Towards a consensus on the clinical applications and interpretations of the nailfold capillaroscopy standards in clinical practice: An initiative by the Egyptian Society of Microcirculation.

Objectives: Based on the mainstream adoption of nailfold capillaroscopy as an investigative tool for rheumatologists, this work was carried out by a panel of experts in the field of capillaroscopy and microcirculation to issue a consensus view on capillaroscopic image acquisition and analysis standardization. Patients and methods: After the key clinical questions were identified by the core team, a systematic review of the published research was carried out focusing on variable capillaroscopic techniques, definitions, and characteristics, including capillary density (number of capillaries), capillary morphology (shape of each capillary), capillary dimensions (width of apical, arterial, and venous limb of the capillary), and the presence of hemorrhages. The expert panel attained a consensus and developed recommendations for the standardization of capillaroscopy in clinical practice. These included recommendations for normality and abnormality and the different capillaroscopic patterns. It also involved recommendations for scoring systems, reliability, and reporting. Results: A panel of 11 experts participated in the two rounds with a response rate of 100%. A total of nine recommendations were obtained. The agreement with the recommendations (a score of 7-9) ranged from 81.8 to 90.9%. A consensus (i.e., ≥75% of respondents strongly agreed or agreed) was reached on all the clinical standards. Conclusion: This work highlighted the main NFC indications, the technical equipment that should be used, how to carry out the procedure, standardization of the terminology of the parameters, and the interpretation of NFC findings. An evidence-based consensus incorporating the advice and experience of a diverse international expert panel was reached.

Atherosclerosis Associated With COVID-19: Acute, Tends to Severely Involve Peripheral Arteries, and May be Reversible.

Arterial stiffness was reported with corona virus disease 2019 (COVID-19). We studied atherosclerosis in COVID-19 directly through duplex ultrasound measurements and their relation to co-morbidities, clinical and laboratory severity markers, and serum interleukin (IL) 6 and 17. Serum IL 6 and 17, average carotid intima-media thickness (cIMT), diameter and peak systolic velocities (PSV) of tibial, ulnar, radial arteries, and ankle brachial index (ABI) were measured in 44 COVID-19 patients and 44 healthy controls. Serum IL6, IL17, PSV, and cIMT were higher while diameter was lower (P ≤ .01) in cases. Clinical severity index correlated positively with age, co-morbidities, ferritin, IL6, IL17, cIMT, and PSV (P ≤ .04) and negatively with diameter and ABI (P = .04). Patients with severe lymphopenia had higher PSV, IL6, and IL17 and lower diameter (P < .00001). Ferritin positively correlated with PSV and negatively with diameter and ABI (P ≤ .01). Those who received an IL6 inhibitor (tocilizumab) showed lower PSV and higher diameter (P ≤ .01). In multiple regression analysis, IL17 and (age, co-morbidities) were related to (PSV, diameter) and cIMT (P ≤ .001, ≤0.02), respectively. COVID-19 may be associated with subclinical acute and may be reversible atherosclerosis severely involving peripheral arteries.

B-cell activating factor and A proliferation-inducing ligand in relation to intima-media thickness as biomarkers of premature atherosclerosis in systemic lupus erythematosus patients.

BACKGROUND: The aim of this study was to assess the correlation of the serum B-cell activating factor (BAFF), A proliferation-inducing ligand (APRIL) and interleukin (IL)-21 with carotid intima-media thickness (cIMT) to evaluate their efficacy as non-invasive biomarkers for the risk of premature development of atherosclerosis. METHODS: ELISA test was used to quantify serum BAFF, APRIL and IL-21 in 40 patients with systemic lupus erythematosus (SLE) and 20 healthy controls (HCs). The obtained results were correlated with disease duration, anti-double stranded DNA, complement proteins levels, lipid profile, cIMT and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: Serum BAFF, APRIL and IL-21 were significantly increased in SLE compared to HCs. Positive correlation was recorded between BAFF (r = 0.51) and APRIL (r = 0.52) with the cIMT. IL-21 correlated positively with SLEDAI (r = 0.33) and negatively with BAFF (r = -0.37) and APRIL (r = -0.44). According to the multiple logistic regression analysis, we found that low-density lipoprotein, serum BAFF and APRIL values were independent factors for cIMT in SLE. To discriminate premature atherosclerosis in patients with SLE, BAFF ≥455 pg/ml yielded 88.9% sensitivity with 100% specificity while APRIL ≥600 pg/ml yielded 95% sensitivity with 100% specificity. IL-21 ≥240 pg/ml yielded 66.7% sensitivity and 100% specificity. CONCLUSIONS: Circulating BAFF and APRIL in patients with SLE were correlated to disease activity and cIMT, suggesting that they could be used as a peripheral blood biomarker for the occurrence of premature atherosclerosis in SLE.

