Oral health status, related behaviours and perceived stress in xerostomia, Sicca and Sjögren's syndromes patients - a cross-sectional study.

BACKGROUND: Mouth dryness increases the risk of some oral health-related conditions. Furthermore, it is unclear if patients with dry mouth engage in appropriate oral health-related behaviours. The study examined oral health, related behaviours, and perceived stress in dry-mouth patients and compared them to matched controls without mouth dryness. METHODS: Information about 182 dry-mouth patients and 302 age- and sex-matched subjects was retrieved. Three dry mouth groups: xerostomia, Sicca syndrome and Sjögren's syndrome, were formed based on patient self-reported and objectively assessed symptoms. The World Health Organization's Oral Health for Adults and Perceived Stress Scale (PSS-10) questionnaires inquired about sociodemographic characteristics, oral health-related behaviours, and self-perceived stress. Clinical oral health assessments included: caries experience measured as total numbers of decayed (DS), missing (MS), filled surfaces (FS), number of remaining teeth, erosive tooth wear and extent of periodontal pocketing. Data were analyzed using bivariate and multivariable tests. RESULTS: The dry-mouth participants had higher mean (SD) DMFS scores than their matched controls: xerostomia patients vs. controls: 74.6 (34.4) and 66.3 (35.4), Sicca syndrome patients vs. controls: 88.3 (34.0) and 70.1 (33.9), and Sjögren's syndrome patients vs. controls: 95.7 (31.5) and 74 (33.2). In comparison to controls, individuals with Sicca and patients with Sjögren's syndromes had lower mean (SD) number of remaining teeth, 15.9 (10.1) vs. 21.7 (8.4) and 13.8 (10.0) vs. 20.1 (9.2), and a lower mean (SD) extent of periodontal pocketing, 20.7 (28.6) vs. 41.1 (31.0), and 21.2 (24.1) vs. 34.8 (34.2), respectively. Xerostomia, Sicca syndrome and Sjögren's syndrome patients had higher odds of using fluoridated toothpaste; OR 1.8 (95%CI 1.1-2.9), OR 5.6 (95%CI 1.7-18.3) and OR 6.9 (95%CI 2.2-21.3), respectively. Participants with Sjögren's syndrome had lower odds of the last dental visit being within the last year; OR 0.2 (95%CI 0.1-0.8). CONCLUSIONS: Dry-mouth patients had higher caries experience and fewer teeth than comparison groups but a lower extent of periodontal pocketing. Even though more participants with dry mouth used fluoridated toothpastes, their oral health-related behaviours were not optimal.

Overlapping Case of Advanced Systemic Sclerosis and IgG4-Related Disease after Autologous Hematopoietic Stem Cell Transplantation.

Both scleroderma and immunoglobulin G4-related disease (IgG4-RD) are systemic fibro-inflammatory diseases characterised by lymphoplasmacytic infiltrates. IgG4-RD and systemic sclerosis (SSc) may share common pathophysiological mechanisms, but no examples of co-occurrence of the diseases have been found. Autologous haematopoietic stem cell transplantation (AHSCT) is implemented in selected rapidly progressive SSc with a high risk of organ failure. However, existing guidelines are based on clinical trials that do not represent the entire patient population and exclude critically ill patients with no therapeutic alternatives. Examples of AHSCT in IgG4-RD are absent. We report the case of a 44-year-old female patient with overlapping progressive diffuse SSc and sinonasal IgG4-RD. After 11 years of ineffective SSc treatment, AHSCT was performed. The 63-month follow-up showed a regression of SSc symptoms. AHSCT was not intended as treatment in the case of IgG4RD, although the first symptoms of the disease developed before transplantation. The sinus lesions progressed after AHSCT and remained indolent only after surgical treatment (bilateral ethmoidectomy, sphenoidotomy, intranasal buccal antrostomy), which allowed histopathological confirmation of IgG4-RD.

The Use of Superb Microvascular Imaging in Evaluating Rheumatic Diseases: A Systematic Review.

