Rheumatoid arthritis (RA) is an invalidating chronic autoimmune disorder characterized by joint inflammation and progressive bone damage. Dietary intervention is an important component in the ...treatment of RA to mitigate oxidative stress, a major pathogenic driver of the disease. Alongside traditional sources of antioxidants, microalgae-a diverse group of photosynthetic prokaryotes and eukaryotes-are emerging as anti-inflammatory and immunomodulatory food supplements. Several species accumulate therapeutic metabolites-mainly lipids and pigments-which interfere in the pro-inflammatory pathways involved in RA and other chronic inflammatory conditions. The advancement of the clinical uses of microalgae requires the continuous exploration of phytoplankton biodiversity and chemodiversity, followed by the domestication of wild strains into reliable producers of said metabolites. In addition, the tractability of microalgal genomes offers unprecedented possibilities to establish photosynthetic microbes as light-driven biofactories of heterologous immunotherapeutics. Here, we review the evidence-based anti-inflammatory mechanisms of microalgal metabolites and provide a detailed coverage of the genetic engineering strategies to enhance the yields of endogenous compounds and to develop innovative bioproducts.
To provide an overview of the main nailfold capillaroscopy (NFC) changes described in dermatomyositis (DM) and polymyositis (PM) and to discuss the current evidence supporting its clinical relevance ...and applications in daily practice.
All relevant literature in the field of NFC and DM and PM published in the last 30 years has been systematically reviewed. A systematic research was performed in the electronic databases PubMed and EMBASE.
A total of 540 publications were identified according to the proposed filters and 27 were included for the review. The articles have been critically analyzed with a focus on technical aspects, examined anatomical areas, main pathological capillaroscopy findings ,and the relationship between NFC alterations and critical parameters of DM and PM.
The overview confirms that NFC is a safe and noninvasive tool able to help the clinician in the diagnosis of DM and PM and to better characterize the phase of disease activity of these patients.
The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the ...previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
Abstract Objective Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, ...inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an “accident of inflammation.” Methods Extensive literature search in PubMed central. Results Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. Conclusions The article highlights the complexity of interwoven pathways of osteopenia.
Correspondence to Professor Maurizio Cutolo; mcutolo@unige.it Introduction Vitamin D and COVID-19 A growing number of concordant reports support a protective role for vitamin D in reducing at least ...the risk/severity of respiratory tract infections (RTIs), especially in the influenza and COVID-19 context.1–5 Major clinical reports show that vitamin D deficiency contribute to acute respiratory distress syndrome (ARDS) SARS-CoV-2 and that case-fatality rates increase with age and the highest SARS-CoV-2 serum concentrations.6 7 In addition, the outbreak of COVID-19 seems to occur mainly in the cold winter time, when serum 25-hydroxyvitamin D (25(OH)D—calcidiol or calcifediol) concentrations are the lowest, as well as the ultraviolet B (UVB) doses, whereas the number of cases in the Southern Hemisphere near the end of summer are lower.8- Targeted 25(OH)D serum concentration measurements and vitamin D supplementation is strongly suggested have important patient and public health benefits.9 The positive role of vitamin D replacement therapy (vDRT) in reducing risk and severity in COVID-19 patients is supported by several clinical evidences and RCTs are undergoing, however, previous experiences of RCT related to vDRT are available from other lung viral infection studies and even in mechanically ventilated adult intensive care unit (ICU) patients.10–14 These important observations are corroborated by several biological/molecular mechanisms through vitamin D can generally reduce risk of infections and downregulate the immune/inflammatory reaction. The discovered presence of the VDR in activated T cells and monocytes, first suggested in 1983 that vitamin D may have a role in the function of the immune system.19 As matter of fact, vitamin D has received increased worldwide attention for its involvement in reducing risk for several chronic diseases, besides infectious diseases, including type 1 diabetes and notably autoimmune rheumatic diseases for the reason that may interfere with the immune system.20 The biological/molecular evidence for the interactions of vitamin D with the immune response is that its final active metabolite, namely calcitriol (1,25(OH)2D3), due to its structural origin from cholesterol, is molecularly considered a steroid hormone (D-hormone) like others (ie, sex hormones, cortisol) and analogously to glucocorticoids (and sex hormones) can exerts immunomodulatory/antinflammatory activities through functional cell steroid receptors21–23 (figure 1). Furthermore, the intensity and quality of the host immune/inflammatory response seems to influence the clinical severity and mortality risk associated with viral diseases (such