be a reasonable choice to assess adherence to the MD in patients with SSc. Future initiatives to study the role of MD in the management of patients with SSc are warranted., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
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- 2024
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24. Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase.
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Ferri C, Raimondo V, Giuggioli D, Gragnani L, Lorini S, Dagna L, Bosello SL, Foti R, Riccieri V, Guiducci S, Cuomo G, Tavoni A, De Angelis R, Cacciapaglia F, Zanatta E, Cozzi F, Murdaca G, Cavazzana I, Romeo N, Codullo V, Pellegrini R, Varcasia G, De Santis M, Selmi C, Abignano G, Caminiti M, L'Andolina M, Olivo D, Lubrano E, Spinella A, Lumetti F, De Luca G, Ruscitti P, Urraro T, Visentini M, Bellando-Randone S, Visalli E, Testa D, Sciascia G, Masini F, Pellegrino G, Saccon F, Balestri E, Elia G, Ferrari SM, Tonutti A, Dall'Ara F, Pagano Mariano G, Pettiti G, Zanframundo G, Brittelli R, Aiello V, Dal Bosco Y, Foti R, Di Cola I, Scorpiniti D, Fusaro E, Ferrari T, Gigliotti P, Campochiaro C, Francioso F, Iandoli C, Caira V, Zignego AL, D'Angelo S, Franceschini F, Matucci-Cerinic M, Giacomelli R, Doria A, Santini SA, Fallahi P, Iannone F, and Antonelli A
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Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic., Patients and Method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines., Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients ( death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001)., Conclusions: An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients' population., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Alessandro Antonelli reports financial support was provided by Italian 10.13039/100009647Ministry of Health, Ricerca Finalizzata (RF-2021-12374986) Destinatario istituzionale: Regione Toscana. Unità Operative:U.O.1: Azienda Ospedaliero-Universitaria Pisana; U.O.2: Azienda Ospedaliero-Universitaria Aldo Moro Bari; U.O.3: Azienda Ospedaliero-Universitaria Modena, CUP Master: D55E22000670001., (© 2023 Published by Elsevier B.V.)
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- 2023
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25. Extension of Lung Damage at Chest Computed Tomography in Severely Ill COVID-19 Patients Treated with Interleukin-6 Receptor Blockers Correlates with Inflammatory Cytokines Production and Prognosis.
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Calandriello L, De Lorenzis E, Cicchetti G, D'Abronzo R, Infante A, Castaldo F, Del Ciello A, Farchione A, Gremese E, Marano R, Natale L, D'Agostino MA, Bosello SL, and Larici AR
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- Humans, Cytokines, Inflammation, Prognosis, Retrospective Studies, Tomography, X-Ray Computed, COVID-19 Drug Treatment, COVID-19 diagnostic imaging, Lung diagnostic imaging, Lung pathology, Receptors, Interleukin-6 antagonists & inhibitors
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Elevated inflammatory markers are associated with severe coronavirus disease 2019 (COVID-19), and some patients benefit from Interleukin (IL)-6 pathway inhibitors. Different chest computed tomography (CT) scoring systems have shown a prognostic value in COVID-19, but not specifically in anti-IL-6-treated patients at high risk of respiratory failure. We aimed to explore the relationship between baseline CT findings and inflammatory conditions and to evaluate the prognostic value of chest CT scores and laboratory findings in COVID-19 patients specifically treated with anti-IL-6. Baseline CT lung involvement was assessed in 51 hospitalized COVID-19 patients naive to glucocorticoids and other immunosuppressants using four CT scoring systems. CT data were correlated with systemic inflammation and 30-day prognosis after anti-IL-6 treatment. All the considered CT scores showed a negative correlation with pulmonary function and a positive one with C-reactive protein (CRP), IL-6, IL-8, and Tumor Necrosis Factor α (TNF-α) serum levels. All the performed scores were prognostic factors, but the disease extension assessed by the six-lung-zone CT score (S24) was the only independently associated with intensive care unit (ICU) admission ( p = 0.04). In conclusion, CT involvement correlates with laboratory inflammation markers and is an independent prognostic factor in COVID-19 patients representing a further tool to implement prognostic stratification in hospitalized patients.
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- 2023
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26. More to B: the growing evidence to inform targeting B cells in scleroderma.
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Bosello SL, Vital EM, and Del Galdo F
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- Humans, B-Lymphocytes, Scleroderma, Localized, Scleroderma, Systemic
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- 2023
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27. Survival and prognostic factors from a multicentre large cohort of unselected Italian systemic sclerosis patients.
