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Objectives: Cardiovascular involvement in systemic lupus erythematosus (SLE) is frequent but little is known about possible distinctive traits of SLE-related myocarditis (myoSLE) in comparison to patients with SLE (onlySLE) or myocarditis alone (onlyMyo)., Methods: A retrospective analysis was performed comparing patients with myoSLE (n = 25) from three centres with consecutive patients with onlySLE (n = 279) and onlyMyo (n = 88). SLE patients were dichotomised by disease duration ≤1 vs >1 year into recent onlySLE/early myoSLE vs longstanding onlySLE/late myoSLE. Further stratification into disease duration of 1-5, 5-10 and >10 years was also performed. SLE disease activity index 2000 (SLEDAI-2K) was used to estimate disease activity. Myocarditis was diagnosed through biopsy or magnetic resonance., Results: Women were significantly more frequent among myoSLE than among onlyMyo (72% vs 43%; p= 0.013). Compared with onlyMyo, myoSLE patients had a higher frequency of conduction abnormalities (22% vs 5%; p= 0.046) and presented with numerically higher frequencies of left ventricular function compromise (48% vs 30%), along with higher pro-brain natriuretic peptide levels. Inflammation markers were higher in myoSLE compared with onlyMyo and to patients with onlySLE with >10 years of disease duration. SLEDAI-2K was significantly higher in late myoSLE than in longstanding onlySLE. Antiphospholipid syndrome was more frequent in myoSLE than in onlySLE. Multivariate analysis showed an association among myoSLE, anti-beta-2-glycoprotein I antibodies (aB2GPI, p= 0.014) and a higher number of involved British Isles Lupus Assessment Group domains in patient history (p= 0.003)., Conclusion: myoSLE has unique clinical traits compared with other forms of myocarditis and is associated with aB2GPI and a more severe SLE course., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO&#95;ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients., Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO&#95;ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO&#95;ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire., Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO&#95;ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain ( P  < 0.001). Patients on glucocorticoid therapy ( n  = 199) had higher scores in all domains, especially in the physical function domain ( P  < 0.001), compared with patients not on glucocorticoid therapy ( n  = 77). Furthermore, patients who had at least one relapse of disease ( n  = 114) had higher scores compared with those who had never had one ( n  = 161) in any domain ( P  < 0.05). Finally, nearly 30% of the patients reported work impairment., Conclusion: The AAV-PRO&#95;ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Population aging and multimorbidity challenge health system sustainability, but the role of assistance-related variables rather than individual pathophysiological factors in determining patient outcomes is unclear. To identify assistance-related determinants of sustainable hospital healthcare, all patients hospitalised in an Internal Medicine Unit (n = 1073) were enrolled in a prospective year-long observational study and split 2:1 into a training (n = 726) and a validation subset (n = 347). Demographics, comorbidities, provenance setting, estimates of complexity (cumulative illness rating scale, CIRS: total, comorbidity, CIRS-CI, and severity, CIRS-SI subscores) and intensity of care (nine equivalents of manpower score, NEMS) were analysed at individual and Unit levels along with variations in healthcare personnel as determinants of in-hospital mortality, length of stay and nosocomial infections. Advanced age, higher CIRS-SI, end-stage cancer, and the absence of immune-mediated diseases were correlated with higher mortality. Admission from nursing homes or intensive care units, dependency on activity of daily living, community- or hospital-acquired infections, oxygen support and the number of exits from the Unit along with patient/physician ratios were associated with prolonged hospitalisations. Upper gastrointestinal tract disorders, advanced age and higher CIRS-SI were associated with nosocomial infections. In addition to demographic variables and multimorbidity, physician number and assistance context affect hospitalisation outcomes and healthcare sustainability.

Competing Interests: Competing interests: None declared.