Background and Objectives: Superb microvascular imaging is an advanced Doppler algorithm that seems to be useful in detecting low-velocity blood flow without using a contrast agent. Increasing evidence suggests that SMI is a more sensitive tool than conventional Doppler techniques for evaluating rheumatic diseases, especially inflammatory arthritis. We aimed to assess the use of SMI in evaluating joints and extraarticular structures. Materials and Methods: Two reviewers independently reviewed the literature to provide a global overview of the possibilities of SMI in rheumatology. Original English-language articles published between February 2014 and November 2022 were identified through database (PubMed, Medline, Ebsco, the Cochrane Library, and ScienceDirect) searching, and analysed to summarise existing evidence according to PRISMA methodology. Inclusion criteria covered original research articles reporting applications of SMI on rheumatic diseases and musculoskeletal disorders secondary to rheumatic conditions. Qualitative data synthesis was performed. Results: A total of 18 articles were included. No systematic reviews fulfilled our inclusion criteria. Most studies focused on characterising the synovial vascularity of rheumatoid arthritis. There have been several attempts to demonstrate SMI's value for evaluating extra-articular soft tissues (fat pads or salivary glands) and large-diameter vessels. The quantitative importance of SMI vascular indices could become a useful non-invasive diagnostic marker. Studies on therapeutic applications are still scarce, and the majority of studies have gaps in reporting the methodology (ultrasound performance technique and settings) of the research. Conclusions: SMI has proved to be useful in characterising low-flow vascularity, and growing evidence indicates that SMI is a non-invasive and lower-cost tool for prognostic assessment, especially in inflammatory arthritis. Preliminary findings also suggest potential interest in evaluating the effect of treatment.

Gingival Tissue MiRNA Expression Profiling and an Analysis of Periodontitis-Specific Circulating MiRNAs.

This study aimed to identify the microRNAs (miRNAs) associated with periodontitis (PD) in gingival tissues, and to evaluate the levels of these selected miRNAs in the saliva and blood plasma among participants with and without rheumatoid arthritis (RA). A genome-wide miRNA expression analysis in 16 gingival tissue samples revealed 177 deregulated miRNAs. The validation of the miRNA profiling results in 80 gingival tissue samples revealed that the PD-affected tissues had a higher expression of miR-140-3p and -145-5p, while the levels of miR-125a-3p were significantly lower in inflamed tissues. After a thorough validation, four miRNAs, namely miR-140-3p, -145-5p, -146a-5p, and -195-5p, were selected for further analysis in a larger sample of salivary (N = 173) and blood plasma (N = 221) specimens. Increased salivary levels of miR-145-5p were associated with higher mean values of pocket probing depth and bleeding on probing index. The plasma-derived levels of miR-140-3p were higher among the participants with PD. In conclusion, the gingival levels of miR-140-3p, -145-5p, and -125a-3p were independently associated with PD presence and severity. The salivary and blood plasma levels of the target miRNAs were diversely related to PD. Similar miRNA associations with PD were observed among the participants with and without RA.

Diagnostic use of superb microvascular imaging in evaluating septic arthritis of the manubriosternal joint: A case report.

BACKGROUND: Septic arthritis of the manubriosternal joint is a diagnostic challenge due to its rarity and anatomical characteristic. Conventional ultrasound, plain radiographs, and computed tomography are not able to confirm or even suspect arthritis early. Superb microvascular imaging is a new advanced Doppler technique in evaluating low-flow microvascular patterns. The higher sensitivity for increased peri-synovial vascularity helps to suspect septic arthritis and forms a methodical approach to using magnetic resonance imaging (MRI). CASE SUMMARY: A 34-year-old immunocompetent woman presented with a fever and a dull ache in the chest radiating to the right arm. Traumatic injury and the most common respiratory and cardiac disorders were ruled out. Blood cultures came back positive for Staphylococcus aureus, and sepsis was confirmed. A small lump was noted on the chest during the first week of hospitalization. Superb microvascular imaging was performed and septic arthritis of the manubriosternal joint was detected. MRI confirmed the diagnosis and showed septic arthritis of the manubriosternal joint with several localized abscesses behind the sternum. The patient was treated for three weeks with intravenous antibiotics and the outcome was favorable: Inflammatory markers became normal, and the lump disappeared. Three months later, the patient was examined for a new episode of mild pain in the sternum and was diagnosed with persistent perichondritis by ultrasound in comparison with MRI. CONCLUSION: Superb microvascular imaging is a useful tool for the early diagnosis of septic arthritis of the manubriosternal joint and following-up.

