New insights on the active degassing system of the Lipari-Vulcano complex (South Italy) inferred from Local Earthquake Tomography.

Seismic tomography is a very powerful and effective approach to look at depths beneath volcanic systems thus helping to better understand their behaviour. The P-wave and S-wave velocity ratio, in particular, is a key parameter useful to discriminate the presence of gas, fluids and melts. We computed the first 3-D overall model of Vp, Vs and Vp/Vs for the Lipari-Vulcano complex, central sector of the Aeolian volcanic archipelago (southern Italy). The investigated area has been characterized in recent times by fumaroles, hydrothermal activity and active degassing. In particular, in the Vulcano Island, several episodes of anomalous increases of fumarole temperature and strong degassing have been recorded in the past decades and the last "crisis", started in September 2021, is still ongoing. For tomographic inversion we collected ~ 4400 crustal earthquakes that occurred in the last thirty years and we used the LOcal TOmography Software LOTOS. The results clearly depicted two low Vp and Vp/Vs anomalies located up to ~ 8 km depths below Vulcano and the western offshore of Lipari, respectively. These anomalies can be associated to the large presence of gas and they furnish a first picture of the gas-filled volumes feeding the main degassing activity of the area.

Muographic monitoring of the volcano-tectonic evolution of Mount Etna.

At Mount Etna volcano, the focus point of persistent tectonic extension is represented by the Summit Craters. A muographic telescope has been installed at the base of the North-East Crater from August 2017 to October 2019, with the specific aim to find time related variations in the density of volcanic edifice. The results are significant, since the elaborated images show the opening and evolution of different tectonic elements; in 2017, a cavity was detected months before the collapse of the crater floor and in 2018 a set of underground fractures was identified, at the tip of which, in June 2019, a new eruptive vent started its explosive activity, still going on (February, 2020). Although this is the pilot experiment of the project, the results confirm that muography could be a turning point in the comprehension of the plumbing system of the volcano and a fundamental step forward to do mid-term (weeks/months) predictions of eruptions. We are confident that an increment in the number of telescopes could lead to the realization of a monitoring system, which would keep under control the evolution of the internal dynamic of the uppermost section of the feeding system of an active volcano such as Mount Etna.

Immunogenicity of meningococcal polysaccharide ACWY vaccine in primary immunized or revaccinated adults.

Meningococcal polysaccharide (Men-Ps) vaccine immunogenicity following either primary immunization or revaccination in adults was evaluated. The study population consisted of subjects who have received tetravalent Men-Ps vaccine once (group 1) or at least twice, with a 2-6 dose range (group 2). Human leucocyte antigen (HLA)-typing was performed by polymerase chain reaction and specific immunoglobulin (Ig)G was measured by enzyme-linked immunosorbent assay. Nine months post-immunization, the percentages of individuals with levels of anti-Men-Ps IgG ≥ 2 µg/ml were comparable in both groups, with the exception of anti-Men-PsW135 IgG, which were significantly higher in group 2. The percentage of subjects doubling IgG levels at 9 months was significantly higher in group 1. The high baseline anti-Men-Ps antibody levels negatively influenced the response to revaccination, suggesting a feedback control of specific IgG. The calculated durability of anti-Men-Ps IgG was 2·5-4·5 years, depending on the Men-Ps, following a single vaccine dose. No interference by other vaccinations nor HLA alleles association with immune response were observed. This study confirms that Men-Ps vaccine in adults is immunogenic, even when administered repeatedly, and underlines the vaccine suitability for large-scale adult immunization programmes that the higher costs of conjugate vaccines may limit in developing countries.

Dome-like behaviour at Mt. Etna: The case of the 28 December 2014 South East Crater paroxysm.

On the 28 December 2014, a violent and short paroxysmal eruption occurred at the South East Crater (SEC) of Mount Etna that led to the formation of huge niches on the SW and NE flanks of the SEC edifice from which a volume of ~3 × 106 m3 of lava was erupted. Two basaltic lava flows discharged at a rate of ~370 m3/s, reaching a maximum distance of ~5 km. The seismicity during the event was scarce and the eruption was not preceded by any notable ground deformation, which instead was dramatic during and immediately after the event. The SO2 flux associated with the eruption was relatively low and even decreased few days before. Observations suggest that the paroxysm was not related to the ascent of volatile-rich fresh magma from a deep reservoir (dyke intrusion), but instead to a collapse of a portion of SEC, similar to what happens on exogenous andesitic domes. The sudden and fast discharge eventually triggered a depressurization in the shallow volcano plumbing system that drew up fresh magma from depth. Integration of data and observations has allowed to formulate a novel interpretation of mechanism leading volcanic activity at Mt. Etna and on basaltic volcanoes worldwide.

Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and plain 2009-10 seasonal influenza vaccines in rheumatoid arthritis patients on biologicals.

Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009-10 influenza season, the safety and immunogenicity of co-administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti-tumour necrosis factor (TNF)-α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1-A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)-γ-, TNF-α- or interleukin (IL)-17A-secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine-producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals.

Cyclosporine A in the long-term management of systemic lupus erythematosus.

To retrospectively evaluate safety and efficacy of long-term treatment with Cyclosporine A (CSA) in patients with systemic lupus erythematosus (SLE) poorly responsive to treatment with corticosteroids (CCS) and/or conventional disease-modifying anti-rheumatic drugs (DMARDs), SLE patients who had received CSA-based induction and maintenance regimens according to disease activity were recorded. Efficacy was assessed using the SLE Disease Activity Index (SLEDAI) and laboratory analyses. Forty SLE patients (including 18 with lupus nephritis, 11 with neurological involvement and 7 with overlap syndromes (4 Sjögren's syndrome, 2 myasthenia gravis and 1 Behçet's disease) were recorded. According to baseline SLEDAI, 30 patients had severe and 10 moderate SLE. Mean SLEDAI scores and relevant laboratory values significantly reduced from baseline (22∓10 vs 5∓6; P < 0.002) during the follow-up period (8∓2 years; range 1-15). Twenty-three (57.5 percent) patients achieved excellent (improvement in the range 70-100 percent) response to treatment (10 of whom were subsequently maintained on CSA monotherapy), 14 (35 percent) had good-fair (improvement in the range 25-69 percent) response and 3 (7.5 percent) had to interrupt therapy (including CSA) for disease worsening. Mild and transient adverse events occurred in 15 (37 percent) patients, including hypertrichosis (17.5 percent), gum hypertrophy (17.5 percent) hypertension (12.5 percent), abdominal pain (7.5 percent), and dyslipidemia (5 percent), but treatment interruption was not required. Low-dose CSA together with other drugs is effective to induce, or as monotherapy to maintain, long-term (at least 2 years) remission, and is generally well tolerated in patients with moderate or severe SLE poorly responsive to CCS and/or conventional DMARDs. Furthermore, the favourable effect of CSA treatment may allow to spare more cytotoxic drugs.

A new chance to maintain remission induced by anti-TNF agents in rheumatoid arthritis patients: CYnAR study II of a 12-month follow-up.

The advent of biological therapies represented the beginning of a new era in the therapy of Rheumatoid Arthritis (RA), as demonstrated in several studies, but still many questions about their safety, especially in long term use, and correct administration time remain unanswered. Once remission is achieved, the orientation of clinicians regarding the maintenance of biological therapy or the switch to another immunosuppressive therapy is still uncertain. In our previous study 21 patients affected by RA who reached remission by the use of a combined therapy of anti-TNF drugs and methotrexate (MTX) underwent CyA-MTX combination therapy for maintaining remission state and were evaluated during a 6-month follow-up. The present study aims to investigate these data by a longer follow-up (12 months) and on a larger population. Fifty-three RA patients, with a disease duration of less than 3 years and DAS28<3.2 that reached a level of low disease activity within 6-8 months from the beginning of anti-TNF and methotrexate therapy, were enrolled in the study. By the suspension of anti-TNF therapy, patients underwent A-Cyclosporine (2-3 mg/kg/day) and methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation rate (ESR), C Reactive Protein (CRP) were all tested at time 0 and every 2 months after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and methotrexate therapy, as well as liver and kidney profiles. Side effects were also recorded. Of 53 patients, 50 completed the study with a 12-month follow-up. Twenty-one (42%) patients maintained clinical parameters within low disease activity values at 12 months, while 29 (58%) patients showed an increase in DAS28 and other parameters: 16 (32%) patients at the 6-month control, 13 (26%) patients at the 12-month control. Our data show that 42% of the patients undergoing A-Cyclosporin and Methotrexate therapy maintained low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

Can Cyclosporine-A associated to methotrexate maintain remission induced by anti-TNF agents in rheumatoid arthritis patients? (Cynar pilot study).