Objectives: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN)., Methods: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease., Results: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases., Conclusion: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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 &lt; 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 &gt;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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan has no recognized role in diagnosis, prognosis, and disease monitoring in patients with arrhythmic myocarditis., Objectives: The purpose of this study was to investigate the value of FDG-PET scan in arrhythmic myocarditis., Methods: The authors enrolled 75 consecutive patients (age 47 ± 14 years, 65% men) undergoing FDG-PET scan for arrhythmic myocarditis. Myocarditis was diagnosed by endomyocardial biopsy (EMB) and, whenever applicable, cardiac magnetic resonance (CMR)., Results: Indications for FDG-PET scan included either contraindication to CMR (n = 50) or mismatch between CMR and EMB (n = 25). Overall, 50 patients (67%) had positive FDG-PET. Sensitivity was 75% referring to EMB, and 73% to CMR. Specificity was 67% referring to EMB, and 59% to CMR. FDG-PET accuracy was lower in the presence of borderline myocarditis, and either late (>30 days) or on-immunosuppression FDG-PET scanning. Anteroseptal distribution pattern, found in 12 of 50 (24%) patients including 7 of 7 cardiac sarcoidosis cases, was associated with greater occurrence of ventricular arrhythmias and atrioventricular blocks in 4.2 ± 1.7 years of follow-up (10 of 12 vs 7 of 38, and 7 of 12 vs 0 of 38, respectively; both P < 0.001). In 39 patients (52%), FDG-PET was repeated by 13 ± 2 months, allowing immunosuppression withdrawal after FDG uptake normalization either by first (76%) or second reassessment (24%)., Conclusions: FDG-PET scan may be a clinically useful diagnostic technique in arrhythmic myocarditis, in particular when CMR is unsuitable because of irregular heartbeat or implantable cardioverter-defibrillator-related artifacts. Anteroseptal FDG distribution is associated with a worse arrhythmic outcome and should raise the suspicion of cardiac sarcoidosis. During follow-up, repeated FDG-PET allows myocarditis monitoring to guide immunosuppression withdrawal., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing eosinophil-rich vasculitis. Specific cardiomyopathy (CM) was described in early studies as the most important predictor of mortality. We aimed to revisit EGPA-related CM and investigate its outcome in recent decades., Methods: We reviewed all EGPA patients managed from 2000 to 2019 in our vasculitis clinic. Baseline characteristics and outcomes were analysed. EGPA-related CM was defined as clinical or extra-clinical manifestations of patent myocardial involvement, after exclusion of other causes., Results: We included 176 patients. The median age was 47 years [interquartile range (IQR) 36-58 years]. Specific CM was observed in 70 patients (40%). Cardiac symptoms were observed in 81% of CM+ patients, including mainly typical or atypical chest pain and peripheral oedema. Abnormal ECG, transthoracic echocardiography and cardiac MRI (CMRI) were found in 72%, 72% and 99% of CM+ patients, respectively, contrasting with abnormalities in 32%, 38% and 60% of CM-negative patients, respectively. Late gadolinium enhancement (LGE) was the most frequent abnormality on CMRI (70%). CM+ patients were less frequently ANCA-positive, had less frequent peripheral neuropathy and had higher eosinophil count. Major adverse cardiovascular events (MACEs) occurred in 13% of patients, both in CM+ and CM- patients. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs. Four patients died, but none from cardiac causes., Conclusion: Specific cardiomyopathy is frequent in EGPA, especially in ANCA-negative patients with high eosinophil counts. Long-term outcome was better than previously reported. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To evaluate effectiveness and safety of infliximab dose escalation in Takayasu arteritis (TAK) patients. To identify factors associated with refractoriness to standard-dose infliximab., Methods: Medical records of infliximab-treated TAK patients from a large single-centre observational cohort were reviewed. Infliximab therapy duration, concomitant therapies, and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained infliximab standard-dose and those who needed dose-escalation was performed. Factors associated with refractoriness to standard dose were analysed., Results: Forty-one patients were included. Starting infliximab dose was 5 mg/kg 6-weekly and 28 patients (68%) needed dose escalation. Persistence/recurrence of clinical symptoms was the most frequent reason for escalation. Median therapy duration was 39 (IQR, 26-61) months in the standard-dose group and 68 (38-87) months in the intensified-dose group. In the intensified-dose-group, infliximab was suspended in eight patients (29%) after a median of 38 (31-71) months, due to loss of response (n = 7) or patient's request (n = 1). Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient) and received a higher cumulative steroid dose (1.7 [1.6-2.3] vs 1.3 [1-1.6] g/month of prednisone). Three patients from the intensified-dose group had serious infections; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, age at diagnosis and age at infliximab start were associated with infliximab escalation., Conclusion: In TAK, dose escalation is safe and allows to optimise infliximab durability in refractory patients. Younger patients seem to be more refractory to standard dosages., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To compare the presenting features and outcomes of patients with cranial-limited (C-) and large-vessel (LV-) giant cell arteritis (GCA). Methods: Data from our GCA cohort were collected retrospectively. Patients who underwent total-body large-vessel imaging within 10 days after commencing steroid therapy were included. Patients with LV involvement were classified as LV-GCA. Presenting features, treatments, and outcomes of LV-GCA and C-GCA patients were compared. Results: 161 patients were included (LV-GCA, n = 100). At baseline, LV-GCA patients were younger than those with C-GCA (73.2 ± 8.9 vs 76 ± 8.8 years, p = 0.018) and had a longer delay to diagnosis (3.5 ± 4.6 vs 2.3 ± 4.9 months, p = 0.001). C-GCA patients had a higher incidence of headache (p = 0.006) and ischaemic optic neuropathy (p < 0.001), whereas LV-GCA patients had more systemic symptoms (fever, p = 0.002; fatigue, p < 0.001; weight loss, p < 0.001; night sweats, p = 0.015) and dry cough (p = 0.031). Corrected cumulative prednisone dose, relapse-free survival, relapse-rate, and incidence of ascending aortic aneurysms were not significantly different between the two subgroups. A steroid-sparing agent was added in 73% of LV- and 55.7% of C-GCA patients (p = 0.027), but was introduced more frequently at baseline in LV-GCA patients (52% vs 23.5%, p = 0.006). LV-GCA patients initially treated with glucocorticoid monotherapy relapsed sooner (relapse-free survival, HR = 0.56, 95% CI 0.41-0.78, p < 0.001) and had a higher relapse rate (relapses per 10 person-years, 6.73 ± 11.50 vs 3.82 ± 10.83, p = 0.011). Conclusion: LV-GCA patients were younger at diagnosis and suffered a longer diagnostic delay. The outcomes of the two subgroups were similar. An earlier introduction of steroid-sparing agents in LV-GCA patients might have played a positive role.

