Endothelial dysfunction in children with newly diagnosed Graves' disease.

The most frequent cause of hyperthyroidism in children is Graves' disease (GD). Vascular endothelium is a specific target of thyroid hormone. The purpose of this study is to assess flow-mediated dilatation (FMD)% and serum von Willebrand factor (vWF) levels in children with newly diagnosed GD to reflect the extent of endothelial dysfunction in those children. In this study, 40 children with newly discovered GD and 40 children who were healthy served as the control group. Both patients and controls had anthropometric assessment, as well as measurements of fasting lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), TSH, and free thyroxine (FT4 and FT3), thyrotropin receptor antibodies TRAbs and vWF. Noninvasive ultrasound was utilized to quantify the carotid arteries' intima-media thickness and the brachial artery's FMD. Patients reported significantly reduced FMD response and greater vWF and hs-CRP levels compared to controls (P = 0.001 for each). In multivariate analysis, we reported that vWF was significantly correlated with TSH (OR 2.5, 95% CI 1.32-5.32, P = 0.001), FT3 (OR 3.4, 95% CI 1.45-3.55, P = 0.001), TRAb (OR 2.1, 95% CI 1.16-2.23, P = 0.01), and FMD% (OR 4.2, 95% CI 1.18-8.23, P = 0.001).  Conclusions: Children with newly diagnosed GD have endothelial dysfunction, which is shown by impaired FMD and increased vWF. These findings support the idea that GD may need to be treated as soon as possible. What is Known: • Graves' disease is the most common cause of hyperthyroidism in children. • vWF is a reliable marker for detection of vascular endothelial dysfunction. What is New: • Children with newly diagnosed Graves' disease may have endothelial dysfunction as reflected by impairment of FMD and raised vWF level. • Measurement of vWF level in children with newly diagnosed Graves' disease can be used for early detection of endothelial dysfunction.

The usefulness of modified distress thermometer in screening adolescents with COVID-19 for psychological distress: A prospective study.

BACKGROUND: Children and adolescents are more vulnerable than other age groups to the psychosocial effects of the coronavirus disease 2019 (COVID-19) pandemic. The modified distress thermometer (m-DT) was recently utilized for measuring the prevalence of psychological distress among adult COVID-19 patients. In the current study, we aimed to test the utilization of this m-DT in screening adolescent patients with COVID-19 for psychological distress. METHODS: Egyptian adolescent subjects with suspected or confirmed cases of COVID-19 at a University Hospital were enrolled. Binary logistic regression tests were conducted to explore the association between the m-DT cutoff scores of 4 and the clinical variables. RESULTS: A total of 48% (87/182) of the study subjects experienced significant (m-DT score ≥4) COVID-19-related distress. There were substantial differences between those with and without considerable distress regarding the length of quarantine, underlying medical disorders, and the presence of chronic respiratory conditions. Length of quarantine time, chronic respiratory disease, worry, and fever were independent factors associated with significant distress in COVID-19 adolescent patients. CONCLUSIONS: Almost half of the enrolled Egyptian adolescents with COVID-19 experienced significant psychological distress. The m-DT was helpful, as the current study had identified length of quarantine time, presence of chronic respiratory disease, worry, and fever as independent factors associated with significant distress in COVID-19 adolescents. Further studies are needed.

Interleukin 18 as a new inflammatory mediator in left ventricular hypertrophy in children with end-stage renal disease.

Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular morbidity and mortality (CV) in end-stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate relation of some inflammatory markers [as hs C-reactive protein (hsCRP) and interleukin (IL) 18] with LVH in children with ESRD on regular hemodialysis (HD). This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin (HB), hsCRP, IL 18, phosphorus, calcium, serum albumin, and lipid profile were evaluated and correlated with LVH. Data were analyzed using Student's t-test, and logistic regression to determine the relationship between LVH and other variables. LVH was present in 33 (66%) participants. Mean left ventricular mass index was 56.88 ± 22.23 g/m.2.7 Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy were present in 4%, 22%, and 44% of the participants. In univariate analysis, children with LVH had significantly lower levels of HB and serum albumin but higher levels of hsCRP, and IL 18 compared to those without LVH. On multivariate analysis: only hsCRP, and IL 18 were significantly associated with LVH. This study shows that elevated hsCRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high-risk group and implementation of targeted anti-inflammatory therapies.