Interleukin 37; a possible marker of arterial stiffness in Behçet's disease.

BACKGROUND: Interleukin 37 (IL-37) is an anti-inflammatory cytokine previously studied in Behçet's disease (BD) and atherosclerosis. However, little is known about its relation to macro and microcirculations in BD. Previous studies relied mainly on common carotid artery (CCA) intima-media thickness (IMT) and ankle brachial index (ABI) to study atherosclerosis in BD with conflicting results. This study evaluated flow parameters of CCA, ABI and nailfold videocapillaroscopy in relation to serum IL-37 in BD. METHODS: Forty BD patients and 30 healthy controls were included. IMT, peak-systolic, end-diastolic velocities, resistivity index of CCA and ABI were measured by duplex ultrasound. Capillary loop, length, diameter and morphology were recorded by nailfold videocapillaroscopy. Serum IL-37 levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to controls, patients had higher mean CCA IMT (p < 0.0001), resistivity index (p < 0.001) and peak-systolic velocity (p=0.09) and lower mean CCA end-diastolic velocity (p=0.002), capillary loop, length, arterial, venous limbs diameter and serum IL-37 (p < 0.001). Patients with ABI ≥ 1.4 "indicating stiff arteries" had higher serum IL-37 (p < 0.05 on left, p>0.05 right sides). Serum IL-37 correlated negatively with left CCA end-diastolic velocity "denoting atherosclerosis" and positively with left posterior tibial artery ABI and CRP (p < 0.03) "denoting inflammation". Multiple regression analysis showed only association with left CCA end-diastolic velocity. CONCLUSIONS: IL-37 may be related to arterial stiffness in BD and could be used as a possible marker of arteriosclerosis in the disease for further investigations. Changes of CCA peak-systolic, end-diastolic velocities, resistivity index and IMT refer to increased atherosclerosis in larger elastic arteries. In smaller muscular "crural" arteries, vasculitis with possible medial disease may be more evident.

The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family.

OBJECTIVE: Lupus nephritis (LN) is a significant consequence of systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first work that focuses on evaluation of serum interleukin (IL-) 21 as a diagnostic biomarker of LN activity, compared to B lymphocyte stimulator (BlyS), tumor necrosis factor ligand superfamily member 13 (TNF-SF13), and traditional techniques of active LN attempting to compare their diagnostic usefulness. METHODS: Serum levels of IL-21, BlyS, and TNF-SF13 during LN were investigated. Twenty-five biopsy-proven, active LN female patients and 15 SLE patients without active LN and 20 healthy controls (HCs) joined this work. RESULTS: Serum IL-21 level was significantly higher in active LN group than in inactive LN group. Correlation analysis showed that serum IL-21 levels were significantly correlated with total SLEDAI (r = 0.41, p = 0.03), renal-SLEDAI (r = 0.48, p = 0.04), renal activity index (AI) (r = 0.93; p < 0.001), and 24-h proteinuria (r = 0.51; p > 0.008). Receiver operating characteristic curve (ROC) revealed the ability of serum IL-21 to discriminate between active and inactive LN with 70% sensitivity at >240 pg/ml cutoff point (AUC 0.809). CONCLUSION: For Egyptian SLE patients, serum levels of IL-21 were superior to TNF-SF13 and BlyS and correlated significantly with the activity indexes of LN, indicating a promising role as a potential biomarker of active LN.

Evaluating the role of serum sclerostin as an indicator of activity and damage in Egyptian patients with rheumatoid arthritis: university hospital experience.

OBJECTIVE: Sclerostin is an osteocyte-derived glycoprotein which inhibits the canonical Wnt pathway essential for osteoblastic activity decreasing bone formation. Its potential role in rheumatoid arthritis (RA) pathogenesis was highlighted by experimental studies. Here we measured the serum sclerostin in RA patients and evaluated its relationship with disease activity and damage. METHODS: One hundred RA patients and 80 age and sex-matched healthy controls were enrolled in the study. Bone biomarkers were evaluated for all participants including total calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D, and intact parathyroid hormone, in addition to fibroblast growth factor-23 (FGF23) and serum sclerostin. For RA patients, carotid intima-media thickness, brachial artery flow dilatation, and musculoskeletal ultrasonography using ultrasonography-7 joint score were done, and DAS28-ESR was calculated. RESULTS: Median serum sclerostin in our patients was 186.5 ± 22.7 pg/ml which was significantly higher than in controls 60.6 ± 7.1 pg/ml (p < 0.002). Serum sclerostin showed no correlation with disease activity, bone erosions, carotid intima-media thickness, brachial flow dilatation, and the examined bone biomarkers. However, it had a strong correlation with FGF23 (r coefficient 0.988, p < 0.000). CONCLUSION: Although serum sclerostin was elevated in RA patients, it could not be used as a prognostic marker for disease activity, bone erosions or atherosclerosis.Key Points• Serum sclerostin may not reflect changes in the joint microenvironment being not correlated with ultrasonography-detected synovitis or erosions.• Serum sclerostin was elevated in RA patients irrespective to their age or gender.• The positive correlation with FGF23 may provide evidence for sclerostin contribution in bone demineralization in RA patients.