Competing Interests: Conflicts of interest and sources of funding: CC received speaking fees from Pfizer, Roche, and Novartis. GDL received speaking fees from Pfizer and received consultation honoraria from Novartis, SOBI, and Celgene. GC received speaking fees and consultation honoraria from Pfizer, Novartis, and SOBI. LD received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI. AT, SilS, GP, SimS, AP and AE declare no conflicts of interest. The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unrestricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and SOBI.

Objectives: Infliximab (IFX) is widely used in patients with refractory Takayasu arteritis (TAK). Recently, the IFX-biosimilar CT-P13 has been introduced for the treatment of inflammatory diseases. The aim of this study was to assess the efficacy and safety of CT-P13 in patients with refractory TAK. Methods: In this prospective, open-label, single-center trial, TAK patients either already on treatment with IFX-originator (switch group) or never treated with IFX (naïve group) received CT-P13 for 52 weeks. The primary outcomes of the study were: (i) number of patients with active disease at month 6; (ii) incidence of treatment-emergent adverse events at month 12. Disease activity was assessed at month 6 and month 12 by clinical evaluation (ITAS-2020, ITAS-ESR, and ITAS-CRP scores) and imaging assessment [magnetic resonance angiography (MRA) and (18F)-FDG-PET]. Results: 23 patients were recruited (21 switch, 2 naïve). At baseline, 7 patients (32%) were classified as active. At month 6, one patient voluntarily dropped out and 7 patients were still active (30%), including one patient started on a different bDMARD at month 2 due to poor disease control. Mean daily dose of prednisone equivalent was significantly lower than baseline (4.2 ± 1.9 mg vs. 4.8 ± 2.1 mg, p = 0.009). At month 12, another patient was excluded because of pregnancy desire. Five patients were classified as active (24%), including two patients started on a different bDMARD at month 2 and month 6. Mean daily dose of prednisone equivalent was significantly lower than baseline (3.3 ± 2.6, p = 0.034). No patient experienced side effects during CT-P13 infusion. Overall, one patient experienced grade 1 adverse event and 9 patients experienced grade 2 adverse events. In no case hospitalization was required. CT-P13 retention rate was 90.9% at month 6 and 90.4% at month 12. Conclusion: In this study, the use of IFX-biosimilar CT-P13 in patients with refractory TAK showed satisfying efficacy and safety profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Campochiaro, Tomelleri, Sartorelli, Sembenini, Papa, Fallanca, Picchio, Cavalli, De Cobelli, Baldissera and Dagna.)

Competing Interests: The authors declare no conflict of interest.

Background: Myocarditis lacks systematic characterization in COVID-19 patients., Methods: We enrolled consecutive patients with newly diagnosed myocarditis in the context of COVID-19 infection. Diagnostic and treatment strategies were driven by a dedicated multidisciplinary disease unit for myocarditis. Multimodal outcomes were assessed during prospective follow-up., Results: Seven consecutive patients (57% males, age 51 ± 9 y) with acute COVID-19 infection received a de novo diagnosis of myocarditis. Endomyocardial biopsy was of choice in hemodynamically unstable patients ( n = 4, mean left ventricular ejection fraction (LVEF) 25 ± 9%), whereas cardiac magnetic resonance constituted the first exam in stable patients ( n = 3, mean LVEF 48 ± 10%). Polymerase chain reaction (PCR) analysis revealed an intra-myocardial SARS-CoV-2 genome in one of the six cases undergoing biopsy: in the remaining patients, myocarditis was either due to other viruses ( n = 2) or virus-negative ( n = 3). Hemodynamic support was needed for four unstable patients (57%), whereas a cardiac device implant was chosen in two of four cases showing ventricular arrhythmias. Medical treatment included immunosuppression (43%) and biological therapy (29%). By the 6-month median follow-up, no patient died or experienced malignant arrhythmias. However, two cases (29%) were screened for heart transplantation., Conclusions: Myocarditis associated with acute COVID-19 infection is a spectrum of clinical manifestations and underlying etiologies. A multidisciplinary approach is the cornerstone for tailored management.

Objectives: Biologic drugs (bDMARD), especially TNF-α-inhibitors (TNFi), are used in refractory Takayasu's arteritis (TAK) patients. Up to 23% of patients are switched to a different bDMARD because of inefficacy. No data are available on which strategy is more efficient after TNFi failure. The aim of our study is to evaluate whether a switch or swap strategy should be preferred in TAK patients failing TNFis., Methods: TAK patients treated with a second bDMARD after the failure of the first TNFi were identified from 3 referral centres. Patients were classified as switch if treated with a different TNFi, and swap if treated with a non-TNFi bDMARD. Baseline features were evaluated. Efficacy and safety of the second bDMARD at 6 and 12 months were assessed and a comparison between switch and swap patients was made., Results: Twenty-four TAK patients were identified. Eleven patients (46%) were switched and 13 patients (54%) were swapped (12 to tocilizumab, 1 to ustekinumab). Baseline features of patients in the 2 groups were comparable. At 12 months, the second bDMARD was suspended in 4 switch (36%) and in 5 swap (42%) patients. Second biologic drug survival and relapse-free survival were equivalent between the two groups at 6 and 12 months. A vascular worsening was observed in 4 switch (40%) and 2 swap (25%) patients. Severe infections, myocardial infarction, ischemic stroke or cancer were recorded in no patient., Conclusions: Our retrospective study suggests that in first-line TNFi failure TAK patients both switch and swap strategies can be considered suitable approaches.

