The presence of abnormal septal motion on echocardiography is a predictor of abnormal cardiac magnetic resonance in systemic sclerosis.

OBJECTIVES: We aimed to perform a comprehensive analysis of the ECG, two-dimensional echocardiography (2DE) and cardiac MRI (CMR) findings in patients with systemic sclerosis (SSc), and also to investigate correlations between CMR findings and some ECG and echocardiography (ECHO) results. METHODS: We retrospectively analysed data from patients with SSc who were regularly seen at our outpatient referral centre, all assessed with ECG, Doppler ECHO and CMR. RESULTS: Ninety-three patients were included; mean (s.d.) age of 48.5 (10.3) years, 86% female, 52% diffuse SSc. Eighty-four (90%) of the patients had sinus rhythm. The most common ECG finding was the left anterior fascicular block, recorded in 26 patients (28%). The abnormal septal motion (ASM) was found in 43 (46%) patients on ECHO. Myocardial involvement (inflammation or fibrosis), as assessed by multiparametric CMR, was present in >50% of our patients. The age- and sex-adjusted model showed that ASM on ECHO increased significantly the odds of increased extracellular volume [odds ratio (OR) 4.43, 95% CI 1.73, 11.38], increased T1 Relaxation time (OR 2.67, 95% CI 1.09, 6.54), increased T2 Relaxation time (OR 2.56, 95% CI 1.05, 6.22), increased signal intensity ratio in T2-weighted imaging (OR 2.56, 95% CI 1.05, 6.22), presence of late gadolinium enhancement (OR 3.85, 95% CI 1.52, 9.76) and mid-wall fibrosis (OR 3.64, 95% CI 1.48, 8.96). CONCLUSION: This study indicates that the presence of ASM on ECHO is a predictor of abnormal CMR in SSc patients, and a precise assessment of ASM may serve as an important point for selecting the patients that should be evaluated by CMR for early detection of myocardial involvement.

Nailfold videocapillaroscopy changes in Takayasu arteritis and their association with disease activity and subclavian artery involvement.

INTRODUCTION: Takayasu arteritis (TA) is a large vessel vasculitis characterized by the involvement of the aorta and its branches. In the present study, the nailfold videocapillaroscopy (NVC) findings of the TA patients were evaluated and compared to healthy individuals. Additionally, the association of NVC abnormalities with disease activity and subclavian artery involvement was also investigated. METHOD: In the present study, NVC changes of 15 TA patients and 15 age- and sex-matched healthy controls were compared. The frequency of hypertension, dyslipidemia, and smoking status was not different between the case and control group. Capillary density, avascular area, tortuosity, micro-hemorrhages, and ramification were investigated. Among capillaries' diameters; capillary length and width, arterial and venous limbs diameters were also compared between two groups. RESULTS: The capillary length and venous limb diameter were lower in TA patients compared to control cases (P-value: 0.026 and 0.049, respectively). Moreover, TA patients have more tortuous capillaries (P-value: 0.035). Among TA patients; capillary length, width, arterial and venous limbs diameter was lower in hands with subclavian involvement (P-value: 0.014, 0.034, 0.009 and 0.022, respectively). Furthermore, the arterial and venous limbs diameter were lower in TA patients with active disease compared to patients with inactive disease (P-value: 0.018 and 0.049, respectively). CONCLUSION: In the present study, we have shown that the hands with subclavian artery involvement have short, thin and tortuous capillaries which could be secondary to hypoperfusion. To the best of our knowledge, this is the first report describing NVC changes in TA.

A randomized clinical trial for the assessment of the efficacy and safety of guluronic acid (G2013) in patients with rheumatoid arthritis.

