Correlation between neurofilament, HMGB1, MMP9, ds DNA blood levels and cognitive impairment in patients with neuropsychiatric systemic lupus erythematosus.

Background: Diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is challenging due to nonspecific biomarkers. High serum levels of neurofilament protein light subunit (NFL), high mobility group box 1 (HMGB1), Matrix metalloproteinase-9 (MMP-9) and have been reported in several autoimmune diseases. The aim of this study was to examine whether their plasma levels could serve as a diagnostic or prognostic biomarker for NPSLE. Methods: There were 90 SLE patients enrolled in this cross-sectional study (87.8% women and 12.2% men with a mean age of 41.67±11.05 years). We assessed the mental status of patients, also we measured the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/ACR (SLICC/ ACR) Damage Index or SDI scores. Serum levels of NFL, HMGB1, MMP9, and ds-DNA were investigated to find a role in the pathophysiology of NPSLE. Results: Among the 90 patients with SLE, 63 (70%) met the criteria of NPSLE syndrome. Our results have shown a notable difference concerning SEDIAC-2k score, SDI score, PANS, MoCA, and Beck anxiety depression, between the two groups (p < 0.05). Although serum level of all measured serum biomarkers (NFL, MMP-9, HMGB1, dsDNA) were higher in patients with NPSLE, the difference was not statistically significant. Interestingly, our results showed that the serum level of NFL was correlated with the serum level of HMGB-1 and MMP-9. (r: 0.411, P=0.003). Conclusion: Serum level of NFL, HMGB-1 and MMP-9 may be used to detect abnormal mental status in patients with SLE.

Lupus Anticoagulant Is Associated with Critical Cases and High Mortality in COVID-19: A Literature Review.

Background: In severe COVID-19 cases, a hypercoagulable state may occur. Antiphospholipid syndrome-related auto-antibodies (APSRAs) contribute to coagulopathy, but their role in COVID- 19 remains unclear. We aimed to investigate the prevalence of positive APSRAs and their effect on clinical outcomes in confirmed COVID-19 patients. Materials and Methods: In this cross-sectional study, severe hospitalized COVID-19 cases were enrolled. Demographic and clinical data were obtained from the day of admission. APSRAs including IgG and/or IgM anticardiolipin (aCL) and anti-ß2-glycoprotein1 (anti-ß2GP1) as well as lupus anticoagulant (LAC) were measured. Results: In this study, 54 severe COVID-19 cases with positive RT-PCR and chest CT scans were recruited. Positive APSRAs were found in 7 (12.9%) patients. Positive LAC was a more prevalent marker as compared to other tests (11.1%). The prevalence of positive aCL (IgM or IgG) and anti-ß2 GPI (IgM or IgG) was 1.8% (in an elderly woman). Lower oxygen saturation was found in the positive APSRAs group as opposed to the negative APSRAs group (70.3±9 vs. 84.8±9.7%). The mortality rate in the positive APSRAs group was significantly higher relative to the negative APSRAs group (83.3% vs. 27.1%; P-value: 0.01). Likewise, the mechanical ventilation requirement in the positive group was also higher (50% vs. 27.1%, P-value: 0.28). Conclusion: This study indicated that LAC might be associated with critical cases and high mortality of COVID-19. Nonetheless, the mortality was not related to macrothrombotic incidence.

Comparison of bone mineral density in forearm and hip regions and evaluation of area of these 2 sites.

Introduction: Osteoporosis is a common disease among middle-aged and older people. Because bone mineral density (BMD) is obtained by dividing bone mineral content by area, accurate measurement of the surface of the studied area plays an important role. Therefore, the purpose of this study was to investigate the area of the hip and forearm regions based on gender and height. Methods: In a cross-sectional descriptive study of 758 individuals (702 female and 56 male, divided into 2 groups of ≥50 years old and <50 years old), experienced personnel performed densitometry of the forearm and femur using a Hologic device. The results were statistically analyzed using SPSS software version 21. Results: In women ≥50 years old who were of white race, one-third of the forearm BMD showed moderate agreement with the femoral neck BMD, and in this group, total forearm BMD showed moderate agreement with the femoral neck BMD. In women <50 years old of Caucasian race, one-third of the forearm BMD showed good agreement with the femoral trochanter. In the same group of individuals, total forearm BMD also showed very good agreement with the femoral trochanter. In women <50 years old of white race, one-third of the forearm BMD showed good agreement with all 4 regions in the femur (trochanter, intertrochanteric, neck, total), and in the same group of individuals, total forearm BMD showed very good agreement with all 4 regions of the femur. Conclusion: According to the results obtained for comparison of forearm one-third with hip areas, it seems that simultaneous measurement of the forearm one-third area and different hip areas increases the accuracy of total BMD measurement.

