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Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5–1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10–20% of mortality, with a mean survival of 5–8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.

Background Although guidelines recommend a multidisciplinary team (MDT) approach for the diagnosis and management of systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD), they lack guidance on MDT composition and function. This Delphi consensus project aimed to define a shared MDT model for managing patients with SARD-ILD. Methods A questionnaire was circulated to an expert panel of 77 Italian pulmonologists, rheumatologists, immunologists, and internal medicine specialists, with statements rated over two voting rounds using a 5-point Likert scale. Results Response rates were 73% and 95% for the first and second rounds, respectively, after which consensus (≥ 66.6% agreement) was achieved for all the statements. Consensus statements and recommendations address the responsibilities of healthcare professionals involved in an MDT, including organization, referrals, management, and standard outcomes. Conclusion Although limited to Italy, the current consensus project is the first attempt to define shared rules for MDTs in the context of SARD-ILD, but further work is needed to achieve international consensus on this topic.

Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the “straight-edge” sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs.

Background Data on the impact of vertebral fractures on lung function in interstitial lung diseases (ILDs) are limited. This study aimed to evaluate the association between vertebral fractures, quantified by the spinal deformity index (SDI), and pulmonary function parameters, independently of ILD pattern and thoracic morphometric indices. Methods This cross-sectional study included adult patients diagnosed with ILD who underwent high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs). PFTs included absolute and percent predicted values of forced vital capacity (ppFVC), absolute and percent predicted total lung capacity (ppTLC), forced expiratory volume in one second (FEV₁), and percent predicted diffusing capacity of carbon monoxide (ppDLCO). The SDI was calculated from T4 to T12 on sagittal HRCT reconstructions. Results A total of 200 patients were analyzed: 76 with idiopathic pulmonary fibrosis (IPF), 65 with systemic sclerosis–associated ILD (SSc-ILD), 31 with idiopathic inflammatory myopathy–associated ILD, and 28 with other ILDs. At least one mild thoracic vertebral fracture was detected in 46 subjects (23%). Each one-point increase in SDI was associated with a 2.9% reduction in ppFVC ( p  < 0.01), a 2.7% reduction in ppTLC ( p  < 0.01). Absolute FVC and TLC declined by 95.6 mL ( p  < 0.05) and 199.5 mL ( p  < 0.05) per SDI point, respectively, with consistent results after multiple imputation. Conclusions Vertebral fractures quantified by SDI are independently associated with reduced lung volumes in ILD patients, beyond fibrotic pattern and thoracic morphometry. These findings reveal a novel bone–lung interaction and support the inclusion of vertebral assessment in the comprehensive evaluation of ILD.

Surface free energy (SFE) of titanium surfaces plays a significant role in tissue engineering, as it affects the effectiveness and long-term stability of both active coatings and functionalization and the establishment of strong bonds to the newly growing bone. A new contact–mechanics methodology based on high-resolution non-destructive elastic contacting nanoindentation is applied here to study SFE of micro- and nano-structured titanium surfaces, right after their preparation and as a function of exposure to air. The effectiveness of different surface treatments in enhancing SFE is assessed. A time-dependent decay of SFE within a few hours is observed, with kinetics related to the sample preparation. The fast, non-destructive method adopted allowed for SFE measurements in very hydrophilic conditions, establishing a reliable comparison between surfaces with different properties.

Interstitial lung disease (ILD) is one of the most serious pulmonary complications of connective tissue diseases (CTDs) and it is characterized by a deep impact on morbidity and mortality. Due to the poor knowledge of CTD-ILD’s natural history and due to the difficulties related to design of randomized control trials, there is a lack of prospective data about the prevalence, follow-up, and therapeutic efficacy. For these reasons, the choice of therapy for CTD-ILD is currently very challenging and still largely based on experts’ opinion. Treatment is often based on steroids and conventional immunosuppressive drugs, but the recent publication of the encouraging results of the INBUILD trial has highlighted a possible effective and safe use of antifibrotic drugs as a new therapeutic option for these subjects. Aim of this review is to summarize the available data and recent advances about therapeutic strategies for ILD in the context of various CTD, such as systemic sclerosis, idiopathic inflammatory myopathy and Sjogren syndrome, systemic lupus erythematosus, mixed connective tissue disease and undifferentiated connective tissue disease, and interstitial pneumonia with autoimmune features, focusing also on ongoing clinical trials.