as influenza and COVID-19) rather than the viral pathogen itself.24 25 Consequently, it is biologically plausible that 1,25(OH)2D3 may exert immunomodulatory effects also in COVID-19 patients, playing a role in the regulation of both innate and adaptive immunity.26 The intracellular conversion of 25(OH)D (calcidiol or calcifediol) into the active metabolite 1,25(OH)2D3, (calcitriol), through the intracrine actions of the enzyme 1-alpha-hydroxylase (CYP27B1), is distinct from the 1,25(OH)2D3 produced in kidneys and released into the systemic circulation; however, both have autocrine and paracrine functions that enhance host immunity, for example, by upregulating the antimicrobial peptides cathelicidin and alpha-defensin26 (figure 1). Conclusion, vitamin D deficiency seems a prevalent and further risk factor for severe COVID-19 male patients.39 Vitamin D and RTIs: lesson from the recent experience The seasonality of viral RTIs such as those caused by influenza virus and rhinovirus has been recognised from long time and is even considered to be one of the major contributor to seasonal variations in human mortality.40 As matter of fact, a recent large study found that sunlight UV radiation dose is negatively correlated with the percent positive patients for SARS-CoV-2 and for four other common human coronaviruses in the USA, and this association is season-related with lowest vitamin D serum concentrations.41 In a large population survey (6789 participants), the prevalence of RTIs and altered lung function showed a strong seasonal pattern and linear association in the opposite direction to the vitamin D serum concentrations.42 A more detailed study evaluating the link between vitamin D concentrations and ARDS, patients with 25(OH)D3 <20 ng/mL showed a significantly higher odds of ARDS compared with patients with 25(OH)D >20 ng/mL after adjustment for age, gender, diagnostic category, staging and degree of cigarette consumption, (p=0.032).7 Interestingly, when 25(OH)D concentrations were analysed with logistic regression as a continuous exposure in 0.4 ng/mL increments, the odds of ARDS decreased by 17% for every 0.4 ng/mL increase in 25(OH)D (OR 0.83 (95% CI 0.69 to 0.98; p=0.033).7 In another study, it was found that each 4 ng/mL increase in 25(OH)D was associated with a 7% lower risk of lung infection (95 % CI 3% to 11 %) after adjustment for lifestyle, socioeconomic factors and adiposity.42 Therefore, it has been argued that vitamin D status should be taken into account as an important contributor in determining the population susceptibility to seasonal epidemic outbreaks, together with the effects of augmented indoor confinement in wintertime (ie, school) and increased circulating reservoirs of respiratory viruses.43 Furthermore, another large observational study evaluating healthy adults during the fall and winter of 2009–2010, investigated the relationship between serum 25(OH)D concentrations and incidence of acute RTIs (ARTIs).44 The result was that only 17% of patients showing serum 25(OH)D concentrations over 38
Abstract Background Despite availability of international evidence-based guidelines for osteoarthritis (OA) management, agreement on the different treatment modalities is lacking. Method A symposium ...of European and US OA experts was held within the framework of the Annual European Congress of Rheumatology to discuss and compare guidelines and recommendations for the treatment of knee OA and to reach a consensus for management, particularly for areas in which there is no clear consensus: non-pharmacological therapy; efficacy and safety of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs); intra-articular (i.a.) hyaluronates (HA); and the role of chondroitin sulfate (CS) and/or glucosamine sulfate (GS). Results All guidelines reviewed agree that knee OA is a progressive disease of the joint whose management requires non-pharmacological and pharmacological approaches. Discrepancies between guidelines are few and mostly reflect heterogeneity of expert panels involved, geographical differences in the availability of pharmacotherapies, and heterogeneity of the studies included. Panels chosen for guideline development should include experts with real clinical experience in drug use and patient management. Implementation of agreed guidelines can be thwarted by drug availability and reimbursement plans, resulting in optimal OA treatment being jeopardized, HA and symptomatic slow-acting drugs for osteoarthritis (SySADOAs) being clear examples of drugs whose availability and prescription can greatly vary geographically. In addition, primary care providers, often responsible for OA management (at least in early disease), may not adhere to clinical care guidelines, particularly for non-pharmacological OA treatment. Conclusion Harmonization of the recommendations for knee OA treatment is challenging but feasible, as shown by the step-by-step therapeutic algorithm developed by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). More easily disseminated and implemented guidance for OA treatment in the primary care setting is key to improved management of OA.
To determine the causes of death and risk factors in systemic sclerosis (SSc).
Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. ...Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation.
We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile.
Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.
