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Objectives Myocarditis is an overlooked manifestation of anti-synthetase syndrome (ASS). Our study describes the clinical and instrumental features of ASS myocarditis and evaluates the performance of cardiac MRI (CMRI) with mapping techniques in assisting diagnosis of ASS myocarditis. Methods Data from patients with ASS were retrospectively analysed. CMRI data for patients diagnosed with myocarditis, including late gadolinium enhancement (LGE), T2 ratio, T1 mapping, extracellular volume (ECV) and T2 mapping, were reviewed. Myocarditis was defined by the presence of symptoms and/or signs suggestive for heart involvement, including increased high-sensitive troponin T (hs-TnT) and/or N-terminal pro-brain natriuretic peptide (NT-proBNP), and at least an instrumental abnormality. The clinical features of patients with ASS with and without myocarditis were compared. A P -value of <0.05 was considered statistically significant. Results Among a cohort of 43 patients with ASS [median age 58 (48.0–66.0) years; females 74.4%; anti-Jo1 53.5%], 13 (30%) were diagnosed with myocarditis. In 54% of those 13 patients, myocarditis was diagnosed at clinical onset. All patients with ASS with myocarditis had at least one CMRI abnormality: increased ECV in all cases, presence of LGE in 91%, and increased T1 and T2 mapping in 91%. The 2009 Lake Louise criteria (LLC) were satisfied by 6 patients, and the 2018 LLC by 10 patients. With the updated LLC, the sensitivity for myocarditis improved from 54.6% to 91.0%. Patients with ASS with myocarditis were more frequently males (53% vs 13%; P  = 0.009) with fever (69% vs 17%; P  = 0.001), and had higher hs-TnT [88.0 (23.55–311.5) vs 9.80 (5.0–23.0) ng/l; P  < 0.001], NT-proBNP [525.5 (243.5–1575.25) vs 59.0 (32.0–165.5; P  = 0.013) pg/ml; P  = 0.013] and CRP [7.0 (1.7–15.75) vs 1.85 (0.5–2.86) mg/l; P  = 0.011] compared with those without myocarditis. Conclusion In ASS, myocarditis is frequent, even at clinical onset. Patients with ASS with myocarditis frequently presented with fever and increased CRP, suggesting the existence of an inflammatory phenotype. The use of novel CMRI mapping techniques may increase diagnostic sensitivity for myocarditis in ASS. [ABSTRACT FROM AUTHOR]

Objective Trained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production. Methods Monocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes. Results GCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production. Conclusions Myelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production. [ABSTRACT FROM AUTHOR]

Objectives To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to identify factors associated with, and variations in prescribing practices over time and across recruiting countries. Methods We included patients with SSc having a visit recorded in the EUSTAR database from January 2013 onward. We analysed the prevalence and the main features of GCs users, their exposure to GCs over time, and their GCs dosages. Multivariable linear regression was used to analyse the factors identified as associated with GCs intake duration. Time trends, and variations in GCs utilization across recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations. Results The 9819 patients included were mostly females (85%), the majority had lcSSc (73%), and the median age was 58 years. At baseline, 34% of patients (n  = 2769/8109) (48% dcSSc vs 29% lcSSc) were on GCs, and the median dose was 7.5 mg/day. GCs users were more frequently males and anti-Scl70 positive, and more commonly had dcSSc and more severe disease. On average, GCs users spent 25% of their follow-up time (median 33.2 months) on GCs, with no significant between-subsets difference. Notably, 33% (n  = 971/2959) and 22% (n  = 647/2959) of patients followed up for >1 year had received GCs for >6 and >12 months, respectively. Multivariable analysis showed that patient and disease characteristics poorly explained the variability in GCs exposure (adjusted- R 2 = 0.06, P  < 0.001). GCs utilization varied within and across countries, and gradually decreased over time (36% in 2013 vs 23% in 2018). Conclusions GCs are widely and long-term prescribed in SSc, with significant between-countries and within-country differences. A gradual decrease in their utilization has been observed. [ABSTRACT FROM AUTHOR]

Objectives Myocarditis in SSc is associated with a poor prognosis. Cardiac magnetic resonance (CMR) is the non-invasive diagnostic modality of choice for SSc myocarditis. Our study investigates the performance of the mapping techniques included in the revised Lake Louise criteria (LLC) for the identification of SSc myocarditis. Methods CMR data (right and left ventricular function and morphology, early and late gadolinium enhancement [LGE], T2 ratio, and T1 mapping, extracellular volume [ECV] and T2 mapping) of SSc patients diagnosed with myocarditis were reviewed. Myocarditis was defined by the presence of symptoms of SSc heart involvement with increased high-sensitive troponin T (hs-TnT) and/or NT-proBNP and at least an abnormality at 24 h ECG Holter and/or echocardiography and/or CMR. A P -value < 0.05 was considered as statistically significant. Results Nineteen patients (median age 54 [46–70] years; females 78.9%; diffuse SSc 52.6%; anti-Scl70+ 52.6%) were identified: 11 (57.9%) had echocardiographic, and 8 (42.8%) 24 h ECG Holter abnormalities. All patients had at least one CMR abnormality: LGE in 18 (94.7%), increased ECV in 10 (52.6%) and T2 mapping >50 ms in 15 (78.9%). Median T1 and T2 mapping were 1085 [1069–1110] ms and 53.1 [52–54] ms, respectively. T1 mapping directly correlated with NT-proBNP (r  = 0.620; P  = 0.005), ESR (r  = 0.601; P  = 0.008), CRP (r  = 0.685; P  = 0.001) and skin score (r  = 0.507; P  = 0.027); ECV correlated with NT-proBNP serum levels (r  = 0.702; P  = 0.001). No correlations emerged between T2 mapping and other parameters. Ten patients satisfied the 2009 LLC, 17 the 2018 LLC. With the new criteria including T2 mapping, the sensitivity improved from 52.6% to 89.5%. Conclusion The CMR mapping techniques improve the sensitivity to detect myocardial inflammation in patients with SSc heart involvement. The evaluation of T2 mapping increases diagnostic accuracy for the recognition of myocardial inflammation in SSc. [ABSTRACT FROM AUTHOR]

