Prevalence of Psychiatric Disorders among Patients with Granulomatosis with Polyangiitis (Wegener's) and the Predictive Role of Personality Traits.

Background: Wegener's disease is an autoimmune condition affecting the respiratory tract and kidneys. Mental health assessment is crucial due to the impact of psychological disorders on the immune system. Despite this, there is limited community-based research on psychiatric disorders and personality traits among patients with Wegener's disease. Objective: This study aimed to investigate the prevalence of psychiatric disorders and examine the predictive role of personality traits among patients with Wegener's disease. Methods: A total of 100 patients met the inclusion and exclusion criteria, and all of them were selected to participate in the study. Out of them, 75 individuals completed the questionnaires. The instruments included the SCL-90 questionnaire and the NEO Big Five personality traits. The data were analysed using Stata software, and the prevalence of psychiatric disorders in different patient groups was determined using the chi-square method. The predictive role of personality traits in mental disorders was examined using multivariate regression. Results: The results revealed that paranoia (53.3%) and depression (44%) had the highest prevalence in terms of psychiatric disorders, while psychosis (17.3%) and hostility (25.33%) had the lowest prevalence. Additionally, the findings demonstrated a positive correlation between most psychiatric disorders and the neuroticism personality trait. Conclusion: Given the influence of mental disorders on the immune system in Wegener's disease, it is essential to provide psychological care for these patients.

Significant heightened methylation levels of RUNX3 gene promoter in patients with systemic lupus erythematosus.

OBJECTIVE: Researchers are actively investigating new diagnostic and prognostic biomarkers that offer improved sensitivity and specificity for systemic lupus erythematosus (SLE). One area of interest is DNA methylation changes. Previous studies have shown a connection between the RUNX3 gene dysfunction and SLE. In this study, the focus was on examining the methylation level of the RUNX3 promoter in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy individuals. METHODS: A total of 80 individuals diagnosed with SLE from Iran, along with 77 healthy individuals, were included. The methylation levels of the RUNX3 gene in the extracted DNA were evaluated using the MethyQESD method. To determine the diagnostic effectiveness of the RUNX3 promoter methylation level, a receiver operating characteristic (ROC) curve was generated. RESULTS: The methylation of the RUNX3 promoter was found to be significantly higher in patients with SLE compared to healthy individuals (p < .001). This difference in methylation levels was observed between SLE patients and healthy individuals and between SLE patients with renal involvement and those without renal involvement (86.29 ± 10.30 vs 40.28 ± 24.21, p < .001). ROC analyses revealed that the methylation level of the RUNX3 promoter had a diagnostic power of 0.769 [95% CI (0.681-0.814)] for SLE. Additionally, there was a positive correlation between the RUNX3 methylation level and levels of creatinine and C4. CONCLUSION: The findings of this study emphasize the potential use of RUNX3 methylation levels in PBMCs of SLE patients as biomarkers for diagnosing the disease, predicting renal damage, and assessing disease activity.

Clinical Manifestations of Wegener Granulomatosis in Iranian Ethnicities Using the K-Means Algorithm: A Descriptive Study.

Introduction Wegener granulomatosis (WG) appears with clinical symptoms, including recurrent respiratory infection, renal manifestations, and nonspecific systemic symptoms. Objective To study the clinical manifestations of WG in Iranian ethnicities, and data on 164 patients were recorded from 2013 to 2018. Methods The data included demographics, symptoms, and the Birmingham Vasculitis Activity Score (BVAS). The symptoms involved the following sites: the nose, sinus, glottis, ears, lungs, kidneys, eyes, central nervous system, mucous membranes, skin, heart, stomach, intestine, as well as general symptoms. The clinical manifestations of nine ethnicities were analyzed. Results In total, 48% of the patients were male and 51% were female, with a median age of 51 years. The BVAS was of 15.4, the sites most involved were the sinus ( n = 155), nose ( n = 126), lungs ( n = 125), and ears ( n = 107). Gastrointestinal ( n = 14) and cardiac ( n = 7) involvement were less common. Among the patients, 48.17% were Persian, 13.41% were Azari, 11.17% were Gilaki, 11.17% were Kurd, and 10.9% were Lor. Conclusion Our findings indicated that the sinus, nose, lungs, and ears were the sites most involved, and gastrointestinal and cardiac involvement were less common. In the present study, involvement of the upper and lower respiratory tract was higher than that reported in Western and Asian case series. Moreover, we report for the first time that, in all patients with ear involvement, the left ear was the first to be affected. The clinical manifestations among Iranian ethnicities were not different, and the Gilaki ethnicity had the highest BVAS, mostly because the weather was humid; therefore, in Iran, in areas with humidity, the rate of the disease was higher.