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Cacciapaglia F, Airò P, Fornaro M, Trerotoli P, De Lorenzis E, Corrado A, Lazzaroni MG, Natalello G, Montini F, Altomare A, Urso L, Verardi L, Bosello SL, Cantatore FP, and Iannone F
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- Female, Humans, Male, Retrospective Studies, Prognosis, Familial Primary Pulmonary Hypertension complications, Scleroderma, Systemic complications, Scleroderma, Systemic epidemiology, Scleroderma, Systemic diagnosis, Hypertension, Pulmonary etiology, Hypertension, Pulmonary complications, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial complications, Pulmonary Arterial Hypertension complications
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Objectives: Survival and death prognostic factors of SSc patients varied during the past decades. We aimed to update the 5- and 10-year survival rates and identify prognostic factors in a multicentre cohort of Italian SSc patients diagnosed after 2009., Material and Methods: Patients who received a diagnosis of SSc after 1 January 2009 and were longitudinally followed up in four Italian rheumatologic centres were retrospectively assessed up to 31 December 2020. Overall survival of SSc patients was described using the Kaplan-Meier method. Predictors of mortality at 10-year follow-up were assessed by the Cox regression model. A comparison of our cohort with the Italian general population was performed by determining the standardized mortality ratio (SMR)., Results: A total of 912 patients (91.6% females, 20% dcSSc) were included. Overall survival rates at 5 and 10 years were 94.4% and 89.4%, respectively. The SMR was 0.96 (95% CI 0.81, 1.13), like that expected in the Italian general population. Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) associated with pulmonary hypertension (PH) significantly reduced survival (P < 0.0001). Main death predictors were male gender (HR = 2.76), diffuse cutaneous involvement (HR = 3.14), older age at diagnosis (HR = 1.08), PAH (HR = 3.21), ILD-associated PH (HR = 4.11), comorbidities (HR = 3.53) and glucocorticoid treatment (HR= 2.02)., Conclusions: In the past decade, SSc patients have reached similar mortality of that expected in the Italian general population. Male gender, diffuse cutaneous involvement, comorbidities and PAH with or without ILD represent the main poor prognostic factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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28. Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology.
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De Angelis R, Ferri C, Giuggioli D, Bajocchi G, Dagna L, Bellando-Randone S, Zanframundo G, Foti R, Cacciapaglia F, Cuomo G, Ariani A, Rosato E, Lepri G, Girelli F, Riccieri V, Zanatta E, Bosello SL, Cavazzana I, Ingegnoli F, De Santis M, Murdaca G, Abignano G, Romeo N, Della Rossa A, Caminiti M, Iuliano AM, Ciano G, Beretta L, Bagnato G, Lubrano E, De Andres I, Giollo A, Saracco M, Agnes C, Cipolletta E, Lumetti F, Spinella A, Magnani L, Campochiaro C, De Luca G, Codullo V, Visalli E, Di Vico C, Gigante A, Pellagrino G, Pigatto E, Lazzaroni MG, Franceschini F, Generali E, Mennillo G, Barsotti S, Mariano GP, Furini F, Vultaggio L, Parisi S, Peroni CL, Rozza D, Zanetti A, Carrara G, Landolfi G, Scirè CA, Bianchi G, Fusaro E, Sebastiani GD, Govoni M, D'Angelo S, Cozzi F, Guiducci S, Doria A, Salvarani C, Iannone F, and Matucci-Cerinic M
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- Humans, Seasons, Rheumatology, Scleroderma, Systemic, Autoimmune Diseases
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Objective: To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort., Methods: Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets., Results: Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001)., Conclusion: The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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29. Chronic related group classification system as a new public health tool to predict risk and outcome of COVID-19 in patients with systemic rheumatic diseases: A population-based study of more than forty thousand patients.
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De Lorenzis E, Parente P, Natalello G, Soldati S, Bosello SL, Barbara A, Sorge C, Axelrod S, Verardi L, Cerasuolo PG, Peluso G, Gemma A, Davoli M, Biliotti D, Bruzzese V, Goletti M, Di Martino M, and D'Agostino MA
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- Humans, Public Health, COVID-19, Autoimmune Diseases, Arthritis, Rheumatoid, Rheumatic Diseases epidemiology
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- 2023
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30. Real-life efficacy and safety of nintedanib in systemic sclerosis-interstitial lung disease: data from an Italian multicentre study.
