Rheumatic Diseases: Pathophysiology, Targeted Therapy, Focus on Vascular and Pulmonary Manifestations

This book aims to summarize the latest advances in the rheumatic diseases, particularly regarding their pathophysiology and targeted therapy, with a focus on the recent efforts of vascular and pulmonary manifestations in order to anticipate new and future directions of these research topics. Rheumatic diseases represent a heterogeneous group of severe autoimmune disorders. The present Special Issue aims to provide an overview of the diversity and complexity of vascular and pulmonary manifestations of rheumatic diseases and to highlight gaps in our knowledge of how to effectively manage them. Despite their significant morbidity, we have a limited understanding of their pathogenesis. The eleven published articles reported here underline the complexity of rheumatic diseases and the difficulty of managing them. The manuscripts provide an overview of the pathophysiology and current management approach of these disorders, highlighting tools that assist with diagnosis, risk stratification, and therapy. A significant number of articles have reported innovative and effective treatments for the most frequent and debilitating complications of rheumatic diseases. The book emphasizes the importance of multidisciplinary teams using the skills of laboratory researchers, clinicians, radiologists, and pathologists. Furthermore, recent findings are presented and discussed, highlighting strategies to combat worsening symptoms of rheumatic diseases. The research described in this book provide an extremely useful example of the results achieved in the field of anti-rheumatic drug development. Detailed information on new breakthroughs can be found in this book. We strongly encourage a wide group of readers to explore the book that we are presenting for inspiration to develop new approaches to the diagnosis and treatment of rheumatic diseases

Macrocirculation versus microcirculation and digital ulcers in systemic sclerosis patients: Macro-microcirculation and scleroderma.

3nonemixedCUTOLO, MAURIZIO; RUARO, BARBARA; Smith, V.Cutolo, Maurizio; Ruaro, Barbara; Smith, V

Higher, but Not Too High, Dose Is Only One Determinant of Corticosteroid Treatment Success in Severe COVID-19

We read with interest the study from Pitre and colleagues, who systematically reviewed 20 randomized controlled trials published through August 2022, concluding that higher doses of corticosteroids (CSs) probably reduce mortality (relative risk, 0.92; 95% confidence interval [CI], 0.85–0.98) and the need for mechanical ventilation (relative risk, 0.91; 95% CI, 0.87–1.03) compared with lower doses in severe-to-critical coronavirus disease (COVID-19), without significantly impacting either the duration of hospitalization or the incidence of nosocomial infections (1)

Editorial: Obstructive sleep apnea syndrome (OSAS). What's new?

This Research Topic entitled “Obstructive sleep apnea syndrome (OSAS). What's new?”, involving authors from different specializations and numerous countries, confirms that OSAS is a hot topic. OSA syndrome is an airway obstruction (i.e. complete or partial) with numerous etiologies (1–4). Different papers have demonstrated that the prevalence of OSAS is 2–4% in men and 1–2% in women of average age. The reference tools for OSAS diagnosis are clinical polysomnography or nocturnal portable multi-channel monitoring. Frequently, continuous positive airway pressure (CPAP) therapy is the first treatment for a patient (5, 6). Long-term CPAP treatment may present limited compliance, and there is no unanimous opinion on other alternative treatments for OSAS in literature on the subject. This special issue discusses several of these “unmet needs”

Assessment of treatment effects on digital ulcer and blood perfusion by laser speckle contrast analysis in a patient affected by systemic sclerosis

Laser speckle contrast analysis (LASCA) is a good tool to evaluate the variation in peripheral blood perfu-sion during long-term follow-up andis able to safely monitor digital ulcer evolution inscleroderma patients. It evaluates blood perfusion in different areas within the skin lesions and surrounding them during standard treatment

Obstructive Sleep Apnea Syndrome in women: gender in sleep respiratory medicine is a first step towards personalized medicine

Obstructive sleep apnea syndrome is the most common sleep disordered breathing. In recent years, literature has focused on the anatomical and functional factors in the pathophysiology of patients to better understand their clinical and polysomnographic features, aiming for personalized treatment. Studies suggest that sleep-disorders breathing in women are underestimated and associated with cardiovascular and metabolic disorders. Women tend to experience more mood disorders and behavioral symptoms, leading to a reduced quality of life. The sleep and respiratory pathophysiology in women are complex and varies with age and hormonal status. This review summarizes recent knowledge on this topic, emphasizing the pathophysiological mechanisms to explain the typical clinical and polysomnographic patterns observed in females. In sleep respiratory medicine, gender- specific approaches are now essential for personalized patient care

