Publications by authors named "Silvia Bosello"

62 Publications

Reply to: Individuality of the composition of the human microbiota by Fernández-Estupiñán et al.

Clin Exp Rheumatol 2021 Jan-Feb;39 Suppl 128(1):34. Epub 2021 Feb 19.

Institute of Rheumatology, Università Cattolica del Sacro Cuore, Rome, and Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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February 2021

Treatment strategy introducing immunosuppressive drugs with glucocorticoids ab initio or very early in giant cell arteritis: A multicenter retrospective controlled study.

J Transl Autoimmun 2020 28;3:100072. Epub 2020 Nov 28.

Rheumatology Unit, Catholic University of the Sacred Heart, Rome, Italy.

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.
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http://dx.doi.org/10.1016/j.jtauto.2020.100072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718148PMC
November 2020

Sarilumab use in severe SARS-CoV-2 pneumonia.

EClinicalMedicine 2020 Oct 2;27:100553. Epub 2020 Oct 2.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze di Laboratorio e Infettivologiche, Rome, Italy.

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 patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO/FiO:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO/FiO: 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.
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http://dx.doi.org/10.1016/j.eclinm.2020.100553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531933PMC
October 2020

Nailfold capillaroscopy findings in patients with coronavirus disease 2019: Broadening the spectrum of COVID-19 microvascular involvement.

Microvasc Res 2021 01 17;133:104071. Epub 2020 Sep 17.

Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Objective: Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients.

Methods: We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered.

Results: We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P = .027) and micro-thrombosis (P < .016), sludge flow (P = .001), and pericapillary edema (P < .001), while recovered patients showed a higher prevalence of enlarged capillaries (P < .001), loss of capillaries (P = .002), meandering capillaries (P < .001), and empty dermal papillae (P = .006).

Conclusion: COVID-19 patients present microvascular abnormalities at NVC. Currently ill and recovered subjects are characterized by a different distribution of elementary capillaroscopic alterations, resembling acute and post-acute microvascular damage. Further studies are needed to assess the clinical relevance of NVC in COVID-19.
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http://dx.doi.org/10.1016/j.mvr.2020.104071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494493PMC
January 2021

What can we learn from rapidly progressive interstitial lung disease related to anti-MDA5 dermatomyositis in the management of COVID-19?

Autoimmun Rev 2020 11 14;19(11):102666. Epub 2020 Sep 14.

Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy; Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2020.102666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489246PMC
November 2020

Multidisciplinary Evaluation of Interstitial Lung Diseases: New Opportunities Linked to Rheumatologist Involvement.

Diagnostics (Basel) 2020 Sep 2;10(9). Epub 2020 Sep 2.

Department of Diagnostic Imaging, Oncological Radiotherapy, and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

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 ( = 0.475, < 0.001) and family history of SARD ( = 0.491, < 0.001) and fair for the identification of extrapulmonary symptoms ( = 0.225, = 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 ( = 0.436, < 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.
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http://dx.doi.org/10.3390/diagnostics10090664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554734PMC
September 2020

Gut microbiota analysis in systemic sclerosis according to disease characteristics and nutritional status.

Clin Exp Rheumatol 2020 May-Jun;38 Suppl 125(3):73-84. Epub 2020 Aug 26.

Institute of Rheumatology, Università Cattolica del Sacro Cuore, and Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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.
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September 2020

Adult Onset Still's Disease and Radiotherapy treatment for breast cancer: Case report about management of this rare association and literature review.

Rep Pract Oncol Radiother 2020 Jul-Aug;25(4):527-532. Epub 2020 May 22.

Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy.

Aim: This manuscript focuses on the first experience in literature of a patient with a complicated Adult Onset Still's Disease-related heart failure who thereafter underwent adjuvant radiotherapy for left breast cancer.

Background: AOSD is a rare autoimmune inflammation-related disease, in which life-threatening pulmonary and cardiac complications can occur. In literature, AOSD is often associated with cancer, as paraneoplastic syndrome, but there are few data about primary AOSD and management of oncological therapies.