Evaluating the Value-Added of the Trabecular Bone Score in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) presents with inflammation in the joints and bony tissues around them. The trabecular bone score (TBS) is a relatively new indicator that predicts fracture risk better than bone mineral density (BMD). The aim of the current study was to measure TBSs and BMD of patients with RA referring to Resalat Hospital, Tehran. METHODS: In this descriptive cross-sectional study, 129 men and women with RA entered the study through convenient sampling during 2016. TBS and BMD were measured in L1-L4. The relationships between age, sex, body mass index (BMI), duration of disease, and daily corticosteroids dose with TBS and BMD were determined by chi-square test, independent samples t test, Pearson correlation, and linear and logistic regression. RESULTS: The TBS of 34.9%, 31.8%, and 33.3% of study subjects were higher than 1.35, 1.25-1.35, and lower than 1.25, respectively. The prevalence of TBS lower than 1.25 was 48.7% in women aged age more than 50 years. Age was the only predictor of low TBS in patients with RA. TBS and BMD were positively correlated in vertebral and hip bones. In women older than 50 years, BMI (-1.292) and age (-1.330) were predictors of low TBS. CONCLUSION: One-third of patients with RA were at risk of fracture. Gender and BMI were two factors which affected the TBS. This index can show the effect of disease on bones, which is related to age.

Association of the Sp1 binding site and -1997 promoter variations in COL1A1 with osteoporosis risk: The application of meta-analysis and bioinformatics approaches offers a new perspective for future research.

As a complex disease, osteoporosis is influenced by several genetic markers. Many studies have examined the link between the Sp1 binding site +1245 G > T (rs1800012) and -1997 G > T (rs1107946) variations in the COL1A1 gene with osteoporosis risk. However, the findings of these studies have been contradictory; therefore, we performed a meta-analysis to aggregate additional information and obtain increased statistical power to more efficiently estimate this correlation. A meta-analysis was conducted with studies published between 1991-2020 that were identified by a systematic electronic search of the Scopus and Clarivate Analytics databases. Studies with bone mineral density (BMD) data and complete genotypes of the single-nucleotide variations (SNVs) for the overall and postmenopausal female population were included in this meta-analysis and analyzed using the R metaphor package. A relationship between rs1800012 and significantly decreased BMD values at the lumbar spine and femoral neck was found in individuals carrying the "ss" versus the "SS" genotype in the overall population according to a random effects model (p < 0.0001). Similar results were also found in the postmenopausal female population (p = 0.003 and 0.0002, respectively). Such findings might be an indication of increased osteoporosis risk in both studied groups in individuals with the "ss" genotype. Although no association was identified between the -1997 G > T and low BMD in the overall population, those individuals with the "GT" genotype showed a higher level of BMD than those with "GG" in the subgroup analysis (p = 0.007). To determine which transcription factor (TF) might bind to the -1997 G > T in COL1A1, 45 TFs were identified based on bioinformatics predictions. According to the GSE35958 microarray dataset, 16 of 45 TFs showed differential expression profiles in osteoporotic human mesenchymal stem cells relative to normal samples from elderly donors. By identifying candidate TFs for the -1997 G > T site, our study offers a new perspective for future research.

A decision tree-based approach for determining low bone mineral density in inflammatory bowel disease using WEKA software.

BACKGROUND: Decision tree classification is a standard machine learning technique that has been used for a wide range of applications. Patients with inflammatory bowel disease (IBD) are at increased risk of developing low bone mineral density (BMD). This study aimed at developing a new approach to select truly affected IBD patients who are indicated for densitometry, hence, subjecting fewer patients for bone densitometry and reducing expenses. MATERIALS AND METHODS: Simple decision trees have been developed by means of WEKA (Waikato Environment for Knowledge Analysis) package of machine learning algorithms to predict factors influencing the bone density among IBD patients. The BMD status was the outcome variable whereas age, sex, duration of disease, smoking status, corticosteroid use, oral contraceptive use, calcium or vitamin D supplementation, menstruation, milk abstinence, BMI, and levels of calcium, phosphorous, alkaline phosphatase, and 25-OH vitamin D were all attributes. RESULTS: Testing showed the decision trees to have sensitivities of 65.7-82.8%, specificities of 95.2-96.3%, accuracies of 86.2-89.8%, and Matthews correlation coefficients of 0.68-0.79. Smoking status was the most significant node (root) for ulcerative colitis and IBD-associated trees whereas calcium status was the root of Crohn's disease patients' decision tree. CONCLUSION: BD specialists could use such decision trees to reduce substantially the number of patients referred for bone densitometry and potentially save resources.

Bone mineral density in Iranian patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. The aim of the study was to investigate the prevalence of decreased bone density and related risk factors in Iranian IBD patients. A total of 126 ulcerative colitis (UC) and 39 Crohn's disease (CD) patients were enrolled. Dual-energy x-ray absorptiometry technique was used to measure bone density, and blood samples were obtained to measure biochemical markers. To find predictive variables for bone mineral density (BMD), stepwise regression analysis was carried out. A total of 53 IBD patients (32.1%) had diminished bone mineral density at either lumbar spine (L1-L4) or femoral neck. Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral neck bone density was significantly decreased among CD patients (p<0.04). There was no significant difference in BMD between men and women. We have found significant differences in BMD T scores at lumbar L1-L4, L2-L4, and femoral neck in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was no significant difference in biochemical markers between UC and CD patients, except that more CD patients were hypocalcemic (p<0.001). Stepwise regression analysis has revealed lumbar spine T score was predicted by age (p<0.0001), corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however, femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009), and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients is in accordance with Western societies. Treatment with corticosteroid has increased this possibility in both groups. Corticosteroid use, age, smoking, and BMI are predictive factors for low bone density.