Etiology, Predisposing Factors, Clinical Features and Diagnostic Procedure of Otomycosis: A Literature Review.

Otomycosis (OM) is a superficial fungal infection of the external auditory canal (EAC) with a worldwide prevalence ranging from 9% to 30%. Commonly, otomycoses are caused by Aspergillus (A.) niger complex and Candida spp. Other causative agents are yeasts of the genera Cryptococcus spp., Rhodotorula spp., Geotrichum candidum, dermatophytes (Trichophyton mentagrophytes), and non-dermatophytes molds (Fusarium spp., Penicillium spp., Mucorales fungi). The widest range of different species causing OM are found in the territories of Iran, India, China, Egypt, Mexico, and Brazil. Fungal infection of the EAC varies from mild to severe forms. It can be acute, subacute, or chronic, and is often unilateral, while the bilateral form is more common in immunocompromised patients. From an epidemiological point of view, tropical and subtropical climates are the most significant risk factor for the development of otomycosis. Other predisposing conditions include clothing habits, EAC hygiene practices, long-term antibiotic therapy, diabetes, and immunodeficiency. Since it is often difficult to distinguish otomycosis from an infection of a different origin, laboratory-based evidence, including standard procedures (microscopy and cultivation), is essential for diagnosis. For the treatment of this superficial fungal infection, there are no official therapeutic guidelines and protocols. However, many antifungals for local application, such as polyene, imidazoles, and allylamines, can be applied, as well as systemic antimycotics (triazoles) in severe forms of infection.

Matrix Metalloproteinase-9 Level in Synovial Fluid-Association with Joint Destruction in Early Rheumatoid Arthritis.

Background and objective: Matrix metalloproteinases (MMPs) are the key enzymes in the pathogenesis of cartilage and joint damage and potentially a new biomarker of the early erosive form of rheumatoid arthritis (RA). Firstly, the study aimed to compare the level of MMP-9 in plasma (PL) and synovial fluid (SF) of patients with RA and osteoarthritis (OA). Secondly, the goal was to examine the association of MMP-9 level in PL and SF with early erosive changes in RA, and finally, to determine the association of MMP-9 level with serological parameters of the disease (rheumatoid factor-RF and anti-citrulline protein antibodies-ACPA). Materials and Methods: A total of 156 subjects were involved in this study (84 patients with RA and 72 patients with OA, who were involved as a control group). MMP-9 level was measured in PL and SF of all subjects by the sandwich enzyme-linked immunosorbent assay (ELISA) method. Standard radiographs of the hands and feet were used to detect joint damage and classification into erosive or non-erosive RA. The Larsen score (LS) was used for the quantitative assessment of joint damage, and its annual change (∆ LS) was used to assess the radiographic progression of the disease. Results: MMP-9 level in PL and SF was significantly higher in RA compared to controls (PL: 19.26 ± 7.54 vs. 14.57 ± 3.11 ng/mL, p< 0.01; SF: 16.17 ± 12.25 vs. 0.75 ± 0.53 ng/mL, p < 0.001) as well as in SF of patients with erosive compared to non-erosive RA (18.43 ± 12.87 vs. 9.36 ± 7.72; p < 0.05). Faster radiographic progression was recorded in erosive compared to non-erosive early RA (11.14 ± 4.75 vs. 6.13 ± 2.72; p < 0.01). MMP-9 level in SF, but not in PL, significantly correlates with the radiographic progression in both erosive and non-erosive RA (ρ = 0.38 and ρ = 0.27). We did not find a significant association between RF and MMP-9 level in early RA, but the ACPA level significantly correlates with MMP-9 level in SF (r = 0.48). Conclusion: The level of MMP-9 in plasma and synovial fluid of patients with RA is significantly higher compared to patients with osteoarthritis. The level of MMP-9 in synovial fluid is significantly higher in erosive than non-erosive early RA. It is significantly associated with the radiographic progression of the disease and the level of anti-citrulline protein antibodies.

Relationship between socio-descriptive characteristics, burnout syndrome, and quality of life of employees.

