Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinician... more Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in ...
Systemic sclerosis (SSc) is a complex, heterogeneous, multi-organ disease, the etiology of which ... more Systemic sclerosis (SSc) is a complex, heterogeneous, multi-organ disease, the etiology of which is not yet fully understood. Although fibrosis of the skin and major organs is a well-known, characteristic sign of this condition, the primary dysfunctions contributing to the disease phenotype appear to be vascular and immune in nature. The mechanisms leading to vasculopathy in SSc include dysregulation of vascular tone and endothelial dysfunction, followed by vascular remodeling, as well as abnormal angiogenesis and vasculogenesis. In addition, coagulopathy also plays a role in the disease process. Together, these factors produce a form of vasculopathy specific to SSc, characterized by vascular intimal proliferation in the macro- and micro-circulation, as well as qualitative and quantitative capillary changes.
Systemic sclerosis (SSc) is a chronic autoimmune disorder with unknown triggering factors, and co... more Systemic sclerosis (SSc) is a chronic autoimmune disorder with unknown triggering factors, and complex pathophysiologic links which lead to fibrosis of skin and internal organs, including the heart, lungs, and gut. However, more than 100 years after the first description of cardiac disease in SSc, sclerodermic cardiomyopathy (SScCmp) is an underrecognized, occult disease with important adverse long-term prognosis. Laboratory tests, electrocardiography (ECG) and cardiovascular multimodality imaging techniques (transthoracic 2D and 3D echocardiography, cardiac magnetic resonance (CMR), and novel imaging techniques, including myocardial deformation analysis) provide new insights into the cardiac abnormalities in patients with SSc. This state-of-the-art review aims to stratify all the cardiac investigations needed to diagnose and follow-up the SScCmp, and discusses the epidemiology, risk factors and pathophysiology of this important cause of morbidity of the SSc patient.
Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but ... more Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. Subjects and methods: The GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with ≥1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL). Results: We randomised 451 patients with established RA and m...
Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacit... more Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. Results: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC = 0.869), MRI (AUC = 0.885) or C-reactive protein (AUC = 0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC = 0.948). Assuming a pr...
Chronic wounds significantly impact quality of life. If not properly managed, they can severely d... more Chronic wounds significantly impact quality of life. If not properly managed, they can severely deteriorate. Image-based wound analysis could aid in objectively assessing the wound status by quantifying important features that are related to healing. However, the high heterogeneity of the wound types, image background composition, and capturing conditions challenge the robust segmentation of wound images. We present Detect-and-Segment (DS), a deep learning approach to produce wound segmentation maps with high generalization capabilities. In our approach, dedicated deep neural networks detected the wound position, isolated the wound from the uninformative background, and computed the wound segmentation map. We evaluated this approach using one data set with images of diabetic foot ulcers. For further testing, 4 supplemental independent data sets with larger variety of wound types from different body locations were used. The Matthews' correlation coefficient (MCC) improved from 0.29 when computing the segmentation on the full image to 0.85 when combining detection and segmentation in the same approach. When tested on the wound images drawn from the supplemental data sets, the DS approach increased the mean MCC from 0.17 to 0.85. Furthermore, the DS approach enabled the training of segmentation models with up to 90% less training data while maintaining the segmentation performance. Keywords Chronic wounds • ulcers • generalizability • out-of-distribution testing • deep learning • deep neural network • wound segmentation • wound detection • skin lesions.
Objectives: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiova... more Objectives: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals. Methods: Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year. Results: 19 902 patients met criteria. 1...
Systemic sclerosis (SSc) early lung involvement (interstitial lung disease (ILD)) is characterise... more Systemic sclerosis (SSc) early lung involvement (interstitial lung disease (ILD)) is characterised by ground glass opacities (GGO) at high-resolution CT (HRCT).1 2 The literature provides conflicting interpretations of GGO’s clinical significance,3–5 and whether it represents inflammation or early fibrotic changes is a dilemma. In fact, HRCT cannot discriminate between ‘active inflammatory’ and ‘established fibrotic’ GGO.6 Instead, 18-F fluoro-deoxy-d-glucose positron-emission tomography/CT (18F-FDG-PET/CT) locates areas of increased metabolic activity,7 8 but no data on the ‘established fibrotic’ GGO metabolic activity has been demonstrated yet. We aimed at evaluating if 18F-FDG-PET/CT scan may identify GGO inflammatory component in SSc-ILD.9 Seven patients with SSc (six females; mean age 59.56±9.15 years, median disease duration 5 years) from the Rheumatology Outpatient Clinic, University of Florence underwent a 18F-FDG-PET/CT to rule out the presence of a neoplasia for a lung nod...