Glomerular Expression of Some Profibrotic Factors in Progressive Childhood Lupus Nephritis.

BACKGROUND: Lupus nephritis (LN) is a major cause of mortality and morbidity in both adult and pediatric patients. However, studies regarding pathogenesis and predictors of renal outcomes in childhood LN are limited. Transforming growth factor-ß1 (TGF-ß1) and Connective tissue growth factor (CTGF) have an important role in proliferative and fibrotic changes in many renal diseases. We aim to evaluate the role of such two profibrotic factors in the progression of childhood onset LN and to detect if their glomerular expression could represent an early predictor of future deterioration of renal function. METHODS: 34 children with new onset of LN were included. Glomerular expressions of TGF-ß1 and CTGF were evaluated by immunohistochemical analysis in the renal tissue of such patients and in control tissue. GFR was estimated at time of renal biopsy at the onset of LN and after 2 years of follow-up. Rate of GFR change (ΔGFR) was calculated and used as indicative of degree of renal disease progression. RESULTS: Glomerular TGF-ß1 and CTGF expressions in children with LN were significantly higher than in control tissue (LN 15.41 ± 9.84 and 15.56 ± 10.51 vs. 2.15 ± 1.45 and 1.35 ± 1.07 in control respectively, with p < 0.001 in both). In addition, the glomerular expressions of TGF-ß1 and CTGF were significantly higher in patients with further decline in GFR (20.68 ± 7.73 and 21.05 ± 8.75) versus (5.75 ± 4.37 and 5.50 ± 3.78) in those without change in GFR with (p = 0.000 for both of them). CONCLUSIONS: Patients with LN have increased glomerular expressions of TGF-ß1 and CTGF, which were higher in those with further decline in GFR. These profibrotic factors are suspected to be involved in pathogenesis of LN and could be evaluated as a target for therapeutic intervention to stop progression of LN. In addition, their glomerular expression could be used as an early predictor of progression of LN, to justify early aggressive therapy in those with suspected rapid progression.

Impact of cytokine genetic polymorphisms on the risk of renal parenchymal infection in children.