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Campochiaro C, De Luca G, Lazzaroni MG, Armentaro G, Spinella A, Vigone B, Ruaro B, Stanziola A, Benfaremo D, De Lorenzis E, Moccaldi B, Bosello SL, Cuomo G, Beretta L, Zanatta E, Giuggioli D, Del Papa N, Airo P, Confalonieri M, Moroncini G, Dagna L, and Matucci-Cerinic M
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- Humans, Female, Adult, Middle Aged, Aged, Male, Retrospective Studies, Immunosuppressive Agents therapeutic use, Lung Diseases, Interstitial, Scleroderma, Systemic drug therapy
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Introduction: Nintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting., Methods: Patients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction. The following parameters were recorded: SSc clinical features, NTD tolerability, pulmonary function tests and modified Rodnan skin score (mRSS)., Results: 90 patients with SSc-ILD (65% female, mean age 57.6±13.4 years, mean disease duration 8.8±7.6 years) were identified. The majority were positive for anti-topoisomerase I (75%) and 77 (85%) patients were on immunosuppressants. A significant decline in %predicted forced vital capacity (%pFVC) in the 12 months prior to NTD introduction was observed in 60%. At 12 months after NTD introduction, follow-up data were available for 40 (44%) patients and they showed a stabilisation in %pFVC (64±14 to 62±19, p=0.416). The percentage of patients with significant lung progression at 12 months was significantly lower compared with the previous 12 months (60% vs 17.5%, p=0.007). No significant mRSS change was observed. Gastrointestinal (GI) side effects were recorded in 35 (39%) patients. After a mean time of 3.6±3.1 months, NTD was maintained after dose adjustment in 23 (25%) patients. In nine (10%) patients, NTD was stopped after a median time of 4.5 (1-6) months. During the follow-up, four patients died., Conclusions: In a real-life clinical scenario, NTD, in combination with immunosuppressants, may stabilise lung function. GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in patients with SSc-ILD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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31. Lung vascular changes as biomarkers of severity in systemic sclerosis-associated interstitial lung disease.
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Bruni C, Occhipinti M, Pienn M, Camiciottoli G, Bartolucci M, Bosello SL, Payer C, Bálint Z, Larici AR, Tottoli A, Tofani L, De Lorenzis E, Lepri G, Bellando-Randone S, Spinella A, Giuggioli D, Masini F, Cuomo G, Lavorini F, Colagrande S, Olschewski H, and Matucci-Cerinic M
- Subjects
- Humans, Female, Middle Aged, Retrospective Studies, Tomography, X-Ray Computed methods, Lung, Biomarkers, Scleroderma, Systemic complications, Scleroderma, Systemic diagnostic imaging, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial complications
- Abstract
Objectives: It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features., Methods: SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted., Results: A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s.d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of <6 mm in diameter. Considering radiological and functional criteria concomitantly, as well as the descriptive trends from the longitudinal evaluations, the normalized PVVs, vessel numbers and densities increased progressively with the increase/worsening of ILD extent and functional impairment., Conclusion: In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
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32. Sudden winter iloprost withdrawal in scleroderma patients during COVID-19 pandemic.
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De Lorenzis E, Natalello G, Verardi L, Cerasuolo PG, Gigante L, D'Agostino MA, and Bosello SL
- Subjects
- Humans, Iloprost adverse effects, Pandemics, Ulcer complications, COVID-19, Raynaud Disease diagnosis, Raynaud Disease drug therapy, Scleroderma, Systemic complications, Scleroderma, Systemic diagnosis, Scleroderma, Systemic drug therapy, Skin Ulcer diagnosis, Skin Ulcer drug therapy
- Abstract
Introduction: Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used., Methods: A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated., Results: The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36-0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density., Conclusions: Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients., Competing Interests: Declaration of competing interest There are no competing interests for any author. All the authors gave substantial contributions to the conception or design of the work, acquisition, analysis or interpretation of data, drafting the work or revising it critically for important intellectual content and final approval of the version published., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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33. The role of PET/CT in connective tissue disorders: systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus.
- Author
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Guarneri A, Perrone E, Bosello SL, D'Agostino MA, and Leccisotti L
- Subjects
- Connective Tissue, Humans, Positron Emission Tomography Computed Tomography, Connective Tissue Diseases diagnostic imaging, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic diagnostic imaging, Scleroderma, Systemic complications, Scleroderma, Systemic diagnostic imaging, Sjogren's Syndrome diagnostic imaging
- Abstract
Advanced imaging techniques are needed to help clinicians in the diagnosis, in the choice of the right time for therapeutic interventions or for modifications and monitoring of treatment response in patients with autoimmune connective tissue diseases. Nuclear medicine imaging, especially PET/CT and PET/MRI, may play an important role in detecting disease activity, assessing early treatment response as well as in clarifying the complex mechanisms underlying systemic sclerosis, Sjögren's syndrome or systemic lupus erythematosus. In addition, [
18 F]FDG PET/CT may help in excluding or detecting coexisting malignancies. Other more specific radiopharmaceuticals are being developed and investigated, targeting specific cells and molecules involved in connective tissue diseases. Further larger studies with standardized imaging protocol and image interpretation are strongly required before including PET/CT in the diagnostic work-up of subsets of patients with autoimmune connective tissue diseases.- Published
- 2022
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34. Correspondence to 'Gender gap in rheumatology: speaker representation at annual conferences' by Monga and Liew-gender discrepancies at annual EULAR congresses: towards the gap narrowing.