The therapeutic effects of mesenchymal stem cell (MSCs) exosomes in covid-19 disease; Focusing on dexamethasone therapy.

The study of diseases, specifically their aetiologies, their step-by-step progressions (pathogenesis), and their impact on normal structure and function, is the focus of pathology, a branch of science and medicine. In therapeutic fields, it is critical to decrease significantly elevated levels of proinflammatory cytokines. The immunomodulatory drugs such as dexamethasone have been used in several of inflammatory diseases such as Covid-19. The use of dexamethasone alone or in combination with other drugs or method such as mesenchymal stem cell (MSC) is one of the most up-to-date discussions about Covid-19. In this review, we first examined the effects of dexamethasone as monotherapy on inflammatory cytokines and then examined studies that used combination therapy of dexamethasone and other drugs such as Baricitinib, Tofacitinib and tocilizumab. Also, therapeutic aspects of MSCs are examined in this review.

Demethylation of CDKN2A in systemic lupus erythematosus and rheumatoid arthritis: a blood biomarker for diagnosis and assessment of disease activity.

INTRODUCTION/OBJECTIVES: Considering the phenotypic and serological heterogeneity of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), significant challenges may intervene with the precise diagnosis. In this regard, numerous studies have shown that changes in DNA methylation levels can be used to distinguish between healthy individuals and those with SLE and RA, as well as to predict disease activity and prognosis. METHODS: In the current study, we evaluated quantitative methylation level of CDKN2A promoter in peripheral blood mononuclear cells (PBMCs) of SLE and RA patients, and healthy controls by methylation-quantification of endonuclease-resistant DNA (MethyQESD), a bisulfite conversion-independent method. RESULTS: Our findings revealed an excessive hypomethylation of CDKN2A in SLE and RA patients compared to healthy individuals (P < 0.001). Besides, by determining efficient cutoff value, the specificity of CDKN2A for correct diagnosis of healthy subjects was measured to be 77.30% and the sensitivity for SLE and RA diagnosis were 81.33%, and 72%, respectively. Furthermore, CDKN2A methylation level was shown to be positively associated with C3 and C4 levels and negatively associated with anti­dsDNA concentration (P < 0.001). Moreover, a statistically significant difference in the DNA methylation levels of CDKN2A promoter was identified between SLE cases with age of ≤ 18 and patients with > 18 years of age (P = 0.025). CONCLUSION: Our findings demonstrated that CDKN2A methylation levels in PBMCs of SLE and RA patients could be used as a promising diagnostic biomarker. The significant association between hypomethylation of CDKN2A promoter and disease activity factors in SLE patients, is suggesting that CDKN2A hypomethylation could be used as an alternative biomarker for assessment of disease activity. Key Points • Several studies have reported increased expression of CDKN2A in SLE and RA suggesting that it may be involved in the pathogenesis of these disorders. • CDKN2A hypomethylation has been implicated in different autoimmune diseases. • Our findings demonstrated that CDKN2A methylation levels in PBMCs of SLE and RA patients could be used as a promising diagnostic and prognostic biomarker.

Neuroprotective and Anti-Inflammatory Effects of Pioglitazone on Parkinson's Disease: A Comprehensive Narrative Review of Clinical and Experimental Findings.

Parkinson's disease (PD) is a chronic and progressive neurological disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). The pathogenesis of PD is strongly related to mitochondrial dysfunction, oxidative stress, and neuroinflammation. This indicates that PD can be treated with anti-oxidative substitutes and anti-inflammatory compounds. The neuroprotective and anti-inflammatory effects of peroxisome proliferator-activated receptor γ (PPAR-γ) agonists decrease cell death and halt the increase in neurodegeneration, which is why they have been given a lot of importance in research. Antidiabetic and anti-inflammatory effects have been observed to be generated by pioglitazone (PG), a selective peroxisome proliferator-activated receptor γ (PPAR-γ) agonist that regulates neural plasticity in various neurodegenerative disorders. The neuroprotective and anti-inflammatory effects of PG are assessed in this article. It was found that the patients with DM who received PG treatment were noticeably at a lower risk of PD. However, some clinical studies have not proven a strong link between the therapeutic effects of PG on PD. As per suggestions of preclinical studies, the therapeutic effects of PG treatment include; increased life expectancy of neurons, decreased oxidative stress, halted microglial activity, lower inflammation (reduced NF-κB, COX-2, and iNOS), reduced mitochondrial dysfunction, rise in motor function (motor agility) and non-motor function (lowered cognitive dysfunction). In conclusion, we determined that PG exerts neuroprotective and anti-inflammatory effects in PD models and it can be considered a potential therapeutic candidate for PD.