Role of long non-coding RNAs expression (ANRIL, NOS3-AS, and APOA1-AS) in development of atherosclerosis in Egyptian systemic lupus erythematosus patients.

To quantify the expression level of three lncRNAs which are known to be relevant to atherosclerosis (ANRIL, NOS3-AS, and APOA1-AS) in SLE patients and to assess their relationship with atherogenic and inflammatory biomarkers. The circulating levels of these lncRNAs were assessed using RT-PCR, in addition to measurement of E-selectin, V-CAM1, oxidized low-density lipoprotein (oxLDL), total nitric oxide (NOx), and lipid profile in 65 SLE patients (35 atherosclerotic and 30 non-atherosclerotic) and 35 healthy subjects. The expression levels of these lncRNAs were higher in SLE patients than in healthy controls. Importantly, a higher overexpression of these lncRNAs was noticed in atherosclerotic SLE patients than in non-atherosclerotic ones. In atherosclerotic SLE patients, level of ANRIL was positively associated with menopause, SLE duration, SLEDAI, and SLICC and negatively correlated with C3. Moreover, NOS3-AS expression was negatively correlated with total NOx level and HDL, while it was positively correlated with TC, LDL-C, hypertension, metabolic syndrome, obesity and dyslipidemia, CIMT, VCAM-1, E-selectin, oxLDL, SLEDAI, and SLICC. With respect to APOA1-AS, its expression was negatively correlated with HDL-C, whereas it was positively correlated with TC, LDL-C, hypertension, dyslipidemia, obesity, metabolic syndrome, menopause, CIMT, RI, V-CAM1, E-selectin, oxLDL, and SLICC. ANRIL, NOS3-AS, and APOA1-AS could be used as predictive biomarkers for atherosclerosis in SLE. Multivariate analyses identified these lncRNAs as independent predictors for atherosclerosis in SLE. These lncRNAs play a pivotal role in development of atherosclerosis via their significant repercussions atherogenic and inflammatory indices.

Evaluation of scars in children after treatment with low-level laser.

Burn scars are known for their tendency to worsen with hypertrophy and contracture, causing esthetic and functional problems. The objective is to analyze the effectiveness of low-level laser therapy on post-burn hypertrophic scar tissue in children. A randomized controlled study included 15 children, ranging from 2 to 10 years of age, presented with post-burn hypertrophic scars. They received He-Ne laser and topical treatment. Each scar was divided into two halves. One half was treated with laser therapy and topical treatment (study area), and the other half was treated with topical treatment only (control area). The children were evaluated before, and after 3 months of the study by Vancouver Scar Scale (VSS), ultrasonography, and laser Doppler perfusion imaging. Significant improvement was reported in the studied area, compared to the control area for patients with P values (P = 0.003) and (P = 0.005), for VSS and U/S scores, respectively. No differences were detected for blood perfusion of the scar between both areas (P = 0.73). In addition, no adverse effects were reported. Photobiomodulation (PBM) is an efficient and safe therapeutic modality for post-burn hypertrophic scars in children, with no side effects, and should be considered a part of combination therapy for better results.

Vascular affection in relation to oxidative DNA damage in metabolic syndrome.