Objective: To evaluate the safety, efficacy and tolerability of guluronic acid (G2013) in order to treat the rheumatoid arthritis patients who had inadequate response to conventional drugs. Methods: A randomized, 12-week clinical trial with two treatment arms: guluronic acid (G2013) and conventional treatment was performed. The diagnosed RA patients according to the ACR/European League against Rheumatism 2010 classification criteria, with an active disease at baseline that had inadequate response to conventional therapy were considered for the study. G2013 was administered orally twice a day with capsules of 500 mg during a period of 12 weeks and the patients were followed up for the safety and efficacy. Results: Our data showed that, the mean changes in the G2013 and control groups were -7.54 and -2.5 for tender joint count; -7.59 and -3.59 for swollen joint count; -30 and -0.9 for physician global assessment; -23.18 and -1.81 for patient global assessment; -14.45 and -1.45 for erythrocyte sedimentation rate, respectively. Improvements seen with G2013 were significantly greater than those with conventional drugs. In total, in 15.3% of G2013-treated patients and 69.2% of conventional-treated patients adverse events (AEs) occurred in this study. Conclusion: These data from routine rheumatology clinical practice highlight the effectivenessof G2013 in combination with conventional therapy with more desirable safety profile compared to the conventional-treated patients. Therefore, G2013 therapy could be an appropriate choice in order to manage the RA disease. (Clinical trial identifier: IRCT2016092813739N5).

Targeting of circulating Th17 cells by ß-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis.

OBJECTIVE: This study aimed at investigating the inhibitory effect of ß-D-mannuronic acid (M2000) on the Th17 circulating levels and IL-17 a related cytokine in rheumatoid arthritis (RA) patients. METHODS: The study included 27 patients with RA who had failed response to treatment. All patients were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks (Clinical trial identifier: IRCT2014011213739N2). The patients based on anti-tumor necrosis factor alpha (TNFα) blocker treatment were classified into two groups (conventional group and etanercept group). They were then allowed to continue their treatment excluding non-steroidal anti-inflammatory drugs (NSAIDs). The frequency of circulating Th17 cells and IL-17 serum level were determined before and 12 weeks after M2000 therapy and were compared to the healthy controls by using flow cytometry analysis and ELISA method, respectively. RESULTS: At baseline, higher circulating Th17 and IL-17 serum levels were significantly observed in both groups of RA patients than in the healthy controls (all P < 0.001). The frequency of Th17 cells significantly decreased in the conventional group as well as in the etanercept group after M2000 therapy but the level of reduction was higher in the conventional group compared to the etanercept group (P < 0.03 and P < 0.04, respectively). The IL-17 serum level significantly decreased in both groups after M2000 therapy (P < 0.01 and P < 0.02, respectively). Furthermore, the frequency of Th17 cells was positively correlated with Disease Activity Score (DAS28) (r = 0.34, P = 0.02). CONCLUSION: M2000 shows the inhibitory effect on the frequency of circulating Th17 cells as well as in the production of IL-17 in RA patients.

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of ß-D-mannuronic acid in rheumatoid arthritis patients.

BACKGROUND: Following the potent efficacy of ß-D-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. METHOD: The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. RESULTS: There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study. CONCLUSION: Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

The effects of ß-D-mannuronic acid (M2000), as a novel NSAID, on COX1 and COX2 activities and gene expression in ankylosing spondylitis patients and the murine monocyte/macrophage, J774 cell line.

Ankylosing spondylitis (AS) is a debilitating chronic inflammatory disease with genetic predisposition, which is characterized by the involvement of spine and sacroiliac joints. Due to the relatively unsuccessful treatments, we designed ß-D-mannuronic (M2000) with the beneficial effects in various experimental models as a novel non-steroidal anti-inflammatory drug (NSAID). The aims of our present study were: first, to compare the therapeutic effects of M2000, as a novel designed NSAID, with naproxen and placebo in Iranian patients with AS during 12 weeks; second, to evaluate the effect of M2000 on gene expression of cyclooxygenase enzyme (COX-1/COX-2), a key enzyme in the initiation of inflammatory pathways in AS patients; and third, to assess the activity of COX-1 and COX-2 enzymes in the presence/absence of M2000 at the different doses in the murine macrophage, J774 cell line. This was a sub-study of phase II, randomized, placebo-controlled trial with three treatment arms: M2000, naproxen, and placebo. The outcome measures were the mean changes from baseline to week 12. The gene expression was assessed by real-time PCR. The COX-1 and COX-2 activities were evaluated by ELISA in J774 cell line induced by LPS and arachidonic acid (AA). Our findings demonstrated that M2000 had beneficial therapeutic effects on pain, stiffness, and inflammation, whereas no adverse effects were observed following the use of M2000 after 12 weeks. The analysis of gene expression showed that M2000 could effectively reduce the expression levels of COX-1 and COX-2 in comparison with untreated patients. In addition, the enzymatic activities in the presence of M2000 were significantly less than LPS- and AA-treated groups. Our results indicate that M2000, as a novel designed NSAID with immunosuppressive properties, can be considered as one of the therapeutic options for the treatment of inflammatory diseases without adverse events. Clinical trial identifier IRCT2013062213739N1/ http://www.IRCT.ir .

New insights toward the pathogenesis of ankylosing spondylitis; genetic variations and epigenetic modifications.

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, characterized by typically an axial arthritis. AS is the prototype of a group of disorders called spondyloarthropathies, which is believed to have common clinical manifestations and genetic predisposition. To date, the exact etiology of AS remains unclear. Over the past few years, however, the role of genetic susceptibility and epigenetic modifications caused through environmental factors have been extensively surveyed with respect to the pathogenesis of AS, resulted in important advances. This review article focuses on the recent advances in the field of AS research, including HLA and non-HLA susceptibility genes identified in genome-wide association studies (GWAS), and aberrant epigenetic modifications of gene loci associated with AS. HLA genes most significantly linked with AS susceptibility include HLA-B27 and its subtypes. Numerous non-HLA genes such as those in ubiquitination, aminopeptidases and MHC class I presentation molecules like ERAP-1 were also reported. Moreover, epigenetic modifications occurred in AS has been summarized. Taken together, the findings presented in this review attempt to explain the circumstance by which both genetic variations and epigenetic modifications are involved in triggering and development of AS. Nonetheless, several unanswered dark sides continue to clog our exhaustive understanding of AS. Future researches in the field of epigenetics should be carried out to extend our vision of AS etiopathogenesis.

Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23.

OBJECTIVE: Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23. METHODS: Peripheral blood monocyte isolated from 10 HLA-B27+ patients and five HLA-B27+ normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR. RESULTS: RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant. CONCLUSIONS: Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.

Anxiety and depression in rheumatoid arthritis: an epidemiologic survey and investigation of clinical correlates in Iranian population.

Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA). This study was conducted in order to evaluate the prevalence of anxiety and depression in Iranian RA patients. In the cross sectional study, 414 RA patients were enrolled prospectively during a period of 6 months from RA clinic of Rheumatology Research Center. Beck's and Cattell's inventories were applied to investigate depression and anxiety in RA patients. RA activity was measured by Disease Activity Score and patients' disability was assessed by Health Assessment Questionnaire. Levels of pain perception were stratified based on Visual Analog Scale. The prevalence of depression was 63.6 % and anxiety was in 84.1 % among RA patients. Mixed anxiety and depression was detected in 60.2 % of the study population. Functional disability was significantly associated with severity of depressive and anxiety symptoms (p < 0.001); however there was no association between disease activity and depression or anxiety (p = 0.420). There was weak correlation between disease activity score and functional disability (Spearman's rho = 0.33; p < 0.01). Severe levels of depression and anxiety were associated with higher levels of pain perception (p < 0.001). Our study stressed the impact of depressive and anxiety symptoms in functional disability and pain perception of RA patients. Our results point out the multidisciplinary management of RA.

Determination of IL1 R2, ANTXR2, CARD9, and SNAPC4 single nucleotide polymorphisms in Iranian patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin, while both genetic and environmental factors have been demonstrated to be etiologically involved. Recent genome-wide association and replication studies have suggested that anthrax toxin receptor 2 (ANTXR2), interleukin-1 receptor 2 (IL1R2), caspase recruitment domain-containing protein 9 (CARD9), and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) seem to be associated with AS pathogenesis. This case-control study was performed on 349 unrelated AS patients and 469 age- and gender-matched healthy controls, to investigate whether these non-MHC genes (IL1R2 rs2310173, ANTXR2 rs4333130, CARD9 rs4077515, and SNAPC4 rs3812571) influence the AS risk in Iranian population. ANTXR2 rs4333130 allele C (p = 0.0328; OR 0.744, 95% CI 0.598-0.927) and genotype CC (p = 0.0108; OR 0.273, 95% CI 0.123-0.605) were found to be significantly protective against AS. No other associations were found between AS and studied genes. The association between ANTXR2 rs4333130 and AS was independent of HLA-B27 status. Moreover, we found clinical disease severity scores (BASDAI and BASFI) and pain score were higher in ANTXR2 rs4333130 CT genotype. However, we observed that CARD9 allele C (p = 0.012) and genotype CC (p = 0.012) were significant protective factors against AS only in HLA-B27-negative patients, and IL1R2 rs2310173 genotype GT was mildly protective against AS only in HLA-B27-negative status. These findings support the role of non-MHC pathogenic pathways in susceptibility to AS and warrants more comprehensive studies focusing on these non-MHC pathways for developing novel therapeutic strategies.

Rituximab as first choice for patients with refractory rheumatoid arthritis: cost-effectiveness analysis in Iran based on a systematic review and meta-analysis.

The aim of this study was to evaluate the effectiveness and cost-effectiveness of using rituximab as first line for patients with refractory rheumatoid arthritis in comparison with continuing conventional DMARDs, from a perspective of health service governors. A systematic review was implemented through searching PubMed, Scopus and Cochrane Library. Quality assessment was performed by Jadad scale. After meta-analysis of ACR index results, QALY gain was calculated through mapping ACR index to HAQ and utility index. To measure the direct and indirect medical costs, a set of interviews with patients were applied. Thirty-two patients were selected from three referral rheumatology clinics in Tehran with definite diagnosis of refractory rheumatoid arthritis in the year before and treatment regimen of either rituximab or DMARDs within last year. Incremental cost-effectiveness ratio was calculated for base case and scenario of generic rituximab. Threefold of GDP per capita was considered as threshold of cost-effectiveness. Four studies were eligible to be considered in this systematic review. Total risk differences of 0.3 for achieving ACR20 criteria, 0.21 for ACR50 and 0.1 for ACR70 were calculated. Also mean of total medical costs of patients for 24 weeks were $3985 in rituximab group and $932 for DMARDs group. Thus, the incremental cost per QALY ratio will be $45,900-$70,223 in base case and $32,386-$49,550 for generic scenario. Rituximab for treatment of patients with refractory rheumatoid arthritis is not considered as cost-effective in Iran in none of the scenarios.

Non-corticosteroid risk factors of symptomatic avascular necrosis of bone in systemic lupus erythematosus: A retrospective case-control study.

OBJECTIVE: Avascular necrosis of bone (AVN) is an important complication of systemic lupus erythematosus (SLE). Corticosteroid therapy has been underlined as a main risk factor for osteonecrosis. However, AVN development in patients who have never received corticosteroid and the absence of AVN in the majority of the patients, who received corticosteroid, propose a role for non-corticosteroid risk factors in AVN development. METHODS: This case-control study included two subsets: oral corticosteroid (66 AVN and 248 non-AVN patients) and pulse-therapy subset (39 AVN and 312 non-AVN patients) who have attended our Lupus clinic from 1979 to 2009. Patients received similar cumulative dose corticosteroid, equal maximum dose and 1-year maximum dose of corticosteroid. The demographic data (including sex, age of disease onset, age at the diagnosis of AVN), organs involvement, SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage index (SLICC/ACR-DI), number of disease flare ups were compared between two subsets. RESULTS: The mean age of SLE onset was younger (P value = 0.04) in the AVN patients. In oral corticosteroid subset, malar rash (P value < 0.001) and oral ulcer (P value = 0.003) were seen more frequently in non-AVN patients, whereas psychosis (P value = 0.03) was significantly more prevalent AVN subset in oral corticosteroid subset. In corticosteroid pulse subset, no significant difference in clinical features was noted. CONCLUSION: In oral corticosteroid subset, younger age of disease onset and psychosis were significantly associated with AVN, whereas malar rash and oral ulcer showed negative association AVN.