population of reference. Conclusions: The incidence rates of hip fracture decreased in France bet... more population of reference. Conclusions: The incidence rates of hip fracture decreased in France between 2002 and 2013 in men and women aged 60 years and over. The decrease is more important after direct standardisation whatever population used as a reference as a results of a difference in age-structure of the population that can be erased by the process of direct standardisation. In conclusion, the incidence of hip fractures continues to grow despite a reduced incidence rate throughout a 12 year-period.
IL-10, and IL-17 levels did not modify [Figure, up]. Interestingly, highest cytokine levels were ... more IL-10, and IL-17 levels did not modify [Figure, up]. Interestingly, highest cytokine levels were achieved with UA at 6mg/dL, and further increases in UA were not followed by further parallel cytokine levels increase. For the B) in vivo study, 14 gouty patients were enrolled, median (p25-75) aged 64.5 (60.0, 70.3) years, 92.9% males. Median disease duration was 10.0 (5.8, 17.8) years, being 21.4% tophaceous. Blood tests showed a significant increase in serum UA after ULT dose modification/discontinuation (p=0.001), TNFa (p=0.004), and IL-6 (p=0.03), and a non-significant trend for IL-1b (p=0.055) [Figure, down]. TNFa levels strongly correlated with SUA levels (r=0.77, p=0.001), while the correlation of the other cytokines with SUA was found to be moderate (r=0.45, p=0.13 for IL-6; r=0.31, p=0.30 for IL-1b). Conclusions: Both in vitro and in vivo studies confirm that UA is able to enhance MSU-induced cytokine inflammatory response in a concentration-dependent manner. References: [1] Blood. 89:577. [2] Nature. 440:237. Acknowledgements: This study was funded by Menarini.
Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified int... more Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment, the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. Aims and methods: EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the American College of Rheumatology diagnostic criteria in participating centres. We aimed to characterise demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. Results: In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were women. On multivariate analysis, scleroderma subsets (dcSSc vs lcSSc), antibody status and age at onset of Raynaud's phenomenon, but not gender, were found to be independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis was more closely associated with clinical manifestations than were SSc subsets. Conclusion: dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction seemed to be superseded by an antibody-based classification in predicting some scleroderma complications. The EUSTAR MEDS database facilitates the analysis of clinical patterns in SSc, and contributes to the standardised assessment and monitoring of SSc internationally.
Objective In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangre... more Objective In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangrene. The aim of this study was to investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods We included patients from the EUSTAR database fulfilling the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. Centres were asked for supplementary data on traditional cardiovascular risk factors. We analysed the cross-sectional relationship between gangrene and its potential risk factors by univariable and multivariable logistic regression. Longitudinal data were analysed by Cox proportional hazards regression. Results 1757 patients were analysed (age 55.9 [14.5] years, disease duration 7.9 [10.3] years, male sex 16.7%, 24.6% diffuse cutaneous subset [dcSSc]). At inclusion, 8.9% of patients had current or previous digital gangrene, 16.1% had current digital ulcers (DUs) and 42.7% had ever had ...
Best Practice & Research Clinical Rheumatology, 2021
Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in &... more Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.
Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origi... more Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, characterized by multisystemic involvement and a potentially severe evolution. Pulmonary arterial hypertension (PAH) is a rare complication of SLE, with low 5-year survival. Case presentation. We are presenting the case of a female patient, aged 56 years old, diagnosed in 1992 with SLE with cutaneous manifestations (butterfly-shaped erythematous rash), joint manifestations (polyarthritis), serositis manifestations (massive pleuropericarditis), and immunological manifestations (positive anti-dsDNA antibodies, decreased C3), ignored therapeutically for a long time. In 2010 she complained of dyspnea on medium exertion and leg edemas, with marked increase of PAPs by echocardiography. She was diagnosed with severe PAH (confirmed by right heart catheterization) and in the “Marius Nasta” National Institute of Pneumology she started a treatment with an endothelin receptor antagonist (Bosentan...
The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim o... more The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. The mean SHAQ and HAQ scores of the 944 patients included were 0.87 ( s . d . = 0.66) and 0.92 ( s . d . = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 ...
Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinician... more Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in ...
