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.

Cranial and extracranial manifestations of giant cell arteritis: a single-center observational study.

INTRODUCTION: Giant cell arteritis (GCA) presents two major phenotypes - cranial (cGCA) and extracranial (exGCA). exGCA may be overlooked. The study aimed to compare the clinical characteristics between cGCA and exGCA. METHODS: Electronic medical records of patients treated between January 2015 and July 2023 at the Department of Rheumatology were searched for the diagnosis of GCA. The clinical characteristics of patients with cGCA, exGCA, and overlapping GCA manifestations were compared. RESULTS: Out of 32 patients with GCA, 20 had cGCA, 7 had exGCA, and 5 had overlap manifestations. The groups did not differ significantly in demographics, clinical signs/symptoms, or laboratory test results. Importantly, the combined group of patients with exGCA and overlap GCA had a statistically significant delay in initiating treatment (median 12 weeks) compared to patients with cGCA (median 4 weeks; p = 0.008). CONCLUSION: Our study confirmed the insidious nature of exGCA, which lacks distinctive clinical symptoms and consequently leads to delayed treatment.

Time Trend Analysis of Comorbidities in Ankylosing Spondylitis: A Population-Based Study from 53,142 Hospitalizations in Poland.

BACKGROUND: (1) Influence of comorbidities on life expectancy and treatment outcomes is one of the main concerns of modern rheumatology, due to their rising prevalence and increasing impact on mortality and disability. The main objective of our study was to analyze the time trends and shifts in the comorbidity profile and mortality over 10 years in the Polish population with ankylosing spondylitis (AS). (2) Data from 2011-2020 years were acquired from the General Hospital Morbidity Study in the National Institute of Public Health-National Institute of Hygiene (NIH-PIB) as ICD-10 codes. Based on ICD10 codes, we calculated the percentage shares for comorbidities, with the relative risk ratios and odds ratios. We analyzed the hospitalization rates and mortality from the overlapping conditions. Also, we analyzed age and sex related differences in the clinical manifestations of AS patients. (3) Results: From 53,142 hospitalizations of patients with AS, we found that the male population presented higher rates of cardiovascular (2.7% vs. 1.3% p < 0.001) and pulmonary conditions (1.2% vs. 0.8% p < 0.025). Inflammatory bowel diseases were more common in the female population than in males (2.3% vs. 1.7%, p < 0.001). In the years 2011-2020, we observed a decline in the number of hospitalized patients due to cardiovascular (p < 0.001) and respiratory system conditions (p < 0.001), yet the relative risk and odd ratios remained high. In the years 2011-2020, 4056 patients received biological treatment (7%). The number of initiated biological therapies correlated negatively with the number of reported hospitalizations due to ischemic heart diseases (IHD) (p < 0.031, r = -0.8). Furthermore, in the logistic regression model, we found strong collinearity between cardiovascular and pulmonary comorbidities (VIF = 14; tolerance = 0.1); also, the number of reported IHD's correlated positively with the number of pulmonary infections (p < 0.031, r = 0.7) (4). CONCLUSIONS: Cardiopulmonary comorbidities are a main factor associated with increased mortality in patients with AS, especially in hospitalized patients. The mortality rates among patients with AS admitted to hospital due to other conditions other than movement disorders exceed the populational risk. The number of biologically treated patients correlated negatively with hospital admissions due to IHD.

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.

Combination Treatment of Locoregionally Aggressive Granulomatosis with Polyangiitis and Cranial Base Infiltration.

OBJECTIVES: To present a personalized approach in three cases of treatment-resistant, locoregionally aggressive forms of cANCA-positive granulomatosis with polyangiitis (GPA) and skull base involvement. METHODS: Three patients with GPA and skull base involvement were described alongside a critical review of the current literature. RESULTS: All presented patients suffered from GPA with an inflammatory tumor at the skull base, alongside cerebellopontine angle involvement, cranial nerve palsies, cerebellar disorders, concomitant hearing loss, and severe otalgia. Symptoms were associated with progressive granulomatous destruction of the temporal bone, laryngopharynx, and central nervous system infiltration. Treatment with cyclophosphamide and high doses of glucocorticoid steroids were ineffective but subsequent therapy with rituximab was successful in the presented cases. The literature review showed that the course of the disease with skull base involvement is associated with poorer clinical and radiological responses to standard pharmacotherapies. CONCLUSION: Granulomatous inflammation localized in the skull base is associated with a more aggressive disease progression and is less likely to respond to pharmacotherapy. Standard induction therapy with cyclophosphamide and glucocorticoid steroids may be ineffective. A better response may be achieved by using rituximab and concomitant local treatment with glucocorticoid steroid injections.

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients.

Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. In 29 IA patients and 16 healthy controls (HC), humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p = 0.026 and p = 0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.

The Assessment of the Quality of Life in Patients with Rheumatoid Foot.

