Quadricuspid Aortic Valve and Rheumatoid Arthritis: A Coincidence or Interconnection.

Quadricuspid aortic valve is a very rare congenital anomaly. Its association with rheumatoid arthritis is exceptional with this being the third case reported in the literature. We report a case of a 52 year old female patient with quadricuspid aortic valve type C accompanied by moderate to severe aortic regurgitation and longstanding, advanced form of rheumatoid arthritis. Having refused surgical aortic valve intervention 4 years ago, the patient is currently under a watchful follow-up strategy. The patient received a diagnosis of rheumatoid arthritis over 15 years before and presently has serious deformities in the hands, legs, feet, and spine. In conclusion, quadricuspid aortic valve and rheumatoid arthritis together are extremely rare. While it is possible that this association is coincidental, considering the genetic background of both disorders, there is a potential for them to be interconnected comorbidities. This report is the first to highlight the association between the 2 disorders.

Efficacy and safety of tocilizumab versus standard care/placebo in patients with COVID-19; a systematic review and meta-analysis of randomized clinical trials.

AIMS: Tocilizumab has emerged as an important therapy in treating patients with coronavirus disease (COVID-19). Our purpose was to evaluate the efficacy and safety of tocilizumab versus standard care/placebo in patients with COVID-19. METHODS: We searched a variety of sources from 1 January 2020 to 5 May 2021. All randomized controlled trials that reported tocilizumab efficacy as a primary agent in COVID-19 patients were considered. RCTs had to include mortality events, incidence of mechanical ventilation and serious adverse events. Two reviewers were independently responsible for data extraction. Assessment of bias and certainty of evidence was carried out using the Cochrane Risk of Bias Tool and GRADE methodology. RR for mortality events was evaluated using a fixed-effects model. RESULTS: A total of 6837 patients were included from 10 RCTs, of which nine were peer-reviewed. Pooled risk ratio (RR) for all-cause mortality in patients with tocilizumab administration was RR = 0.88 (95% CI: 0.81-0.95, P = .0009). RR for incidence of mechanical ventilation at 28-30 days was 0.79 (95% CI: 0.71-0.88). Serious adverse events (SAE) with tocilizumab use were associated with lower RR (RR = 0.91, 95% CI: 0.76-1.09) but the certainty of evidence was downgraded to moderate due to serious risk of bias. CONCLUSION: In COVID-19 patients with moderate to critical COVID-19, use of tocilizumab reduces all-cause mortality and progression to mechanical ventilation. This efficacy was not associated with higher number of serious adverse events.

Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

AIM: This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). METHODS: In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. RESULTS: Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic progression comparing to the group of patients with monotherapy. CONCLUSIONS: Based on our results achieved during 2 years we can conclude that ETN in combination with MTX reduced disease activity, slowed radiographic progression and improved clinical manifestations more effectively than MTX alone. No serious adverse events were noticed in the group with combination treatment.

The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. OBJECTIVE: The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). MATERIALS AND METHODS: This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2-4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. CONCLUSION: Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required.

Late onset rheumatoid arthritis an observational study.

Rheumatoid arthritis (RA) may have an onset at older age. The onset of the disease at the age of 60 and over is called late-onset rheumatoid arthritis (LORA). The aim of this study was to analyze the clinical, laboratory, radiological, and treatment characteristics of patients with LORA compared to those with early-onset RA (EaORA), provided that all the patients had an approximately equal duration of the disease. This is an observational single-center study, which involved 120 patients with an established diagnosis of RA, of which 60 patients had LORA, and 60 patients EaORA. The disease activity, measured by the Disease Activity Score 28 (DAS28-ESR), was significantly higher in the LORA group compared to the EaORA group (p<0.05). Significantly more patients with LORA had involvement of the shoulders (LORA vs. EaORA, 30% vs. 15%; p <0.05) and knees (LORA vs. EaORA, 46.7% vs. 16.7%; p <0.05). Radiological erosive changes were significantly more frequent in the LORA group in comparison with EaORA (p <0.05). There was no difference between the groups regarding rheumatoid factor (RF) positivity (p>0.05), while the number of patients positive for anti-citrullinated protein antibody (ACPA) was signifi cantly greater in the EaORA group (p<0.05). The values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly higher in the LORA than in the EaORA group. Hemoglobin levels were lower in the LORA group (11.96±1.64 g/dL) than in the EaORA group (12.18±1.56 g/dL). The most used disease-modifying antirheumatic drugs (DMARDs) were methotrexate and sulfasalazine, while biological drugs were not used. In conclusion, based on the results of our study, LORA has some features that distinguish it from EaORA, such as higher disease activity, more frequent involvement of large joints, and more pronounced structural damage. This should be taken in account in clinical practice, especially regarding treatment choices.

