Efficacy and safety of the biosimilar denosumab candidate (Arylia) compared to the reference product (Prolia®) in postmenopausal osteoporosis: a phase III, randomized, two-armed, double-blind, parallel, active-controlled, and noninferiority clinical trial.

BACKGROUND/OBJECTIVE: Osteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients. METHODS: In this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L1-L4), total hip, and femoral neck. The secondary endpoints were safety assessment, the incidence of new vertebral fractures, and the trend of bone turnover markers (BTMs). RESULTS: A total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of - 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [- 1.34 to 2.11], 0.04 [- 1.61 to 1.69], and 0.41 [- 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs. CONCLUSION: The efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03293108 ; Registration date: 2017-09-19.

Disease modifying drugs in idiopathic sclerosing orbital inflammatory syndrome.

PURPOSE: Idiopathic sclerosing orbital inflammatory syndrome (ISOIS) is a rare, progressive and hard to control disease. There is a deep gap of evidence regarding application of disease-modifying drugs (DMD) regimen as a potentially effective treatment for orbital inflammatory diseases. We aimed to report the results of using DMDs and discuss the concept of applying this modality of treatment in patients with ISOIS. METHODS: This was a prospective interventional case series conducted in a tertiary university-based hospital. Biopsy proven patients with active ISOIS were included. Systematic criteria were developed to define and measure disease activity and monitor response to treatment. A DMD regimen including an anti-tumor necrosis factor alpha (anti-TNF alpha) agent plus azathioprine and low-dose corticosteroids were used. Comprehensive ophthalmic, orbital and systemic assessments were performed during each visit. RESULTS: Five eligible patients with primary ISOIS were included. Mean age was 34.20 (SD = 13.33, range 19-53) years. Three had unilateral and two had bilateral involvement. Four had diffuse orbital involvement pattern and progressive worsening of visual functions, reduced extraocular motility and proptosis. In one patient the disease was localized to extraocular muscle and lacrimal gland. Disease activity was decreased and stabilized after DMDs regimen in all patients. Mean follow up was 32.80 (SD = 30.80, range: 12-86) months. CONCLUSION: Biologic DMD (b-DMD) including anti-TNF alpha, corticosteroid and azathioprine were effective in decreasing disease activity and could change course of the disease. This study supports the concept of using b-DMD regimen in treatment of ISOIS.

Pansclerotic Morphea Following COVID-19: A Case Report and Review of Literature on Rheumatologic and Non-rheumatologic Dermatologic Immune-Mediated Disorders Induced by SARS-CoV-2.

While mucocutaneous manifestations of COVID-19 have been frequently reported and added to our knowledge every day during the pandemic, another issue is the COVID-related diseases that can present as intensified lesions of underlying diseases, a new disease, or changes in the behavior of an old lesion. Given that immune system overreaction and cytokine storm are among the most prominent events in COVID-19, the incidence of autoimmune diseases is expected to increase after COVID-19, as confirmed in several reports. To increase the body of knowledge about short- and long-term outcomes of COVID-19 for specialists, it is essential that similar cases be reported and collected for years to come. The present study investigated a case of pansclerotic morphea that rapidly progressed a few weeks after infection with COVID-19 in a 57-year-old woman with no history of any autoimmune skin or rheumatic diseases. She was prescribed outpatient COVID-19 treatment of azithromycin, vitamins D and C, and then quarantined for 2 weeks. The manifestations of the disease were exacerbated at each follow-up and sampling visit at short intervals. This kind of pansclerotic morphea is reported for the first time.

High frequency of concurrent anti-C1q and anti-dsDNA but not anti-C3b antibodies in patients with Lupus Nephritis.