Role of T Cells in the Pathogenesis of Rheumatoid Arthritis: Focus on Immunometabolism Dysfunctions.

Evidence demonstrated that metabolic-associated T cell abnormalities could be detected in the early stage of RA development. In this context, molecular evaluations have revealed changes in metabolic pathways, leading to the aggressive phenotype of RA T cells. A growing list of genes is downregulated or upregulated in RA T cells, and most of these genes with abnormal expression fall into the category of metabolic pathways. It has been shown that RA T cells shunt glucose towards the pentose phosphate pathway (PPP), which is associated with a high level of nicotinamide adenine dinucleotide phosphate (NADPH) and intermediate molecules. An increased level of NADPH inhibits ATM activation and thereby increases the proliferation capabilities of the RA T cells. Defects in the DNA repair nuclease MRE11A cause failures in repairing mitochondrial DNA, resulting in inhibiting the fatty acid oxidation pathway and further elevated cytoplasmic lipid droplets. Accumulated lipid droplets employ to generate lipid membranes for the cell building program and are also used to form the front-end membrane ruffles that are accomplices with invasive phenotypes of RA T cells. Metabolic pathway involvement in RA pathogenesis expands the pathogenic concept of the disease beyond the common view of autoimmunity triggered by autoantigen recognition. Increased knowledge about metabolic pathways' implications in RA pathogenesis paves the way to understand better the environment/gene interactions and host/microbiota interactions and introduce potential therapeutic approaches. This review summarized emerging data about the roles of T cells in RA pathogenesis with a focus on immunometabolism dysfunctions and how these metabolic alterations can affect the disease process.

Diaphragmatic Ultrasound Advantages in Chronic Obstructive Pulmonary Disease (COPD) Patients: A Systematic Review and Metaanalysis.

Background: Diaphragmatic ultrasound is increasingly used to assess patients with Chronic Obstructive Pulmonary Disease (COPD). The present study aims to investigate diaphragmatic dysfunction in COPD patients through a systematic review and meta-analysis. Methods: In December 2022,The researchers studied four international databases such as Medline/PubMed, ProQuest, ISI/WOS, and Scopus. Joanna Briggs Institute (JBI) checklist was used to review and control the quality of articles. Results: Finally, 6 articles were included in the analysis. Based on the meta-analysis results, forced expiratory volume (FEV1) was significantly lower in COPD patients compared to the control group (Hedges's g= -2.99, 95 % CI -4.78, -1.19; P =0.001). Forced vital capacity (FVC) was significantly lower in COPD patients compared to the control group (Hedges's g= -1.12, 95 % CI -1.91, - 0.33; P =0.005). COPD patients had significantly lower FEV1/FVC than the control group (Hedges's g= -1.57, 95 % CI -2.33, -0.81; P <0.001). Conclusion: The present study showed that the diaphragm ultrasound (DUS) method could identify the difference in FEV1, FVC, and FEV1/FVC indices in two groups of COPD patients and healthy people.

Analysis of SDC2 gene promoter methylation in whole blood for noninvasive early detection of colorectal cancer.