Assessing scleroderma patterns with superb microvascular imaging: is it possible? New prospects for ultrasound.

Nailfold videocapillaroscopy is the gold standard for the early differentiation of primary and secondary Raynaud's phenomenon. Advances in high-frequency ultrasound with superb microvascular imaging show significant potential for exploring structural changes that were previously inaccessible. Ultrasound makes it possible to assess not only the superficial layers of the skin but also structural microvascular abnormalities in the deep layers of the nail fold. There is potential for identifying a 'scleroderma pattern', which presents with the loss of continuous vascular arches above and below the nail plate in transverse and longitudinal scans of the nail folds. The 'active' pattern presents with the loss of the junctions between vascular signals, which is not seen in the 'early' pattern. Severely reduced vascularity with avascular areas in both of the nail fold zones is seen in a 'late' pattern. The quality of the evaluation is highly dependent on how experienced the sonographer is. This is the first detailed description of every pattern assessed through superb microvascular imaging, including high-quality images for a better understanding of the technique.

Analysis of Epigenetic Changes in Vitamin D Pathway Genes in Rheumatoid Arthritis Patients.

Background: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex etiopathogenesis launched by multiple risk factors, including epigenetic alterations. RA is possibly linked to vitamin D that is epigenetically active and may alter DNA methylation of certain genes. Therefore, the study aimed to evaluate the relationship between DNA methylation status of vitamin D signaling pathway genes (VDR, CYP24A1, CYP2R1), vitamin D level and associations with RA. Materials and Methods: Totally 76 participants (35 RA patients and 41 healthy controls) were enrolled from a case-control vitamin D and VDR gene polymorphisms study regarding age and vitamin D concentration. CpG islands in promoter regions of the VDR, CYP24A1, CYP2R1 genes were chosen for DNA methylation analysis by means of pyrosequencing. Chemiluminescent microplate immunoassay was used to assess 25(OH)D serum levels. RA clinical data, i.e. the disease activity score C-reactive protein 28 (DAS28 - CRP) as well as patient-reported outcome questionnaires were recorded. Results: The study showed similar methylation pattern in the promoter regions of vitamin D pathway genes in RA and control group with p>0.05 (VDR gene 2.39% vs. 2.48%, CYP24A1 gene 16.02% vs. 15.17% and CYP2R1 2.53% vs. 2.41%). CYP24A1 methylation intensity was significantly higher in compare to methylation intensity of VDR and CYP2R1 genes in both groups (p<0.0001). A tendency of higher vitamin D concentration in cases having methylated VDR (57.57±28.93 vs. 47.40±29.88 nmol/l), CYP24A1 (53.23±26.22 vs. 48.23±34.41 nmol/l) and CYP2R1 (60.41±30.73 vs. 44.54±27.63 nmol/l) genes and a positive correlation between VDR, CYP2R1 methylation intensity and vitamin D level in RA affected participants was revealed (p>0.05). A significantly higher CYP24A1 methylation intensity (p=0.0104) was detected in blood cells of vitamin D deficient (<50 nmol/l) RA patients vs. vitamin D deficient controls. Conclusions: Our data suggests some indirect associations between DNA methylation status of vitamin D pathway genes and vitamin D level in RA.

The manifestation of myositis in tick-borne encephalitis as a prophet of severe disease course: a rare case report.