Pulmonary fibrosis: one manifestation, various diseases

This research topic collection entitled “Pulmonary Fibrosis: one manifestation, various diseases”, involving authors from different countries, confirms that this disease is a hot topic (Confalonieri P et al.,2022, Orlandi M et al., 2022). There are over 200 different types of pulmonary fibrosis (PF), the most common is the idiopathic pulmonary fbrosis (IPF), called idiopathic because it has no known cause. Another rare form is familial PF, for which several studies reported correlation with few genes. An important group of PF are due to other diseases, for example, autoimmune diseases such as rheumatoid arthritis, systemic sclerosis or Sjogren’s syndrome (Ruaro et al., 2022, Trombetta AC et al., 2017, Bernero Eet al., 2013). PF could correlate to viral infections (e.g. COVID-19), gastroesophageal reflux disease (GERD) (Baratella E et al, 2021, Ruaro et al., 2018), and the exposure to various materials (including naturally occurring such as bird or animal droppings, and occupational such as asbestos or silica). Furthermore, smoking, radiation treatments, and certain drugs can increase risk of developing PF. In the first article (Saketkoo et al.) of the collection, the authors evaluate the use of International Classification of Functioning, Disability, and Health (ICF) approved by World Health Organization (WHO) in patients affected by interstitial lung diseases (ILD)

Raynaud’s phenomenon is associated with an increased risk of cardiovascular disease and venous thromboembolism

Objectives: Raynaud's phenomenon (RP) is common affecting 3–5 % of the population; however, there are little data concerning vascular outcomes. We aimed to estimate risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) in individuals with RP without underlying relevant systemic autoimmune rheumatic diseases (SARDs). Methods: A cohort study using data from North American electronic healthcare organization records. RP was defined using ≥2 ICD codes (I73.0), excluding those with SARDs. Comparators had ≥2 irritable bowel syndrome (IBS) ICD codes (K58); selected as a condition with similar demographics but not typically associated with adverse CVD outcomes. Cohorts were stratified by age (<45 and ≥45 years). Co-primary outcomes were 1) major adverse cardiovascular events (MACE), and 2) VTE. Secondary outcomes included: myocardial infarction, stroke, any CVD. Risk of each outcome was compared using 1:1 propensity score matched Cox proportional hazard models. Results: Among 30,088 matched pairs aged <45, hazard ratios (HR [95 % CI]) of MACE (HR 1.23 [1.07, 1.42]) and VTE (HR 1.32 [1.20, 1.46]) were higher in RP (excluding SARD) than IBS. Similarly, in 60,145 matched pairs ages ≥45, MACE (HR 1.17 [1.13, 1.22]) and VTE (HR 1.20 [1.14, 1.26]) were higher in RP. Risk of secondary outcomes was higher in RP, although estimates for DVT in both analyses and myocardial infarction in patients under 45 lacked precision. Conclusions: RP was associated with an increased risk of CVD and VTE, independent of age and traditional cardiovascular risk factors. Future research is warranted to confirm, explore pathobiological mechanisms, and develop therapeutic strategies

Editorial: Pulmonary fibrosis: One manifestation, various diseases

This research topic collection entitled “Pulmonary Fibrosis: one manifestation, various diseases”, involving authors from different countries, confirms that this disease is a hot topic (Confalonieri P et al.,2022, Orlandi M et al., 2022). There are over 200 different types of pulmonary fibrosis (PF), the most common is the idiopathic pulmonary fbrosis (IPF), called idiopathic because it has no known cause. Another rare form is familial PF, for which several studies reported correlation with few genes. An important group of PF are due to other diseases, for example, autoimmune diseases such as rheumatoid arthritis, systemic sclerosis or Sjogren’s syndrome (Ruaro et al., 2022, Trombetta AC et al., 2017, Bernero Eet al., 2013). PF could correlate to viral infections (e.g. COVID-19), gastroesophageal reflux disease (GERD) (Baratella E et al, 2021, Ruaro et al., 2018), and the exposure to various materials (including naturally occurring such as bird or animal droppings, and occupational such as asbestos or silica). Furthermore, smoking, radiation treatments, and certain drugs can increase risk of developing PF

A Review: The Potential Involvement of Growth Arrest-Specific 6 and Its Receptors in the Pathogenesis of Lung Damage and in Coronavirus Disease 2019

The tyrosine kinase receptors of the TAM family-Tyro3, Axl and Mer-and their main ligand Gas6 (growth arrest-specific 6) have been implicated in several human diseases, having a particularly important role in the regulation of innate immunity and inflammatory response. The Gas6/TAM system is involved in the recognition of apoptotic debris by immune cells and this mechanism has been exploited by viruses for cell entry and infection. Coronavirus disease 2019 (COVID-19) is a multi-systemic disease, but the lungs are particularly affected during the acute phase and some patients may suffer persistent lung damage. Among the manifestations of the disease, fibrotic abnormalities have been observed among the survivors of COVID-19. The mechanisms of COVID-related fibrosis remain elusive, even though some parallels may be drawn with other fibrotic diseases, such as idiopathic pulmonary fibrosis. Due to the still limited number of scientific studies addressing this question, in this review we aimed to integrate the current knowledge of the Gas6/TAM axis with the pathophysiological mechanisms underlying COVID-19, with emphasis on the development of a fibrotic phenotype