Objectives: Considering the limitations of the current approaches to colorectal cancer (CRC) screening, scientists strived to find noninvasive and more powerful biomarkers for the early diagnosis of CRC. Nowadays, there are different sources of biomarkers for CRC diagnosis. Blood-based samples including circulating cell-free tumor DNA (ctDNA) and DNA extracted from leukocytes in peripheral blood might be promising sources of noninvasive cancer biomarkers such as cancer-specific methylation patterns. In this study, we aimed to evaluate the noninvasive early diagnosis of CRC via quantitative promotor methylation analysis of SDC2 gene in whole blood. Materials and Methods: Sixty-five CRC patients and 65 healthy participants were enrolled to assess promoter methylation of SDC2 gene in whole blood using the methylation quantification endonuclease-resistant DNA (MethyQESD) technique. Results: Our findings demonstrated drastic hypermethylation of SDC2 in blood samples from CRC subjects (37.91%) compared with non-malignant individuals (17.02%) (P < 0.001). The sensitivity for detection of CRC by methylation of SDC2 was 81.54%, with a specificity of 69.23%. The ROC curve analysis demonstrated that the AUC was 0.847 (P < 0.001), indicating that the status of SDC2 promoter methylation in whole blood is an excellent biomarker of CRC diagnosis. Furthermore, our results showed that methylation level in CRC patients significantly increased in higher tumor stages, demonstrating that an increased percentage of methylation is correlated with tumor progression (P < 0.001). Conclusion: SDC2 promoter methylation status in blood samples is a valuable cancer biomarker and holds high power and accuracy in distinguishing CRC patients from healthy subjects in the early stages of the disease.

The Efficacy and Safety of Rituximab in ANCA-Associated Vasculitis: A Systematic Review.

Background and aim: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease developed by autoantibody production against human neutrophilic granulocytes, including proteinase-3 (PR3) and myeloperoxidase (MPO). The management of AAV patients is difficult due to the multiorgan involvement, high rate of relapse, and complications of immunosuppressive agents that make it challenging. This study aims to investigate the efficacy and safety of rituximab (RTX) therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) subtypes. Method: The PubMed/Medline database was searched for any studies related to RTX therapy in ANCA-associated vasculitis (GPA and MPA subtypes), from inception to 1 August 2022, and proceeded in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Our search resulted in 1082 initial records. After the elimination of review papers, irrelevant studies, and non-English records, 223 articles were included, and the data related to the efficacy and safety of RTX therapy were extracted. Several randomized and non-randomized studies showed that RTX is an effective treatment option for patients with AAV. Most of the studies showed the very effective effect of RTX in controlling disease in AAV patients, including pediatrics, adults, and elderlies, although RTX cannot completely prevent relapse. However, maintenance therapy helps delay the disease's relapse and causes sustained remission. Not only the licensed dose (375 mg/m2 intravenous per week for 4 weeks) could induce disease remission, but studies also showed that a single infusion of RTX could be effective. Although RTX could resolve many rare manifestations in AAV patients, there are few reports showing treatment failure. Additionally, few sudies have reported the unexpeted worsening of the disease after RTX administration. Generally, RTX is relatively safe compared to conventional therapies, but some serious adverse effects, mainly infections, cytopenia, hypogammaglobinemia, malignancy, and hypersensitivity have been reported. Conclusions: RTX is an effective and relatively safe therapeutic option for AAV. Studies on the evaluation of the safety profiles of RTX and the prevention of severe RTX-related side effects in AAV patients are required.

The association between dietary glycemic index and cardio-metabolic risk factors in obese individuals.

BACKGROUND: The dietary glycemic index (GI) has been introduced as a novel index to elucidate the potential of foods to increase postprandial glucose. According to the limited available data about the association of GI with cardio-metabolic risk factors such as lipid profile, blood glucose markers, and blood pressure in developing countries, the current study was conducted to investigate this association in apparently obese individuals. METHOD AND MATERIAL: Three hundred forty-seven obese adults were recruited in the present cross-sectional study. A validated 147-food item semi-quantitative food frequency questionnaire (FFQ) was used to evaluate the usual dietary intake of study participants. Dietary GI was calculated using the international GI database. Fatty acid desaturase (FADs)2 gene variants were determined according to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ANOVA was used to compare study variables across different tertile of GI. RESULTS: We found significant differences in terms of anthropometric parameters [weight (P = 0.038), waist circumference (WC) (P = 0.023), weight to hip ratio (WHR) (P = 0.007), and fat-free mass (FFM) (P < 0.001)] between different tertiles of GI. Similarly, energy and macronutrient intakes had a significant difference across dietary GI, and subjects with a higher dietary intake of energy and macronutrients (carbohydrate, protein, and total fat) were assigned to the third tertile of dietary GI (P < 0.001). While there was no significant difference in terms of cardio-metabolic risk factors in different dietary GI tertiles. Moreover, the total GI score was non-significantly higher in the TT genotype of FADS2 gene polymorphism compared with other genotypes. While no significant difference was observed between FADS2 genotype frequencies in different GI tertiles. CONCLUSION: Calculated dietary GI was associated with several cardio-metabolic risk factors in obese individuals. However, further prospective studies and clinical trials are needed to confirm our findings.

