Heavy metal levels are positively associated with serum periostin and miRNA-125b levels, but inversely associated with miRNA-26a levels in pediatric asthma cases. A case-control study.

BACKGROUND: The study investigated heavy metals levels [urinary cadmium (U-Cd), erythrocytic cadmium (E-Cd), urinary arsenic (U-As), and whole blood lead (WB-Pb)] in children with bronchial asthma (BA) and tested their associations with serum periostin, miRNA-125b and miRNA-26a levels, and with asthma severity clinically and laboratory [blood eosinophils count (BEC) and serum total immunoglobin E (IgE)]. Also, we tested cut-off points, for the studied parameters, to distinguish BA cases from healthy children. METHODS: This case-control study included 158 children divided into control group; n = 72 and BA group; n = 86. Heavy metals were measured by an inductively coupled plasma-optical emission spectrophotometer. Serum periostin and IgE levels were measured by their corresponding ELISA kits. miRNAs relative expressions were estimated by RT-qPCR using the 2-ΔΔCT method. RESULTS: Heavy metals, serum periostin, and miR-125b levels were significantly high in BA group (p < 0.001). Heavy metals levels correlated positively with serum periostin, miR-125b and IgE levels, BEC, and asthma severity. The reverse was observed regarding serum miR-26a levels. Receiver operating characteristics (ROC) curve analysis showed good to excellent abilities of U-Cd, E-Cd, U-As, WB-Pb, serum periostin, miRNA-125b, and miRNA - 26a, and total IgE levels to distinguish BA cases from healthy children. CONCLUSIONS: Heavy metal toxicity in children is associated with BA severity, increased serum periostin and miRNA-125b levels, and decreased miRNA-26a levels. Specific measures to reduce children's exposure to heavy metals should be taken. Future research should consider blocking miRNA-125b action or enhancing miRNA-26a action to manage BA cases.

Prevalence and impact of malnutrition on outcomes and mortality of under-five years children with pneumonia: a study from Upper Egypt.

Malnutrition has adverse impacts on under-five children with pneumonia. The purpose of this study was to address the prevalence and impact of malnutrition on under-five years children with pneumonia, admitted to a tertiary large children hospital in Upper Egypt. This study is a prospective case-control study. All under-five children diagnosed with pneumonia who were admitted to Assiut University Children's Hospital (AUCH) from January 1st to December 31st, 2021, were enrolled. Based on their nutritional assessment, the studied participants were classified into 2 groups: (1): Children with pneumonia and with nutritional deficiency considered as cases, and (2): Children with pneumonia and without nutritional deficiency considered as controls. Three hundred-fifty cases and 154 control subjects were enrolled, respectively. 93.4%, 31.1%, and 61.7% of the cases had underweight, stunting, and wasting, respectively. Among those cases, there were significant differences between survivors and non-survivors with regard to some clinicodemographic factors, laboratory parameters, and anthropometric parameters. Lack of compulsory vaccination, presence of sepsis, and blood transfusion (OR 2.874, 95% CI 0.048 - 2.988, p = 0.004, 2.627, 0.040 - 2.677, p = 0.009, and 4.108, 0.134 - 3.381, p < 0.001, respectively) were significant independent predictors for mortality among malnourished children with pneumonia.    Conclusion: Malnutrition has a high prevalence in under-five children with pneumonia in our locality. It has adverse effects on the outcomes and in-hospital mortality of those children. Lack of compulsory vaccination, presence of sepsis, and blood transfusion were significant independent predictors of mortality in malnourished children with pneumonia. Larger multicenter studies are warranted. What is Known: • Malnutrition has adverse impacts on under-five children with pneumonia. • Malnutrition could be a reason for in-hospital mortality among under-five children with pneumonia. What is New: • Malnutrition has a high prevalence in under-five children with pneumonia in Upper Egypt, with its adverse effects on the outcomes and mortality of those children. • Lack of vaccination, presence of sepsis, and blood transfusion are significant independent predictors of mortality in malnourished children with pneumonia in Upper Egypt.

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.

Urinary C-peptide creatinine ratio is a significant indicator of non-alcoholic fatty liver disease in children with obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the commonest etiology of chronic hepatic problems in children with obesity. This study aimed to assess whether urinary C-peptide creatinine ratio (UCPCR) might be a potential indicator of NAFLD in obese children. METHODS: The study included 240 children with simple obesity. Hepatic ultrasonic examination, anthropometric and laboratory measurements including fasting plasma glucose, fasting insulin, fasting C peptide, liver, renal profile, lipid profile, and UCPCR were obtained in all cases. According to the results of the hepatic ultrasonography, cases were classified into two categories, those with NAFLD (n=98) and without NAFLD (n= 142). RESULTS: In cases with NAFLD, UCPCR was significantly higher than those without NAFLD (P &lt; 0.001). A significant positive correlation between UCPCR and waist circumference (WC SDS), triglyceride, fasting C-peptide, HOMA-IR and alanine aminotransferase (ALT) was found (P &lt; 0.001 for each). Adjusting for other variables, UCPCR was the most significant predictor of NAFLD in children with obesity with higher odds ratio (OR = 3.26) than fasting C peptide (OR = 2.87), triglyceride (OR = 1.89), ALT (OR = 2.20), WC SDS (OR = 1.32) and age (OR=1.27) . UCPCR cut-off value of 0.755 nmol/mmol was able to discriminate cases with NAFLD from those without NAFLD with a sensitivity of 95%, a specificity of 87%. CONCLUSIONS: We concluded that UCPCR is a useful, practical and non-invasive predictor of NAFLD in children with obesity with high sensitivity and specificity.

Adherence to Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea.

Adherence to either continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) therapy in patients with obstructive sleep apnea syndrome (OSAS) represents a real challenge to sleep medicine physicians. Many risk factors/predictors for nonadherence exist, and usually, it is multifactorial. Long-term nonadherence with CPAP therapy has been associated with the use of CPAP for <4 hours/night during early treatment, moderate to severe obstructive sleep apnea (OSA), poor self-efficacy, and unsupportive bed partner. The American Academy of Sleep Medicine (AASM) recommends follow-up of patients with OSA within the first two weeks of CPAP use to optimize adherence. Measures to improve adherence to positive airway pressure (PAP) therapy go through an integrated approach that involves behavioral therapy and prompt management of side effects. Pharmacologic therapy in the form of a sedative-hypnotic sleep aid has a minor role in managing nonadherence to CPAP based on the greater risk of side effects. This article will briefly discuss the risk factors and management of nonadherence to PAP therapy in patients with OSAS.

Can pregnancy aggravate the criticality of COVID-19 infection in obese asthmatic peripartum woman? A peripartum COVID-19 mortality case report.

As coronavirus disease 2019 (COVID-19) sweeps all over the world, Information about COVID-19 is evolving rapidly and interim guidance by multiple organisations is constantly being updated and expanded. Early with discovery of COVID 19, it was reported that pregnancy did affect the progress of the disease severity. Recently, Centres for Disease Control and Prevention (CDC) reported that pregnancy is a risk factors for COVID-19 severity. The current case report is presenting a peripartum COVID-19 positive mortality case.

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.

Prevalence, risk factors, and impact of lung Cancer on outcomes of idiopathic pulmonary fibrosis: a study from the Middle East.

BACKGROUND: No studies have addressed the impact of lung cancer (LC) on prognosis of patients with idiopathic pulmonary fibrosis (IPF) in Upper Egypt. We aimed to evaluate the prevalence and risk factors for LC among IPF patients and its impact on their outcomes and survival in Upper Egypt. METHODS: A total of 246 patients with IPF who had complete clinical and follow up data were reviewed. They were categorized into 2 groups: 34 patients with biopsy-proven LC and IPF (LC-IPF) and 212 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared. RESULTS: Prevalence of LC was 13.8%. Pack/years was the most significant predictor for LC development in IPF (Odds ratio; 3.225, CI 1.257-1.669, p = 0.001). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC; median survival, 35 months vs 55 months; p = 0.000. LC accompanying IPF was one of the most significant independent predictors of survival in IPF patients (Hazard ratio 5.431, CI 2.186-13.492, p = 0.000). Mortality in LC-IPF patients was mainly due to LC progression in 36% and LC therapy-related complications in 22%. CONCLUSIONS: Prevalence of LC in IPF patients was 13.8%. Lung cancer has significant impacts on patients with IPF in Upper Egypt, in terms of clinical outcomes and survival. Smoking is the most significant independent predictor of LC development in IPF patients. A poorer survival was observed for patients with IPF developing LC, mainly due to LC progression, and to complications of its therapies. Further prospective, multicenter and larger studies are warranted.

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.