Lupus Nephritis (LN) in patients with Systemic Lupus Erythematosus (SLE) is one of the most serious and prevalent manifestations. The procedure of renal biopsy is harmful and accompanied by potential hazards. Therefore, introducing reliable biomarkers to predict LN is exceedingly worthwhile. In the present study, we compared the diagnostic values of circulating autoantibodies against dsDNA, C1q, C3b, SSA, SSB, and Sm alone or in combination to predict LN. This study evaluated the abovementioned autoantibodies in 40 healthy controls (HCs) and 95 SLE patients with different kidney involvements, including absent (n = 40), inactive (n = 20), and active (n = 35) LN using EIA method. The frequency and odds ratio of anti-dsDNA (71.4%, OR = 4.2), anti-C1q (62.9%, OR = 5.1), and the simultaneous existence of anti-C1q and anti-dsDNA (51.4%, OR = 6) antibodies were significantly higher in the active LN group compared with both inactive and absent LN groups. Moreover, the levels of anti-C1q and anti-dsDNA antibodies positively correlated with disease activity in patients with SLE. The prevalence of these autoantibodies was associated with the severity of LN biopsies. These data suggest that anti-C1q and anti-dsDNA antibodies and also their simultaneous presence may be valuable diagnostic biomarkers for LN prediction in patients with SLE.

Serum levels of adiponectin and vitamin D correlate with activity of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which numerous cells and mediators affect inflammatory conditions and disease severity. To compare the serum levels of adiponectin, vitamin D, copper, and zinc in patients with RA and to investigate the relationship between these parameters and RA severity. Ninety patients with RA and 30 healthy controls participated in this cross-sectional case-control study between November 2016 and April 2017; according to the ACR/EULAR criteria for RA. Serum levels of adiponectin were determined by ELISA; copper and zinc by colorimetric spectrophotometry; and vitamin D by HPLC. Kruskal-Wallis and Spearman tests were performed using SPSS software and data were depicted by GraphPad Prism software. Compared with healthy controls, the serum level of adiponectin was significantly increased, whereas vitamin D was significantly decreased in patients with RA. Adiponectin and vitamin D levels were inversely correlated in RA subgroups (P < 0.001, r = - 0.410). Adiponectin and vitamin D correlated with RA severity. Furthermore, no significant difference was found in copper and zinc levels between RA groups and controls. The definitive roles of adiponectin, vitamin D, copper, and zinc are not completely determined in RA development. Based on disease activity, these parameters can modulate inflammatory conditions, thus they have the potential to be used as promising therapeutic biomarkers to follow up the severity of disease, as well as the progression and treatment success in patients with RA.

Erythropoietin in Treatment of Methanol Optic Neuropathy.

BACKGROUND: Methanol poisoning can cause an optic neuropathy that is usually severe and irreversible and often occurs after ingestion of illicit or homemade alcoholic beverages. In this study, we evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy. METHODS: In a prospective, noncomparative interventional case series, consecutive patients with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification. Treatment with intravenous recombinant human EPO consisted of 20,000 units/day for 3 successive days. Depending on clinical response, some patients received a second course of EPO. VA, funduscopy, and spectral domain optical coherence tomography were assessed during the study. Main outcome measure was VA. RESULTS: Thirty-two eyes of 16 patients with methanol optic neuropathy were included. Mean age was 34.2 years (±13.3 years). The mean time interval between methanol ingestion and treatment with intravenous EPO was 9.1 days (±5.56 days). Mean follow-up after treatment was 7.5 months (±5.88 months). Median VA in the better eye of each patient before treatment was light perception (range: 3.90-0.60 logMAR). Median last acuity after treatment in the best eye was 1.00 logMAR (range: 3.90-0.00 logMAR). VA significantly increased in the last follow-up examination (P < 0.0001). Age and time to EPO treatment after methanol ingestion were not significantly related to final VA. No ocular or systemic complications occurred in our patient cohort. CONCLUSIONS: Intravenous EPO appears to improve VA in patients with methanol optic neuropathy and may represent a promising treatment for this disorder.

A randomized blinded comparative study of clinical response to surface anatomy guided injection versus sonography guided injection of hyaloronic acid in patients with primary knee osteoarthritis.

