Microvascular Changes Are Associated with Proteinuria and EMG Changes in Patients with Type 2 Diabetes Using Video Capillaroscopy.

Objectives: Video capillaroscopy is a diagnostic method for evaluating microvascular changes in type 2 diabetes mellitus (T2DM). This study evaluated microvascular changes, including microvascular architecture, capillary distribution (morphology and density), and angiogenesis conditions in T2DM patients via video capillaroscopy. Methods: A total of 256 patients with T2DM enrolled in this study. Based on electromyography (EMG)-nerve conduction velocity results, patients were divided into patients with normal and abnormal EMG. Microalbuminuria was assessed using biochemical urine analysis. Finally, video capillaroscopy was performed to evaluate changes in microvascular architecture, capillary distribution, and angiogenesis status. Results: The differences between microalbuminuria in patients with normal and abnormal EMG were not significant. Other microvascular changes were not significant between normal and abnormal EMG groups. The patients with greater microalbuminuria were at risk of abnormal EMG 2.8 times higher than those with fewer microalbuminuria (odds ratio = 2.804; 1.034-7.601). However, EMG is not a risk factor for microvascular architecture alternation in T2DM (odds ratio = 1.069; 0.323-3.546). Conclusions: Microvascular alternations are common in T2DM and early detection of these changes could help to avoid the progress of nephropathic complications. Also, video capillaroscopy provides a promising diagnostic method for the detection of microvascular alternations in T2DM.

Plasma Extracellular Vesicle LncRNA H19 as a Potential Diagnostic Biomarker for Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory bowel disease (IBD) is a complex gastrointestinal disease with 2 main subtypes of Crohn's disease (CD) and ulcerative colitis (UC), whose diagnosis mainly depends on the medical history, clinical symptoms, endoscopic, histologic, radiological, and serological findings. Extracellular vesicles (EVs) are now considered an additional mechanism for intercellular communication, allowing cells to exchange biomolecules. Long noncoding RNAs (lncRNAs) that are enriched in EVs have been defined as an ideal diagnostic biomarker for diseases. In this study, we investigated the expression differences of 5 lncRNAs in tissue and plasma EVs of active IBD patients compared with patients in the remission phase and healthy controls to introduce an EV-lncRNA as a noninvasive IBD diagnostic biomarker. METHODS: Twenty-two active IBD patients, 14 patients in the remission phase, 10 active rheumatoid arthritis (RA) patients, 14 irritable bowel syndrome (IBS) patients, and 22 healthy individuals were recruited in the discovery cohort. In addition, 16 patients with active IBD, 16 healthy controls, 10 inactive IBD patients, 12 active RA patients, and 14 IBS patients were also included in the validation cohort. The expression levels of 5 lncRNAs in tissue and EV-plasma were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) . Machine learning and receiver operating characteristic (ROC) curve analysis were performed to investigate the distinguishing ability of the candidate biomarkers. RESULTS: While the expression levels of lncRNAs CDKN2B-AS1, GAS5, and TUG1 were significantly downregulated, lncRNAs H19 and CRNDE were overexpressed in active IBD lesions. Expression of H19 was detected in plasma EVs whose isolation had been confirmed via dynamic light scattering, microscopy images, and western blotting. The classification results demonstrated the excellent ability of H19 in distinguishing IBD/active from IBD/remission, healthy control, RA, and IBS (area under the ROC curve = 0.95, 0.97,1, and 0.97 respectively). CONCLUSIONS: Our study suggests that circulating EV-lncRNA H19 exhibited promising potential for the diagnosis of active IBD.

The upregulation of lncRNA H19 in active IBD tissues and plasma extracellular vesicles indicated the possible association of H19 with the disease activity. In addition, the high sensitivity and specificity of this marker proposed it as a potential biomarker for the diagnosis of IBD patients.