BACKGROUND: The negative effects of rheumatoid arthritis (RA) are multi-dimensional. Foot deformities lead to disability, pain, and impaired quality of life. OBJECTIVE: Identifying the difficulties in functioning rheumatoid foot and assessing the quality of life in this aspect. MATERIALS AND METHODS: The material included 50 patients of Rheumatology Policlinic of the Central Clinical Hospital of Interior Affairs in Warsaw and a matched control group of 50 individuals without RA. The degree of foot joint damage was assessed using the Manchester scale, lower limb movement and quality of life using the American Orthopedic Foot and Ankle Society Score and HAQ. RESULTS: The duration of symptoms was 16.0 ± 8.9 years. High activity of RA measured by the DAS was observed in 20% of patients, moderate in 26%, and low in 54%. The most common foot deformities were: hammer toes (82%), longitudinal flat feet (74%), and hyperkeratosis (56%). The least frequent were: stiff toe (38%) and overlapping fingers (28%). In the RA group, the outcomes of the FAOS questionnaire were statistically significantly worse than in the control group in all categories (p<0.001). The worst-rated domain was the sport and recreation subscale (median 55.0), the best daily activity (median 86.8). The strongest relationship was demonstrated between the FAOS and HAQ indices. Spearman's HAQ correlation coefficient with the ADL subscale was r=-0.85, p<0.001; with the QOL, sport/recreation and pain subscales moderate, it was r=-0.72; r= 0.71, p <0.001. CONCLUSION: Lower limb movement function and quality of life are worse in RA patients; pain accompanies climbing and descending stairs; running and jumping require effort.

Heart disease in the course of systemic sclerosis - an observational study.

Introduction: Cardiac involvement is one of the major mortality factors in systemic sclerosis (SSc). This observational study aimed to compare patients with and without heart involvement in the course of SSc. Material and methods: Electronic medical records of patients treated between January 2021 and August 2022 in the Department of Rheumatology were searched for the diagnosis of SSc (ICD-10 code M47). The clinical characteristics of patients with and without heart involvement in the course of SSc were compared. Results: Out of 36 patients with SSc, 7 patients were diagnosed with heart disease in the course of SSc. The major type of cardiac involvement was myocarditis (71%). The majority of patients with heart involvement had elevated troponin (86%) and NT-proBNP (71%) concentrations. The most common finding observed in echocardiography was diastolic failure (71%). The most frequent abnormality found in 24-hour Holter ECG was isolated supraventricular extrasystoles (100%). Risk factors for developing heart disease in the course of SSc were male gender (p = 0.018), diffuse type of SSc (p = 0.03), higher values of modified Rodnan skin score (p < 0.001), gastrointestinal tract involvement (p = 0.027) and myositis (p = 0.018). Conclusions: Optimal screening for heart disease is needed in this group of patients.

Humoral and cellular immunogenicity of COVID-19 booster dose vaccination in inflammatory arthritis patients.

Introduction: Previous studies have shown a reduction in the effectiveness of primary COVID-19 vaccination in patients with rheumatic diseases. However, limited data is available regarding the effectiveness of the COVID-19 vaccine booster dose, especially on cellular response. The study aimed to assess the humoral and cellular immunogenicity of a booster dose in patients with inflammatory arthritis (IA). Patients and methods: 49 IA and 47 age and sex-matched healthy controls (HC) were included in a prospective cohort study. Both groups completed primary COVID-19 vaccination and after more than 180 days received a BNT162b2 booster shot. Humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before and after 4 weeks from the booster dose of the vaccine. Results: After the booster dose, all participants showed an increased humoral response, although significantly reduced antibody levels were observed in IA patients compared to HC (p=0.004). The cellular response was significantly lower both before (p<0.001) and after (p<0.001) the booster dose in IA patients as compared to HC. Among the immunomodulatory drugs, only biological and targeted synthetic drugs lowered the humoral response after booster vaccination. However, the cellular response was decreased after all immunomodulatory drugs except IL-17 inhibitors and sulfasalazine. Conclusion: Our data indicate that patients with rheumatic diseases present lower humoral and cellular responses after the COVID-19 booster vaccine in comparison to HC. This may translate into a recommendation for subsequent booster doses of the COVID-19 vaccine for rheumatic patients.

The Clinical Utility of Dual-Energy Computed Tomography in the Diagnosis of Gout-A Cross-Sectional Study.

Dual-energy computed tomography (DECT) is an imaging technique that detects monosodium urate (MSU) deposits. This study aimed to assess the clinical utility of DECT in the diagnosis of gout. A total of 120 patients with clinical suspicion of gout who underwent DECT were retrospectively enrolled. The sensitivity and specificity of DECT alone, American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria without DECT, and ACR/EULAR criteria with DECT were assessed. Additionally, an analysis of gout risk factors was performed. When artifacts were excluded, any MSU volume provided the best diagnostic value of DECT (AUC = 0.872, 95% CI 0.806−0.938). DECT alone had a sensitivity of 90.4% and specificity of 74.5%. Although ACR/EULAR criteria without DECT provided better diagnostic accuracy than DECT alone (AUC = 0.926, 95% CI 0.878−0.974), the best value was obtained when combing both (AUC = 0.957, 95% CI 0.924−0.991), with 100% sensitivity and 76.6% specificity. In univariate analysis, risk factors for gout were male sex, presence of tophi, presence of MSU deposits on DECT, increased uric acid in serum (each p < 0.001), and decreased glomerular filtration rate (GFR) (p = 0.029). After logistic regression, only increased serum uric acid (p = 0.034) and decreased GFR (p = 0.018) remained independent risk factors for gout. Our results suggest that DECT significantly increases the sensitivity of the ACR/EULAR criteria in the diagnosis of gout.

Comparison of treatment of severe rheumatoid arthritis patients with biological agents and JAK-STAT inhibitors. An observational study.

Introduction: Treatment of severe rheumatoid arthritis (RA) is currently based either on biological agents or Janus kinase/signal transducer and activator of transcription inhibitors, most often in combination with methotrexate (MTX). Aim of the study: The aim of the study was to compare the effectiveness and side effects of bio- logic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs treatment. Material and methods: The analysis included 108 RA patients with active disease treated with MTX 25 mg per week. Eighty patients (group I) were treated with bDMARDs and 28 patients (group II) with JAK-STAT inhibitors. The duration of morning stiffness, pain on Visual Analogue Scale (VAS), 28-joints Disease Activity Score (DAS28) and Simplified Disease Activity Score (SDAI) were assessed. Classical radiographic images of patients' hands and feet using the Larsen and Dale's criteria were evaluated. The effects of treatment with bDMARDs and tsDMARDs were analyzed. Results: All studied patients presented at least Larsen and Dale's stage 3 of X-ray changes typical for RA. There were no statistically significant differences in disease duration, ESR, CRP, DAS28 and SDAI values between studied groups. Patients from group II previously used higher numbers of bDMARDs than group I treated with bDMARDs. Low disease activity after treatment was achieved by all patients; therefore patients from group II (treated with tsDMARDs) achieved lower values of patients' global assessment on VAS. Conclusions: The results of the present observational study indicated that treatment with JAK inhibitors is very promising. These drugs are not inferior in effectiveness to bDMARDs. It is important to monitor patients for thromboembolic events before and during JAK treatment.

Sleep-Specific Processing of Auditory Stimuli Is Reflected by Alpha and Sigma Oscillations.

Recent research revealed a surprisingly large range of cognitive operations to be preserved during sleep in humans. The new challenge is therefore to understand functions and mechanisms of processes, which so far have been mainly investigated in awake subjects. The current study focuses on dynamic changes of brain oscillations and connectivity patterns in response to environmental stimulation during non-REM sleep. Our results indicate that aurally presented names were processed and neuronally differentiated across the wake-sleep spectrum. Simultaneously recorded EEG and MEG signals revealed two distinct clusters of oscillatory power increase in response to the stimuli: (1) vigilance state-independent θ synchronization occurring immediately after stimulus onset, followed by (2) sleep-specific α/σ synchronization peaking after stimulus offset. We discuss the possible role of θ, α, and σ oscillations during non-REM sleep, and work toward a unified theory of brain rhythms and their functions during sleep.SIGNIFICANCE STATEMENT Previous research has revealed (residual) capacity of the sleeping human brain to interact with the environment. How sensory processing is realized by the neural assemblies in different stages of sleep is however unclear. To tackle this question, we examined simultaneously recorded MEG and EEG data. We discuss the possible role of θ, α, and σ oscillations during non-REM sleep. In contrast to versatile θ band response that reflected early stimulus processing step, succeeding α and σ band activity was sensitive to the saliency of the incoming information, and contingent on the sleep stage. Our findings suggest that the specific reorganization of mechanisms involved in later stages of sensory processing takes place upon falling asleep.

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.

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.

Assessment of Rheumatoid Hand Function as a Characteristic Feature of Rheumatoid Arthritis in Patients Treated with Methotrexate or Methotrexate with Biological Agents with or without Deformation of Hands.

BACKGROUND: The hand is an excellent work tool that provides the functional ability to mechanical work. The hand is affected in rheumatoid arthritis (RA) patients, it is a significant problem in the functional sphere as a result of deformities, the grasping function limitation and muscle strength. OBJECTIVES: The aim of the study was the assessment of grip strength, endurance and manipulation abilities of rheumatoid hands with or without deformities treated with methotrexate (MTX) or MTX plus biologics (MTX+BIO). METHODS: The study involved 80 RA women, (40 received MTX+BIO, 40 MTX), treated at the Rheumatology Department of the Central Clinical Hospital of Interior Affairs in Warsaw. VASpain, DAS28, SDAI, HAQ, HAQ hands, estimation of hand grip strength, endurance, and manipulation ability were analyzed. RESULTS: In group MTX+BIO, values of DAS28 (3.7±1.3 vs. 4.3±1.2, p=0.019), HAQ (0.72 ± 0.57 vs. 1.08± 0.87, p=0.011) and HAQ-hand (0.85±0.65 vs. 1.19±0.68, p=0.024) were statistically lower than in MTX group. Hand deformations were recorded in 35 (43.7%) cases, 16 (40%) in MTX group, 19 (47.5%) in MTX+BIO. Comparison of grip strength, endurance, and manipulation ability showed better results in MTX+BIO group with deformities (significance level from 0.013 to 0.046) than in MTX group. Relative differences in hand function in MTX + BIO group ranged from 10.8% (maximal power grip strength) to 127.6% (minimal hand endurance), after disease duration adjustment - from 28.2% (maximal power grip strength) to 148.4% (minimal hand endurance). CONCLUSION: Measuring grip strength, hand endurance, manipulation abilities are useful in RA patients with hand deformities.

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.

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.

Comparison of Granulomatosis with Polyangiitis Clinical Features in Patients Depending on Involvement or Absence of Kidney Involvement.

BACKGROUND: GPA is necrotizing inflammation of the small vessels with granulomas. Kidney involvement deteriorated its prognosis. OBJECTIVE: Comparison of GPA patients with Kidney (KI) and without Kidney Involvement (nKI). MATERIALS AND METHODS: We conducted a cross-sectional study of 50 consecutive adult GPA patients, 25 KI from Nephrology and 25 nKI from the Rheumatology Department of Central Clinical Hospital Ministry of Interior in Warsaw. We analyzed clinical features, organ involvement, laboratory, serological, imaging, histopathological data, BVAS and treatment. RESULTS: The mean age of KI patients was statistically older than nKI (67.3±9.5 vs. 55.1±15.9, p=0.002). Generalized, severe, disease resistance was observed respectively in 92% vs. 44%, p<0.001. The number of red blood cells (3.47 vs. 4.41T/l, p<0.001), hemoglobin (10.0 vs. 12.9 g/dl, p<0.001) was lower in KI, higher mean serum creatinine (3.95 vs. 0.89 mg/dl, p<0.001), lower GFR (20.1 vs. 79.3, p<0.001), higher CRP (median: 43.4 vs. 2.0 mg/l, p<0.001), BVAS (16.6±4.4 vs. 10.1±6.2, p<0.001), c-ANCA (median: 119.0 vs. 15.2CU, p=0.017). Nodules in 28% KI, in 4% nKI (p=0.048) in chest X-ray, infiltration in 43.5% KI, in 15% nKI (p=0.042) in HRCT were observed. Skin granulomas were found in 61.5% nKI vs. 18.2% KI, (p=0.047). Renal biopsy revealed in KI patients focal segmental glomerulonephritis in 11.8%, crescentic glomerulonephritis in 17.6%, and pauci-immune crescentic glomerulonephritis in 70.6%. CONCLUSION: In patients with KI we found generalized, severe, resistant GPA, higher BVAS more frequently than inpatients without KI. The results of laboratory parameters were worse in patients with KI. Aggressive immunosuppressive treatment is often used in the KI group.

Decoding Brain Responses to Names and Voices across Different Vigilance States.

Past research has demonstrated differential responses of the brain during sleep in response especially to variations in paralinguistic properties of auditory stimuli, suggesting they can still be processed "offline". However, the nature of the underlying mechanisms remains unclear. Here, we therefore used multivariate pattern analyses to directly test the similarities in brain activity among different sleep stages (non-rapid eye movement stages N1-N3, as well as rapid-eye movement sleep REM, and wake). We varied stimulus salience by manipulating subjective (own vs. unfamiliar name) and paralinguistic (familiar vs. unfamiliar voice) salience in 16 healthy sleepers during an 8-h sleep opportunity. Paralinguistic salience (i.e., familiar vs. unfamiliar voice) was reliably decoded from EEG response patterns during both N2 and N3 sleep. Importantly, the classifiers trained on N2 and N3 data generalized to N3 and N2, respectively, suggesting similar processing mode in these states. Moreover, projecting the classifiers' weights using a forward model revealed similar fronto-central topographical patterns in NREM stages N2 and N3. Finally, we found no generalization from wake to any sleep stage (and vice versa) suggesting that "processing modes" or the overall processing architecture with respect to relevant oscillations and/or networks substantially change from wake to sleep. However, the results point to a single and rather uniform NREM-specific mechanism that is involved in (auditory) salience detection during sleep.