Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica.

OBJECTIVE: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach. METHODS: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared. RESULTS: We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate. CONCLUSIONS: Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.

Prevalence and characteristics of subclinical giant cell arteritis in polymyalgia rheumatica.

OBJECTIVE: The main objective of this study was to analyse the prevalence and characteristics of subclinical GCA in patients with PMR. METHODS: This was a cross-sectional multicentre international study of consecutive patients with newly diagnosed PMR without symptoms or signs suggestive of GCA. All patients underwent US of the temporal superficial, common carotid, subclavian and axillary arteries. Patients with halo signs in at least one examined artery were considered to have subclinical GCA. The clinical, demographic and laboratory characteristics of the PMR group without subclinical vasculitis were compared with subclinical GCA, and the pattern of vessel involvement was compared with that of a classical single-centre GCA cohort. RESULTS: We included 346 PMR patients, 267 (77.2%) without subclinical GCA and 79 (22.8%) with subclinical GCA. The PMR patients with subclinical GCA were significantly older, had a longer duration of morning stiffness and more frequently reported hip pain than PMR without subclinical GCA. PMR with subclinical GCA showed a predominant extracranial large vessel pattern of vasculitic involvement compared with classical GCA, where the cranial phenotype predominated. The patients with PMR in the classical GCA group showed a pattern of vessel involvement similar to classical GCA without PMR but different from PMR with subclinical involvement. CONCLUSION: More than a fifth of the pure PMR patients had US findings consistent with subclinical GCA. This specific subset of patients showed a predilection for extracranial artery involvement. The optimal screening strategy to assess the presence of vasculitis in PMR remains to be determined.

JAK inhibitors improve ATP production and mitochondrial function in rheumatoid arthritis: a pilot study.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.

Association of serum and synovial adipokines (chemerin and resistin) with inflammatory markers and ultrasonographic evaluation scores in patients with knee joint osteoarthritis- a pilot study.

Chemerin and resistin are adipokines studied as potential markers for early diagnosis and disease severity in patients with knee osteoarthritis (KOA) Therefore, we aimed to investigate the associations serum and synovial levels of chemerin and resistin with inflammatory parameters and ultrasonographic scores (US) in KOA individuals. Serum was collected from 28 patients with KOA and synovial fluid was obtained from 16 of them. Another 31 age and sex matched cases with no joint disease were included as healthy controls. Concentrations of chemerin, resistin, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were determined with ELISA. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum uric acid (UA) were measured in the patients group. Participants with KOA underwent US assessment using the Outcome Measures in Rheumatology (OMERACT) scores. Patients with KOA had statistically significant higher level of serum resistin than healthy controls [11.05 (3.78-24.13) ng/mL and 7.23 (3.83-12.19) respectively, p < 0.001]. A strong correlation was found between serum chemerin and ESR (r = 0.434, p = 0.021), uric acid (r = 0.573, p = 0.001) as well as the US (r=-0.872, p < 0.001). Serum resistin demonstrated significant association with TNF-alpha (r = 0.398, p = 0.044). In conclusion, both chemerin and resistin might contribute to inflammatory changes associated with KOA. Further studies are needed to elucidate their potential role in the pathogenesis of the disease.

The COVID-19 pandemic's impact on rheumatic disease patients' satisfaction with access to medical services.

The COVID-19 hurt various lifestyle aspects, especially the treatment and follow-up of patients with chronic diseases such as autoimmune inflammatory rheumatic diseases (RD). The new circumstances changed the frequency of medical examinations and the way patients with rheumatic diseases are followed up. The objective is to study the impact of COVID-19 on RD patients' satisfaction with access to medical services. A national multicenter observational cross-sectional anonymous online survey was conducted on patients with RD using a specially developed web-based platform and structured questionnaire https://rheumatologycovid19.bg/ . The study was carried out with the support of intra-university project №6/2022 MU-Plovdiv. 1288 patients participated, with an average age of 47.03 (SD ± 12.80 years), of whom 992 (81.6%) were women. The questionnaire contained 41 questions grouped into 5 panels. Descriptive statistics were used-mean, alternative analysis, logistic regression and Decision Tree using the CRT (classification and regression trees) method. The study found that RD patients' satisfaction with access to medical services was influenced by communication type and the frequency of visits to the rheumatologist, difficulties in prescribing and finding medicines and the presence of comorbidities. The likelihood of patients' satisfaction with their rheumatologist was 5.5 and 3 times higher for in-person and other means of communication, respectively, compared to those without any communication. The relative share of patients who communicated by phone was larger (59%) compared to pre-pandemic (41%), where direct contact with the physician prevailed (80%). The results of the study confirmed the need to optimize remote access to medical care for patients with RD during the pandemic.