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Conigliaro P, Bosello SL, Iannuccelli C, Gremese E, Spinelli FR, Vadacca M, and Chimenti MS
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2022
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35. Interstitial Lung Disease Associated With Autoimmune Rheumatic Diseases: Checklists for Clinical Practice.
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Bosello SL, Beretta L, Del Papa N, Harari S, Palmucci S, Pesci A, Rechichi G, Varone F, and Sebastiani M
- Abstract
Background: Interstitial lung diseases (ILDs) are often associated with rheumatic diseases. Their early diagnosis and management are not only difficult, but also crucial, because they are associated with major morbidity and mortality and can be the first cause of death in autoimmune rheumatic diseases (ARDs). Objectives: By using methodologies, such as Nominal Group Technique (NGT) and Delphi Survey, the aims of this study were (1) to measure consensus between pulmonologists, radiologists, and rheumatologists experienced in the management of ARD-ILD; (2) to highlight the importance of a multidisciplinary approach; and (3) to provide clinicians with a practical tool aimed at improving the prompt recognition and follow-up of ILD associated with ARDs and of any possible rheumatic conditions underlying ILD. Results: During the NGT round, the Steering Committee defined 57 statements to be used in the Delphi survey. A total of 78 experts participated in the Delphi survey, namely 28 pulmonologists, 33 rheumatologists, and 17 radiologists. During this round, consensus on agreement was reached in 47 statements, while disagreement was not reached in any statements. A secondary questionnaire was drafted by the Steering Committee to obtain clearer indications on ILD-ARD "red-flags" and follow-up. Delphi Panelists took part also in the second-questionnaire survey. Answers from both surveys were used to draft two checklists of "red flags" sign or symptom suggestive of ILD and ARD, respectively, and two checklists on identification and monitoring of rheumatoid arthritis (RA) and systemic sclerosis (SSc) ILD. Limitations: This study is a consensus work, which cannot produce empiric data, and is limited to the Italian scenario. Conclusions: This work showed a high level of agreement, but also shows some divergent opinions between different experts. This underlines the importance of a multidisciplinary approach. Eventually, we believe the drafted checklists can help clinicians in the diagnosis and follow-up of ILD-ARD., Competing Interests: LB reports personal fees from Boehringer Ingelheim, Janssen, GSK, AZ, Werfen. SH has relationships with drug companies Boehringer Ingelheim and Roche. In addition to being investigator in trials involving these companies, relationships include lectures and membership of scientific advisory boards and grant for research. FV reports personal fees from Boehringer Ingelheim and Roche. MS reports personal fees from Boehringer Ingelheim, Janssen, Pfizer, Lilly, Bristol-Myers Squibb. SB has relationships with drug companies Boehringer Ingelheim, Roche, Janssen, AbbVie, and Pfizer. Relationships include lectures and membership of scientific advisory boards. SP reports personal fees from Boehringer Ingelheim and Roche SpA, not related to this submitted paper. GR reports personal fees from Boehringer Ingelheim and Roche SpA, not related to this submitted paper. AP has relationships with drug companies Boehringer Ingelheim and Roche. In addition to being investigator in trials involving these companies, relationships include lectures and membership of scientific advisory boards and grant for research. ND has relationships with drug companies Boehringer Ingelheim and Jansenn, Relationships include lectures and membership of scientific advisory boards. This study received funding from Boehringer Ingelheim. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2021 Bosello, Beretta, Del Papa, Harari, Palmucci, Pesci, Rechichi, Varone and Sebastiani.)
- Published
- 2021
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36. Adult-onset Still's disease following COVID-19 vaccination.
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Leone F, Cerasuolo PG, Bosello SL, Verardi L, Fiori E, Cocciolillo F, Merlino B, Zoli A, and D'Agostino MA
- Abstract
Competing Interests: We declare no competing interests. The patient provided informed consent to publish this case.
- Published
- 2021
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37. An unusual lung involvement in scleroderma: lipoid pneumonia.
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Verardi L, Calandriello L, De Lorenzis E, Natalello G, Gigante L, Cicchetti G, Larici AR, Gremese E, D'Agostino MA, and Bosello SL
- Subjects
- Humans, Lung diagnostic imaging, Tomography, X-Ray Computed, Pneumonia, Lipid diagnostic imaging, Pneumonia, Lipid etiology
- Published
- 2021
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38. COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.