Introduction: Burnout syndrome develops as a consequence of chronic stress among employees. The study objective was to examine what socio-descriptive characteristics of employees might be associated with the appearance of the occupational burnout and to evaluate the relationship between job burnout and the quality of life among security employees of the professional private security sector in Central Serbia. Methods: A multicenter cross-sectional questionnaire-based study was performed. A multivariate logistic regression analysis and ANOVA post choc test was applied. Results: A total of 353 respondents (330 male and 23 female) participated in the study. Female sex and older age were associated with a higher risk of total burnout and the development of emotional exhaustion while male sex, higher education, and managerial position were associated with higher personal achievement and lower risk of total burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with a lower quality of life of employees. A significant negative correlation was found between total burnout and the Physical Health Composite Score (PHC) score with a correlation coefficient (rs) of -0.265 (95%CI from -0.361 to -0.163); between total burnout and the and Mental Health Composite Score (MHC) score with a rs of -0.391 (95%CI from -0.480 to -0.301); and between total burnout and TQL score with a rs of -0.351 (95%CI from -0.445 to -0.258). Conclusion: Female sex and older age were associated with a higher risk of total burnout and the development of EE while a managerial position and higher education were protective factors in relation to the development of burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with a lower quality of life of the employees. Shift work significantly reduced the total quality of life, while managerial positions increased the quality of life.

Knowledge about HPV Infection and the HPV Vaccine among Parents in Southeastern Serbia.

Background and Objectives: The vaccine against human papilloma virus (HPV) infection is recommended, according to the Serbian National Immunization Program, for children and adolescents aged 9−19 years. Three doses are given keeping in mind the recommendation that the second dose should be administered at least one month after the first dose, and the third at least three months after the second dose. No children who participated in this first study received the third dose because they did not meet these criteria. The study explored parents' knowledge about HPV infection and their awareness of the HPV vaccine. Materials and Methods: A cross-sectional questionnaire-based study was carried out in the city of Nis, in southeastern Serbia. According to the 2011 population census, the sample of children aged 9 to 19 was 850, and during the observed period, 631 children received the vaccine. A total of 615 fully completed questionnaires filled out by parents were included in the study. The study was carried out from 6 June 2022 to 7 October 2022. Multivariable logistic regression analysis was used. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. The statistical significance was p < 0.05. Results: A total of 615 children were included in the study (499 were vaccinated with the first dose and 116 with the second). Out of 499 children vaccinated with the first dose, 398 (79.6%) were girls, which is significantly higher than the rate for boys (101). The independent variable sex was statistically significant at the level of p = 0.84, OR = 2.664 (95% CI from 0.879 to 7.954). Boys are 164% less likely to be vaccinated with the HPV vaccine than girls. We determined that the independent variable place of residence was significant at the level of p = 0.041, (OR = 3.809, 95% CI from 1.702 to 8.525). Based on these findings, we determined that parents who came from rural areas were 82% less likely to know about HPV infection and HPV vaccination. Children under 15 years of age were significantly more vaccinated than those ≥15 years (OR = 3.698, 95% CI from 1.354 to 12.598). The independent variable parental education was significant at the level of OR = 0.494, 95% CI from 0.301 to 0.791. Parents who had medical education showed significantly higher awareness about the infection caused by HPV and about the HPV vaccine (p = 0.004) than parents with no medical education. The possibility that a parent would decide to vaccinate a child significantly increased upon a pediatrician's recommendation, p = 0.000 with OR = 0.250 (95% CI from 0.127 to 0.707). Health insurance coverage of HPV vaccination for children aged 9−19 years significantly increased the probability of a positive parental decision to vaccinate a child, p = 0.001 with OR = 3.034 (95% CI from 1.063 to 8.662). Conclusion: We identified several significant factors that were important for HPV vaccination such as: children under 15 years, female sex, urban place of residence, medical education of parents, pediatrician's recommendation of the HPV vaccination, and HPV vaccination free of charge. Health education and the promotion of HPV vaccination as well as healthy sexual behavior are important factors in the preservation and improvement of the health of the whole population.

Low-Frequency Magnetic Resonance Imaging Identifies Hand Joint Subclinical Inflammation in Systemic Sclerosis.