Diagnostic and prognostic role of serum interleukin-6 and carotid ultrasonography to detect subclinical atherosclerosis in patients with RA and ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

High-resolution musculoskeletal ultrasonography and elastography for eosinophilic fasciitis diagnosis and follow-up: a case-based review.

Eosinophilic fasciitis (EF) remains a rare condition without precise diagnostic criteria due to common symptoms with other autoimmune diseases requiring broad differential diagnosis. This paper describes the use of high-resolution musculoskeletal ultrasonography and elastography in the diagnosis and follow-up of eosinophilic fasciitis through the case of a 56-year-old male patient. In addition to laboratory data, instrumental data, and biopsy, musculoskeletal ultrasonography (US) was used both in the diagnostic process and in the follow-up period for an objective assessment of the changes in the patient's condition and response to treatment. The US showed disorganization of the myofibrils adjacent to the superficial fascia, edema, and thickening of the fascia and subcutaneous edema. In addition, the use of shear-wave elastography (SWE) demonstrated significantly reduced skin elasticity. High-frequency musculoskeletal ultrasound in combination with SWE is an effective method both for the diagnosis of EF and for the follow-up of the changes occurring after therapy. Based on the fact that it can easily differentiate the substrate of involvement, such as skin, subcutaneous tissue, or muscle fascia, ultrasound can be used to distinguish EF from other skin and muscle diseases.

First multi-center retrospective study assessed the compliance with and persistence of biological therapies in Bulgarian population with rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory joint disease that causes progressive joint damage, leading to severe disability. Early diagnosis, optimal therapy, and strict adherence to the prescribed medication are key factors that allow for the cessation of the disease progression and the preserving of the patient's quality of life. The objective of this study was to estimate the compliance to and persistence of biologic disease-modifying anti-rheumatic drugs (bDMARDs) among the Bulgarian population with RA. This retrospective observational cohort study included 179 patients, who were tracked over a 36-month period. During baseline and subsequent follow-up visits (at months 6, 12, 24, and 36), we monitored the disease activity, side effects, medication tolerability and effectiveness, compliance, and persistence to the prescribed biologic agent. The compliance with bDMARDs among Bulgarian patients with RA was 85.5% in the first year, 76.0% in the second year, and 63.7% in the third year. The Infliximab cohort showed the lowest compliance rate (50%), with the other subgroups bDMARDs having similar results (64-70%) during the period of observation. The median therapy duration across all patient cohorts is 61.9 months (IQR 55.7-67.6). Our study did not establish any significant impact of gender, age and disease duration, concomitant treatment with methotrexate, type of biologic agent and previous exposure to biological agents on the treatment adherence. The compliance with and persistence of the prescribed bDMARD among the Bulgarian population with RA is unsatisfactory. Therapy interruption and nonadherence to recommended therapy are associated with disease progression and patient disability. The consequences include not only financial burdens but also psychosocial and physical impacts.

Adherence to biological therapies in patients with rheumatoid arthritis: a retrospective cohort study.

The advent of biologic disease-modifying antirheumatic drugs has dramatically changed the comprehensions of treatment and long-term prognosis in patients with rheumatoid arthritis. The potent therapeutic results can only be achieved if the patients adhere to prescribed medications. The objective of this study was to estimate the impact of age, gender, duration of the disease, concomitant Methotrexate therapy, prior exposure to biologic agents, disease activity, functional capacity, and health-related quality of life on adherence to biologic treatment among Bulgarian population with rheumatoid arthritis. This was a retrospective observational cohort study that included 179 patients. At the baseline visit and subsequent follow-up assessments at 6, 12, 24 and 36 months, patients were interviewed by a physician and underwent physical examinations. We monitored the changes in disease activity, functional capacity and health-related quality of life on each time point. Univariate and multivariate binary logistic regression was used to determine the prognostic value of possible predictors of treatment adherence. Our findings showed that only DAS28 score [odd ratio (OR) = 1.174; 95% CI 1.74-2.362] and HAQ score (OR 2.803; 95% CI 1.428-5.503) remained significant for the treatment adherence throughout the study period. The adherence to the biologic disease-modifying anti-rheumatic drugs among Bulgarian patients with rheumatoid arthritis is suboptimal. A multifaceted and comprehensive knowledge of the influencing factors can be useful for the development of different strategies that can improve treatment adherence.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Ochronotic arthropathy in the context of spondyloarthritis differential diagnosis: a case-based review.

Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.

Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.

Serum protein levels of YKL-40 and plasma miR-214 expression in patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease with incompletely revealed etiology and pathophysiology. There are still no specific and reliable biomarkers. Here we examined YKL-40 as a biomarker of inflammation and fibrosis, and suggest a possible mechanism for its regulation. METHODS: Forty female patients with SSc (26 with diffuse cutaneous (dcSSc) and 14 with limited cutaneous SSc (lcSSc)) and 14 healthy female controls were enrolled in this cross-sectional study. Bioinformatic tools identified miR-214 binding site in the 3'-untranslated region (3'UTR) of YKL-40 mRNA. Serum levels of YKL-40 were examined by ELISA, while YKL-40 mRNA and miR-214 was measured by qPCR. RESULTS: The in silico analysis revealed several microRNAs (miRNAs) targeting YKL-40 mRNA, from which miR-214 was selected. YKL-40 serum levels were significantly higher in patients compared to controls (p = .0042). In contrary, miR-214 expression in plasma of SSc patients was significantly down-regulated compared to controls (p = .0058). Receiver operating characteristic (ROC) and area under the curve (AUC) analysis showed that both serum YKL-40 and plasma miR-214 levels had good capacity to distinguish patients with SSc, dcSSc and lcSSc from healthy subjects. CONCLUSION: YKL-40 and miR-214 have different expression profile in SSc. Increased serum levels of YKL-40 could be associated with down-regulation of miR-214 expression in plasma. Both, YKL-40 concentrations and miR-214 plasma fold change values might serve as possible biomarkers in SSc.

Enthesopathy and involvement of synovio-entheseal complex in systemic sclerosis: an ultrasound pilot study.

OBJECTIVES: SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients. METHODS: One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis. RESULTS: In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0-7.0) than in controls (median 1.0, interquartile range 0.0-3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035). CONCLUSION: These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.

Hand ultrasound patterns in rheumatoid and psoriatic arthritis: the role of ultrasound in the differential diagnosis.

Many rheumatic diseases may present with an inflammatory joint syndrome, affecting the small joints of the hands, of which rheumatoid (RA) and psoriatic arthritis (PsA) being one of the most common. The aim of this systematic review was to focus on the literature evidence regarding the added value of ultrasound (US) of the hand in the differential diagnosis between RA and PsA. Pubmed and Scopus were searched to identify original manuscripts, published in the last 20 years utilising ultrasonography to reveal specific hand US patterns. Studies were eligible if they: (1) included adults (over 18 years) with a diagnosis of RA/PsA; (2) were published in the English language; (3) were published in peer-reviewed journals; (4) included description of the US machine; (5) used US for assessment of hand joints, periarticular tissues and nails. The search yielded 322 published studies, of which 16 were deemed relevant and were included in the present study. Overall, there was heterogeneity with regard to the pathology examined. Based on the included studies analysis, hand US patterns have several basic features to be considered-location of gray scale (GS) inflammatory findings, involvement of periarticular soft tissue, distribution and extent of Doppler signal (intra- and peri-articular), bone reaction, shape and location of erosions, involvement of tendons without synovial sheath, involvement of enthesis and nail abnormalities. Future research could focus on determining the sensitivity and specificity of the different US detected hand patterns in patients with early arthritis.

Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62 ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28 ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80 pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46 pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52 ng/ml ± 102.81; median 136.20 ng/ml) vs. lcSSc patients (89.31 ng/ml ± 50.36; median 68.03 ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64 pg/ml ± 46.37; median 16.36 pg/ml) vs. lcSSc patients (13.22 pg/ml ± 8.95; median 8.65 pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc.

Musculoskeletal ultrasound for predicting remission in patients with rheumatoid arthritis: results from a 1-year prospective study.