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MacDonald L, Alivernini S, Tolusso B, Elmesmari A, Somma D, Perniola S, Paglionico A, Petricca L, Bosello SL, Carfì A, Sali M, Stigliano E, Cingolani A, Murri R, Arena V, Fantoni M, Antonelli M, Landi F, Franceschi F, Sanguinetti M, McInnes IB, McSharry C, Gasbarrini A, Otto TD, Kurowska-Stolarska M, and Gremese E
- Subjects
- Arthritis, Rheumatoid metabolism, B7-H1 Antigen immunology, Bronchoalveolar Lavage Fluid immunology, CD48 Antigen immunology, COVID-19 chemically induced, COVID-19 metabolism, Fatty Acid-Binding Proteins immunology, Humans, Lectins immunology, Lipopolysaccharide Receptors immunology, Lipopolysaccharide Receptors metabolism, Lung diagnostic imaging, Lung immunology, Lung metabolism, Lung pathology, Macrophages immunology, Macrophages metabolism, Membrane Glycoproteins immunology, Monocytes metabolism, Neutrophils metabolism, Osteopontin blood, Receptor Protein-Tyrosine Kinases metabolism, Receptors, Immunologic immunology, S100A12 Protein immunology, S100A12 Protein metabolism, Synovial Membrane immunology, Tomography, X-Ray Computed, Ficolins, Arthritis, Rheumatoid immunology, COVID-19 immunology, Monocytes immunology, Neutrophils immunology, Osteopontin immunology
- Abstract
We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.
- Published
- 2021
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39. Reply to: Individuality of the composition of the human microbiota by Fernández-Estupiñán et al.
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Natalello G, Bosello SL, Sanguinetti M, and Gremese E
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- Humans, Individuality, Microbiota
- Published
- 2021
40. Safety and efficacy of rituximab biosimilar (CT-P10) in systemic sclerosis: an Italian multicentre study.
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Campochiaro C, De Luca G, Lazzaroni MG, Zanatta E, Bosello SL, De Santis M, Cariddi A, Bruni C, Selmi C, Gremese E, Matucci-Cerinic M, Doria A, Airò P, and Dagna L
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antirheumatic Agents therapeutic use, Scleroderma, Systemic drug therapy
- Abstract
Objectives: Recent data have shown a significant efficacy of rituximab (RTX) in SSc. An RTX biosimilar (RTX-B) is a more affordable option. We assessed the safety and efficacy of an RTX-B (CT-P10) in SSc., Methods: SSc patients treated with RTX-B with at least 6 months of follow-up were retrospectively identified from six Italian referral centres. SSc patients naïve to RTX-B (RTX-Bn) or already treated with RTX originator and switched to an RTX-B (RTX-Bs) were evaluated. A comprehensive assessment of disease characteristics and organ involvement at baseline and after 6 months was obtained., Results: Thirty-three SSc patients were selected: 29 (87.9%) females, mean age 51.6 years (s.d. 14.2), mean disease duration 9.8 years (s.d. 8.1); 21 (64.5%) with dcSSc, 20 (60.1%) anti-topoisomerase I, 7 (21.2%) anti-RNA polymerase III and 6 (18.2%) anti-centromere positive. Seventeen (51.5%) were RTX-Bn and 16 were on RTX-Bs (48.5%). RTX was introduced because of skin progression in 18 patients (54.5%), interstitial lung disease (ILD) worsening in 11 (33.3%) and arthritis in 12 (36.4%). All patients were previously treated with immunosuppressants. At RTX-B introduction, 21 (63.6%) patients were on concomitant immunosuppressants: 15 (71.4%) on MMF and 6 (28.6%) on MTX. Twenty-three (69.7%) were on low-dose steroids. After 6 months, a significant reduction of the modified Rodnan skin score (mRSS), 28-joint DAS and CRP was observed (P = 0.002, 0.005 and 0.008, respectively); the mRSS significantly improved both in RTX-Bn (P < 0.024) and RTX-Bs patients (P < 0.031). No significant changes were observed for lung function tests, either in the entire cohort or in the subgroup of ILD patients. Only one RTX-Bs patient experienced transient neutropenia., Conclusion: Our data suggest that RTX-B can represent a cheaper option in SSc patients, as it is effective in improving skin and joint involvement and in stabilizing lung function., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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41. Treatment strategy introducing immunosuppressive drugs with glucocorticoids ab initio or very early in giant cell arteritis: A multicenter retrospective controlled study.
- Author
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Quartuccio L, Isola M, Bruno D, Treppo E, Gigante L, Angelotti F, Capecchi R, Vitiello G, Cavallaro E, Tavoni A, Bosello SL, Cammelli D, De Vita S, and Gremese E
- Abstract
Objective: Glucocorticoids (GC) are associated with side effects in giant cell arteritis (GCA). Immunosuppressive therapies (ITs) have given conflicting results in GCA, regarding GC sparing effect. Primary endpoint is to evaluate whether very early introduction of ITs in GCA minimize the rate of GC-induced adverse events, in terms of infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures., Methods: A multicenter retrospective case-control study included 165 patients. One group included 114 patients who were treated with at least one IT given at diagnosis or within 3 months from the start of GC. A second group included 51 GCA who received only GC or an IT more than 3 months later., Results: The most frequently used ITs were: methotrexate (138 patients), cyclophosphamide (48 patients) and tocilizumab (27 patients). No difference was observed as concerns the follow-up time between groups [48.5 (IQR 26-72) vs 40 (IQR 24-69), p = 0.3)]. The first group showed a significantly lower incidence of steroid-induced diabetes (8/114, 7% vs 12/51, 23.5%; p = 0.003) and no differences for the rate of infections (p = 0.64). The group was also exposed to lower doses of GC at first (p < 0.0001) and third (p < 0.0001, rank-sum test) month. Forty-four patients in the first group (38.6%) compared with 34 in the second one (66.7%) experienced at least one relapse (p = 0.001)., Conclusion: Very early introduction of IT in GCA lowered the incidence of steroid-induced diabetes, possibly due to the lower doses of GC in the first three months. Relapse rate was even lower., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)
- Published
- 2020
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42. What can we learn from rapidly progressive interstitial lung disease related to anti-MDA5 dermatomyositis in the management of COVID-19?
- Author
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De Lorenzis E, Natalello G, Gigante L, Verardi L, Bosello SL, and Gremese E
- Subjects
- Autoantibodies, Betacoronavirus, COVID-19, Disease Progression, Humans, Pandemics, SARS-CoV-2, Coronavirus Infections pathology, Dermatomyositis pathology, Lung Diseases, Interstitial pathology, Pneumonia, Viral pathology
- Abstract
Competing Interests: Declaration of Competing Interest There are no competing interests for any author.
- Published
- 2020
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43. Sarilumab use in severe SARS-CoV-2 pneumonia.
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Gremese E, Cingolani A, Bosello SL, Alivernini S, Tolusso B, Perniola S, Landi F, Pompili M, Murri R, Santoliquido A, Garcovich M, Sali M, De Pascale G, Gabrielli M, Biscetti F, Montalto M, Tosoni A, Gambassi G, Rapaccini GL, Iaconelli A, Zileri Del Verme L, Petricca L, Fedele AL, Lizzio MM, Tamburrini E, Natalello G, Gigante L, Bruno D, Verardi L, Taddei E, Calabrese A, Lombardi F, Bernabei R, Cauda R, Franceschi F, Landolfi R, Richeldi L, Sanguinetti M, Fantoni M, Antonelli M, and Gasbarrini A
- Abstract
Background: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia., Methods: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead., Findings: Of the 53 SARS-CoV-2
pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2 /FiO2 :146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2 /FiO2 : 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%., Interpretation: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety., Competing Interests: All authors declare no conflict of interest with the submitted manuscript., (© 2020 The Authors.)- Published
- 2020
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44. Multidisciplinary Evaluation of Interstitial Lung Diseases: New Opportunities Linked to Rheumatologist Involvement.
- Author
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De Lorenzis E, Bosello SL, Varone F, Sgalla G, Calandriello L, Natalello G, Iovene B, Cicchetti G, Gigante L, Verardi L, Gremese E, Richeldi L, and Larici AR
- Abstract
Multidisciplinary team (MDT) discussion is the gold standard in the management of interstitial lung disease (ILD). The rheumatologist is not routinely involved in MDT, even if up to 20% of ILD are related to systemic autoimmune rheumatic diseases (SARD). The study aims to assess the agreement and its variation over time between rheumatologists and pulmonologists in the screening of SARD and between rheumatologists and an MDT extended to rheumatologists (eMDT) in evaluating the progression of SARD. We computed the agreement between the pulmonologist and rheumatologist in the identification of red flags for SARDs of 81 ILD cases and between the rheumatologist alone and eMDT in the confirmation of 70 suspected SARD-ILD progressions. The agreement between rheumatologists and pulmonologists was moderate for the detection of autoimmunity test positivity ( κ = 0.475, p < 0.001) and family history of SARD ( κ = 0.491, p < 0.001) and fair for the identification of extrapulmonary symptoms ( κ = 0.225, p = 0.064) or routine laboratory abnormalities consistent with SARD. The average agreement between the rheumatologist and eMDT in the identification of ILD progression was moderate ( κ = 0.436, p < 0.001). The class of agreement improved from the first to the third semester. The average agreement with the rheumatologist ranged from fair to moderate, suggesting that a shared evaluation of SARD-ILD in eMDT could improve the diagnostic work-up and the evaluation of ILD progression.
