Evaluation of assessable telemedicine in patients with rheumatoid arthritis: A systematic review.

OBJECTIVE: Nowadays, the use of telemedicine diagnosis and treatment of various diseases has been considered by physicians, especially in such diseases as rheumatoid arthritis (RA), where patients have more weakness and inability to move. This systematic review aimed to evaluate the extent of measurable and nonmeasurable factors in patients with RA and their satisfaction with this method of care. METHODS: The articles published by March 3, 2022, were searched in four databases, including Web of Sciences, Medline, PubMed, and Scopus. This research was conducted using the seven steps of the Cochrane Handbook as a guide. The searched keywords included telemedicine, tele-rheumatoid, rheumatoid arthritis, and immune diseases. RESULTS: A total of 18 articles were included in the present study. In most of these studies, physicians and patients were satisfied with this approach. Nonetheless, there was a dearth of studies on the measurement of evaluable and nonevaluable factors. CONCLUSION: Studies on the benefits of telemedicine for rheumatology are still limited. The effectiveness of this new healthcare approach in diagnosing and evaluating disease activity is still unclear. Some studies demonstrated patient and physician satisfaction with this treatment. In some cases, there is a tendency to show a high risk of bias. In addition, it is unclear to what extent the use of rheumatology traps affects the establishment of medical relationships. It is recommended that more clinical trials be conducted to examine this relationship.

Periodontal Disease in Patients with Newly Diagnosed Systemic Lupus Erythematosus.

Statement of the Problem: Most of the studies assessing the relationship between systemic lupus erythematosus (SLE) and periodontal disorder are focused on patients with previously diagnosed SLE whose periodontal hygiene may be influenced by immunosuppressive therapies. Purpose: This study aimed to evaluate the frequency of periodontal disease among patients with newly diagnosed lupus before starting immunosuppressive therapy and its association with presenting laboratory and clinical symptoms of lupus. Materials and Method: This case-control cross-sectional study was conducted on 36 consecutive newly diagnosed SLE patients before starting any treatment. The control group consisted of first-degree relatives of the patients whose demographic and social characteristics matched with the patients and who had no personal history of a disease. Periodontal indices included community periodontal index (CPI) and plaque index (PI). Results: Participants in both groups had some degree of periodontal disorder. The mean value of CPI was 1.47±0.82 and 1.31±0.72 in SLE patients and healthy subjects (P=0.84), respectively. Moreover, the mean values of PI were 1.15±0.55 and 1.17±0.46 in SLE patients and controls, (P=0.37), respectively. Besides, the frequency of periodontal disorders based on CPI score (positive: higher than two) was 22.2% in SLE patients and 16.7% in controls (P=0.55). Moreover, there was no association between periodontal disease and lupus-related clinical and laboratory characteristics in our patients. Conclusion: The frequency of periodontal disorders is similar between newly diagnosed lupus patients without undergoing immunomodulatory therapies and healthy controls with the same demographic and social characteristics. Moreover, periodontitis was not associated with clinical and laboratory symptoms of our patients.

Expression pattern of glucocorticoid receptor α gene and associations with clinicolaboratory features in patients with systemic lupus erythematosus.

Background: Glucocorticoid receptor α (GRα) gene is a transcription factor with clinically significant immune-modulating properties in various autoimmune diseases. However, the expression pattern of the GRα gene and associations with clinical features in patients with systemic lupus erythematosus (SLE) is controversial. This study aimed to assess the correlation between the GRα expression and different clinical and laboratory-related parameters in SLE patients. Methods: A total of 45 women with newly diagnosed SLE and 31 gender and age-matched healthy controls were enrolled in this cross-sectional study. The real-time quantitative PCR (qRT-PCT) method evaluated the differences in GRα expression in peripheral blood mononuclear cells from cases and controls. The correlation between the GRα gene expression levels, clinicolaboratory features, and potential prognostic application was also analyzed. Results: Compared to the healthy individuals, the GRα gene expression in newly diagnosed SLE patients who did not receive any treatment was numerically reduced, but this reduction did not achieve statistical significance (P=0.87). No significant correlation was also found with the activity and severity of SLE according to SLEDAI2K (P=0.41). The GRα gene expression showed a negative correlation with CRP (P=0.034) and a positive correlation with lupus anticoagulant (P=0.039) levels in SLE. The receiver operating characteristic (ROC) curve analysis indicated that the GRα expression level might be a predictor biomarker for low CRP and positive lupus anticoagulant in SLE, respectively. Conclusion: This study proposed that expression of the GRα in newly diagnosed lupus patients has no statistically significant difference with healthy age and sex-matched controls. Besides, its expression does not correlate with lupus disease activity according to SLEDAI2k. However, further studies in this area are required.