Objective: To describe the efficacy and safety of biologics for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA)., Methods: A retrospective European collaborative study was conducted in patients with EGPA who received treatment with biologics for refractory and/or relapsing disease., Results: Among the 147 patients with EGPA included in the study, 63 received rituximab (RTX), 51 received mepolizumab (MEPO), and 33 received omalizumab (OMA). At the time of inclusion, the median Birmingham Vasculitis Activity Score (BVAS) was 8.5 (interquartile range [IQR] 5-13) in the RTX group, while the median BVAS in the OMA group was 2 (IQR 1-4.5) and the median BVAS in the MEPO group was 2 (IQR 1-5). In patients receiving RTX, the median BVAS declined both at 6 months (median 1, IQR 0-4.5) and at 12 months (median 0, IQR 0-2), and the frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 49%, 24%, 24%, and 3%, respectively. For the treatment of glucocorticoid (GC)-dependent asthma, patients who received MEPO had a much better GC-sparing effect and overall response than did patients who received OMA. The frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 15%, 33%, 48%, and 4%, respectively, in the OMA group and 78%, 10%, 8%, and 4%, respectively, in the MEPO group. Remission rates at 12 months were 76% and 82% among patients receiving MEPO at a doses of 100 mg and 300 mg, respectively., Conclusion: These results suggest that RTX could be effective in treating relapses of EGPA vasculitis. MEPO is highly effective with a good safety profile in patients with GC-dependent asthma. Our data suggest that 100 mg MEPO monthly could be an acceptable dosage for first-line therapy in selected instances of EGPA, recognizing, however, that this has not been compared to the validated dosage of 300 mg monthly., (© 2020, American College of Rheumatology.)

Objective: The COVID-19 pandemic has raised questions about the management of systemic immunosuppressive treatments for rheumatic conditions. It is well known that rheumatic patients are at risk of developing infections because of their immunocompromised state. Moreover, drugs such as hydroxychloroquine or tocilizumab that are widely used to treat rheumatic diseases are now being used to treat COVID-19. The aim of this multicentre retrospective study of rheumatic patients in the Italian regions of Lombardy and Marche was to determine whether patients receiving biological or small molecules treatment are more susceptible to the development of COVID-19 than the general population., Methods: The local registry data of 10,260 rheumatic patients being treated with bDMARDs or small molecules were evaluated from 15 March to 23 April 2020. The final analysis was based on the registry data relating to 7.204, telephone contacts and/or outpatient visits., Results: Forty-seven of the 7.204 patients were diagnosed with COVID-19, seven of whom died; the patients who had symptoms resembling those of COVID-19 but had negative swabs were considered negative for the disease. The overall infection rate was 0.65, and the crude case fatality risk (CFR) in the patients with COVID-19 was 14.9%. There was no difference in the mortality rate among the patients receiving the different individual biological drugs or small molecules., Conclusions: Our findings suggest that the susceptibility of rheumatic patients to COVID-19 is the same as that of the general population, but confirm that age, disease duration, and the number of co-morbidities are associated with an increased risk of a severe form of the disease. It seems that immunosuppressants drugs do not effectively represent a risk factor for COVID- 19., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To describe the features of large-vessel vasculitis (LVV) as it affects the aorta and its branches in patients with relapsing polychondritis (RP)., Methods: Retrospective data and systematic literature review., Results: Twenty-one patients were identified. LVV diagnosis was subsequent to RP and associated with extrachondral involvement in the majority of patients. Supraaortic vessels were more frequently involved (82%). Fourteen patients (67%) were treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) and 7 (33%) with a biological DMARD (bDMARD). Vascular interventional procedures were performed in 10 patients (48%). Premature death due to cardiovascular complications was reported in 3 cases (14%)., Conclusion: Extraaortic LVV is a serious and overlooked RP manifestation. All patients with RP should be investigated for LVV.

