Pain in systemic connective tissue diseases

Pain is frequent in patients with connective tissue diseases (CTDs), particularly those affected by systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) in which it is virtually ubiquitous and can have different causes. The SLE classi fi cation criteria include pain associated with musculoskeletal involve- ment, which are frequently the initial symptom of SLE and can include arthralgia, arthritis and/or myalgia. Chronic widespread pain, the cornerstone of fi bromyalgia (FM), is also frequently associated with CTDs. Chronic pain has a considerable impact on mental health, and the professional and family lives of patients. It can be due to many disorders, but there are few reports concerning its prevalence during the course of other diseases. It is essential to identify the origin of pain in CTDs in order to avoid dangerous over-treatment in patients with co-existing widespread pain. Effective pain management is a primary goal of patient care, although it has not been investigated in detail in patients with SSc

Enforcing Statistical Orthogonality in Massive MIMO Systems via Covariance Shaping

This paper tackles the problem of downlink transmission in massive multiple-input multiple-output(MIMO) systems where the equipments (UEs) exhibit high spatial correlation and the channel estimation is limited by strong pilot contamination. Signal subspace separation among the UEs is, in fact, rarely realized in practice and is generally beyond the control of the network designer (as it is dictated by the physical scattering environment). In this context, we propose a novel statistical beamforming technique, referred to asMIMO covariance shaping, that exploits multiple antennas at the UEs and leverages the realistic non-Kronecker structure of massive MIMO channels to target a suitable shaping of the channel statistics performed at the UE-side. To optimize the covariance shaping strategies, we propose a low-complexity block coordinate descent algorithm that is proved to converge to a limit point of the original nonconvex problem. For the two-UE case, this is shown to converge to a stationary point of the original problem. Numerical results illustrate the sum-rate performance gains of the proposed method with respect to reference scenarios employing the multiple antennas at the UE for spatial multiplexing.Comment: Submitted for journal publicatio

An integrated approach to the assessment of balance and functional mobility in individuals with history of severe traumatic brain injury

Individuals who experienced severe Traumatic Brain Injury (sTBI) are often characterized by relevant motor dysfunctions which are likely to negatively affect activities of daily living and quality of life and often persist for years. However, detailed objective information about their magnitude are scarce. The aim of this study was to quantitatively assess the extent of motor deficits in terms of postural control effectiveness under static and dynamic conditions and to investigate the existence of possible correlations between the results of clinical tests and instrumental measures. Postural sway and functional mobility (i.e., instrumented Timed Up and Go test, iTUG) were objectively measured in 18 individuals with sTBI and 18 healthy controls using a pressure plate and a wearable inertial sensor. Additionally, participants with history of sTBI completed the Rivermead Mobility Index (RMI). One-way ANOVA and Spearman's rank correlation analysis were employed to examine differences between the two groups and determine potential correlations between the instrumental tests and clinical scales. The results show that people with sTBI were characterized by larger sway area and longer iTUG walking sub-phase. Significant correlations were also detected between RMI scores and iTUG total duration, as well as the walking phase. Taken together, these findings suggest that, even years after the initial injury, individuals with sTBI appear characterized by impaired postural control and functional mobility, which appears correlated with the RMI score. The integration of instrumental measures with clinical scales in the routine assessment and treatment of individuals with sTBI would result in more comprehensive, objective, and sensitive evaluations, thus improving precision in treatment planning, enabling ongoing progress monitoring, and highlighting the presence of motor deficits even years after the initial injury. Such integration is of importance for enhancing the long-term quality of life for individuals with sTBI

Potential Role of Anti-interleukin (IL)-6 Drugs in the Treatment of COVID-19: Rationale, Clinical Evidence and Risks

The epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. This public health emergency has triggered a race to find medications to improve the prognosis of this disease. There is currently great interest in drug repositioning to manage SARS-CoV-2 infection, that is, the evaluation of the potential benefits of a drug that has already been proven safe and effective in humans for other approved indications. As interleukin-6 (IL-6) acts as a key driver of the inflammation associated with coronavirus disease 2019 (COVID-19), IL-6 and IL-6 receptor (IL-6R) inhibition appear to be promising targets for the treatment of COVID-19 patients. It is important to critically analyze the available evidence concerning the use of the available anti-IL-6 (siltuximab) and anti-IL-6R (tocilizumab and sarilumab) agents in COVID-19 patients, in terms of both benefit and risk. In this review, the pathogenesis of the cytokine storm induced by COVID-19, the role of IL-6 in this cytokine storm, the rationale for the use of anti-IL-6 agents, and key information on potential benefits and safety monitoring of these biologicals in COVID-19 patients is discussed

Cross Cultural Adaptation and Validation of Italian Version of the Leeds Assessment of Neuropathic Symptoms and Signs Scale and Pain DETECT Questionnaire for the Distinction between Nociceptive and Neuropathic Pain

Objective. This study aimed to validate Italian versions of Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale and Pain DETECT questionnaire (PD-Q) and evaluate the ability of these questionnaires to discriminate between nociceptive and neuropathic pain. Design. Multicenter prospective validation cohort study. Subjects and Setting. One hundred patients were included with a diagnosis formulated by a specialist in outpatient settings (50 affected by knee osteoarthritis as nociceptive pain and 50 affected by trigeminal or postherpetic neuralgia as neuropathic pain). Methods. The Italian versions of both questionnaires according to Italian cultural characteristics were performed according to the following steps: (1) translation of the questionnaires from English into Italian; (2) review by a bilingual individual for consistency; (3) proposed version after a mail round between experts; (4) backward translation; (5) comparison with the original English version by the experts; (6) approved version of the questionnaires. One hundred patients were enrolled and completed the two questionnaires administered by a specialist or blinded nursing staff, at the baseline and after 24/48 hours. Internal consistency, stability, validity, and discriminative power were analyzed. Results. Statistically significant differences were reported about the ability of both questionnaires to discriminate between patients affected by neuropathic or nociceptive pain. Internal consistency for the Italian version of the LANSS was 0.76, and for PD-Q, it was 0.80, assessed by Cronbach’s α; LANSS showed a good test-retest reliability with an ICC of 0.76, and PD-Q showed a high test-retest reliability with an ICC of 0.96. For interrater reliability, there was a concordance rate of 83.3% between reference diagnosis and LANSS (Cohen’s kappa = 0.67, CI 95% 0.52–0.75). Conclusions. This study validated the Italian versions of LANSS and PD-Q as reliable instruments with good psychometric characteristics, for pain evaluation, discriminating between nociceptive and neuropathic pain. Our findings were similar to those observed in the original study. Furthermore, we have reported the test-retest reliability for both questionnaires, not addressed in original validation studies

Privileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors

Human Carbonic Anhydrases (hCA) are enzymes that contribute to cancer's development and progression. Isoforms IX and XII have been identified as potential anticancer targets, and, more specifically, hCA IX is overexpressed in hypoxic tumor cells, where it plays an important role in reprogramming the metabolism. With the aim to find new inhibitors towards IX and XII isoforms, the hybridization of the privileged scaffolds isatin, dihydrothiazole, and benzenesulfonamide was investigated in order to explore how it may affect the activity and selectivity of the hCA isoforms. In this respect, a series of isatin thiazolidinone hybrids have been designed and synthesized and their biological activity and selectivity on hCA I, hCA II, hCA IX, and hCA XII explored. The new compounds exhibited promising inhibitory activity results on isoforms IX and XII in the nanomolar range, which has highlighted the importance of substituents in the isatin ring and in position 3 and 5 of thiazolidinone. In particular, compound 5g was the most active toward hCA IX, while 5f was the most potent inhibitor of hCA XII within the series. When both potency and selectivity were considered, compound 5f appeared as one of the most promising. Additionally, our investigations were supported by molecular docking experiments, which have highlighted the putative binding poses of the most promising compound

The Rheumatology drugs for COVID-19 management: Which and when?

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patient

Evolution of Rheumatoid-Arthritis-Associated Interstitial Lung Disease in Patients Treated with JAK Inhibitors: A Retrospective Exploratory Study

Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD). Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests. Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46–75.78) treated with JAKi. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%). Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study

Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA)