Evaluation of PD-1 Gene Expression Profile and Methylation of the Regulatory Regions in Patients with Ankylosing Spondylitis.

Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of autoimmune diseases such as AS pathogenesis. Objective: To investigate PD-1 gene expression and its epigenetic regulation by detecting methylated CpG islands in the regulatory sites of the gene. This will provide insight into the mechanisms involved in the disease. Methods: 30 AS patients and 30 healthy individuals were examined to detect the 16 CpG islands in intron 1 using bisulfite conversion and methylation-specific PCR technique. In addition, RNA samples were isolated from fresh peripheral blood mononuclear cells (PBMCs), and after complementary DNA (cDNA) synthesis, the expression level of the PD-1 gene was evaluated using Real-Time PCR. Results: The CpG islands located in the intronic zone of the PD-1 gene were hyper-methylated in both the patients with AS and the healthy controls. The gene expression of PD-1 was significantly downregulated in AS patients compared with the controls (p=0.017). A negative correlation between the Bath Ankylosing Spondylitis Disease Activity Index and PD-1 gene expression was also revealed. Conclusion: The low level of PD-1 gene expression is implicated in the pathogenesis of AS. However, in both groups, the methylation level of the intron 1 CpG islands of the PD-1 gene suggests that other regulatory mechanisms are more relevant to PD-1 gene expression than methylation in the intron.

Aryl hydrocarbon receptor gene expression in ankylosing spondylitis and its correlation with interleukin-17, RAR-related orphan receptor gamma t expression, and disease activity indices.

Objectives: Considering the role of T helper (Th)17 cells in the pathogenesis of ankylosing spondylitis (AS), the aim of this study was to determine the correlation between aryl hydrocarbon receptor (AHR) gene expression and the expression of Th17-related genes including interleukin (IL)-17 and RAR-related orphan receptor gamma t (RORγt) transcription factor. Patients and methods: Thirty patients with AS (26 males, 4 females; mean age: 36.1±8.1 years) and 30 age- and sex-matched healthy individuals (26 males, 4 females; mean age: 36.2±14.6 years) were recruited for the case-control study between June 2021 and January 2022. Ribonucleic acid (RNA) was extracted from peripheral blood cells and expression levels of AHR, IL-17, RORγt, and AHR repressor (AHRR) genes were evaluated using real-time polymerase chain reaction technique. The serum level of IL-17 was evaluated with enzyme-linked immunosorbent assay. Results: The results showed a nonsignificant elevation of AHR, IL-17, and RORγt gene expression in the patient group compared to the control. There was a direct correlation between AHR gene expression and IL-17 and RORγt genes and a negative correlation between AHR and AHRR expression. Moreover, AHR gene expression showed a weak correlation with disease activity indices, including Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Global Score, and Ankylosing Spondylitis Quality of Life. Moreover, the serum level of IL-17 was higher in AS patients compared to the healthy group (p=0.02). Conclusion: Upregulated expression of the AHR gene in ankylosing spondylitis and its correlation with IL-17 and ROR-γ t gene expression suggests that it could be a potential diagnostic and therapeutic target for AS.

The effects of intermittent fasting diet on quality of life, clinical symptoms, inflammation, and oxidative stress in overweight and obese postmenopausal women with rheumatoid arthritis: study protocol of a randomized controlled trial.

BACKGROUND: Rheumatoid arthritis (RA) is known as a chronic systemic autoimmune disorder that primarily targets synovial joints, and may cause pain and functional limitations. Studies show diet can have beneficial effects on symptoms and oxidative stress of this disease. Intermittent fasting (IF) is a dietary approach with cycles of fasting and intake. The current study aims to investigate the effect of IF on quality of life, clinical symptoms, inflammation, and oxidative stress in overweight and obese postmenopausal women with RA. METHODS: The current study is a randomized clinical trial, in which 44 patients with mild to moderate severity of RA will be randomly allocated to receive either IF (n = 22) or the usual diet (n = 22) for 8 weeks. Anthropometric measures and biochemical indicators including serum concentrations of erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and total oxidant and antioxidant capacity (TOC and TAC) will be assessed at the baseline and end of the study. Also, disease severity will be assessed by Disease Activity Score-28 (DAS-28) and clinical disease activity index (CDAI), and disability index will be assessed by Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaire. DISCUSSION: Studies show fasting has beneficial effects on inflammatory markers and results in an improvement in the health of different populations. Literature review shows it seems there is no study in this field to evaluate the effects of IF on RA patients, and they are limited to other types of fasting. However, studies show IF can have many positive effects on chronic and autoimmune diseases. Therefore, IF may have positive effects on these patients. TRIAL REGISTRATION: IRCT20230217057441N1. Registered on 14 February 2023. https://en.irct.ir/user/trial/68669 .

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) +49A>G (rs231775) gene polymorphism is not associated with COVID-19 severity and mortality in an Iranian population.

Introduction: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates T cell immune responses as an immune activation inhibitor. Literature reviews suggest that COVID-19 is associated with dysregulation of the inflammatory immune response. The purpose of the present hospital-based case-control study was to evaluate the genetic association of the CTLA4 +49A > G (rs231775) Single Nucleotide Polymorphism (SNP) with COVID-19 severity and mortality among the Iranian people. Method: Genomic DNA of peripheral blood nuclear cells was extracted from the 794 COVID-19 patients and 167 control individuals. The polymorphic site of rs231775 was genotyped using the PCR-RFLP technique. Also, to identify whether this genetic variation was related to CTLA-4 mRNA expression, total RNA was extracted from 178 COVID-19 patients and 70 controls. The mRNA levels of CTLA-4 were determined using real-time PCR. Result: There were no statistically significant differences found in the genotype and allele frequencies among the different genetic models with regards to the severity and mortality of COVID-19. Furthermore, there was no significant association between rs231775 genotypes and CTLA-4 mRNA expression in patients. Conclusion: Our findings demonstrated that SARS-CoV-2 infection is not associated with rs231775 in the Iranian people. More investigations are crucial to show how this genetic variation affects other ethnic groups. Given the importance of CTLA-4 in regulating immune responses, further studies are recommended to examine other CTLA-4 SNPs and the function of this gene in COVID-19 patients.

Comparison of Plasma Levels of MicroRNA-155-5p, MicroRNA-210-3p, and MicroRNA-16-5p in Rheumatoid Arthritis Patients with Healthy Controls in a Case-control Study.

Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation and destruction of the joints. The objective of the current study was to evaluate the expression of microRNA (miR)-155-5p, miR-210-3p, and miR-16-5p in the plasma of patients with rheumatoid arthritis in comparison with a healthy control group to attain an expression profile for earlier diagnosis and treatment. To carry out this study, 100 individuals were chosen as two equally sized groups of rheumatoid arthritis patients and healthy controls. Five milliliters of blood were drawn from each individual, and plasma RNA was extracted using Trisol solution. Complementary DNAs were synthesized using the Moloney leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Finally, real-time polymerase chain reaction (PCR) was implemented using the SYBR Green kit. The mean expression of miR-155-5p, miR-210-3p, and miR-16-5p were 2.46±2.79, 1.97±1.90, and 69.62±88.44 in the rheumatoid arthritis group, and 0.34±0.33, 9.82±9.34, and 7.94±7.09 in the healthy group, respectively. Additionally, significant differences were revealed in the relative  expression of the selected microRNAs in 4 subgroups of rheumatoid arthritis patients with different disease activities based on the disease activity score 28 (DAS28). ROC curve analysis showed that miR-155-5p (area under the curve, AUC=0.90, sensitivity=80%, specificity=81%), miR-210-3p (AUC=0.75, sensitivity=66%, specificity=71%), and miR-16-5p (AUC=0.96, sensitivity=89%, specificity=82%) could be potential biomarkers for rheumatoid arthritis diagnosis. Increased expressions of miR-16-5p and miR-155-5p and decreased expression of miR-210-3p in rheumatoid arthritis patients compared with healthy individuals demonstrate the effectiveness of these microRNAs in disease incidence and progression. Thus, the expression levels of these microRNAs can be used for diagnostic and therapeutic purposes.

Percentage of Th1 and Th17 cells and serum level of IL-17 and IFN-γ cytokines in COVID-19-associated mucormycosis.