Background: Little is known about the risk stratification of patients with myocarditis undergoing ventricular tachycardia (VT) ablation., Objectives: This study sought to describe VT ablation results and identify factors associated with arrhythmia recurrences in a cohort of patients with myocarditis., Methods: The authors enrolled 125 consecutive patients with myocarditis, undergoing VT ablation. Before ablation, disease stage was evaluated, to identify active (AM) versus previous myocarditis (PM). The primary study endpoint was assessment of VT recurrences by 12-month follow-up. Predictors of VT recurrences were retrospectively identified., Results: All patients (age 51 ± 14 years, 91% men, left ventricular ejection fraction 52% ± 9%) had history of myocarditis diagnosed by endomyocardial biopsy (59%) and/or cardiac magnetic resonance (90%). Furthermore, all had multiple episodes of drug-refractory VTs. Multimodal pre-procedural staging identified 47 patients with AM (38%) and 78 patients with PM (62%). All patients showed low-voltage areas (LVA) at electroanatomical map (97% epicardial or endoepicardial); of them, 25 (20%) had wide borderzone (WBZ, constituting >50% of the whole LVA). VT recurrences were documented in 25 patients (20%) by 12 months, and in 43 (34%) by last follow-up (median 63 months; interquartile range: 39 to 87). At multivariable analysis, AM stage was the only predictor of VT recurrences by 12 months (hazard ratio: 9.5; 95% confidence interval: 2.6 to 35.3; p < 0.001), whereas both AM stage and WBZ were associated with arrhythmia recurrences anytime during follow-up. No VT episodes were found after redo ablation was performed in 23 patients during PM stage., Conclusion: Our findings suggest that VT ablation should be avoided during AM, but is often of benefit for recurrent VT after the acute phase of myocarditis., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate the effects of immunosuppression on arrhythmic myocarditis., Background: The effects of immunosuppressive therapy (IST) on ventricular arrhythmia (VA) have not been reported in patients with immune-mediated biopsy-proven myocarditis. Furthermore, myocarditis arrhythmic risk is still unpredictable., Methods: We enrolled 255 patients with biopsy-proven virus-negative myocarditis and VA (major: ventricular fibrillation, ventricular tachycardia; minor: nonsustained ventricular tachycardia, Lown grade ≥2 premature ventral complexes) at presentation. Serum cardiac autoantibodies (antiheart antibodies, anti-intercalated disk autoantibodies [AIDA]) were detected by a standardized indirect immunofluorescence technique. Whenever accepted and noncontraindicated, IST was started. Control individuals (IST - ) were chosen after 1:1 matching to IST + patients by age, sex, ethnicity, left ventricular ejection fraction, VA type, and treatment., Results: A total of 58 matched patient couples (age 42 ± 13 years; 67% male) were analyzed in the main study cohort. IST duration was 12 ± 1 months. By the 24-month prospective follow-up, major VA occurred in 6 IST + versus 10 IST - patients (p = 0.42), with no episodes following IST termination. As compared to IST - patients, IST + patients showed a significant reduction in minor VA burden, as well as improvement in clinical, laboratory, and imaging findings (all p < 0.05). Major VA onset and positive AIDA status were independently associated with major VA at follow-up (hazard ratio [HR]: 14.2; 95% confidence interval [CI]: 2.9 to 68.7 and HR: 8.0; 95% CI: 2.6 to 25.2, respectively; both p < 0.001). Furthermore, in the whole study population (N = 255), IST was independently associated with protection from major VA (HR: 0.3; 95% CI: 0.2 to 0.7; p = 0.01) at 38 ± 21 months of follow-up., Conclusions: In patients with immune-mediated virus-negative myocarditis presenting with VA, IST is associated with positive effects on minor VA and nonarrhythmic endpoints. Short-term effects are limited on major VA, which were independently associated with major VA onset and positive AIDA., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM)., Methods: We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0-3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used., Results: We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P = 0.002]. Myocardial fibrosis directly correlated with skin score (r = 0.625, P = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r = 0.756, P = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P = 0.041) and we found heart failure only in SSc patients (25%) (P = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P < 0.001]., Conclusion: SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Virus-negative or autoimmune myocarditis(VNM) is an inflammatory disease affecting the myocardium that may occur as a distinct disease with exclusive cardiac involvement, or in the context of systemic autoimmune or inflammatory disorders. The pathogenesis of VNM involves both innate and acquired immunity and is not completely elucidated: an early immune-mediated pathogenic process lead to subacute and chronic stages and eventually results in tissue remodeling, fibrosis, contractile dysfunction, dilated cardiomyopathy and arrhythmic burden, accounting for a dismal prognosis. Treatment interventions effectively curbing the acute inflammatory process at an early stage can prevent late cardiac remodeling and improve patient's outcome. The mainstay of treatment of VNM remains symptomatic therapy of heart failure and arrhythmia, while the use of immunosuppressive treatments has long been considered controversial until recently, and strategies effectively targeting the inflammatory and immune-mediated substrate of the disease remain elusive. Only steroids and azathioprine have been tested in clinical trials, and nowadays represent the therapy of choice. A substantial proportion of patients are resistant to first line strategies, suggesting that some critical inflammatory mechanisms are not responsive to conventional immunosuppression with steroids and azathioprine, or experience drug-related adverse events. Thus, second-line targeted therapeutic strategies to treat VNM are eagerly awaited. Recent data on the pathogenic mechanisms underlying myocardial inflammation are paving the way to novel, promising treatment strategies for myocarditis, which could reformulate future treatment