Materials And Methods: A patient who needed adjuvant breast cancer radiotherapy underwent tumour board evaluation to define feasibility of an RT in a patient with of a history of a heart life-threatening complication 2 years before AOSD. Results of the review were discussed by a multidisciplinary panel of experts that chose the type of surgery, radiotherapy and monitoring of patient.

Results: Literature review confirmed association of AOSD with BC in some pts and uniqueness of this treatment management experience. Patient underwent RT according to schedule of 40.05/2.67 Gy/fx on residual left breast and 10/2 Gy/fx on tumour bed with the gating technique. The panel chose to keep immunosuppressive therapy with anakinra. No complications were observed at clinical, ECG and laboratory examinations. Maximum toxicity was G2 skin. At first follow up AOSD signs of flare were negative.

Conclusion: In conclusion, when oncological treatments, especially radiotherapy, are mandatory for AOSD pts, multidisciplinary management and tailored monitoring are necessary to avoid acute adverse effects and allow pts to complete therapies.
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http://dx.doi.org/10.1016/j.rpor.2020.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251537PMC
May 2020

Safety and efficacy of rituximab biosimilar (CT-P10) in systemic sclerosis: an Italian multicentre study.

Rheumatology (Oxford) 2020 Dec;59(12):3731-3736

Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan.

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.
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http://dx.doi.org/10.1093/rheumatology/keaa136DOI Listing
December 2020

Ultrasonography involvement of carotid, upper and lower limb arteries in a large cohort of systemic sclerosis patients.

Int J Rheum Dis 2020 May 20;23(5):681-692. Epub 2020 Apr 20.

Rheumatology Unit, University of Verona, Verona, Italy.

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.
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http://dx.doi.org/10.1111/1756-185X.13824DOI Listing
May 2020

Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of the scleroderma spectrum.

Clin Exp Rheumatol 2020 May-Jun;38 Suppl 125(3):40-47. Epub 2020 Apr 14.

Istituto Clinico Humanitas, Rozzano, Milano, Italy.

Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation).

Methods: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc.

Results: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features.

Conclusions: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.
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September 2020

Comment on: Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis.

Rheumatology (Oxford) 2020 07;59(7):1782-1783

Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1093/rheumatology/keaa066DOI Listing
July 2020

Systemic sclerosis myocarditis has unique clinical, histological and prognostic features: a comparative histological analysis.

Rheumatology (Oxford) 2020 Sep;59(9):2523-2533

Rheumathology Division, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome.

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.
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http://dx.doi.org/10.1093/rheumatology/kez658DOI Listing
September 2020

Sixth-month remission as a predictor for twelve-month remission in polymyalgia rheumatica.

Clin Exp Rheumatol 2020 May-Jun;38(3):436-441. Epub 2019 Dec 11.

UOC di Reumatologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

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.
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September 2020

Measuring the T-cell down-regulation of TCR-zeta, ZAP-70 and CD28 in arthritis patients: An old tool for new biomarkers.

Eur J Immunol 2019 12 22;49(12):2195-2203. Epub 2019 Aug 22.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli - Catholic University of the Sacred Heart, Rome, Italy.

Low T-cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down-expression of TCR-related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR-ZETA, ZAP-70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)-derived T cells. In PB, ZETA-downregulation in CD4 CD28 and consequent CD4 CD28lowZETAlow cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA-downregulation extends to CD8 CD28null and/or CD8 CD28 cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETA-downregulation in CD4 CD28 may also lead to CD4 CD28 ZETAnull cell expansion, which strongly correlates with HAQ. In SF, ZETA-downregulation in CD8 CD28null and consequent CD8 CD28nullZETAlow/null cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP-downregulation in CD8 CD28 and consequent CD8 CD28lowZAPlow cell expansion strongly correlate with HAQ and DAS. ZETA-downregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down-regulation in CD8 CD28null, and non-rheumatoid arthritides showing significant down-regulation in CD4 CD28 . Altogether, we identified new molecular and cellular biomarkers of arthritis-related T-cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies.
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http://dx.doi.org/10.1002/eji.201847849DOI Listing
December 2019

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study.