Tick-borne encephalitis (TBE) is one of the most serious neurological tick-transmitted diseases. The initial phase usually occurs with non-specific symptoms such as fever, headache, and muscular pain. The clinical spectrum of the second phase of the disease typically ranges from mild meningitis to severe meningoencephalitis. Our case demonstrates a rare clinical case of acute myositis as manifestation of TBE virus infection. A 33-year-old female was admitted to the Rheumatology centre with a fever followed by proximal muscle pain and weakness. Despite the tick bite history and marginally positive anti-TBE virus IgM titre, the patient did not present any neurological symptoms. Laboratory test results showed elevated creatine kinase (CK) and myoglobin. Other infections, idiopathic inflammatory myopathies, were excluded. TBE virus infection was confirmed by rapid seroconversion of specific IgG class antibodies in serum. The second phase of the disease was followed by neurological symptoms and a repeated increase of CK and myoglobin. We suggest that in the case of acute myositis of unknown cause and the history of thick bite, TBE virus infection should be considered and creatine kinase might be considered as a laboratory marker of disease activity that correlates with the severity of the disease.

Power Doppler artifacts in evaluating inflammatory arthritis of small joints: comparison with a superb microvascular imaging technique.

Conventional Doppler techniques provide clinical information about tissue vascularisation, but they have limitations in detecting low-velocity blood flow. The innovative Doppler technique called superb microvascular imaging provides visualization of microvascular flow never seen before with the ultrasound. The new tool suppresses the noise caused by motion artifacts with an innovative filter system without removing the weak signal arising from small vessel flow, hence it achieves a greater sensitivity than power Doppler. Explanation of motion artifact genesis reveals SMI imaging principles and helps to distinguish false-positive results. Due to the higher SMI sensitivity to flow, there are nuances in the interpretation of other artifacts as well as motion. The paper presents commonly encountered artifacts of power Doppler compared with a novel microvascular imaging technique focused on a small joints inflammation. The main attention is intent on the practical recommendations for ultrasound machine settings and evaluation of comparable images.

Gingival crevicular fluid microRNA associations with periodontitis.

PURPOSE: The present study was performed to assess the associations of gingival crevicular fluid (GCF) microRNAs miR-140-3p, miR-145-5p, miR-146a-5p, and miR-195-5p with periodontitis (PD) and to evaluate the possible influence of rheumatoid arthritis (RA) in this context. METHOD: GCF samples were collected from 134 individuals with PD and 76 periodontally healthy individuals, with or without RA. After miRNA extraction from GCF, the levels of miR-140-3p, miR-145-5p, miR-146a-5p, and miR-195-5p were assessed using RT-qPCR. RESULTS: MiR-146a-5p levels were significantly lower among the patients with PD than among the healthy individuals (P < 0.001) and negatively correlated with PD severity based on PD stage and periodontal outcome parameters (P < 0.05). Patients with severe PD had higher GCF levels of miR-140-3p and miR-145-5p than did periodontally healthy individuals (P < 0.05). Significant AUC values for diagnosis of severe PD were revealed for miR-140-3p (AUC = 0.614, P = 0.022), miR-145-5p (AUC = 0.621, P = 0.016) and miR-146a-5p (AUC = 0.702, P < 0.001). Combination of the aforementioned miRNAs increased the diagnostic performance (AUC = 0.709, P < 0.001). CONCLUSION: It was demonstrated that miR-140-3p, miR-145-5p and miR-146a-5p were associated with PD and would be potentially effective for GCF-based non-invasive periodontitis diagnostics in patients with and without RA.

The Promising Role of a Superb Microvascular Imaging Technique in the Evaluation of Raynaud's Syndrome in Systemic Sclerosis: Theory and Practical Challenges.

In recent years, a novel Doppler ultrasonography (US) modality-superb microvascular imaging (SMI)-has been presented as a reliable method to evaluate small vessel blood flow with minimised motion artefacts. In this review, we present the challenges of incorporating SMI in daily practice with detailed and comparable US images of a fingertip. The main focus of this paper is the discussion of all tested US techniques, artefacts, and practical challenges for evaluating Raynaud's syndrome in systemic sclerosis. Despite a few reports on SMI use in assessing nailfold capillaries, there is still a need for more evidence of its value and possibilities for its standardisation.

Multidisciplinary diagnostic dilemma in differentiating Madelung's disease - the value of superb microvascular imaging technique: A case report.

BACKGROUND: Madelung's disease, also known as multiple symmetrical lipomatosis, is a rare, underrecognized disorder of fat metabolism that results in unusual accumulation of subcutaneous fat deposits around the neck, shoulders, upper arms, trunk, hips, and upper thighs. Our case demonstrates the importance of differential diagnosis and the value of a superb microvascular imaging technique for suspecting and confirming Madelung's disease. Timely diagnosis and alcohol abstinence could prevent the progression of growing fatty masses and prevent surgery. CASE SUMMARY: A 62-year-old male was admitted to the Rheumatology center complaining of symmetric subcutaneous tumors in the area of the parotid and submandibular salivary glands, small soft masses in the occiput and upper third of the forearm, rashes on calves. A high titer of rheumatoid factor and low concentrations of serum complements were detected. The high-end ultrasound and magnetic resonance imaging examinations of all affected areas of the soft tissues showed predominantly adipose tissue (lipomas) without suspicion of liposarcoma. The biopsy from the small salivary gland revealed no pathology. After evaluating the patient's clinical presentation (symmetrical lipomatosis, cirrhosis, gynecomastia, anemia, hyperuricemia), Madelung's disease, type I, along with the psoriatic rash and psoriatic arthritis and secondary liver cirrhosis were established. CONCLUSION: Madelung's disease consists of many co-occurring disorders imitating and overlapping with other conditions. Ultrasonography is the first choice for suspecting and confirming symmetrical lipomatosis.

Analysis of periodontitis-associated miRNAs in gingival tissue, gingival crevicular fluid, saliva and blood plasma.

OBJECTIVE: Periodontitis (PD) is a chronic inflammatory disease which is associated with multiple systemic comorbidities, including rheumatoid arthritis (RA), meanwhile the etiopathology of PD may be modulated by various factors including microRNA (miRNA). The present study aimed to reveal miRNAs associated with PD in gingival tissue, gingival crevicular fluid (GCF), saliva, plasma and to assess the possible influence of RA. DESIGN: The cross-sectional study included 30 patients with PD and 31 periodontally healthy participants. A total of 25 participants were additionally diagnosed with RA. Microarray analysis of eight gingival tissue samples was performed and four PD-associated miRNAs were selected: miR-199a-5p, miR-483-5p, miR-3198 and miR-4299. Target miRNAs were further assessed by means of RT-qPCR in 61 gingival tissue samples and corresponding bodily fluids - GCF, saliva and plasma. RESULTS: The upregulation of miR-199a-5p and downregulation of miR-4299 in gingival tissue was associated with the presence of PD and RA (P < 0.05). GCF level of miR-3198 was higher amongst participants with PD (P = 0.019) and showed a good diagnostic ability (AUC = 0.72, P = 0.008). Increased miR-199a-5p salivary level and decreased miR-199a-5p plasma level were observed amongst patients with worse clinical status of PD (P < 0.05). MiR-3198 and miR-4299 combination in GCF demonstrated AUC value of 0.86 and reached sensitivity of 68 % and specificity of 96 %. CONCLUSIONS: Aberrant expression of miR-199a-5p, miR-483-5p, miR-3198, miR-4299 in gingival tissues is associated with the presence and/or severity of PD. MiR-3198, miR-4299 level in GCF and miR-199a-5p level in plasma strongly correlated with PD, demonstrating significant diagnostic performance.

Vitamin D and VDR Gene Polymorphisms' Association with Rheumatoid Arthritis in Lithuanian Population.

Background and Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune, multi-factorial disease, in which environmental and genetic factors play a major role. RA is possibly linked to vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms, and research demonstrates that FokI variant susceptibility is associated with increased disease risk among Caucasians. The aim of this study was to evaluate vitamin D deficiency prevalence and its correlation to RA clinical parameters, and to determine the possible association of VDR gene polymorphisms and RA susceptibility in the Lithuanian population. Materials and Methods: Overall, 206 RA patients and 180 age- and sex-matched healthy controls were enrolled at Vilnius University Hospital Santaros Klinikos after informed consent was obtained. The disease activity score 28 C-reactive protein (DAS28 CRP), rheumatoid arthritis impact of disease (RAID) score, and health assessment questionnaire (HAQ) were recorded in RA patients, and 25(OH)D serum levels were evaluated by chemiluminescent microparticle immunoassay for all subjects. Four VDR gene polymorphisms, BsmI, FokI, ApaI, and TaqI, were assessed using real-time PCR instruments and genotyping assays in both groups. Results: The study registered a high prevalence of 25(OH)D deficiency (<50 nmol/L) in RA patients (61.55% (n = 127)). The mean serum concentration in RA patients (44.96 ± 21.92 (nmol/L)) was significantly lower than in the healthy controls (54.90 ± 22.82 (nmol/L)), p < 0.0001. A significant inverse correlation between vitamin D level, DAS28 CRP, and HAQ scores was confirmed in RA patients, with p < 0.05. Still, there was no significant association between the overall risk of RA disease for any allele or genotype of the four VDR loci tested. Conclusions: The study confirmed that vitamin D deficiency is prevalent among RA patients and the 25(OH)D level is significantly lower compared with healthy controls. Lower vitamin D concentration was related with increased disease activity and disability scores. However, genetic analysis of four VDR polymorphisms did not confer the susceptibility to RA in Lithuanian population.

Associations of periodontal status in periodontitis and rheumatoid arthritis patients.

PURPOSE: The aim of this study was to assess the association between the clinical status of rheumatoid arthritis (RA) and periodontitis (PD) in patients diagnosed with PD and to evaluate the impact of RA treatment on the severity of PD. METHODS: The study included 148 participants with PD, of whom 64 were also diagnosed with RA (PD+RA group), while 84 age-matched participants were rheumatologically healthy (PD-only group). PD severity was assessed by the following periodontal parameters: clinical attachment loss, probing pocket depth (PPD), bleeding on probing (BOP), alveolar bone loss, and number of missing teeth. RA disease characteristics and impact of disease were evaluated by the Disease Activity Score 28 using C-reactive protein, disease duration, RA treatment, the RA Impact of Disease tool, and the Health Assessment Questionnaire. Outcome variables were compared using parametric and non-parametric tests and associations were evaluated using regression analysis with the calculation of odds ratios (ORs). RESULTS: Participants in the PD+RA group had higher mean PPD values (2.81 ± 0.59 mm vs. 2.58 ± 0.49 mm, P=0.009) and number of missing teeth (6.27±4.79 vs. 3.93±4.08, P=0.001) than those in the PD-only group. A significant association was found between mean PPD and RA (OR, 2.22; 95% CI, 1.16-4.31; P=0.016). Within the PD+RA group, moderate to severe periodontal disease was significantly more prevalent among participants with higher RA disease activity (P=0.042). The use of biologic disease-modifying antirheumatic drugs (bDMARDs) was associated with a lower BOP percentage (P=0.016). CONCLUSIONS: In patients with PD, RA was associated with a higher mean PPD and number of missing teeth. The severity of PD was affected by the RA disease clinical activity and by treatment with bDMARDs, which were associated with a significantly lower mean BOP percentage.

Investigating the relationship between the severity of periodontitis and rheumatoid arthritis: a cross-sectional study.

OBJECTIVES: This paper evaluates the prevalence and severity of periodontitis (PD) in patients with rheumatoid arthritis (RA), focusing on the link between the severity of PD with RA disease activity/disability scores, the influence of RA treatment on PD, and levels of vitamin D. METHODS: A total of 93 RA patients were enrolled in the cross-sectional study and analyzed accordingly as RA-PD (N = 63, 67.8%) and RA-only (N = 30, 32.2%) groups. A number of associations between rheumatological clinical data, i.e., Disease Activity Score (DAS28 CRP), health assessment questionnaires, and PD severity (measured by periodontal outcome parameters) with regard to serum levels of vitamin D were assessed. The outcome variables were compared by parametric and non-parametric tests. RESULTS: A total of 29% of RA patients were diagnosed with severe PD. The RA-PD group presented a higher mean DAS28 CRP score in moderate-severe PD compared to periodontally healthy-initial stage PD subjects (4.49 ± 1.22 vs. 3.86 ± 1.58, p = 0.033). RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) were less likely to be diagnosed with PD (p = 0.022) and revealed significantly lower PD outcome parameters, i.e., bleeding on probing (%) and bone loss (%) (p < 0.05). Vitamin D concentration was significantly lower in RA-PD group with diagnosed advanced severe PD (IV stage) compared to moderate PD (II stage) (39.61 ± 17.12 vs. 52.07 ± 18.23 nmol/l, p = 0.031). CONCLUSIONS: The study revealed a high prevalence of severe PD in RA patients, being significantly associated with higher RA disease activity and lower vitamin D level in RA-PD group, while bDMARD treatment was related to lower PD outcome parameters. Key Points • Severe PD is prevalent amongst RA patients and is associated with RA disease activity. The higher RA DAS28 CRP score is associated with moderate-severe PD compared to periodontally healthy-initial stage PD in RA patients. • Biologic DMARDs treatment used for RA is linked to lower PD rates and PD outcome parameters. • Significantly lower vitamin D level is found in advanced severe PD compared to moderate PD stage in RA-PD subjects.

The Expression of Inflammasomes NLRP1 and NLRP3, Toll-Like Receptors, and Vitamin D Receptor in Synovial Fibroblasts From Patients With Different Types of Knee Arthritis.

Activated rheumatoid arthritis (RA) synovial fibroblasts (SFs) are among the most important cells promoting RA pathogenesis. They are considered active contributors to the initiation, progression, and perpetuation of the disease; therefore, early detection of RASF activation could advance contemporary diagnosis and adequate treatment of undifferentiated early inflammatory arthritis (EA). In this study, we investigated the expression of nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing (NLRP)1, NLRP3 inflammasomes, Toll-like receptor (TLR)1, TLR2, TLR4, vitamin D receptor (VDR), and secretion of matrix metalloproteinases (MMPs) in SFs isolated from patients with RA, osteoarthritis (OA), EA, and control individuals (CN) after knee surgical intervention. C-reactive protein, general blood test, anticyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and vitamin D (vitD) in patients' sera were performed. Cells were stimulated or not with 100 ng/ml tumor necrosis factor alpha (TNF-α) or/and 1 nM or/and 0.01 nM vitamin D3 for 72 h. The expression levels of NLRP1, NLRP3, TLR1, TLR2, TLR4, and VDR in all examined SFs were analyzed by quantitative real-time PCR (RT-qPCR). Additionally, the secretion of IL-1ß by SFs and MMPs were determined by ELISA and Luminex technology. The expression of NLRP3 was correlated with the levels of CRP, RF, and anti-CCP, suggesting its implication in SF inflammatory activation. In the TNF-α-stimulated SFs, a significantly lower expression of NLRP3 and TLR4 was observed in the RA group, compared with the other tested forms of arthritis. Moreover, upregulation of NLRP3 expression by TNF-α alone or in combination with vitD3 was observed, further indicating involvement of NLRP3 in the inflammatory responses of SFs. Secretion of IL-1ß was not detected in any sample, while TNF-α upregulated the levels of secreted MMP-1, MMP-7, MMP-8, MMP-12, and MMP-13 in all patient groups. Attenuating effects of vitD on the expression of NLRP3, TLR1, and TLR4 suggest potential protective effects of vitD on the inflammatory responses in SFs. However, longer studies may be needed to confirm or fully rule out the potential implication of vitD in SF activation in inflammatory arthritis. Both VDR and NLRP3 in the TNF-α-stimulated SFs negatively correlated with the age of patients, suggesting potential age-related changes in the local inflammatory responses.