strategies for VNM. In this review, we summarize the current therapeutic opportunities, beyond corticosteroids, to treat VNM, including conventional and biologic immunosuppressive drugs and cytokine blocking agents., Competing Interests: Declaration of Competing Interest Prof Dagna received consultation honoraria from Novartis, Roche, Sanofi-Genzyme, and SOBI. Drs. De Luca and Campochiaro received consultation honoraria from SOBI. The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Roche, Sanofi-Genzyme, and SOBI., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: We retrospectively investigated drug retention rate (DRR) and reasons for discontinuation of seven biologic disease-modifying anti-rheumatic drugs (bDMARDs) in Takayasu's arteritis (TA) in a real-world setting., Methods: TA patients followed-up in our center fulfilling the 1990 ACR criteria and treated with ≥1 bDMARD were selected. Data about disease duration, number of bDMARDs, reasons for bDMARDs discontinuation, and concomitant conventional synthetic (cs)DMARDs were collected. Survival curves were examined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRR was calculated. Hazard ratio (HR) for concomitant csDMARDs and for previous bDMARDs was evaluated. A comparative sub-analysis between anti-TNFα drugs and tocilizumab was performed., Results: We identified 50 patients and 86 bDMARD-courses. No significant differences were observed in age and disease duration between the seven groups. Infliximab was the most frequent first-line bDMARD (78.6%). At bDMARDs initiation, all patients were prescribed prednisone (mean dose, 13.5 ± 10.3 mg/day) and 85.2% concomitant csDMARD therapy. 43% of treatment courses were stopped by 24 months. Golimumab had the highest DRR (71.4%), followed by infliximab (69%), adalimumab (56.3%), abatacept (50%), tocilizumab (41.1%), anakinra (0%) and rituximab (0%), p = 0.016. Concomitant csDMARDs therapy showed positive effects on DRR (HR=2.87, 95% CI=1.19-6.92, p = 0.019). Anti-TNFα drugs had significantly higher DRR compared to tocilizumab (67.2% vs 41.1%, p = 0.028). Even in these subgroups, csDMARDs showed positive effects on DRR (HR=3.79, 95% CI=1.49-9.6, p = 0.005)., Conclusions: Anti-TNFα agents had the highest DRR overall and a higher DRR in a head-to-head comparison with tocilizumab. Concomitant csDMARDs had a significant positive effect on bDMARDs DRR., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: virus-negative lymphocytic myocarditis (VNLM) is a severe inflammatory heart disease with elusive therapies. We aimed to assess the efficacy of mycophenolate-mofetil (MMF) in patients with VNLM., Methods: patients were enrolled in this prospective cohort study and were treated with MMF, as the initial treatment in case of concomitant systemic immune diseases (SIDs), or as rescue therapy in isolated myocarditis intolerant/resistant to azathioprine. All were initially evaluated for endomyocardial biopsy; ECG, 24-h Holter, echocardiography, troponin T and NT-proBNP were obtained in all patients at baseline and after 6 months. The primary end-point was the change in left-ventricular ejection-fraction (LVEF) on echocardiogram after 6 months., Secondary Outcomes: decrease in serum NT-proBNP and troponin-T levels, reduction of LV end-diastolic-volume (LVEDV), amelioration of regional wall motion abnormalities (RWMA), and modification of clinical status., Results: 20 patients (10 females, median age at diagnosis 32 [41-59] years) were enrolled. Baseline echocardiography revealed a reduced LVEF (<55%) in 11 patients (55%) and a median LV-EF of 53.5 [44-60.5]%. Baseline median troponin T and NT-proBNP were 50.5 (14.4-288.5)ng/L and 257.0 (90.5-912.0)pg/ml, respectively. After 6 months, the median LVEF significantly improved (57 [50-61]%,p = 0.016), irrespective of concomitant steroid dose. Consistently, after 6 months LVEDV decreased from 135 ± 50 ml to 114 ± 38 ml (p < 0.001), and only 6 patients had RWMA, compared to 14 at baseline (p = 0.016). The amelioration of cardiac function was paralleled by a reduction of median troponin T (12.0 [10.0-24.0],p = 0.02) and NT-proBNP(79.5 [74.5-223-2],p = 0.007) and by a reduction in the number of patients with dyspnea NYHA class II-III(p = 0.02). None of the patients required drug discontinuation., Conclusions: MMF migh be a safe and effective therapeutic option in VNLM, both as first-line agent and as a rescue therapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective : To compare clinical characteristics and pattern of vascular involvement at disease onset according to gender specificity in patients with Takayasu arteritis (TA). Methods : Data from 117 TA patients (11 male, 106 female), diagnosed according to the American College of Rheumatology criteria, from our centre were retrospectively collected. Differences between men and women regarding demographic features, diagnostic delay, signs and symptoms attributed to TA, and arteries involved at diagnosis were compared. Data were obtained from three published articles describing gender differences in TA. A global analysis of these three cohorts plus ours (a total of 578 patients; 108 men, 470 women) was performed. Results : In our TA cohort, age at disease onset and age at diagnosis were not significantly different between genders. Diagnostic delay was higher in men. Male patients showed higher involvement of iliac arteries (right, p = 0.016; left, p = 0.021); females suffered more frequently from upper limb claudication (p = 0.026). In the overall analysis, men had higher prevalence of arterial hypertension (p = 0.007) and more frequent involvement of abdominal aorta (p = 0.026), renal arteries (right, p < 0.001; left, p < 0.001), and iliac arteries (right, p = 0.009; left, p = 0.002). Women more frequently exhibited upper limb claudication (p = 0.042) and involvement of left subclavian artery (p = 0.005), carotid arteries (right, p < 0.001; left, p < 0.001), and supradiaphragmatic aorta (ascending, p = 0.050; arch, p < 0.001; descending, p = 0.003). Inflammatory markers were more frequently raised in women (p = 0.005). Conclusions : In TA patients, gender has a strong influence on pattern of vascular involvement and consequently on clinical presentation. Specifically, women have a higher involvement of the supradiaphragmatic vessels, whereas in men the abdominal vessels are more frequently affected.

