Osteoporosis and diabetes - possible links and diagnostic difficulties.

Objectives: In this review, the authors aimed to clarify the relationship between the occurrence of osteoporosis and diabetes, analyze the differences between the pathogenesis of osteoporosis in different types of diabetes and propose the most effective diagnostic strategy and fracture risk assessment in diabetic patients. Material and methods: A analysis of publications in MEDLINE, COCHRANE and SCOPUS databases was performed, searching for reports on the diagnostics, fracture risk assessment, prevention, and treatment of osteoporosis in patients with diabetes mellitus (DM) published in the years 2016-2022. The key words for the search were: diabetes, osteoporosis, and low-energy fracture. Results: Bone complications of T1DM are more severe than T2DM, because of the lack of anabolic effect of insulin on bones. In T2DM the risk of fractures is elevated; however, identifying the mechanisms underlying the increased risk of fractures in T2DM is not clear. The FRAX tool is not appropriate for assessing the fracture risk in young patients with T1DM. It is quite useful in older patients with T2DM, but in these patients the calculated fracture risk may be underestimated. In T2DM the fracture risk often does not correspond to BMD value as measured by dual-energy X-ray absorptiometry (DXA). Diagnostic tools such as the trabecular bone score may play a significant role in this group of patients. Conclusions: Optimal strategies to identify and treat high risk individuals require further research and proper definition. The diagnostic criteria for osteoporosis should be clearly defined as well as fracture risk assessment and choice of anti-osteoporotic medication. In all cases of secondary osteoporosis, treatment of the underlying disease is the most important. The relationship between high risk of fractures and diabetes is inseparable, and its full understanding seems to be the key to effective management.

Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: a retrospective study based on POLVAS registry.

OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Comprehensive microRNA and transcriptomic profiling of rheumatoid arthritis monocytes: role of microRNA-146b in pro-inflammatory progression.

OBJECTIVE: To explore global miRNA and transcriptomic profiling of monocytes from RA patients compared with healthy controls in order to predict which aberrantly expressed miRNA can negatively modulate inflammatory molecules. METHODS: Using next-generation sequencing, we have performed simultaneous global analysis of miRNA (miRNA-seq) and transcriptome (RNA-seq) of monocytes from RA patients and healthy controls. Global analysis of miRNA of SSc monocytes was also performed. Following differential analysis and negative correlation, miRNA-RNA pairs were selected. RESULTS: We found that 20 specific miRNA candidates are predicted to silence inflammatory mediators, out of 191 significantly changed miRNAs in RA monocytes. Based on the highest scoring in terms of negative correlation (r = -0.97, P = 1.75e-07, false discovery rate = 0.04) and the number of seeds in miRNA responsible for negative regulation, we selected miRNA-146b and its target gene anti-inflammatory retinoic acid receptor alpha (RARA). Similarly to next-generation sequencing, qPCR analysis also confirmed negative correlation between miRNA-146b and RARA expression (r = -0.45, P = 0.04). Additionally, miRNA-146b expression in RA monocytes significantly correlated with clinical parameters including DAS28 for RA with CRP (DAS28-CRP) and ESR (DAS28-ESR), whereas overexpression of miRNA-146b was able to functionally reduce RARA expression in the human monocytic cell line THP-1. Finally, circulating miRNA-146b expression in sera and SFs was significantly elevated in RA patients. CONCLUSIONS: Overall, in this study we have identified a new miRNA-146b candidate that is predicted to negatively regulate the anti-inflammatory RARA transcript, whereas circulating miRNA-146b level can be used as a biomarker predicting pro-inflammatory RA progression and disease activity.

Clinical Utility of Trabecular Bone Score (TBS) in Fracture Risk Assessment of Patients with Rheumatic Diseases Treated with Glucocorticoids.