BACKGROUND AND AIM: Comparison between the effect of sonographic guided and blind knee injection of hyaluronic acid has been evaluated in this study. METHODS AND MATERIALS: Sixty-one patients with primary knee osteoarthritis were randomly allocated into two groups and received intrabursal injection of hyaloronic acid over 3 weeks. The difference between baseline amounts of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score and visual analogue scale (VAS) score and these amounts after 6 and 12 weeks were calculated and subsequently compared between the two groups. RESULTS: Among all scores and indices, WOMAC pain and function subscales changed significantly (both in the short-term and long-term follow-up). The mean differences of WOMAC subscale pain in those who had received intra-articular injection under the guidance of sonography were significantly higher than those in patients who had received blind injections after 6 and 12 weeks. The mean differences of WOMAC subscale function in those who had received ultrasonography guided intra-articular injection were significantly higher than those in patients, who had received blind injections after 6 and 12 weeks. The mean in differences of the 10-cm VAS (both at rest and after 50-feet walk) in the two groups was statistically significant after 6 weeks, but did not remain significant after 12 weeks. CONCLUSION: Application of sonography might improve the response of patients to intra-articular injection of hyaloronic acid, at least in certain clinical indices.

Are general practitioners well informed about fibromyalgia?

AIM: Fibromyalgia syndrome (FMS) is a common rheumatologic disorder characterized by easy fatigability, widespread musculoskeletal pain and sleep disorder. In spite of its high prevalence, general practitioners, as primary care providers, seem to have inadequate knowledge about FMS. This study aimed to assess Iranian general practitioners' knowledge about FMS and its treatment. METHOD: A detailed questionnaire (including items on signs and symptoms, diagnostic criteria and treatment) was completed by 190 general practitioners (54.7% male; mean age: 41 years). Data analysis was performed with SPSS for Windows 15.0 and awareness about all aspects of FMS was reported as percentages. RESULTS: About one-third (30%) of the participants had seen at least one case of FMS during their practice. Most subjects (62.7%) claimed to know 1-6 tender points. Only 3.2% knew 16-18 points. The common proposed symptoms of FMS were widespread pain (72.6%), excessive fatigue (72.6%), weakness (60.5%), sleep disorder (36.3%), anxiety (34.7%) and depression (34.2%). Wrong symptoms including elevated erythrocyte sedimentation rate and C-reactive protein, arthritis, joint swelling, weight loss and abnormal radiologic findings were selected by 27.9%, 18.9%, 14.7%, 12.6% and 2.1% of the physicians, respectively. Moreover, selective serotonin reuptake inhibitors, tricyclic antidepressant and pregabalin were identified as treatment options for FMS by, respectively, 45.8%, 22.1% and 15.3% of the participants. Finally, 52.1% and 23.7% of the subjects incorrectly considered nonsteroidal anti-inflammatory drugs and corticosteroids as treatment modalities for FMS. CONCLUSION: Iranian general practitioners are not well informed about FMS. Therefore, FMS should be specifically integrated in continuing medical education programs and undergraduate medical training curriculum.

Prevalence of Cognitive Disorders in Patients with Systemic Lupus Erythromatosus; a Cross-sectional Study in Rasoul-e-Akram Hospital, Tehran, Iran.

BACKGROUND: Neuropsychological manifestations are present in 60% of patients with Systemic Lupus Erythematosus (SLE) among which cognitive dysfunction is the most common. This study aims to determine the prevalence of cognitive disorders in SLE patients, and the relationship between cognitive disorder domains and depression and anxiety. METHODS: In this cross-sectional study, 54 patients with SLE and 48 healthy subjects were included. Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT) and Trail Making Test part A (TMT-A) were used to screen for cognitive impairments. All subjects were evaluated with the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) to determine depression and anxiety as probable confounding variables. RESULTS: The mean MMSE scores in SLE and control group patients (26.12 ± 3.58 and 28.01 ± 1.99, respectively) were significantly different (P = 0.001). The sub-scores in all areas assessed with MMSE were lower in SLE patients; however, it was only significant in the areas of orientation, recall and language (P < 0.05). SLE patients showed a significantly poorer performance in TMT compared to healthy controls (P = 0.01). The CDT according to the Watson scoring system showed significant difference between the two groups (P = 0.03). The Sunderland scoring system also indicated poorer performance in the SLE group, but the difference was not significant. CONCLUSION: Our study showed that cognitive disorders are more than 3-fold higher in SLE patients compared to normal subjects. The most impaired domains include orientation, Memory (recall), Language, Executive function, and psychomotor speed. Anxiety and depression are mostly correlated with domains included in the MMSE test.