Objectives: The aim of this work was to determine hand joint inflammation in systemic sclerosis (SSc); patients with rheumatoid arthritis (RA) with hand joint involvement were used as controls. Our investigation also aimed at examining the relationship between these subclinical inflammatory changes in the hands, verified by low-frequency MRI, and clinical (especially cardiopulmonary) manifestations, disease activity, and functional capacity in patients with diffuse cutaneous (dcSSc) and limited cutaneous SSc (lcSSc). Methods: Out of 250 SSc patients, the selection included 82 patients with signs and symptoms of joint involvement, and 35 consecutive RA patients. These patients underwent clinical and laboratory investigations, and hand X-ray and MRI of the dominant hand. Synovitis/tenosynovitis, bone edema, and erosions were investigated, and the bone changes were quantified and scored using the RAMRIS method. HAQ index, modified Rodnan skin score, examination of internal organ involvement, and serological markers for SSc, as well as rheumatoid factor (RF) and cyclic citrullinated peptides antibodies (ACPA), were performed on all experimental group subjects. Results: MRI of the dominant hand showed a significantly higher number of cases with synovitis (78%) than the number of patients with clinically swollen joints (17.1%; p < 0.001); bone edema was found in 62 (75.6%) SSc patients. MRI also showed a higher number of erosions (52; 63.4%) compared to those (22; 27.5%) detected with X-ray (p < 0.001). The average values of the total MRI score of synovitis/edema and erosions in the wrist (p < 0.001) and MCP joints (p < 0.001) were statistically higher in RA than in SSc patients (p < 0.001). The probability of the MRI-detected inflammatory changes was considerably higher in SSc patients who had vascular complications (digital ulceration, OR = 4.68; 95% IP: 1.002−22.25; p < 0.05), in patients with more severe functional impairment (OR = 8.22; 95% IP: 1.74−38.89; p < 0.01), and in patients with active disease (OR = 3.132; 95% IP: 1.027−9.551; p < 0.05). In our investigation, patients with a limited form of the disease and with inflammatory changes on MR more often had higher functional impairment compared to the other group without MRI inflammation. Conclusions: Our data show that in SSc MRI can detect a significant subclinical joint inflammation. RAMRIS confirmed the high degree of joint inflammation in RA, but also revealed a great deal of joint inflammation in SSc. That inflammation is associated with systemic inflammation (disease activity), vascular complications, and more severe forms of the disease, as synovitis cannot be precisely diagnosed by the clinical examination of joints. These results suggest that a careful joint investigation is necessary in SSc, and that in symptomatic patients, MRI may identify joint inflammation. In clinical practice, this evidence might drive to an early targeted therapy, thus preventing joint erosions.

Is Osteoarthritis Always Associated with Low Bone Mineral Density in Elderly Patients?

Background and Objectives: The relationship between osteoarthritis (OA) and osteoporosis (OP) has been analysed for over four decades. However, this relationship has remained controversial. Numerous observational and longitudinal studies have shown an inverse association between the two diseases and a protective effect of one against the other. On the other hand, some studies show that patients with OA have impaired bone strength and are more prone to fractures. The study's main objective was to determine the bone mineral density (BMD) of the spine and hip (femoral neck) of postmenopausal women of different ages, with radiologically determined OA of the hip and knee, as well as to determine the correlation between BMD values and age in the experimental group. Materials and Methods: The retrospective cohort study included 7018 patients with osteoarthritis of peripheral joints and the spine, examined by a rheumatologist in an outpatient rheumatology clinic at the Institute for Treatment and Rehabilitation, Niska Banja from July 2019 to March 2021. A nested anamnestic study was conducted within the cohort study of patients, and it included two groups: an experimental group composed of 60 postmenopausal women, and a control group composed of the same number of women. Out of 120 patients, 24 did not meet the criteria for the continuation of the study (due to technical errors­radiographic and/or densitometry artefacts). Fifty-six postmenopausal women (aged 45−77 years) with hip and knee radiological OA were examined as an experimental group. The participants were divided into two subgroups according to age (45−60 years and over 61 years). The control group included 40 healthy postmenopausal women of the same age range, without radiological OA, with normal BMD of the hip and spine. All patients with OA met the American College of Radiology (ACR) criteria. OA of the hip and knee was determined radiologically according to Kellgren and Lawrence (K&L) classification, and patients were included in the study if a K&L grade of at least ≥ 2 was present. Hip and spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Results: Compared to the control group, we found statistically significantly lower BMD and T-scores of the spine in older postmenopausal women: BMD (g/cm2), p = 0.014; T-score, p = 0.007, as well as of the hip: BMD (g/cm2), p = 0.024; T-score p < 0.001. The values of BMD and T-score of the spine and hip are lower in more severe forms of OA (X-ray stage 3 and 4, according to K&L), p < 0.001. We found negative correlation between BMD and T-score and age only for the hip: BMD (g/cm2), ρ = 0.378, p = 0.005; T-score ρ = −0.349, p = 0.010. Conclusions: Older postmenopausal women with radiographic hip and knee OA had significantly lower BMD of the hip and spine as compared to the control group without OA, pointing to the need for the prevention and treatment of OA, as well as early diagnosis, monitoring, and treatment of low bone mineral density.

