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  • 1
    In: Rheumatology, Oxford University Press (OUP), ( 2024-05-15)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1474143-X
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  • 2
    In: Rheumatology, Oxford University Press (OUP), Vol. 59, No. 9 ( 2020-09-01), p. 2523-2533
    Abstract: 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  & lt; 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.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1474143-X
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  • 3
    In: Microvascular Research, Elsevier BV, Vol. 133 ( 2021-01), p. 104071-
    Type of Medium: Online Resource
    ISSN: 0026-2862
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1471172-2
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 61, No. 7 ( 2022-07-06), p. e192-e193
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 7 ( 2022-07-06), p. e192-e193
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474143-X
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  • 5
    In: RMD Open, BMJ, Vol. 9, No. 1 ( 2023-02), p. e002850-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2056-5933
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2812592-7
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  • 6
    In: Nanotechnology Development, PAGEPress Publications, Vol. 2, No. 1 ( 2012-01-04), p. 5-
    Abstract: A lateral flow (LF) device combined with quantum dots (QDs) technology was developed for rapid detection of a specific mycobacterial flavoprotein reductase ( 〈 em 〉 fprA 〈 /em 〉 ). In order to develop the LF assay based on a double-antibody sandwich format, two monoclonal antibodies recognizing different epitopes located in separated 〈 em 〉 fprA 〈 /em 〉 domains were identified. The first monoclonal antibody was immobilized onto the detection zone of a porous nitrocellulose membrane, whereas another monoclonal antibody was conjugated to QDs nanoparticles as a detection system. Using these monoclonal antibodies we recorded a good fluorescence signal, the intensity of which was directly proportional to the concentration of 〈 em 〉 fprA 〈 /em 〉 protein. The use of antibodies conjugated with fluorescent semiconductor QDs via biotin-streptavidin bridge, allowed the detection of 〈 em 〉 fprA 〈 /em 〉 protein at concentrations as low as 12.5 pg/μL in less than 10 min. The reported technology could be useful in the diagnostic investigation of 〈 em 〉 Mycobacterium tuberculosis 〈 /em 〉 and other human pathogens in clinical specimens.
    Type of Medium: Online Resource
    ISSN: 2038-968X , 2038-9671
    Language: Unknown
    Publisher: PAGEPress Publications
    Publication Date: 2012
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  • 7
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-8-27)
    Abstract: Background: Cardiovascular events (CVEs) are the first cause of death in patients with psoriatic arthritis (PsA). Depression is a recognized risk factor in cardiovascular events and is frequently associated with PsA. Flow-mediated dilatation (FMD) is a widely used method for assessing endothelial dysfunction, a parameter with strong prognostic implications for CVEs. The study aims to explore the relationship between FMD, depressive symptoms and serum cytokines in a cohort of patients with PsA. Patients and Methods: FMD was assessed in 50 consecutive PsA patients aged between 30 and 75 years without known cerebrovascular and coronary heart disease or diabetes. Depressive symptoms were reported using the related subscale of the Hospital Anxiety and Depression Scale (HDS). Disease features, activity indexes, and adjusted Framingham risk score (aFRS) were calculated. Serum level of IL-6, TNF-α, and IL-17A were also assessed. Results: In PsA patients (age 50.7 ± 10.2 years, male 42%, disease duration 5.9 ± 3.3 years, Disease Activity in PSoriatic Arthritis (DAPSA) score 14.0 ± 9.4) FMD inversely correlated with the severity of depressive symptoms according to HDS (ρ = −0.339, p = 0.016), age (ρ = −0.507, p = 0.001), aFRS (rs = −0.453, p & lt; 0.001), duration of PsA (ρ = −0.507, p = 0.001), intensity of pain (ρ = −0.507, p = 0.001), and DAPSA (ρ = −0.507, p = 0.001). No statistically significant correlation was found between FMD or HDS and serum cytokines concentrations. HDS predicted FMD in a model adjusted for age, aFRS, PsA duration, and pain intensity (β = −0.271, p = 0.008), with depressive symptoms contributing directly to 6.4% of the variance. Conclusions: Depressive symptoms correlate with endothelial dysfunction with an exposure-response pattern in our cohort of PsA patients.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 8
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 2 ( 2023-02-01), p. 696-706
    Abstract: 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 & lt;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.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 9
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. Supplement_2 ( 2023-04-24)