Objective. In the absence of national and European guidelines on the treatment of rheumatoid arthritis (RA) with interstitial lung disease (ILD), the Italian Society of Rheumatology decided to develop national clinical practice guidelines on the management of patients with RA-ILD in accordance with the requirements of the National Guideline System of the National Institute of Health. Methods. The development process included a systematic review of the available evidence and its adaptability to the Italian context, followed by a consultation with experts in rheumatology, respiratory diseases, radiology, and representatives of the health professions and patients. Results. The panel decided to develop recommendations in three main scenarios. The first section of recommendations is focused on drugs indicated for RA to assess their safety and efficacy in RA-ILD. The second set of recommendations covered the drugs indicated for the treatment of ILD in patients with RA-ILD (to assess their efficacy and safety in patients with RA). The third part of these guidelines dealt with drugs indicated for the treatment of RA-ILD upon first-line failure. Moreover, the lack or absence of scientific evidence in literature on certain topics, such as the value of a multidisciplinary treatment approach and lung transplantation, led to the decision to proceed through expert consensus to develop good clinical practice guidelines. Conclusions. These guidelines represent a fundamental step towards improving the health management of patients with rheumatological diseases in Italy by providing specific and evidence-based guidelines for the management of RA-ILD. Their use is intended to promote health and reduce the burden of morbidity and mortality in this vulnerable population.

Lung involvement represents a fearful complication in rheumatoid arthritis (RA), potentially involving all compartments of the pulmonary system. Regarding interstitial lung disease (ILD), the HRCT represents the gold standard technique for its diagnosis; however, the examination is burdened by radiation exposure and high costs. In addition, although some risk factors for ILD are known, no algorithms exist to know which patients to submit to HRCT and when. In this context, lung ultrasound (LUS) showed promising results for at least 10 years, demonstrating correlation with high resolution computed tomography (HRCT) findings in other rheumatic diseases. Here, LUS may represent a screening test providing additional information to clinical examination and pulmonary function tests. The data deriving from LUS experience in other rheumatic diseases could steer the future towards the use of this technique also in RA patients, and in this review, we report the most relevant literature regarding LUS in RA-ILD.

Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients. High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables. We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36-120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56-55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05-0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06-0.82) and the flatness (HR 0.42, 95% CI 0.18-0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82-2.83) was also retained as a confounder. Radiomic analysis may predict RA-ILD patients' mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease.

The present study investigated the influence of nanoscale residual stress depth gradients on the nano-mechanical behavior and adhesion energy of aluminium nitride (AlN) and Al/AlN sputtered thin films on a (100) silicon substrate. By using a focused ion beam (FIB) incremental ring-core method, the residual stress depth gradient was assessed in the films in comparison with standard curvature residual stress measurements. The adhesion energy was then quantified by using a nanoindentation-based model. Results showed that the addition of an aluminum layer gave rise to additional tensile stress at the coating/substrate interface, which can be explained in terms of the differences of thermal expansion coefficients with the silicon substrate. Therefore, the coatings without the Al layer showed better adhesion because of a more homogeneous compressive residual stress in comparison with the coating having the Al layer, even though both groups of coatings were produced under the same bias voltage. Results are discussed, and some general suggestions are made on the correlation between coating/substrate property combinations and the adhesion energy of multilayer stacks. The results suggested that the Al bond layer and inhomogeneous residual stresses negatively affected the adhesion of AlN to a substrate such as silicon.