- Published
- 2020
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45. No higher risk of respiratory symptoms in Italian rheumatological patients under IL-6R-inhibitor therapy in SARS-CoV-2 pandemic.
- Author
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Alivernini S, Petricca L, Perniola S, Fedele AL, Gigante MR, Capacci A, Paglionico A, Varriano V, De Lorenzis E, Lanzo L, Melpignano F, Rubortone P, Tanti G, Tur C, Bruno D, Gigante L, Natalello G, Verardi L, Di Mario C, Tolusso B, Mirone L, Lizzio MM, Zoli A, Peluso G, Bosello SL, and Gremese E
- Subjects
- COVID-19, Coronavirus Infections chemically induced, Humans, Italy, Pandemics, Pneumonia, Viral chemically induced, Receptors, Interleukin-6 antagonists & inhibitors, Respiration Disorders chemically induced, Risk Factors, SARS-CoV-2, Betacoronavirus, Biological Products adverse effects, Coronavirus Infections physiopathology, Immunosuppressive Agents adverse effects, Pneumonia, Viral physiopathology, Respiration Disorders virology, Rheumatic Diseases drug therapy
- Published
- 2020
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46. Systemic sclerosis myocarditis has unique clinical, histological and prognostic features: a comparative histological analysis.
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De Luca G, Campochiaro C, De Santis M, Sartorelli S, Peretto G, Sala S, Canestrari G, De Lorenzis E, Basso C, Rizzo S, Thiene G, Palmisano A, Esposito A, Selmi C, Gremese E, Della Bella P, Dagna L, and Bosello SL
- Subjects
- Biopsy methods, Dyspnea diagnosis, Dyspnea etiology, Echocardiography methods, Electrocardiography, Ambulatory methods, Female, Fibrosis, Humans, Magnetic Resonance Imaging, Cine methods, Male, Middle Aged, Prognosis, Retrospective Studies, Immunosuppressive Agents therapeutic use, Myocarditis etiology, Myocarditis mortality, Myocarditis physiopathology, Myocarditis therapy, Myocardium pathology, Scleroderma, Systemic complications
- Abstract
Objective: To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM)., Methods: We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0-3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used., Results: We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P = 0.002]. Myocardial fibrosis directly correlated with skin score (r = 0.625, P = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r = 0.756, P = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P = 0.041) and we found heart failure only in SSc patients (25%) (P = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P < 0.001]., Conclusion: SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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47. Ultrasonography involvement of carotid, upper and lower limb arteries in a large cohort of systemic sclerosis patients.
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Caimmi C, De Marchi S, Bosello SL, Giuggioli D, Caramaschi P, Di Giorgio A, Spinella A, Astorino G, Canestrari G, Cocchiara E, Gremese E, Viapiana O, and Rossini M
- Subjects
- Adult, Aged, Carotid Arteries diagnostic imaging, Female, Humans, Italy epidemiology, Male, Middle Aged, Predictive Value of Tests, Prevalence, Scleroderma, Systemic epidemiology, Vascular Diseases epidemiology, Arteries diagnostic imaging, Lower Extremity blood supply, Scleroderma, Systemic diagnostic imaging, Ultrasonography, Doppler, Color, Upper Extremity blood supply, Vascular Diseases diagnostic imaging
- Abstract
Objectives: Data on macrovascular involvement in systemic sclerosis (SSc) are still debatable. The aim of this study was to estimate its prevalence and possible determinants in a large cohort., Methods: One hundred and fifty-five outpatients with SSc were enrolled. Data about disease characteristics and cardiovascular risk factors were collected and patients underwent ecocolor Doppler ultrasonography of arteries of the neck and lower (LL) and upper (UL) limbs., Results: Mean age was 57.9 ± 14.5 years and most were female (88.4%) with a limited subset (63.2%). Mean disease duration was 11.4 ± 8.1 years. Twenty-three (14.8%) had hypertension, 7 (4.8%) diabetes, 64 (41.3%) hypercholesterolemia and 63 (40.6%) were active/past smokers. Seventy-nine (49%) patients had plaques at carotids, 49 (32.9%) at LL and 7 (4.9%) at UL. In multivariate analysis, patients with carotid plaques had more often a limited pattern (P = .001), patients with distal LL plaques pulmonary arterial hypertension (P = .006) and patients with proximal LL plaques lower diffusing capacity for carbon monoxide adjusted to hemoglobin and its ratio to alveolar volume (P = .004). In patients with UL plaques traditional cardiovascular risk factors were not more common, while forced vital capacity was lower (P = .023). Finally, upper limb and proximal LL plaques were as common in early disease patients as in longstanding ones, although the former were younger., Conclusions: This study shows that macrovascular involvement is quite common in SSc and that some disease characteristics linked to microvascular involvement are associated with atherosclerotic plaques, which can be present even in early disease. Our study suggests that a complete evaluation of macrocirculation is mandatory for rheumatologists treating SSc patients., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)
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- 2020
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48. Sixth-month remission as a predictor for twelve-month remission in polymyalgia rheumatica.