Hemophagocytic lymphohistiocytosis accompanying Still's disease: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare hematologic disease that occurs due to immune system dysfunction. Clinical manifestations of this disease are fever, increased ferritin level, cytopenia, and hemophagocytosis in the biopsy report of the bone marrow. We report a 36-year-old woman referred to our hospital with persistent fever, arthralgia in interphalangeal joints, and cutaneous rash on the trunk, was subsequently diagnosed as an adult-onset Still's disease (AOSD), and after bone marrow aspiration, HLH was diagnosed with her.

Granulomatosis with polyangiitis with salivary glands involvement: Presenting a case and describing its clinical, pathophysiological, and therapeutic aspects.

Granulomatosis with polyangiitis (GPA), a rare form of small vessel vasculitis, may be manifested by multisystem involvement misleading its definitive diagnosis. The involvement of salivary glands is a very rare characteristic of GPA. Herein, we described a case of GPA with submandibular salivary gland involvement followed by reviewing the literature on similar cases. The case was a 31-year-old man, a known case of seronegative peripheral arthritis that referred recently with bilateral enlargement of the parotid and submandibular glands. Pulmonary nodules were also evident in the patient's CT scan. Fine-needle aspiration under ultrasound guidance indicated the presence of degenerated squamoid cells, giant cells, and inflammatory cells with a priority of neutrophils in the submandibular gland, as well as the presence of a cyst containing fluid without the evidence of malignancy in the parotid gland. The positivity for the Anti-neutrophil Cytoplasmic Antibody (C-ANCA) marker was also revealed. The patient was treated with methotrexate, prednisolone, and rituximab which led to a gradual reduction in the size of the glands and the improvement of the patient's clinical symptoms within 1 month after the treatment. Enlargement of salivary glands in the context of inflammatory disorders can raise doubts about the existence of GPA, and therefore imaging evaluation and histopathological assessment with an ANCA test will be necessary to confirm or rule out it.

Cutaneous vasculitis after COVID-19 vaccination in a 41-year-old male.

Leukocytoclastic vasculitis could be a possible adverse event of different SARS-CoV-2 vaccines. Clinicians and manufacturers should be aware of this adverse event for appropriate diagnosis and treatment.

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.

A comparison between femoral neck and LS-BMD with LS-TBS in T2DM patients: a case control study.

BACKGROUND: Despite having higher bone mineral density (BMD) values, type 2 diabetes mellitus (T2DM) patients are at increased risk of fracture. Trabecular bone score (TBS) obtained by evaluating bone microarchitecture might be a more accurate factor for determining bone strength in T2DM patients. In this study, we aimed at investigating the mean values of lumbar spine (LS) TBS, LS-BMD, and femoral neck BMD in T2DM patients and controls, as well as the ability of LS-TBS and BMD in distinguishing between T2DM patients and controls. METHODS: This case-control study was conducted on 150 patients with T2DM (129 women, 21 men) and 484 controls (424 women, 60 men) in Tehran, Iran. LS-TBS along with femoral neck BMD and LS-BMD was computed using dual-energy X-ray absorptiometry images. Diagnostic accuracy and discriminative capacity of LS-TBS, femoral neck BMD, and LS-BMD between the case and control groups were assessed. RESULTS: T2DM patients showed significantly lower LS-TBS values compared to the control group in the total population and in women. However, in T2DM patients, femoral neck BMD and LS-BMD were found to be significantly higher in the total population and in men, respectively, compared to the control group. Based on area under the curve (AUC) and after adjusting for age and BMI, TBS, LS-BMD, and femoral neck BMD were shown to have the acceptable ability in distinguishing T2DM patients and controls. CONCLUSION: Besides higher BMD and lower TBS values in T2DM patients compared to controls, a similar acceptable discriminative ability of LS-TBS, LS-BMD, and femoral neck BMD in differentiating between T2DM patients and controls was observed in the total population and in women.

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.

Less influence of body mass index on bone mineral density of radius as compared to proximal femur: Possible role in the diagnosis of osteoporosis.