Comparison of the efficacy and safety of methotrexate alone or in combination with leflunomide in the treatment of juvenile idiopathic arthritis: a double-blind, placebo-controlled, randomized trial.

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder in children. Although methotrexate (MTX) is the first line disease-modifying antirheumatic drug for JIA, many patients do not respond well or cannot tolerate MTX. The aim of this study was to compare the effect of combination therapy of MTX and leflunomide (LFN) with MTX in patients who do not respond to MTX. Material and methods: Eighteen patients (2-20 years old) with polyarticular, oligoarticular or extended oligoarticular subtypes of JIA who did not respond to conventional JIA therapy participated in this double-blind, placebo-controlled, randomized trial. The intervention group received LFN and MTX for 3 months while the control group received oral placebo and MTX at a similar dose to the intervention group. Response to treatment was assessed every 4 weeks using the American College of Rheumatology Pediatric criteria (ACRPed) scale. Results: Clinical criteria, including number of active joints and restricted joints, physician and patient global assessment, Childhood Health Assessment Questionnaire (CHAQ38) score, and serum erythrocyte sedimentation ratelevel, did not differ significantly between groups at baseline and at the end of the 4th and 8th weeks of treatment. Only the CHAQ38 score was significantly higher in the intervention group at the end of the 12th week of treatment. Analysis of the effect of treatment on study parameters revealed that only the global patient assessment score differed significantly between groups (p = 0.003). Conclusions: The results of this study showed that combining LFN with MTX does not improve clinical outcomes of JIA and may increase side effects in patients who do not respond to MTX.

Complications and Efficacy of Sinopharm Vaccine among Liver and Kidney Transplantation.

BACKGROUND: There are various vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, vaccination may lead to some complications. OBJECTIVE: This study aimed to investigate the complications of transplant recipients who received the Sinopharm COVID-19 vaccine. METHODS: This was a retrospective cross-sectional study conducted among 667 transplant recipients (211 liver transplant recipients and 456 kidney transplant recipients) who received the Sinopharm COVID-19 vaccine from March to August 2021 and had medical records in Montaserieh Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The demographic and clinical information, as well as patient's symptoms after each dose of the vaccine, were recorded. RESULTS: Only 16.8% and 13.7% of the patients experienced some symptoms following the first and second doses of the Sinopharm vaccine, respectively. No significant difference was observed between patients younger than 50 years and those aged 50 years and over in terms of the complication rate of the Sinopharm vaccine (P>0.005). Vaccine failure was reported in 10% of the cases; however, the mortality rate due to infection with the Delta variant of COVID-19 in this population was reported to be 0.7%. CONCLUSION: Based on the obtained results, adverse reactions of the Sinopharm COVID-19 vaccine are generally mild, predictable, and non-life-threatening both in the first and second doses. Vaccine failure was reported in 10% of the cases; however, mortality due to infection with the Delta variant of COVID-19 was reported in less than 1% of the cases.

Serum Level of Soluble Human Leukocyte Antigen G in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis.

BACKGROUND: This study aimed to evaluate the serum level of human leukocyte antigen G [HLA-G] in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls; moreover, it attempted to assess its relationship with SLE and RA disease activity indices. METHODS: This descriptive study was conducted on 31 SLE patients (17 cases with a recent diagnosis and 14 cases with a previous diagnosis), 21 RA patients (7 cases with a recent diagnosis and 14 cases with a previous diagnosis), and 18 healthy controls who visited Ghaem Hospital affiliated to Mashhad University of Medical Sciences, Mahhad, Iran. SLE and RA activity indices were measured and recorded. Furthemore, soluble isoforms, including shed HLA-G1 and HLA-G5, were measured in serum samples via the ELISA method. RESULTS: A comparison of the five groups showed no significant differences in the serum level of sHLA-G. However, sHLA-G serum level was significantly higher in SLE and RA patients compared to healthy controls (P<0.05). sHLA-G level showed no correlation with disease duration and activity in SLE and RA patients (P>0.05). However, a strong positive correlation was observed between the serum level of sHLA-G and 24-h urine protein in the previously diagnosed SLE group (r=0.83, P=0.01). CONCLUSION: It seems that the serum level of sHLA-G is higher in RA and SLE patients compared to healthy controls. Furthermore, a strong correlation was found between sHLA-G serum levels and 24-h urine protein in cases with a previous diagnosis of SLE.

Simultaneous occurrence of knee septic arthritis and coronavirus disease 2019 (COVID-19): A case report.

Background: Coronavirus disease 2019 (COVID-19) pandemic is increasingly recognized as a serious, worldwide public health concern. Most of the patients with COVID-19 are asymptomatic or show mild symptoms. It is important to identify the unusual manifestations and their long-term complication. Case presentation: A case of COVID-19 in 45 years old man with septic arthritis due to Staphylococcus aureus is presented. COVID-19 was diagnosed using real-time polymerase chain reaction without obvious clinical manifestation. The patient had no history of trauma or inflammatory arthritis and had progressive left knee pain and limitation of movement. Knee X-ray was normal. Aspiration of the knee joint fluid showed a cloudy and purulent appearance. The patient was admitted to hospital and immediately treated with vancomycin 1gr/12 hr. A polymerized chain reaction (PCR) test for COVID-19 was performed, which was positive 24 h after hospitalization. Staphylococcus aureus was reported in synovial fluid culture which was sensitive to vancomycin and ciprofloxacin, thus vancomycin was continued. On the 4th day of hospitalization the patient had cough, therefore underwent CT scan lungs and ground-glass opacities (GGO) characteristic of COVID-19 were noticed. Favipiravir and interferon were started. Patient's knee aspiration was performed for 5 consecutive days. On the 6th day of hospitalization, joint fluid markedly decreased and the patient's oxygen saturation was 96%. One week after hospitalization, the patient was discharged and a month later knee examination was completely normal. Conclusions: Septic arthritis should be considered in the manifestations or co-morbidity of COVID-19 patients with joint pain, swelling or redness.

ABO and Rh blood groups in patients with lupus and rheumatoid arthritis.

BACKGROUND: Systemic lupus erythematous (SLE) and rheumatoid arthritis (RA) are autoimmune diseases in which the antigen-antibody system plays an important role. As blood group and Rh are determined by the presence or absence of antigens on the surface of red blood cells (RBCs), we aimed to determine the distribution of ABO and Rh blood groups in SLE and RA patients and its association with disease manifestations. METHODS: This short communication is based on a study that was conducted on 434 SLE and 828 RA patients. We evaluated the distribution of ABO and Rh blood groups in RA and SLE patients. RESULTS: This study projected that in lupus patients, Coombs-positive autoimmune hemolytic anemia and arthritis were more common among the B blood type and Rh-positive group, respectively. Furthermore, there was no relation between ABO and Rh blood group and rheumatoid factor (RF) and anti-Cyclic Citrullinated Peptide (anti-CCP) seropositivity. Moreover, there was no difference in distribution of blood groups in RA and SLE patients. CONCLUSION: The higher frequency of blood group B in hemolytic anemia, and positive Rh in arthritis in lupus patients, develop the hypothesis of probable role of ABO blood group antigen in some manifestations of lupus.

A double-blind placebo-controlled randomized trial of oral saffron in the treatment of rheumatoid arthritis.

OBJECTIVE: Recently, saffron (Crocus sativus L. from the Iridaceae family) has been characterized by its antioxidant, anti-inflammatory and analgesic effects. This study aimed to evaluate the effect of saffron on disease activity in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: This is a double-blind, placebo-controlled, randomized clinical trial (RCT) performed on 55 newly- diagnosed RA patients without previous treatment, who were randomly divided into intervention (included 28 cases) and control groups (consisted of 27 individuals). Standard therapy including prednisolone, oral methotrexate, folic acid, vitamin D, calcium, and alendronate, was administered similarly in both groups. Patients received a 100 mg saffron pill/day (pure saffron powder) or placebo besides the standard protocol. The placebo had the same shape as the saffron pills. Follow up of DAS28ESR disease activity score was done on the 30th, 45th and 90th day of the study. RESULTS: There was no difference between the intervention and control groups regarding to the DAS28ESR at the end of the study. However, a significant decrease in DAS28-ESR was observed in each group compared to the first visit (p=0.001). The results also showed no significant difference in the incidence of side effects in both groups. CONCLUSION: In summary, patients who received pure saffron pills (100 mg/day) in addition to standard therapy did not have a significant difference in improvement of disease activity from the patients on standard therapy.

Serum B cell activating factor (BAFF) and sarcoidosis activity.

OBJECTIVES: This study aims to determine the relationship between the severity of sarcoidosis and serum B-cell activating factor (BAFF) concentrations. PATIENTS AND METHODS: This cross-sectional study was conducted between December 2015 and March 2018 on 55 patients with sarcoidosis (16 males, 39 females; mean age, 39.9; range 25 to 60 years) and 28 healthy subjects (7 males, 20 females; mean age, 39; range 25 to 60 years). The sarcoidosis patients were divided into active chronic sarcoidosis and acute sarcoidosis groups. The diagnosis of sarcoidosis was based on clinical, radiological, and pathologic findings. Also, the diagnosis of the active disease was based on the level of angiotensin-converting enzyme, active skin, eye, and lung lesions. Scadding score was also measured, and other patient information was collected by pre-designed questionnaires. RESULTS: The most involved organs were the skin (92.7%) and joints (92.3%), respectively. The mean BAFF concentration in both active chronic sarcoidosis (p=0.001) and acute sarcoidosis (p=0.001) groups was significantly higher than the control group, but the mean level of BAFF in these two groups was not significantly different (p=0.351). Between two groups of patients, only calcium (p=0.001) and forced vital capacity (p=0.021) were higher in the acute group of sarcoidosis. Also, among the factors associated with active chronic sarcoidosis and acute sarcoidosis, none was significantly correlated with BAFF. CONCLUSION: Serum BAFF concentration was higher in patients with sarcoidosis, while this was not significantly different from increasing severity of symptoms. There was no significant difference in BAFF levels between acute sarcoidosis and active chronic types.

Correlations and Influence of TAP2 Genes Polymorphisms and Systemic Lupus Erythematosus Propensity.

OBJECTIVES: The present study was designed to evaluate the association of transporters associated with antigen processing (TAP2) polymorphisms TAP2-379Ile > Val (rs1800454), TAP2-665Thr > Ala (rs241447) and TAP2-565Ala > Thr (rs2228396) as a candidate gene with susceptibility to the Systemic Lupus Erythematosus (SLE). METHODS: To analyze these three polymorphic variants, 88 patients with SLE and 100 healthy controls from northeastern Iran were enrolled from May 2018 to July 2019. Genomic DNA polymorphisms were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. Data were analyzed by SPSS software. RESULTS: In this cross-sectional study, there was a stratification between patients and controls. The distribution of the frequency of Ala73 (41.5%) allele at TAP2/665 and Ile 19 (10.8%) allele at TAP2/379 was higher in patients. Additionally, the Ala/Ala 13(14.8%) and Ala/Thr 49(55.7%) genotypes distributions at 665 positions were higher in SLE patients compared to the controls. Furthermore, frequencies of TAP2*H allele significantly increased in SLE patients 10(5.71%) (P=0.01). Frequency of TAP2*A allele in the control group was 120(60%) (p=0.06) due to the dominant genetic model. This allele has a protective effect against SLE. There was no relationship between TAP2*D, TAP2*E, TAP2*F and TAP2*G alleles with the outbreak of SLE. CONCLUSION: Our data indicated that genetic variants in TAP2 gene may be associated with SLE disease. A correlation between Ala allele at TAP2/665 and Ile allele at TAP2/379 polymorphisms and pathogenesis of SLE was observed.

Serum Level of Soluble Lymphocyte-Activation Gene 3 Is Increased in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is described as a systemic and chronic autoimmune disease characterized by inflammatory polyarthritis. Lymphocyte-activation gene 3 (LAG3) is a membrane glycoprotein expressed on activated, exhausted, and regulatory T cells. LAG3 plays a major role in the function of Treg cells. LAG3 also has a soluble form (sLAG3) with a controversial role. OBJECTIVE: To evaluate the serum level of sLAG3 in rheumatoid arthritis patients in comparison with healthy subjects and assess its association with the disease activity. METHODS: This cross-sectional study was performed on 105 patients with RA referred to Ghaem hospital of Mashhad, Iran. We divided the participants into four groups: 1) 35 untreated patients with newly diagnosed RA, 2) 35 active RA patients, 3) 35 patients in the remission phase of the disease, and 4) 35 healthy individuals matched in terms of age and sex. After completing the interview and questionnaire, the sLAG3 was evaluated by commercial ELISA. RESULTS: The serum level of sLAG3 significantly increased in RA patients (76.78 ng/ml) as compared with the healthy participants (51.67, p=0.002). However, there was no significant difference between RA patients in the remission phase of the disease (114.11 ng/ml) and those with moderate to high disease activity (63.06 ng/ml, p=0.076). CONCLUSION: This study provided insights into the role of sLAG3 in the immunopathogenesis of RA disease, but further investigations are also warranted.