Systemic sclerosis (SSc) is a disorder characterized by immune system alterations, vasculopathy and fibrosis. SSc-related interstitial lung disease (ILD) represents a common and early complication, ...being the leading cause of mortality. Monocytes/macrophages seem to have a key role in SSc-related ILD. Interestingly, the classically (M1) and alternatively (M2) activated monocyte/macrophage phenotype categorization is currently under revision. Our aim was to evaluate if circulating monocyte/macrophage phenotype could be used as biomarker for lung involvement in SSc. To this purpose we developed a wide phenotype characterization of circulating monocyte/macrophage subsets in SSc patients and we evaluated possible relations with lung involvement parameter values.
A single centre cross-sectional study was performed in fifty-five consecutive SSc patients, during the year 2017. All clinical and instrumental tests requested for SSc follow up and in particular, lung computed tomography (CT) scan, pulmonary function tests (PFTs), Doppler echocardiography with systolic pulmonary artery pressure (sPAP) measurement, blood pro-hormone of brain natriuretic peptide (pro-BNP) evaluation, were performed in each patient in a maximum one-month period. Flow cytometry characterization of circulating cells belonging to the monocyte/macrophage lineage was performed using specific M1 (CD80, CD86, TLR2 and TLR4) and M2 surface markers (CD204, CD163 and CD206). Non-parametric tests were used for statistical analysis.
A higher percentage of circulating CD204
CD163
CD206
TLR4
CD80
CD86
and CD14
CD206
CD163
CD204
TLR4
CD80
CD86
mixed M1/M2 monocyte/macrophage subsets, was identified to characterize patients affected by SSc-related ILD and higher systolic pulmonary artery pressure. Mixed M1/M2 monocyte/macrophage subset showed higher percentages in patients positive for anti-topoisomerase antibody, a known lung involvement predictor.
The present study shows for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentages are associated with ILD, sPAP and anti-topoisomerase antibody positivity in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidemiology of chronic musculoskeletal pain Cimmino, Marco A., MD; Ferrone, Carmela, MD; Cutolo, Maurizio, MD
Best practice & research. Clinical rheumatology,
04/2011, Letnik:
25, Številka:
2
Journal Article
Recenzirano
Chronic widespread pain (CWP) due to musculoskeletal conditions is a major social burden. The case definition of CWP relies on pain, chronicity (more than 3 months’ duration) and widespread ...distribution (both sides of the body including the axial skeleton). Health Interview Survey (HIS) and Health Examination Survey (HES) have been used to assess the frequency of CWP in the general population. Unfortunately, both techniques are poorly standardised, which hampers comparison of data pertaining to different populations and countries. A major effort in the European Union (EU) is the development of common strategies to investigate musculoskeletal pain through HIS. Issues to be addressed include: (1) loss of daily life functions due to pain; (2) pain duration and rhythm; (3) affected sites; and (4) type of pain. We know that musculoskeletal pain affects between 13.5% and 47% of the general population, with CWP prevalence varying between 11.4% and 24%. Risk factors for musculoskeletal pain include age, gender, smoking, low education, low physical activity, poor social interaction, low family income, depression, anxiety and sleep disorders, as well as performing manual work, being a recent immigrant, non-Caucasian and widowed, separated or divorced.
The aim of this pilot study was to assess peripheral blood perfusion (PBP) by a new technique, the laser speckle contrast analysis (LASCA), in systemic sclerosis (SSc) patients showing different ...patterns of nailfold microangiopathy. Correlations between LASCA and single laser Doppler flowmetry (LDF) analysis were also checked.
Sixty-one SSc patients and 61 healthy subjects were enrolled. PBP was evaluated using LASCA and LDF. Scleroderma patterns and microangiopathy evolution score (MES) were assessed by nailfold videocapillaroscopy (NVC).
As detected by LASCA and LDF, PBP was lower in SSc patients than in healthy subjects (p<0.0001), showing SSc patients with the 'Early', 'Active' or 'Late' NVC pattern a progressively lower PBP (p=0.04 and p=0.002, respectively). There was a negative correlation between PBP and MES values (p=0.006 and p=0.002 for LASCA and LDF, respectively). A positive correlation was detected between LASCA and LDF values, in all subjects (p<0.0001). However, LASCA evaluates larger skin areas, is significantly less time consuming, is more accepted by patients and shows lower intra-operator variability than LDF.
LASCA detected lower PBP in SSc patients than in healthy subjects, and for the first time, LASCA perfusion values were found correlated with progression of NVC patterns of microangiopathy.
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