Alpha 1-antitrypsin activity is markedly decreased in Wegener's granulomatosis.

Alpha 1-antitrypsin (A1AT) is the most abundant proteinase inhibitor in plasma and the main inhibitor of Proteinase 3, the target antigen of antineutrophil cytoplasmic antibodies (ANCAs) that predominant in Wegeners' granulomatosis. Α1AT deficiency correlated with ANCA-associated vasculitis. This study explores the trypsin inhibitory capacity (TIC), specific activity, and phenotypic deficiency of Α1AT in Wegener's granulomatosis. Twenty-seven WG patients were studied. ANCA was tested by IIF and ELISA. Serum a1-anti-trypsin levels were quantified in WG patients and healthy controls by immunoturbidimetric assay. Serum TIC was assessed by the enzymatic colorimetric assay. Phenotypes of A1AT were detected by Isoelectric Focusing. A1AT concentration was equivalent in patients and controls; however, serum TIC (P = 0.001) and specific activity of A1AT (P = 0.001) were dramatically lower in WG patients. Five patients had deficient phenotypes of A1AT: MZ (n = 3), MS (n = 1) and SS (n = 1). This was correlated with an increase in the prevalence of deficient phenotypes of A1AT in WG (P = 0.01). Trypsin inhibitory capacity and specific activity of A1AT were decreased in WG patients and may be involve in disease pathogenesis and can worsen the clinical manifestations. This A1AT deficiency probably resulted from oxidative inactivation and/or enzymatic degradation of A1AT. This could result in localized deficiency of A1AT in vessel wall interfaces and lead to severe disease.

Evaluating the reliability of Persian version of ankylosing spondylitis quality of life (ASQoL) questionnaire and related clinical and demographic parameters in patients with ankylosing spondylitis.

Ankylosing spondylitis quality of life (ASQoL) is an instrument for assessing quality of life (QoL). The aims of this study were to assess the reliability of Persian version of ASQoL questionnaire and evaluation of QoL status and related factors in ankylosing spondylitis (AS). One hundred and sixty-three Iranian patients with AS who fulfilled modified New York criteria were enrolled. Patients were evaluated using questionnaires including demographic and clinical variables, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), fatigue, Bath AS Metrology Index, pain and ASQoL. Reliability and validity of Persian version of ASQoL were evaluated by test-re-test agreement, internal consistency and correlation with specific scales. Relationship of parameters with ASQoL was analyzed by multiple regression. Age, disease duration and ASQoL score (mean ± SD) were 37.74 ± 9.88, 14.49 ± 8.47 and 8.02 ± 5.28 years, respectively. Test-re-test reproducibility for ASQoL was good as assessed by intra-class correlation coefficient (ICC: 0.97, P < 0.001). Internal consistency was high (Cronbach's alpha: 0.91). Convergent validity was confirmed by correlation of ASQoL score with specific scales (BASFI, r = 0.74, BASDAI, r = 0.6, fatigue, r = 0.56, depression, r = 0.24, intermalleolar distance, r = -0.44 and educational level, r = -0.37). Persian version of ASQoL is a valid and reliable scale to assess QoL in AS. Function, fatigue, mood, hip mobility and education are the factors which should be noted to achieve the best QoL.