Incidence of Tuberculosis in Inflammatory Rheumatic Diseases: Results from a Lithuanian Retrospective Cohort Study.

Background and objective: With an increase in survival rates among rheumatic patients, comorbidities and infections, in particular, have gained more importance, especially after the introduction of biologicals to the treatment algorithms. Tuberculosis (TB) infection has always been given a special attention in patients with rheumatic diseases (RD). Although Lithuanian population has one of the highest TB incidence rates among European countries, the incidence of TB in the rheumatic patients' population is still unknown. The aim of this study was to assess the incidence rate of TB in an inflammatory RD retrospective cohort and to compare that rate with a rate in a general population. Methods: Patients with the first-time diagnosis of inflammatory RD during the period between 1 January 2012 and 31 December 2017 were identified from the Lithuanian Compulsory Health Insurance Information System database SVEIDRA. All cases were cross-checked with Health Information center at the Institute of Hygiene, for the vital status of these patients and date of death if the fact of death was documented, and with Tuberculosis Register operated by Vilnius University Hospital Santaros Klinikos, for the confirmation of TB cases. Sex and age standardized incidence ratios (SIR) were calculated by dividing the observed numbers of TB among rheumatic patients by the expected number of cases, calculated using national rates from Lithuanian Department of Statistics Official Statistics website. Results: Overall, 8779 patients with newly diagnosed RD were identified during the 2013-2017 period, these included 458 patients who used biological disease modifying drugs (bDMARDs). The mean duration of the follow-up period was 2.71 years. The cohort consisted mainly of women (70%) and a half of the cohort were rheumatoid arthritis (RA) patients (53%). Mean age of patients at the time of RD diagnosis was 56 years (range = 18-97 years). There were 9 TB cases identified during 23,800 person years of follow-up: 2 cases among them were treated with bDMARDs. The mean calculated annual TB incidence in RD cohort was 37.81 per 100,000 person years, which is consistent with the incidence rate predicted by national estimates, with a resultant SIR of 0.90 (0.41-1.70). The unadjusted hazard ratio for bDMARD use versus no bDMARD use was 4.54 (0.94; 21.87) in a total cohort and very similar in rheumatoid arthritis cohort; in both cohorts, it was not a statistically significant risk. Conclusions: Here, we present the first nationwide cohort study to assess the incidence of TB in a broad spectrum of inflammatory RD. Although limited by short follow-up period, this study shows that TB incidence in RD cohort does not exceed TB incidence in the general Lithuanian population.

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.

Sjögren's Syndrome: Concerted Triggering of Sicca Conditions.

AIM: The aim of this study was to evaluate the expression of persistence of mumps virus and some cells that interact with viral infection in the focus of the autoimmune epithelitis and peripheral blood of Sjögren's syndrome patients in comparison to patients with rheumatoid arthritis (RA) and nonautoimmune sicca syndrome (nSS). MATERIALS AND METHODS: 126 patients (119 women and 7 men) were grouped into four groups: (1) patients with primary Sjögren's syndrome (pSS), (2) patients with secondary Sjögren's syndrome due to rheumatoid arthritis (sSS), (3) patients with rheumatoid arthritis (RA), and (4) patients with nonautoimmune sicca syndrome (nSS). Immunohistochemical analysis of immune response to the suggested silent persistence of mumps virus in the minor labial salivary gland biopsies and flow cytometric analysis of blood cells was done. RESULTS: Immunohistochemical signs of mumps virus persistence were found in the minor salivary glands of all study groups. Also, a significantly different immune response to virus infection (protein IFI16, interferons gamma and beta, dendritic cells, and receptor for natural killers) was revealed in the minor salivary glands of the study groups. Cytometric analysis of the blood cells revealed a dropping amount of circulating natural killers and dendritic cells in patients with SS. Significant correlations between immunohistochemical staining and serological findings were revealed. CONCLUSIONS: Abundant immunohistochemical signs of mumps virus protein in the salivary glands and depletion of circulating immune cells make a background for thought of presumable mumps or/and other virus participation in epithelial damage causing sicca syndrome in predisposed patients.