Clin Exp Med 2019 Aug 15;19(3):357-366. Epub 2019 Apr 15.

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.
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http://dx.doi.org/10.1007/s10238-019-00553-yDOI Listing
August 2019

Quantitative and semi-quantitative computed tomography analysis of interstitial lung disease associated with systemic sclerosis: A longitudinal evaluation of pulmonary parenchyma and vessels.

PLoS One 2019 12;14(3):e0213444. Epub 2019 Mar 12.

Institute of Radiology, Pole of Imaging, Laboratory and Infectivology Sciences, Diagnostic Imaging Area, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Objectives: To evaluate interstitial lung disease associated with systemic sclerosis (SSc-ILD) and its changes during treatment by using quantitative analysis (QA) compared to semi-quantitative analysis (semiQA) of chest computed tomography (CT) scans. To assess the prognostic value of QA in predicting functional changes.

Materials And Methods: We retrospectively selected 35 consecutive patients with SSc-ILD with complete pulmonary functional evaluation, Doppler-echocardiography, immunological tests, and chest CT scan at both baseline and follow-up after immunosuppressive therapy. CT images were analyzed by two chest radiologists for semiQA and by a computational platform for texture analysis of ILD patterns (CALIPER) for QA. Concordance between semiQA and QA was tested. Traction bronchiectasis severity was scored. Analysis of ROC curves was performed.

Results: Seventy CT scans were analyzed and QA failed in 4/70 scans. Thus, the final population included 31/35 patients (51.3±12.1 years). QA had a weak-to-good concordance with semiQA (ICC reticular:0.275; ICC ground-glass:0.667) and QA correlated better than semiQA (r = -0.3 to -0.74 vs r = -0.3 to -0.4) with functional parameters. Both methods correlated with traction bronchiectases score and pulmonary artery diameter at CT. A pulmonary artery diameter ≥29mm distinguished patients with lower lung volumes and ILD extent greater than 39% (p<0.001). Changes in QA patterns during treatment were not accurate (AUC: 0.50 to 0.70; p>0.05) in predicting disease progression as assessed by functional parameters, whereas variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco% (AUC = 0.74; 95%CI: 0.54 to 0.93; p = 0.03).

Conclusions: Pulmonary QA of CT images can objectively quantify specific patterns of ILD changes during treatment in patients with SSc-ILD. Changes in QA patterns do not correlate with functional changes, but variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco%. Pulmonary artery diameter at CT reflects the interstitial involvement, identifying patients with more severe prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213444PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414027PMC
December 2019

Microvascular heart involvement in systemic autoimmune diseases: The purinergic pathway and therapeutic insights from the biology of the diseases.

Autoimmun Rev 2019 04 7;18(4):317-324. Epub 2019 Feb 7.

Institute of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli - Presidio Columbus, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2019.02.002DOI Listing
April 2019

Cardiac troponin T and NT-proBNP as diagnostic and prognostic biomarkers of primary cardiac involvement and disease severity in systemic sclerosis: A prospective study.

Eur J Intern Med 2019 02 23;60:46-53. Epub 2018 Oct 23.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy.

Objectives: The aim of our study was to define the role of high-sensitive cardiac troponin T (hs-cTnT) and NT-proBNP in identifying Systemic Sclerosis (SSc) patients with cardiac involvement and at higher risk of cardiac death.

Methods: Plasma hs-cTnT and NT-proBNP concentrations were measured in 245 SSc-patients.