Systemic sclerosis (SSc) is a complex, heterogeneous, multi-organ disease, the etiology of which ... more Systemic sclerosis (SSc) is a complex, heterogeneous, multi-organ disease, the etiology of which is not yet fully understood. Although fibrosis of the skin and major organs is a well-known, characteristic sign of this condition, the primary dysfunctions contributing to the disease phenotype appear to be vascular and immune in nature. The mechanisms leading to vasculopathy in SSc include dysregulation of vascular tone and endothelial dysfunction, followed by vascular remodeling, as well as abnormal angiogenesis and vasculogenesis. In addition, coagulopathy also plays a role in the disease process. Together, these factors produce a form of vasculopathy specific to SSc, characterized by vascular intimal proliferation in the macro- and micro-circulation, as well as qualitative and quantitative capillary changes.
Systemic sclerosis (SSc) is a chronic autoimmune disorder with unknown triggering factors, and co... more Systemic sclerosis (SSc) is a chronic autoimmune disorder with unknown triggering factors, and complex pathophysiologic links which lead to fibrosis of skin and internal organs, including the heart, lungs, and gut. However, more than 100 years after the first description of cardiac disease in SSc, sclerodermic cardiomyopathy (SScCmp) is an underrecognized, occult disease with important adverse long-term prognosis. Laboratory tests, electrocardiography (ECG) and cardiovascular multimodality imaging techniques (transthoracic 2D and 3D echocardiography, cardiac magnetic resonance (CMR), and novel imaging techniques, including myocardial deformation analysis) provide new insights into the cardiac abnormalities in patients with SSc. This state-of-the-art review aims to stratify all the cardiac investigations needed to diagnose and follow-up the SScCmp, and discusses the epidemiology, risk factors and pathophysiology of this important cause of morbidity of the SSc patient.
Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but ... more Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. Subjects and methods: The GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with ≥1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL). Results: We randomised 451 patients with established RA and m...
Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacit... more Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. Results: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC = 0.869), MRI (AUC = 0.885) or C-reactive protein (AUC = 0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC = 0.948). Assuming a pr...
Chronic wounds significantly impact quality of life. If not properly managed, they can severely d... more Chronic wounds significantly impact quality of life. If not properly managed, they can severely deteriorate. Image-based wound analysis could aid in objectively assessing the wound status by quantifying important features that are related to healing. However, the high heterogeneity of the wound types, image background composition, and capturing conditions challenge the robust segmentation of wound images. We present Detect-and-Segment (DS), a deep learning approach to produce wound segmentation maps with high generalization capabilities. In our approach, dedicated deep neural networks detected the wound position, isolated the wound from the uninformative background, and computed the wound segmentation map. We evaluated this approach using one data set with images of diabetic foot ulcers. For further testing, 4 supplemental independent data sets with larger variety of wound types from different body locations were used. The Matthews' correlation coefficient (MCC) improved from 0.29 when computing the segmentation on the full image to 0.85 when combining detection and segmentation in the same approach. When tested on the wound images drawn from the supplemental data sets, the DS approach increased the mean MCC from 0.17 to 0.85. Furthermore, the DS approach enabled the training of segmentation models with up to 90% less training data while maintaining the segmentation performance. Keywords Chronic wounds • ulcers • generalizability • out-of-distribution testing • deep learning • deep neural network • wound segmentation • wound detection • skin lesions.
Objectives: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiova... more Objectives: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals. Methods: Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year. Results: 19 902 patients met criteria. 1...
Systemic sclerosis (SSc) early lung involvement (interstitial lung disease (ILD)) is characterise... more Systemic sclerosis (SSc) early lung involvement (interstitial lung disease (ILD)) is characterised by ground glass opacities (GGO) at high-resolution CT (HRCT).1 2 The literature provides conflicting interpretations of GGO’s clinical significance,3–5 and whether it represents inflammation or early fibrotic changes is a dilemma. In fact, HRCT cannot discriminate between ‘active inflammatory’ and ‘established fibrotic’ GGO.6 Instead, 18-F fluoro-deoxy-d-glucose positron-emission tomography/CT (18F-FDG-PET/CT) locates areas of increased metabolic activity,7 8 but no data on the ‘established fibrotic’ GGO metabolic activity has been demonstrated yet. We aimed at evaluating if 18F-FDG-PET/CT scan may identify GGO inflammatory component in SSc-ILD.9 Seven patients with SSc (six females; mean age 59.56±9.15 years, median disease duration 5 years) from the Rheumatology Outpatient Clinic, University of Florence underwent a 18F-FDG-PET/CT to rule out the presence of a neoplasia for a lung nod...