Clinical characteristics and medical management of Iranian patients with ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease with variable clinical expression. Ethnic, racial and geographical factors have been associated with disease occurrence and expression. We intended to describe the clinical characteristics and assess the disease severity and treatment status in Iranian AS patients. METHODS: A total of 320 AS patients were assessed for demographic variables, clinical manifestations, human leukocyte antigen (HLA) status, disease severity, functional capacities, quality of life and treatment status. RESULTS: A gender ratio of 3.8:1, an average age onset of 27 ± 7.3 and a mean diagnostic delay of 8 years were observed. Eleven percent had juvenile onset AS. Positive family history was higher than that observed in most other countries. Enthesitis was a very common finding involving more than two-thirds of our patients. Uveitis was the leading extra-articular manifestation. We found an HLA-B27 prevalence of 73% and four HLA-B27 subtypes. Disease activity was high and the functional status was poor as indicated by mean Bath AS Disease Activity, Functional and Metrology indices. Quality of life was considerably impaired in our patients. We found a low percentage of patients on biological medications and a relatively higher percentage on disease modifying anti-rheumatic drugs and corticosteroids. CONCLUSIONS: Our results demonstrate a broad characterization of Iranian AS patients providing a better understanding of this disease. A national multicenter registry would enable larger- scale prospective studies to be carried out further evaluating the disease burden on patients and society.

Estimating the prevalence and disease characteristics of rheumatoid arthritis in Tehran: A WHO -ILAR COPCORD Study (from Iran COPCORD study, Urban Study stage 1).

BACKGROUND: To estimate the prevalence and characteristics of Rheumatoid Arthritis (RA) in an urban area of Tehran. METHODS: A total of 50 clusters were randomly selected in Tehran and 10291 subjects completed the COPCORD Core Questionnaire during 2004 and 2005. Patients with rheumatic complaints were examined and diagnosed by subspecialty fellows in rheumatology. Laboratory and radiology tests were also performed if required. RESULTS: A total of 35 subjects (5 men and 30 women) were diagnosed with RA, with a prevalence of 0.33% (95% CI: 0.22-0.46). Our results demonstrated that RA was six times more common in women than men. The mean age (± SD) of patients was 52.3 (± 17.6) years. Morning stiffness > 1 hour was reported in 37.1% of patients. Rheumatic signs were commonly found in wrist (60%), knee (60%), metacarpophalangeal (48.6%) and proximal interphalangeals of hand (40%). Approximately 46% of patients had difficulty carrying out daily activities. CONCLUSION: According to our study, the prevalence of RA in Iran seems to be lower than western countries. However, the prevalence of RA in Iran seems to be approximately in the middle point comparing the APLAR region (from 0.7% in Australia (rural) to 0.12% in Thailand).

Presentation of psoriatic arthritis in the literature: a twenty-year bibliometric evaluation.

Psoriatic arthritis is an inflammatory arthritis disabling patients with psoriasis. Bibliometric studies are tools for evaluating scientific productions in different countries, universities as well as publications related to a special topic. We aimed to perform a scientometric study to evaluate articles published under "Psoriatic arthritis" topic and also attempted to compare publications of different authors, countries, universities, and journals related to this topic. Study was performed on all articles published between 1989 and 2009. The ISI web of science was our main source. Two key words, "Psoriatic arthritis" and "Psoriatic arthropathy," were used to conduct search. Original articles were subject of further evaluation. A whole number of 3,727 article was result of our search. From this number, 1,961 (52.6 %) were original articles. Whole original articles were cited 38,613 times with average citations per item of 19.69. Gladman DD was the most popular author in this field. Articles were mostly in English (91.3 %). USA was the leading country in producing article under this topic with 463 (23.6 %) publications. University of Toronto was the first rank institution while publishing 125 (6.4 %) articles. More than half of articles were published under "Rheumatology" subject. "Journal of Rheumatology," "Annals of the Rheumatic Diseases," and "Arthritis and Rheumatism" were three journals with highest number of articles on this topic. There has been growing interest in psoriatic arthritis subject during these two decades. Between countries, institutions and journals; USA, university of Toronto, "Journal of Rheumatology," "Annals of The Rheumatic Diseases," and "Arthritis and Rheumatism" have special contributions to body of literature published under this topic, respectively.

Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and environmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal individuals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL-1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42-0.95; P < 0.05 relative to reference genotype and OR = 0.62, CI = 0.42-0.93; P < 0.05 relative to homozygous genotypes). For all other studied alleles and genotypes, there were no significant differences concerning genotype frequencies between patients and controls. A significant increase in IL-1RN rs315952 T allele frequency was noted in patients with a hematologic manifestation (OR = 1.75; 95 % CI = 1.07-2.84; P = 0.033). Polymorphism in IL-1RN rs315952 was significantly associated with SLE in Iranian patients, rs315952CT genotype being a protective factor. We found that IL-1RN rs315952 T allele frequency was significantly higher in patients with hematologic manifestations. Variation at this locus may affect IL-1 receptor antagonist activity, supporting the hypothesis that altered or imbalanced IL1 production may affect the risk of developing SLE.

Post COVID-19 neuropsychiatric complications and therapeutic role for TNF-α inhibitors: a case series study.

Background: The post-COVID syndrome is the various physical and neuropsychiatric symptoms after the acute phase of COVID-19. The understanding of pathophysiology of this syndrome and its treatment need to further studies. This study aimed to present three cases of neuropsychiatric symptoms after COVID-19 and effective treatments in these patients. Case presentation: Three patients with new or progressively neuropsychiatric symptoms such as seizures, attention difficulties, insomnia, confusion and etc., were referred to our clinic about 8 months after severe COVID-19 infection. The patients were assessed with extensive workup includes a neurological exam, brain MRI, LORETA scan, and biochemical and levels of inflammatory serum markers. All patients had elevated levels of TNF-α, poor neurological exam, and abnormal reports of MRI or LORETA scan. Diagnosis of post- COVID neuropsychiatric complications was made for the patients.TNF inhibition with Adalimumab (40 mg/weekly for a month) was initiated for the patients and led to a dramatic improvement of all symptoms. Conclusions: To our knowledge, this report is the first case series study that suggests TNF inhibitors in the treatment of post-COVID-19 syndrome, especially neuropsychological complications. However, future studies should evaluate the best therapeutic options for this syndrome.

The effect of probiotic cheese consumption on inflammatory and anti-inflammatory markers, disease severity, and symptoms in patients with rheumatoid arthritis: study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: In recent decades, several studies have shown changes in the intestinal microflora among patients with rheumatoid arthritis (RA). Therapeutic measures using probiotics have shown favorable effects on the recovery of these patients. However, most studies have used probiotic supplements. In this study, we aimed to investigate the effect of probiotic cheese consumption on inflammatory and anti-inflammatory factors, disease severity, and symptoms in these patients. METHODS: This study is a randomized, double-blind clinical trial, in which forty patients with mild to moderate severity of RA will be randomly allocated to receive either 30 g/day probiotic cheese (n = 20) or only low-salt and low-fat cheese without any added probiotic (n = 20) for 12 weeks. Assessment of anthropometric measures and biochemical indicators, including serum concentrations of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10), will be done at the study baseline and end of the trial. In addition, disease severity and disability will be assessed by DAS-28 and the HAQ-DI questionnaire, respectively. DISCUSSION: Diet is the leading environmental factor affecting the gut microbiota. A prebiotic-rich diet and probiotics might be beneficial in this regard. To the best of our knowledge, the effect of probiotic supplements on inflammation in these patients has widely been assessed; however, there is only one study that examined the effect of probiotic-containing food in these patients. Further studies are needed to investigate the effect of probiotic-containing foods on inflammatory markers and symptoms in patients with RA. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201120049449N1 . Registered on 14 February 2021.