Biological therapies, such as etanercept, adalimumab and infliximab, have demonstrated good efficacy in inducing rheumatoid arthritis to low disease activity levels. Nevertheless, their cost, as well as the related risk of side effects, especially in long-term therapies, are still high. Furthermore, there is a good deal of evidence proving loss of efficacy of such therapies in the long term, often necessitating the shift from one specific anti-TNF biological treatment to another. There are also other open debates on the amount of time a patient should undergo an anti-TNF therapy, on the possibility of inducing a complete remission in early arthritis and, once remission or low disease activity is obtained, on the possibility of interrupting the anti-TNF-based therapy. In this study we investigated whether A-Cyclosporin and Methotrexate association may be effective in maintaining low disease activity obtained by anti-TNF therapies. Twenty-three rheumatoid arthritis-affected patients, whose diagnosis was made according to ACR criteria, with a disease duration of less than 3 years, and DAS28<3.2 that reached a level of low disease activity within 6-8 months from beginning anti-TNF and Methotrexate therapy, were enrolled in the study. After the suspension of anti-TNF therapy, patients were started on A-Cyclosporine (2-3 mg/kg/day) and Methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation Rate (ESR), and C Reactive Protein (CRP) were all tested at time 0 and at 6 months, as well as liver and kidney profiles, after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and Methotrexate therapy. Side effects were also recorded. Of 23 patients undergoing the A-Cyclosporin and Methotrexate therapy for maintaining low disease activity in rheumatoid arthritis obtained by 6-8 months of anti-TNF therapy, 21 completed the study with a 6 month follow-up. Thirteen patients maintained clinical parameters within low disease activity values, while 8 patients showed an increase in DAS28 and other parameters. Only two patients showed an increase in blood pressure that was diagnosed after two months from the beginning of the A-Cyclosporin and Methotrexate therapy. The reduction in the dosage of A-Cyclosporin from 3mg/kg/day to 2mg/kg/day caused a slow normalization of blood pressure values. Our data seem to suggest that more than half of the patients undergoing A-Cyclosporin and Methotrexate therapy seemed to maintain low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFalpha blockers: safety and immunogenicity.

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the second year for healthy controls and in the third year for patients. No significant difference in disease activity and anti-nuclear antibodies was observed as a consequence of vaccine administration, whereas T regulatory cells showed a significant increase 30 days after immunization in RA patients. This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination.

Imaging progression despite clinical remission in early rheumatoid arthritis patients after etanercept interruption.

The aim of this preliminary study is to evaluate clinical and imaging response in twenty patients with early Rheumatoid Arthritits (eRA) treated with Etanercept (Etn) + Methotrexate (Mtx) and to investigate whether clinical and MRI remission may be maintained after biological therapy interruption. Assessment included: radiography, Visser score and anti-CCP antibodies at baseline; disease activity score in 44 joints (DAS44), rheumatoid factor (RF), Magnetic Resonance Imaging (MRI) of hands and wrists at baseline (T0), 12 (T1), and 24 months (T2). MRI was scored for synovitis, bone oedema and erosions (OMERACT study); patients who reached clinical and imaging remission at T1 were considered eligible for interrupting Etn. At T1 8/20 (40 percent) patients showed a total remission, DAS44 from 5 (T0) to 1.4 (T1); p<0.02, whereas the other 12/20 (60 percent) showed an improvement, without complete remission, DAS44 from 4.8 (T0) to 2.8 (T1); p<0.05. Etn was therefore interrupted in the first group of patients (group A), whereas it was continued in the other group (group B). At T2, group A maintained clinical remission and group B showed further not significant DAS44 reduction from T1. At T1, a significant reduction in synovitis, bone oedema and total score (p<0.01) was observed both in group A and in group B. At T2, group A showed an increase in all the MRI scores that was significant for the synovitis and total score, whereas group B exhibited a further not significant reduction. This preliminary study reports an excellent clinical and imaging response in eRA patients treated with Etn with total remission in 40 percent of them after a 1-year therapy period. However, it indicates that joint damage may progress, despite a sustained clinical remission, after Etn suspension.

Two-year follow-up in an early rheumatoid arthritis patient treated with etanercept: radiological involvement despite clinical remission.

This case report describes an excellent clinical and radiological response in an eRA patient treated with Etanercept; however, it indicates that joint damage may progress, despite a sustained clinical remission, after Etanercept suspension.