The considerable number of the 2019 coronavirus disease (COVID-19) patients who developed mucormycosis infections in West and Central Asia urged a need to investigate the underlying causes of this fatal complication. It was hypothesized that an immunocompromised state secondary to the excessive administration of anti-inflammatory drugs was responsible for the outburst of mucormycosis in COVID-19 patients. Therefore, we aimed to study the implication of two major subsets of adaptive immunity T helper (Th)-1 and Th17 cells in disease development. Thirty patients with COVID-19-associated mucormycosis, 38 with COVID-19 without any sign or symptom of mucormycosis, and 26 healthy individuals were included. The percentage of Th1 and Th17 cells in peripheral blood, as well as the serum levels of interleukin (IL)-17 and interferon-gamma (IFN-γ), were evaluated using flow cytometry and ELISA techniques, respectively. Th17 cell percentage in patients with COVID-19-associated mucormycosis was significantly lower than in COVID-19 patients (P-value: <0.001) and healthy subjects (P-value: 0.01). In addition, the serum level of IL-17 in COVID-19 patients was significantly higher than that of healthy individuals (P-value: 0.01). However, neither the frequency of Th1 cells nor the serum level of IFN-γ was different between the study groups. Given the critical role of Th17 cells in the defense against mucosal fungal infections, these findings suggest that low numbers of Th17 and insufficient levels of IL-17 might be a predisposing factor for the development of mucormycosis during or after COVID-19 infection.

Considering the critical role of Th17 cells in defense against mucosal fungal infections, the low numbers of Th17 and insufficient amounts of IL-17 might be a predisposing factor to develop mucormycosis during or after COVID-19 infection.

Prevalence and complication of COVID-19 in patients with ankylosing spondylitis (AS) and its relationship with TNF-a inhibitors.

INTRODUCTION: Ankylosing spondylitis (AS) is a condition that is treated with nonsteroidal anti-inflammatory drugs and biological drugs such as anti tumor necrosis factor alpha (TNF-α). This study examined the prevalence of COVID-19 among individuals with AS and compare it between those receiving and not receiving TNF-α inhibitors. METHODS: A cross-sectional study was conducted at the rheumatology clinic of Imam Khomeini Hospital in Tehran, Iran. The study included patients with AS who sought treatment at the clinic. Demographic information, laboratory and radiographic findings, and disease activity were recorded through interviews and examinations using a questionnaire. RESULTS: A total of 40 patients were studied over the course of 1 year. Among them, 31 patients were administered anti-TNF-α drugs, with 15 patients (48.3%) receiving subcutaneous Altebrel (Etanercept), 3 patients (9.6%) receiving intravenous Infliximab, and 13 patients (41.9%) receiving subcutaneous Cinnora (Adalimumab). Of the total, 7 patients (17.5%) tested positive for COVID-19, 1 of whom was confirmed through both CT scan and polymerase chain reaction (PCR) testing, while the remaining 6 patients were confirmed only through PCR testing. All patients tested positive for COVID-19 were male, and 6 of them had received Altebrel. Among the 9 AS patients who did not receive TNF inhibitors, 1 patient contracted SARS-CoV-2. The clinical symptoms experienced by these patients were mild, and hospitalization was not required. However, 1 patient who had insulin-dependent type 1 diabetes and was receiving Infliximab required hospitalization. This patient exhibited more severe COVID-19 symptoms, including high fever, pulmonary involvement, dyspnea, and decreased oxygen saturation. No cases of COVID-19 were reported in the Cinnora treatment group. The use of any of the drugs did not demonstrate a significant relationship with the occurrence of COVID-19 in patients. CONCLUSIONS: The use of the TNF-α inhibitors in patients with AS, may be associated with reduced hospitalization and death rate in COVID-19 cases.

Association of programmed cell death 1 (PD-1) gene polymorphism (rs10204525) with COVID-19 severity and mortality: A case-control study in the Iranian population.