The recent ascent of right-wing populist movements in several countries has rekindled interest in understanding the causes of the rise of fascism in the interwar years. In this article, we argue that there was a strong link between the surge of support for the Socialist Party after World War I and the subsequent emergence of fascism in Italy. We first develop a source of variation in socialist support across Italian municipalities in the 1919 election based on war casualties from the area. We show that these casualties are unrelated to a battery of political, economic, and social variables before the war and had a major effect on socialist support (partly because the socialists were the main antiwar political movement). Our main result is that this boost to socialist support (that is "exogenous" to the prior political leaning of the municipality) led to greater local fascist activity as measured by local party branches and fascist political violence, and to significantly larger vote share of the Fascist Party in the 1921 and 1924 elections. We provide evidence that landowner associations and greater presence of local elites played an important role in the rise of fascism. Finally, we find greater likelihood of Jewish deportations in 1943–45 and lower vote share for Christian Democrats after World War II in areas with greater early fascist activity. [ABSTRACT FROM AUTHOR]

The article presents a case study which characterized the functional and metabolic outcomes of an activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation in a patient affected by Langerhans-related histiocytosis. Topics include case of a patient with articular, pituitary and skin involvement, comparison between the supernatant of tissue lesions and tissue culture medium, and clinical effectiveness MAPK pathway inhibition with selective MEK inhibitors in histiocytosis patients.

Objective The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. Methods This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Results Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). Conclusion CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD. [ABSTRACT FROM AUTHOR]

Objective To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD). Methods (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl−, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case–control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl− SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset. Results Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl−, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. Conclusion The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome. [ABSTRACT FROM AUTHOR]

The authors reflect on updates in the development of treatments for systemic sclerosis (SSc). Other topics include the systematic literature review showing the successful reduction of mortality and severity of vascular manifestations of SSc like pulmonary artery hypertension (PAH), scleroderma renal crisis (SRC), and digital ulcers (DU), and the various treatments like phosphodiesterase type-5 inhibitors, intravenous (iv) iloprost, and endotelin receptor-1 antagonists.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy and safety of apremilast in treating oral ulcers (OUs), the cardinal and high-disabling feature of Behçet's disease (BD). Methods Twelve consecutive patients affected by BD with recurrent/relapsing OUs resistant and/or intolerant to conventional therapy were enrolled and prospectively followed. The primary endpoint was the number of OUs at week 12. Secondary endpoints were modification from baseline to week 12 in Behçet's Syndrome Activity Score (BSAS), Behçet's Disease Current Activity Form (BDCAF) score, Behçet's Disease Quality of Life (BDQOL) scale and pain of OUs, as measured by a visual analogue scale (VAS). All adverse events (AEs) were recorded during follow-up. Non-parametric tests (Wilcoxon rank test) were used and a P -value <0.05 was considered statistically significant. Results After 12 weeks of apremilast, there was a significant reduction in the number of OUs [0.58 (s. d. 0.67) vs 3.33 (s. d. 1.45) at baseline, P = 0.02] that was paralleled by improvement in disease activity: BSAS was 16.8 (s. d. 9.1) [from 45.9 (s. d. 19.6) at baseline] (P = 0.02), BDCAF score was 0.72 (s. d. 0.65) [ vs 2.45 (s. d. 1.0) at baseline] (P = 0.04) and the VAS score for pain decreased to 23.3 (s. d. 13.7) [ vs 67.9 (s. d. 17.2) at baseline] (P = 0.02). Consistently, an improvement of BDQOL was assessed (P = 0.02). Clinical improvement led to complete steroid discontinuation in six patients and a tapering of the prednisone dose in two patients (P = 0.016). Colchicine was discontinued in six of nine patients (P = 0.031). AEs related to apremilast occurred in four patients (mainly due to gastrointestinal AEs), leading to drug discontinuation in all of them. Conclusion Our preliminary real-world data support the use of apremilast as an effective therapeutic strategy against BD-related recurrent OUs resistant or intolerant to first-line therapy. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study on the psychological, physical and behavioural changes in patient-reported outcomes in people living with fibromyalgia (FM) during the COVID-19 pandemic lockdowns in Italy. In the study, a Revised FM Impact Questionnaire (FIQR) assessment was conducted to analyze the subjects' health domains. Results showed the lockdowns have both positive and negative effects like worsened anxiety and increased physical activity, respectively.