Impact of age and cardiovascular risk factors on the incidence of adverse events in patients with rheumatoid arthritis treated with Janus Kinase inhibitors: data from a real-life multicentric cohort.

Inhibiting Janus Kinases (JAK) is a crucial therapeutic strategy in rheumatoid arthritis (RA). However, the use of JAK inhibitors has recently raised serious safety concerns. The study aims to evaluate the safety profile of JAKi in patients with RA and identify potential risk factors (RFs) for adverse events (AEs). Data of RA patients treated with JAKi in three Italian centers from January 2017 to December 2022 were retrospectively analyzed. 182 subjects (F:117, 64.3%) underwent 193 treatment courses. 78.6% had at least one RF, including age ≥ 65 years, obesity, smoking habit, hypertension, dyslipidemia, hyperuricemia, diabetes, previous VTE or cancer, and severe mobility impairment. We identified 70 AEs (28/100 patients/year), among which 15 were serious (6/100 patients/year). A high disease activity was associated with AEs occurrence (p = 0.03 for CDAI at T0 and T6; p = 0.04 for SDAI at T0 and T6; p = 0.01 and p = 0.04 for DAS28ESR at T6 and T12, respectively). No significant differences in AEs occurrence were observed after stratification by JAKi molecules (p = 0.44), age groups (p = 0.08) nor presence of RFs (p > 0.05 for all of them). Neither the presence of any RFs, nor the cumulative number of RFs shown by the patient, nor age ≥ 65 did predict AEs occurrence. Although limited by the small sample size and the limited number of cardiovascular events, our data do not support the correlation between cardiovascular RFs-including age-and a higher incidence of AEs during JAKi therapy. The role of uncontrolled disease activity in AEs occurrence should by emphasized.

ToRaRI (Tofacitinib in Rheumatoid Arthritis a Real-Life experience in Italy): Effectiveness, safety profile of tofacitinib and concordance between patient-reported outcomes and physician's global assessment of disease activity in a retrospective study in Central-Italy.

INTRODUCTION: The use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered in daily practice. In consideration of ORAL-Surveillance trial and the new EULAR recommendations, real-world data are needed to assess Jak-Is safety and effectiveness. The multicenter study presented here aimed to evaluate effectiveness and safety of tofacitinib in a real-life cohort. METHODS: A retrospective analysis was performed from September 2021 to December 2022. Data were collected when tofacitinib was started (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. The primary objective was to analyze the efficacy and safety of tofacitinib. Safety was assessed by recording adverse events (AEs) with and without discontinuation. The secondary objective was to assess the difference between Patient-Reported Outcomes (PROs) and Physician's Global Assessment of disease activity (PhGA). RESULTS: 122 patients were included in the study from the following rheumatology Centers: Pisa, Ancona, Florence (two Centers), Siena, and Sardinia. A statistically significant improvement in DAS-28-CRP, CDAI and SDAI score was observed at T3, T6, compared to baseline (p < 0.001). Improvement was confirmed in patients who reach T12. Patients naïve to bDMARDs showed a shorter remission time and higher remission rates. There was also a statistically significant improvement in PROs compared to baseline (p < 0.001). The improvement was rapid and was consistent with PhGA. The 12-month retention rate for tofacitinib was 89.35%. Reasons to stop tofacitinib were: insufficient response (7), gastrointestinal symptoms (2), infection (1), malignancy (1), Zoster (1), pruritus sine materia (1). CONCLUSIONS: Tofacitinib is safe and effective in our RA cohort. It induces higher remission rates in patients naive to bDMARDs, suggesting that there may be a benefit using it as first-line therapy. Additionally, improvement in PROs was consistent with PhGA scores, demonstrating how tofacitinib affects both the objective and subjective components of disease activity. Key Points 1. JAK inhibitors are considered at a similar level as biologic agents in terms of effectiveness. 2. After ORAL-Surveillance results, real-world data are needed to assess the benefit/risk profile of Jaki. 3. Disagreement between patients and physicians has been previously reported with biologic therapy among patients with rheumatoid arthritis, with patients rating disease activity higher than physicians. 4. Jak inhibitors could reduce this discrepancy, due to their mechanism of action.

Fibrosing Progressive Interstitial Lung Disease in Rheumatoid Arthritis: A Multicentre Italian Study.