population of reference. Conclusions: The incidence rates of hip fracture decreased in France bet... more population of reference. Conclusions: The incidence rates of hip fracture decreased in France between 2002 and 2013 in men and women aged 60 years and over. The decrease is more important after direct standardisation whatever population used as a reference as a results of a difference in age-structure of the population that can be erased by the process of direct standardisation. In conclusion, the incidence of hip fractures continues to grow despite a reduced incidence rate throughout a 12 year-period.
IL-10, and IL-17 levels did not modify [Figure, up]. Interestingly, highest cytokine levels were ... more IL-10, and IL-17 levels did not modify [Figure, up]. Interestingly, highest cytokine levels were achieved with UA at 6mg/dL, and further increases in UA were not followed by further parallel cytokine levels increase. For the B) in vivo study, 14 gouty patients were enrolled, median (p25-75) aged 64.5 (60.0, 70.3) years, 92.9% males. Median disease duration was 10.0 (5.8, 17.8) years, being 21.4% tophaceous. Blood tests showed a significant increase in serum UA after ULT dose modification/discontinuation (p=0.001), TNFa (p=0.004), and IL-6 (p=0.03), and a non-significant trend for IL-1b (p=0.055) [Figure, down]. TNFa levels strongly correlated with SUA levels (r=0.77, p=0.001), while the correlation of the other cytokines with SUA was found to be moderate (r=0.45, p=0.13 for IL-6; r=0.31, p=0.30 for IL-1b). Conclusions: Both in vitro and in vivo studies confirm that UA is able to enhance MSU-induced cytokine inflammatory response in a concentration-dependent manner. References: [1] Blood. 89:577. [2] Nature. 440:237. Acknowledgements: This study was funded by Menarini.
Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified int... more Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment, the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. Aims and methods: EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the American College of Rheumatology diagnostic criteria in participating centres. We aimed to characterise demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. Results: In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were women. On multivariate analysis, scleroderma subsets (dcSSc vs lcSSc), antibody status and age at onset of Raynaud's phenomenon, but not gender, were found to be independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis was more closely associated with clinical manifestations than were SSc subsets. Conclusion: dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction seemed to be superseded by an antibody-based classification in predicting some scleroderma complications. The EUSTAR MEDS database facilitates the analysis of clinical patterns in SSc, and contributes to the standardised assessment and monitoring of SSc internationally.
Objective In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangre... more Objective In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangrene. The aim of this study was to investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods We included patients from the EUSTAR database fulfilling the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. Centres were asked for supplementary data on traditional cardiovascular risk factors. We analysed the cross-sectional relationship between gangrene and its potential risk factors by univariable and multivariable logistic regression. Longitudinal data were analysed by Cox proportional hazards regression. Results 1757 patients were analysed (age 55.9 [14.5] years, disease duration 7.9 [10.3] years, male sex 16.7%, 24.6% diffuse cutaneous subset [dcSSc]). At inclusion, 8.9% of patients had current or previous digital gangrene, 16.1% had current digital ulcers (DUs) and 42.7% had ever had ...
Best Practice & Research Clinical Rheumatology, 2021
Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in &... more Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.
Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origi... more Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, characterized by multisystemic involvement and a potentially severe evolution. Pulmonary arterial hypertension (PAH) is a rare complication of SLE, with low 5-year survival. Case presentation. We are presenting the case of a female patient, aged 56 years old, diagnosed in 1992 with SLE with cutaneous manifestations (butterfly-shaped erythematous rash), joint manifestations (polyarthritis), serositis manifestations (massive pleuropericarditis), and immunological manifestations (positive anti-dsDNA antibodies, decreased C3), ignored therapeutically for a long time. In 2010 she complained of dyspnea on medium exertion and leg edemas, with marked increase of PAPs by echocardiography. She was diagnosed with severe PAH (confirmed by right heart catheterization) and in the “Marius Nasta” National Institute of Pneumology she started a treatment with an endothelin receptor antagonist (Bosentan...
The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim o... more The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. The mean SHAQ and HAQ scores of the 944 patients included were 0.87 ( s . d . = 0.66) and 0.92 ( s . d . = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 ...
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Papers by Carina Mihai