A functional microRNA binding site variant in IL-23R gene in systemic lupus erythematosus and rheumatoid arthritis: is there any correlation?

BACKGROUND: IL-23 receptor (IL-23R) dysregulation has been shown to have critical roles in pathogenesis of different autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) via suppression of regulatory T cells (Tregs) as well as differentiation, expansion, and survival of T helper 17 (Th17) cells, followed by upregulation of interleukin 17 (IL-17). Here, we assessed the association of a functional microRNAs (miRNAs)-related single nucleotide polymorphism (miR-SNPs: rs10889677) in IL-23R, which was correlated with its overexpression and increased risk for SLE and RA in the Iranian population. METHODS: Genotype and allele distribution of rs10889677 variant were investigated in 105 RA patients, 100 SLE cases and 105 healthy controls via polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Our findings suggested that AA genotype, but not AC genotype, was associated with increased risk of RA (AA vs. CC; OR: 3.27; 95%CI [1.467-7.551]). The allele A was more frequent in RA group compared to controls (A allele vs. C allele; OR: 1.92; 95%CI [1.282-2.894]). This common variant was not significantly correlated with SLE risk in our population (P > 0.05). However, stratification analysis indicated that RA patients with AA genotype show higher serum concentration levels of C-reactive protein (CRP) (P: 0.008). No obvious correlation was noticed between different genotypes in SLE cases, except for a slight difference in terms of oral ulcer manifestation incidence (P: 0.038). CONCLUSION: This study suggests a significant relationship between rs10889677 variant in IL-23R with increased risk of RA and some clinical features in RA and SLE patients.

Leukocyte telomere length and obesity in children and adolescents: A systematic review and meta-analysis.

Background: Several studies have revealed the negative effects of adiposity on telomere length shortening. However, the results of the studies assessing the negative relationship between obesity and leukocyte telomere length (LTL) are not consistent. This systematic review and meta-analysis are aimed to pool the results of articles assessing the relationship between obesity and LTL among children and adolescents. Methods: To retrieve the related studies, four online databases including PubMed, Embase, ProQuest, and Scopus were searched until May 2022. Observational studies evaluating the relationship between obesity and LTL among apparently healthy children and adolescents (aged ≤18 years) were included in the study. We considered the studies that had reported a mean ± standard deviation of LTL. The random-effects model was used to assess the pooled weighted mean difference (WMD) and a 95% confidence interval (CI). Results: The search yielded seven studies from an initial 3,403 records identified. According to the results of seven articles with 4,546 participants, obesity was associated with LTL shortening among children and adolescents (WMD = -0.081; 95% CI: -0.137 to -0.026; p = 0.004; I2 = 99.9%). Also, no publication bias was observed. According to the results of subgrouping, significant results were only attributed to the studies conducted in Europe, with high quality scores, among overweight and obese adolescents, with a baseline LTL lower than 1, and performed in community-based school settings. Also, according to the subgrouping and meta-regression results, the obesity definition criteria and baseline LTL were the possible sources of between-study heterogeneity. Conclusion: We observed shorter LTL among overweight and obese children and adolescents. To obtain more reliable results, further longitudinal prospective studies with large sample sizes and more consistent and accurate definitions of obesity are required.

Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: a groundbreaking cell-free approach.

Accumulating proofs signify that pleiotropic effects of mesenchymal stromal cells (MSCs) are not allied to their differentiation competencies but rather are mediated mainly by the releases of soluble paracrine mediators, making them a reasonable therapeutic option to enable damaged tissue repair. Due to their unique immunomodulatory and regenerative attributes, the MSC-derived exosomes hold great potential to treat neurodegeneration-associated neurological diseases. Exosome treatment circumvents drawbacks regarding the direct administration of MSCs, such as tumor formation or reduced infiltration and migration to brain tissue. Noteworthy, MSCs-derived exosomes can cross the blood-brain barrier (BBB) and then efficiently deliver their cargo (e.g., protein, miRNAs, lipid, and mRNA) to damaged brain tissue. These biomolecules influence various biological processes (e.g., survival, proliferation, migration, etc.) in neurons, oligodendrocytes, and astrocytes. Various studies have shown that the systemic or local administration of MSCs-derived exosome could lead to the favored outcome in animals with neurodegeneration-associated disease mainly by supporting BBB integrity, eliciting pro-angiogenic effects, attenuating neuroinflammation, and promoting neurogenesis in vivo. In the present review, we will deliver an overview of the therapeutic benefits of MSCs-derived exosome therapy to ameliorate the pathological symptoms of acute and chronic neurodegenerative disease. Also, the underlying mechanism behind these favored effects has been elucidated.