BACKGROUND: Programmed cell death 1 (PD-1), as a negative immune regulator, regulates the activation of T cells and maintains the immune system's homeostasis. Previous studies suggest that the effective immune response against COVID-19 contributes to the outcome of the disease. The present study aims to evaluate whether the PD-1 rs10204525 polymorphism is associated with PDCD-1 expression and COVID-19 severity and mortality in the Iranian population. METHODS: The PD-1 rs10204525 was genotyped in 810 COVID-19 patients and 164 healthy individuals as a control group using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, we assessed the expression of PDCD-1 in peripheral blood nuclear cells by real-time PCR. RESULTS: Regarding disease severity and mortality, no significant differences were detected between study groups in alleles and genotypes frequency distribution under different inheritance models. We found that the expression of PDCD-1 was significantly lower in COVID-19 patients with AG and GG genotypes than in the control group. Regarding disease severity, mRNA levels of PDCD-1 were significantly lower in moderate and critical patients carrying AG genotype than in control (P = 0.005 and P = 0.002, respectively) and mild (P = 0.014 and P = 0.005, respectively) individuals. Additionally, the severe and critical patients with GG genotype displayed a significantly lower level of PDCD-1 compared with the control (P = 0.002 and P < 0.001, respectively), mild (P = 0.004 and P < 0.001, respectively), and moderate (P = 0.014 and P < 0.001, respectively) ones. Regarding disease mortality, the expression of PDCD-1 was significantly lower in non-survivor COVID-19 patients with GG genotype than in survivors. CONCLUSION: Considering the lack of significant differences in PDCD-1 expression in different genotypes in the control group, lower expression of PDCD-1 in COVID-19 patients carrying the G allele suggests the impact of this single-nucleotide polymorphism on the transcriptional activity of PD-1.

Effects of N-acetylcysteine on systemic lupus erythematosus disease activity and its associated complications: a randomized double-blind clinical trial study.

BACKGROUNDS: N-acetylcysteine (NAC) has broadly been used as an anti-oxidant agent in various types of diseases. This study aimed to assess the effect of NAC on the systemic lupus erythematosus (SLE) disease activity and outcome. METHODS: In this randomized, double-blind clinical trial study, 80 SLE patients were recruited that were classified into two groups: 40 patients received NAC (1800 mg/day; 3 times per day with 8-h intervals) for 3 months and 40 patients as the control group received normal therapies. Laboratory measurements and disease activity based on the British Isles Lupus Assessment Group (BILAG) and SLE Disease Activity Index (SLEDAI) were determined before the initiation of treatment and after the study time period. RESULTS: A statistically significant decrease in BILAG (P= 0.023) and SLEDAI (P= 0.034) scores after receiving NAC for a 3-month period was observed. BILAG (P= 0.021) and SLEDAI (P= 0.030) scores were significantly lower in NAC-receiving patients compared to the control group after 3 months. The disease activity in each organ based on BILAG score after treatment indicated a significant decrease in the NAC group compared to the baseline level in general (P=0.018), mucocutaneous (P=0.003), neurological (P=0.015), musculoskeletal (P=0.048), cardiorespiratory (P=0.047), renal (P=0.025), and vascular (P=0.048) complications. Analysis indicated a significant increase in CH50 level in the NAC group after treatment compared to the baseline level (P=0.049). No adverse event was reported by the study subjects. CONCLUSIONS: It appears that the administration of 1800 mg/day NAC to SLE patients can decrease the SLE disease activity and its complications.

Outcomes of coronavirus disease 19 patients with a history of rheumatoid arthritis: A retrospective registry-based study in Iran.

BACKGROUND: We aimed to study the outcomes of coronavirus disease 2019 (COVID-19) in patients with a history of rheumatoid arthritis (RA) in Iran, where most patients receive corticosteroids and are at high risk for COVID-19 infection. METHOD: We collected the demographic, diagnostic, and treatment data of all COVID-19 patients by the clinical COVID-19 registry system. We recruited 38 RA patients and 2216 non-RA patients from the COVID-19 registry. The primary outcome was mortality due to COVID-19. We also studied the risk of intensive care unit admission and intubation in RA patients compared to non-RA patients. We used multiple logistic regression analysis to study the association between RA and the risk of COVID-19 outcomes. RESULT: We recruited 38 RA patients and 2216 non-RA patients from the COVID-19 registry. The RA patients had a higher mean age (59.9 years) than the non-RA patients (57.7 years). The group of RA patients had a larger proportion of women (76.3%) than the non-RA patients (40.8%). The death rate due to COVID-19 was significantly higher in RA patients than non-RA patients (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.24-5.81). The OR was higher among those who received prednisolone than among those who did not (OR = 3.59, 95% CI = 1.54-7.81). The odds of intubation were statistically significant among patients who received corticosteroid therapy (OR = 2.58, 95% CI = 1.07-6.18). CONCLUSION: The risk of COVID-19 outcomes was higher in RA patients than non-RA patients, especially for RA patients who received a low dose of prednisolone. The results of this study can be used to triage RA patients who get infected by COVID-19. Further studies with larger sample sizes are required to more precisely define the high-risk groups.

A patient with scleroderma associated with severe acro-osteolysis: A case report.