BACKGROUND: Acute pyelonephritis is associated with renal scarring in up to 30% of patients. Renal scarring may cause significant long-term morbidity. The pathogenesis of acute pyelonephritis remains unclear, although it involves interaction among uroepithelium, the immune system cells, and the locally produced cytokines. That some UTI-prone children develop acute pyelonephritis, and eventually renal parenchymal scarring, suggests a genetic role. Interleukin-6, interleukin-8, chemokine receptor-1 (CXCR1), and tumor necrosis factor-alpha (TNFα), the key regulators of the host immune responses, are proteins whose secretion is controlled by genes. We postulated that functional polymorphic variants of their genes might have a role in APN susceptibility. OBJECTIVES: We sought to investigate a possible association of the common functional polymorphisms in genes encoding IL-6, IL-8, CXCR1, and TNFα with the risk of APN in children. METHODS: Urine culture was used to diagnose 300 children with UTI, of mean age of 51.31 ± 37.4 months (2-180 months). 99Tc-DMSA scans diagnosed 86 children with APN. Follow-up scans identified new renal scars in 18 children. Six functional single-nucleotide polymorphisms (SNPs) in genes encoding IL-6, IL-8, CXCR1, and TNFα were genotyped in all subjects (IL-6 rs1800795 (-174G/C), IL-6 rs1800796 (-572G/C), IL-8 rs2227306 (781C/T), IL8 rs4073 (-251A/T), CXCR1 rs2234671 (2607G/C), and TNFα rs1800629 (-308G/A)). RESULTS: TT genotype of IL-8 -251A/T polymorphism was significantly higher in APN patients (26.7%) than those with lower UTI (11.7%, p = 0.01) and control individuals (12.2%, p = 0.002). T allele was significantly more common in APN than in lower UTI (p = 0.025) and was significantly more common in APN (46%) than in the controls (p = 0.001). Similarly, TT genotype of IL-8 781C/T polymorphism was significantly more common in APN patients (31.4%) than those with lower UTI (17.3%, p = 0.003) and the controls (14.3%, p = 0.001). T allele was significantly more common in APN (55%) than lower UTI (40%, p = 0.005) and controls (37%, p = 0.001). However, IL-8 -251A/T and +781C/T SNPs did not qualify as an independent risk for parenchymal infection (OR 1.9, 95% CI 0.68-2.6, p = 0.13 and OR 2.3, 95% CI 0.89-3.7, p = 0.091, respectively). Lower UTI did not differ from the controls. The frequency of the genotypes and alleles of IL-6, CXCR1, and TNFα SNPs did not differ significantly among the different groups of the study. CONCLUSION: IL-8 -251A/T and +781C/T SNPs are associated with susceptibility to renal parenchymal infection in children and could be implicated in APN risk. However, none of these variants could clearly and independently predict this risk.

Glomerular Glucocorticoid Receptors Expression and Clinicopathological Types of Childhood Nephrotic Syndrome.

Glucocorticoids are primary therapy of idiopathic nephrotic syndrome (INS). However, not all children respond to steroid therapy. We assessed glomerular glucocorticoid receptor expression in fifty-one children with INS and its relation to response to steroid therapy and to histopathological type. Clinical, laboratory and glomerular expression of glucocorticoid receptors were compared between groups with different steroid response. Glomerular glucocorticoid expression was slightly higher in controls than in minimal change early responders, which in turn was significantly higher than in minimal change late responders. There was significantly lower glomerular glucocorticoid receptor expression in steroid-resistance compared to early responders, late responders and controls. Glomerular glucocorticoid expression was significantly higher in all minimal change disease (MCD) compared to focal segmental glomerulosclerosis. In INS, response to glucocorticoid is dependent on glomerular expression of receptors and peripheral expression. Evaluation of glomerular glucocorticoid receptor expression at time of diagnosis of NS can predict response to steroid therapy.

Glucocorticoid receptors expression and histopathological types in children with nephrotic syndrome.

UNLABELLED: Abstract Background: Some children with idiopathic nephrotic syndrome (NS) patients fail to respond even when given high dose of steroid. The aim of this study was to assess the GCR expression on the T lymphocytes of children with NS and its relation to the response to steroid and to histopathological type. METHODS: Forty-six pediatric patients with idiopathic NS and 20 age and sex matched apparently healthy children as controls were included. Flow cytometry was employed to determine the percentage of CD3+/GCR+ cells which then correlated with pattern of steroid response. Renal biopsy was done for steroid-dependent and steroid-resistant cases for determination of the underlying histopathological type. RESULTS: The mean percentage of T lymphocyte expression of GCRs (CD3+/GCR) was significantly higher in early steroid responders than in late responders and was slightly lower than the controls. There was a significantly lower GCRs expression in steroid-resistant patients in comparison to early responders, late responders and controls. Renal biopsy showed that most cases of late responders were of the focal segmental glomerulosclerosis (FSGS) type. The mean percentage of lymphocyte expression of GCRs was significantly higher in patients with minimal change disease (MCD) compared to patients with FSGS. CONCLUSION: Evaluation of the expression of intracellular GCRs in T lymphocytes at time of diagnosis of NS can predict the response to steroid therapy and can help in determination of the outcome of NS patients regarding future relapses.