BACKGROUND: The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown. OBJECTIVES AND METHODS: The aim of the present multicentre study was to investigate the prevalence and possible associated factors of fibrosing progressive patterns in a cross-sectional cohort of RA-ILD patients. RESULTS: One hundred and thirty-four RA-ILD patients with a diagnosis of RA-ILD, who were confirmed at high-resolution computed tomography and with a follow-up of at least 24 months, were enrolled. The patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity > 10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24-month period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnea. According to radiologic features, ILD was classified as usual interstitial pneumonia (UIP) in 50.7% of patients, nonspecific interstitial pneumonia in 19.4%, and other patterns in 29.8%. Globally, a fibrosing progressive pattern was recorded in 36.6% of patients (48.5% of patients with a fibrosing pattern) with a significant association to the UIP pattern. CONCLUSION: We observed that more than a third of RA-ILD patients showed a fibrosing progressive pattern and might benefit from antifibrotic treatment. This study shows some limitations, such as the retrospective design. The exclusion of respiratory symptoms' evaluation might underestimate the prevalence of progressive lung disease but increases the value of results.

Systemic vasculitis: one year in review 2023.

Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.

Airborne Sound Power Levels and Spectra of Noise Sources in Port Areas.

Airborne port noise has historically suffered from a lack of regulatory assessment compared to other transport infrastructures. This has led to several complaints from citizens living in the urban areas surrounding ports, which is a very common situation, especially in countries facing the Mediterranean sea. Only in relatively recent years has an effort been made to improve this situation, which has resulted in a call for and financing of numerous international cooperation research projects, within the framework of programs such as EU FP7, H2020, ENPI-CBC MED, LIFE, and INTERREG. These projects dealt with issues and aspects of port noise, which is an intrinsically tangled problem, since several authorities and companies operate within the borders of ports, and several different noise sources are present at the same time. In addition, ship classification societies have recently recognized the problem and nowadays are developing procedures and voluntary notations to assess the airborne noise emission from marine vessels. The present work summarizes the recent results of research regarding port noise sources in order to provide a comprehensive database of sources that can be easily used, for example, as an input to the noise mapping phase, and can subsequently prevent citizens' exposure to noise.

Association between frailty index, lung function, and major clinical determinants in chronic obstructive pulmonary disease.

BACKGROUND: Airflow limitation alone is unable to capture the complexity of chronic obstructive pulmonary disease (COPD), better explained by comprehensive disease-specific indexes. Frailty is a clinical condition characterized by high vulnerability to internal and external stressors and represents a strong predictor of adverse outcomes. AIMS: Primary objective was to test the association between indexes of lung function and COPD severity with frailty index (FI), and secondary to evaluate the association between FI and comorbidities, cognitive and physical function, BODE index, and mortality. METHODS: 150 stable COPD outpatients were enrolled and followed up to 4 years. At baseline, participants performed a geriatric multidimensional assessment, pulmonary function tests, arterial blood gas analysis, 6-min walking test, and bioimpedance analysis. BODE and FI were calculated. Spearman's ρ was used to assess correlations. Mortality was assessed using Kaplan-Meier curves. RESULTS: Participants were followed up for a median of 39 months. Mean age was 73 years and median frailty index 0.15 (IQR 0.11-0.19). FI was higher in frequent exacerbators (≥ 2/year) (mean 0.18 vs 0.15, p 0.01) and dyspnoeic patients (mMRC ≥ 2) (mean 0.21 vs 0.14, p < 0.01) and correlated with lung volumes, expiratory flows, and pressure of arterial oxygen. FI was positively correlated with the number of comorbidities, depressive symptoms, cognitive decline, and BODE index. Mortality was higher in patients with BODE higher than 3 (HR 3.6, 95% CI 1.2-10.9), and not associated with FI. DISCUSSION: FI positively correlates with all clinical drivers orienting the choice of treatment in COPD. CONCLUSIONS: FI associates with lung function and COPD severity, but does not associate with mortality.

The Role of Three-Dimensional Printing Technology as an Additional Tool in Unilateral Condylar Hyperplasia Surgical Planning.

The purpose of this study is to evaluate whether additive manufactory technology through the use of 3D mandible and skull cast models can provide additional support to the virtual surgical planning for patients affected by unilateral condylar hyperplasia (UCH). This study describes 2 patients affected by active UCH. Cone beam computed tomography (CBCT) scans were converted in STL files and then sent to a 3D printer that provided 3D cast models of patient's mandible and skull. Surgical planning was conducted performing linear measurement both on 3D virtual images and on 3D cast models. Proportional condylectomy was then simulated with the virtual software and on the 3D cast models as well. After 18 months, new CBCT scans of the patients were acquired and new 3D cast models were printed. Measurements performed on the 3D cast models were close and reliable if compared to measurements obtained on 3D virtual images. None of the patients underwent further surgeries obtaining stable results in terms of symmetry. 3D printing technologies have a relevant support for a more accurate planning and surgical treatment in UCH.