INTRODUCTION: Obesity has become an important issue affecting both males and females. Obesity is now regarded as an independent risk factor for atherosclerosis-related diseases. Metabolic syndrome is associated with increased risk for development of cardiovascular disease. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine concentration has been used to express oxidation status. METHODS: Twenty-seven obese patients with metabolic syndrome, 25 obese patients without metabolic syndrome and 31 healthy subjects were included in our study. They were subjected to full history and clinical examination; fasting blood sugar (FBS), 2 hour post prandial blood sugar (2HPP), lipid profile, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and carotid duplex, A/B index and tibial diameters were all assessed. RESULTS: There was a statistically significant difference (p = 0.027) in diameter of the right anterior tibial artery among the studied groups, with decreased diameter of the right anterior tibial artery in obese patients with metabolic syndrome compared to those without metabolic syndrome; the ankle brachial index revealed a lower index in obese patients with metabolic syndrome compared to those without metabolic syndrome. There was a statistically insignificant difference (p = 0.668) in the 8-oxodG in the studied groups. In obese patients with metabolic syndrome there was a positive correlation between 8-oxodG and total cholesterol and LDL. CONCLUSION: Urinary 8-oxodG is correlated to total cholesterol and LDL in obese patients with metabolic syndrome; signifying its role in the mechanism of dyslipidemia in those patients. Our study highlights the importance of anterior tibial artery diameter measurement and ankle brachial index as an early marker of atherosclerosis, and how it may be an earlier marker than carotid intima-media thickness.

Photobiomodulation effect on children's scars.

The management of burn scars has become one of the major clinical challenges in the developing countries which involve enormous treatment cost; this needs new methods for better cost benefit relationship. The objective of the study is to analyze the effectiveness of low-level laser therapy on post-burn scar tissue in children. A randomized controlled study included 15 children, ranging from 2 to 10 years of age, presenting with burn scars. They received diode laser and topical treatment. Each scar was divided into two halves. One half was treated with laser therapy and topical treatment (study area), and the other half was treated with topical treatment only (control area). The children were evaluated before and after 3 months of the study by Vancouver Scar Scale (VSS), ultrasonography (U/S), and laser Doppler perfusion imaging. Significant improvement was reported in the studied area compared to the control area for patients with P values (P = 0.005) and (P = 0.0001) for VSS and U/S scores, respectively. No difference was detected for blood perfusion to the scar between both areas (P = 0.18). In addition, no adverse effect was reported. Photobiomodulation is an efficient and safe therapeutic modality for post-burn hypertrophic scars in children and should be considered a part of combination therapy for better results.

Serum Transforming Growth Factor-Beta 1 Level in Egyptian Systemic Lupus Erythematosus Patients.

OBJECTIVES: This study aims to assess the role of transforming growth factor-beta 1 (TGF-ß1) in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: The study included 40 female SLE patients (mean age 25.5±6.2 years; range 15 to 39 years) diagnosed according to the American College of Rheumatology criteria and 30 female healthy controls (mean age 26.2±5.9 years; range 16 to 39 years). Disease activity was assessed using SLE Disease Activity Index. Patients were diagnosed with lupus nephritis if they met the criteria for renal disorder. SLE patients and controls were compared in terms of TGF-ß1, low and high density lipoprotein, and triglyceride levels. RESULTS: Mean serum TGF-ß1 level of patients with SLE was 1385.7±483.1 pg/mL, with a significant difference compared to control group (2079.6±125.4 pg/mL; p<0.001). TGF-ß1 was statistically significantly correlated with SLE disease duration. However, there was no statistically significant correlation between TGF-ß1 and erythrocyte sedimentation rate, C-reactive protein, 24-hour urinary protein, complement 3, serum cholesterol, low density lipoprotein, or serum triglyceride. TGF-ß1 was statistically significantly correlated with discoid rash. There was a statistically significant correlation between SLE Disease Activity Index and serum cholesterol, and triglyceride. CONCLUSION: Systemic lupus erythematosus patients had lower levels of TGF-ß1, without any significant correlation with SLE Disease Activity Index or lipid profile. TGF-ß1 had a significant correlation with discoid lupus.

Microparticles (CD146) and Arterial Stiffness Versus Carotid Intima Media Thickness as an Early Predictors of Vascular Affection in Systemic Lupus Patients.

OBJECTIVES: This study aims to evaluate cluster of differentiation 146 (CD146) and pulse wave velocity (PWV) as non-invasive methods for prediction of early vascular affection in systemic lupus erythematosus (SLE) patients without symptoms of vascular disease, to detect the outcome and reproducibility of these methods, and to correlate CD146 and PWV with lipid profile, intima media thickness (IMT), and ankle brachial index. PATIENTS AND METHODS: Thirty female SLE patients (mean age 26.6±6.6 years; range 15 to 35 years) fulfilling the American College of Rheumatology 1997 revised criteria for SLE classification, and 15 age and sex matched healthy controls were included. All participants were performed full clinical assessments including measurement of Systemic Lupus Erythematosus Disease Activity Index, lipid profile, CD146, carotid IMT, PWV, and rise time as an indication of how fast the waveform rises. RESULTS: Cluster of differentiation 146 levels were elevated in patients with SLE compared to controls (p<0.001). There was a statistically significant difference between patients and controls in the femoral, lower thigh, and ankle rise time. There was a statistically significant correlation between IMT and ages of patients, Systemic Lupus Erythematosus Disease Activity Index, and brachial-below knee PWV, while there was no correlation between IMT and disease duration, lipid profile, brachial-femoral PWV, and brachial-ankle PWV. There was statistically significant correlations between brachial-femoral PWV and serum cholesterol level, and between brachial-ankle PWV and low density lipoprotein cholesterol. CONCLUSION: Our results showed that SLE vascular affection is more pronounced in small arteries. Also, elevated CD146 and brachial-femoral PWV are useful early markers of vascular affection in SLE as well as rise time may be a marker for arterial stiffness.