Chronic glucocorticoid therapy is associated with osteoporosis and can cause fractures in up to 50% of patients. Increased risk of fractures in patients with glucocorticoid-induced osteoporosis does not result only from the decreased bone mineral density (BMD) but also bone microarchitecture deterioration. Trabecular bone score (TBS) is a method complementary to DXA, providing additional information about trabecular bone structure. The aim of this study was to assess the clinical utility of TBS in fracture risk assessment of patients treated with glucocorticoids. Patients with rheumatic diseases treated with glucocorticoids for at least 3 months were enrolled. All recruited patients underwent DXA with additional TBS assessment. We analyzed the frequency of osteoporosis and osteoporotic fractures and assessed factors that might be associated with the risk of osteoporotic fractures. A total of 64 patients were enrolled. TBS and TBS T-score values were significantly lower in patients with osteoporosis compared to patients without osteoporosis. Low energy fractures occurred in 19 patients. The disturbed bone microarchitecture was found in 30% of patients with fractures without osteoporosis diagnosis based on BMD. In the multivariate analysis, only TBS and age were significantly associated with the occurrence of osteoporotic fractures. TBS reflects the influence of glucocorticoid therapy on bone quality better than DXA measured BMD and provides an added value to DXA in identifying the group of patients particularly prone to fractures.

Subphenotypes of ANCA-associated vasculitis identified by latent class analysis.

OBJECTIVES: ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV. METHODS: In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry. RESULTS: LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. CONCLUSIONS: Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.

Patterns of dyslipidemia in young patients with seronegative spondyloarthropathies without cardiovascular diseases.

OBJECTIVES: Patients with seronegative spondyloarthritis (SpA) - psoriatic arthritis (PsA) and ankylosing spondylitis (AS) - have a higher risk of cardiovascular morbidity and mortality. The aim of the present study was to evaluate the incidence and type of dyslipidemia, a potent atherosclerosis risk factor, in SpA patients. MATERIAL AND METHODS: It was a two-center, case-control study. Patients diagnosed with PsA and AS aged 23-60 years, with disease duration < 10 years, were enrolled. The inflammatory activity, serum levels of C-reactive protein (CRP) and lipid profile were evaluated in each patient. In patients > 40 years old, the 10-year risk of fatal cardiovascular disease (CVD), using Systematic Coronary Risk Evaluation (SCORE), was estimated. RESULTS: In total 79 patients with SpA were included in the study, with PsA diagnosed, n = 39 (mean age 45.1 ±9.6 years; 21, 53.9%, women), and with AS diagnosed, n = 40 (age 40.3 ±9.5; 12.3%, women), control group (CG): n = 88 (age 42.3 ±8.1; 42, 47.7% women). Based on the interview and laboratory tests, dyslipidemia was diagnosed in 19 (47.5%) patients with AS and in 28 (71.8%) patients with PsA. Most patients had hypercholesterolemia or mixed hyperlipidemia. Types of dyslipidemia were similar. In SpA patients (PsA and AS), the level of triglycerides (TG) and atherogenic index (AI) were significantly higher than in the CG, respectively TG in SpA: 116 (83-156) and in the CG: 91.2 (72.6-134.6) mg/dl, p = 0.0182; AI in SpA: 3.77 ±1.26 and in the CG: 2.58 ±1.27, p < 0.0001.The low-density cholesterol (LDL) level was significantly lower in SpA patients than in the CG, SpA: 109.1 ±29.4 vs. CG: 125.2 ±35.9 mg/dl, p = 0.0023. There was a strong negative correlation between CRP levels and HDL cholesterol levels in patients with PsA, rho = 0.42, p = 0.0132. Mean SCORE values were 2.33% in PsA patients and 2.38% in AS patients, which results in moderate 10-year risk of death from CVD. CONCLUSIONS: In young patients with spondyloarthropathies, inflammatory factors significantly influence dyslipidemia patterns, which result in higher TG and lower LDL cholesterol levels. In patients with PsA, dyslipidemia was diagnosed more often than in patients with AS.

EULAR/eumusc.net standards of care for rheumatoid arthritis: cross-sectional analyses of importance, level of implementation and care gaps experienced by patients and rheumatologists across 35 European countries.

OBJECTIVE: As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. METHODS: Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. RESULTS: Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. CONCLUSIONS: Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (ß=-0.5 (95% CI -0.9 to -0.2) and ß=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.