Association between urinary adiponectin level and renal involvement in systemic lupus erythematous.

AIM: To assess association between urinary levels of adiponectin and severity of renal involvement in SLE patients. Also, this study aims to determine the value of urinary adiponectin levels to discriminate renal involvement in these patients. METHODS: In a multi-center cross-sectional survey, 50 consecutive patients diagnosed as having systemic lupus erythematosus (SLE) according to American College of Rheumatology criteria were classified into two groups with or without renal involvement (microscopic hematuria, reduced glomerular filtration rate < 25% of normal value, and proteinuria > 500 mg/24 h) which was confirmed by renal biopsy. Urinary adiponectin was measured by enzyme-linked immunosorbent assay. SLE disease activity levels were assessed by SLE Disease Activity Index (SLEDAI) score. RESULTS: Comparing urinary levels of adiponectin between the two groups indicated considerable discrepancy in this index between the groups with and without renal involvement (146.33 ± 258.83 ng/mL vs. 22.96 ± 44.33 ng/mL, P = 0.023). Also, urinary adiponectin/creatinine ratio was significantly higher in the former group (221.72 ± 414.58 vs. 19.99 ± 41.19, P = 0.019). Our study showed a higher mean SLEDAI score in those with renal involvement than others (23.60 ± 2.53 vs. 9.12 ± 3.03, P < 0.001). Multivariable linear regression analysis with the presence of potential confounders showed that the level of urinary adiponectin was significantly higher in those with renal involvement than other patients (ß = 0.470, P = 0.023). The optimal cut-off point for urinary adiponectin levels to discriminate renal involvement from normal renal state was 7.5 ng/mL, yielding a sensitivity of 80% and specificity of 52%. CONCLUSION: Urinary levels of adiponectin are significantly elevated in SLE patients with renal involvement. The measurement of this biomarker can be helpful to discriminate impaired from normal renal function in SLE patients.

Investigating the levels of serum vitamin d in patients with rheumatoid arthritis referred to rasoul-akram hospital during 2011-2012.

Vitamin D3 has a role in many autoimmune diseases and appears to play a function in controlling Rheumatoid Arthritis (RA). The aim of this study is to evaluate the relationship between serum level of vitamin D and RA disease activity score. The serum level of vitamin D in 75 RA patients referred to the rheumatology clinic of Rasoul-Akram hospital was measured. Patients were classified into low, moderate and high RA activity groups based on the DAS-28 criteria (Disease Activity Score in 28 joints) and the mean values of serum vitamin D were compared between the three groups. The mean serum levels of vitamin D in high activity group (17.057±7.7 mg/ml) was significantly less than moderate (30.5±11.3 mg/ml) and low (36.7±19.5 mg/ml) activity groups (P<0.001). The outcome of this study shows that serum level of vitamin D is inversely correlated with the activity of RA.

Prevalence of fibromyalgia in hemodialysis patients.

This study sought to determine the prevalence of fibromyalgia syndrome and to identify whether fibromyalgia was associated with various clinical symptoms and laboratory parameters in hemodialysis patients. One hundred and forty-eight hemodialysis patients were examined for fibromyalgia symptoms according to the American College of Rheumatology criteria. Demographic characteristics, as well as causes of kidney failure, dialysis duration, and symptoms related to fibromyalgia were investigated. Of 148 patients, 18 (12.2%) were diagnosed with fibromyalgia. Patients with fibromyalgia had significantly poorer sleeping satisfaction than the control group (P = .02).The Beck Depression Inventory score was higher in 77.8% of the fibromyalgia patients than that in the control group (P = .006), but there was no significant difference in the anxiety score between the two groups (P = .86).In conclusion, there was a higher prevalence of fibromyalgia in hemodialysis patients than previously reported. Sleep disturbances and depression levels correlated with fibromyalgia.

Calcium and vitamin D supplementation and risk of kidney stone formation in postmenopausal women.