- Author
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Birra D, Bosello SL, Peluso G, and Zoli A
- Subjects
- Blood Sedimentation, C-Reactive Protein analysis, Female, Giant Cell Arteritis drug therapy, Humans, Male, Polymyalgia Rheumatica drug therapy, Prednisone therapeutic use, Prognosis, Remission Induction, Giant Cell Arteritis diagnosis, Polymyalgia Rheumatica diagnosis
- Abstract
Objectives: To investigate clinical and laboratory prognostic factors of remission after one year of follow-up in patients with polymyalgia rheumatica (PMR) treated with low-dose prednisone., Methods: In this observational study, in a monocentric Italian Rheumatology Unit, we enrolled eighty-one consecutive PMR patients. Clinical and laboratory tests were performed every 3 months. Clinical remission was defined as the lack of symptoms, while laboratory remission was defined as erythrocyte sedimentation rate ≤40 mm/h and C-reactive protein (CRP) ≤0.5 mg/dl., Results: Thirty-eight patients reached complete (clinical and laboratory) remission after 12 months of follow-up. A significant lower percentage of complete remission was seen in female gender compared to male (33.9 % vs. 78.2%, p=0.0001) at univariate analysis. No significant differences were found at baseline according to response to therapy during follow-up, while CRP values at the sixth month were significantly lower in patients who reached complete remission after one year (median: 0.4 mg/dl vs. 1 mg/dl, p=0.017). CRP<0.5 mg/dl at 6 months was independently associated with complete remission at 12 months in the multivariate analysis., Conclusions: The sixth month of therapy is a target for the management of PMR because it can help to identify patients at greater risk of exacerbations, who may benefit from a tighter follow-up and more aggressive therapeutic strategy. Higher CRP values at 6 months appear to be associated with a higher risk of longer steroid therapy.
- Published
- 2020
49. Gut microbiota analysis in systemic sclerosis according to disease characteristics and nutritional status.
- Author
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Natalello G, Bosello SL, Paroni Sterbini F, Posteraro B, De Lorenzis E, Canestrari GB, Gigante L, Verardi L, Ferraccioli G, Sanguinetti M, and Gremese E
- Subjects
- Dysbiosis, Feces, Humans, Nutritional Status, RNA, Ribosomal, 16S, Gastrointestinal Microbiome, Scleroderma, Systemic
- Abstract
Objectives: Systemic sclerosis (SSc) is a rare multi-organ disorder with a prominent gastrointestinal (GI) involvement. Altered gut microbiota is now considered a pivotal factor associated with the development of immune-mediated and inflammatory diseases. We performed a 16S ribosomal RNA (rRNA) gene-sequencing analysis of fecal microbiota in a cohort of SSc patients and matched healthy controls (HCs), with the aim to obtain some hints about a possible role of dysbiosis in the onset, progression, and severity of the disease., Methods: We analysed stool samples from 63 SSc patients with different disease duration, phenotype, and nutritional status and from 17 HCs through 16S ribosomal RNA (rRNA) gene-sequencing., Results: Microbial richness was lower for patients with long-standing disease. A similar observation was made for patients with diffuse cutaneous SSc (dsSSc) compared to those with limited variant (lcSSc) and for patients who reported a recent weight loss. Consistent with previous reports, we noted a deviation of the intestinal microbial composition in patients with SSc compared to HCs, with a greater expression of Lactobacillus and Streptococcus and a depletion of Sutterella. Nutritional status, assessed using BMI as a surrogate, appeared to have a marked impact on the gut microbiota, with overweight patients showing lower richness compared both to underweight and normal-BMI patients., Conclusions: Our findings expand the current knowledge of gut microbiota in SSc and could be useful to identify patients who would most benefit from treatments aimed at restoring the eu-biosis.
- Published
- 2020
50. Gender equality in Rheumatology.
- Author
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Bosello SL, Chimenti MS, Conigliaro P, Iannuccelli C, Gremese E, Spinelli FR, and Vadacca M
- Subjects
- Career Mobility, Decision Making, Faculty, Medical statistics & numerical data, Faculty, Medical trends, Female, Humans, Italy, Leadership, Male, Physician Executives statistics & numerical data, Research Personnel statistics & numerical data, Research Support as Topic economics, Rheumatology trends, Salaries and Fringe Benefits statistics & numerical data, Sex Factors, Sex Ratio, Gender Equity, Rheumatology statistics & numerical data
- Abstract
Not available.
- Published
- 2020
- Full Text
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