Electrocardiographic criteria which have the best prognostic significance in hypertensive patients with echocardiographic hypertrophy of left ventricle: 15-year prospective study.

BACKGROUND: Electrocardiography is the first-choice technique for detecting left ventricular hypertrophy in patients with arterial hypertension. It is necessary to know the probable outcome for every patient during the treatment, with the aim of improving cardiovascular event prevention. HYPOTHESIS: Certain electrocardiographic criteria for left ventricular hypertrophy may predict outcomes of patients with left ventricular hypertrophy during a 15-year follow-up. METHODS: Fifteen-year prospective study of 83 consecutive patients (53 male and 30 female; mean age 55.3 ± 8.1) with echocardiographic left ventricular hypertrophy (left ventricular mass index 170.3 ± 31.6 g/m2 ). Electrocardiographic left ventricular hypertrophy was determined by means of Gubner-Ungerleider voltage, Lewis voltage, voltage of R wave in aVL lead, Lyon-Sokolow voltage, Cornell voltage and Cornell product, voltage RV6 and RV5 ratio, Romhilt-Estes score, Framingham criterion and Perugia criterion. RESULTS: One or more composite events were registered in 32 (38.5%) patients during 15-year follow-up. Positive Lyon-Sokolow score (17.6% vs. 47.3%; P < 0.05), Lewis voltage (9.8% vs. 21.9%; P < 0.05), Cornell voltage (15.7% vs. 37.5%; P < 0.05), and Cornell product (9.8% vs. 34.4%; P < 0.01) were more frequent in a group of patients with composite events. Odd ratio for Cornell product was 4.819 (95% CI 1.486-15.627). CONCLUSION: Patients with echocardiographic left ventricular hypertrophy who had positive Lewis voltage, Lyon-Sokolow voltage, Cornell voltage, and Cornell product showed worse 15-year outcome. The strongest predictor of cardiovascular events was positive result of Cornell product.

Efficacy and Safety of PF-06651600 (Ritlecitinib), a Novel JAK3/TEC Inhibitor, in Patients With Moderate-to-Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate.

OBJECTIVE: To evaluate the efficacy and safety of PF-06651600 (ritlecitinib), an irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, in comparison with placebo in patients with rheumatoid arthritis (RA). METHODS: An 8-week, phase II, double-blind, parallel-group study was conducted. Seventy patients who were seropositive for anti-citrullinated protein antibodies and/or rheumatoid factor were randomized 3:2 to receive oral PF-06651600 (200 mg once daily) or placebo for 8 weeks. Eligible patients had an inadequate response to methotrexate, and the study design allowed up to 50% of patients to have previously received 1 tumor necrosis factor inhibitor that was inadequately effective and/or not tolerated. The primary end point was change from baseline in the Simplified Disease Activity Index (SDAI) score at week 8, assessed by Bayesian analysis using an informative prior distribution for placebo response. RESULTS: Mean change from baseline in the SDAI score at week 8 was greater in the PF-06651600 group (-26.1 [95% credible interval -29.7, -22.4]) than in the placebo group (-16.8 [95% credible interval -20.9, -12.7]; P < 0.001). Most adverse events (AEs) were mild in severity, and no treatment-related serious AEs, severe AEs, or deaths were reported. The most common classes of AE were infections and infestations as well as skin and subcutaneous tissue disorders; there was 1 mild case of herpes simplex in the PF-06651600 group that was considered to be treatment related, which resolved within 3 days without study treatment discontinuation or antiviral therapy. CONCLUSION: Treatment with the oral JAK3/TEC inhibitor PF-06651600 (200 mg once daily) was associated with significant improvements in RA disease activity and was generally well-tolerated in this small 8-week study.