Vitamin D as a risk factor for premature atherosclerosis in patients with type 2 diabetes.

BACKGROUND: Several cardiovascular risk factors have been recognized in patients with diabetes and vitamin D deficiency is emerging as a new risk. The aim of this study was to determine the effect of vitamin D deficiency on the incidence of premature atherosclerosis in patients with type 2 diabetes. METHODS: A total of 78 patients with type 2 diabetes were subjected to history taking, physical examination, fasting glucose level, homeostasis model assessment of insulin resistance, lipid profile, 25(OH) vitamin D measurement, and carotid Doppler. RESULTS: Patients with normal carotid intima-media thickness (CIMT) had sufficient vitamin D. Of those with increased CIMT 23.1% had insufficient vitamin D while 76.9% had sufficient vitamin D (six patients had plaques, one of them had vitamin D insufficiency, and the other five patients had sufficient vitamin D). There was a statistically significant difference in the serum level of vitamin D between patients with increased CIMT, and those with normal intima, with a decreased level in the first group. There was a significant negative correlation between vitamin D and fasting blood glucose. There was a statistically significant correlation in left CIMT between the vitamin D sufficiency group and the vitamin D insufficiency group, with higher values in the second group. There was no statistically significant difference in serum cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol in patients with increased CIMT and those with normal intima. CONCLUSIONS: Decreased vitamin D levels in patients with diabetes lead to increased CIMT. The absence of a statistically significance difference in lipid profile between increased and normal CIMT groups raises the possibility of underlying causes for atherosclerosis in patients with diabetes other than dyslipidemia.

Plasma Osteopontin Level in Chronic Liver Disease and Hepatocellular Carcinoma.

BACKGROUND: Osteopontin (OPN) is a secreted glycoprotein and is frequently associated with various tumors. OBJECTIVES: We sought to investigate the clinical usefulness of the level of plasma OPN, compared to α-fetoprotein (AFP), as a biomarker for hepatocellular carcinoma (HCC) and to evaluate its diagnostic value in nonalcoholic fatty liver disease (NAFLD) and its relationship with clinical and laboratory features of HCC and NAFLD. PATIENTS AND METHODS: The study was performed on 120 subjects classified into 5 groups: Group I included 25 chronic non-cirrhotic hepatitis C virus (HCV)-infected patients; Group II encompassed 25 patients with chronic HCV infection with liver cirrhosis; Group III comprised 25 patients with chronic HCV with liver cirrhosis and HCC; Group IV was comprised of 25 patients with NAFLD; and Group V consisted of 20 healthy age- and sex-matched controls. All the participants were subjected to history taking and clinical and abdominal ultrasonographic examinations as well as the following laboratory investigations: liver function tests, complete blood count, blood sugar, hepatitis B surface antigen, hepatitis C virus antibodies, HCV-RNA by qualitative polymerase chain reaction (for Groups I, II, and III) and serum AFP and plasma OPN levels. RESULTS: There were statistically significant differences in plasma OPN levels between the HCC group (401 ± 72 ng/mL) and the other groups, between the cirrhotic group (258.3 ± 35 ng/mL) and the non-cirrhotic group (HCV group, 168.7 ± 41 ng/mL; fatty liver group, 106.7 ± 35 ng/mL), and between the chronic non-cirrhotic HCV group and the fatty liver group (I and IV) and the controls (35.1 ± 6 ng/mL). In the HCC group, the diagnostic value of OPN was comparable to that of AFP at a cutoff value of 280 ng/mL, achieving sensitivity, specificity, and overall accuracy of 100%, 98%, and 96%, respectively. Regarding the validity of plasma OPN as a predictor of fatty change, our results revealed a diagnostic accuracy of 50% with 70% sensitivity, 45% specificity, 50% positive predictive value, and 75% negative predictive value at a cutoff value of 134 ng/mL. CONCLUSIONS: Plasma OPN is comparable to AFP as a diagnostic marker and is related to the severity of liver involvement in HCC patients. Plasma OPN is of diagnostic potential value in NAFLD.