INTRODUCTION: Calcium and vitamin D are essential structural components of the skeletal system, which prevent osteoporosis after menopause. However, there is a controversial debate on the association between the intake of calcium and vitamin D supplements and the increased risk of formation of kidney calculi in postmenopausal women. which yet have to be confirmed. This study aimed to compare the metabolic changes after supplementation of calcium and vitamin D and examine the risk of stone formation. MATERIALS AND METHODS: Fifty-three postmenopausal women referred to rheumatology clinic who had no history of kidney calculi, bone diseases (apart from osteoporosis), metabolic, and rheumatic disorders and had not been receiving calcium, diuretics and calcitonin were investigated. Renal ultrasonography and blood tests were performed and the urine calcium levels were measured for a period of 24 hours for all patients. The examinations were repeated after a 1- year period of treatment with supplemental calcium (100 mg/d) and vitamin D (400 IU/d) and compared with the data before the treatment. RESULTS: After 1 year, asymptomatic lithiasis was confirmed in 1 of 53 patients (1.9%) using ultrasonographic examination. No significant differences were found between the 24-hour urine and blood calcium levels before and after the treatment. CONCLUSIONS: Our findings showed that oral intake of calcium and vitamin D after 1 year has no effect on the urinary calcium excretion rate and the formation of kidney calculi in postmenopausal women.

Acute kidney injury in intensive care unit: incidence, risk factors and mortality rate.

Acute kidney injury (AKI) is a risk factor for increased mortality in critically ill patients. To assess the incidence, risk factors and outcome of patients who develop AKI in the intensive care units (ICUs), we retrospectively studied 235 patients admitted to the ICU of Shahid Mohamadi Hospital, Hormozgan, Iran, and compared those who developed AKI and those who did not. There were 31.1% of patients who developed AKI during ICU admission. There was a significant difference in the mean age, serum sodium (Na), potassium (K), urea, blood urea nitrogen (BUN) and creatinine (Cr) levels and also platelets, on admission, between patients with and without AKI. Acute physiology and chronic health evaluation (APACHE) II score on admission was significantly higher in AKI patients and Glasgow coma scale (GCS) was significantly lower. The mortality of AKI patients (72.6%) was significantly higher than non-AKI patients (25.91%). The number of underlying diseases and GCS and APACHE II score on admission were significantly different between the expired and survived patients. We conclude that age, first serum K level and APACHE II score on admission time were powerful independent predictors of developing AKI in ICU patients. The GCS on admission and the presence of two or more underlying diseases accurately predict the mortality in AKI positive ICU patients.

Erythropoietin: a novel treatment for traumatic optic neuropathy-a pilot study.

BACKGROUND: To determine the visual outcome and safety of intravenous erythropoietin in patients with indirect traumatic optic neuropathy (TON). METHODS: In a university-based hospital, from December 2008 to March 2010, seven cases with indirect TON (EPO group) received three intravenous (IV) injections of 10,000 IU of recombinant human erythropoietin in three successive days. They were compared to eight patients with indirect TON who had received no specific treatment from December 2006 to November 2008 (observation group). The primary end point was best-corrected visual acuity (BCVA) in both groups at last follow-up and secondary measure was systemic adverse effects of medication in the EPO group. RESULTS: Mean ages of patients in the observation and EPO groups were 23.3 (SD = 10.8) and 19.7 (SD = 12.1) years, respectively. Mean follow-up in the observation and EPO groups were 5.8 (SD = 3.8) and 7.0 (SD = 5.8) months, respectively. Mean best-corrected visual acuity (BCVA) significantly (p = 0.028) improved from 1.82 logMAR (SD = 1.27) at initial visit to 0.94 logMAR (SD = 0.82) at last follow-up in the EPO group, whereas the observation group showed an insignificant (p = 0.285) improvement from 2.55 log MAR (SD = 0.62) to 2.32 logMAR (SD = 0.83). Mean final BCVA was significantly higher in the EPO group than in the observation group (p = 0.012). Two cases developed mild transient systemic hypotension during EPO injection. CONCLUSIONS: Intravenous erythropoietin may be a new effective and safe treatment for patients with indirect TON.