It has been shown that body mass index (BMI) and obesity may affect the mineral density of bones, regionally on weight-bearing bones or systemically through hormones and cytokines. The objective of this study was to evaluate the effect of BMI on bone mineral density (BMD) of the radius. In this cross-sectional study, 260 patients, 233 postmenopausal women and 27 men over 50, were included who underwent a bone densitometry scanning using dual-energy X-ray absorptiometry after obtaining an informed consent. The scanning was performed in three areas (i.e., spine, proximal femur, and radius), then densitometric data (BMD, T- and Z-score) were extracted. Regression analysis was performed to evaluate the effect of independent variables of age, gender, and BMI on the BMD of the above regions. By grouping the patients in two categories (BMI <25 as normal or underweight and BMI >25 as overweight and obese), the discordance in the diagnosis following the inclusion of radius into interpretation (diagnosis based on 2 vs. 3 areas), was assessed by an agreement test. The study is approved by the ethics committee of the university. Of 260 participants in the present study, mean and standard deviation for age were 61.48 ± 8.95 for all patients, 65.81 ± 10.59 for male and 60.98 ± 8.62 for women. An increasing effect of BMI was found to be statistically significant in weight-bearing areas (total femur and femoral neck) and BMI increase was not associated with increased BMD of radius. An agreement test between two diagnoses is used that showed a discordance of 28.5% in diagnosis (diagnosis based on 2 vs. 3 areas) with a kappa coefficient of 0.547 (P = 0.001). In total, 25.4% was minor discordance and 3.1% was major discordance. Based on the results of this study, it is concluded that the BMI is not associated with increased BMD in bones that are not weight bearing, such as radius. Therefore, it may be preferred to include the densitometric data of radius into the diagnosis.

microRNAs are potentially regulating the survivin gene in PBMCs from systemic sclerosis patients.

Background: Survivin is an important anti-apoptotic protein and is involved in increasing auto-reactivity during the autoimmune diseases like systemic sclerosis (SSc).Aims: In the current study, we investigate the expression level of total survivin (survivin-TS) and its three important variants alongside with evaluation of the expression level of important microRNAs (miRNAs) that are involved in survivin expression regulation.Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls, 25 diffuse cutaneous SSc (DcSSc), and 25 limited cutaneous SSc (LcSSc) patients. RNA was extracted and single-strand cDNA was synthesized. Quantitative real-time PCR was used to evaluate the expression level of survivin-TS and its variants as well the miRNAs.Results: Overexpression of survivin-2B and downregulation of survivin wild-type (survivin-WT) were found in total-SSc patients; however, expression level of survivin-TS had no significant difference. The expression levels of miR-335-5p, miR-485-5p, miR-16-5p, miR-150-5p, miR-34a-5p, miR-218-5p and miR-708-5p were higher in total-SSc patients. Significantly negative correlations were found between transcript levels of miR-150-5p, miR-16-5p, and miR-485-5p with survivin-TS mRNA expression.Conclusion: Survivin variants had altered expression in total-SSc patients. In addition, miRNAs might potentially and negatively regulate the survivin-TS expression. Altered expression of survivin, regulated by miRNAs, may result in apoptosis resistance and auto-reactivity in lymphocytes from patients and have important roles in SSc pathogenicity.

The Correlation between Trabecular Bone Score and Lumbar Spine Bone Mineral Density in Patients with Normal and High Body Mass Index.

BACKGROUND: Trabecular bone score (TBS) measures the underlying quality of bone texture using dual-energy X-ray absorptiometry (DXA) images. The present study aimed to investigate the correlation between lumbar spine bone mineral density (BMD) and TBS, and subsequently determine whether the association varies with the body mass index (BMI). METHODS: Data from 548 patients were collected and categorized into three groups according to the relationship between BMD and age. BMD of the lumbar spine (LS) using DXA and TBS from DXA images were measured. Pearson's correlation coefficient (SPSS software, version 24.0) was used to investigate the association between LS-BMD and TBS, as well as the effect of BMI and age on these parameters. P<0.05 was considered statistically significant. RESULTS: The total mean TBS was 1.31±0.12. LS-BMD and TBS values significantly decreased with age in both sexes. A statistically significant correlation was found between TBS and LS-BMD (r=0.601). An increase in BMI was associated with a higher LS-BMD score and a lower TBS level. The correlation coefficient between LS-BMD and TBS reduced as the BMI increased. By comparing TBS with BMD, the majority of the patients with osteopenia and osteoporosis had fully degraded and partially degraded TBS, respectively. CONCLUSION: TBS was positively correlated with LS-BMD and decreased with age. Moreover, the extent of the correlation varied with respect to BMI.