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases.

Many kinds of arrhythmias may occur in patients with myocarditis at any stage of the disease. However, compared to the other clinical presentations, arrhythmic myocarditis has been poorly described in the literature. Arrhythmias occurring in either ongoing or previous myocardial inflammation are complex and heterogeneous, and the disease itself is often underdiagnosed, thus limiting data collection and interpretation. However, different from the other clinical presentations, arrhythmic myocarditis requires specific diagnostic, prognostic, and therapeutic considerations. The aim of this review is to critically summarize the state of the art on myocarditis presenting with arrhythmias in terms of epidemiology, etiology, diagnosis, prognosis, and treatment., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Myocarditis has been described in association with many systemic immune-mediated diseases (SIDs). However, the role of SIDs in influencing clinical presentation and outcome of patients with a new diagnosis of biopsy-proved myocarditis, has never been investigated so far., Methods: We enrolled 25 consecutive cases with biopsy-proved myocarditis in the context of SIDs, and controls with isolated myocarditis, matched 1:1 by age, gender, ethnicity and clinical presentation. All of the patients presented with acute symptoms, normal coronary arteries, and no previous history of myocarditis. Detailed diagnostic workup, including blood exams, echocardiogram, arrhythmia monitoring and cardiac magnetic resonance (CMR) were obtained at baseline and at defined time points, up to 12-month follow-up (FU)., Results: At presentation, patients with SIDs had more commonly inflammatory biomarkers elevation, signs of associated pericarditis, and replacement fibrosis at histology, as compared to controls (18 vs. 6, 20 vs. 12, and 21 vs. 11, respectively; all p < 0.05). The Lake Louise criteria at CMR were negative in 19 vs. 10 patients with and without underlying SIDs, respectively (p = 0.021). Baseline ECG, in-hospital arrhythmia telemonitoring and echocardiographic findings were not significantly different between groups (all p = n.s.). At 12-month FU, the composite major endpoint of cardiac death, end-stage heart failure or malignant ventricular arrhythmias was significantly more common in cases than in controls (7 vs. 1, respectively, p = 0.049)., Conclusion: In patients with a new diagnosis of myocarditis, the presence of underlying SIDs is associated with distinct baseline clinical features and a significantly worse 1-year outcome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: This study investigated the incidence and clinical significance of arterial graft-associated uptake of fluorodeoxyglucose in large-vessel vasculitis (LVV)., Background: The role of 18 F-labeled fluorodeoxyglucose-positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) in the management of LVV remains to be defined. Although [ 18 F]FDG uptake at arterial graft sites raises concerns regarding active arteritis or infection, its clinical significance in LVV has never been formally studied., Methods: An observational prospective study sought to identify patients with Takayasu arteritis (TA) undergoing [ 18 F]FDG-PET/CT more than 6 months after graft surgery from a large cohort of patients from 2 tertiary referral centers. [ 18 F]FDG uptake by the graft and native arteries was scored on a scale of 0 to 3 relative to hepatic uptake, and periprosthetic maximum standardized uptake value (SUV max ) was calculated. Periprosthetic [ 18 F]FDG uptake in active disease was compared with that in inactive disease, and arterial progression was assessed by prospective magnetic resonance angiography (MRA)., Results: Twenty-six subjects with TA were enrolled. All were afebrile with negative blood culture. Periprosthetic uptake was significant in 23 of 26 patients, and the mean SUV max was 4.21 ± 1.46. Median periprosthetic [ 18 F]FDG uptake score (3; interquartile range [IQR]: 3 to 3) was higher than in native aorta (1; IQR: 0 to 1; p < 0.001). Graft-specific [ 18 F]FDG uptake was unrelated to disease activity. Despite the high frequency of graft-associated [ 18 F]FDG uptake, sequential MRAs did not reveal arterial progression in 25 of 26 patients; the 1 remaining case showed minor progression limited to native arteries. Nine patients underwent repeated PET/CT scanning without showing changes in graft-specific uptake, despite increased treatment., Conclusions: Significant [ 18 F]FDG uptake that is confined to arterial graft sites in patients with LVV does not reflect clinically relevant disease activity or progression. To minimize exposure to immunosuppression and in the face of negative blood culture, clinically quiescent arteritis, normal or stably raised C-reactive protein levels, we elected not to escalate treatment and monitor progression with MRA., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: The object of this study was to assess whether 18 F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu's arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions <4 mm thick., Methods: We studied 30 patients with TA, evaluated from October 2010 to April 2014 by both PET/CT and magnetic resonance imaging (MRI). All arterial lesions were evaluated by PET both qualitatively (positive/negative) and semiquantitatively (maximum standardized uptake value, SUV max ), and the thickness of lesions in the MRI field of view was evaluated. In a per-patient analysis, the relationships between the PET data and acute-phase reactants and NIH criteria for active TA were evaluated. In a per-lesion analysis, the relationships between the PET features of each lesion and MRI morphological data were evaluated. The effects of the presence of arterial grafts were also evaluated., Results: Increased FDG uptake was seen in 16 of 30 patients (53%) and in 46 of 177 vascular lesions (26%). Significant periprosthetic FDG uptake was seen in 6 of 7 patients (86%) with previous vascular surgery and in 10 of 11 of grafts (91%). Graft-associated uptake influenced the PET results in three patients (10%) and the SUV max values in five patients (17%). Of 39 lesions with significant FDG uptake, 15 (38%) were <4 mm thick. Lesion thickness was correlated with lesion SUV max in FDG-avid lesions only. FDG arterial uptake was not associated with systemic inflammation or NIH criteria., Conclusions: PET/CT reveals unique and fundamental features of arterial involvement in TA. PET/CT may be useful in the assessment of local inflammatory and vascular remodelling events independent of systemic inflammation during follow-up, even in lesions in which the arterial wall is <4 mm. The presence of arterial grafts is a potential confounder. Prospective studies are required to correlate PET findings with relevant clinical outcomes.