A comprehensive review about the utilization of immune checkpoint inhibitors and combination therapy in hepatocellular carcinoma: an updated review.

A pharmacological class known as immune checkpoint inhibitors (ICIs) has been developed as a potential treatment option for various malignancies, including HCC. In HCC, ICIs have demonstrated clinically significant advantages as monotherapy or combination therapy. ICIs that target programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1), as well as cytotoxic T lymphocyte antigen 4 (CTLA-4), have made significant advances in cancer treatment. In hepatocellular carcinoma (HCC), several ICIs are being tested in clinical trials, and the area is quickly developing. As immunotherapy-related adverse events (irAEs) linked with ICI therapy expands and gain worldwide access, up-to-date management guidelines become crucial to the safety profile of ICIs. This review aims to describe the evidence for ICIs in treating HCC, emphasizing the use of combination ICIs.

miRNA-binding site polymorphism in IL-15RA gene in rheumatoid arthritis and systemic lupus erythematosus: correlation with disease risk and clinical characteristics.

INTRODUCTION/OBJECTIVES: MiRSNPs may interfere with mRNA stability through effects on microRNAs (miRNAs)-mRNA interactions via direct changes in miRNA binding site or effect on the secondary structure of this region and changes in accessibility of this region to miRNAs. Studies have confirmed that an elevated level of interleukin-15 receptor alpha (IL-15RA) has an important role in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, for the first time, we aimed to evaluate the possible correlation between a miRSNP, rs2296135, in IL-15RA gene with the risk of SLE and RA. METHODS: In this case-control study, 100 SLE patients, 100 RA patients, and 110 healthy participants were enrolled to assess rs2296135 genotypes with real-time PCR high-resolution melting method. RESULTS: According to our findings, AA genotype and A allele of rs2296135 were considerably associated with enhanced risk of RA (for AA genotype, OR = 2.29; 95% CI [1.06-5.02]; for A allele, OR = 1.65; 95% CI [1.10-2.48]). However, this common variant was not significantly correlated with SLE risk in population under study. Stratification analysis in the RA group verified that patients with the A allele had considerably higher serum concentrations of C-reactive protein (CRP) (P < 0.001). In SLE subjects, the frequency of arthritis (P: 0.021) and renal involvement (P: 0.025) in patients with A allele was significantly higher than in other SLE individuals. CONCLUSION: The current study proposes a substantial association between rs2296135 polymorphism in IL-15RA gene with augmented risk of RA and some clinical characteristics in RA and SLE patients.

Diffuse Neurobrucellosis of Cerebellum, Brainstem, Spinal Cord, and Cauda Equina: A case report and Literature review.

Neurobrucellosis is an uncommon serious complication of brucellosis. Diagnosis of neurobrucellosis could be difficult due to non-specific clinical and radiological findings. So, in endemic regions, neurobrucellosis should be included in the differential diagnosis list of patients with recent neurological disorders. We report an unusual case of neurobrucellosis with neurologic deficits in the central and peripheral nervous system and MRI lesions in the brainstem, spinal cord, and nerve roots Also, related articles are reviewed in the discussion section.

Screen time increases overweight and obesity risk among adolescents: a systematic review and dose-response meta-analysis.

BACKGROUND: Adolescence is a critical period in human life, associated with reduced physical activity and increased sedentary behaviors. In this systematic review and dose-response meta-analysis, we evaluated the association between screen time and risk of overweight/obesity among adolescents. METHODS: A systematic search in electronic databases, including PubMed, Embase, and Scopus was performed up to September 2021. All published studies evaluating the association between screen time and risk of overweight/obesity among adolescents were retrieved. Finally, a total of 44 eligible studies were included in the meta-analysis. RESULTS: The results of the two-class meta-analysis showed that adolescents at the highest category of screen time were 1.27 times more likely to develop overweight/obesity (OR = 1.273; 95% CI = 1.166-1.390; P < 0.001; I-squared (variation in ES attributable to heterogeneity) = 82.1%). The results of subgrouping showed that continent and setting were the possible sources of heterogeneity. Moreover, no evidence of non-linear association between increased screen time and risk of overweight/obesity among adolescents was observed (P-nonlinearity = 0.311). CONCLUSION: For the first time, the current systematic review and meta-analysis revealed a positive association between screen time and overweight/obesity among adolescents without any dose-response evidence. TRIAL REGISTRATION: The protocol of the current work has been registered in the PROSPERO system (Registration number: CRD42021233899 ).