    Abstract: CCL24 is a novel target that was found to play a dual role in advancing pro-inflammatory and pro-fibrotic processes in systemic sclerosis (SSc). Previous studies reported that skin and serum CCL24 levels are elevated in SSc and that blocking of CCL24 was effective in preventing and attenuating experimental-induced fibrosis in murine models as well as interfering with endothelial cell activation. Here we tested the concentration of CCL24 in an observational cohort of patients with SSc and available clinical follow-up to determine its clinical value in predicting fibrotic and vascular complications of the disease. Methods Consecutive patients from a single-centre observational cohort were enrolled in this analysis. Clinical data were collected according to the EUSTAR minimal essential data set. Serum Concentration of CCL24 was measured by Luminex assay (Myriad RBM) and defined as “high” for patients over the upper quartile of the healthy control population (110 ng/ml). Interstitial lung disease (ILD) was defined by at least 10% parenchymal involvement at a high-resolution CT scan of the chest, while digital ulcer (DU) disease was defined by the presence of current or history of DU in the previous 6 months. Progressive fibrotic ILD was defined as previously described, according to Erice's criteria within 24 months. Clinical features were compared between CCL24 high vs low by Chi-Square and T-student tests. R software was employed for statistical analysis. Results 189 SSc patients (13% male) fulfilling 2013 ACR/EULAR classification criteria were enrolled in this study. Median (IQR) disease duration was 4 (IQR 2-10) years. 37 (27%) had diffuse cutaneous SSc, 60 (32%) had ILD, and 90 (48%) had DU disease. 52 patients (26%) were CCL24 High. These patients had a higher prevalence of DU (60%, p = 0.042), a higher median (IQR) mRSS [4(2-7) vs 2(0-5), p = 0.036) and showed a higher prevalence of ILD (42% vs 28%, p = 0.055); this was more significant among patients with limited cutaneous SSc (7% vs 12%, p = 0.037). Most importantly, among patients with PF-ILD (19/43 with available 24-month follow-up), 44% had significantly higher CCL24 serum concentration at baseline, compared to stable patients (1150 [817-1593] vs 725 [460-955]; p = 0.017). Consistent with these findings, in patients with ILD, having high CCL24 gave double the chance of progressing within 24 months (66% vs 32% of CCL24 low; p = 0.03). Conclusion We show here that within the context of an observational cohort of unselected patients, CCL24 serum concentration is associated with the presence of DU as well as worse skin and lung fibrotic involvement, suggesting that this molecule may be involved in both vascular and fibrotic manifestations of SSc. These results informed the rationale for a target-enriched basket randomized controlled trial to test the biological and clinical effect of CCL24 inhibition in SSc across cutaneous disease subsets. Disclosure E. De Lorenzis: None. A. Mor: None. R. Ross: None. S. Di Donato: None. R. Aricha: None. H. Levi: None. I. Vaknin: None. F. Del Galdo: Other; FDG received consultancies and research support from Abbvie, AstraZeneca, Boheringer-Ingelheim, Capella, Chemomab, Ergomed, Janssen, Kymab, Mitsubishi-Tanabe.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 10
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. Supplement_2 ( 2023-04-24)
    Abstract: Hand impairment is a major driver of disability and reduced quality of life in Systemic Sclerosis (SSc) patients. It is multifactorial and the risk and predictability of functional deterioration are unknown. The aim of this study is to describe hand function changes and predictors of functional deterioration in an observational cohort of SSc patients. Methods Consecutive SSc patients were longitudinally evaluated every 6 months for 3 years for SSc-related hand involvement. Patient-reported hand symptoms were captured with Cochin Hand Disability Score (CHFS), Raynaud Condition Score (RCS) and overall pain intensity on a visual analogue scale (VAS pain). Their minimal clinical important difference (MCID) and patient-acceptable symptom state (PASS) were evaluated according to validated thresholds. Clinical association with CHFS change over time and 36-month clinically meaningful worsening (MCID-Wor) were assessed via ANOVA and binomial logistic regression, respectively. Results One-hundred-seventy-six SSc patients were enrolled in this analysis, 13.6% of them were male and the mean age was 55.1± 12.3 years, the median disease duration was 5.0 years and 31.8% presented a diffuse cutaneous variant. Overall, CHFS worsened over time (p  & lt; 0.001); 34.1% of patients reported a clinically significant worsening by the end of follow-up. Accordingly, the proportion of participants reporting CHFS≥PASS increased from 26.1% at baseline to 34.7% at the last follow-up. MCID-W after 36 months was associated with diffuse cutaneous variant [OR 2.44 (95% CI 1.27-4.76), p = 0.008], baseline active-late capillaroscopy pattern [OR 3.00 (95% CI 1.17-7.70), p = 0.013] , VAS pain [OR 1.02 (95% CI 1.01-1.03), p = 0.003], RCS [OR 1.03 (95% CI 1.02-1.04), p  & lt; 0.001], forearm-hand-finger skin score [OR 1.12 (95% CI 1.00-1.26), p = 0.044] , history of digital ulcers [OR 2.39 (95% CI 1.24-4.61), p = 0.008] or flexor contractures [OR 2.52 (95% CI 1.29-4.92), p = 0.007] , as well as baseline CHFS [OR 1.03 (95% CI 1.01-1.05), p = 0.001]. A regression model based on these clinical variables could correctly classify 76.7% of cases. Conclusion SSc-related hand disability affects more than one-third of patients and tends to worsen over time in both cutaneous subsets despite the current standard of care. Identifying patients at risk of deteriorating hand function should inform targeted intervention strategies to prevent hand disability in SSc. Disclosure E. De Lorenzis: None. V. Kakkar: None. S. Di Donato: None. M. Wilson: None. L. Green: None. B. Alcacer-Pitarch: None. F. Del Galdo: Other; FDG received consultancies and research support from Abbvie, AstraZeneca, Boheringer-Ingelheim, Capella, Chemomab, Ergomed, Janssen, Kymab, Mitsubishi-Tanabe.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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