Salivary interleukin 6, interleukin 8, interleukin 17A, and tumour necrosis factor α levels in patients with periodontitis and rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) and periodontitis share risk factors and inflammatory pathways that could be related to cytokines, such as interleukin (IL)-6, IL-8, IL-17A, and tumour necrosis factor-α (TNF-α). The aim of this study was to compare periodontal status and salivary levels of selected cytokines between patients diagnosed with RA and periodontitis. RA patients were assessed for the potential influence of anti-rheumatic therapy. MATERIAL AND METHODS: One hundred and six patients were enrolled in a cross-sectional study. Medical assessment and periodontal examination were performed in 35 patients with chronic periodontitis, in 35 patients with RA and chronic periodontitis, and in 36 controls. Unstimulated whole saliva samples were analysed for IL-6, IL-8, IL-17A, and TNF-α. RESULTS: Significant differences in biomarkers and periodontal parameters were found among groups. Study groups exhibited higher mean pocket depth (PD), number of PD > 4 mm, and mean clinical attachment loss, when compared with controls. The RA group had lower bleeding on probing index and PD, but higher values of plaque indices than the periodontitis group. Concentration of evaluated cytokines were higher in the RA and periodontitis groups, compared with controls. The periodontitis group showed also higher levels of IL-6, IL-17A, and TNF-α in comparison to RA. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticosteroids. CONCLUSIONS: Salivary levels of IL-6, IL-8, IL-17A, and TNF-α can be affected by periodontitis, RA, and presumably DMARDs. DMARD therapy appears to reduce destructive and inflammatory processes in periodontal tissues because lower values of PD, BOP, and salivary levels of IL-6, IL-17A, and TNF-α were found in RA.

Acute Achilles tendon rupture after treatment with levofloxacin in a patient with giant cell arteritis.

The authors report a case of a 67-year-old woman with giant cell arteritis with acute Achilles tendon rupture, which occurred after 3 days of levofloxacin therapy introduced because of newly diagnosed erosive gastritis associated with Helicobacter pylori infection. The Achilles tendon rupture was surgically treated and the patient made a complete recovery. In view of the widespread use of levofloxacin in practice, this case report raises important clinical implications. Tendinopathies are a known complication, quite rare in the healthy population, but the risk of rupture significantly increases in the population of patients over 60 years of age, with chronic usage of glucocorticosteroids, impaired renal function and recipients of organ transplants. What needs underlining, there are also described differences between individual fluoroquinolones as a cause of tendon damage in this group. Considering the widespread use of this group of drugs in patients, knowledge about the risk of adverse events including tendinopathy promotes safe use of fluoroquinolones.

Cardiovascular risk assessment in rheumatoid arthritis - controversies and the new approach.

The current methods of cardiovascular (CV) risk assessment in the course of inflammatory connective tissue diseases are a subject of considerable controversy. Comparing different methods of CV risk assessment in current rheumatoid arthritis (RA) guidelines, only a few of them recommend the use of formal risk calculators. These are the EULAR guidelines suggesting the use of SCORE and the British Society for Rheumatology guidelines performed in collaboration with NICE preferring the use of QRISK-2. Analyzing the latest American and British reports, two main concepts could be identified. The first one is to focus on risk calculators developed for the general population taking into account RA, and the calculator that might fulfill this role is the new QRISK-2 presented by NICE in 2014. The second concept is to create RA-specific risk calculators, such as the Expanded Cardiovascular Risk Prediction Score for RA. In this review we also discuss the efficiency of a new Pooled Cohort Equation and other calculators in the general and RA population.

Symptom-modifying effects of oral avocado/soybean unsaponifiables in routine treatment of knee osteoarthritis in Poland. An open, prospective observational study of patients adherent to a 6-month treatment.