Results: hs-cTnT and NT-proBNP levels were higher in SSc-patients than in healthy controls. Hs-cTnT levels were higher than 0.014 ng/ml in 32.3% SSc-patients, while NT-proBNP was above 125 pg/ml in 31.8% of them, irrespective of classical cardiovascular risk factor and of pulmonary arterial hypertension. Elevated hs-cTnT and NT-proBNP were associated with diffuse skin involvement and directly correlated with the skin score. Patients with increased cardiac markers presented a lower left-ventricular ejection fraction (LVEF) and a higher rate of right bundle branch block (RBBB) on electrocardiogram (ECG) compared to patients with normal cardiac enzymes. During the follow-up, 12 SSc-patients experience a disease-related death; 9 of these were directly related to cardiac involvement (sudden cardiac death or heart failure) and the majority of them occurred among patients with increase of at least one cardiac biomarker. Long-term survival was worse in patients with increase of both cardiac biomarkers.

Conclusions: Evaluation of hs-cTnT and NT-proBNP levels may provide a tool to screen non-invasively SSc-patients for heart involvement. A higher incidence of impaired systolic function, ECG abnormalities and a poor outcome in SSc-patients with elevated cardiac enzymes suggests that they may be valuable screening biomarkers to detect a cardiac damage at early stages and to improve risk stratification.
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http://dx.doi.org/10.1016/j.ejim.2018.10.013DOI Listing
February 2019

European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis.

Rheumatology (Oxford) 2019 02;58(2):254-259

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.

Objectives: To validate enhanced liver fibrosis (ELF) test and its components-amino-terminal propeptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and HA-as biomarkers of fibrosis in SSc in an independent, international, multicentre cohort.

Methods: Two hundred and fifty-four SSc patients from six Rheumatology Centres were included. Sera were collected and stored according to EUSTAR biobanking recommendations and analysed through automated high throughput diagnostics. Statistical analysis was performed with SPSS software.

Results: Two hundred and forty-seven SSc patients (mean age 55.7 ± 13.9 years, 202 F) were analysed. ELF score, TIMP-1 and PIIINP levels were higher in males (P = 0.0197, P = 0.0107, P = 0.0108 respectively) and in dcSSc (P = 0.001, P = 0.0008, P < 0.0001 respectively). ELF score and the single markers significantly correlated with modified Rodnan skin score (r = 0.37, P < 0.0001), disease activity and severity (P < 0.0001 for all markers, except for HA P = 0.0001) and inversely with forced vital capacity, (FVC) % (TIMP-1, r = -0.21, P = 0.0012; PIIINP, r = -0.26, P = 0.0001), TLC% (ELF score, r = -0.20, P = 0.0036; TIMP-1, r = -0.32, P < 0.0001; PIIINP, r = -0.28, P < 0.0001), diffusion capacity of the lung for carbon monoxide (DLCO) % (P < 0.0001 for all markers, except for HA P = 0.0115). Multivariate analysis indicated that age (P < 0.001), modified Rodnan skin score (P < 0.001) and DLCO% (P = 0.005) were independently associated with ELF score.

Conclusion: Between the first and this validation studies, the value of the ELF score as independent marker of skin and lung involvement in SSc is confirmed in 457 patients. A longitudinal study is on-going to identify an SSc specific algorithm with predictive value for skin and lung progression.
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http://dx.doi.org/10.1093/rheumatology/key271DOI Listing
February 2019

Characterization of inflammatory cell infiltrate of scleroderma skin: B cells and skin score progression.

Arthritis Res Ther 2018 04 18;20(1):75. Epub 2018 Apr 18.

Unità Operativa Complessa di Reumatologia, Istituto di Reumatologia e Scienze Affini, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: The purpose of this study was to investigate the frequency and the distribution of inflammatory cell infiltrate in two sets of cutaneous biopsies derived from clinically affected and unaffected skin in patients with systemic sclerosis (SSc) and to test correlation between the cell infiltrate and the progression of skin involvement.

Methods: Skin was immunohistochemically assessed to identify CD68, CD3, CD20 and CD138-positive (+) cells in clinically affected and unaffected skin in 28 patients with SSc. Patients were followed for 6 months and the characteristics of the infiltrate were analyzed according to disease duration, clinical features and skin involvement progression.