Dietary compounds as potential modulators of microRNA expression in psoriasis.

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between 'good and bad' miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other 'omics', may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.

Analysis on the risk factors for organ damage in patients with systemic lupus erythematosus: a cross-sectional single-center experience.

BACKGROUND: Organ damage in patients with systemic lupus erythematosus (SLE) occurs as a consequence of the disease itself, the therapy applied and the accompanying conditions and complications. Organ damage predicts further organ damage and is associated with an increased risk of death. OBJECTIVE: This study aimed to assess the degree of irreversible organ changes in SLE patients, using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI); to establish correlations between organ damage and disease activity, quality of life, intensity of fatigue and serological factors; and to ascertain the risk factors for organ damage. DESIGN AND SETTING: Cross-sectional single-center study conducted at the Institute for Treatment and Rehabilitation "Niska Banja", Nis, Serbia. METHODS: 83 patients with SLE were enrolled: 58 patients formed the group with organ damage (SDI ≥ 1), and 25 patients without organ damage served as controls (SDI = 0). RESULTS: Organ damage correlated with age (P = 0.002), disease duration (P = 0.015), disease activity (grade 1, P = 0.014; and grade 2, P = 0.007), poor quality of life, severe fatigue (P = 0.047) and treatment with azathioprine (P = 0.037). The following factors were protective: use of hydroxychloroquine (P = 0.048) and higher scores obtained for the physical (P = 0.011), mental (P = 0.022) and general health (P = 0.008) domains. CONCLUSION: It is very important to evaluate risk factors for organ damage in the body, including physicians' overall assessment, to try to positively influence better treatment outcomes.

Analysis on the risk factors for organ damage in patients with systemic lupus erythematosus: a cross-sectional single-center experience

ABSTRACT BACKGROUND: Organ damage in patients with systemic lupus erythematosus (SLE) occurs as a consequence of the disease itself, the therapy applied and the accompanying conditions and complications. Organ damage predicts further organ damage and is associated with an increased risk of death. OBJECTIVE: This study aimed to assess the degree of irreversible organ changes in SLE patients, using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI); to establish correlations between organ damage and disease activity, quality of life, intensity of fatigue and serological factors; and to ascertain the risk factors for organ damage. DESIGN AND SETTING: Cross-sectional single-center study conducted at the Institute for Treatment and Rehabilitation "Niška Banja", Niš, Serbia. METHODS: 83 patients with SLE were enrolled: 58 patients formed the group with organ damage (SDI ≥ 1), and 25 patients without organ damage served as controls (SDI = 0). RESULTS: Organ damage correlated with age (P = 0.002), disease duration (P = 0.015), disease activity (grade 1, P = 0.014; and grade 2, P = 0.007), poor quality of life, severe fatigue (P = 0.047) and treatment with azathioprine (P = 0.037). The following factors were protective: use of hydroxychloroquine (P = 0.048) and higher scores obtained for the physical (P = 0.011), mental (P = 0.022) and general health (P = 0.008) domains. CONCLUSION: It is very important to evaluate risk factors for organ damage in the body, including physicians' overall assessment, to try to positively influence better treatment outcomes.

Monocyte chemoattractant protein-1 as a marker of systemic lupus erythematosus: an observational study.

There is a pivotal need for new markers to be tested in every day clinical practice for systemic lupus erythematosus (SLE) and lupus nephritis (LN). The levels of monocyte chemoattractant protein-1 (MCP-1) in the serum and urine of 72 SLE patients (27 with LN and 45 without LN involvement) and 30 healthy individuals were studied to establish their clinical significance. The SLE Disease Activity Index (SLEDAI) was used to establish the disease activity. Urine and serum MCP-1 was determined using the sandwich enzyme immunosorbent assay. Urinary, but not serum MCP-1, positively correlated with proteinuria (r = 0.839; p < 0.001) and negatively correlated with glomerular filtration, evaluated using the modification of diet in renal disease (MDRD) formula (r = - 0.293; p < 0.05), and with C3 complement component in active LN patients (r = - 0.519, p = 0.019). Both serum and urinary MCP-1 demonstrated a positive correlation with SLEDAI (r = 0.318; p < 0.01 and r = 0.431; p < 0.001). We also demonstrated that the levels of serum and urinary MCP-1 were significantly higher in patients with SLE compared to healthy controls, regardless of the disease activity and renal involvement. We recommend MCP-1 measurement in the routine laboratory follow-up of the SLE patients.