Comparison of the Therapeutic Effects of Rivaroxaban Versus Warfarin in Antiphospholipid Syndrome: A Systematic Review.

OBJECTIVES: This study aims to review the studies evaluating the therapeutic effects of rivaroxaban versus those of warfarin in patients with antiphospholipid syndrome (APS). MATERIALS AND METHODS: The study included randomized clinical trials, comparative studies, cross-sectional investigations, and case series that focused on the effects of warfarin and rivaroxaban and compared the effects of these anticoagulants in patients with APS. The relevant articles published until 2018 were searched in several databases, including PubMed, Scopus, ScienceDirect, Google Scholar, Embase, and Web of Science. RESULTS: The findings of the reviewed studies showed that rivaroxaban can be used as an effective and safe alternative to warfarin in APS patients. However, the effectiveness of rivaroxaban in the prevention of thrombosis in high-risk APS patients is suspected. CONCLUSION: Given the high risk of using rivaroxaban in thrombotic APS patients with labile international normalized ratio (INR) or poor adherence to INR monitoring, it is not suggested to use this agent for these patients.

Diagnostic Role of Survivin in Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which is characterized by the hyperplasia of synovial tissue. Survivin is a member of the inhibitor of apoptosis protein family, which facilitates the formation of functional T-cell receptor and differentiation of memory T cells. Survivin plays an important role in the expression of major histocompatibility complex molecules and mature dendritic cells, which play the main role in the etiology of RA. This systematic review was conducted to investigate the evidence on the role of survivin as a diagnostic and predictive value in RA patients. All published articles related to the subject of interest and published up to 30 March 2018 were searched in three databases, including Google Scholar, PubMed, and Web of Science. After a detailed evaluation of the full-text version of the papers, 23 articles were entered into the study. The elevation of survivin in the preclinical phase of RA and its association with anti-cyclic citrullinated peptide (CCP) antibodies suggested it as a predictor of RA. Recently, survivin has been introduced as the biomarker of joint damage and poor response to antirheumatic treatment in RA patients. Based on the evidence, survivin level had high specificity and sensitivity in the diagnosis of RA patients. The results of the reviewed studies demonstrated that a positive survivin level was associated with the presence of anti-CCP antibodies.

Relationship Between Polymorphisms of Interleukin-1 Receptor Antagonist (IL-1Ra) Genes and Susceptibility to Systemic Lupus Erythematosus in Iranian Population.

OBJECTIVES: Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran. METHODS: Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene. RESULTS: Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29). CONCLUSION: Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here.

Efficacy of Acceptance and Commitment Therapy in Reducing Disappointment, Psychological Distress, and Psychasthenia among Systemic Lupus Erythematosus (SLE) Patients.

Objective: The aim of this study was to evaluate the efficacy of acceptance and commitment therapy (ACT) in the reduction of disappointment, psychological distress, and psychasthenia among patients with systemic lupus erythematosus (SLE). Method : This quasi-experimental study was conducted on 24 females with lupus who referred to the Rheumatoid Disease Research Center (RDRC) of Ghaem hospital in Mashhad, Iran. This study had a pretest-posttest control group design. The participants were randomly assigned into 2 groups of experimental and control. The experimental group was treated with ACT. Data were collected using the Beck's Hopelessness Scale, Kessler's Psychological Distress Inventory, and Krupp's Psychasthenia Inventory. Results: Mean age and mean duration of illness were 37.25±4.61 and 5.12±2.33 years, respectively. The mean disappointment score and psychological distress in the experimental group were lower compared to those in control group at the post experimental stage (P<0.001). Moreover, there was a significant difference between the experimental and control groups in the mean scores of psychasthenia in the posttest stage (P<0.001). Conclusion: According to the obtained results of this study, the enhancement of psychological flexibility based on ACT positively affected disappointment, psychological distress, and psychasthenia among the lupus patients. Therefore, it can be concluded that this therapeutic approach could reduce psychasthenia in patients through clarification of the values.

Serum hepcidin level and rheumatoid arthritis disease activity.