Results: In all SSc cutaneous specimens, cellular infiltrates were found in a perivascular location predominantly in the mid and deeper portions of the dermis. All the analyzed biopsies showed a CD3 and CD68 cell infiltrate and the mean number of CD3 and of CD68 cells was higher in clinically involved skin (CD3, 71.7 ± 34.6 and CD68, 26.3 ± 8.4, respectively) than in clinically uninvolved skin (CD3, 45.7 ± 36.0 and CD68, 13.6 ± 6.1, respectively) (p < 0.001 for both comparisons). CD20 cells were found in 17 (60.7%) patients and in these patients the mean number of CD20 cells was higher in clinically involved (4.7 ± 5.9) than in uninvolved skin (1.9 ± 2.9), (p = 0.04). There was a greater number of CD20 cells in patients with early SSc compared with patients with long-standing disease. CD138 cells were found in 100% of biopsies of clinically involved skin and in 89.3% of biopsies of uninvolved skin. The mean number of CD138 cells was higher in clinically involved skin (3.6 ± 2.3) than in clinically uninvolved skin (1.9 ± 1.7), (p < 0.001). Seven patients experienced more than 20% worsening in the skin score after 6 months of follow up; all of them had a CD20 skin infiltrate on biopsy of clinically involved skin.

Conclusions: Our results confirm that mononuclear cells are present in the skin of all patients with SSc, underlining the role of inflammatory cell infiltrates in skin involvement in SSc. B cells in the skin seem to characterize patients with early diffuse skin disease and to correlate with skin progression.
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http://dx.doi.org/10.1186/s13075-018-1569-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907298PMC
April 2018

Free light chains of immunoglobulins in patients with systemic sclerosis: correlations with lung involvement and inflammatory milieu.

J Clin Pathol 2018 Jul 31;71(7):620-625. Epub 2018 Jan 31.

Institute of Rheumatology and Affine Sciences, Department of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.

Aim: Humoral immunity and B cells are thought to play an important role in the pathophysiology of the systemic sclerosis (SSc). The production of free light chains (FLC) of immunoglobulins is abnormally high in several pathological autoimmune conditions and reflects B cell activation. Furthermore, FLCs demonstrated different biological activities including their capability to modulate the immune system, proteolytic activity and complement cascade activation. The aims of this study are to determine the FLC levels in patients with SSc compared with healthy controls (HC) and to study their possible association with organ involvement and disease characteristics.

Methods: Sixty-five patients with SSc and 20 HC were studied. Clinical and immunological inflammatory characteristics were assessed for all the patients with SSc. κ-FLC and λ-FLC, interleukin 6 (IL-6) and B cell activating factor levels were measured.

Results: The mean serum κ-FLC levels and FLC ratio were significantly higher in patients with SSc compared with HC, while the serum λ-FLC levels were comparable.The levels of FLC were comparable in patients with diffuse skin disease and limited skin involvement, while κ-FLC levels were increased in patients with restrictive lung (forced vital capacity (FVC) <80%) disease (26.4±7.4 mg/L) when compared with patients with FVC ≥80% (19.6±7.3 mg/L, P=0.009). In patients with SSc, the levels of serum κ-FLC level directly correlated with the IL-6 levels (R=0.3, P=0.001) and disease activity (R=0.4, P=0.003).

Conclusions: FLC levels are elevated in SSc and high levels are associated with lung involvement and with a higher degree of inflammation, supporting a possible role of B cell activation in the pathophysiology of the disease.
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http://dx.doi.org/10.1136/jclinpath-2017-204656DOI Listing
July 2018

Environmental Pollution by Benzene and PM and Clinical Manifestations of Systemic Sclerosis: A Correlation Study.

Int J Environ Res Public Health 2017 10 26;14(11). Epub 2017 Oct 26.

Institute of Public Health-Hygiene Section, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.