PERICARDIAL FEATURES OF IN-HOSPITAL RHEUMATOLOGY PATIENTS: AN OBSERVATIONAL STUDY.

Rheumatic disorders can be associated with pericarditis, but severe forms of pericarditis are rare. The aim of this observational study was to evaluate pericardial features in patients with different rheumatic diseases. Thirty-five patients hospitalized at the Clinic of Rheumatology, University Clinical Center of Kosovo, from October 1 to October 21, 2014 were included in the study. Demographic data, history, laboratory, ECG, and echocardiography data, with special emphasis on the analysis of the pericardium, were obtained from each patient. Echocardiography was especially focused on the amount of pericardial fluid and pericardial thickness in the posterior wall of the heart. Mean patient age was 51.5 ± 13.8 years. 65.7% of the patients were women. Out of the patients that we analyzed, 88.6% had an inflammatory rheumatologic disease. 11.3% of the patients had mild symptoms, in 68.7% the symptoms were moderate, and in 20% severe. In all patients, pericardial hyperechogenicity was marked, with a mean pericardial thickness of 4.68 ± 1.66 mm. Pericardial effusion in a small amount was present in 57.1% of patients, with a mean pericardial fluid amount of 3.3 ± 1.9 mm. The severity of rheumatic disease had a positive and significant correlation with the presence of pericardial effusion (r= 0.29, p=0.04) and its amount (r= 0.28, p=0.05). The patients had not been aware of the pericardial involvement and did not have any clinical symptoms. In conclusion, in this short-term small observational study pericardial changes were a frequent finding in the rheumatology patients. In general, the pericarditis was subclinical and with small amounts of effusion. The disease activity of rheumatic disorders can be associated with pericarditis. Further studies with larger samples of patients and of longer duration are needed to further explore this issue.

Association of Body Weight and Body Mass Index with Bone Mineral Density in Women and Men from Kosovo.

BACKGROUND AND OBJECTIVE: Body weight and body mass index (BMI) are considered potentially modifiable determinants of bone mass. Therefore, the aim of this study was to explore the association between body weight and body mass index (BMI) with total hip and lumbar spine bone mineral density (BMD). METHODS: This cross-sectional study included a population of 100 women and 32 men from Kosovo into three BMI groups. All the study subjects underwent dual-energy X-ray absorptiometry (DXA) measurements. RESULTS: Total hip BMD levels of obese menopausal and premenopausal women and men were significantly higher compared to overweight or normal weight subjects, while lumbar spine BMD levels of only menopausal women and men were higher among obese subjects. Age-adjusted linear regression analysis showed that BMI is a significant independent associate of lumbar spine and total hip BMD in menopausal women and men. CONCLUSION: Despite positive association between BMI and lumbar spine and total hip BMD in menopausal women, presence of more obese and osteoporotic subjects among menopausal women represent a population at risk for fractures because of poor balance and frequent falls; therefore, both obesity and osteoporosis prevention efforts should begin early on in life.

IMPACT OF MORNING STIFFNESS, EDUCATION, AND AGE ON THE FUNCTIONAL STATUS OF PATIENTS WITH RHEUMATOID ARTHRITIS.

The purpose of this study was to explore the relationship between disability status and duration of morning stiffness in hands with regard to age, level of education, and gender in patients with rheumatoid arthritis (RA). Also, the authors wanted to investigate this relationship with regard to the presence of rheumatoid factor, i.e., the serological status. A retrospective study was conducted in 250 patients with the classic form of RA (186 females, s64 males, mean age Xb = 49.96 y ears, range 25-60 years, disease duration 1-27 years, Xb = 6.41) previously diagnosed with RA according to the ACR (American College of Rheumatology 1987 criteria). All patients were in Steinbrocker functional classes II and III. The probability level was expressed by p < 0.01 and p < 0.05. The relationship between the variables was measured by point-biserial correlation. The correlation between duration of morning stiffness and functional class was positive but low [(r = 0.10, y = 0.00x + 2.37, p > 0.05) seronegative, (r = 0.12, y = 0.00x + 2.30, p > 0.05) seropositive]. High positive values were obtained for the linear correlation coefficient between duration of the disease and functional class (p < 0.01). Also, high values were obtained regarding the coefficient of correlation between age and functional class [(r = 0.29, p < 0.01) seronegative, (r = 0.47, p < 0.01) seropositive]. Uneducated patients were significantly more represented in functional class III [ 23 (50%) seronegative, 19 (42.2%) seropositive] than in functional class II [16 (20.3%) seronegative, 22 (27.5%) seropositive]. In conclusion, in this study of patients with rheumatoid arthritis, increased duration of morning stiffness was associated with functional disability. Functional disability increased with the duration of the disease, depended on age and educational level, and was more pronounced in older age, regardless of RA serological status. With regard to serological status and sex, the differences were non-significant.