QTc dispersion and Cornell duration product can predict 10-year outcomes in hypertensive patients with left ventricular hypertrophy.

BACKGROUND: Persistent and adequate treatment of patients with arterial hypertension leads to more favorable disease outcome. HYPOTHESIS: Aside for the present left ventricular hypertrophy (LVH), there are other non-invasive parameters which can represent additional predictors of unfavorable prognosis in patients with essential arterial hypertension during the 10-year follow-up. METHODS: A hypertensive group with LVH (124 patients; age 57.0 ± 8.0; 84 males and 40 females) was included in the study and examined noninvasively. Patients used regular medication therapy during the follow-up period. RESULTS: During the 10-year follow-up period, unfavorable outcome was recorded for 40 (32.3%) patients. Patients with unfavorable outcome had higher baseline values of left ventricular mass index (178.9 ± 29.5 g/m2 vs 165.5 ± 29.5 g/m2 ; P < 0.05) and QTc dispersion (64.1 ± 24.7 ms vs 54.8 ± 19.4 ms; P < 0.05). Frequency of positive Cornell product was higher in the group of patients with unfavorable outcome (35% vs 22.2%; P < 0.01). Positive Lyon-Sokolow score did not show statistical significance (25% vs 11.9%; P = 0.06). Cornell product (ß = 0.234; P < 0.01) and QTc dispersion >65 ms (ß = 0.184; P < 0.05) had prognostic significance in LVH (multiple regression analysis: R = 0.314, R = 0.099, adjusted R = 0.084, standard error of the estimate = 0.449, P < 0.05). CONCLUSIONS: Patients with a positive Cornell product and larger QTc dispersion had more unfavorable 10-year outcomes compared with other patients with LVH.

Mapping and predicting mortality from systemic sclerosis.

OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. RESULTS: We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. CONCLUSION: Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.

Influence of disease activity on functional capacity in patients with rheumatoid arthritis.

BACKGROUND/AIM: Progressive erosive changes in cartilage and bone in rheumatoid arthritis (RA) ultimately lead to joint deformities and disability which may be early, severe and permanent. Consequently, there is the reduction of functional ability and changes in the quality of life. The aim of this study was to estimate the impact of disease activity on functional status of patients with RA. METHODS: A prospective investigation included 74 patients with RA who were treated in the Rheumatology Clinic of the "Niska Banja" Institute. Assessment of functional status (capacity) was measured by the Health Assessment Questionnaire (HAQ) with the values from 0 to 3 that patients fill out on their own. The patients were then divided into three groups: the group I with the HAQ values from 0.125 to 1.000, the group II with the values from 1.125 to 2.000 and the group III with the values from 2.125 to 3.000. Disease activity was measured by Disease Activity Score (DAS28). The assessment also included sedimentation rate (SE) influence, IgM rheumatoid factor (RF) and C-reactive protein (CRP) positivity, age, and disease duration. RESULTS: The patients with the most severe functional damage estimated by the HAQ--the group III, had the highest values of DAS28 SE (7.4 ± 0.8) compared to the group II (6.5 ± 1.2) and the group I (3.4 ± 1.2). The group III also showed the highest values of DAS28 CRP (7.1 ± 0.8) compared to the group II (6.7 ± 0.8) and the group I (3.6 ± 0.4). Compared with the patients with small and moderate functional damage, the patients in the group III had positive IgM RF and CRP as well as higher SE values more frequently and the difference was statistically significant. In the univariate logistic model, the tested parameters of DAS28 SE, DAS 28 CRP, SE, RF and CRP represent significant predictors of functional disability. The most significant factors that increase the odds of patient having the most severe functional damage include DAS28 SE which increases the odds by 5.5 times (OR = 5.450, 95% CI = 3.211-7.690, p = 0.001), DAS28 CRP by 5.1 times (OR = 5.111, 95% CI = 2.123-10.636, p < 0.01), and the presence of increased CRP (OR = 5.219, 95% CI = 1.305-18.231, p = 0.019) by 5.2 times. CONCLUSION: Functional status evaluated by the HAQ is a standard for as- sessment of RA due to its convenience and good correlation with parameters of disease activity. The most significant factors that increase the odds that the patient has the greatest functional damage are DAS28 SE, DAS28 CRP and the pres- ence of CRP.