Rare Complication in Third Maxillary Molar Extraction: Dislocation in Infratemporal Fossa.

AIM: Removal of impacted third maxillary molar is frequently carried out without difficulties and low rate of intraoperative complications. The rare and particularly challenger to manage it is the third molar dislocation into the infratemporal fossa (IF). In this clinical report, the authors present their solution to manage and resolve this particular complication. METHODS: A 28-year-old woman was referred to the emergency rescue unit of the authors' hospital by her dentistry, after the attempt to extract the left impacted maxillary third molar. During the procedure the tooth accidentally dislodged and was lost sight of it. The patient had significant mouth-opening limitation, omolateral mid face swelling and pain. Computer tomography was immediately performed to determine the exact position of the tooth, showing the dental element dislocated into the IF. RESULTS: Considering all of possible complications the best surgical option must guarantee a direct approach and a constant eye contact of the tooth, even in case of further displacement during the procedure, and allow early surgery. The authors used an endoscopic transoral approach through the preexisted access and solved all the issues reducing morbidity. CONCLUSION: Removing tooth from the IF could be burdened by serious risk of bleeding and/or nerve injury. The endoscopic approach provides direct view of the IF reducing morbidity.

How reproducible is the acoustical characterization of porous media?

There is a considerable number of research publications on the characterization of porous media that is carried out in accordance with ISO 10534-2 (International Standards Organization, Geneva, Switzerland, 2001) and/or ISO 9053 (International Standards Organization, Geneva, Switzerland, 1991). According to the Web of ScienceTM (last accessed 22 September 2016) there were 339 publications in the Journal of the Acoustical Society of America alone which deal with the acoustics of porous media. However, the reproducibility of these characterization procedures is not well understood. This paper deals with the reproducibility of some standard characterization procedures for acoustic porous materials. The paper is an extension of the work published by Horoshenkov, Khan, Bécot, Jaouen, Sgard, Renault, Amirouche, Pompoli, Prodi, Bonfiglio, Pispola, Asdrubali, Hübelt, Atalla, Amédin, Lauriks, and Boeckx [J. Acoust. Soc. Am. 122(1), 345-353 (2007)]. In this paper, independent laboratory measurements were performed on the same material specimens so that the naturally occurring inhomogeneity in materials was controlled. It also presented the reproducibility data for the characteristic impedance, complex wavenumber, and for some related pore structure properties. This work can be helpful to better understand the tolerances of these material characterization procedures so improvements can be developed to reduce experimental errors and improve the reproducibility between laboratories.

A review and comparative analysis of European priority indices for noise action plans.

The European Union has provided in recent years (and is going to update) several tools to harmonise noise mapping methodologies through directives and guidelines. Unfortunately the same efforts have not been put in the harmonisation of approaches for Noise Action Plans, the effective instruments to manage noise impacts. As a consequence, each European Member State at national or even at local level defined its own methodology, usually considerably different one from the others. Nevertheless, the most common approach to deal with noise impact at a policy, economic and strategy level is the use of priority indices focused to highlight areas or buildings where mitigation actions are more advisable or urgent. The aim of the present research is to provide a review of the most used European priority indices and also to test some of them in a study area. The comparative analysis demonstrates that the method chosen for the prioritisation deeply affects the ranking of the areas where noise measures need to be realized. Some methods tend to give high priority to noise sensitive locations, others to high populated buildings, and others to the areas where noise levels are high. The study proves how much common approaches are needed also for Noise Action Plans to reach a coherent noise policy within European boundaries.

The perceived quality of soundscape in three urban parks in Rome.

The present paper reports a socio-acoustic survey carried out in three large urban parks in Rome, selected on the basis of the outcome of a preliminary online survey. According to the experimental protocol applied in a previous study carried out in Milan and Naples, binaural recordings in 85 sites and interviews with 266 users of the three parks were performed only during the day in summertime. On the basis of selected acoustical descriptors, the sonic environment of the three parks was categorized and, thanks to statistical analysis, three clusters were identified. The results confirm that the sound environment in urban parks is often considered as "good" or "excellent" even if the sound pressure level is nearly always higher than the limits commonly used to define quiet areas. This is due to the influence of other factors, such as the presence of trees, natural features, and the tranquility; all of these components cannot be neglected in the assessment of the soundscape because they directly affect the psychological state of the person.