OBJECTIVES: Observational studies provide insights into real-life situations. Therefore, we assessed the effects of oral avocado/soybean unsaponifiable (ASU) capsules on pain relief and functional ability in patients, while they were receiving a routine treatment for knee osteoarthritis (OA). MATERIAL AND METHODS: An open, prospective, observational 6-month study was conducted in 99 centers in Poland in a group of 4822 patients with symptomatic knee OA receiving one 300 mg ASU capsule/day as a routine medication. The patients had no diagnoses of other rheumatic diseases and were not treated with other symptomatic slow-acting drugs for osteoarthritis (SYSADOAs). Data on OA symptoms and therapy were collected from the initiation of ASU treatment (visit 0) and during 3 consecutive control visits performed every 2 months (visits 1-3). Functional Lequesne index, severity of joint pain of one symptomatic knee (Laitinen index and VAS), use of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), adherence to treatment and adverse events were evaluated and recorded using electronic Case Report Forms. RESULTS: Four thousand one hundred and eighty-six patients (86.8%) attended all 4 visits. In 94.2% of patients (mean age 60.7 ±11.6 years SD, 73.4% female) at least one OA risk factor was identified. There was a significant improvement in functional ability between the last and baseline visits as evidenced by the median Lequesne index decreasing from 8 to 4 points (p < 0.001). Measures of pain intensity also fell significantly (p < 0.001) throughout the study: median Laitinen score decreased from 6 to 3 points, median pain at rest VAS - from 1.8 to 0 cm and median pain during walking VAS - from 5.6 to 1.9 cm. The significant differences were also noted between consecutive visits. The proportion of patients using analgesics and NSAIDs declined from 58.8% at the baseline visit to 24.9% at the last visit 3 (p < 0.001). Defined daily dose of NSAIDs decreased significantly from 1 at the baseline visit to 0.67 at the visit 3. Severe adverse events associated with ASU treatment were not observed. CONCLUSIONS: It was the first observational study in Poland evaluating the effects of routine knee OA treatment with oral ASU. Only a small group of patients (13.2%) treated with ASU discontinued the study. The majority of patients adherent to the ASU treatment for 6 months showed gradual alleviation of joint pain, improvement in functional ability and a significant reduction in NSAIDs intake.

Secretory activity of subcutaneous abdominal adipose tissue in male patients with rheumatoid arthritis and osteoarthritis - association with clinical and laboratory data.

INTRODUCTION: Adipose tissue exerts widespread effects on the metabolism and immune system, but its activity differs between the genders. In the general population low-grade adipose tissue inflammation contributes to development of diseases of affluence. Little is known about the systemic impact of peripheral fat tissue in osteoarthritis (OA) and rheumatoid arthritis (RA), characterized by chronic, low- and high-grade systemic inflammation, respectively. To clarify this we evaluated the secretory activity of subcutaneous abdominal adipose tissue (SAAT) obtained from male patients affected with RA (n = 21) and OA (n = 13), and assessed its association with body mass and composition, demographic, clinical and laboratory data. MATERIAL AND METHODS: Basal and interleukin (IL)-1ß-triggered secretion of selected adipocytokines from SAAT explants was measured by specific enzyme-linked immunosorbent assays (ELISA). Patients' body composition was evaluated by bioelectric impendence technique. RESULTS: Rheumatoid SAAT secreted more adiponectin and macrophage migration inhibitory factor (MIF) than respective osteoarthritis tissue. In both RA and OA patient groups, stimulation of SAAT explants with IL-1ß (1 ng/ml/100 mg tissue) significantly up-regulated release of pro-(IL-6, IL-8, tumor necrosis factor - TNF) and anti-inflammatory (IL-10) cytokines but had no effect on the secretion of adiponectin, leptin, MIF and hepatocyte growth factor (HGF). Compared with RA, patients with OA were more obese. In RA patients SAAT-released adiponectin and TNF inversely correlated with body mass index (BMI) and visceral fat rating (FVSC). In addition, SAAT-secreted adiponectin and leptin positively correlated with DAS28 and disease duration, respectively. In the OA group tissue-released TNF positively correlated with patients' age. CONCLUSIONS: We conclude that in RA male patients adipocytokines originating from SAAT are of clinical importance because: (i) adiponectin and TNF may contribute to maintenance of normal body composition and mass, (ii) in addition adiponectin may play a pathogenic role. Moreover, in both RA and OA male patients secretory activity of SAAT may vary with time.

Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Guidelines for the diagnosis and management of osteoporosis in Poland. Update 2022.

Guidelines to provide an update of the previously published Polish recommendations for the management of women and men with osteoporosis have been developed in line with advances in medical knowledge, evidence-based data, and new concepts in diagnostic and therapeutic strategies. A Working Group of experts from the Multidisciplinary Osteoporosis Forum and from the National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw performed a thorough comprehensive review of current relevant publications in the field (including all age groups of people and management of secondary osteoporosis), and they evaluated epidemiological data on osteoporosis in Poland and the existing standards of care and costs. A voting panel of all co-authors assessed and discussed the quality of evidence to formulate 29 specific recommendations and voted independently the strength of each recommendation. This updated practice guidance highlights a new algorithm of the diagnostic and therapeutic procedures for individuals at high and very high fracture risk and presents a spectrum of general management and the use of medication including anabolic therapy. Furthermore, the paper discusses the strategy of primary and secondary fracture prevention, detection of fragility fractures in the population, and points to vital elements for improving management of osteoporosis in Poland.