Osteoporosis--a risk factor for cardiovascular diseases: a follow-up study.

INTRODUCTION: Cardiovascular (CV) diseases and bone fractures due to osteoporosis are the leading causes of death in the elderly. OBJECTIVE: The aim of this study was to demonstrate a correlation between the overall risk for CV events, and low bone density in postmenopausal women, and its impact on the incidence of serious CV events. METHODS: Our prospective study involved 300 postmenopausal women. All the examinees were divided into three groups based on their measured bone density: Group I--84 examinees with osteoporosis; Group II--115 examinees with osteopenia; and Group III--101 examinees with normal bone density. In all examinees the overall ten-year risk for a fatal CV event was calculated using the SCORE system tables. RESULTS: After a 36-month follow-up, CV events occurred in 19 (6.3%) examinees. Significant differences in the incidence of CV events were demonstrated between the patients with osteoporosis, osteopenia, and normal bone density (χ2 = 28.7; p < 0.001), as well as between those with a high and low CV risk (χ2 = 22.6; p < 0.001). Multivariate logistic regression analysis showed that smoking (OR: 2.23; 95% CI: 1.02 to 6.19; p = 0.035), and increase of overall CV score (OR: 1.36; 95% CI: 1.17 to 1.58; p < 0.001) are associated with increased CV event risk, while the increase of T score value is associated with decreased risk of CV event (OR: 0.42; 95% CI: 0.25 to 0.73; p = 0.002). CONCLUSION: Measurement of bone density with a standard assessment of the total CV risk could be useful for selecting women who need intensive prevention and treatment of atherosclerosis.

Anti-dsDNA, anti-nucleosome and anti-C1q antibodies as disease activity markers in patients with systemic lupus erythematosus.

INTRODUCTION: In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE) and their use in everyday clinical practice. OBJECTIVE: Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. METHODS: The study enrolled 85 patients aged 45.3 +/- 9.7 years on the average, with SLE of average duration 10.37 +/- 7.99 years, hospitalized at the Institute,,Niska Banja" during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany). RESULTS: Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p < 0.01). SLE patients with SLEDAI > or = 11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p < 0.01) and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05), as well as a higher mean level of anti-nucleosome antibodies (107.79 +/- 83.46 U/ml vs. 57.81 +/- 63.15 U/ml; p < 0.05), compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01), anti-nucleosome (r = 0.443; p < 0.001), and anti-C1q antibodies (r = 0.382; p < 0.001). Only anti-C1q antibodies demonstrated correlation with proteinuria (r = 0.445; p < 0.001). CONCLUSION: Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis activity, suggesting their potential usefulness in making predictions about lupus nephritis and assessment of disease activity.

Nailfold capillary abnormalities in erectile dysfunction of systemic sclerosis: a EUSTAR group analysis.