Background: Chromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA)., Methods: Plasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1-76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling., Results: Levels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension., Conclusions: The plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available.

Introduction: Progression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement., Methods: A cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography., Results: Patients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-α or interleukin-6., Conclusions: Arterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.

Takayasu arteritis (TA) is a rare and idiopathic large-vessel arteritis typically affecting young women which has important morbidity and mortality. There are no animal models of TA and pathogenesis is still mysterious. Clinical assessment lacks accurate activity indexes and is based on the integration of clinical, laboratory and radiological data. TA rarity has hampered randomized clinical trials and the achievement of high-quality evidence to guide clinical activity. Prevention of vascular progression, with progressive vessel wall remodelling and hyperplasia, is the main therapeutic goal. Medical therapy remains the mainstay of management and comprises traditional immunosuppressive agents and anti-inflammatory drugs, such as steroids and blockers of pivotal cytokines, TNF-α and IL-6. These strategies however only partially limit vascular progression, indicating that local molecular events are involved. Here we discuss recent data suggesting that selected cellular components of TA lesions should be evaluated as novel therapeutic targets.

Theory predicts that mate choice can lead to an increase in female fecundity if the secondary sexual traits used by females to assess male quality covary with the number of sperm transferred during copulation. Where females mate multiply, such a relationship between male attractiveness and ejaculate size may, additionally (or alternatively), serve to augment the effect of indirect selection by biasing paternity in favour of preferred males. In either case, a positive correlation between male attractiveness and the size of ejaculates delivered at copulation is predicted. To date, some of the most convincing (indirect) evidence for this prediction comes from the guppy, a species of fish exhibiting a resource-free mating system in which attractive males tend to have larger sperm reserves. We show that, during solicited copulations, male guppies with preferred phenotypes actually transfer more sperm to females than their less-ornamented counterparts, irrespective of the size of their initial sperm stores. Our results also reveal that, during coercive copulations, the relationship between ejaculate size and the male's phenotype breaks down. This latter result, in conjunction with our finding that mating speed--a factor under the female's control-is a significant predictor of ejaculate size, leads us to speculate that females may exert at least partial control over the number of sperm inseminated during cooperative matings.

According to economic principles an inappropriate prescription is the choice of an antimicrobial with higher/equivalent cost and lower effectiveness (or higher cost and equivalent/lower efficacy) than an alternative (in this case, the former is specified as a "dominated" drug). To identify cost-effective antibiotics we applied the principles of incremental cost-effectiveness analysis (ICEA) to microbiological data of San Bortolo Hospital. Its 27 wards were grouped in 9 functional areas. The resistance patterns of 8 urinary pathogens in the 1997 microbiology data base were assessed. The measure of antibiotic effectiveness was expressed as the percentage of isolates susceptible to each antibiotic tested. The difference in cost (i.e. the incremental change) between each antibiotic and the next more expensive alternative was calculated, and compared with the incremental change in effectiveness. Calculations were made for each pathogen. The antibiotics remaining after exclusion of all "dominated" antibiotics were pooled on a list defined as "Specific Area Formulary". The implications of the use of economic principles within a general antimicrobial policy are discussed.

"Trans-placental" exposure to polycyclic aromatic hydrocarbons (PAHs) in newborn babies of mothers smoking during pregnancy was investigated and compared with that in newborn babies of non smoking mothers. PAHs intake was evaluated by measuring urinary levels of 1-hydroxypyrene, a pyrene metabolita and a biological index of exposure. 42 mothers-babies couples (31 smoking and 11 non smoking mothers) were examined. Urinary concentrations of 1-hydroxypyrene in 42 controls, 18 non smoking and 24 smoking women, were determined at the same time. Mean values of 1-hydroxypyrene in non smoking women in labour and their babies were 0.15 (SD 0.11) and 0.15 (SD 0.10) micrograms/g creatinine respectively. In controls the mean was 0.15 (SD 0.09) micrograms/g creat. Mean values of 0.23 (SD 0.17) and 0.20 (SD 0.15) micrograms/g creatinine were determined in smoking mothers and their newborn babies, whereas in smoking controls 1-hydroxypyrene was 0.42 (SD 0.45) micrograms/g creatinine. The highest levels of 1-hydroxypyrene were detected in smokers (both controls and women in labour). Babies of smoking mothers also showed a higher mean value of 1-hydroxypyrene than babies of non smokers. However the only statistically significant difference found was between smoking and non smoking controls.