OBJECTIVE: The present study aimed to determine the relationship between the serum hepcidin level and disease activity in patients with rheumatoid arthritis (RA). METHODS: This study was conducted on 80 patients with RA (36 cases with anemia of chronic disease [ACD] and 44 patients without ACD). Disease activity was measured by the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR). According to the DAS28-ESR score, 52 and 28 cases were categorized as inactive to moderately active RA (DAS28-ESR≤5.1) and highly active RA (DAS28-ESR>5.1), respectively. In addition, the serum hepcidin level was evaluated in all patients to determine its correlation with the DAS28-ESR score. RESULTS: There was no significant difference between the RA with ACD and RA without ACD groups in terms of the median (interquartile range) hepcidin level (1207 [985.2] vs. 923.8 [677.3] ng/mL; P=0.57). Likewise, no significant difference was observed between the active RA and inactive to moderately active RA groups in this regard (1131.8 [991.3] vs. 1090.9 [631.4] ng/mL; P=0.53). CONCLUSION: Hepcidin has no association with disease activity in RA. Therefore, it is not necessary to measure hepcidin to determine the RA activity.

Preoperative Evaluation and Management of Patients Receiving Biologic Therapies.

The preoperative care of patients undergoing orthopedic surgery and treated with biologic agents is of great significance. Perioperative use of biologic agents could lead to such complications as infection and delayed postoperative wound healing. This narrative review aimed to evaluate the current information on the use of biologic agents in patients undergoing orthopedic surgery, determine the rate of associated postoperative complications, and identify the appropriate time for the continuation or discontinuation of biologic therapy in these patients. It can be stated that all biologic agents increase the risk of infections depending on their half-lives. Biologic agents are suggested to be withheld for at least twice their half-lives before major surgeries. However, in case of minor operations, they can be continued given the low risk of infection and impaired wound healing in these cases. LEVEL OF EVIDENCE: I.

International multicenter randomized, placebo-controlled phase III clinical trial of ß-D-mannuronic acid in rheumatoid arthritis patients.

BACKGROUND: The oral administration of drug ß-D-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. METHOD: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. RESULTS: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. CONCLUSION: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of ß-D-mannuronic acid as a new highly safe and efficient drug in the treatment of RA.

Selenium and Autoimmune Diseases: A Review Article.

BACKGROUND: Selenium is an essential trace element with fundamental effects on human biology. Trace elements deficiency is not an uncommon finding in autoimmune diseases. This deficiency may be a consequence of autoimmune diseases or may contribute to their etiology. With regard to evidence showing the association between selenium deficiency and generation of reactive oxygen species and subsequent inflammation, reviewing the role of selenium in collagen vascular diseases could help researchers to devise strategies for managing these diseases. OBJECTIVE: The present study aimed to evaluate the role of selenium and autoimmune rheumatic diseases. DATA SOURCES: PubMed, Scopus, Science Direct, and Google Scholar. STUDY ELIGIBILITY CRITERIA: All the studies on the use of selenium without any limitations in terms of the preparation method, administration route, or formulation process were included in the study. The exclusion criteria were: 1) Articles published in languages other than English, 2) Administration of chemical and hormonal drugs rather than selenium, 3) Investigation of the effects of selenium on the autoimmune problems in animal models, and 4) Insufficiency of the presented data or poor description of the applied methods. Furthermore, review articles, meta-analyses, expert opinions, editorial letters, case reports, consensus statements, and qualitative studies were excluded from the study. DATA EXTRACTION: In this systematic review, articles were evaluated through searching following keywords in combination with selenium: "autoimmune rheumatic diseases "or "scleroderma" or "systemic sclerosis" or "Behcet's disease" or "Sjögren syndrome" or "systemic lupus erythematosus" or "musculoskeletal diseases" or "rheumatoid arthritis" or "vasculitis" or "seronegative arthritis" or "antiphospholipid antibody syndrome". RESULTS: Of 312 articles, 280 were excluded and 32 articles were entered in this study. Based on the majority of studies assessing selenium level in patients with collagen vascular diseases, lower selenium levels were observed in these patients. Moreover, the majority of articles showed an improvement in clinical symptoms of collagen vascular diseases compared to controls after the treatment of patients with different dosages of L-selenomethionine. CONCLUSION: A decrease in the serum level of selenium was noted in patients with autoimmune diseases, which may be a risk factor for inflammation and initiation of autoimmunity in these patients. A sufficient quantity of selenium has been shown to contribute to the management of complications of autoimmune diseases and even improved survival in patients with autoimmune diseases, which may be due to the anti-inflammatory effects of selenium. Since this issue is of clinical importance, it can be considered in potential nutrition interventions and have beneficial effects on some autoimmune diseases.