OBJECTIVE: The objective of this study was to analyse an association between nailfold capillary abnormalities and the presence and severity of erectile dysfunction (ED) in men with SSc. METHODS: A cross-sectional analysis of the prospective European League Against Rheumatism (EULAR) Scleroderma Trial and Research database was performed. Men with SSc were included if they had undergone nailfold capillaroscopy and simultaneous ED assessment with the 5-item International Index for Erectile Function (IIEF-5). RESULTS: Eighty-six men met the inclusion criteria. Eight men (9.3%) had not had sexual intercourse and could not be assigned an IIEF-5 score. Sixty-nine of the 78 men (88.5%) with an IIEF-5 score had nailfold capillary abnormalities, of whom 54 (78.3%) suffered from ED. Nine men (11.5%) had no nailfold capillary abnormalities, of whom six (66.7%) had ED (P = 0.44). ED was more frequent in older men (P = 0.002) and in men with diffuse disease (P = 0.06). Men with abnormal capillaroscopy had a higher median EULAR disease activity than men without (P = 0.02), a lower diffusing capacity of the lung (P = 0.001) and a higher modified Rodnan skin score (P = 0.04), but mean IIEF-5 scores did not differ [15.7 (S.D. 6.2) vs 15.7 (S.D. 6.3)]. IIEF-5 scores did not differ between men with early (n = 12), active (n = 27) or late (n = 27) patterns (IIEF-5 scores of 17.9, 16.3 and 14.7, respectively). There were no differences in the prevalence of early, active and late capillaroscopy patterns between men with or without ED. CONCLUSION: Neither the presence or absence of abnormal capillaroscopy findings nor the subdivision into early, active and late patterns is associated with coexistent ED in SSc.

Association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipid syndrome.

OBJECTIVES: The aim of this study was to investigate the association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipd syndrome (APS), as well as their connection with type and level of antiphospholipid antibodies. METHODS: Our prospective study comprises 333 patients: 218 with primary and 115 with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of aCL(IgG/IgM), ß2GPI(IgG/IgM) and LA and served to evaluate associations with distinct neurological manifestations. RESULTS: The presence of aCL IgG was more common (p=0.001) in SAPS and LA in PAPS patients (p=0.002). High ß2GPI IgM levels (>100PLU/ml) were more common in epilepsy (p=0.00001) in PAPS, and in transient ischaemic attack (p=0.029) in SAPS. High ß2GPI IgG levels (>100PLU/ml) were more common in epilepsy (p=0.035) in SAPS. Chorea, migraine and epilepsy occurred more often in SAPS and headache and depression in PAPS. We found statistical significance considering the presence of aCL IgG and acute ischaemic encephalopathy in SAPS, aCL IgM and epilepsy in SAPS, aCL IgM and migraine in PAPS, ß2GPI IgG and chorea in SAPS and ß2GPI IgM and TIA and epilepsy in PAPS. LA was linked to depression, transient global amnaesia and migraine in PAPS. Patients with non-stable angina pectoris were more likely to develop TIA in both PAPS and SAPS, epilepsy and transient global amnaesia in PAPS and acute ischaemic encephalopathy in SAPS. Patients with valve vegetations were more prone to epilepsy and depression. CONCLUSIONS: Certain aPL type and levels are associated with distinct neurological non-thrombotic manifestation, suggesting their predictive role. There is strong link between some non-thrombotic neurological and cardiac manifestations in APS patients, suggesting the complexity and evolutionary nature of APS.

The clinical significance of antibody determination to cyclic citrullinated peptides in systemic sclerosis.

INTRODUCTION: Anti-citrullinated peptides antibodies (ACPA) are present in 80% of sera of rheumatoid arthritis (RA) patients with high specificity for diagnosis and prediction for the development of early erosive arthritis. A few studies have reported a low frequency ACPA in systemic sclerosis (SSc) patients with the presence of arthritis. OBJECTIVE: The aim of our study was to determine the frequency of ACPA in systemic sclerosis (SSc) patients, their correlation with clinical manifestations and radiographic features. METHODS: The study included 82 patients with SSc, mean age 54.4 years, 59 with the limited (ISSc) and 23 with the diffuse (dSSc) form of the disease. The control group included 28 healthy age and sex matched subjects. ACPA and rheumatoid factor (RF) were determined in all SSc patients and healthy subjects in whom standard radiography of hands and wrists was also done. RESULTS: The presence of ACPA was detected in 11 (13.4%) of SSc patients. Their level was not increased in any of the controls. Positive RF was found in 15.9% of SSc patients. Arthritis was present in 17.1%, as well as marginal bone erosions. There was a statistically significant association between positive ACPA and arthritis (p < 0.0001) and positive ACPA and marginal bone erosions (p = 0.0002). CONCLUSION: The research confirmed the correlation between ACPA with clinical signs of arthritis and radiographic damage of hand joints. ACPA is a useful diagnostic marker in the identification of SSc patients with arthritis and anatomic bone damage enabling the use of adequate therapy in order to prevent joint damage and poor quality of life.