Predicting factors for relapse in patients with granulomatosis with polyangiitis: results from a long-term cohort.

OBJECTIVE: To investigate the predictive factors and the best predictive model for relapse in granulomatosis with polyangiitis (GPA) patients. METHODS: All patients referred to our tertiary university hospital with confirmed diagnosis of GPA based on 1990-ACR criteria and/or revised Chapel Hill nomenclature, who were followed more than 24 months between 2012 and 2021 were included. Patients were classified into relapsing and non-relapsing groups. Disease activity was assessed based on Birmingham Vasculitis Activity Score (BVAS) and BVAS for GPA (BVAS-GPA). All demographic, clinical, laboratory, and radiologic parameters were compared between two groups. RESULTS: Data of 133 patients (male = 52 (39.1%); mean age = 46.5 ± 14.5 years) with a mean follow-up period of 49.4 ± 24.1 months were evaluated. Of those, 91 (68.4%) experienced at least one relapse episode. The mean duration of relapse-free-survival (RFS) was 12.5 months with 1-year, 3-year, and 5-year RFS rates of 46.6%, 34.6%, and 31.6%, respectively. The risk of relapse was higher if patients had higher BVAS or BVAS-GPA score (P-values < 0.001), constitutional syndrome (P-value = 0.01), neutrophil-to-lymphocyte ratio (NLR) (P-value = 0.01), C-reactive-protein (P-value = 0.03), alanine transaminase > 40 units/L (P-value = 0.04), and microscopic hematuria (P-value = 0.001). In backward logistic regression analysis, baseline BVAS score ≥ 12 (Ex(B) = 4.21, P-value = 0.03), and NLR > 2.5 (Ex(B) = 12.00, P-value = 0.007) remained statistically significant at the last step of the model with 75.8% sensitivity, 76.9% specificity, and 76.3% accuracy in predicting the relapsing patients. The frequency of relapse episodes was significantly lower in treatment group of rituximab-rituximab (0.3 ± 0.6) compared to cyclophosphamide-methotrexate (1.2 ± 1.3) and cyclophosphamide-azathioprine (1.8 ± 1.5) treatment protocols (P-value = 0.002). CONCLUSION: High-risk patients according to proposed model should be prioritized for more intensive care, more aggressive treatment, and closer follow-ups. KEY POINTS: • During the mean follow-up period of 50 months, 68.4% experienced at least one relapse episode • Patients with baseline BVAS > 12, renal involvement, and elevated NLR are more vulnerable to relapsing disease • Patients on rituximab for induction and maintenance less experienced relapse episodes compared to other treatment regimens.

Ocular manifestation in a patient with IgG4 related disease.

BACKGROUND: IgG4-related disease is a newly recognized fibroinflammatory disease presenting with multiple features including mass forming lesion; a dense lymphoplasmacytic infiltrate; a characteristic histopathological appearance and often elevated serum of IgG4. This disease can potentially affect any organ and interestingly, the affected organs share common histopathological features including a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and mild to moderate eosinophilia. CASE PRESENTATION: A 45-year-old man presented complaining of proptosis and gradual decrease in visual acuity of right eye. He had undergone many work-ups but without any definitive diagnosis. Through a combination of clinical and para-clinical investigations, the diagnosis of IgG4-RD was established. 693 mg/dL). Aggressive treatment (pulse of cyclophosphamide and pulse of corticosteroid) was started hoping to save the patient's vision. Two weeks following the treatment, there was improvement with his visual acuity and proptosis. CONCLUSION: In any patient with chronic tumor like lesions and pseudotumors without the evidence of malignancy, we should think of IgG4-related disease. In this circumstance, biopsy may lead us to the definitive diagnosis. Early diagnosis and treatment of IgG4-RD may inhibit further irreversible organ damages.