To assess the role of musculoskeletal ultrasound as a predictor for the achievement of DAS28 remission in patients with rheumatoid arthritis (RA). One hundred and forty-one patients underwent physical and ultrasound examination at five visits (at baseline and after 1, 3, 6 and 12 months). Patients were divided into two groups according to the type of treatment, which involved synthetic (sDMARDs) and biologic (bDMARDs) disease-modifying antirheumatic drugs. Ultrasound assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint (the German US7 score) was performed on gray scale (GS) and on power Doppler ultrasound (PDUS). The rate of clinical remission and clinical and sonographic predictors for the achievement of DAS28 remission at month 12 were assessed. In the sDMARDs group at month 12, 43.6% of the patients achieved DAS28 remission, 5.1%-SDAI, 3.8%-CDAI, and 3.8%-Boolean remission. In the bDMARDs group, 49.2% achieved DAS28 remission, 6.3%-SDAI, 4.8%-CDAI, and 4.8%-Boolean remission. Predictors for DAS28 clinical remission in the sDMARDs group were low baseline DAS28 (p = 0.002), short disease duration (p = 0.007) and lower baseline PDUS score (p = 0.038). In the bDMARDs group low baseline DAS28 (p < 0.001) and PDUS score (p = 0.035) predicted DAS28 remission. Shorter disease duration, lower baseline DAS28 and PDUS scores are associated with a higher probability of achieving DAS28 remission at month 12 in patients with RA. Musculoskeletal ultrasound and in particular the German US7-scoring system may be used as a predictor for the achievement of clinical remission in RA patients.

Sexual Fears and Avoidant Sexual Behavior in Medical Students.

UNLABELLED: Sexual fears, sometimes in the form of phobias, lead to aversive or sexually avoidant behavior blocking sexual closeness and resulting in deep personal and interpersonal distress. OBJECTIVE: To determine the types of sexual fears and aversive behavior in young people of reproductive age (students) and their degree of markedness as to encourage a further implementation of prevention programs and interventions. MATERIALS AND METHODS: The study included 116 fifth-year medical students in Plovdiv Medical University. Of these, 55 men and 61 women were assessed with the Sexual Aversion Scale, a 30-item self-rating questionnaire. The Diagnostic and Statistical Manual of Mental Disorders criteria of sexual aversion were used. The statistical analyses used were descriptive statistics and independent samples t-test. RESULTS: Sexual fears and aversive or blocking behavior are mild to moderate, mean score of 1.54 ± 0.04, without statistically significant gender differences. Both sexes have established fear-related sexual aversive motives of sexual behavior related to the risk of unwanted pregnancy and HIV infection. Women have significantly higher average scores for the following statements: fear of sexual intercourse (1.61 vs 1.25), avoidance of situations in which they may be involved sexually (1.95 vs 1.51), avoidance of genital sexual contact (1.44 vs 1.16), fear of catching a sexually transmitted disease (2.46 vs 2.09 ), fear of pregnancy (2.61 vs 2.15) and concerns what other people think of them (2.34 vs 1.93 ). CONCLUSIONS: Sexual fears and aversive or blocking behavior were mild to moderate. In both sexes similar fears--aversive or blocking patterns of sexual behavior were found, mainly associated with the fear of unwanted pregnancy and the risk of HIV infection, more expressed in women.

Inflammation, mitochondrial and lysosomal dysfunction as key players in rheumatoid arthritis?

Rheumatoid arthritis (RA) is an inflammatory joint disease characterized by persistent synovitis and inflammation. The exact mechanism of mitochondrial function in the presence of inflammation and dysregulation of autophagic processes in the pathogenesis of RA is still unclear. The aim of our study is to determine mitochondrial function, gene and protein levels of biomolecules related to inflammation (YKL-40) and autophagy (LAMPs) and to search a connection between them in the RA context. Twenty newly diagnosed RA patients and ten healthy individuals were included in the study. Disease severity was assessed by ultrasonography. Conventional clinico-laboratory parameters, immunological markers and protein levels of LAMPs and YKL-40 were examined in plasma. Gene expression analysis for the quantitative measurement of LAMPs and YKL-40 were conducted in white blood cells (WBC). A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in peripheral blood mononuclear cells (PBMCs). Increase in spare respiratory capacity in PBMCs of RA patients was detected. Decreased LAMPs plasma protein levels and increased protein levels of YKL-40 in RA patients compared to healthy individuals were measured. No significant differences were found in gene expressions. Correlations between mitochondrial, ultrasonographic and protein levels of the biomarkers related with inflammation and autophagy were established. New data on mitochondrial dysfunction in RA patients and links to inflammation and mitophagy are reported. The relationship between dysregulation of mitophagy and joint diseases deserves to be thoroughly investigated as it would be a promising therapeutic approach.