Systemic sclerosis is an autoimmune chronic sclerotic disease that can damage organs and cause serious complications for the patient such as musculoskeletal manifestations, Gastrointestinal involvement, pulmonary involvement, and renal disease. Acro-osteolysis is one of the musculoskeletal manifestations that causes corrosion of the bones in the fingertips of the hand and feet. In this paper, we have reported the rarely current evidence of severe Acro-osteolysis of the distal phalanges of the hands by radiological x-ray.

Myositis autoantibodies in Iranian myositis patients: assessment the frequency and clinical relevancy.

INTRODUCTION: Dermatomyositis (DM) and polymyositis (PM) are known as two major types of idiopathic inflammatory myopathies (IMMs). During the past years, growing data strongly suggest the clinical significance of myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs). The present study aimed to determine the profile of MSAs and MAAs, subsequently to address the clinical significance of these autoantibodies in Iranian myositis patients. METHODOLOGY: In this cross-sectional study, 28 DM and 24 PM patients were entered. Demographic and clinical characteristics were collected by direct examination and patients' medical record. The existence of MSAs and MAAs was assessed by indirect immunofluorescence then using immunoblotting (FA 1510-1005-1, DL 1530-1601-4 G; Euroimmun, Germany). Data were analyzed using the SPSS software (v22; SPSS Inc. Chicago, IL, USA). RESULTS: The mean age of the patients was 46.18 ± 12.95 years and male/female ratio was 28.8/71.2. Autoantibodies were positive in 63.46% of myositis patients. Interestingly, anti-TIF1γ and anti-PL7 were significantly associated with malignancy (P < 0.001, P = 0.008; respectively). The existence of autoantibody and anti-Jo1 had significant relation with interstitial lung disease (ILD) (P = 0.034, P = 0.006; respectively). Joint involvements including arthritis and arthralgia were significantly associated with anti-Ro52 and anti-Jo1 (P = 0.04, P = 0.02; respectively). CONCLUSION: Taken together, it can be concluded that certain myositis autoantibodies present clinical significance which is in line with the literature. The use of these autoantibodies as biomarkers by line blotting along with indirect immunofluorescence facilitates diagnosis of inflammatory myopathies and makes it more accurate as well as better management of myositis patients if used based on a science-based manner. Key Points • Identification of MSAs and MAAs facilitates the diagnosis of inflammatory myopathies and provides better myositis patient's management if used according to a science-based manner. • Anti-rod and ring antibody was detected in a patient with ovarian cancer-induced dermatomyositis. • Malignancy and ILD are integrated parts of myositis which can be associated with MSAs and MAAs.

Plasma Levels of MicroRNA-146a-5p, MicroRNA-24-3p, and MicroRNA-125a-5p as Potential Diagnostic Biomarkers for Rheumatoid Arthris.

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the articular tissue. This study aims to evaluate the expression of microRNA (miR)-146a-5p, miR-24-3p, and miR-125a-5p in the plasma of RA patients and compare them with those of healthy controls to obtain a specific expression profile for earlier diagnosis and assistance in treating patients. This study was performed on 50 RA patients and 50 healthy controls. Five microliters of blood were taken from each patient/control. Plasma RNA was extracted using the Trisol solution. cDNAs were synthesized; using moloney murine leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Real-time PCR was performed using SYBR green kit. The mean expression of miR-146a-5p, miR-24-3p, and miR-125a-5p in the RA group were 8.1±1.9, 6.5±1.2, and 6.8±2.2 and in the healthy group were 4.8±1.6, 3.6±2.2, and 3.4±1.7, respectively. Significant differences were also observed in the mean expression of these three miRNAs in four subgroups of RA patients with different disease activity based on disease activity score 28 (DAS28) (p<0.05). ROC curve analysis showed that miR-146a-5p (AUC=0.8, sensitivity= 96%, specificity=86%), miR-24-3p (AUC=0.7, Sensitivity=95%, Specificity=75%) and miR-125a-5p (AUC=0.71, sensitivity=93%, specificity=84%) could be used as suitable biomarkers for RA diagnosis. Increased expressions of miR-146a-5p, miR-24-3p, and miR-125a-5p in RA patients indicate that the miRNAs are involved in disease incidence and progression, and the measurement of their expression can play an essential role in the diagnosis and treatment of the disease.

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial.