Analysis of the genetic component of systemic sclerosis in Iranian and Turkish populations through a genome-wide association study.

Objectives: SSc is an autoimmune disease characterized by alteration of the immune response, vasculopathy and fibrosis. Most genetic studies on SSc have been performed in European-ancestry populations. The aim of this study was to analyse the genetic component of SSc in Middle Eastern patients from Iran and Turkey through a genome-wide association study. Methods: This study analysed data from a total of 834 patients diagnosed with SSc and 1455 healthy controls from Iran and Turkey. DNA was genotyped using high-throughput genotyping platforms. The data generated were imputed using the Michigan Imputation Server, and the Haplotype Reference Consortium as a reference panel. A meta-analysis combining both case-control sets was conducted by the inverse variance method. Results: The highest peak of association belonged to the HLA region in both the Iranian and Turkish populations. Strong and independent associations between the classical alleles HLA-DRB1*11: 04 [P = 2.10 × 10-24, odds ratio (OR) = 3.14] and DPB1*13: 01 (P = 5.37 × 10-14, OR = 5.75) and SSc were observed in the Iranian population. HLA-DRB1*11: 04 (P = 4.90 × 10-11, OR = 2.93) was the only independent signal associated in the Turkish cohort. An omnibus test yielded HLA-DRB1 58 and HLA-DPB1 76 as relevant amino acid positions for this disease. Concerning the meta-analysis, we also identified two associations close to the genome-wide significance level outside the HLA region, corresponding to IRF5-TNPO3 rs17424921-C (P = 1.34 × 10-7, OR = 1.68) and NFKB1 rs4648133-C (P = 3.11 × 10-7, OR = 1.47). Conclusion: We identified significant associations in the HLA region and suggestive associations in IRF5-TNPO3 and NFKB1 loci in Iranian and Turkish patients affected by SSc through a genome-wide association study and an extensive HLA analysis.

A randomized trial comparing four Helicobacter pylori eradication regimens: standard triple therapy, ciprofloxacin based triple therapy, quadruple and sequential therapy.

OBJECTIVE: Helicobacter pylori infection is found in at least 80% of people in developing countries. This randomized controlled trial was performed to evaluate the efficacy of 4 different H. pylori eradication regimens in Iranian patients. METHODS: We enrolled 428 patients referred to Razi hospital in Rasht city with dyspepsia. Patients were randomly assigned to four treatment groups of 107 patients (A-D). Group A received omeprazole, amoxicillin, metronidazole and bismuth, all given twice daily for 2 weeks. Group B received omeprazole, amoxicillin and clarithromycin, all given twice daily for 10 days. Group C patients were given omeprazole and amoxicillin, both twice daily for two weeks and ciprofloxacin twice a day for the first week. Group D received 10 days sequential treatment with omeprazole and amoxicillin for 5 days and omeprazole, clarithromycin and metronidazole all twice daily for the remaining 5 days. H. pylori status was rechecked by stool antigen test 8 weeks after treatment. H. pylori eradication rate (both "Intention to Treat" and "per Protocol") and adverse effects of the drugs were recorded after 8 weeks. RESULTS: Eradication rates in group A to D were, 84.1%, 90.7%, 65.4% and 80.4% respectively in "Intention to Treat" and 85.7%, 90.7%, 70%, and 81.1% respectively in "per Protocol" analyses. Patient compliance was significantly lower in Group C, whereas patient compliance in other groups was not significantly different. CONCLUSION: Standard 10 days triple therapy had the highest success (p=0.0001) rate in our study while quadruple therapy was the second successful regimen. Sequential therapy was not found to be an acceptable treatment option.