Atmospheric air pollution has been associated with a range of adverse health effects. The environment plays a causative role in the development of Systemic Sclerosis (SSc). The aim of the present study is to explore the association between particulate (PM) and benzene (B) exposure in Italian patients with systemic sclerosis and their clinical characteristics of the disease. A correlation study was conducted by enrolling 88 patients who suffer from SSc at the Fondazione Policlinico "A. Gemelli" in Rome (Italy) in the period from January 2013 to January 2014. The average mean concentrations of B (in 11 monitoring sites) and PM (in 14 sites) were calculated using data from the Regional Environmental Protection Agency's monitoring stations located throughout the Lazio region (Italy) and then correlated with the clinical characteristics of the SSc patients. Of the study sample, 92.5% were female. The mean age was 55 ± 12.9 years old and the mean disease duration from the onset of Raynaud's phenomenon was 13.0 ± 9.4 years. The Spearman's correlation showed that concentrations of B correlate directly with the skin score (R = 0.3; ≤ 0.05) and inversely with Diffusing Lung Carbon Monoxide (DLCO) results (R = -0.36; = 0.04). This study suggests a possible role of B in the development of diffuse skin disease and in a worse progression of the lung manifestations of SSc.
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http://dx.doi.org/10.3390/ijerph14111297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707936PMC
October 2017

QTc interval prolongation in Systemic Sclerosis: Correlations with clinical variables and arrhythmic risk.

Int J Cardiol 2017 07;239:33

Institute of Rheumatology and Affine Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy.

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http://dx.doi.org/10.1016/j.ijcard.2017.03.088DOI Listing
July 2017

Baseline Shoulder Ultrasonography Is Not a Predictive Marker of Response to Glucocorticoids in Patients with Polymyalgia Rheumatica: A 12-month Followup Study.

J Rheumatol 2017 02 15;44(2):241-247. Epub 2016 Dec 15.

From the Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.

Objective: In this study, we evaluated whether ultrasound (US) subdeltoid bursitis (SB) and/or biceps tenosynovitis (BT) presence at baseline could represent a predictive marker of response to standard therapy after 12 months of followup, and whether a positive US examination could highlight the need of higher maintenance dosage of glucocorticoids (GC) at 6 and 12 months in patients with polymyalgia rheumatica (PMR).

Methods: Sixty-six consecutive patients with PMR underwent bilateral shoulder US evaluations before starting therapy and after 12 months of followup. Absence of girdle pain and morning stiffness (clinical remission) and laboratory variables were evaluated. After diagnosis, all patients were treated with prednisone.

Results: At baseline, SB and/or BT were present in 46 patients (70%), of whom 33 (72%) became negative while 13 (28%) remained positive at the 12-month US evaluation. All patients rapidly achieved a clinical remission, and at 6 months 26 (39%) also achieved a laboratory variable normalization. According to US positivity at baseline, no difference was found in remission or relapse rate after 12 months. Thirty patients (46%) at 6 months and 7 (11%) at 12 months were still taking more than 5 mg/day of prednisone. According to the US pattern at baseline, no difference was found in the mean GC dose at 6 and 12 months.

Conclusion: In patients with PMR, the presence of SB and/or BT on US at diagnosis is not a predictive marker of GC response or of a higher GC dosage to maintain remission in a 12-month prospective followup study.
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http://dx.doi.org/10.3899/jrheum.160090DOI Listing
February 2017

The prognostic significance of the Birmingham Vasculitis Activity Score (BVAS) with systemic vasculitis patients transferred to the intensive care unit (ICU).

Medicine (Baltimore) 2016 Nov;95(48):e5506

Division of Rheumatology, Institute of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, Catholic University School of Medicine, Rome Operative Unit of Rheumatology, Department of Internal Medicine, University of Padua, Padua, Italy.