Associations of IL-18 with Altered Cardiovascular Risk Profile in Psoriatic Arthritis and Ankylosing Spondylitis.

OBJECTIVE: To investigate the associations of IL-18 serum levels with serum lipids, cardiovascular risk, and disease activity in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with axial (axPsA) and peripheral (perPsA) joint involvement. METHODS: 155 adult patients (PsA 61/AS 94) were enrolled in the study. Standard disease activity indices, BASDAI, and ASDAS, were calculated for AS and PsA and DAPSA for PsA. Sera from peripheral blood samples were obtained after night fasting. Serum concentrations of cytokines (IL-18, IL-17) were measured by ELISA, while lipid profile with total cholesterol (TC), triglycerides (TG), low-density cholesterol-(LDL), high-density cholesterol (HDL), and C-reactive protein (CRP) concentrations were determined using routine procedures. The atherogenic index was calculated using the standard formula AI = TC/HDL. RESULTS: Patients with PsA and peripheral joint involvement (perPsA) had significantly higher IL-18 serum levels than axial PsA and AS patients (medians 160 vs. 116 vs. 80 pg/mL). In patients with PsA and in the subgroup with PsA+ ischemic heart disease (IHD), IL-18 positively correlated with atherogenic index (AI) (rho = 0.46 and rho = 0.67, respectively) and TG serum concentrations (rho = 0.4 and rho = 0.675), while negatively with HDL levels (rho = -0.37 and rho = -0.608). In PsA + IHD subgroup IL-18 serum levels correlated positively also with disease activity (DAPSA) (rho = 0.613). Importantly, in patients with perPsA, characterized by the highest IL-18 serum levels, cardiovascular risk, and frequency of both hypertriglyceridemia and IHD, positive correlations between IL-18 and IL-17 (rho = 0.47, p = 0.002), TG (rho = 0.45 p = 0.01) levels and AI (rho = 0.63 p = 0.021) were found. Whereas linear regression models revealed that IL-17, TG concentrations and the tender joint count had an impact on IL-18 Conclusions: We confirmed that patients with perPsA are characterized by a more pronounced proinflammatory and proatherogenic cardiovascular risk profile than patients with axPsA and AS. Importantly our study indicates that in PsA, but not in AS, elevated serum concentration of IL-18 is associated with higher disease activity and proatherogenic lipid profile, leading to a higher cardiovascular risk. Thus, our results point out IL-18 as a critical contributor in these pathological processes and possible therapeutic targets.

Seasonally Dependent Change of the Number of Fractures after 50 Years of Age in Poland-Analysis of Combined Health Care and Climate Datasets.

Aim: The incidence of fractures correlates with many independent and interrelated factors. The aim of the study was to examine trends in fracture incidence and to find possible reasons for changes. Materials and methods: A complete dataset of Polish population aged above 50 from the National Heath Fund­which is a single, state-owned payer for the health service procedures in Poland­covering the years between 2010 and 2015 was analyzed along with climate dataset. Results: The analysis indicated that there was a substantial and statistically significant decrease in the incidence of forearm and hip fractures (p = 0.007 and 0.007, respectively). On the other side, there was a statistically significant increase in incidence of humerus and lumbar fractures (p = 0.002, p < 0.001, respectively). The observed changes (especially decrease in forearm and hip fracture incidence) happened mostly in the cold season and were correlated to mean-temperature changes during the assessed time period. Conclusion: In the analysis based on the dataset obtained from fracture-related database collected in Poland in the years 2010−2015 in the population of patients over 50 years of age, we observed that the changes of fracture incidence during the observation period are associated with and may be dependent on the season (warmer versus colder) and on mean temperature increase during the observation period.

Circulating miRNA Correlates with Lipid Profile and Disease Activity in Psoriatic Arthritis, Rheumatoid Arthritis, and Ankylosing Spondylitis Patients.