Course and prognosis in seropositive and seronegative rheumatoid arthritis.

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis (RA), diagnosed with negative rheumatoid factor (RF) tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis. The aim of the study was to establish a scientific comparative analysis between RA seronegative and seropositive, regarding course and prognoses of the disease. Two hundred fifty patients with rheumatoid arthritis according to the (American College of Rheumatology) criteria were retrospectively studied by analysis the course and prognoses of disease. All examinees were between 25-60 years of age (Xb=49.9, SD=10.3) with disease duration between 1-27 years (Xbox=6.41, SD=6.47). Course of the disease with "remissions and exacerbations", progressive continual course and bad prognoses, were more presented in seropositive group ofpatients. Partial remission was more common in seronegative patients but according to serostatus and gender has not shown statistically significant difference. Duration of the disease was a specific prognostic sign for both subsets [(r=0.32, p<0.01) seronegative, (r=0.22, p<0.05) seropositive], while age was only a specific prognostic sign for the seropositive subset [(r=0.01, p>0.05) seronegative, (r=0.18, p<0.05) seropositive]. Seropositive and seronegative RA distinguish in course and prognostic feature, but not enough to differentiate them in two different forms of the disease. Regarding the sero-status, differences within sex, with some exceptions, are not relevant.

Radiographic estimation in seropositive and seronegative rheumatoid arthritis.

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA). Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49, p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%) seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups.

The role of anti-cyclic citrullinated peptide antibodies in predicting rheumatoid arthritis.

The study presents the results of predicting role of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis, compared to rheumatoid factor. 32 patients with rheumatoid arthritis were identified from a retrospective chart review. The results of our study show that presence of the rheumatoid factor has less diagnostic and prognostic significance than the anti-cyclic citrullinated peptide, and suggests its superiority in predicting an erosive disease course.

Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis.

Although considered a "joint disease," rheumatoid arthritis is associated with the involvement of extra-articular manifestations. The aim of the study is the investigation and comparison of frequency and type of extra-articular manifestations in a well defined community based cohort of patients with seropositive and seronegative rheumatoid arthritis. Using the ACR (1987) criteria for rheumatoid arthritis, patients have been classified into the 2nd and 3rd functional class (ARA). The studied group consisted of 125 seronegative patients with titters lower than 1:64 as defined by Rose-Waaler test, whereas the control group consisted of 125 seropositive patients with titters of 1:64 or higher. All patients were between 25-60 years of age (Xb=49,96), with disease duration between 1-27 years (Xb=6,41). In order to present the findings of the study, the structure, prevalence, arithmetic mean (Xb), standard deviation (SB), variation quotient (QV%) and variation interval (Rmax-Rmin) have been used. Probability level has been expressed by p<0,01 and p<0,05. Correlation between the number of extra-articular manifestations and duration of the disease has been calculated by means of Pearson linear correlation. Higher presence of diffuse lung fibrosis, central and peripheral nervous system damages have been confirmed in the seropositive group, and osteoporosis in the seronegative; however, no statistical difference has been found. In extra-articular manifestations, "rheumatoid core" in the seropositive subset (chi2=4,80, p<0,05) presented significant statistical difference. Rheumatoid nodules were more frequent in seropositive subset (12%:16%), in both sexes; however, they were not of significant statistical difference. Neuropathy and lung diseases were also frequently present in seropositive group, but no statistical difference has been found regarding the statistical difference. Longer duration of the disease resulted in an increase of the number of extra-articular manifestations. Calculated linear correlation by Pearson, resulted as positive and high correlation in total (r=0,36, p<0,01), and for groups [(r=0,52, p<0,01) seronegative, (r=0,25, p<0,01) seropositive], nevertheless no significant statistical difference was found regarding the sero-status. In conclusion, extra-articular manifestations are more frequent in the seropositive patients. The longer the duration of the disease the larger the number of extra-articular manifestations. Differences with regard to sero-status and sex, with some exceptions, are not observed.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study.

INTRODUCTION: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. METHODS: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. RESULTS: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. CONCLUSIONS: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

The effects of combined therapy of rheumatoid arthritis on the acute phase reactants.

The paper presents the results of studies of acute phase reactants in the 60 treated patients with rheumatoid arthritis. Patients were divided into two groups, depending on the applied treatment: group I (n = 30) was treated with methotrexate, sulfasalazine and hydroxychloroquine, and group II (n = 30) with methotrexate. The results of our study shows that there is a statistically significant reduction in the value of acute phase reactants and clinical parameters after treatment in both investigated groups of patients, and also a significant statistical difference between the first and second group of treated patients.