Systemic vasculitides represent a heterogeneous group of diseases that share clinical features including respiratory distress, renal dysfunction, and neurologic disorders. These diseases may often cause life-threatening complications requiring admission to an intensive care unit (ICU). The aim of the study was to evaluate the validity and responsiveness of Birmingham Vasculitis Activity Score (BVAS) score to predict survival in patients with systemic vasculitides admitted to ICU.A retrospective study was carried out from 2004 to 2014 in 18 patients with systemic vasculitis admitted to 2 different Rheumatology divisions and transferred to ICU due to clinical worsening, with a length of stay beyond 24 hours. We found that ICU mortality was significantly associated with higher BVAS scores performed in the ward (P = 0.01) and at the admission in ICU (P = 0.01), regardless of the value of Acute Physiology And Chronic Health Evaluation (APACHE II) scores (P = 0.50). We used receiver-operator characteristic (ROC) curve analysis to evaluate the possible cutoff value for the BVAS in the ward and in ICU and we found that a BVAS > 8 in the ward and that a BVAS > 10 in ICU might be a useful tool to predict in-ICU mortality.BVAS appears to be an excellent tool for assessing ICU mortality risk of systemic vasculitides patients admitted to specialty departments. Our experience has shown that performing the assessment at admission to the ward is more important than determining the evaluation before the clinical aggravation causing the transfer to ICU.
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http://dx.doi.org/10.1097/MD.0000000000005506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134801PMC
November 2016

Thymosin β and β in Sjögren's syndrome: saliva proteomics and minor salivary glands expression.

Arthritis Res Ther 2016 10 6;18(1):229. Epub 2016 Oct 6.

Division of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.

Background: In the present study, we investigated whether thymosin β (Tβ) in saliva and in minor salivary glands is differentially expressed in patients with primary Sjögren's syndrome (pSS) and patients with autoimmune diseases (systemic sclerosis [SSc], systemic lupus erythematosus [SLE], and rheumatoid arthritis [RA], with and without sicca syndrome [ss]).

Methods: Saliva specimens of nine patients with pSS, seven with ss/SSc, seven with ss/SLE, seven with ss/RA, seven with SSc, seven with SLE, and seven with RA, as well as ten healthy subjects, were analyzed using a high-performance liquid chromatograph coupled with a mass spectrometer equipped with an electrospray ionization source to investigate the presence and levels of Tβ, Tβ sulfoxide, and Tβ. Immunostaining for Tβ and Tβ was performed on minor salivary glands of patients with pSS and ss.

Results: Tβ levels were statistically higher in patients with pSS with respect to the other subgroups. Tβ was detectable in 66.7 % of patients with pSS and in 42.8 % of those with ss/SSc, while Tβ sulfoxide was detectable in 44.4 % of patients with pSS and in 42.9 % of those with ss/SSc. Tβ and Tβ sulfoxide were not detectable in patients without associated ss and in healthy control subjects. Regarding thymosin immunostaining, all patients had immunoreactivity for Tβ, and a comparable distribution pattern in the four different subgroups of patients was observed. Tβ immunoreactivity was present in patients with ss/SSc and those with ss/SLE, while it was completely absent in patients with pSS and those with ss/RA.

Conclusions: Our data show that higher salivary Tβ expression characterizes patients with pSS, while Tβ sulfoxide and Tβ salivary expression was selectively present in patients with sicca symptoms. Moreover, at the immunohistochemical level in patients with pSS, minor salivary glands showed a peculiar pattern characterized by immunostaining for Tβ in acinar cells in the absence of any reactivity for Tβ. These findings, taken together, suggest a different role for Tβ and Tβ in patients with pSS who have ss and other autoimmune disease.
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http://dx.doi.org/10.1186/s13075-016-1134-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053072PMC
October 2016

Prognostic Role of Ventricular Ectopic Beats in Systemic Sclerosis: A Prospective Cohort Study Shows ECG Indexes Predicting the Worse Outcome.

PLoS One 2016 21;11(4):e0153012. Epub 2016 Apr 21.

Institute of Rheumatology and Affine Sciences - Department of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.

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,p<0.0001). Patients with VEBS>1190/24h 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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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153012PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839708PMC
February 2017