INTRODUCTION: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients. METHODS: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day-1 for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population. RESULTS: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study. CONCLUSIONS: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.

Effects of a Multispecies Probiotic Supplement on Bone Health in Osteopenic Postmenopausal Women: A Randomized, Double-blind, Controlled Trial.

OBJECTIVE: The development of alternative approaches to prevent and/or treat osteoporosis, as a chronic progressive bone disease, is being considered currently. Among dietary supplements, probiotics may have favorable effects on bone metabolism. Therefore, the aim of this study was to evaluate the effects of a multispecies probiotic supplementation on bone biomarkers and bone density in osteopenic postmenopausal women. METHODS: This randomized double-blind placebo-controlled clinical trial was performed on 50 patients with osteopenia aged 50-72 years. Participants were randomly assigned to take either a multispecies probiotic supplement (GeriLact; n = 25) or placebo (n = 25) for 6 months. GeriLact contains 7 probiotic bacteria species. Participants received 500 mg Ca plus 200 IU vitamin D daily. Bone mineral density (BMD) of lumbar spine and total hip and blood biomarkers including bone-specific alkaline phosphatase (BALP), osteocalcin (OC), collagen type 1 cross-linked C-telopeptide (CTX), deoxypyridinoline (DPD), parathyroid hormone (PTH), 25-OH vitamin D, and serum pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß) were assessed at baseline and at the end of the study. RESULTS: The multispecies probiotic significantly decreased BALP (p = 0.03) and CTX (p = 0.04) levels in comparison with the control group but had no effect on BMD of the spine and total hip. Moreover, there was a statistically significant decrease in serum PTH (p = 0.01) and TNF-α (p = 0.02) in the intervention group compared to the placebo group. CONCLUSIONS: These results may suggest the favorable effects of the multispecies probiotic supplementation for 6 months on bone health in postmenopausal women due to slowing down the rate of bone turnover.

Characteristics and relationship of periodontal disease with juvenile idiopathic and rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory disease of the joints. It is correlated with periodontal disease due to similar factors that exist in both diseases. The present study assessed the relationship of periodontal disease with RA and juvenile idiopathic arthritis (JIA). MATERIALS AND METHODS: In this case-control study, 30 RA and 30 JIA patients along with similar number of matched controls were selected among patients referred to Imam Khomeini Hospital, Tehran, Iran. Periodontal parameters including pocket depth (PD), clinical attachment level (CAL), O'Leary and Bay plaque index (PI) and bleeding on probing (BOP) were determined in cases and controls. Erythrocyte sedimentation rate, number of painful and inflamed joints and severity of disease were evaluated in RA and JIA patients. Mann-Whitney U-test nonparametric, Spearman and Pearson's correlation coefficients, and Chi-square tests were used as statistical analysis (α = 0.05). RESULTS: PD (4.17 vs. 3.6 mm; P < 0.0001), CAL (4.89 vs. 4.18 mm; P < 0.002), percentage of sites with PD >4 mm (58.83% vs. 44.33%; P < 0.002), percentage of sites with CAL >3 mm (74.13% vs. 64.4%; P < 0.001), percentage of sites with BOP (9.67% vs. 6.87%; P < 0.0001) and PI index (85.73% vs. 80.63%; P < 0.0001) were significantly higher in RA patients than controls. In this group, direct and significant correlations were found between serologic findings, disease severity and number of painful and inflamed joints with periodontal factors. In JIA patients, no significant relationships were found between JIA findings and periodontal parameters. CONCLUSION: Considering the limitations of this study, there was a relationship between RA and periodontal disease. Severity of periodontal disease increases in patients with RA, while no increased risk of periodontal disease or its severity was observed among JIA patients.

Coexistence of ankylosing spondylitis and hereditary multiple exostoses:coincidence or association.

Coexisting ankylosing spondylitis and hereditary multiple exostoses have rarely been reported (three patients) previously. A 27-year-old man with hereditary multiple exostoses is presented as a fourth report. At the age of 15 years, the patient had multiple exostoses around the knee, ankle and shoulder joints. He was diagnosed with ankylosing spondylitis 3 years ago. The patient's sister and his 3 brothers also have multiple exostoses without any family history of spondyloarthropathy or inflammatory arthritis. The aim of this report is to discuss an interesting coexistence of these two diseases. The increasing number of reported patients who have a coexistence of these two diseases might suggest that the association of these two diseases is stronger than a coincidence.