This study aimed to investigate the associations of microRNA (miRs) signatures with cytokines, serum lipids, and disease activity in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA). In total, 65 patients (PsA n = 25, AS n = 25, RA n = 15) and 25 healthy controls (HC) were enrolled into the study. The expression of miR-223-5p, miR-92b-3p, miR-485-3p, miR-10b-5p, let-7d-5p, miR-26a-2-3p, miR-146b-3p, and cytokines levels were measured in sera. DIANA-mirPath analysis was used to predict pathways targeted by the dysregulated miRs. Disease activity scores were calculated. Lipid profile, uric acid, glucose level, and C-reactive protein (CRP) concentrations were determined in the blood. Based on lipid profiles, the PsA group had hypertriglyceridaemia, and RA patients revealed mixed dyslipidaemia, while in AS, no specific changes were found. miR expression analysis revealed upregulation of miR-26a-2-3p and miR-10b-5p in PsA, miR-485-3p in AS, and let-7d-5p in RA. Several correlations between disease activity indexes, metabolites levels, and expression of miRs were observed in PsA, RA, and AS patients. Finally, in ROC analysis, miR-26a-2-3p/miR-485-3p, and let-7d-5p/miR-146b-3p tandems revealed high sensitivity and specificity in distinguishing between PsA, AS, and RA. Our study illustrates the superiority of miR expressions in distinguishing between RA, PsA, and AS. In PsA, a unique regulatory pathway exists through miR-26a-2-3p, miR-223-5p, miR-10b-5p, and miR-92b-3p that converges proatherogenic metabolism and disease activity.

Association of antineutrophil cytoplasmic antibody (ANCA) specificity with demographic and clinical characteristics of patients with ANCA­associated vasculitides.

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the presence of proteinase­3 (PR3) or myeloperoxidase (MPO) ANCA. In over 90% of cases, PR3­ANCA is associated with granulomatosis with polyangiitis (GPA). However, it is also rarely found in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). On the other hand, MPO­ANCA being characteristic of MPA (>90% of cases), is also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. OBJECTIVES: In this study, we analyzed the clinical and demographic characteristics of AAV subgroups identified by ANCA serotype. PATIENTS AND METHODS: We conducted a multicenter study of AAV patients (417 GPA, 106 MPA, 102 EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. The data were systematically collected according to a standardized protocol. RESULTS: In the ANCA-positive group (anti­MPO, anti­PR3) a male-to-female ratio was 1:1, whereas in the ANCA-negative group it was 1:2, regardless of AAV diagnosis. Anti­MPO antibodies were present in significantly older patients. Patients with MPO+GPA and MPO+EGPA were older than those with corresponding ANCA­negative GPA and EGPA as well as PR3+AAV. Moreover, ANCA­negative AAV was characterized by a low risk of end­stage kidney disease and death. CONCLUSIONS: The presence and specificity of ANCA in AAV patients are related to sex and age, determine their organ involvement and influence mortality as previously shown. Patients with MPO­ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3­ANCA-positive patients are much more clinically heterogeneous. ANCA-negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis.

Trabecular Bone Score (TBS) in Patients with Early Ankylosing Spondylitis-Limited Utility.

PURPOSE: Ankylosing spondylitis (AS) not only results in pathological ossification of the spine, but can also be associated with osteoporosis. Due to the presence of syndesmophytes and possible involvement of the hip joints, classical dual X-ray absorptiometry (DXA) is of limited use in patients with advanced stages of AS. Trabecular bone score (TBS) is a method complementary to DXA, providing additional information about bone microarchitecture. There is a growing body of evidence for the usefulness of TBS in AS patients. The aim of this study was to assess the clinical utility of TBS in patients with AS. METHODS: Patients with AS underwent DXA with additional TBS assessment. A cross-sectional analysis of the frequency of osteoporosis and bone microarchitecture deterioration and their association with patients' characteristics was done. RESULTS: A total of 51 male patients, mean age 40.7 years, were enrolled. Osteoporosis was diagnosed in seven patients (13.7%). Lumbar bone mineral density (BMD) was higher (p < 0.001) than femoral BMD, indicating abnormal BMD readings in the spine caused by syndesmophytes. Patients with DXA-diagnosed osteoporosis had lower TBS (p = 0.03) and TBS T-score (p = 0.043) values compared to patients without osteoporosis. However, disturbed bone microarchitecture (TBS < 1.23) was present in only three patients (5.9%). None of the patients had a history of an osteoporotic fracture. A lower TBS T-score (p = 0.032) was demonstrated in patients with sacroiliitis grade 4 than in patients with sacroiliitis grade 2, with no significant differences in BMD and T-score values. CONCLUSION: Among patients with early AS, the clinical utility of TBS is limited-it does not add value to DXA.